Search results for: multi-drug therapies

Authors: David Pettitt, Benjamin Davies, Georg Holländer, David Brindley

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Cellular based therapies, whose origins can be traced from the intertwined concepts of tissue engineering and regenerative medicine, have the potential to transform the current medical landscape and offer an approach to managing what were once considered untreatable diseases. However, despite a large increase in basic science activity in the cell therapy arena alongside a growing portfolio of cell therapy trials, the number of industry products available for widespread clinical use correlates poorly with such a magnitude of activity, with the number of cell-based therapeutics in mainstream use remaining comparatively low. This research serves to quantitatively assess the barriers to the clinical adoption of cell-based therapeutics through identification of unique barriers, specific challenges and opportunities facing the development and adoption of such therapies.

Keywords: cell therapy, clinical adoption, commercialization, translation

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Authors: Ramona-Niculina Jurcau, Ioana-Marieta Jurcau, Dong Hun Kwak, Nicolae-Alexandru Colceriu

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Background: Stress management (SM) is a topic of great academic interest and equally a task to accomplish. In addition, it is recognized the beneficial role of unconventional therapies (UCT) in stress modulation. Aims: The aim was to evaluate medical (MS) versus non-medical students’ (NMS) opinions about academic stress management (ASM) using UCT. Methods: MS (n=103, third year males and females) and NMS (n=112, males and females, from humanities faculties, different years of study), out of their academic program, voluntarily answered to a questionnaire concerning: a) Classification of the four most important academic stress factors; b) The extent to which their daily life influences academic stress; c) The most important SM methods they know; d) Which of these methods they are applying; e) the UCT they know or about which they have heard; f) Which of these they know to have stress modulation effects; g) Which of these UCT, participants are using or would like to use for modulating stress; and if participants use UTC for their own choose or following a specialist consultation in those therapies (SCT); h) If they heard about the following UCT and what opinion they have (using visual analogue scale) about their use (following CST) for the ASM: Phytotherapy (PT), apitherapy (AT), homeopathy (H), ayurvedic medicine (AM), traditional Chinese medicine (TCM), music therapy (MT), color therapy (CT), forest therapy (FT). Results: Among the four most important academic stress factors, for MS more than for NMS, are: busy schedule, large amount of information taught; high level of performance required, reduced time for relaxing. The most important methods for SM that MS and NMS know, hierarchically are: listen to music, meeting friends, playing sport, hiking, sleep, regularly breaks, seeing positive side, faith; of which, NMS more than MS, are partially applying to themselves. UCT about which MS and less NMS have heard, are phytotherapy, apitherapy, acupuncture, reiki. Of these UTC, participants know to have stress modulation effects: some plants, bee’s products and music; they use or would like to use for ASM (the majority without SCT) certain teas, honey and music. Most of MS and only some NMS heard about PT, AT, TCM, MT and much less about H, AM, CT, TT. NMS more than MS, would use these UCT, following CST. Conclusions: 1) Academic stress is similarly reflected in MS and NMS opinions. 2) MS and NMS apply similar but very few UCT for stress modulation. 3) Information that MS and NMS have about UCT and their ASM application is reduced. 4) It is remarkable that MS and especially NMS, are open to UCT use for ASM, following an SCT.

Keywords: academic stress, stress management, stress modulation, medical students, non-medical students, unconventional therapies

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Khushbu Priyadarshi, Chandramani Pathak

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Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.

Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein

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Authors: Masud Karim, Md. Solaiman Mia, Saifuddin Md. Tareeq, Md. Hasanuzzaman

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Autism Spectrum Disorder (ASD) is a neurodevelopment disorder. Such disorder is found in childhood life. Children with ASD have less capabilities in communication and social skills. Therapies are used to develop communication and social skills. Recently researchers have been trying to use robots in such therapies. In this paper, we have presented social skill learning test cases for children with ASD. Autism conditions are measured in 30 children in a special school. Among them, twelve children are selected who have equal ASD conditions. Then six children participated in training with humans, and another six children participated in training with robots. The learning session continued for one week and three hours each day. We have taken an assessment test before the learning sessions. After completing the learning sessions, we have taken another assessment test. We have found better performances from children who have participated in robotic sessions rather than the children who have participated in human sessions.

Keywords: children with ASD, NAO robot, human-robot interaction, social skills

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Authors: Milad Gholizadeh

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

Keywords: imminology, asthma, COPD, CXCR2 antagonists

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Authors: Senthil Rajan Dharmalingam, Shamala Nadaraju, Srinivasan Ramamurthy

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Doxorubicin is the most widely used anticancer drugs in chemotherapy treatment. However, problems related to the development of multidrug resistance (MDR) and acute cardiotoxicity have led researchers to investigate alternative forms of administering doxorubicin for cancer therapy. Several methods have been attempted to overcome MDR, including the co-administration of a chemosensitizer inhibiting the efflux caused by ATP binding cassette transporters with anticancer drugs, and the bypass of the efflux mechanism. Co encapsulation of doxorubicin (Dox) and cyclosporine A (CSA) into poly (DL-lactide-co-glycolide) nanoparticles was emulsification-solvent evaporation method using polyvinyl alcohol as emulsion stabilizers. The Dox-CSA loaded nanoparticles were evaluated for particle size, zeta potential and PDI by light scattering analysis and thermal characterizations by differential scanning calorimetry (DSC). Loading efficiency (LE %) and in-vitro dissolution samples were evaluated by developed and validated HPLC method. The optimum particle size obtained is 298.6.8±39.4 nm and polydispersity index (PDI) is 0.098±0.092. Zeta potential is found to be -29.9±4.23. Optimum pH to increase Dox LE% was found 7.1 which gave 42.5% and 58.9% increase of LE% for pH 6.6 and pH 8.6 compared respectively. LE% achieved for Dox is 0.07±0.01 % and CSA is 0.09±0.03%. Increased volume of PVA and weight of PLGA shows increase in size of nanoparticles. DSC thermograms showed shift in the melting peak for the nanoparticles compared to Dox and CSA indicating encapsulation of drugs. In conclusion, these preliminary studies showed the feasibility of PLGA nanoparticles to entrap Dox and CSA and require future in-vivo studies to be performed to establish its potential.

Keywords: doxorubicin, cyclosporine, PLGA, nanoparticles

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Authors: Iddrisu Ibrahim, Joseph Atia Ayariga, Junhuan Xu, Daniel Abugri, Boakai Robertson, Olufemi S. Ajayi

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The emergence of multidrug resistance poses a huge risk to public health globally. Yet these recalcitrant pathogens continue to rise in incidence rate, with resistance rates significantly outpacing the speed of antibiotic development. This, therefore, presents an aura of related health issues such as untreatable nosocomial infections arising from organ transplants and surgeries, as well as community-acquired infections that are related to people with compromised immunity, e.g., diabetic and HIV patients, etc. There is a global effort to fight multidrug-resistant pathogens spearheaded by the World Health Organization, thus calling for research into novel antimicrobial agents to fight multiple drug resistance. Previously, our laboratory demonstrated that Cannabidiol (CBD) was an effective antimicrobial against Salmonella typhimurium (S. typhimurium). However, we observed resistance development over time. To understand the mechanisms S. typhimurium uses to develop resistance to Cannabidiol (CBD), we studied the abundance of bacteria lipopolysaccharide (LPS) and membrane sterols of both susceptible and resistant S. typhimurium. Using real-time quantitative polymerase chain reaction (RT-qPCR), we also analyzed the expression of selected genes known for aiding resistance development in S. typhimurium. We discovered that there was a significantly higher expression of blaTEM, fimA, fimZ, and integrons in the CBD-resistant bacteria, and these were also accompanied by a shift in abundance in cell surface molecules such as lipopolysaccharide (LPS) and sterols.

Keywords: antimicrobials, resistance, cannabidiol, gram-negative bacteria, integrons, blaTEM, Fim, LPS, ergosterols

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Authors: P. S. Jagadeesh Kumar, Mingmin Pan, Xianpei Li, Yanmin Yuan, Tracy Lin Huan

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Researchers are doing enchanting research into the inherited features of Alzheimer’s disease and probable consistent therapies. In Alzheimer’s, memories are extinct in reverse order; memories formed lately are more transitory than those from formerly. Reminiscence therapy includes the conversation of past actions, trials and knowledges with another individual or set of people, frequently with the help of perceptible reminders such as photos, household and other acquainted matters from the past, music and collection of tapes. In this manuscript, the competence of reminiscence therapy for Alzheimer’s disease is measured using logistic regression based linear bootstrap aggregating. Logistic regression is used to envisage the experiential features of the patient’s memory through various therapies. Linear bootstrap aggregating shows better stability and accuracy of reminiscence therapy used in statistical classification and regression of memories related to validation therapy, supportive psychotherapy, sensory integration and simulated presence therapy.

Keywords: Alzheimer’s disease, linear bootstrap aggregating, logistic regression, reminiscence therapy

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Authors: Juliana Janet R. Martin-Puzon, Demetrio L. Valle, Windell L. Rivera

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This study aimed to determine the presence of bioactive phytochemical constituents and evaluate the in vitro antibacterial activities of Glinus oppositifolius or carpet weed, a plant valued for its use in traditional medicine and as a vegetable. The leaves, stems, and roots were extracted using chloroform, ethanol, and methanol. Phytochemical screening revealed that the entire G. oppositifolius plant, i.e. roots, stems, and leaves, is a rich source of alkaloids, flavonoids, glycosides, saponins, sterols, tannins, and triterpenes. The antibacterial activity of the leaf and stem extracts were evaluated through disc diffusion, minimum inhibitory concentration, and bactericidal concentration assays against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended spectrum β-lactamase-producing (ESβL+), carbapenem-resistant Enterobacteriaceae (CRE), and metallo-β-lactamase-producing (MβL+) Pseudomonas aeruginosa and Acinetobacter baumannii. The leaf extracts revealed antibacterial activities, inhibiting the growth of non-resistant and multidrug-resistant (MDR) strains of the Gram-negative bacteria E. coli, P. aeruginosa, and A. baumanii. In conclusion, the various biological activities of G. oppositifolius, including its antibacterial activity, are due to the presence of diverse bioactive secondary metabolites. The presence of phytochemical compounds in G. oppositifolius is scientific evidence on its use for treatment of many ailments. Thus, the results demonstrate the great potential of the plant as a new, alternative source of antimicrobials and other components with therapeutic value.

Keywords: antibacterial, Glinus oppositifolius, multidrug-resistant, secondary metabolites

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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Authors: Caterina Grandi, Lukas Lochner, Marco Padovan, Mirco Rizzi, Paola Sperinde, Fabio Vittadello, Luisa Cavada

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Background: In recent years, the use of Complementary Alternative Medicine (CAM) has achieved worldwide popularity. With the increased public interest in CAMs, attention to it within Health Care Schools and Colleges has also improved. Studies generally assess the knowledge and attitudes regarding CAMs in medical and nursing students. The current study focused on the knowledge, attitudes and practice of CAM in healthcare students. Aim: To assess the knowledge and attitudes regarding complementary and alternative medicine (CAM) in healthcare students in South Tyrol, a region in Northern Italy. Methodology: This cross-sectional study was carried out among 361 students. Self-administered questionnaire was adapted and modified by the researchers from several questionnaires. The instrument consisted of three sections: 1) demographical characteristics (gender, place of residence and year of study); 2) general attitudes towards CAM, evaluated through 11 items using a Likert scale (agree, partly agree, partly disagree, disagree); 3) knowledge and use about any particular CAM practices (acupuncture, aromatherapy, creative therapies, diet/nutritional therapies, phytotherapy/herbal therapies, compresses, massage therapy, Ayurvedic therapy, Tibetan medicine, naturopathy, homeopathy, pet therapy, reflexology, therapeutic touch, chiropractic/osteopathy). Results: The sample consisted of 63 males and 297 females, 58% living in villages. 151 students (42%) were in the first year, 99 (27%) in the second and 106 (30%) in the third. Both men and women agreed with statements about the utility and benefits of CAMs. Women were significantly more likely than men to agree that the CAM practices should be included in the curriculum (p < 0.004), that the health professionals should be able to advice their patients about commonly used CAM methods (p < 0.002) and that the clinical care should integrate CAM practices (p < 0.04). Students in the second year showed the highest mean score for the statement 'CAM includes ideas and methods from which conventional medicine could benefit' (p = 0.049), highlighting a positive attitude, while students in the third year achieved the lowest mean score for the negative statement 'The results of CAM are in most cases due to a placebo effect'. Regarding this statement, participants living in villages disagreed significantly than students living in the city (p < 0.001). Females appeared to be significantly more familiar with homeopathy (p < 0.002), aromatherapy (p < 0.033), creative therapies (p < 0.001) and herbal therapies (p<0.002) than males. Moreover, women were likely to use CAM more frequently than men, particularly to solve psychological problems (p < 0.004). In addition, women perceived the benefit significantly more positive than men (p < 0.001). Students in the second year revealed to use the CAM mostly to improve the quality of life (p < 0.023), while students in the third year used CAMs particularly for chronic diseases (p < 0.001). Conclusions: Results from this study suggested that female students show more positive attitudes on CAM than male students. Moreover, the prevalence of CAM use and its perceived benefits differ between males and females, so that women are more willing to use CAM practices.

Keywords: attitude, CAM, complementary and alternative medicine, healthcare students, knowledge

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Authors: Elsa Makue Nguuffo, Esther Del Florence Moni Ndedi, Jacky Njiki Bikoï, Jean Paul Assam Assam, Maximilienne Ascension Nyegue

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Aims: The present study aims to evaluate the kinetic parameters of essential oils (EOs) and combinations fromDrypetes gossweileri Stem Bark, Ocimum gratissimum leaves, Cymbopogon citratusleaves after evaluation of their antibacterial activityonmultidrug-resistant strains ofShigella. Material and Methods:fiveclinical strains of Shigellaisolated from patients with diarrhoeaincluding Shigella flexneri, and 4 otherstrains of Shigella sppwere selected. Their antibiotic profile was established using agar test diffusion with seven antibiotics belonging to seven classes.EOs were extracted from each plant using hydrodistillation process. The activity of Ciprofloxacin®, OEs, and their combination formulatedinthe followingratios(w/w/w): C1: 1/1/1; C2: 2/1/1; C3: 1/2/1, C4:1/1/2 was evaluated microdilution assay. The various interactions of OEs in the different combinations were determined then the OE and the most active combination were retained to determine their kinetic parameters on S. flexneri. Results: Antibiotic susceptibility tests revealed that most Shigella isolates (n = 4) were resistant to six antibiotics tested. Ciprofloxacin (40%), Nalidixic acid (60%), Tetracycline (80%), Amoxicillin (100%), Cefotaxime (80%), Erythromycin (100%), and Cotrimoxazole (80%) were the profiles found in the different strains of Shigella. About the antibacterial activity of OEs, Drypetes gossweileriOE and C2 combination had shown a higher Shigellicide property with a Minimal Inhibitory Concentration(MIC) respectivelyranging from 0.078 mg/mL to 0.312 mg/mL and 0.012 to 1.562 mg/mL. Combinations of OEs showed various interactions whose synergistic effects were mostly encountered. The best deactivation was obtained by the combination C2 at 16 MIC withb= 1.962. Conclusion: the susceptibility of Shigella to OEs and their combinations justifies their use in traditional medicine in the treatment of shigellosis.

Keywords: shigella, multidrug-resistant, EOs, kinetic

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Authors: Umairah Natasya Binti Mohd Omeershffudin, Suresh Kumar

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Klebsiella pneumoniae, a Gram-negative enteric bacterium that causes nosocomial and urinary tract infections. Particular concern is the global emergence of multidrug-resistant (MDR) strains of Klebsiella pneumoniae. Characterization of antibiotic resistance determinants at the genomic level plays a critical role in understanding, and potentially controlling, the spread of multidrug-resistant (MDR) pathogens. In this study, drug-resistant Klebsiella pneumoniae strain 825795-1 was investigated with extensive computational approaches aimed at identifying novel drug targets among hypothetical proteins. We have analyzed 1099 hypothetical proteins available in genome. We have used in-silico genome subtraction methodology to design potential and pathogen-specific drug targets against Klebsiella pneumoniae. We employed bioinformatics tools to subtract the strain-specific paralogous and host-specific homologous sequences from the bacterial proteome. The sorted 645 proteins were further refined to identify the essential genes in the pathogenic bacterium using the database of essential genes (DEG). We found 135 unique essential proteins in the target proteome that could be utilized as novel targets to design newer drugs. Further, we identified 49 cytoplasmic protein as potential drug targets through sub-cellular localization prediction. Further, we investigated these proteins in the DrugBank databases, and 11 of the unique essential proteins showed druggability according to the FDA approved drug bank databases with diverse broad-spectrum property. The results of this study will facilitate discovery of new drugs against Klebsiella pneumoniae.

Keywords: pneumonia, drug target, hypothetical protein, subtractive genomics

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Authors: Shamila Manie, Soraya Maart, Ayesha Osman

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Introduction: People diagnosed with multidrug resistant pulmonary tuberculosis (MDR-PTB) is subjected to prolonged hospitalization in South Africa. It has thus become essential for research to shift its focus from a purely medical approach, but to include social and environmental factors when looking at the impact of the disease on those affected. Aim: To explore the factors affecting individuals with multi-drug resistant pulmonary tuberculosis during long-term hospitalization using the comprehensive ICF core-sets for obstructive pulmonary disease (OPD) and cardiopulmonary (CPR) conditions at Brooklyn Chest Hospital (BCH). Methods: A quantitative descriptive, cross-sectional study design was utilized. A convenient sample of 19 adults at Brooklyn Chest Hospital were interviewed. Results: Most participants reported a decrease in exercise tolerance levels (b455: n=11). However it did not limit participation. Participants reported that a lack of privacy in the environment (e155) was a barrier to health. The presence of health professionals (e355) and the provision of skills development services (e585) are facilitators to health and well-being. No differences exist in the functional ability of HIV positive and negative participants in this sample. Conclusion: The ICF Core Sets appeared valid in identifying the barriers and facilitators experienced by individuals with MDR-PTB admitted to BCH. The hospital environment must be improved to add to the QoL of those admitted, especially improving privacy within the wards. Although the social grant is seen as a facilitator, greater emphasis must be placed on preparing individuals to be economically active in the labour for when they are discharged.

Keywords: multidrug resistant tuberculosis, MDR ICF core sets, health-related quality of life (HRQoL), hospitalization

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Authors: Callistus I. Iheme, Kenneth E. Asika, Emmanuel I. Ugwor, Chukwuka U. Ogbonna, Ugonna H. Uzoka, Nneamaka A. Chiegboka, Chinwe S. Alisi, Obinna S. Nwabueze, Amanda U. Ezirim, Judeanthony N. Ogbulie

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Antimicrobial resistance (AMR) is a major threat to the global health sector. Zinc oxide nanocomposites (ZnONCs), composed of zinc oxide nanoparticles and phytochemicals from Azadirachta indica aqueous leaf extract, were assessed for their physico-chemicals, in silico and in vitro antimicrobial properties on multidrug-resistant Escherichia coli enzymes. Gas chromatography coupled with mass spectroscope (GC-MS) analysis on the ZnONCs revealed the presence of twenty volatile phytochemical compounds, among which is scoparone. Characterization of the ZnONCs was done using ultraviolet-visible spectroscopy (UV-vis), energy dispersive spectroscopy (EDX), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and x-ray diffractometer (XRD). Dehydrogenase enzyme converts colorless 2,3,5-triphenyltetrazolium chloride to the red triphenyl formazan (TPF). The rate of formazan formation in the presence of ZnONCs is proportional to the enzyme activities. The color formation is extracted and determined at 500 nm, and the percentage of enzyme activity is calculated. To determine the bioactive components of the ZnONCs, characterize their binding to enzymes, and evaluate the enzyme-ligand complex stability, respectively Discrete Fourier Transform (DFT) analysis, docking, and molecular dynamics simulations will be employed. The results showed arrays of ZnONCs nanorods with maximal absorption wavelengths of 320 nm and 350 nm and thermally stable at the temperature range of 423.77 to 889.69 ℃. In vitro study assessed the dehydrogenase inhibitory properties of the ZnONCs, conjugate of ZnONCs and ampicillin (ZnONCs-amp), the aqueous leaf extract of A. indica, and ampicillin (standard drug). The findings revealed that at the concentration of 500 μm/mL, 57.89 % of the enzyme activities were inhibited by ZnONCs compared to 33.33% and 21.05% of the standard drug (Ampicillin), and the aqueous leaf extract of the A. indica respectively. The inhibition of the enzyme activities by the ZnONCs at 500 μm/mL was further enhanced to 89.74 % by conjugating with Ampicillin. In silico study on the ZnONCs revealed scoparone as the most viable competitor of nicotinamide adenine dinucleotide (NAD⁺) for the coenzyme binding pocket on E. coli malate and histidinol dehydrogenase. From the findings, it can be concluded that the scoparone components of the nanocomposites in synergy with the zinc oxide nanoparticles inhibited E. coli malate and histidinol dehydrogenase by competitively binding to the NAD⁺ pocket and that the conjugation of the ZnONCs with ampicillin further enhanced the antimicrobial efficiency of the nanocomposite against multidrug resistant E. coli.

Keywords: antimicrobial resistance, dehydrogenase activities, E. coli, zinc oxide nanocomposites

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Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

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Authors: Sadaf Ilyas

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Recombinant cytokines have been employed successfully as potential therapeutic agent. Some cytokine therapies are already used as a part of clinical practice, ranging from early exploratory trials to well established therapies that have already received approval. Interleukin 15 is a pleiotropic cytokine having multiple roles in peripheral innate and adaptive immune cell function. It regulates the activation, proliferation and maturation of NK cells, T-cells, monocytes/macrophages and granulocytes, and the interactions between them thus acting as a bridge between innate and adaptive immune responses. Unraveling the biology of IL-15 has revealed some interesting surprises that may point toward some of the first therapeutic applications for this cytokine. In this study, the human interleukin 15 gene was isolated, amplified and ligated to a TA vector which was then transfected to a bacterial host, E. coli Top10F’. The sequence of cloned gene was confirmed and it showed 100% homology with the reported sequence. The confirmed gene was then subcloned in pET Expression system to study the IPTG induced expression of IL-15 gene. Positive expression was obtained for number of clones that showed 15 kd band of IL-15 in SDS-PAGE analysis, indicating the successful strain development that can be studied further to assess the potential therapeutic intervention of this cytokine in relevance to human diseases.

Keywords: Interleukin 15, pET expression system, immune therapy, protein purification

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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: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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Authors: Ayşegül Bilge, Merve Uğuryol, Şeyda Dülgerler, Mustafa Yıldız

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The purpose of this research is to prove the Attitude towards Using Complementary Treatments Scale reliability and validity. The research is a methodological type of research that has been planned to determine the validity and reliability of the Attitude towards Using Complementary Treatments Scale. The scale has been developed by the researchers. In the scale, there are 23 questions including complementary and modern therapies individuals apply when they have health problems 4-item Likert-type evaluation has been carried out in preparing the questionnaire. High score obtained from the scale indicates a positive attitude towards complementary therapies. In the course of validity assessment of the scale, expert opinion has been received, and the content validity of the scale has been determined by using Kendall coefficient correlation test (Wa=0.200, p = 0.460). In the course of the reliability assessment of the scale, total score correlations of 23 materials have been examined, and those under 0.20 correlation limit has been removed from the scale correlation. As a result, the scale was left to be 13 items. In the internal consistency tests of the analyses, Cronbach's alpha value has been found to be 0.79. As a result, of the validity analyses of the Attitude towards Using Complementary Treatments Scale, the content and language validity analyses has been found to be at the expected level. It has been determined to be a highly reliable scale as the result of the reliability analyses. In conclusion, Attitude towards Using Complementary Treatments Scale is a valid and reliable scale.

Keywords: alternative health care, complementary treatment, instrument development, nursing practice

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Authors: Lea Lachaud, Aida Raoult, Marion Trousselard, Francois B. Vialatte

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This paper addresses mindfulness from a psychological and neuroscientific perspective, by studying how it modulates attention. Being mindful defines a state characterized by 1-an attention directed to the subjective experience of present moment, 2-an unconditional acceptance of this experience, and 3-the rejection of systematic rationalization in favor of plain awareness. The aim of this study is to investigate whether perceptual salience filters are lowered in a ‘mindful’ condition by exploring the role of being mindful in focused visual attention. Over the past decade, mindfulness therapies have seen a surge in popularity. While the outcomes of these therapies have been widely discussed, the mechanisms whereby meditation affects the brain remain mostly unknown. To explore the role of mindfulness in focused visual attention, we conducted a change blindness experiment on 24 subjects, 12 of them being mindful according to the Freiburg Mindfulness Inventory (FMI) scale. Our results suggest that mindful subjects are less affected by change blindness than non-mindful subjects. Furthermore, EEG measurements performed during the experiments may expose neural correlates specific to the mindful state on P300 evoked potentials. Finally, the analysis of both amplitude and latency caused by the perception of a change over 864 recordings may reveal biomarkers that are typical of this state. The paper concludes by discussing the implications of these results for further research.

Keywords: EEG, change blindness, mindfulness, p300, perception, visual attention

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Authors: Farah Naja, Mohamad Alameddine

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Background: The difficulty of compliance to therapeutic and lifestyle management of type 2 diabetes mellitus (T2DM) encourages patients to use complementary and alternative medicine (CAM) therapies. Little is known about the prevalence and mode of CAM use among diabetics in the Eastern Mediterranean Region in general and Lebanon in particular. Objective: To assess the prevalence and modes of CAM use among patients with T2DM residing in Beirut, Lebanon. Methods: A cross-sectional survey of T2DM patients was conducted on patients recruited from two major referral centers - a public hospital and a private academic medical center in Beirut. In a face-to-face interview, participants completed a survey questionnaire comprised of three sections: socio-demographic, diabetes characteristics and types and modes of CAM use. Descriptive statistics, univariate and multivariate logistic regression analyses were utilized to assess the prevalence, mode and correlates of CAM use in the study population. The main outcome in this study (CAM use) was defined as using CAM at least once since diagnosis with T2DM. Results: A total of 333 T2DM patients completed the survey (response rate: 94.6%). Prevalence of CAM use in the study population was 38%, 95% CI (33.1-43.5). After adjustment, CAM use was significantly associated with a “married” status, a longer duration of T2DM, the presence of disease complications, and a positive family history of the disease. Folk foods and herbs were the most commonly used CAM followed by natural health products. One in five patients used CAM as an alternative to conventional treatment. Only 7 % of CAM users disclosed the CAM use to their treating physician. Health care practitioners were the least cited (7%) as influencing the choice of CAM among users. Conclusion: The use of CAM therapies among T2DM patients in Lebanon is prevalent. Decision makers and care providers must fully understand the potential risks and benefits of CAM therapies to appropriately advise their patients. Attention must be dedicated to educating T2DM patients on the importance of disclosing CAM use to their physicians especially patients with a family history of diabetes, and those using conventional therapy for a long time.

Keywords: nutritional supplements, type 2 diabetes mellitus, complementary and alternative medicine (CAM), conventional therapy

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Authors: Demetrio L. Valle Jr., Juliana Janet M. Puzon, Windell L. Rivera

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From the various medicinal plants available in the Philippines, crude ethanol extracts of twelve (12) Philippine medicinal plants, namely: Senna alata L. Roxb. (akapulko), Psidium guajava L. (bayabas), Piper betle L. (ikmo), Vitex negundo L. (lagundi), Mitrephora lanotan (Blanco) Merr. (Lanotan), Zingiber officinale Roscoe (luya), Curcuma longa L. (Luyang dilaw), Tinospora rumphii Boerl (Makabuhay), Moringga oleifera Lam. (malunggay), Phyllanthus niruri L. (sampa-sampalukan), Centella asiatica (L.) Urban (takip kuhol), and Carmona retusa (Vahl) Masam (tsaang gubat) were studied. In vitro methods of evaluation against selected Gram-positive and Gram-negative multidrug-resistant (MDR), bacteria were performed on the plant extracts. Although five of the plants showed varying antagonistic activities against the test organisms, only Piper betle L. exhibited significant activities against both Gram-negative and Gram-positive multidrug-resistant bacteria, exhibiting wide zones of growth inhibition in the disk diffusion assay, and with the lowest concentrations of the extract required to inhibit the growth of the bacteria, as supported by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Further antibacterial studies of the Piper betle L. leaf, obtained by three extraction methods (ethanol, methanol, supercritical CO2), revealed similar inhibitory activities against a multitude of Gram-positive and Gram-negative MDR bacteria. Thin layer chromatography (TLC) assay of the leaf extract revealed a maximum of eight compounds with Rf values of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV-366 nm. TLC- agar overlay bioautography of the isolated compounds showed the compounds with Rf values of 0.86 and 0.13 having inhibitory activities against Gram-positive MDR bacteria (MRSA and VRE). The compound with an Rf value of 0.86 also possesses inhibitory activity against Gram-negative MDR bacteria (CRE Klebsiella pneumoniae and MBL Acinetobacter baumannii). Gas Chromatography-Mass Spectrometry (GC-MS) was able to identify six volatile compounds, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include 4-(2-propenyl)phenol and eugenol; and the new four compounds were ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, and 3-fluoro-2-propynenitrite. Phytochemical screening and investigation of its antioxidant, cytotoxic, possible hemolytic activities, and mechanisms of antibacterial activity were also done. The results showed that the local variant of Piper betle leaf extract possesses significant antioxidant, anti-cancer and antimicrobial properties, attributed to the presence of bioactive compounds, particularly of flavonoids (condensed tannin, leucoanthocyanin, gamma benzopyrone), anthraquinones, steroids/triterpenes and 2-deoxysugars. Piper betle L. is also traditionally known to enhance wound healing, which could be primarily due to its antioxidant, anti-inflammatory and antimicrobial activities. In vivo studies on mice using 2.5% and 5% of the ethanol leaf extract cream formulations in the excised wound models significantly increased the process of wound healing in the mice subjects, the results and values of which are at par with the current antibacterial cream (Mupirocin). From the results of the series of studies, we have definitely proven the value of Piper betle L. as a source of bioactive compounds that could be developed into therapeutic agents against MDR bacteria.

Keywords: Philippine herbal medicine, multidrug-resistant bacteria, Piper betle, TLC-bioautography

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Authors: Zuhrotun Ulya, Muchammad Syamsulhadi, Debree Septiawan

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Patients with bipolar disorder are three times more likely to suffer cardiovascular disorders than the general population, which will influence their level of morbidity and rate of mortality. Bipolar disorder also affects the pulmonary system. The choice of long term-monotherapy and other combinative therapies have clinical impacts on patients. This study investigates the case of a woman who has been suffering from bipolar disorder for 16 years, and who has a history of Steven Johnson Syndrome. At present she is suffering also from cardiovascular and pulmonary disorder. An analysis of the results of this study suggests that there is a relationship between cardiovascular disorder, drug therapies, Steven Johnson Syndrome and mood stabilizer obtained from the PubMed, Cochrane, Medline, and ProQuest (publications between 2005 and 2015). Combination therapy with mood stabilizer is recommended for patients who do not have side effect histories from these drugs. The replacement drugs and combinations may be applied, especially for those with bipolar disorders, and the combination between atypical antipsychotic groups and mood stabilizers is often made. Clinicians, however, should be careful with the patients’ physical and metabolic changes, especially those who have experienced long-term therapy and who showed a history of Steven Johnson Syndrome (for which clinicians probably prescribed one type of medicine).

Keywords: cardiopulmonary disease, bipolar disorder, SJS, therapy

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Authors: Haftay Abraha Tadesse, Atsebaha Gebrekidan Kahsay, Mahumd Abdulkader

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Background: Salmonella species and Escherichia coli are important foodborne pathogens affecting humans and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. This study was aimed to determine the prevalence, antimicrobial susceptibility patterns and associated risk factors for Salmonella species and E. coli in raw meat from butchery houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from January to September 2019. Socio-demographic data and risk factors were collected using a predesigned questionnaire. Meat samples were collected aseptically from the butchery houses and transported using icebox to Mekelle University, College of Veterinary Sciences for the isolation and identification of Salmonella species and E. coli, Antimicrobial susceptibility patterns were determined using Kirby disc diffusion method. Data obtained were cleaned and entered into Statistical Package for the Social Sciences version 22 and logistic regression models with odds ratio were calculated. P-value < 0.05 was considered as statistically significant. Results: A total of 153 out of 384 (39.8%) of the meat specimens were found to be contaminated. The contamination of Salmonella species and E. coli were 15.6% (n=60) and 20.8%) (n=80), respectively. Mixed contamination (Salmonella species and E. coli) was observed in 13 (3.4 %) of the analyzed. Poor washing hands regularly (AOR = 8.37; 95% CI: 2.75-25.50) and not using gloves during meat handling (AOR=11. 28; 95% CI: (4.69 27.10) were associated with an overall bacterial contamination.About 95.5% of the tested isolates were sensitive to chloramphenicol and norfloxacin while the resistance of amoxyclav_amoxicillin and erythromycin were both isolated bacteria species. The overall multidrug resistance pattern for Salmonella and E. coli were 51.4% (n=19) and 31.8% (14), respectively. Conclusion: Of the 153 (153/384) contaminated raw meat, 60 (15.6%) and 80 (20.8%) were contaminated by Salmonella species and E. coli, respectively. Poor hand washing practice and not using glove during meat handling showed significant association with bacterial contamination. Multidrug-resistant showed in Salmonella species and E. coli were 19 (51.4%) and 14 (31.8%), respectively.

Keywords: antimicrobial susceptibility test, butchery houses, e. coli, salmonella species

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Authors: Rachid Kacem

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Excessive recruitment of Neutrophils into the lungs is a hallmark of several chronic inflammatory disorders such as emphysema and COPD. The resulting of this recruitment is the pathogenesis of lungs which is characterized by an imbalance between leukocyte serine proteinases mainly neutrophil elastase and the physiological inhibitors. The development of emphysema and remodeling of airway tissue occurred when neutrophil migrate into the lungs with more release of elastase and other proteolytic enzymes. Many reports have demonstrated that the extracts from medicinal plants such as Nigella sativa (L.) seeds extracts have anti-elastase activity; this is mainly due to the enrichment of the extracts with many bioactive molecules mainly phenolic compounds. Neutrophil serine proteases including human neutrophil elastase are involved in many inflammatory diseases, such as chronic obstructive pulmonary disease and emphysema. Since the current therapies for these diseases are inadequate and have numerous adverse effects, there is an acute need of potential alternative therapies. The natural protease inhibitors have received increasing attention as useful tools for potential utilization in pharmacology. This work is elucidating the most important natural phenolic substances that have been reported recently for their effectiveness as natural anti-elastase molecules, and hence, to the possibility of their use in the field of pharmaceuticals.

Keywords: medicinal plants, phenols, elastase, anti-elastase, chronic obstructive pulmonary disease, COPD, emphysema

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Authors: S. Junaid S. Qazi, Denice C. Bay, Raymond Chew, Raymond J. Turner

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EmrE, a member of the small multidrug resistance protein family in bacteria is considered to be the archetypical member of its family. It confers host resistance to a wide variety of quaternary cation compounds (QCCs) driven by proton motive force. Generally, purification yield is a challenge in all membrane proteins because of the difficulties in their expression, isolation and solubilization. EmrE is extremely hydrophobic which make the purification yield challenging. We have purified EmrE protein using two different approaches: organic solvent membrane extraction and hexahistidine (his6) tagged Ni-affinity chromatographic methods. We have characterized changes present between ligand affinity of untagged and his6-tagged EmrE proteins in similar membrane mimetic environments using biophysical experimental techniques. Purified proteins were solubilized in a buffer containing n-dodecyl-β-D-maltopyranoside (DDM) and the conformations in the proteins were explored in the presence of four QCCs, methyl viologen (MV), ethidium bromide (EB), cetylpyridinium chloride (CTP) and tetraphenyl phosphonium (TPP). SDS-Tricine PAGE and dynamic light scattering (DLS) analysis revealed that the addition of QCCs did not induce higher multimeric forms of either proteins at all QCC:EmrE molar ratios examined under the solubilization conditions applied. QCC binding curves obtained from the Trp fluorescence quenching spectra, gave the values of dissociation constant (Kd) and maximum specific one-site binding (Bmax). Lower Bmax values to QCCs for his6-tagged EmrE shows that the binding sites remained unoccupied. This lower saturation suggests that the his6-tagged versions provide a conformation that prevents saturated binding. Our data demonstrate that tagging an integral membrane protein can significantly influence the protein.

Keywords: small multidrug resistance (SMR) protein, EmrE, integral membrane protein folding, quaternary ammonium compounds (QAC), quaternary cation compounds (QCC), nickel affinity chromatography, hexahistidine (His6) tag

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Authors: A. Abubakar, A. Parsa, S. Walker

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Despite advances made in the diagnosis and management of drug-sensitive tuberculosis (TB) over the past decades, treatment of multidrug-resistant tuberculosis (MDR-TB) remains challenging and complex particularly in high burden countries including Nigeria. Treatment of MDR-TB is cost-prohibitive with success rate generally lower compared to drug-sensitive TB and if care is not taken it may become the dominant form of TB in future with many treatment uncertainties and substantial morbidity and mortality. Addressing these challenges requires collaborative efforts thorough sustained researches to evaluate the current treatment guidelines, particularly in high burden countries and prevent progression of resistance. To our best knowledge, there has been no research exploring the acceptability, effectiveness, and cost-effectiveness of community-based-MDR-TB treatment model in Nigeria, which is among the high burden countries. The previous similar qualitative study looks at the home-based management of MDR-TB in rural Uganda. This research aimed to explore patient’s views and acceptability of community-based-MDR-TB treatment model and to evaluate and compare the effectiveness and cost-effectiveness of community-based versus hospital-based MDR-TB treatment model of care from the Nigerian perspective. Knowledge of patient’s views and acceptability of community-based-MDR-TB treatment approach would help in designing future treatment recommendations and in health policymaking. Accordingly, knowledge of effectiveness and cost-effectiveness are part of the evidence needed to inform a decision about whether and how to scale up MDR-TB treatment, particularly in a poor resource setting with limited knowledge of TB. Mixed methods using qualitative and quantitative approach were employed. Qualitative data were obtained using in-depth semi-structured interviews with 21 MDR-TB patients in Nigeria to explore their views and acceptability of community-based MDR-TB treatment model. Qualitative data collection followed an iterative process which allowed adaptation of topic guides until data saturation. In-depth interviews were analyzed using thematic analysis. Quantitative data on treatment outcomes were obtained from medical records of MDR-TB patients to determine the effectiveness and direct and indirect costs were obtained from the patients using validated questionnaire and health system costs from the donor agencies to determine the cost-effectiveness difference between community and hospital-based model from the Nigerian perspective. Findings: Some themes have emerged from the patient’s perspectives indicating preference and high acceptability of community-based-MDR-TB treatment model by the patients and mixed feelings about the risk of MDR-TB transmission within the community due to poor infection control. The result of the modeling from the quantitative data is still on course. Community-based MDR-TB care was seen as the acceptable and most preferred model of care by the majority of the participants because of its convenience which in turn enhanced recovery, enables social interaction and offer more psychosocial benefits as well as averted productivity loss. However, there is a need to strengthen this model of care thorough enhanced strategies that ensure guidelines compliance and infection control in order to prevent the progression of resistance and curtail community transmission.

Keywords: acceptability, cost-effectiveness, multidrug-resistant TB treatment, community and hospital approach

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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