Search results for: transdermal drug delivery

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Serhat Tüzün, Tufan Demirel

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Decision Support Systems (DSS) have been investigated by researchers and technologists for more than 35 years. This paper analyses the developments in the architecture and software of these systems, provides a systematic analysis for different Web-based DSS approaches and Intelligent Decision-making Technologies (IDT), with the suggestion for future studies. Decision Support Systems literature begins with building model-oriented DSS in the late 1960s, theory developments in the 1970s, and the implementation of financial planning systems and Group DSS in the early and mid-80s. Then it documents the origins of Executive Information Systems, online analytic processing (OLAP) and Business Intelligence. The implementation of Web-based DSS occurred in the mid-1990s. With the beginning of the new millennia, intelligence is the main focus on DSS studies. Web-based technologies are having a major impact on design, development and implementation processes for all types of DSS. Web technologies are being utilized for the development of DSS tools by leading developers of decision support technologies. Major companies are encouraging its customers to port their DSS applications, such as data mining, customer relationship management (CRM) and OLAP systems, to a web-based environment. Similarly, real-time data fed from manufacturing plants are now helping floor managers make decisions regarding production adjustment to ensure that high-quality products are produced and delivered. Web-based DSS are being employed by organizations as decision aids for employees as well as customers. A common usage of Web-based DSS has been to assist customers configure product and service according to their needs. These systems allow individual customers to design their own products by choosing from a menu of attributes, components, prices and delivery options. The Intelligent Decision-making Technologies (IDT) domain is a fast growing area of research that integrates various aspects of computer science and information systems. This includes intelligent systems, intelligent technology, intelligent agents, artificial intelligence, fuzzy logic, neural networks, machine learning, knowledge discovery, computational intelligence, data science, big data analytics, inference engines, recommender systems or engines, and a variety of related disciplines. Innovative applications that emerge using IDT often have a significant impact on decision-making processes in government, industry, business, and academia in general. This is particularly pronounced in finance, accounting, healthcare, computer networks, real-time safety monitoring and crisis response systems. Similarly, IDT is commonly used in military decision-making systems, security, marketing, stock market prediction, and robotics. Even though lots of research studies have been conducted on Decision Support Systems, a systematic analysis on the subject is still missing. Because of this necessity, this paper has been prepared to search recent articles about the DSS. The literature has been deeply reviewed and by classifying previous studies according to their preferences, taxonomy for DSS has been prepared. With the aid of the taxonomic review and the recent developments over the subject, this study aims to analyze the future trends in decision support systems.

Keywords: decision support systems, intelligent decision-making, systematic analysis, taxonomic review

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Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

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Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

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One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

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Authors: A. Gonzalez Aguna, J. M. Santamaria Garcia, J. L. Gomez Gonzalez, R. Barchino Plata, M. Fernandez Batalla, S. Herrero Jaen

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Background: Computer Science is a field that transcends other disciplines of knowledge because it allows to support all kinds of physical and mental tasks. Health centres have a greater number and complexity of technological devices and the population consume and demand services derived from technology. Also, nursing education plans have included competencies related to and, even, courses about new technologies are offered to health professionals. However, nurses still limit their performance to the use and evaluation of products previously built. Objective: Develop a teaching-learning methodology for acquiring skills on designing applications for care. Methodology: Blended learning teaching with a group of graduate nurses through official training within a Master's Degree. The study sample was selected by intentional sampling without exclusion criteria. The study covers from 2015 to 2017. The teaching sessions included a four-hour face-to-face class and between one and three tutorials. The assessment was carried out by written test consisting of the preparation of an IEEE 830 Standard Specification document where the subject chosen by the student had to be a problem in the area of care. Results: The sample is made up of 30 students: 10 men and 20 women. Nine students had a degree in nursing, 20 diploma in nursing and one had a degree in Computer Engineering. Two students had a degree in nursing specialty through residence and two in equivalent recognition by exceptional way. Except for the engineer, no subject had previously received training in this regard. All the sample enrolled in the course received the classroom teaching session, had access to the teaching material through a virtual area and maintained at least one tutoring. The maximum of tutorials were three with an hour in total. Among the material available for consultation was an example of a document drawn up based on the IEEE Standard with an issue not related to care. The test to measure competence was completed by the whole group and evaluated by a multidisciplinary teaching team of two computer engineers and two nurses. Engineers evaluated the correctness of the characteristics of the document and the degree of comprehension in the elaboration of the problem and solution elaborated nurses assessed the relevance of the chosen problem statement, the foundation, originality and correctness of the proposed solution and the validity of the application for clinical practice in care. The results were of an average grade of 8.1 over 10 points, a range between 6 and 10. The selected topic barely coincided among the students. Examples of care areas selected are care plans, family and community health, delivery care, administration and even robotics for care. Conclusion: The applied methodology of learning-teaching for the design of technologies demonstrates the success in the training of nursing professionals. The role of expert is essential to create applications that satisfy the needs of end users. Nursing has the possibility, the competence and the duty to participate in the process of construction of technological tools that are going to impact in care of people, family and community.

Keywords: care, learning, nursing, technology

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Authors: Marie Bountrogianni, Leonora Zefi, Krystle Phirangee, Naza Djafarova

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Faculty development is critical for any institution as it impacts students’ learning experiences and faculty performance with regards to course delivery. With that in mind, The Chang School at Ryerson University embarked on an initiative to develop a comprehensive, relevant faculty development program for online faculty and instructors. Teaching Adult Learners Online (TALO) is a professional development program designed to build capacity among online teaching faculty to enhance communication/facilitation skills for online instruction and establish a Community of Practice to allow for opportunities for online faculty to network and exchange ideas and experiences. TALO is comprised of four online modules and each module provides three hours of learning materials. The topics focus on online teaching and learning experience, principles and practices, opportunities and challenges in online assessments as well as course design and development. TALO offers a unique experience for online instructors who are placed in the role of a student and an instructor through interactivities involving discussions, hands-on assignments, peer mentoring while experimenting with technological tools available for their online teaching. Through exchanges and informal peer mentoring, a small interdisciplinary community of practice has started to take shape. Successful participants have to meet four requirements for completion: i) participate actively in online discussions and activities, ii) develop a communication plan for the course they are teaching, iii) design one learning activity/or media component, iv) design one online learning module. This study adopted a mixed methods exploratory sequential design. For the qualitative phase of this study, a thorough literature review was conducted on what constitutes effective faculty development programs. Based on that review, the design team identified desired competencies for online teaching/facilitation and course design. Once the competencies were identified, a focus group interview with The Chang School teaching community was conducted as a needs assessment and to validate the competencies. In the quantitative phase, questionnaires were distributed to instructors and faculty after the program was launched to continue ongoing evaluation and revisions, in hopes of further improving the program to meet the teaching community’s needs. Four faculty members participated in a one-hour focus group interview. Major findings from the focus group interview revealed that for the training program, faculty wanted i) to better engage students online, ii) to enhance their online teaching with specific strategies, iii) to explore different ways to assess students online. 91 faculty members completed the questionnaire in which findings indicated that: i) the majority of faculty stated that they gained the necessary skills to demonstrate instructor presence through communication and use of technological tools provided, ii) increased faculty confidence with course management strategies, iii) learning from peers is most effective – the Community of Practice is strengthened and valued even more as program alumni become facilitators. Although this professional development program is not mandatory for online instructors, since its launch in Fall 2014, over 152 online instructors have successfully completed the program. A Community of Practice emerged as a result of the program and participants continue to exchange thoughts and ideas about online teaching and learning.

Keywords: community of practice, customized, faculty development, inclusive design

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Authors: Maisam Rafiee, Chikashi Deguchi, Akio Odake, Minoru Matsui, Takanori Sata

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Cities in Afghanistan have been rapidly urbanized; however, many parts of these cities have been developed with no detailed land use plan or infrastructure. In other words, they have been informally developed without any government leadership. The new government started the In-situ Upgrading Project in Kabul to upgrade roads, the water supply network system, and the surface water drainage system on the existing street layout in 2002, with the financial support of international agencies. This project is an appropriate emergency improvement for living life, but not an essential improvement of living conditions and infrastructure problems because the life expectancies of the improved facilities are as short as 10–15 years, and residents cannot obtain land tenure in the unplanned areas. The Land Readjustment System (LRS) conducted in Japan has good advantages that rearrange irregularly shaped land lots and develop the infrastructure effectively. This study investigates the effects of the In-situ Upgrading Project on private investment, land prices, and residents’ satisfaction with projects in Kart-e-Char, where properties are registered, and in Afshar-e-Silo Lot 1, where properties are unregistered. These projects are located 5 km and 7 km from the CBD area of Kabul, respectively. This study discusses whether LRS should be applied to the unplanned area based on the questionnaire and interview responses of experts experienced in the In-situ Upgrading Project who have knowledge of LRS. The analysis results reveal that, in Kart-e-Char, a lot of private investment has been made in the construction of medium-rise (five- to nine-story) buildings for commercial and residential purposes. Land values have also incrementally increased since the project, and residents are commonly satisfied with the road pavement, drainage systems, and water supplies, but dissatisfied with the poor delivery of electricity as well as the lack of public facilities (e.g., parks and sport facilities). In Afshar-e-Silo Lot 1, basic infrastructures like paved roads and surface water drainage systems have improved from the project. After the project, a few four- and five-story residential buildings were built with very low-level private investments, but significant increases in land prices were not evident. The residents are satisfied with the contribution ratio, drainage system, and small increase in land price, but there is still no drinking water supply system or tenure security; moreover, there are substandard paved roads and a lack of public facilities, such as parks, sport facilities, mosques, and schools. The results of the questionnaire and interviews with the four engineers highlight the problems that remain to be solved in the unplanned areas if LRS is applied—namely, land use differences, types and conditions of the infrastructure still to be installed by the project, and time spent for positive consensus building among the residents, given the project’s budget limitation.

Keywords: in-situ upgrading, Kabul city, land readjustment, land value, planned area, private investment, residents' satisfaction, unplanned area

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Authors: Rahbel Rahman, Rogério Meireles Pinto, Margareth Santos Zanchetta

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Background: Existing shortcomings of current health-service delivery include poor teamwork, competencies that do not address consumer needs, and episodic rather than continuous care. Brazil’s Sistema Único de Saúde (Unified Health System, UHS) is acknowledged worldwide as a model for delivering community-based care through Estratégia Saúde da Família (FHS; Family Health Strategy) interdisciplinary teams, comprised of Community Health Agents (in Portuguese, Agentes Comunitário de Saude, ACS), nurses, and physicians. FHS teams are mandated to collectively offer clinical care, disease prevention services, vector control, health surveillance and social services. Our study compares medical providers (nurses and physicians) and community-based providers (ACS) on their perceptions of work environment, professional skills, cognitive capacities and job context. Global health administrators and policy makers can leverage on similarities and differences across care providers to develop interprofessional training for community-based primary care. Methods: Cross-sectional data were collected from 168 ACS, 62 nurses and 32 physicians in Brazil. We compared providers’ demographic characteristics (age, race, and gender) and job context variables (caseload, work experience, work proximity to community, the length of commute, and familiarity with the community). Providers perceptions were compared to their work environment (work conditions and work resources), professional skills (consumer-input, interdisciplinary collaboration, efficacy of FHS teams, work-methods and decision-making autonomy), and cognitive capacities (knowledge and skills, skill variety, confidence and perseverance). Descriptive and bi-variate analysis, such as Pearson Chi-square and Analysis of Variance (ANOVA) F-tests, were performed to draw comparisons across providers. Results: Majority of participants were ACS (64%); 24% nurses; and 12% physicians. Majority of nurses and ACS identified as mixed races (ACS, n=85; nurses, n=27); most physicians identified as males (n=16; 52%), and white (n=18; 58%). Physicians were less likely to incorporate consumer-input and demonstrated greater decision-making autonomy than nurses and ACS. ACS reported the highest levels of knowledge and skills but the least confidence compared to nurses and physicians. ACS, nurses, and physicians were efficacious that FHS teams improved the quality of health in their catchment areas, though nurses tend to disagree that interdisciplinary collaboration facilitated their work. Conclusion: To our knowledge, there has been no study comparing key demographic and cognitive variables across ACS, nurses and physicians in the context of their work environment and professional training. We suggest that global health systems can leverage upon the diverse perspectives of providers to implement a community-based primary care model grounded in interprofessional training. Our study underscores the need for in-service trainings to instill reflective skills of providers, improve communication skills of medical providers and curative skills of ACS. Greater autonomy needs to be extended to community based providers to offer care integral to addressing consumer and community needs.

Keywords: global health systems, interdisciplinary health teams, community health agents, community-based care

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Authors: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

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Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Collen T. Masilo, Brane Semolic, Pieter Steyn

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The Internet Protocol Television (IPTV) and Hybrid Fibre-Coaxial (HFC) Broadband industrial sector landscape are rapidly changing and organisations within the industry need to stay competitive by exploring new business models so that they can be able to offer new services and products to customers. The business challenge in this industrial sector is meeting or exceeding high customer expectations across multiple content delivery modes. The increasing challenges in the IPTV and HFC broadband industrial sector encourage service providers to form strategic partnerships with key suppliers, marketing partners, advertisers, and technology partners. The need to form enterprise collaborative networks poses a challenge for any organisation in this sector, in selecting the right strategic partners who will ensure that the organisation’s services and products are marketed in new markets. Partners who will ensure that customers are efficiently supported by meeting and exceeding their expectations. Lastly, selecting cooperation partners who will represent the organisation in a positive manner, and contribute to improving the performance of the organisation. Companies in the IPTV and HFC broadband industrial sector tend to form informal partnerships with suppliers, vendors, system integrators and technology partners. Generally, partnerships are formed without thorough analysis of the real reason a company is forming collaborations, without proper evaluations of prospective partners using specific selection criteria, and with ineffective performance monitoring of partners to ensure that a firm gains real long term benefits from its partners and gains competitive advantage. Similar tendencies are illustrated in the research case study and are based on Skyline Communications, a global leader in end-to-end, multi-vendor network management and operational support systems (OSS) solutions. The organisation’s flagship product is the DataMiner network management platform used by many operators across multiple industries and can be referred to as a smart system that intelligently manages complex technology ecosystems for its customers in the IPTV and HFC broadband industry. The approach of the research is to develop the most efficient business model that can be deployed to improve a strategic partnership programme in order to significantly improve the performance and growth of organisations participating in a collaborative network in the IPTV and HFC broadband industrial sector. This involves proposing and implementing a new strategic partnership model and its main features within the industry which should bring about significant benefits for all involved companies to achieve value add and an optimal growth strategy. The proposed business model has been developed based on the research of existing relationships, value chains and business requirements in this industrial sector and validated in 'Skyline Communications'. The outputs of the business model have been demonstrated and evaluated in the research business case study the IPTV and HFC broadband service provider 'Skyline Communications'.

Keywords: growth, partnership, selection criteria, value chain

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Authors: Lourenco Camnahas, Eileen Willis, Greg Fisher, Jessie Gunson, Pascale Dettwiller, Charlene Thornton

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Stock-out of pharmaceuticals is a common issue at all level of health services in Timor-Leste, a small post-conflict country. This lead to the research questions: what are the current methods used to quantify pharmaceutical supplies; what factors contribute to the on-going pharmaceutical stock-out? The study examined factors that influence the pharmaceutical supply chain system. Methodology: Privett and Goncalvez dependency model has been adopted for the design of the qualitative interviews. The model examines pharmaceutical supply chain management at three management levels: management of individual pharmaceutical items, health facilities, and health systems. The interviews were conducted in order to collect information on inventory management, logistics management information system (LMIS) and the provision of pharmaceuticals. Andersen' behavioural model for healthcare utilization also informed the interview schedule, specifically factors linked to environment (healthcare system and external environment) and the population (enabling factors). Forty health professionals (bureaucrats, clinicians) and six senior officers from a United Nations Agency, a global multilateral agency and a local non-governmental organization were interviewed on their perceptions of factors (healthcare system/supply chain and wider environment) impacting on stock out. Additionally, policy documents for the entire healthcare system, along with population data were collected. Findings: An analysis using Pozzebon’s critical interpretation identified a range of difficulties within the system from poor coordination to failure to adhere to policy guidelines along with major difficulties with inventory management, quantification, forecasting, and budgetary constraints. Weak logistics management information system, lack of capacity in inventory management, monitoring and supervision are additional organizational factors that also contributed to the issue. There were various methods of quantification of pharmaceuticals applied in the government sector, and non-governmental organizations. Lack of reliable data is one of the major problems in the pharmaceutical provision. Global Fund has the best quantification methods fed by consumption data and malaria cases. There are other issues that worsen stock-out: political intervention, work ethic and basic infrastructure such as unreliable internet connectivity. Major issues impacting on pharmaceutical quantification have been identified. However, current data collection identified limitations within the Andersen model; specifically, a failure to take account of predictors in the healthcare system and the environment (culture/politics/social. The next step is to (a) compare models used by three non-governmental agencies with the government model; (b) to run the Andersen explanatory model for pharmaceutical expenditure for 2 to 5 drug items used by these three development partners in order to see how it correlates with the present model in terms of quantification and forecasting the needs; (c) to repeat objectives (a) and (b) using the government model; (d) to draw a conclusion about the strength.

Keywords: inventory management, pharmaceutical forecasting and quantification, pharmaceutical stock-out, pharmaceutical supply chain management

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Authors: S. MacDougall-Davis, S. Wysling, R. Willmore

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Background: The application of good non-technical skills, also known as crew resource management (CRM), is central to the delivery of safe, effective healthcare. The authors have been running remote trauma courses for over 10 years, primarily focussing on developing participants’ CRM in time-critical, high-stress clinical situations. The course has undergone an iterative process over the past 10 years. We employ a number of experiential learning techniques for improving CRM, including small group workshops, military command tasks, high fidelity simulations with reflective debriefs, and a ‘flipped classroom’, where participants are asked to create their own simulations and assess and debrief their colleagues’ CRM. We created a randomised simulation study to assess the impact of our course on UK medical students’ CRM, both at an individual and a teams level. Methods: Sixteen students took part. Four clinical scenarios were devised, designed to be of similar urgency and complexity. Professional moulage effects and experienced clinical actors were used to increase fidelity and to further simulate high-stress environments. Participants were block randomised into teams of 4; each team was randomly assigned to one pre-course simulation. They then underwent our 5 day remote trauma CRM course. Post-course, students were re-randomised into four new teams; each was randomly assigned to a post-course simulation. All simulations were videoed. The footage was reviewed by two independent CRM-trained assessors, who were blinded to the before/after the status of the simulations. Assessors used the internationally validated team emergency assessment measure (TEAM) to evaluate key areas of team performance, as well as a global outcome rating. Prior to the study, assessors had scored two unrelated scenarios using the same assessment tool, demonstrating 89% concordance. Participants also completed pre- and post-course questionnaires. Likert scales were used to rate individuals’ perceived NTS ability and their confidence to work in a team in time-critical, high-stress situations. Results: Following participation in the course, a significant improvement in CRM was observed in all areas of team performance. Furthermore, the global outcome rating for team performance was markedly improved (40-70%; mean 55%), thus demonstrating an impact at Level 4 of Kirkpatrick’s hierarchy. At an individual level, participants’ self-perceived CRM improved markedly after the course (35-70% absolute improvement; mean 55%), as did their confidence to work in a team in high-stress situations. Conclusion: Our study demonstrates that with a short, cost-effective course, using easily reproducible teaching sessions, it is possible to significantly improve participants’ CRM skills, both at an individual and, perhaps more importantly, at a teams level. The successful functioning of multi-disciplinary teams is vital in a healthcare setting, particularly in high-stress, time-critical situations. Good CRM is of paramount importance in these scenarios. The authors believe that these concepts should be introduced from the earliest stages of medical education, thus promoting a culture of effective CRM and embedding an early appreciation of the importance of these skills in enabling safe and effective healthcare.

Keywords: crew resource management, non-technical skills, training, simulation

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Authors: M. Fry, L. Fitzpatrick, Julie Considine, R. Z. Shaban, Kate Curtis

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Introduction: The vast majority of older Australians lives independently and are self-managing at home, despite a growing number living with a chronic illness that requires health intervention. Evidence shows that between 50% and 80% of people presenting to the emergency department (ED) are in pain. Australian EDs manage 7.2 million attendances every year and 1.4 million of these are people aged 65 years or more. Research shows that 28% of ED patients aged 65 years or more have Cognitive impairment (CI) associated with dementia, delirium and neurological conditions. Background: Traditional ED service delivery may not be suitable for older people who present with multiple, complex and ongoing illnesses. Likewise, ED clinical staff often perceive that their role should be focused more on immediate and potential lifethreatening illness and conditions which are episodic in nature. Therefore, the needs of older people and their family/carers may not be adequately addressed in the context of an ED presentation. Aim: We aimed to explore the utilisation and characteristics of older people presenting to four metropolitan EDs. Method: The findings being presented are part of a program of research exploring pain management practices for older persons with long bone fractures. The study was conducted across four metropolitan emergency departments of older patients (65years and over) and involved a 12-month randomised medical record audit (n=255). Results: ED presentations across four ED sites in 2012 numbered 168021, with 44778 (26.6%) patients aged 65 and over. Of the 44778 patients, the average age was 79.1 years (SD 8.54). There were more females 23932 (53.5%). The majority (26925: 85.0%) of older persons self-referred to the ED and lived independently. The majority arrived by ambulance (n=18553: 41.4%) and were allocated triage category was 3 (n=19,507:43.65%) or Triage category 4 at (n=15,389: 34.43%). The top five triage symptom presentations involved pain (n=8088; 18.25%), dyspnoea (n=4735; 10.7%), falls (n=4032; 9.1%), other (n=3984; 9.0%), cardiac (n=2987; 6.7%). The top five system based diagnostic presentations involved musculoskeletal (n=8902; 20.1%), cardiac (n=6704:15.0%), respiratory (n=4933; 11.0%), neurological (n=4909; 11.0%), gastroenterology (n=4321; 9.7%). On review of one tertiary hospital database the vital signs on average at time triage: Systolic Blood Pressure 143.6mmHg. Heart Rate 83.4 beats/minute; Respiratory Rate 18.5 breaths/ minute; Oxygen saturation 97.0% and Tympanic temperature 36.7 and Blood Glucose Level 7.4mmols/litre. The majority presented with a Glasgow Coma Score of 14 or higher. On average the older person stayed in the ED 4:56 (SD 3:28minutes).The average time to be seen was 39 minutes (SD 48 minutes). The majority of older persons were admitted (n=27562: 61.5%), did not wait for treatment (n= 8879: 0.02%) discharged home (n=16256: 36.0%). Conclusion: The vast majority of older persons are living independently, although many require admission on arrival to the ED. Many arrived in pain and with musculoskeletal injuries and or conditions. New models of care need to be considered, which may better support self-management and independent living of the older person and the National Emergency Access Targets.

Keywords: chronic, older person, aged care, emergency department

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Authors: Raptis Sotirios

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Health and social care (HSc) services planning and scheduling are facing unprecedented challenges due to the pandemic pressure and also suffer from unplanned spending that is negatively impacted by the global financial crisis. Data-driven can help to improve policies, plan and design services provision schedules using algorithms assist healthcare managers’ to face unexpected demands using fewer resources. The paper discusses services packing using statistical significance tests and machine learning (ML) to evaluate demands similarity and coupling. This is achieved by predicting the range of the demand (class) using ML methods such as CART, random forests (RF), and logistic regression (LGR). The significance tests Chi-Squared test and Student test are used on data over a 39 years span for which HSc services data exist for services delivered in Scotland. The demands are probabilistically associated through statistical hypotheses that assume that the target service’s demands are statistically dependent on other demands as a NULL hypothesis. This linkage can be confirmed or not by the data. Complementarily, ML methods are used to linearly predict the above target demands from the statistically found associations and extend the linear dependence of the target’s demand to independent demands forming, thus groups of services. Statistical tests confirm ML couplings making the prediction also statistically meaningful and prove that a target service can be matched reliably to other services, and ML shows these indicated relationships can also be linear ones. Zero paddings were used for missing years records and illustrated better such relationships both for limited years and in the entire span offering long term data visualizations while limited years groups explained how well patients numbers can be related in short periods or can change over time as opposed to behaviors across more years. The prediction performance of the associations is measured using Receiver Operating Characteristic(ROC) AUC and ACC metrics as well as the statistical tests, Chi-Squared and Student. Co-plots and comparison tables for RF, CART, and LGR as well as p-values and Information Exchange(IE), are provided showing the specific behavior of the ML and of the statistical tests and the behavior using different learning ratios. The impact of k-NN and cross-correlation and C-Means first groupings is also studied over limited years and the entire span. It was found that CART was generally behind RF and LGR, but in some interesting cases, LGR reached an AUC=0 falling below CART, while the ACC was as high as 0.912, showing that ML methods can be confused padding or by data irregularities or outliers. On average, 3 linear predictors were sufficient, LGR was found competing RF well, and CART followed with the same performance at higher learning ratios. Services were packed only if when significance level(p-value) of their association coefficient was more than 0.05. Social factors relationships were observed between home care services and treatment of old people, birth weights, alcoholism, drug abuse, and emergency admissions. The work found that different HSc services can be well packed as plans of limited years, across various services sectors, learning configurations, as confirmed using statistical hypotheses.

Keywords: class, cohorts, data frames, grouping, prediction, prob-ability, services

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Authors: Bonnie R. Brammall, Rhonda M. Garad, Helena J. Teede, Cheryce L. Harrison

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Introduction: Reproductive aged women are at high-risk for accelerated weight gain and obesity development, with pregnancy recognised as a critical contributory life phase. Healthy lifestyle interventions during the preconception and antenatal period improve maternal and infant health outcomes. Yet, interventions from preconception through to postpartum and translation and implementation into real-world healthcare settings remain limited. OptimalMe is a randomised, hybrid implementation effectiveness study of evidence-based healthy lifestyle intervention. Here, we report engagement, acceptability of the intervention during preconception, and self-reported behaviour change outcomes as a result of the preconception phase of the intervention. Methods: Reproductive aged women who upgraded their private health insurance to include pregnancy and birth cover, signalling a pregnancy intention, were invited to participate. Women received access to an online portal with preconception health and lifestyle modules, goal-setting and behaviour change tools, monthly SMS messages, and two coaching sessions (randomised to video or phone) prior to pregnancy. Results: Overall n=527 expressed interest in participating. Of these, n=33 did not meet inclusion criteria, n=8 were not contactable for eligibility screening, and n=177 failed to engage after the screening, leaving n=309 who were enrolled in OptimalMe and randomised to intervention delivery method. Engagement with coaching sessions dropped by 25% for session two, with no difference between intervention groups. Women had a mean (SD) age of 31.7 (4.3) years and, at baseline, a self-reported mean BMI of 25.7 (6.1) kg/m², with 55.8% (n=172) of a healthy BMI. Behaviour was sub-optimal with infrequent self-weighing (38.1%), alcohol consumption prevalent (57.1%), sub-optimal pre-pregnancy supplementation (61.5%), and incomplete medical screening. Post-intervention 73.2% of women reported engagement with a GP for preconception care and improved lifestyle behaviour (85.5%), since starting OptimalMe. Direct pre-and-post comparison of individual participant data showed that of 322 points of potential change (up-to-date cervical screening, elimination of high-risk behaviours [alcohol, drugs, smoking], uptake of preconception supplements and improved weighing habits) 158 (49.1%) points of change were achieved. Health coaching sessions were found to improve accountability and confidence, yet further personalisation and support were desired. Engagement with video and phone sessions was comparable, having similar impacts on behaviour change, and both methods were well accepted and increased women's accountability. Conclusion: A low-intensity digital health and lifestyle program with embedded health coaching can improve the uptake of preconception care and lead to self-reported behaviour change. This is the first program of its kind to reach an otherwise healthy population of women planning a pregnancy. Women who were otherwise healthy showed divergence from preconception health and lifestyle objectives and benefited from the intervention. OptimalMe shows promising results for population-based behaviour change interventions that can improve preconception lifestyle habits and increase engagement with clinical health care for pregnancy preparation.

Keywords: preconception, pregnancy, preventative health, weight gain prevention, self-management, behaviour change, digital health, telehealth, intervention, women's health

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Abiodun Amusan, Olugbenga Akinola, Kazeem Akano, María Hernández-Castañeda, Jenna Dick, Akintunde Sowunmi, Geoffrey Hart, Grace Gbotosho

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Introduction: Artemisinin-based Combination Therapy (ACTs) is the cornerstone malaria treatment option in most malaria-endemic countries. Unfortunately, the malaria control effort is constantly being threatened by resistance of Plasmodium falciparum to ACTs. The recent evidence of artemisinin resistance in East Africa and its possibility of spreading to other African regions portends an imminent health catastrophe. This study aimed at evaluating the occurrence, prevalence, and influence of artemisinin-resistance markers on treatment outcomes in Ibadan before and after post-adoption of artemisinin combination therapy (ACTs) in Nigeria in 2005. Method: The study involved day zero dry blood spot (DBS) obtained from malaria patients during retrospective (2000-2005) and prospective (2021) studies. A cohort in the prospective study received oral dihydroartemisinin-piperaquine and underwent a 42-day follow-up to observe treatment outcomes. Genomic DNA was extracted from the DBS samples using a QIAamp blood extraction kit. Fragments of P. falciparum kelch13 (Pfkelch13), P. falciparum coronin (Pfcoronin), P. falciparum multidrug resistance 2 (PfMDR2), and P. falciparum chloroquine resistance transporter (PfCRT) genes were amplified and sequenced on a sanger sequencing platform to identify artemisinin resistance-associated mutations. Mutations were identified by aligning sequenced data with reference sequences obtained from the National Center for Biotechnology Information. Data were analyzed using descriptive statistics and student t-tests. Results: Mean parasite clearance time (PCT) and fever clearance time (FCT) were 2.1 ± 0.6 days (95% CI: 1.97-2.24) and 1.3 ± 0.7 days (95% CI: 1.1-1.6) respectively. Four mutations, K189T [34/53(64.2%)], R255K [2/53(3.8%)], K189N [1/53(1.9%)] and N217H [1/53(1.9%)] were identified within the N-terminal (Coiled-coil containing) domain of Pfkelch13. No artemisinin resistance-associated mutation usually found within the β-propeller domain of the Pfkelch13 gene was found in these analyzed samples. However, K189T and R255K mutations showed a significant correlation with longer parasite clearance time in the patients (P<0.002). The observed Pfkelch13 gene changes did not influence the baseline mean parasitemia (P = 0.44). P76S [17/100 (17%)] and V62M [1/100 (1%)] changes were identified in the Pfcoronin gene fragment without any influence on the parasitological parameters. No change was observed in the PfMDR2 gene, while no artemisinin resistance-associated mutation was found in the PfCRT gene. Furthermore, a sample each in the retrospective study contained the Pfkelch13 K189T and Pfcoronin P76S mutations. Conclusion: The study revealed absence of genetic-based evidence of artemisinin resistance in the study population at the time of study. The high frequency of K189T Pfkelch13 mutation and its correlation with increased parasite clearance time in this study may depict geographical variation of resistance mediators and imminent artemisinin resistance, respectively. The study also revealed an inherent potential of parasites to harbour drug-resistant genotypes before the introduction of ACTs in Nigeria.

Keywords: artemisinin resistance, plasmodium falciparum, Pfkelch13 mutations, Pfcoronin

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Authors: Trenten Theis, Trevor Daubert, Kennedy Kluthe, Austin Nuxoll

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Staphylococcus aureus is a gram-positive bacterium responsible for an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union annually. Recurring S. aureus bacteremia is associated with biofilm-mediated infections and can occur in 5 - 20% of cases, even with the use of antibiotics. Despite these infections being caused by drug-susceptible pathogens, they are surprisingly difficult to eradicate. One potential explanation for this is the presence of persister cells—a dormant type of cell that shows a high tolerance to antibiotic treatment. Recent studies have shown a connection between low intracellular ATP and persister cell formation. Specifically, this decrease in ATP, and therefore increase in persister cell formation, is due to an interrupted tricarboxylic acid (TCA) cycle. However, S. aureus persister cells’ role in pathogenesis remains unclear. Initial studies have shown that a fumC (TCA cycle gene) knockout survives challenge from aspects of the innate immune system better than wild-type S. aureus. Specifically, challenges from two antimicrobial peptides--LL-37 and hBD-3—show a log increase in survival of the fumC::N∑ strain compared to wild type S. aureus after 18 hours. Furthermore, preliminary studies show that the fumC knockout has a log more survival within a macrophage. These data lead us to hypothesize that the fumC knockout is better suited to other aspects of the innate immune system compared to wild-type S. aureus. To further investigate the mechanism for increased survival of fumC::N∑ within a macrophage, we tested bacterial growth in the presence of reactive oxygen species (ROS), reactive nitrogen species (RNS), and a low pH. Preliminary results suggest that the fumC knockout has increased growth compared to wild-type S. aureus in the presence of all three antimicrobial factors; however, no difference was observed in any single factor alone. To investigate survival within a host, a nine-day biofilm-associated catheter infection was performed on 6–8-week-old male and female C57Bl/6 mice. Although both sexes struggled to clear the infection, female mice were trending toward more frequently clearing the HG003 wild-type infection compared to the fumC::N∑ infection. One possible reason for the inability to reduce the bacterial burden is that biofilms are largely composed of persister cells. To test this hypothesis further, flow cytometry in conjunction with a persister cell marker was used to measure persister cells within a biofilm. Cap5A (a known persister cell marker) expression was found to be increased in a maturing biofilm, with the lowest levels of expression seen in immature biofilms and the highest expression exhibited by the 48-hour biofilm. Additionally, bacterial cells in a biofilm state closely resemble persister cells and exhibit reduced membrane potential compared to cells in planktonic culture, further suggesting biofilms are largely made up of persister cells. These data may provide an explanation as to why infections caused by antibiotic-susceptible strains remain difficult to treat.

Keywords: antibiotic tolerance, Staphylococcus aureus, host-pathogen interactions, microbial pathogenesis

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Authors: Sini George

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Active learning pedagogies are valued for their success in increasing 21st-century learners’ engagement, developing transferable skills like critical thinking or quantitative reasoning, and creating deeper and more lasting educational gains. 'Blended learning' is an active learning pedagogical approach in which direct instruction moves from the group learning space to the individual learning space, and the resulting group space is transformed into a dynamic, interactive learning environment where the educator guides students as they apply concepts and engage creatively in the subject matter. This project aimed to develop a blended learning instructional approach to teaching concepts around pharmaceutical calculations to year 1 pharmacy students. The wrong dose, strength or frequency of a medication accounts for almost a third of medication errors in the NHS therefore, progression to year 2 requires a 70% pass in this calculation test, in addition to the standard progression requirements. Many students were struggling to achieve this requirement in the past. It was also challenging to teach these concepts to students of a large class (> 130) with mixed mathematical abilities, especially within a traditional didactic lecture format. Therefore, short screencasts with voice-over of the lecturer were provided in advance of a total of four teaching sessions (two hours/session), incorporating core content of each session and talking through how they approached the calculations to model metacognition. Links to the screencasts were posted on the learning management. Viewership counts were used to determine that the students were indeed accessing and watching the screencasts on schedule. In the classroom, students had to apply the knowledge learned beforehand to a series of increasingly difficult set of questions. Students were then asked to create a question in group settings (two students/group) and to discuss the questions created by their peers in their groups to promote deep conceptual learning. Students were also given time for question-and-answer period to seek clarifications on the concepts covered. Student response to this instructional approach and their test grades were collected. After collecting and organizing the data, statistical analysis was carried out to calculate binomial statistics for the two data sets: the test grade for students who received blended learning instruction and the test grades for students who received instruction in a standard lecture format in class, to compare the effectiveness of each type of instruction. Student response and their performance data on the assessment indicate that the learning of content in the blended learning instructional approach led to higher levels of student engagement, satisfaction, and more substantial learning gains. The blended learning approach enabled each student to learn how to do calculations at their own pace freeing class time for interactive application of this knowledge. Although time-consuming for an instructor to implement, the findings of this research demonstrate that the blended learning instructional approach improves student academic outcomes and represents a valuable method to incorporate active learning methodologies while still maintaining broad content coverage. Satisfaction with this approach was high, and we are currently developing more pharmacy content for delivery in this format.

Keywords: active learning, blended learning, deep conceptual learning, instructional approach, metacognition, pharmaceutical calculations

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Authors: S. N. T. I. Sampath, J. M. S. Jayasinghe, A. P. Attanayake, V. Karunaratne

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Diabetes mellitus is one of the major public health posers throughout the world today that incidence and associated with increasing mortality. Insufficient regulation of the blood glucose level might be serious effects for health and its necessity to identify new therapeutics that have ability to reduce hyperglycaemic condition in the human body. Even though synthetic antidiabetic drugs are more effective to control diabetes mellitus, there are considerable side effects have been reported. Thus, there is an increasing demand for searching new natural products having high antidiabetic activity with lesser side effects. The purposes of the present study were to evaluate different physical parameters and in-vitro and in-vivo antidiabetic potential of the selected combined medicinal plant extracts mixture composed of leaves of Murraya koenigii, cloves of Allium sativum, fruits of Garcinia queasita and seeds of Piper nigrum. The selected plants parts were mixed and ground together and extracted sequentially into the hexane, ethyl acetate and methanol. Solvents were evaporated and they were further dried by freeze-drying to obtain a fine powder of each extract. Various physical parameters such as moisture, total ash, acid insoluble ash and water soluble ash were evaluated using standard test procedures. In-vitro antidiabetic activity of combined plant extracts mixture was screened using enzyme assays such as α-amylase inhibition assay and α-glucosidase inhibition assay. The acute anti-hyperglycaemic activity was performed using oral glucose tolerance test for the streptozotocin induced diabetic Wistar rats to find out in-vivo antidiabetic activity of combined plant extracts mixture and it was assessed through total oral glucose tolerance curve (TAUC) values. The percentage of moisture content, total ash content, acid insoluble ash content and water soluble ash content were ranged of 7.6-17.8, 8.1-11.78, 0.019-0.134 and 6.2-9.2 respectively for the plant extracts and those values were less than standard values except the methanol extract. The hexane and ethyl acetate extracts exhibited highest α-amylase (IC50 = 25.7 ±0.6; 27.1 ±1.2 ppm) and α-glucosidase (IC50 = 22.4 ±0.1; 33.7 ±0.2 ppm) inhibitory activities than methanol extract (IC50 = 360.2 ±0.6; 179.6 ±0.9 ppm) when compared with the acarbose positive control (IC50 = 5.7 ±0.4; 17.1 ±0.6 ppm). The TAUC values for hexane, ethyl acetate, and methanol extracts and glibenclamide (positive control) treated rats were 8.01 ±0.66; 8.05 ±1.07; 8.40±0.50; 5.87 ±0.93 mmol/L.h respectively, whereas in diabetic control rats the TAUC value was 13.22 ±1.07 mmol/L.h. Administration of plant extracts treated rats significantly suppressed (p<0.05) the rise in plasma blood glucose levels compared to control rats but less significant than glibenclamide. The obtained results from in-vivo and in-vitro antidiabetic study showed that the hexane and ethyl acetate extracts of selected combined plant mixture might be considered as a potential source to isolate natural antidiabetic agents and physical parameters of hexane and ethyl acetate extracts will helpful to develop antidiabetic drug with further standardize properties.

Keywords: diabetes mellitus, in-vitro antidiabetic assays, medicinal plants, standardization

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Authors: Sarwan Dhir, Suma Basak, Dipika Parajulee

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Alfalfa is renowned for its nutritional and biopharmaceutical value as a perennial forage legume. However, establishing a rapid plant regeneration protocol using somatic embryogenesis and efficient transformation frequency are the crucial prerequisites for gene editing in alfalfa. This study was undertaken to establish and improve the protocol for somatic embryogenesis and subsequent plant regeneration. The experiments were conducted in response to natural sensitivity using various antibiotics such as cefotaxime, carbenicillin, gentamycin, hygromycin, and kanamycin. Using 3-week-old leaf tissue, somatic embryogenesis was initiated on Gamborg’s B5 basal (B5H) medium supplemented with 3% maltose, 0.9µM Kinetin, and 4.5µM 2,4-D. Embryogenic callus (EC) obtained from the B5H medium exhibited a high rate of somatic embryo formation (97.9%) after 3 weeks when the cultures were placed in the dark. Different developmental stages of somatic embryos and cotyledonary stages were then transferred to Murashige and Skoog’s (MS) basal medium under light, resulting in a 94% regeneration rate of plantlets. Our results indicate that leaf segments can grow (tolerate) up to 450 mg/L of cefotaxime and 400 mg/L of carbenicillin in the culture medium. However, the survival threshold for hygromycin at 12.5 mg/L, kanamycin at 250 mg/L, gentamycin at 50 mg/L, and timentin (300 mg/L). The experiment to improve the protocol for achieving efficient transient gene expression in alfalfa through genetic transformation with the Agrobacterium tumefaciens pCAMBIA1304 vector was also conducted. The vector contains two reporter genes such as β-glucuronidase (GUS) and green fluorescent protein (GFP), along with a selectable hygromycin B phosphotransferase gene (HPT), all driven under the CaMV 35s promoter. Various transformation parameters were optimized using 3-week-old in vitro-grown plantlets. The different parameters such as types of explant, leaf ages, preculture days, segment sizes, wounding types, bacterial concentrations, infection periods, co-cultivation periods, different concentrations of acetosyringone, silver nitrate, and calcium chloride were optimized for transient gene expression. The transient gene expression was confirmed via histochemical GUS and GFP visualization under fluorescent microscopy. The data were analyzed based on the semi-quantitative observation of the percentage and number of blue GUS spots on different days of agro-infection. The highest percentage of GUS positivity (76.2%) was observed in 3-week-old leaf segments wounded using a scalpel blade of 11 size- after 3 days of post-incubation at a bacterial concentration of 0.6, with 2 days of preculture, 30 min of bacterial-leaf segment co-cultivation, with the addition of 150 µM acetosyringone, 4 mM calcium chloride, and 75 µM silver nitrate. Our results suggest that various factors influence T-DNA delivery in the Agrobacterium-mediated transformation of alfalfa. The stable gene expression in the putative transgenic tissue was confirmed using PCR amplification of both marker genes, indicating that gene expression in explants was not solely due to Agrobacterium, but also from transformed cells. The improved protocol could be used for generating transgenic alfalfa plants using genome editing techniques such as CRISPR/Cas9.

Keywords: Medicago sativa l. (Alfalfa), agrobacterium tumefaciens, β-glucuronidase, green fluorescent protein, transient gene

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Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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Authors: Ma Chu Jui

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Culture plays a pivotal role in shaping societal responses to change and fostering adaptability. In the realm of healthcare provision, hospitals serve as dynamic settings molded by the cultural consciousness of healthcare professionals. This intricate interplay extends to their expectations of leadership, communication styles, and attitudes towards patient care. Recognizing the cultural inclinations of healthcare professionals becomes imperative in navigating this complex landscape. This study will utilize Hofstede's Value Survey Module 2013 (VSM 2013) as a comprehensive analytical tool. The targeted participants for this research are in-service nursing professionals with a tenure of at least three months, specifically employed in the nursing department of an Eastern hospital. This quantitative approach seeks to quantify diverse cultural tendencies among the targeted nursing professionals, elucidating not only abstract cultural concepts but also revealing their cultural inclinations across different dimensions. The study anticipates gathering between 400 to 500 responses, ensuring a robust dataset for a comprehensive analysis. The focused approach on nursing professionals within the Eastern hospital setting enhances the relevance and specificity of the cultural insights obtained. The research aims to contribute valuable knowledge to the understanding of cultural tendencies among in-service nursing personnel in the nursing department of this specific Eastern hospital. The VSM 2013 will be initially distributed to this specific group to collect responses, aiming to calculate scores on each of Hofstede's six cultural dimensions—Power Distance Index (PDI), Individualism vs. Collectivism (IDV), Uncertainty Avoidance Index (UAI), Masculinity vs. Femininity (MAS), Long-Term Orientation vs. Short-Term Normative Orientation (LTO), and Indulgence vs. Restraint (IVR). the study unveils a significant correlation between different cultural dimensions and healthcare professionals' tendencies in understanding leadership expectations through PDI, grasping behavioral patterns via IDV, acknowledging risk acceptance through UAI, and understanding their long-term and short-term behaviors through LTO. These tendencies extend to communication styles and attitudes towards patient care. These findings provide valuable insights into the nuanced interconnections between cultural factors and healthcare practices. Through a detailed analysis of the varying levels of these cultural dimensions, we gain a comprehensive understanding of the predominant inclinations among the majority of healthcare professionals. This nuanced perspective adds depth to our comprehension of how cultural values shape their approach to leadership, communication, and patient care, contributing to a more holistic understanding of the healthcare landscape. A profound comprehension of the cultural paradigms embraced by healthcare professionals holds transformative potential. Beyond a mere understanding, it acts as a catalyst for elevating the caliber of healthcare services. This heightened awareness fosters cohesive collaboration among healthcare teams, paving the way for the establishment of a unified healthcare ethos. By cultivating shared values, our study envisions a healthcare environment characterized by enhanced quality, improved teamwork, and ultimately, a more favorable and patient-centric healthcare landscape. In essence, our research underscores the critical role of cultural awareness in shaping the future of healthcare delivery.

Keywords: hofstede's cultural, cultural dimensions, cultural values in healthcare, cultural awareness in nursing

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Authors: Loyd R. Hook, Maryam Moharek

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With the envisioned future growth of low altitude urban aircraft operations for airborne delivery service and advanced air mobility, strategies to coordinate and deconflict aircraft flight paths must be prioritized. Autonomous coordination and planning of flight trajectories is the preferred approach to the future vision in order to increase safety, density, and efficiency over manual methods employed today. Difficulties arise because any conflict resolution must be constrained by all other aircraft, all airspace restrictions, and all ground-based obstacles in the vicinity. These considerations make pair-wise tactical deconfliction difficult at best and unlikely to find a suitable solution for the entire system of vehicles. In addition, more traditional methods which rely on long time scales and large protected zones will artificially limit vehicle density and drastically decrease efficiency. Instead, strategic planning, which is able to respond to highly dynamic conditions and still account for high density operations, will be required to coordinate multiple vehicles in the highly constrained low altitude urban environment. This paper develops and evaluates such a planning algorithm which can be implemented autonomously across multiple aircraft and situations. Data from this evaluation provide promising results with simulations showing up to 10 aircraft deconflicted through a relatively narrow low-altitude urban canyon without any vehicle to vehicle or obstacle conflict. The algorithm achieves this level of coordination beginning with the assumption that each vehicle is controlled to follow an independently constructed flight path, which is itself free of obstacle conflict and restricted airspace. Then, by preferencing speed change deconfliction maneuvers constrained by the vehicles flight envelope, vehicles can remain as close to the original planned path and prevent cascading vehicle to vehicle conflicts. Performing the search for a set of commands which can simultaneously ensure separation for each pair-wise aircraft interaction and optimize the total velocities of all the aircraft is further complicated by the fact that each aircraft's flight plan could contain multiple segments. This means that relative velocities will change when any aircraft achieves a waypoint and changes course. Additionally, the timing of when that aircraft will achieve a waypoint (or, more directly, the order upon which all of the aircraft will achieve their respective waypoints) will change with the commanded speed. Put all together, the continuous relative velocity of each vehicle pair and the discretized change in relative velocity at waypoints resembles a hybrid reachability problem - a form of control reachability. This paper proposes two methods for finding solutions to these multi-body problems. First, an analytical formulation of the continuous problem is developed with an exhaustive search of the combined state space. However, because of computational complexity, this technique is only computable for pairwise interactions. For more complicated scenarios, including the proposed 10 vehicle example, a discretized search space is used, and a depth-first search with early stopping is employed to find the first solution that solves the constraints.

Keywords: strategic planning, autonomous, aircraft, deconfliction

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Authors: Mingxin Li, Liya Ni

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Autonomous parking is a valuable feature applicable to many robotics applications such as tour guide robots, UV sanitizing robots, food delivery robots, and warehouse robots. With auto-parking, the robot will be able to park at the charging zone and charge itself without human intervention. As compared to self-driving vehicles, auto-parking is more challenging for a small-scale mobile robot only equipped with a front camera due to the camera view limited by the robot’s height and the narrow Field of View (FOV) of the inexpensive camera. In this research, auto-parking of a small-scale mobile robot with a front camera only was achieved in a four-step process: Firstly, transfer learning was performed on the AlexNet, a popular pre-trained convolutional neural network (CNN). It was trained with 150 pictures of empty parking slots and 150 pictures of occupied parking slots from the view angle of a small-scale robot. The dataset of images was divided into a group of 70% images for training and the remaining 30% images for validation. An average success rate of 95% was achieved. Secondly, the image of detected empty parking space was processed with edge detection followed by the computation of parametric representations of the boundary lines using the Hough Transform algorithm. Thirdly, the positions of the entrance point and center of available parking space were predicted based on the robot kinematic model as the robot was driving closer to the parking space because the boundary lines disappeared partially or completely from its camera view due to the height and FOV limitations. The robot used its wheel speeds to compute the positions of the parking space with respect to its changing local frame as it moved along, based on its kinematic model. Lastly, the predicted entrance point of the parking space was used as the reference for the motion control of the robot until it was replaced by the actual center when it became visible again by the robot. The linear and angular velocities of the robot chassis center were computed based on the error between the current chassis center and the reference point. Then the left and right wheel speeds were obtained using inverse kinematics and sent to the motor driver. The above-mentioned four subtasks were all successfully accomplished, with the transformed learning, image processing, and target prediction performed in MATLAB, while the motion control and image capture conducted on a self-built small scale differential drive mobile robot. The small-scale robot employs a Raspberry Pi board, a Pi camera, an L298N dual H-bridge motor driver, a USB power module, a power bank, four wheels, and a chassis. Future research includes three areas: the integration of all four subsystems into one hardware/software platform with the upgrade to an Nvidia Jetson Nano board that provides superior performance for deep learning and image processing; more testing and validation on the identification of available parking space and its boundary lines; improvement of performance after the hardware/software integration is completed.

Keywords: autonomous parking, convolutional neural network, image processing, kinematics-based prediction, transfer learning

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Authors: Aberdam Edith, Sangari Linda, Petit Isabelle, Aberdam Daniel

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Background and Rationale: Transparent avascularised cornea is essential for normal vision and depends on limbal stem cells (LSC) that reside between the cornea and the conjunctiva. Ocular burns or injuries may destroy the limbus, causing limbal stem cell deficiency (LSCD). The cornea becomes vascularised by invaded conjunctival cells, the stroma is scarring, resulting in corneal opacity and loss of vision. Grafted autologous limbus or cultivated autologous LCS can restore the vision, unless the two eyes are affected. Alternative cellular sources have been tested in the last decades, including oral mucosa or hair follicle epithelial cells. However, only partial success has been achieved by the use of these cells since they were not able to uniformly commit into corneal epithelial cells. Human pluripotent stem cells (iPSC) display both unlimited growth capacity and ability to differentiate into any cell type. Our goal was to design a standardized and reproducible protocol to produce transplantable autologous LSC from patients through cell reprogramming technology. Methodology: First, keratinocyte primary culture was established from a small number of plucked hair follicles of healthy donors. The resulting epithelial cells were reprogrammed into induced pluripotent stem cells (iPSCs) and further differentiate into corneal epithelial cells (CEC), according to a robust protocol that recapitulates the main step of corneal embryonic development. qRT-PCR analysis and immunofluorescent staining during the course of differentiation confirm the expression of stage specific markers of corneal embryonic lineage. First appear ectodermal progenitor-specific cytokeratins K8/K18, followed at day 7 by limbal-specific PAX6, TP63 and cytokeratins K5/K14. At day 15, K3/K12+-corneal cells are present. To amplify the iPSC-derived LSC (named COiPSC), intact small epithelial colonies were detached and cultivated in limbal cell-specific medium. In that culture conditions, the COiPSC can be frozen and thaw at any passage, while retaining their corneal characteristics for at least eight passages. To evaluate the potential of COiPSC as an alternative ocular toxicity model, COiPSC were treated at passage P0 to P4 with increasing amounts of SDS and Benzalkonium. Cell proliferation and apoptosis of treated cells was compared to LSC and the SV40-immortalized human corneal epithelial cell line (HCE) routinely used by cosmetological industrials. Of note, HCE are more resistant to toxicity than LSC. At P0, COiPSC were systematically more resistant to chemical toxicity than LSC and even to HCE. Remarkably, this behavior changed with passage since COiPSC at P2 became identical to LSC and thus closer to physiology than HCE. Comparative transcriptome analysis confirmed that COiPSC from P2 are similar to a mixture of LSC and CEC. Finally, by organotypic reconstitution assay, we demonstrated the ability of COiPSC to produce a 3D corneal epithelium on a stromal equivalent made of keratocytes. Conclusion: COiPSC could become valuable for two main applications: (1) an alternative robust tool to perform, in a reproducible and physiological manner, toxicity assays for cosmetic products and pharmacological tests of drugs. (2). COiPSC could become an alternative autologous source for cornea transplantation for LSCD.

Keywords: Limbal stem cell deficiency, iPSC, cornea, limbal stem cells

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Authors: Supriyo Das, Elbir Jove, Ajay Singh, Sophie Corbet, Noel Carr, Martin Deetz

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Water is a critical commodity in the healthcare and medical field. The utility of medical-grade water spans from washing surgical equipment, drug preparation to the key element of life-saving therapy such as hydrotherapy and hemodialysis for patients. A properly treated medical water reduces the bioburden load and mitigates the risk of infection, ensuring patient safety. However, any compromised condition during the production of medical-grade water can create a favorable environment for microbial growth putting patient safety at high risk. Therefore, proper upstream treatment of the medical water is essential before its application in healthcare, pharma and medical space. Reverse Osmosis (RO) is one of the most preferred treatments within healthcare industries and is recommended by all International Pharmacopeias to achieve the quality level demanded by global regulatory bodies. The RO process can remove up to 99.5% of constituents from feed water sources, eliminating bacteria, proteins and particles sizes of 100 Dalton and above. The combination of RO with other downstream water treatment technologies such as Electrodeionization and Ultrafiltration meet the quality requirements of various pharmacopeia monographs to produce highly purified water or water for injection for medical use. In the reverse osmosis process, the water from a liquid with a high concentration of dissolved solids is forced to flow through an especially engineered semi-permeable membrane to the low concentration side, resulting in high-quality grade water. However, these specially engineered RO membranes need to be sanitized either chemically or at high temperatures at regular intervals to keep the bio-burden at the minimum required level. In this paper, we talk about Dupont´s FilmTec Heat Sanitizable Reverse Osmosis membrane (HSRO) for the production of medical-grade water. An HSRO element must be pre-conditioned prior to initial use by exposure to hot water (80°C-85°C) for its stable performance and to meet the manufacturer’s specifications. Without pre-conditioning, the membrane will show variations in feed pressure operations and salt rejection. The paper will discuss the critical variables of pre-conditioning steps that can affect the overall performance of the HSRO membrane and demonstrate the data to support the need for pre-conditioning of HSRO elements. Our preliminary data suggests that there can be up to 35 % reduction in flow due to initial heat treatment, which also positively affects the increase in salt rejection. The paper will go into detail about the fundamental understanding of the performance change of HSRO after the pre-conditioning step and its effect on the quality of medical water produced. The paper will also discuss another critical point, “regular hot water sanitization” of these HSRO membranes. Regular hot water sanitization (at 80°C-85°C) is necessary to keep the membrane bioburden free; however, it can negatively impact the performance of the membrane over time. We will demonstrate several data points on hot water sanitization using FilmTec HSRO elements and challenge its robustness to produce quality medical water. The last part of this paper will discuss the construction details of the FilmTec HSRO membrane and features that make it suitable to pre-condition and sanitize at high temperatures.

Keywords: heat sanitizable reverse osmosis, HSRO, medical water, hemodialysis water, water for Injection, pre-conditioning, heat sanitization

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Authors: Nahla Elsherbiny, Ahmed Ahmed, Hamada Mohammed, Mohamed Ali

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Background: The enterococci may be considered as opportunistic agents particularly in immunocompromised patients. It is one of the top three pathogens causing many healthcare associated infections (HAIs). Resistance to several commonly used antimicrobial agents is a remarkable characteristic of most species which may carry various genes contributing to virulence. Objectives: to determine the prevalence of enterococci species in different intensive care units (ICUs) causing health care-associated infections (HAIs), intestinal carriage and environmental contamination. Also, to study the antimicrobial susceptibility pattern of the isolates with special reference to vancomycin resistance. In addition to phenotypic and genotypic detection of gelatinase, cytolysin and biofilm formation among isolates. Patients and Methods: This study was carried out in the infection control laboratory at Assiut University Hospitals over a period of one year. Clinical samples were collected from 285 patients with various (HAIs) acquired after admission to different ICUs. Rectal swabs were taken from 14 cases for detection of enterococci carriage. In addition, 1377 environmental samples were collected from the surroundings of the patients. Identification was done by conventional bacteriological methods and confirmed by analytical profile index (API). Antimicrobial sensitivity testing was performed by Kirby Bauer disc diffusion method and detection of vancomycin resistance was done by agar screen method. For the isolates, phenotypic detection of cytolysin, gelatinase production and detection of biofilm by tube method, Congo red method and microtiter plate. We performed polymerase chain reaction (PCR) for detection of some virulence genes (gelE, cylA, vanA, vanB and esp). Results: Enterococci caused 10.5% of the HAIs. Respiratory tract infection was the predominant type (86.7%). The commonest species were E.gallinarum (36.7%), E.casseliflavus (30%), E.faecalis (30%), and E.durans (3.4 %). Vancomycin resistance was detected in a total of 40% (12/30) of those isolates. The risk factors associated with acquiring vancomycin resistant enterococci (VRE) were immune suppression (P= 0.031) and artificial feeding (P= 0.008). For the rectal swabs, enterococci species were detected in 71.4% of samples with the predominance of E. casseliflavus (50%). Most of the isolates were vancomycin resistant (70%). Out of a total 1377 environmental samples, 577 (42%) samples were contaminated with different microorganisms. Enterococci were detected in 1.7% (10/577) of total contaminated samples, 50% of which were vancomycin resistant. All isolates were resistant to penicillin, ampicillin, oxacillin, ciprofloxacin, amikacin, erythromycin, clindamycin and trimethoprim-sulfamethaxazole. For the remaining antibiotics, variable percentages of resistance were reported. Cytolysin and gelatinase were detected phenotypically in 16% and 48 % of the isolates respectively. The microtiter plate method showed the highest percentages of detection of biofilm among all isolated species (100%). The studied virulence genes gelE, esp, vanA and vanB were detected in 62%, 12%, 2% and 12% respectively, while cylA gene was not detected in any isolates. Conclusions: A significant percentage of enterococci was isolated from patients and environments in the ICUs. Many virulence factors were detected phenotypically and genotypically among isolates. The high percentage of resistance, coupled with the risk of cross transmission to other patients make enterococci infections a significant infection control issue in hospitals.

Keywords: antimicrobial resistance, enterococci, ICUs, virulence factors

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Authors: Md. Nuru Miah, A. F. M. Akhter Uddin

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Medicinal plants are grown naturally in a tropical environment in Bangladesh and used as drug and therapeutic agents in the health care system. According to Bangladesh Agricultural Research Institute (BARI), there are 722 species of medicinal plants in the country. Of them, 255 plants are utilized by the manufacturers of Ayurvedic and Unani medicines. Medicinal plants like Aloevera, Ashwagonda, shotomul,Tulsi, Vuikumra, Misridana are extensively cultivated in some selected areas as well; where Aloevera scored the highest position in production. In the early 1980, Ayurvedic and Unani companies procured 80 percent of medicinal plants from natural forests, and the rest 20 percent was imported. Now the scenario has changed; 80 percent is imported, and the rest 20 percent is collected from local products(Source: Astudy on sectorbased need assessment of Business promotion council-Herbal products and medicinal plants, page-4). Uttara Development Program Society, a leading Non- Government development organization in Bangladesh, has been implementing a value chain development project under promoting Agricultural commercialization and Enterprises of Pally Karma Sahayak Foundation (PKSF) funded by the International Fund for Agricultural Development (IFAD) in Natore Sadar Upazila from April 2017 to sustainably develop the technological interventions for products and market development. The ultimate goal of the project is to increase income, generate employment and develop this sector as a sustainable business enterprise. Altogether 10,000 farmers (Nursery owners, growers, input supplier, processors, whole sellers, and retailers) are engaged in different activities of the project. The entrepreneurs engaged in medicinal plant cultivation did not know and follow environmental and good agricultural practices. They used to adopt traditional methodology in production and processing. Locally the farmers didn’t have any positive initiative to expand their business as well as developvalue added products. A lot of diversified products could be possible to develop and marketed with the introduction of post-harvest processing technology and market linkage with the local and global buyer. Training is imparted to the nursery owners and herbal growers on production technologies, sowing method, use of organic fertilizers/compost/pesticides, harvesting procedures, and storage facilities. Different types of herbal tea like Rosella, Moringa, Tulshi, and Basak are being produced and packed locally with a good scope of its marketing in different cities of the country. The project has been able to achieve a significant impact in the development of production technologies, but still, there is room for further improvement in processing, packaging, and marketing level. The core intervention of the current project to develop some entrepreneurs for branding, packaging, promotion, and marketing while considering environment friendly practices. The present strategies will strengthen the knowledge and skills of the entrepreneurs for the production and marketing of their products, maintaining worldwide accepted compliance system for easy access to the global market.

Keywords: aloe vera, herbs and shrubs, market, interventions

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