Search results for: macrophage targeting
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 709

Search results for: macrophage targeting

19 Deciphering Tumor Stroma Interactions in Retinoblastoma

Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

Abstract:

Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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18 Dietetics Practice in the Scope of Disease Prevention in Community Settings: A School-Based Obesity Prevention Program

Authors: Elham Abbas Aljaaly, Nahlaa Abdulwahab Khalifa

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The active method of disease prevention is seen as the most affordable and sustainable action to deal with risks of non-communicable diseases such as obesity. This eight-week project aimed to pilot the feasibility and acceptability of a school-based programme, which is proposed to prevent and modify overweight status and possible related risk factors among student girls 'at the intermediate level' in Jeddah city. The programme was conducted through comprehensible approach targeting physical environment and school policies (nutritional/exercise/behavioural approach). The programme was designed to cultivate the personal and environmental awareness in schools for girls. This was applied by promoting healthy eating and physical activity through policies, physical education, healthier options for school canteens, and the creation of school health teams. The prevention programme was applied on 68 students (who agreed to participate) from grades 7th, 8th and 9th. A pre and post assessment questionnaire was employed on 66 students. The questionnaires were designed to obtain information on students' knowledge about health, nutrition and physical activity. Survey questions included information about nutrients, food consumption patterns, food intake and lifestyle. Physical education included training sessions for new opportunities for physical activities to be performed during school or after school hours. A running competition 'to enhance students’ performance for physical activities' was also conducted during the school visit. A visit to the school canteen was conducted to check, observe, record and assess all available food/beverage items and meals. The assessment method was a subjective method for the type of food/beverages if high in saturated fat, salt and sugar (HFSS) or non-HFSS. The school canteen administrators were encouraged to provide healthy food/beverage items and a sample healthy canteen was provided for implementation. Two healthy options were introduced to the school canteen. A follow up for students’ preferences for the introduced options and the purchasing power were assessed. Thirty-eight percent of young girls (n=26) were not participating in any form of physical activities inside or outside school. Skipping breakfast was stated by 42% (n=28) of students with no daily consumption (19%, n=13) for fruit/vegetables. Significant changes were noticed in students’ (n=66) overall responses to the pre and post questions (P value=.001). All students had participated in the conducted running competition sessions and reported satisfaction and enjoyment about the sessions. No absence was reported by the research team for attending physical education and activity sessions throughout the delivered programme. The purchasing power of the introduced healthy options of 'Salad and oatmeal' was increased to 18% in 8 weeks at the school canteen, and slightly affected the purchase for other less healthy options. The piloted programme indorsed better health and nutrition knowledge, healthy eating and lifestyle attitude, which could help young girls to obtain sustainable changes. It is expected that the outcomes of the programme will be a cornerstone for the futuristic national study that will assist policy makers and participants to build a knowledgeable health promotion scenario and make sure that school students have access to healthy foods, physical exercise and healthy lifestyle.

Keywords: adolescents, diet, exercise, behaviours, overweight/obesity, prevention-intervention programme, Saudi Arabia, schoolgirls

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17 Tailoring Workspaces for Generation Z: Harmonizing Teamwork, Privacy, and Connectivity

Authors: Maayan Nakash

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The modern workplace is undergoing a revolution, with Generation Z (Gen-Z) at the forefront of this transformative shift. However, empirical investigations specifically targeting the workplace preferences of this generation remain limited. Through direct examination of their tendencies via a survey approach, this study offers vital insights for aligning organizational policies and practices. The results presented in this paper are part of a comprehensive study that explored Gen Z's viewpoints on various employment market aspects, likely to decisively influence the design of future work environments. Data were collected via an online survey distributed among a cohort of 461 individuals from Gen-Z, born between the mid-1990s and 2010, consisting of 241 males (52.28%) and 220 females (47.72%). Responses were gauged using Likert scale statements that probed preferences for teamwork versus individual work, virtual versus personal interactions, and open versus private workspaces. Descriptive statistics and analytical analyses were conducted to pinpoint key patterns. We discovered that a high proportion of respondents (81.99%, n=378) exhibited a preference for teamwork over individual work. Correspondingly, the data indicate strong support for the recognition of team-based tasks as a tool contributing to personal and professional development. In terms of communication, the majority of respondents (61.38%) either disagreed (n=154) or slightly agreed (n=129) with the exclusive reliance on virtual interactions with their organizational peers. This finding underscores that despite technological progress, digital natives place significant value on physical interaction and non-mediated communication. Moreover, we understand that they also value a quiet and private work environment, clearly preferring it over open and shared workspaces. Considering that Gen-Z does not necessarily experience high levels of stress within social frameworks in the workplace, this can be attributed to a desire for a space that allows for focused engagement with work tasks. A One-Sample Chi-Square Test was performed on the observed distribution of respondents' reactions to each examined statement. The results showed statistically significant deviations from a uniform distribution (p<.001), indicating that the response patterns did not occur by chance and that there were meaningful tendencies in the participants' responses. The findings expand the theoretical knowledge base on human resources in the dynamics of a multi-generational workforce, illuminating the values, approaches, and expectations of Gen-Z. Practically, the results may lead organizations to equip themselves with tools to create policies tailored to Gen-Z in the context of workspaces and social needs, which could potentially foster a fertile environment and aid in attracting and retaining young talent. Future studies might include investigating potential mitigating factors, such as cultural influences or individual personality traits, which could further clarify the nuances in Gen-Z's work style preferences. Longitudinal studies tracking changes in these preferences as the generation matures may also yield valuable insights. Ultimately, as the landscape of the workforce continues to evolve, ongoing investigations into the unique characteristics and aspirations of emerging generations remain essential for nurturing harmonious, productive, and future-ready organizational environments.

Keywords: workplace, future of work, generation Z, digital natives, human resources management

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16 Study of Objectivity, Reliability and Validity of Pedagogical Diagnostic Parameters Introduced in the Framework of a Specific Research

Authors: Emiliya Tsankova, Genoveva Zlateva, Violeta Kostadinova

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The challenges modern education faces undoubtedly require reforms and innovations aimed at the reconceptualization of existing educational strategies, the introduction of new concepts and novel techniques and technologies related to the recasting of the aims of education and the remodeling of the content and methodology of education which would guarantee the streamlining of our education with basic European values. Aim: The aim of the current research is the development of a didactic technology for the assessment of the applicability and efficacy of game techniques in pedagogic practice calibrated to specific content and the age specificity of learners, as well as for evaluating the efficacy of such approaches for the facilitation of the acquisition of biological knowledge at a higher theoretical level. Results: In this research, we examine the objectivity, reliability and validity of two newly introduced diagnostic parameters for assessing the durability of the acquired knowledge. A pedagogic experiment has been carried out targeting the verification of the hypothesis that the introduction of game techniques in biological education leads to an increase in the quantity, quality and durability of the knowledge acquired by students. For the purposes of monitoring the effect of the application of the pedagogical technique employing game methodology on the durability of the acquired knowledge a test-base examination has been applied to students from a control group (CG) and students form an experimental group on the same content after a six-month period. The analysis is based on: 1.A study of the statistical significance of the differences of the tests for the CG and the EG, applied after a six-month period, which however is not indicative of the presence or absence of a marked effect from the applied pedagogic technique in cases when the entry levels of the two groups are different. 2.For a more reliable comparison, independently from the entry level of each group, another “indicator of efficacy of game techniques for the durability of knowledge” which has been used for the assessment of the achievement results and durability of this methodology of education. The monitoring of the studied parameters in their dynamic unfolding in different age groups of learners unquestionably reveals a positive effect of the introduction of game techniques in education in respect of durability and permanence of acquired knowledge. Methods: In the current research the following battery of methods and techniques of research for diagnostics has been employed: theoretical analysis and synthesis; an actual pedagogical experiment; questionnaire; didactic testing and mathematical and statistical methods. The data obtained have been used for the qualitative and quantitative of the results which reflect the efficacy of the applied methodology. Conclusion: The didactic model of the parameters researched in the framework of a specific study of pedagogic diagnostics is based on a general, interdisciplinary approach. Enhanced durability of the acquired knowledge proves the transition of that knowledge from short-term memory storage into long-term memory of pupils and students, which justifies the conclusion that didactic plays have beneficial effects for the betterment of learners’ cognitive skills. The innovations in teaching enhance the motivation, creativity and independent cognitive activity in the process of acquiring the material thought. The innovative methods allow for untraditional means for assessing the level of knowledge acquisition. This makes possible the timely discovery of knowledge gaps and the introduction of compensatory techniques, which in turn leads to deeper and more durable acquisition of knowledge.

Keywords: objectivity, reliability and validity of pedagogical diagnostic parameters introduced in the framework of a specific research

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15 Implementation of Building Information Modelling to Monitor, Assess, and Control the Indoor Environmental Quality of Higher Education Buildings

Authors: Mukhtar Maigari

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The landscape of Higher Education (HE) institutions, especially following the CVID-19 pandemic, necessitates advanced approaches to manage Indoor Environmental Quality (IEQ) which is crucial for the comfort, health, and productivity of students and staff. This study investigates the application of Building Information Modelling (BIM) as a multifaceted tool for monitoring, assessing, and controlling IEQ in HE buildings aiming to bridge the gap between traditional management practices and the innovative capabilities of BIM. Central to the study is a comprehensive literature review, which lays the foundation by examining current knowledge and technological advancements in both IEQ and BIM. This review sets the stage for a deeper investigation into the practical application of BIM in IEQ management. The methodology consists of Post-Occupancy Evaluation (POE) which encompasses physical monitoring, questionnaire surveys, and interviews under the umbrella of case studies. The physical data collection focuses on vital IEQ parameters such as temperature, humidity, CO2 levels etc, conducted by using different equipment including dataloggers to ensure accurate data. Complementing this, questionnaire surveys gather perceptions and satisfaction levels from students, providing valuable insights into the subjective aspects of IEQ. The interview component, targeting facilities management teams, offers an in-depth perspective on IEQ management challenges and strategies. The research delves deeper into the development of a conceptual BIM-based framework, informed by the insight findings from case studies and empirical data. This framework is designed to demonstrate the critical functions necessary for effective IEQ monitoring, assessment, control and automation with real time data handling capabilities. This BIM-based framework leads to the developing and testing a BIM-based prototype tool. This prototype leverages on software such as Autodesk Revit with its visual programming tool i.e., Dynamo and an Arduino-based sensor network thereby allowing for real-time flow of IEQ data for monitoring, control and even automation. By harnessing the capabilities of BIM technology, the study presents a forward-thinking approach that aligns with current sustainability and wellness goals, particularly vital in the post-COVID-19 era. The integration of BIM in IEQ management promises not only to enhance the health, comfort, and energy efficiency of educational environments but also to transform them into more conducive spaces for teaching and learning. Furthermore, this research could influence the future of HE buildings by prompting universities and government bodies to revaluate and improve teaching and learning environments. It demonstrates how the synergy between IEQ and BIM can empower stakeholders to monitor IEQ conditions more effectively and make informed decisions in real-time. Moreover, the developed framework has broader applications as well; it can serve as a tool for other sustainability assessments, like energy analysis in HE buildings, leveraging measured data synchronized with the BIM model. In conclusion, this study bridges the gap between theoretical research and real-world application by practicalizing how advanced technologies like BIM can be effectively integrated to enhance environmental quality in educational institutions. It portrays the potential of integrating advanced technologies like BIM in the pursuit of improved environmental conditions in educational institutions.

Keywords: BIM, POE, IEQ, HE-buildings

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14 [Keynote Speech]: Evidence-Based Outcome Effectiveness Longitudinal Study on Three Approaches to Reduce Proactive and Reactive Aggression in Schoolchildren: Group CBT, Moral Education, Bioneurological Intervention

Authors: Annis Lai Chu Fung

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While aggression had high stability throughout developmental stages and across generations, it should be the top priority of researchers and frontline helping professionals to develop prevention and intervention programme for aggressive children and children at risk of developing aggressive behaviours. Although there is a substantial amount of anti-bullying programmes, they gave disappointingly small effect sizes. The neglectful practical significance could be attributed to the overly simplistic categorisation of individuals involved as bullies or victims. In the past three decades, the distinction between reactive and proactive aggression has been well-proved. As children displaying reactively aggressive behaviours have distinct social-information processing pattern with those showing proactively aggressive behaviours, it is critical to identify the unique needs of the two subtypes accordingly when designing an intervention. The onset of reactive aggression and proactive aggression was observed at earliest in 4.4 and 6.8 years old respectively. Such findings called for a differential early intervention targeting these high-risk children. However, to the best of the author’s knowledge, the author was the first to establish an evidence-based intervention programme against reactive and proactive aggression. With the largest samples in the world, the author, in the past 10 years, explored three different approaches and their effectiveness against aggression quantitatively and qualitatively with longitudinal design. The three approaches presented are (a) cognitive-behavioral approach, (b) moral education, with Chinese marital arts and ethics as the medium, and (c) bioneurological measures (omega-3 supplementation). The studies adopted a multi-informant approach with repeated measures before and after the intervention, and follow-up assessment. Participants were recruited from primary and secondary schools in Hong Kong. In the cognitive-behavioral approach, 66 reactive aggressors and 63 proactive aggressors, aged from 11 to 17, were identified from 10,096 secondary-school children with questionnaire and subsequent structured interview. Participants underwent 10 group sessions specifically designed for each subtype of aggressor. Results revealed significant declines in aggression levels from the baseline to the follow-up assessment after 1 year. In moral education through the Chinese martial arts, 315 high-risk aggressive children, aged 6 to 12 years, were selected from 3,511 primary-school children and randomly assigned into four types of 10-session intervention group, namely martial-skills-only, martial-ethics-only, both martial-skills-and-ethics, and physical fitness (placebo). Results showed only the martial-skills-and-ethics group had a significant reduction in aggression after treatment and 6 months after treatment comparing with the placebo group. In the bioneurological approach, 218 children, aged from 8 to 17, were randomly assigned to the omega-3 supplement group and the placebo group. Results revealed that compared with the placebo group, the omega-3 supplement group had significant declines in aggression levels at the 6-month follow-up assessment. All three approaches were effective in reducing proactive and reactive aggression. Traditionally, intervention programmes against aggressive behaviour often adapted the cognitive and/or behavioural approach. However, cognitive-behavioural approach for children was recently challenged by its demanding requirement of cognitive ability. Traditional cognitive interventions may not be as beneficial to an older population as in young children. The present study offered an insightful perspective in aggression reduction measures.

Keywords: intervention, outcome effectiveness, proactive aggression, reactive aggression

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13 Characterization of the Lytic Bacteriophage VbɸAB-1 against Drug Resistant Acinetobacter baumannii Isolated from Hospitalized Pressure Ulcers Patients

Authors: M. Doudi, M. H. Pazandeh, L. Rahimzadeh Torabi

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Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of variety of bacterial infection. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. In present study, analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F, and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin.According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Plasmaviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients.

Keywords: acinetobacter baumannii, extremely drug- resistant, phage therapy, surgery wound

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12 Impact of Simulated Brain Interstitial Fluid Flow on the Chemokine CXC-Chemokine-Ligand-12 Release From an Alginate-Based Hydrogel

Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

Abstract:

The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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11 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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10 The Distribution of Prevalent Supplemental Nutrition Assistance Program-Authorized Food Store Formats Differ by U.S. Region and Rurality: Implications for Food Access and Obesity Linkages

Authors: Bailey Houghtaling, Elena Serrano, Vivica Kraak, Samantha Harden, George Davis, Sarah Misyak

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United States (U.S.) Department of Agriculture Supplemental Nutrition Assistance Program (SNAP) participants are low-income Americans receiving federal dollars for supplemental food and beverage purchases. Participants use a variety of (traditional/non-traditional) SNAP-authorized stores for household dietary purchases - also representing food access points for all Americans. Importantly consumers' food and beverage purchases from non-traditional store formats tend to be higher in saturated fats, added sugars, and sodium when compared to purchases from traditional (e.g., grocery/supermarket) formats. Overconsumption of energy-dense and low-nutrient food and beverage products contribute to high obesity rates and adverse health outcomes that differ in severity among urban/rural U.S. locations and high/low-income populations. Little is known about the SNAP-authorized food store format landscape nationally, regionally, or by urban-rural status, as traditional formats are currently used as the gold standard in food access research. This research utilized publicly available U.S. databases to fill this large literature gap and to provide insight into modes of food access for vulnerable U.S. populations: (1) SNAP Retailer Locator which provides a list of all authorized food stores in the U.S., and; (2) Rural-Urban Continuum Codes (RUCC) that categorize U.S. counties as urban (RUCC 1-3) or rural (RUCC 4-9). Frequencies were determined for the highest occurring food store formats nationally and within two regionally diverse U.S. states – Virginia in the east and California in the west. Store format codes were assigned (e.g., grocery, drug, convenience, mass merchandiser, supercenter, dollar, club, or other). RUCC was applied to investigate state-level differences in urbanity-rurality regarding prevalent food store formats and Chi Square test of independence was used to determine if food store format distributions significantly (p < 0.05) differed by region or rurality. The resulting research sample that represented highly prevalent SNAP-authorized food stores nationally included 41.25% of all SNAP stores in the U.S. (N=257,839), comprised primarily of convenience formats (31.94%) followed by dollar (25.58%), drug (19.24%), traditional (10.87%), supercenter (6.85%), mass merchandiser (1.62%), non-food store or restaurant (1.81%), and club formats (1.09%). Results also indicated that the distribution of prevalent SNAP-authorized formats significantly differed by state. California had a lower proportion of traditional (9.96%) and a higher proportion of drug (28.92%) formats than Virginia- 11.55% and 19.97%, respectively (p < 0.001). Virginia also had a higher proportion of dollar formats (26.11%) when compared to California (10.64%) (p < 0.001). Significant differences were also observed for rurality variables (p < 0.001). Prominently, rural Virginia had a significantly higher proportion of dollar formats (41.71%) when compared to urban Virginia (21.78%) and rural California (21.21%). Non-traditional SNAP-authorized formats are highly prevalent and significantly differ in distribution by U.S. region and rurality. The largest proportional difference was observed for dollar formats where the least nutritious consumer purchases are documented in the literature. Researchers/practitioners should investigate non-traditional food stores at the local level using these research findings and similar applied methodologies to determine how access to various store formats impact obesity prevalence. For example, dollar stores may be prime targets for interventions to enhance nutritious consumer purchases in rural Virginia while targeting drug formats in California may be more appropriate.

Keywords: food access, food store format, nutrition interventions, SNAP consumers

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9 Cardiolipin-Incorporated Liposomes Carrying Curcumin and Nerve Growth Factor to Rescue Neurons from Apoptosis for Alzheimer’s Disease Treatment

Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

Abstract:

Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

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8 The Lytic Bacteriophage VbɸAB-1 Against Drug-Resistant Acinetobacter Baumannii Isolated from Hospitalized Pressure Ulcers Patients

Authors: M. Doudi, M. H. Pazandeh, L. Rahimzadeh Torabi

Abstract:

Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of a variety of bacterial infections. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi-drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. The present study analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, the range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin. According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Podoviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients. The findings of our research indicated that isolated phages could be an effective antimicrobial and an appreciate candidate for prophylaxis against pressure ulcers.

Keywords: acinetobacter baumannii, extremely drug-resistant, phage therapy, surgery wound

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7 4-Channel CWDM Optical Transceiver Applying Silicon Photonics Ge-Photodiode and MZ-Modulator

Authors: Do-Won Kim, Andy Eu Jin Lim, Raja Muthusamy Kumarasamy, Vishal Vinayak, Jacky Wang Yu-Shun, Jason Liow Tsung Yang, Patrick Lo Guo Qiang

Abstract:

In this study, we demonstrate 4-channel coarse wavelength division multiplexing (CWDM) optical transceiver based on silicon photonics integrated circuits (PIC) of waveguide Ge-photodiode (Ge-PD) and Mach Zehnder (MZ)-modulator. 4-channel arrayed PICs of Ge-PD and MZ-modulator are verified to operate at 25 Gbps/ch achieving 4x25 Gbps of total data rate. 4 bare dies of single-channel commercial electronics ICs (EICs) of trans-impedance amplifier (TIA) for Ge-PD and driver IC for MZ-modulator are packaged with PIC on printed circuit board (PCB) in a chip-on-board (COB) manner. Each single-channel EIC is electrically connected to the one channel of 4-channel PICs by wire bonds to trace. The PICs have 4-channel multiplexer for MZ-modulator and 4-channel demultiplexer for Ge-PD. The 4-channel multiplexer/demultiplexer have echelle gratings for4 CWDM optic signals of which center wavelengths are 1511, 1531, 1553, and 1573 nm. Its insertion loss is around 4dB with over 15dB of extinction ratio.The dimension of 4-channel Ge-PD is 3.6x1.4x0.3mm, and its responsivity is 1A/W with dark current of less than 20 nA.Its measured 3dB bandwidth is around 20GHz. The dimension of the 4-channel MZ-modulator is 3.6x4.8x0.3mm, and its 3dB bandwidth is around 11Ghz at -2V of reverse biasing voltage. It has 2.4V•cmbyVπVL of 6V for π shift to 4 mm length modulator.5x5um of Inversed tapered mode size converter with less than 2dB of coupling loss is used for the coupling of the lensed fiber which has 5um of mode field diameter.The PCB for COB packaging and signal transmission is designed to have 6 layers in the hybrid layer structure. 0.25 mm-thick Rogers Duroid RT5880 is used as the first core dielectric layer for high-speed performance over 25 Gbps. It has 0.017 mm-thick of copper layers and its dielectric constant is 2.2and dissipation factor is 0.0009 at 10 GHz. The dimension of both single ended and differential microstrip transmission lines are calculated using full-wave electromagnetic (EM) field simulator HFSS which RF industry is using most. It showed 3dB bandwidth at around 15GHz in S-parameter measurement using network analyzer. The wire bond length for transmission line and ground connection from EIC is done to have less than 300 µm to minimize the parasitic effect to the system.Single layered capacitors (SLC) of 100pF and 1000pF are connected as close as possible to the EICs for stabilizing the DC biasing voltage by decoupling. Its signal transmission performance is under measurement at 25Gbps achieving 100Gbps by 4chx25Gbps. This work can be applied for the active optical cable (AOC) and quad small form-factor pluggable (QSFP) for high-speed optical interconnections. Its demands are quite large in data centers targeting 100 Gbps, 400 Gbps, and 1 Tbps. As the demands of high-speed AOC and QSFP for the application to intra/inter data centers increase, this silicon photonics based high-speed 4 channel CWDM scheme can have advantages not only in data throughput but also cost effectiveness since it reduces fiber cost dramatically through WDM.

Keywords: active optical cable(AOC), 4-channel coarse wavelength division multiplexing (CWDM), communication system, data center, ge-photodiode, Mach Zehnder (MZ) modulator, optical interconnections, optical transceiver, photonics integrated circuits (PIC), quad small form-factor pluggable (QSFP), silicon photonics

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6 The Development, Composition, and Implementation of Vocalises as a Method of Technical Training for the Adult Musical Theatre Singer

Authors: Casey Keenan Joiner, Shayna Tayloe

Abstract:

Classical voice training for the novice singer has long relied on the guidance and instruction of vocalise collections, such as those written and compiled by Marchesi, Lütgen, Vaccai, and Lamperti. These vocalise collections purport to encourage healthy vocal habits and instill technical longevity in both aspiring and established singers, though their scope has long been somewhat confined to the classical idiom. For pedagogues and students specializing in other vocal genres, such as musical theatre and CCM (contemporary commercial music,) low-impact and pertinent vocal training aids are in short supply, and much of the suggested literature derives from classical methodology. While the tenants of healthy vocal production remain ubiquitous, specific stylistic needs and technical emphases differ from genre to genre and may require a specified extension of vocal acuity. As musical theatre continues to grow in popularity at both the professional and collegiate levels, the need for specialized training grows as well. Pedagogical literature geared specifically towards musical theatre (MT) singing and vocal production, while relatively uncommon, is readily accessible to the contemporary educator. Practitioners such as Norman Spivey, Mary Saunders Barton, Claudia Friedlander, Wendy Leborgne, and Marci Rosenberg continue to publish relevant research in the field of musical theatre voice pedagogy and have successfully identified many common MT vocal faults, their subsequent diagnoses, and their eventual corrections. Where classical methodology would suggest specific vocalises or training exercises to maintain corrected vocal posture following successful fault diagnosis, musical theatre finds itself without a relevant body of work towards which to transition. By analyzing the existing vocalise literature by means of a specialized set of parameters, including but not limited to melodic variation, rhythmic complexity, vowel utilization, and technical targeting, we have composed a set of vocalises meant specifically to address the training and conditioning of adult musical theatre voices. These vocalises target many pedagogical tenants in the musical theatre genre, including but not limited to thyroarytenoid-dominant production, twang resonance, lateral vowel formation, and “belt-mix.” By implementing these vocalises in the musical theatre voice studio, pedagogues can efficiently communicate proper musical theatre vocal posture and kinesthetic connection to their students, regardless of age or level of experience. The composition of these vocalises serves MT pedagogues on both a technical level as well as a sociological one. MT is a relative newcomer on the collegiate stage and the academization of musical theatre methodologies has been a slow and arduous process. The conflation of classical and MT techniques and training methods has long plagued the world of voice pedagogy and teachers often find themselves in positions of “cross-training,” that is, teaching students of both genres in one combined voice studio. As MT continues to establish itself on academic platforms worldwide, genre-specific literature and focused studies are both rare and invaluable. To ensure that modern students receive exacting and definitive training in their chosen fields, it becomes increasingly necessary for genres such as musical theatre to boast specified literature and a collection of musical theatre-specific vocalises only aids in this effort. This collection of musical theatre vocalises is the first of its kind and provides genre-specific studios with a basis upon which to grow healthy, balanced voices built for the harsh conditions of the modern theatre stage.

Keywords: voice pedagogy, targeted methodology, musical theatre, singing

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5 Biotech Processes to Recover Valuable Fraction from Buffalo Whey Usable in Probiotic Growth, Cosmeceutical, Nutraceutical and Food Industries

Authors: Alberto Alfano, Sergio D’ambrosio, Darshankumar Parecha, Donatella Cimini, Chiara Schiraldi.

Abstract:

The main objective of this study regards the setup of an efficient small-scale platform for the conversion of local renewable waste materials, such as whey, into added-value products, thereby reducing environmental impact and costs deriving from the disposal of processing waste products. The buffalo milk whey derived from the cheese-making process, called second cheese whey, is the main by-product of the dairy industry. Whey is the main and most polluting by-product obtained from cheese manufacturing consisting of lactose, lactic acid, proteins, and salts, making whey an added-value product. In Italy, and in particular, in the Campania region, soft cheese production needs a large volume of liquid waste, especially during late spring and summer. This project is part of a circular economy perspective focused on the conversion of potentially polluting and difficult to purify waste into a resource to be exploited, and it embodies the concept of the three “R”: reduce, recycle, and reuse. Special focus was paid to the production of health-promoting biomolecules and biopolymers, which may be exploited in different segments of the food and pharmaceutical industries. These biomolecules may be recovered through appropriate processes and reused in an attempt to obtain added value products. So, ultrafiltration and nanofiltration processes were performed to fractionate bioactive components starting from buffalo milk whey. In this direction, the present study focused on the implementation of a downstream process that converts waste generated from food and food processing industries into added value products with potential applications. Owing to innovative downstream and biotechnological processes, rather than a waste product may be considered a resource to obtain high added value products, such as food supplements (probiotics), cosmeceuticals, biopolymers, and recyclable purified water. Besides targeting gastrointestinal disorders, probiotics such as Lactobacilli have been reported to improve immunomodulation and protection of the host against infections caused by viral and bacterial pathogens. Interestingly, also inactivated microbial (probiotic) cells and their metabolic products, indicated as parabiotic and postbiotics, respectively, have a crucial role and act as mediators in the modulation of the host’s immune function. To boost the production of biomass (both viable and/or heat inactivated cells) and/or the synthesis of growth-related postbiotics, such as EPS, efficient and sustainable fermentation processes are necessary. Based on a “zero-waste” approach, wastes generated from local industries can be recovered and recycled to develop sustainable biotechnological processes to obtain probiotics as well as post and parabiotic, to be tested as bioactive compounds against gastrointestinal disorders. The results have shown it was possible to recover an ultrafiltration retentate with suitable characteristics to be used in skin dehydration, to perform films (i.e., packaging for food industries), or as a wound repair agent and a nanofiltration retentate to recover lactic acid and carbon sources (e.g., lactose, glucose..) used for microbial cultivation. On the side, the last goal is to obtain purified water that can be reused throughout the process. In fact, water reclamation and reuse provide a unique and viable opportunity to augment traditional water supplies, a key issue nowadays.

Keywords: biotech process, downstream process, probiotic growth, from waste to product, buffalo whey

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4 Cardiac Hypertrophy in Diabetes; The Role of Factor Forkhead Box Class O-Regulation by O-GlcNAcylation

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

Abstract:

Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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3 Improving Sanitation and Hygiene Using a Behavioral Change Approach in Public and Private Schools in Kampala, Uganda

Authors: G. Senoga, D. Nakimuli, B. Ndagire, B. Lukwago, D. Kyamagwa

Abstract:

Background: The COVID-19 epidemic affected the education sector, with some private schools closing while other children missed schooling for fear contracting COVID-19. Post COVID-19, PSIU in collaborated with Kampala City Council Authority Directorate of Education and Social Science, Water and Sanitation department, and Directorate of Public Health and Environment to improve sanitation and hygiene among pupils and staff in 50 public and private school system in Kampala city. The “Be Clean, Stay Healthy Campaign” used a behavioral change approach in educating, reinforcing and engaging learners on proper hand washing behaviors, proper toilet usage and garbage disposal. In April 2022, 40 Washa lots were constructed, to reduce the pupil - hand wash station ratio; distributed KCCA approved printed materials; oriented 50 teachers, WASH committees to execute and implement hygiene promotion. To ensure sustainability, WASH messages were memorized and practiced through hand washing songs, Pledge, prayer, Poems, Skits, Music, dance and drama, coupled with participatory, practical demonstrations using peer to peer approach, guest speakers at assemblies and in classes. This improved hygiene and sanitation practices. Premised on this, PSI conducted an end line assessment to explore the impact of a hand washing campaign in regards to improvements in hand washing practices and hand hygiene among pupils, accessibility, functionality and usage of the constructed hygiene and sanitation facilities. Method: A cross-sectional post intervention assessment using a mixed methods approach, targeting headteachers, wash committee members and pupils less <17 years was used. Quantitative approaches with a mix of open-ended questions were used in purposively selected respondents in 50 schools. Primary three to primary seven pupils were randomly selected, data was analyzed using the Statistical Package for Social Scientists (SPSS) Outcomes and Findings: 46,989 pupils (51% female), 1,127 and 524 teaching and non-teaching staff were reached by the intervention, respectively. 96% of schools trained on sanitation, sustainable water usage and hygiene constituted 17-man school WASH committees with teacher, parents and pupils representatives. (31%) of the WASH committees developed workplans, (78%) held WASH meetings monthly. This resulted into improved sanitation, water usage, waste management, proper use of toilets, and improved pupils’ health with reduced occurrences of stomach upsets, diarrhoea initially attributed to improper use of latrines and general waste management. Teachers reported reduced number of school absenteeism due to improved hygiene and general waste management at school, especially proper management of sanitary pads. School administrations response rate in purchase of hygiene equipment’s and detergents like soap improved. Regular WASH meetings in classes, teachers and community supervision ensured WASH facilities are used appropriately. Conclusion and Recommendations: Practical behaviour change innovations improves pupil’s knowledge and understanding of hygiene messages and usage. Over 70% of pupils had clear recall of key WASH Messages. There is need for continuous water flow in the Washa lots, harvesting rain water would reduce water bills while complementing National water supply coupled with increasing on Washa lots in densely populated schools.

Keywords: handwashing, hygyiene, sanitation, behaviour change

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2 Innovative Practices That Have Significantly Scaled up Depot Medroxy Progesterone Acetate-SC Self-Inject Services

Authors: Oluwaseun Adeleke, Samuel O. Ikani, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu

Abstract:

Background The Delivering Innovations in Selfcare (DISC) project promotes universal access to quality selfcare services beginning with subcutaneous depot medroxy progesterone acetate (DMPA-SC) contraceptive self-injection (SI) option. Self-inject (SI) offers women a highly effective and convenient option that saves them frequent trips to providers. Its increased use has the potential to improve the efficiency of an overstretched healthcare system by reducing provider workloads. State Social and Behavioral Change Communications (SBCC) Officers lead project demand creation and service delivery innovations that have resulted in significant increases in SI uptake among women who opt for injectables. Strategies Service Delivery Innovations The implementation of the "Moment of Truth (MoT)" innovation helped providers overcome biases and address client fear and reluctance to self-inject. Bi-annual program audits and supportive mentoring visits helped providers retain their competence and motivation. Proper documentation, tracking, and replenishment of commodities were ensured through effective engagement with State Logistics Units. The project supported existing state monitoring and evaluation structures to effectively record and report subcutaneous depot medroxy progesterone acetate (DMPA-SC) service utilization. Demand creation Innovations SBCC Officers provide oversight, routinely evaluate performance, trains, and provides feedback for the demand creation activities implemented by community mobilizers (CMs). The scope and intensity of training given to CMs affect the outcome of their work. The project operates a demand creation model that uses a schedule to inform the conduct of interpersonal and group events. Health education sessions are specifically designed to counter misinformation, address questions and concerns, and educate target audience in an informed choice context. The project mapped facilities and their catchment areas and enlisted the support of identified influencers and gatekeepers to enlist their buy-in prior to entry. Each mobilization event began with pre-mobilization sensitization activities, particularly targeting male groups. Context-specific interventions were informed by the religious, traditional, and cultural peculiarities of target communities. Mobilizers also support clients to engage with and navigate online digital Family Planning (FP) online portals such as DiscoverYourPower website, Facebook page, digital companion (chat bot), interactive voice response (IVR), radio and television (TV) messaging. This improves compliance and provides linkages to nearby facilities. Results The project recorded 136,950 self-injection (SI) visits and a self-injection (SI) proportion rate that increased from 13 percent before the implementation of interventions in 2021 to 62 percent currently. The project cost-effectively demonstrated catalytic impact by leveraging state and partner resources, institutional platforms, and geographic scope to scale up interventions. The project also cost effectively demonstrated catalytic impact by leveraging on the state and partner resources, institutional platforms, and geographic scope to sustainably scale-up these strategies. Conclusion Using evidence-informed iterations of service delivery and demand creation models have been useful to significantly drive self-injection (SI) uptake. It will be useful to consider this implementation model during program design. Contemplation should also be given to systematic and strategic execution of strategies to optimize impact.

Keywords: family planning, contraception, DMPA-SC, self-care, self-injection, innovation, service delivery, demand creation.

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1 Identification of the Antimicrobial Property of Double Metal Oxide/Bioactive Glass Nanocomposite Against Multi Drug Resistant Staphylococcus aureus Causing Implant Infections

Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

Abstract:

The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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