Search results for: toehold mediated DNA switch

Authors: Richard Mababu Mukiur

Abstract:

Leadership is an important drive that plays a key role in the success and development of organizations, particularly in the current context of digital transformation, highly competitivity and globalization. Leaders are persons that hold a dominant and privileged position within an organization, field, or sector of activities and are able to manage, motivate and exercise a high degree of influence over other in order to achieve the institutional goals. They achieve commitment and engagement of others to embrace change, and to make good decisions. Leadership studies in higher education institutions have examined how effective leaders hold their organizations, and also to find approaches which fit best in the organizations context for its better management, transformation and improvement. Moreover, recent studies have highlighted the impact of leadership styles on organizational performance and innovation capacities, since some styles give better results than others. Effective leadership is part of learning process that take place through day-to-day tasks, responsibilities, and experiences that influence the organizational performance, innovation and engagement of employees. The adoption of appropriate leadership styles can improve organization results and encourage learning process, team skills and performance, and employees' motivation and engagement. In the case of case of Information Technology sector, leadership styles are particularly crucial since this sector is leading relevant changes and transformations in the knowledge society. In this context, the main objective of this study is to analyze managers leadership styles with their relation to organizational performance and innovation that may be mediated by learning organization process and demographic variables. Therefore, it was hypothesized that the transformational and transactional leadership will be the main style adopted in Information Technology sector and will influence organizational performance and innovation capacity. A sample of 540 participants from Information technology sector has been determined in order to achieve the objective of this study. The Multifactor Leadership Questionnaire was administered as the principal instrument, Scale of innovation and Learning Organization Questionnaire. Correlations and multiple regression analysis have been used as the main techniques of data analysis. The findings indicate that leadership styles have a relevant impact on organizational performance and innovation capacity. The transformational and transactional leadership are predominant styles in Information technology sector. The effective leadership style tend to be characterized by the capacity of generating and sharing knowledge that improve organization performance and innovation capacity. Managers are adopting and adapting their leadership styles that respond to the new organizational, social and cultural challenges and realities of contemporary society. Managers who encourage innovation, foster learning process, share experience are useful to the organization since they contribute to its development and transformation. Learning process capacity and demographic variables (age, gender, and job tenure) mediate the relationship between leadership styles, innovation capacity and organizational performance. The transformational and transactional leadership tend to enhance the organizational performance due to their significant impact on team-building, employees' engagement and satisfaction. Some practical implications and future lines of research have been proposed.

Keywords: leadership styles, tranformational leadership, organisational performance, organisational innovation

Procedia PDF Downloads 190

Authors: Miyoko Taniguchi

Abstract:

Conflict and violence have prevailed over the last four decades in conflict-affected areas in Muslim Mindanao, despite the signing of several peace agreements between the Philippine government and Islamic separatist insurgents (the Moro National Liberation Front (MNLF) and the Moro Islamic Liberation Front (MILF)), and peacebuilding activities on the ground. In the meantime, the peace talks had been facilitated and mediated by international actors such as the Organization of Islamic Cooperation (OIC) and its member countries such as Indonesia, and Malaysia, and Japan. In 2014, both the Government of the Philippines (GPH) and the MILF finally reached a Comprehensive Peace Agreement (CAB) in 2014 under the Aquino III administration, though a Bangsamoro Basic Law (BBL) based on the CAB was not enacted at the Catholic-majority of the Philippine Congress. After a long process of deliberations at the Congress, Republic Act 11054, known as the Bangsamoro Organic Law (BOL), was enacted in 2018 under the Duterate administration. In the beginning, President Duterte adopted an 'inclusive approach' that involves the MILF, all factions of the MNLF, non-Islamized indigenous peoples, and other influential clan leaders to align all peace processes under a single Bangsamoro peace process. A notable difference from past administrations, there is an explicit recognition of all agreements and legislations based on the rights of each stakeholder. This created a new identity as 'Bangsamoro', the residents of Muslim Mindanao, enhancing political legitimacy. Besides, it should be noted an important role of 'insider mediators' -a platform for the Bangsamoro from diverse sectors attempting to work within their respective organizations in Moro society. Give the above background, this paper aims at probing the effectiveness of insider mediation as one of the alternative approaches for mediation in the peace process. For the objectives, this research uses qualitative methods such as process-tracing and semi-structured interviews from diverse groups of stakeholders at from the state to the regional level, including the government officials involved in peace process under the Presidential Office, rebels (MILF and MNLF), civil society organizations involved in lobbying and facilitating peace process, especially in the legislative process. The key outcomes and findings are that the Insider Mediators Group, formed in 2016, had taken on a significant role in facilitating the achievement of a wider consensus among stakeholders on major Moro issues such as BBL’s passing during the last administration to call for unity among the Bangsamoro. Most of its members are well-educated professionals affiliated with the MILF, the MNLF, and influential clans. One of the group’s biggest achievements has been the lobbying and provision of legal advice to legislators who were not necessarily knowledgeable about the peace process during the deliberation of the bicameral conference of the BBL, which eventually led to its passage. It can be concluded that in the long run, strengthening vertical and horizontal relations between the Moro society and the State and among the Moro peoples that can be viewed as a means to sustainable peace.

Keywords: insider mediation, Mindanao, peace process, Moro Islamic liberation front

Procedia PDF Downloads 92

Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

Abstract:

The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

Procedia PDF Downloads 308

Authors: Bello Gonzalez T. D. J., Setten Van M., Essen Van A., Brouwer M., Veldman K. T.

Abstract:

Resistance to fluoroquinolones (FQ) has evolved increasingly over the years, posing a significant challenge for the treatment of human infections, particularly gastrointestinal tract infections caused by zoonotic bacteria transmitted through the food chain and environment. In broiler chickens, a relatively high proportion of FQ resistance has been observed in Escherichia coli indicator, Salmonella and Campylobacter isolates. We hypothesize that flumequine (Flu), used as a secondary choice for the treatment of poultry infections, could potentially be associated with a high proportion of FQ resistance. To evaluate this hypothesis, we used an in vitro fermentation chicken caeca model. Two continuous single-stage fermenters were used to simulate in real time the physiological conditions of the chicken caeca microbial content (temperature, pH, caecal content mixing, and anoxic environment). A pool of chicken caecal content containing FQ-resistant E. coli obtained from chickens at slaughter age was used as inoculum along with a spiked FQ-susceptible Campylobacter jejuni strain isolated from broilers. Flu was added to one of the fermenters (Flu-fermenter) every 24 hours for two days to evaluate the selection and maintenance of FQ resistance over time, while the other served as a control (C-Fermenter). The experiment duration was 5 days. Samples were collected at three different time points: before, during and after Flu administration. Serial dilutions were plated on Butzler culture media with and without Flu (8mg/L) and enrofloxacin (4mg/L) and on MacConkey culture media with and without Flu (4mg/L) and enrofloxacin (1mg/L) to determine the proportion of resistant strains over time. Positive cultures were identified by mass spectrometry and matrix-assisted laser desorption/ionization (MALDI). A subset of the obtained isolates were used for Whole Genome Sequencing analysis. Over time, E. coli exhibited positive growth in both fermenters, while C. jejuni growth was detected up to day 3. The proportion of Flu-resistant E. coli strains recovered remained consistent over time after antibiotic selective pressure, while in the C-fermenter, a decrease was observed at day 5; a similar pattern was observed in the enrofloxacin-resistant E. coli strains. This suggests that Flu might play a role in the selection and persistence of enrofloxacin resistance, compared to C-fermenter, where enrofloxacin-resistant E. coli strains appear at a later time. Furthermore, positive growth was detected from both fermenters only on Butzler plates without antibiotics. A subset of C. jejuni strains from the Flu-fermenter revealed that those strains were susceptible to ciprofloxacin (MIC < 0.12 μg/mL). A selection of E. coli strains from both fermenters revealed the presence of plasmid-mediated quinolone resistance (PMQR) (qnr-B19) in only one strain from the C-fermenter belonging to sequence type (ST) 48, and in all from Flu-fermenter belonged to ST189. Our results showed that Flu selective impact on PMQR-positive E. coli strains, while no effect was observed in C. jejuni. Maintenance of Flu-resistance was correlated with antibiotic selective pressure. Further studies into antibiotic resistance gene transfer among commensal and zoonotic bacteria in the chicken caeca content may help to elucidate the resistance spread mechanisms.

Keywords: fluoroquinolone-resistance, escherichia coli, campylobacter jejuni, in vitro model

Procedia PDF Downloads 28

Authors: Nien-Te Kuo, Yi-Sung Cheng, Kuo-Chien Chang

Abstract:

Cultural festival tourism is now seen by many as an opportunity to facilitate community development because it has significant influences on the economic, social, cultural, and political aspects of local communities. The potential for tourist attraction has been recognized as a useful tool to strengthen local economies from governments. However, most community festivals in Taiwan are short-lived, often only lasting for a few years or occasionally not making it past a one-off event. Researchers suggested that most governments and other stakeholders do not recognize the importance of building a partnership with residents when developing community tourism. Thus, the sustainable community tourism development still remains a key issue in the existing literature. The success of community tourism is related to the attitudes and lifestyles of local residents. In order to maintain sustainable tourism, residents need to be seen as development partners. Residents’ support intention for tourism development not only helps to increase awareness of local culture, history, the natural environment, and infrastructure, but also improves the interactive relationship between the host community and tourists. Furthermore, researchers have identified the social capital theory as the core of sustainable community tourism development. The social capital of residents has been seen as a good way to solve issues of tourism governance, forecast the participation behavior and improve support intention of residents. In addition, previous studies have pointed out the role of community participation and place identity in increasing resident support intention for tourism development. A lack of place identity is one of the main reasons that community tourism has become a mere formality and is not sustainable. It refers to how much residents participate during tourism development and is mainly influenced by individual interest. Scholars believed that the place identity of residents is the soul of community festivals. It shows the community spirit to visitors and has significant impacts on tourism benefits and support intention of residents in community tourism development. Although the importance of community participation and place identity have been confirmed by both governmental and non-governmental organizations, real-life execution still needs to be improved. This study aimed to use social capital theory to investigate the social structure between community residents, participation levels in festival tourism, degrees of place identity, and resident support intention for future community tourism development, and the causal relationship that these factors have with cultural festival tourism. A quantitative research approach was employed to examine the proposed model. Structural equation model was used to test and verify the proposed hypotheses. This was a case study of the Kaohsiung Zuoying Wannian Folklore Festival. The festival was located in the Zuoying District of Kaohsiung City, Taiwan. The target population of this study was residents who attended the festival. The results reveal significant correlations among social capital, community participation, place identity and support intention. The results also confirm that impacts of social capital on support intention were significantly mediated by community participation and place identity. Practical suggestions were provided for tourism operators and policy makers. This work was supported by the Ministry of Science and Technology of Taiwan, Republic of China, under the grant MOST-105-2410-H-328-013.

Keywords: community participation, place identity, social capital, support intention

Procedia PDF Downloads 298

Authors: Isaac Martin, Abigail Lark, Sandra Morales, Eric W. Alton, Jane C. Davies

Abstract:

Objectives: The cystic fibrosis (CF) lung is a unique microbiological niche, wherein harmful bacteria persist for many years despite antibiotic therapy. Pseudomonas aeruginosa (Pa), the major culprit leading to lung decline and increased mortality, thrives in the lungs of patients with CF due to several factors that have been linked with poor antibiotic performance. Our group is investigating alternative therapies including bacteriophage cocktails with which we have previously demonstrated efficacy against planktonic organisms. In this study, we explored the effects of a 4-phage cocktail on Pa grown in two different conditions, intended to mirror the CF lung: a) alongside standard antibiotic treatment in pre-formed biofilms (structures formed by Pa-secreted exopolysaccharides which provide both physical and cell division barriers to antimicrobials and host defenses and b) in an acidic environment postulated to be present in the CF airway due both to the primary defect in bicarbonate secretion and secondary effects of inflammation. Methods: 16 Pa strains from CF patients at the Royal Brompton Hospital were selected based on sensitivity to a) ceftazidime/ tobramycin and b) the phage cocktail in a conventional plaque assay. To assess efficacy of phage in biofilms, 96 well plates with Pa (5x10⁷ CFU/ ml) were incubated in static conditions, allowing adherent bacterial colonies to form for 24 hr. Ceftazidime and tobramycin (both at 2 × MIC) were added, +/- bacteriophage (4x10⁸ PFU/mL) for a further 24 hr. Cell viability and biomass were estimated using fluorescent resazurin and crystal violet assays, respectively. To evaluate the effect of pH, strains were grown planktonically in shaking 96 well plates at pH 6.0, 6.6, 7.0 and 7.5 with tobramycin or phage, at varying concentrations. Cell viability was quantified by fluorescent resazurin assay. Results: For the biofilm assay, treatment groups were compared with untreated controls and expressed as percent reduction in cell viability and biomass. Addition of the 4-phage cocktail resulted in a 1.3-fold reduction in cell viability and 1.7-fold reduction in biomass (p < 0.001) when compared to standard antibiotic treatment alone. Notably, there was a 50 ± 15% reduction in cell viability and 60 ± 12% reduction in biomass (95% CI) for the 4 biofilms demonstrating the most resistance to antibiotic treatment. 83% of strains tested (n=6) showed decreased bacterial killing by tobramycin at acidic pHs (p < 0.01). However, 25% of strains (n=12) showed improved phage killing at acidic pHs (p < 0.05), with none showing the pattern of reduced efficacy at acidic pH demonstrated by tobramycin. Conclusion: The 4-phage anti-Pa cocktail tested against Pa performs well in pre-formed biofilms and in acidic environments; two conditions intended to mimic the CF lung. To our knowledge, these are the first data looking at the effects of subtle pH changes on phage-mediated bacterial killing in the context of Pa infection. These findings contribute to a growing body of evidence supporting the use of nebulised lytic bacteriophage as a treatment in the context of lung infection.

Keywords: biofilm, cystic fibrosis, pH, Pseudomonas aeruginosa, lytic bacteriophage

Procedia PDF Downloads 154

Authors: Michel Patiño-Sáenz, Martín Haissiner, Jorge Martínez-Cotrina, Daniel Pastor, Hernando Santamaría-García, Maria-Alejandra Tangarife, Agustin Ibáñez, Sandra Baez

Abstract:

It has been shown that gruesome descriptions of harm can increase the punishment given to a transgressor. This biasing effect is mediated by negative emotions, which are elicited upon the presentation of gruesome descriptions. However, there is a lack of studies inquiring the influence of such descriptions on moral decision-making in people involved in the criminal justice system. Such populations are of special interest since they have experience dealing with gruesome evidence, but also formal education on how to assess evidence and gauge the appropriate punishment according to the law. Likewise, they are expected to be objective and rational when performing their duty, because their decisions can impact profoundly people`s lives. Considering these antecedents, the objective of this study was to explore the influence gruesome written descriptions on moral decision-making in this group of people. To that end, we recruited attorneys, judges and public prosecutors (Criminal justice group, CJ, n=30) whose field of specialty is criminal law. In addition, we included a control group of people who did not have a formal education in law (n=30), but who were paired in age and years of education with the CJ group. All participants completed an online, Spanish-adapted version of a moral decision-making task, which was previously reported in the literature and also standardized and validated in the Latin-American context. A series of text-based stories describing two characters, one inflicting harm on the other, were presented to participants. Transgressor's intentionality (accidental vs. intentional harm) and language (gruesome vs. plain) used to describe harm were manipulated employing a within-subjects and a between-subjects design, respectively. After reading each story, participants were asked to rate (a) the harmful action's moral adequacy, (b) the amount of punishment deserving the transgressor and (c) how damaging was his behavior. Results showed main effects of group, intentionality and type of language on all dependent measures. In both groups, intentional harmful actions were rated as significantly less morally adequate, were punished more severely and were deemed as more damaging. Moreover, control subjects deemed more damaging and punished more severely any type of action than the CJ group. In addition, there was an interaction between intentionality and group. People in the control group rated harmful actions as less morally adequate than the CJ group, but only when the action was accidental. Also, there was an interaction between intentionality and language on punishment ratings. Controls punished more when harm was described using gruesome language. However, that was not the case of people in the CJ group, who assigned the same amount of punishment in both conditions. In conclusion, participants with job experience in the criminal justice system or criminal law differ in the way they make moral decisions. Particularly, it seems that they are less sensitive to the biasing effect of gruesome evidence, which is probably explained by their formal education or their experience in dealing with such evidence. Nonetheless, more studies are needed to determine the impact this phenomenon has on the fulfillment of their duty.

Keywords: criminal justice system, emotions, gruesome descriptions, intentionality, moral decision-making

Procedia PDF Downloads 159

Authors: K. S. Poutanen, P. Dussort, A. Erkner, S. Fiszman, K. Karnik, M. Kristensen, C. F. M. Marsaux, S. Miquel-Kergoat, S. Pentikäinen, P. Putz, R. E. Steinert, J. Slavin, D. J. Mela

Abstract:

Dietary fiber (DF) intake has been associated with lower body weight or less weight gain. These effects are generally attributed to putative effects of DF on appetite. Many intervention studies have tested the effect of DFs on appetite-related measures, with inconsistent results. However, DF includes a wide category of different compounds with diverse chemical and physical characteristics, and correspondingly diverse effects in human digestion. Thus, inconsistent results between DF consumption and appetite are not surprising. The specific contribution of different compounds with varying physico-chemical properties to appetite control and the mediating mechanisms are not well characterized. This systematic review aimed to assess the influence of specific DF characteristics, including viscosity, gel forming capacity, fermentability, and molecular weight, on appetite-related outcomes in healthy humans. Medline and FSTA databases were searched for controlled human intervention trials, testing the effects of well-characterized DFs on subjective satiety/appetite or energy intake outcomes. Studies were included only if they reported: 1) fiber name and origin, and 2) data on viscosity, gelling properties, fermentability, or molecular weight of the DF materials tested. The search generated 3001 unique records, 322 of which were selected for further consideration from title and abstract screening. Of these, 149 were excluded due to insufficient fiber characterization and 124 for other reasons (not original article, not randomized controlled trial, or no appetite related outcome), leaving 49 papers meeting all the inclusion criteria, most of which reported results from acute testing (<1 day). The eligible 49 papers described 90 comparisons of DFs in foods, beverages or supplements. DF-containing material of interest was efficacious for at least one appetite-related outcome in 51/90 comparisons. Gel-forming DF sources were most consistently efficacious but there were no clear associations between viscosity, MW or fermentability and appetite-related outcomes. A considerable number of papers had to be excluded from the review due to shortcomings in fiber characterization. To build understanding about the impact of DF on satiety/appetite specifically there should be clear hypotheses about the mechanisms behind the proposed beneficial effect of DF material on appetite, and sufficient data about the DF properties relevant for the hypothesized mechanisms to justify clinical testing. The hypothesized mechanisms should also guide the decision about relevant duration of exposure in studies, i.e. are the effects expected to occur during acute time frame (related to stomach emptying, digestion rate, etc.) or develop from sustained exposure (gut fermentation mediated mechanisms). More consistent measurement methods and reporting of fiber specifications and characterization are needed to establish reliable structure-function relationships for DF and health outcomes.

Keywords: appetite, dietary fiber, physico-chemical properties, satiety

Procedia PDF Downloads 202

Authors: Anna Marie Fisker, Daniele Sepe, Mette Bøgh Jensen, Daniela Rimei

Abstract:

In the space of just a few years, the European policy framework on cultural heritage has been completely overhauled, moving towards a people-centred and holistic approach, and eliminating the divisions between the tangible, intangible and digital dimensions. The European Union regards cultural heritage as a potential shared resource, highlighting that all stakeholders share responsibility for its transmission to future generations. This new framework will potentially change the way in which cultural institutions manage, protect and provide access to their heritage. It will change the way in which citizens and communities engage with their cultural heritage and naturally influence the way that professionals deal with it. Participating in the creation of cultural heritage awareness can lead to an increased perception of its value, be it economic, social, environmental or cultural. It can also strengthen our personal identity, sense of belonging and community citizenship. Open Atelier, a Creative Europe project, is based on this foundation, with the goal through co-creation to develop the use, understanding and engagement with our cultural heritage. The project aim to transform selected parts of the heritage into an “experience lab” – an interactive, co-creative, dynamic and participatory space, where cultural heritage is the point of departure for new interactions and experiences between the audience and the museum and its professionals. Through a workshop-based approach built on interdisciplinary collaboration and co-creative processes, Open Atelier has started to design, develop, test, and evaluate a set of Experiences. The first collaborative initiative was set out in the discourse and knowledge of a highly creative period in Denmark where a specific group of Scandinavian artists, the Skagen Painters, gathered in the village of Skagen, the northernmost part of Denmark from the late 1870s until the turn of the century. The Art Museums of Skagen have a large collection of photos from the period, that has never been the subject of more thorough research. The photos display a variation of many different subjects: community, family photos, reproductions of art works, costume parties, family gatherings etc., and carry with them the energies of those peoples’ work and life and evoke instances of communication with the past. This paper is about how we in Open Atelier connect these special stories, this legacy, with another place, in another time, in another context and with another audience. The first Open Atelier Experience – the performance “Around the Lighthouse” – was an initiative resulted from the collaboration between AMAT, an Italian creative organisation, and the Art Museums of Skagen. A group of Italian artists developed a co-creative investigation and reinterpretation of a selection of these historical photos. A poetic journey through videos and voices, aimed at exploring new perspectives on the museum and its heritage. An experiment on how to create new ways to actively engage audiences in the way cultural heritage is explored, interpreted, mediated, presented, and used to examine contemporary issues. This article is about this experiment and its findings, and how different views and methodologies can be adopted to discuss the cultural heritage in museums around Europe and their connection to the community.

Keywords: cultural heritage, community, innovation, museums

Procedia PDF Downloads 50

Authors: Wanvipa Thongborisute, Punyaphat Sirithanabadeekul, Pichit Suvanprakorn, Anan Jiraviroon

Abstract:

Background: Acne vulgaris is one of the most common dermatologic problems, and can have a significant psychological and physical effect on patients. Propionibacterium acnes' roles in acne vulgaris involve the activation of toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) pathways. By activating these pathways, inflammatory events of acne lesions, comedogenesis and sebaceous lipogenesis can occur. Currently, there are several topical agents commonly use in treating acne vulgaris that are known to have an effect on TLRs, such as retinoic acid and adapalene, but these drugs still have some irritating effects. At present, there is an alarming increase in rate of bacterial resistance due to irrational used of antibiotics both orally and topically. For this reason, acne treatments should contain bioactive molecules targeting at the site of action for the most effective therapeutic effect with the least side effects. Sparganium stoloniferumis a Chinese aquatic herb containing a compound called Sparstolonin B (SsnB), which has been reported to selectively blocks Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4)-mediated inflammatory signals. Therefore, this topical TLR2 and TLR4 antagonist, in a form of Sparganium stoloniferum-derived compound containing SsnB, should give a benefit in reducing inflammation of acne vulgaris lesions and providing an alternative treatments for patients with this condition. Materials and Methods: The objectives of this randomized double blinded split faced placebo controlled trial is to study the safety and efficacy of the Sparganium stoloniferum-derived compound. 32 volunteered patients with mild to moderate degree of acne vulgaris according to global acne grading system were included in the study. After being informed and consented the subjects were given 2 topical treatments for acne vulgaris, one being topical 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) and the other, placebo. The subjects were asked to apply each treatment to either half of the face daily morning and night by randomization for 8 weeks, and come in for a weekly follow up. For each visit, the patients went through a procedure of lesion counting, including comedones, papules, nodules, pustules, and cystic lesions. Results: During 8 weeks of experimentation, the result shows a reduction in total lesions number between the placebo and the treatment side show statistical significance starting at week 4, where the 95% confidence interval begin to no longer overlap, and shows a trend of continuing to be further apart. The decrease in the amount of total lesions between week 0 and week 8 of the placebo side shows no statistical significant at P value >0.05. While the decrease in the amount of total lesions of acne vulgaris of the treatment side comparing between week 0 and week 8 shows statistical significant at P value <0.001. Conclusion: The data demonstrates that 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) is more effective in treating acne vulgaris comparing to topical placebo in treating acne vulgaris, by showing significant reduction in the total numbers of acne lesions. Therefore, this topical Sparganium stoloniferum extraction could become a potential alternative treatment for acne vulgaris.

Keywords: acne vulgaris, sparganium stoloniferum, sparstolonin B, toll-like receptor 2, toll-like receptor 4

Procedia PDF Downloads 154

Authors: Estela Díaz

Abstract:

This article aims to make three contributions. First, build on the literature on ethical decision-making literature by exploring factors that influence the intention of adopting veganism. Second, study the superiority of extended models of the Theory of Planned Behavior (TPB) for understanding the process involved in forming the intention of adopting veganism. Third, analyze the moderating effect of gender on TPB given that attitudes and behavior towards animals are gender-sensitive. No study, to our knowledge, has examined these questions. Veganism is not a diet but a political and moral stand that exclude, for moral reasons, the use of animals. Although there is a growing interest in studying veganism, it continues being overlooked in empirical research, especially within the domain of social psychology. TPB has been widely used to study a broad range of human behaviors, including moral issues. Nonetheless, TPB has rarely been applied to examine ethical decisions about animals and, even less, to veganism. Hence, the validity of TPB in predicting the intention of adopting veganism remains unanswered. A total of 476 non-vegan Spanish university students (55.6% female; the mean age was 23.26 years, SD= 6.1) responded to online and pencil-and-paper self-reported questionnaire based on previous studies. TPB extended models incorporated two background factors: ‘general attitudes towards humanlike-attributes ascribed to animals’ (AHA) (capacity for reason/emotions/suffer, moral consideration, and affect-towards-animals); and ‘general attitudes towards 11 uses of animals’ (AUA). SPSS 22 and SmartPLS 3.0 were used for statistical analyses. This study constructed a second-order reflective-formative model and took the multi-group analysis (MGA) approach to study gender effects. Six models of TPB (the standard and five competing) were tested. No a priori hypotheses were formulated. The results gave partial support to TPB. Attitudes (ATTV) (β = .207, p < .001), subjective norms (SNV) (β = .323, p < .001), and perceived control behavior (PCB) (β = .149, p < .001) had a significant direct effect on intentions (INTV). This model accounted for 27,9% of the variance in intention (R2Adj = .275) and had a small predictive relevance (Q2 = .261). However, findings from this study reveal that contrary to what TPB generally proposes, the effect of the background factors on intentions was not fully mediated by the proximal constructs of intentions. For instance, in the final model (Model#6), both factors had significant multiple indirect effect on INTV (β = .074, 95% C = .030, .126 [AHA:INTV]; β = .101, 95% C = .055, .155 [AUA:INTV]) and significant direct effect on INTV (β = .175, p < .001 [AHA:INTV]; β = .100, p = .003 [AUA:INTV]). Furthermore, the addition of direct paths from background factors to intentions improved the explained variance in intention (R2 = .324; R2Adj = .317) and the predictive relevance (Q2 = .300) over the base-model. This supports existing literature on the superiority of enhanced TPB models to predict ethical issues; which suggests that moral behavior may add additional complexity to decision-making. Regarding gender effect, MGA showed that gender only moderated the influence of AHA on ATTV (e.g., βWomen−βMen = .296, p < .001 [Model #6]). However, other observed gender differences (e.g. the explained variance of the model for intentions were always higher for men that for women, for instance, R2Women = .298; R2Men = .394 [Model #6]) deserve further considerations, especially for developing more effective communication strategies.

Keywords: veganism, Theory of Planned Behavior, background factors, gender moderation

Procedia PDF Downloads 315

Authors: Patrick Weber, Daniel Gredig

Abstract:

Background and Purpose: Research has well documented the impact of discrimination and micro-aggressions on the wellbeing of gay men and, especially, adolescents. For the prevention of homophobic behavior against gay adolescents, however, the focus has to shift on those who discriminate: For the design and tailoring of prevention and intervention, it is important to understand the factors responsible for homophobic behavior such as, for example, verbal abuse. Against this background, the present study aimed to assess homophobic – in terms of verbally abusive – behavior against gay people among high school students. Furthermore, it aimed to establish the predictors of the reported behavior by testing an explanatory model. This model posits that homophobic behavior is determined by negative attitudes and knowledge. These variables are supposed to be predicted by the acceptance of traditional gender roles, religiosity, orientation toward social dominance, contact with gay men, and by the perceived expectations of parents, friends and teachers. These social-cognitive variables in turn are assumed to be determined by students’ gender, age, immigration background, formal school level, and the discussion of gay issues in class. Method: From August to October 2016, we visited 58 high school classes in 22 public schools in a county in Switzerland, and asked the 8th and 9th year students on three formal school levels to participate in survey about gender and gay issues. For data collection, we used an anonymous self-administered questionnaire filled in during class. Data were analyzed using descriptive statistics and structural equation modelling (Generalized Least Square Estimates method). The sample included 897 students, 334 in the 8th and 563 in the 9th year, aged 12–17, 51.2% being female, 48.8% male, 50.3% with immigration background. Results: A proportion of 85.4% participants reported having made homophobic statements in the 12 month before survey, 4.7% often and very often. Analysis showed that respondents’ homophobic behavior was predicted directly by negative attitudes (β=0.20), as well as by the acceptance of traditional gender roles (β=0.06), religiosity (β=–0.07), contact with gay people (β=0.10), expectations of parents (β=–0.14) and friends (β=–0.19), gender (β=–0.22) and having a South-East-European or Western- and Middle-Asian immigration background (β=0.09). These variables were predicted, in turn, by gender, age, immigration background, formal school level, and discussion of gay issues in class (GFI=0.995, AGFI=0.979, SRMR=0.0169, CMIN/df=1.199, p>0.213, adj. R2 =0.384). Conclusion: Findings evidence a high prevalence of homophobic behavior in the responding high school students. The tested explanatory model explained 38.4% of the assessed homophobic behavior. However, data did not found full support of the model. Knowledge did not turn out to be a predictor of behavior. Except for the perceived expectation of teachers and orientation toward social dominance, the social-cognitive variables were not fully mediated by attitudes. Equally, gender and immigration background predicted homophobic behavior directly. These findings demonstrate the importance of prevention and provide also leverage points for interventions against anti-gay bias in adolescents – also in social work settings as, for example, in school social work, open youth work or foster care.

Keywords: discrimination, high school students, gay men, predictors, Switzerland

Procedia PDF Downloads 310

Authors: D. K. Kumador, E. A. Muthivhi

Abstract:

Historically, reforms in early childhood education in Ghana have focused narrowly on structural and pedagogical aspects with little attention paid to the broader sociocultural framework within which schooling and child development systems interact. This preliminary study investigates inclusive early childhood education within rapidly changing Ghanaian socio-cultural context, and its consequences for the development of children with learning disabilities. The study addresses an important topic, which is largely under-researched outside of Europe, North America, and Australasia. While inclusive education has been widely accepted globally at the level of policy, its implementation is uneven, as is shown in numerous studies across an array of countries and education systems. Despite this burgeoning area of research internationally, there have been far fewer studies conducted in African settings and fewer still that use cultural-historical activity theory as an investigative approach. More so, specific literature on the subject in the Ghanaian context is non-existent and, as such, coming to a deeper understanding of the sociocultural practices that shape, and possibly impede, inclusive early childhood education in an African country, Ghana, is a worthwhile research endeavour. Using cultural-historical activity theory as a methodological framework, this study employed classroom observations, and in-depth interviews and focus group discussions of preschool teachers in three kindergarten centres in the Greater Accra Region of Ghana to qualitatively explore inclusive early childhood education and the development of children with learning disabilities. The findings showed that literature from Ghana rarely discusses child informed consent as an on-going process that must be articulated throughout the research process from data collection to analysis, reporting and dissemination. Further, the study showed that the introduction and implementation of inclusive education framework – with its concomitant revisions in the curriculum, policies, and school rules, as well as enhanced community and parent involvement – into existing schooling practices, generated contradictions in inclusive teachers’ approaches to teaching and learning, and classroom management. Generally, contradictions in the understanding and acceptability of approaches to teaching and learning occur when a new way of doing things is incorporated into existing practices. These contradictions are thought to be a source of change and development. Thus, they guide teachers to unlearn outmoded practices, relearn or learn new approaches that are beneficial to the development of all children. Nonetheless, the findings of the current study showed that preschool teachers’ belief systems and perceptions of disabilities mediated the outcomes of such contradictions. Also, that was evidenced in the way they engaged children with learning disabilities compared to their typically developing counterparts, showing disregard for what was prescribed by new policies and school rules. The findings have implications for research with young children and the development outcomes of children with learning disabilities in inclusive early childhood education settings.

Keywords: CHAT, classroom management, cultural-historical activity theory, ghana, inclusive early childhood education, schooling practices, young children with learning disabilities

Procedia PDF Downloads 99

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 347

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

Abstract:

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

Procedia PDF Downloads 244

Authors: Sonika Sharma, Mohan G. Vairale, Sibnarayan Datta, Soumya Chatterjee, Dharmendra Dubey, Rajesh Prasad, Raghvendra Budhauliya, Bidisha Das, Vijay Veer

Abstract:

Bacteriophages are viruses that parasitize specific bacteria and multiply in metabolising host bacteria. Bacteriophages hunt for a single or a subset of bacterial species, making them potential antibacterial agents. Utilizing the ability of phages to control bacterial populations has several applications from medical to the fields of agriculture, aquaculture and the food industry. However, harnessing phage based techniques in wastewater treatments to improve quality of effluent and sludge release into the environment is a potential area for R&D application. Phage mediated bactericidal effect in any wastewater treatment process has many controlling factors that lead to treatment performance. In laboratory conditions, titer of bacteriophages (coliphages) isolated from effluent water of a specially designed anaerobic digester of human night soil (DRDO Biotoilet) was successfully increased with a modified protocol of the classical double layer agar technique. Enrichment of the same was carried out and efficacy of the phage enriched medium was evaluated at different conditions (specific media, temperature, storage conditions). Growth optimization study was carried out on different media like soybean casein digest medium (Tryptone soya medium), Luria-Bertani medium, phage deca broth medium and MNA medium (Modified nutrient medium). Further, temperature-phage yield relationship was also observed at three different temperatures 27˚C, 37˚C and 44˚C at laboratory condition. Results showed the higher activity of coliphage 27˚C and at 37˚C. Further, addition of divalent ions (10mM MgCl2, 5mM CaCl2) and 5% glycerol resulted in a significant increase in phage titer. Besides this, effect of antibiotics addition like ampicillin and kanamycin at different concentration on plaque formation was analysed and reported that ampicillin at a concentration of 1mg/ml ampicillin stimulates phage infection and results in more number of plaques. Experiments to test viability of phage showed that it can remain active for 6 months at 4˚C in fresh tryptone soya broth supplemented with fresh culture of coliforms (early log phase). The application of bacteriophages (especially coliphages) for treatment of effluent of human faecal matter contaminated effluent water is unique. This environment-friendly treatment system not only reduces the pathogenic coliforms, but also decreases the competition between nuisance bacteria and functionally important microbial populations. Therefore, the phage based cocktail to treat fecal pathogenic bacteria present in black water has many implication in wastewater treatment processes including ‘DRDO Biotoilet’, which is an ecofriendly appropriate and affordable human faecal matter treatment technology for different climates and situations.

Keywords: wastewater, microbes, virus, biotoilet, phage viability

Procedia PDF Downloads 402

Authors: Tony Wilson

Abstract:

This paper sets out a practices perspective or practices theory, which has become pervasive from business to sociological studies. In doing so, it locates the perspective historically (in the work of the philosopher Heidegger) and provides a contemporary illustration of its application to communication, consumer and cultural studies as central to this conference theme. The structured account of practices (as articulated in eight ‘axioms’) presented towards the conclusion of this paper is an initial statement - planned to encourage further detailed qualitative and systematic research in areas of interest to the conference. Practice theories of equipped and situated construction of participatory meaning (as in media and marketing consuming) are frequently characterized as lacking common ground, or core principles. This paper explores whether by retracing a journey to earlier philosophical underwriting, a shared territory promoting new research can be located as current philosophical hermeneutics. Moreover, through returning to hermeneutic first principles, the paper shows that a series of spatio-temporal metaphors become available - appropriate to analyzing communication as a process across disciplines in which it is considered. Thus one can argue, for instance, that media users engage (enter) digital text from their diverse ‘horizons of expectation’, in a productive enlarging ‘fusion’ of horizons of understanding, thereby ‘projecting’ a new narrative, integrated in a ‘hermeneutic circle’ of meaning. A politics of communication studies may contest a horizon of understanding - so engaging in critical ‘distancing’. Marketing’s consumers can occupy particular places on a horizon of understanding. Media users pass over borders of changing, revised perspectives. Practices research can now not only be discerned in multiple disciplines but equally crosses disciplines. The ubiquitous practice of media use by managers and visitors in a shopping mall - the mediatization of malls - responds to investigating not just with media study expertise, but from an interpretive marketing perspective. How have mediated identities of person or place been changed? Emphasizing understanding of entities in a material environment as ‘equipment’, practices theory enables the quantitative correlation of use and demographic variable as ‘Zeug Score’. Human behavior is fundamentally habitual - shaped by its tacit assumptions - occasionally interrupted by reflection. Practices theory acknowledges such action to be minimally monitored yet nonetheless considers it as constructing narrative. Thus presented in research, ‘storied’ behavior can then be seen to be (in)formed and shaped from a shifting hierarchy of ‘horizons’ or of perspectives - from habituated to reflective - rather than a single seamless narrative. Taking a communication practices perspective here avoids conflating tacit, transformative and theoretical understanding in research. In short, a historically grounded and unifying statement of contemporary practices theory will enhance its potential as a tool in communication, consumer and cultural research, landscaping interpretative horizons of human behaviour through exploring widely the culturally (in)formed narratives equipping and incorporated (reflectively, unreflectively) in people’s everyday lives.

Keywords: communication, consumer, cultural practices, hermeneutics

Procedia PDF Downloads 238

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

Abstract:

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

Procedia PDF Downloads 309

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

Procedia PDF Downloads 39

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

Abstract:

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

Procedia PDF Downloads 308

Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

Abstract:

A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

Procedia PDF Downloads 67

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

Abstract:

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

Procedia PDF Downloads 155

Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

Abstract:

Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

Keywords:

Procedia PDF Downloads 151

Authors: Rijnbout-St.James Willem, Lindner Volkhard, Scholand Mary Beth, Ashton M. Tillett, Di Gennaro Michael Jude, Smith Silvia Enrica

Abstract:

Introduction: Fibrosing lung diseases are characterized by changes in the lung interstitium and are classified based on etiology: 1) environmental/exposure-related, 2) autoimmune-related, 3) sarcoidosis, 4) interstitial pneumonia, and 4) idiopathic. Among interstitial lung diseases (ILD) idiopathic forms, idiopathic pulmonary fibrosis (IPF) is the most severe. Pathogenesis of IPF is characterized by an increased presence of proinflammatory mediators, resulting in alveolar injury, where injury to alveolar epithelium precipitates an increase in collagen deposition, subsequently thickening the alveolar septum and decreasing gas exchange. Identifying biomarkers implicated in the pathogenesis of lung fibrosis is key to developing new therapies and improving the efficacy of existing therapies. The transforming growth factor-beta (TGF-B1), a mediator of tissue repair associated with WNT5A signaling, is partially responsible for fibroblast proliferation in ILD and is the target of Pirfenidone, one of the antifibrotic therapies used for patients with IPF. Canonical TGF-B signaling is mediated by the proteins SMAD 2/3, which are, in turn, indirectly regulated by Collagen Triple Helix Repeat Containing 1 (CTHRC1). In this study, we tested the following hypotheses: 1) CTHRC1 is more elevated in the ILD cohort compared to unaffected controls, and 2) CTHRC1 is differently expressed among ILD types. Material and Methods: CTHRC1 levels were measured by ELISA in 171 plasma samples from the deidentified University of Utah ILD cohort. Data represent a cohort of 131 ILD-affected participants and 40 unaffected controls. CTHRC1 samples were categorized by a pulmonologist based on affectation status and disease subtypes: IPF (n = 45), sarcoidosis (4), nonspecific interstitial pneumonia (16), hypersensitivity pneumonitis (n = 7), interstitial pneumonia (n=13), autoimmune (n = 15), other ILD - a category that includes undifferentiated ILD diagnoses (n = 31), and unaffected controls (n = 40). We conducted a single-factor ANOVA of plasma CTHRC1 levels to test whether CTHRC1 variance among affected and non-affected participants is statistically significantly different. In-silico analysis was performed with Ingenuity Pathway Analysis® to characterize the role of CTHRC1 in the pathway of lung fibrosis. Results: Statistical analyses of CTHRC1 in plasma samples indicate that the average CTHRC1 level is significantly higher in ILD-affected participants than controls, with the autoimmune ILD being higher than other ILD types, thus supporting our hypotheses. In-silico analyses show that CTHRC1 indirectly activates and phosphorylates SMAD3, which in turn cross-regulates TGF-B1. CTHRC1 also may regulate the expression and transcription of TGFB-1 via WNT5A and its regulatory relationship with CTNNB1. Conclusion: In-silico pathway analyses demonstrate that CTHRC1 may be an important biomarker in ILD. Analysis of plasma samples indicates that CTHRC1 expression is positively associated with ILD affectation, with autoimmune ILD having the highest average CTHRC1 values. While characterizing CTHRC1 levels in plasma can help to differentiate among ILD types and predict response to Pirfenidone, the extent to which plasma CTHRC1 level is a function of ILD severity or chronicity is unknown.

Keywords: interstitial lung disease, CTHRC1, idiopathic pulmonary fibrosis, pathway analyses

Procedia PDF Downloads 165

Authors: Man Ying Kang, Joshua Kin Man Nan

Abstract:

The prolonged pandemic has posed alarming public health challenges to various parts of the world, and face-to-face mental health treatment is largely discounted for the control of virus transmission, online psychological services and self-help mental health kits have become essential. Online self-help mindfulness-based interventions have proved their effects on fostering mental health for different populations over the globe. This paper was to test the effectiveness of an online short-term audio-based mindfulness (SAM) program in enhancing wellbeing, dispositional mindfulness, and reducing stress and negative affect in community settings in China, and to explore possible mechanisms of how dispositional mindfulness, stress, and negative affect influenced the intervention effects on wellbeing. Community-dwelling adults were recruited via online social networking sites (e.g., QQ, WeChat, and Weibo). Participants (n=100) were randomized into the mindfulness group (n=50) and a waitlist control group (n=50). In the mindfulness group, participants were advised to spend 10–20 minutes listening to the audio content, including mindful-form practices (e.g., eating, sitting, walking, or breathing). Then practice daily mindfulness exercises for 3 weeks (a total of 21 sessions), whereas those in the control group received the same intervention after data collection in the mindfulness group. Participants in the mindfulness group needed to fill in the World Health Organization Five Well-Being Index (WHO), Positive and Negative Affect Schedule (PANAS), Perceived Stress Scale (PSS), and Freiburg Mindfulness Inventory (FMI) four times: at baseline (T0) and at 1 (T1), 2 (T2), and 3 (T3) weeks while those in the waitlist control group only needed to fill in the same scales at pre- and post-interventions. Repeated-measure analysis of variance, paired sample t-test, and independent sample t-test was used to analyze the variable outcomes of the two groups. The parallel process latent growth curve modeling analysis was used to explore the longitudinal moderated mediation effects. The dependent variable was WHO slope from T0 to T3, the independent variable was Group (1=SAM, 2=Control), the mediator was FMI slope from T0 to T3, and the moderator was T0NA and T0PSS separately. The different levels of moderator effects on WHO slope was explored, including low T0NA or T0PSS (Mean-SD), medium T0NA or T0PSS (Mean), and high T0NA or T0PSS (Mean+SD). The results found that SAM significantly improved and predicted higher levels of WHO slope and FMI slope, as well as significantly reduced NA and PSS. FMI slope positively predict WHO slope. FMI slope partially mediated the relationship between SAM and WHO slope. Baseline NA and PSS as the moderators were found to be significant between SAM and WHO slope and between SAM and FMI slope, respectively. The conclusion was that SAM was effective in promoting levels of mental wellbeing, positive affect, and dispositional mindfulness as well as reducing negative affect and stress in community settings in China. SAM improved wellbeing faster through the faster enhancement of dispositional mindfulness. Participants with medium-to-high negative affect and stress buffered the therapy effects of SAM on wellbeing improvement speed.

Keywords: mindfulness, negative affect, stress, wellbeing, randomized control trial

Procedia PDF Downloads 82

Authors: Felix Lankester, Alicia Davis, Safari Kinung'hi, Catherine Bunga, Shayo Alkara, Imam Mzimbiri, Jonathan Yoder, Sarah Cleaveland, Guy H. Palmer

Abstract:

Achieving the London Declaration goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires cost-effective strategies that attain high and comprehensive coverage. The first objective of this trial was to assess the impact on cost and coverage of employing a novel integrative One Health approach linking two NTD control programs: mass drug administration (MDA) for soil-transmitted helminths in humans (STH) and mass dog rabies vaccination (MDRV). The second objective was to compare the coverage achieved by the MDA, a community-wide deworming intervention, with that of the existing national primary school-based deworming program (NSDP), with particular focus on the proportion of primary school-age children reached and their school enrolment status. Our approach was unconventional because, in line with the One Health approach to disease control, it coupled the responsibilities and resources of the Ministries responsible for human and animal health into one program with the shared aim of preventing multiple NTDs. The trial was carried out in hard-to-reach pastoral communities comprising 24 villages of the Ngorongoro District, Tanzania, randomly allocated to either Arm A (MDA and MDRV), Arm B (MDA only) or Arm C (MDRV only). Objective one: The percentage of people in each target village that received treatment through MDA in Arms A and B was 63% and 65%, respectively (χ2 = 1, p = 0.32). The percentage of dogs vaccinated in Arm A and C was 70% and 81%, respectively (χ2 =9, p = 0.003). It took 33% less time for a single person and a dog to attend the integrated delivery than two separate events. Cost per dose (including delivery) was lower under the integrated strategy, with delivery of deworming and rabies vaccination reduced by $0.13 (54%) and $0.85 (19%) per dose, respectively. Despite a slight reduction in the proportion of village dogs vaccinated in the integrated event, both the integrated and non-integrated strategies achieved the target threshold of 70% required to eliminate rabies. Objective two: The percentages of primary school age children enrolled in school that was reached by this trial (73%) and the existing NSDP (80%) were not significantly different (F = 0.9, p = 0.36). However, of the primary school age children treated in this trial, 46% were not enrolled in school. Furthermore, 86% of the people treated would have been outside the reach of the NSDP because they were not primary school age or were primary school age children not enrolled in school. The comparable reach, the substantial reductions in cost per dose delivered and the decrease in participants’ time support this integrated One Health approach to control multiple NTDs. Further, the recorded level of non-enrolment at primary school suggests that, in remote areas, school-based delivery strategies could miss a large fraction of school-age children and that programs that focus delivery solely at the level of the primary school will miss a substantial proportion of both primary school age children as well as other individuals from the community. We have shown that these populations can be effectively reached through extramural programs.

Keywords: canine mediated human rabies, integrated health interventions, mass drug administration, neglected tropical disease, One Health, soil-transmitted helminths

Procedia PDF Downloads 143

Authors: Fadi Al Khatib, Raouf Mbarki, Malek Adouni

Abstract:

In various sport and recreational activities, the patellofemoral joint undergoes large forces and moments while accommodating the significant knee joint movement. In doing so, this joint is commonly the source of anterior knee pain related to instability in normal patellar tracking and excessive pressure syndrome. One well-observed explanation of the instability of the normal patellar tracking is the patellofemoral ligaments and patellar tendon damage. Improved knowledge of the damage mechanism mediating ligaments and tendon injuries can be a great help not only in rehabilitation and prevention procedures but also in the design of better reconstruction systems in the management of knee joint disorders. This damage mechanism, specifically due to excessive mechanical loading, has been linked to the micro level of the fibred structure precisely to the tropocollagen molecules and their connection density. We argue defining a clear frame starting from the bottom (micro level) to up (macro level) in the hierarchies of the soft tissue may elucidate the essential underpinning on the state of the ligaments damage. To do so, in this study a multiscale fibril reinforced hyper elastoplastic Finite Element model that accounts for the synergy between molecular and continuum syntheses was developed to determine the short-term stresses/strains patellofemoral ligaments and tendon response. The plasticity of the proposed model is associated only with the uniaxial deformation of the collagen fibril. The yield strength of the fibril is a function of the cross-link density between tropocollagen molecules, defined here by a density function. This function obtained through a Coarse-graining procedure linking nanoscale collagen features and the tissue level materials properties using molecular dynamics simulations. The hierarchies of the soft tissues were implemented using the rule of mixtures. Thereafter, the model was calibrated using a statistical calibration procedure. The model then implemented into a real structure of patellofemoral ligaments and patellar tendon (OpenKnee) and simulated under realistic loading conditions. With the calibrated material parameters the calculated axial stress lies well with the experimental measurement with a coefficient of determination (R2) equal to 0.91 and 0.92 for the patellofemoral ligaments and the patellar tendon respectively. The ‘best’ prediction of the yielding strength and strain as compared with the reported experimental data yielded when the cross-link density between the tropocollagen molecule of the fibril equal to 5.5 ± 0.5 (patellofemoral ligaments) and 12 (patellar tendon). Damage initiation of the patellofemoral ligaments was located at the femoral insertions while the damage of the patellar tendon happened in the middle of the structure. These predicted finding showed a meaningful correlation between the cross-link density of the tropocollagen molecules and the stiffness of the connective tissues of the extensor mechanism. Also, damage initiation and propagation were documented with this model, which were in satisfactory agreement with earlier observation. To the best of our knowledge, this is the first attempt to model ligaments from the bottom up, predicted depending to the tropocollagen cross-link density. This approach appears more meaningful towards a realistic simulation of a damaging process or repair attempt compared with certain published studies.

Keywords: tropocollagen, multiscale model, fibrils, knee ligaments

Procedia PDF Downloads 102

Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

Abstract:

Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

Procedia PDF Downloads 270

Authors: Rupak Kumar Sarma, Ratul Saikia

Abstract:

Macrophytes encompass major functional group in eutrophic wetland ecosystems. As a key functional element of freshwater lakes, they play a crucial role in regulating various wetland biogeochemical cycles, as well as maintain the biodiversity at the ecosystem level. The high carbon-rich underground biomass of macrophyte populations may harbour diverse microbial community having significant potential in maintaining different biogeochemical cycles. The present investigation was designed to study the macrophyte-microbe interaction in coupled nitrification and denitrification, considering Deepor Beel Lake (a Ramsar conservation site) of North East India as a model eutrophic system. Highly eutrophic sites of Deepor Beel were selected based on sediment oxygen demand and inorganic phosphorus and nitrogen (P&N) concentration. Sediment redox potential and depth of the lake was chosen as the benchmark for collecting the plant and sediment samples. The average highest depth in winter (January 2016) and summer (July 2016) were recorded as 20ft (6.096m) and 35ft (10.668m) respectively. Both sampling depth and sampling seasons had the distinct effect on variation in macrophyte community composition. Overall, the dominant macrophytic populations in the lake were Nymphaea alba, Hydrilla verticillata, Utricularia flexuosa, Vallisneria spiralis, Najas indica, Monochoria hastaefolia, Trapa bispinosa, Ipomea fistulosa, Hygrorhiza aristata, Polygonum hydropiper, Eichhornia crassipes and Euryale ferox. There was a distinct correlation in the variation of major sediment physicochemical parameters with change in macrophyte community compositions. Quantitative estimation revealed an almost even accumulation of nitrate and nitrite in the sediment samples dominated by the plant species Eichhornia crassipes, Nymphaea alba, Hydrilla verticillata, Vallisneria spiralis, Euryale ferox and Monochoria hastaefolia, which might have signified a stable nitrification and denitrification process in the sites dominated by the selected aquatic plants. This was further examined by a systematic analysis of microbial populations through culture dependent and independent approach. Culture-dependent bacterial community study revealed the higher population of nitrifiers and denitrifiers in the sediment samples dominated by the six macrophyte species. However, culture-independent study with bacterial 16S rDNA V3-V4 metagenome sequencing revealed the overall similar type of bacterial phylum in all the sediment samples collected during the study. Thus, there might be the possibility of uneven distribution of nitrifying and denitrifying molecular markers among the sediment samples collected during the investigation. The diversity and abundance of the nitrifying and denitrifying molecular markers in the sediment samples are under investigation. Thus, the role of different aquatic plant functional types in microorganism mediated nitrogen cycle coupling could be screened out further from the present initial investigation.

Keywords: denitrification, macrophyte, metagenome, microorganism, nitrification

Procedia PDF Downloads 146

Authors: Jyh-Ping Chen, Yu-Tin Lai

Abstract:

Wound healing is a complicated process involving overlapping hemostasis, inflammation, proliferation, and maturation phases. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. Poly(lactic-co-glycolic acid) (PLGA) is an U.S. FDA approved biodegradable polymer to be used as ideal wound dressing material. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that are the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcumin-loaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479 nm and with alignment angles within  0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are well-known transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.

Keywords: Curcumin, heparin, nanofibrous membrane, poly(lactic-co-glycolic acid) (PLGA), wound dressing

Procedia PDF Downloads 132