Search results for: disability acceptance

Authors: Farwa Rizvi, Joanne Williams, Humaira Maheen, Elizabeth Hoban

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There is an increase in risky sexual behavior and unsafe sex in adolescent girls and young women aged 15 to 24 years in Cambodia, which negatively affects their reproductive health by increasing the risk of contracting sexually transmitted infections and unintended pregnancies. Risky sexual behavior includes ‘having sex at an early age, having multiple sexual partners, having sex while under the influence of alcohol or drugs, and unprotected sexual behaviors’. A systematic review of quantitative research conducted in Cambodia was undertaken, using the theoretical framework of the Social Ecological Model to identify the personal, social and cultural factors associated with risky sexual behavior and unsafe sex in young Cambodian women. PRISMA guidelines were used to search databases including Medline Complete, PsycINFO, CINAHL Complete, Academic Search Complete, Global Health, and Social Work Abstracts. Additional searches were conducted in Science Direct, Google Scholar and in the grey literature sources. A risk-of-bias tool developed explicitly for the systematic review of cross-sectional studies was used. Summary item on the overall risk of study bias after the inter-rater response showed that the risk-of-bias was high in two studies, moderate in one study and low in one study. The search strategy included a combination of subject terms and free text terms. The medical subject headings (MeSH) terms included were; contracept* or ‘birth control’ or ‘family planning’ or pregnan* or ‘safe sex’ or ‘protected intercourse’ or ‘unprotected intercourse’ or ‘protected sex’ or ‘unprotected sex’ or ‘risky sexual behaviour*’ or ‘abort*’ or ‘planned parenthood’ or ‘unplanned pregnancy’ AND ( barrier* or obstacle* or challenge* or knowledge or attitude* or factor* or determinant* or choic* or uptake or discontinu* or acceptance or satisfaction or ‘needs assessment’ or ‘non-use’ or ‘unmet need’ or ‘decision making’ ) AND Cambodia*. Initially, 300 studies were identified by using key words and finally, four quantitative studies were selected based on the inclusion criteria. The four studies were published between 2010 and 2016. The study participants ranged in age from 10-24 years, single or married, with 3 to 10 completed years of education. The mean age at sexual debut was reported to be 18 years. Using the perspective of the Social Ecological Model, risky sexual behavior was associated with individual-level factors including young age at sexual debut, low education, unsafe sex under the influence of alcohol and substance abuse, multiple sexual partners or transactional sex. Family level factors included living away from parents, orphan status and low levels of family support. Peer and partner level factors included peer delinquency and lack of condom use. Low socioeconomic status at the society level was also associated with risky sexual behaviour. There is scant research on sexual and reproductive health of adolescent girls and young women in Cambodia. Individual, family and social factors were significantly associated with risky sexual behaviour. More research is required to inform potential preventive strategies and policies that address young women’s sexual and reproductive health.

Keywords: adolescents, high-risk sex, sexual activity, unplanned pregnancies

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Authors: Marit D. Murry, Amy K. Marks

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The transition to college is a critical period that affords abundant opportunities for growth in conjunction with novel challenges for emerging adults. During this time, emerging adults are garnering experiences and acquiring hosts of new information that they are required to synthesize and use to inform life-shaping decisions. This stage is characterized by instability and exploration, which necessitates a diverse set of coping skills to successfully navigate and positively adapt to their evolving environment. However, important sociocultural factors result in differences that occur developmentally for minority emerging adults (i.e., emerging adults with an identity that has been or is marginalized). While the transition to college holds vast potential, not all are afforded the same chances, and many individuals enter into this stage at varying degrees of readiness. Understanding the nuance and diversity of student preparedness for college and contextualizing these factors will better equip systems to support incoming students. Emerging adulthood for ethnic, racial minority students presents itself as an opportunity for growth and resiliency in the face of systemic adversity. Ethnic, racial identity (ERI) is defined as an identity that develops as a function of one’s ethnic-racial group membership. Research continues to demonstrate ERI as a resilience factor that promotes positive adjustment in young adulthood. Adaptive coping responses (e.g., engaging in help-seeking behavior, drawing on personal and community resources) have been identified as possible mechanisms through which ERI buffers youth against stressful life events, including discrimination. Additionally, trait mindfulness has been identified as a significant predictor of general psychological health, and mindfulness practice has been shown to be a self-regulatory strategy that promotes healthy stress responses and adaptive coping strategy selection. The current study employed a person-centered approach to explore emerging patterns across ethnic identity development and psychological well-being criterion variables among college freshmen. Data from 283 incoming college freshmen at Northeastern University were analyzed. The Brief COPE Acceptance and Emotional Support scales, the Five Factor Mindfulness Questionnaire, and MIEM Exploration and Affirmation measures were used to inform the cluster profiles. The TwoStep auto-clustering algorithm revealed an optimal three-cluster solution (BIC = 848.49), which classified 92.6% (n = 262) of participants in the sample into one of the three clusters. The clusters were characterized as ‘Mixed Adjustment’, ‘Lowest Adjustment’, and ‘Moderate Adjustment.’ Cluster composition varied significantly by ethnicity X² (2, N = 262) = 7.74 (p = .021) and gender X² (2, N = 259) = 10.40 (p = .034). The ‘Lowest Adjustment’ cluster contained the highest proportion of students of color, 41% (n = 32), and male-identifying students, 44.2% (n = 34). Follow-up analyses showed higher ERI exploration in ‘Moderate Adjustment’ cluster members, also reported higher levels of psychological distress, with significantly elevated depression scores (p = .011), psychological diagnoses of depression (p = .013), anxiety (p = .005) and psychiatric disorders (p = .025). Supporting prior research, students engaging with identity exploration processes often endure more psychological distress. These results indicate that students undergoing identity development may require more socialization and different services beyond normal strategies.

Keywords: adjustment, coping, college, emerging adulthood, ethnic-racial identity, psychological well-being, resilience

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Authors: Joshua Doe, George Amoako

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Purpose: In an increasingly digital world, the realm of sports fandom has extended its borders, creating a vibrant ecosystem of online communities centered around football clubs. This study ventures into the intricate interplay of motivations that drive football fans to respond to brand activism and its profound implications for brand antagonism and engagement among two of Ghana's most revered premier football clubs. Methods: A sample of 459 fervent fans from these two rival clubs were engaged through self-administered questionnaires expertly distributed via social media and online platforms. Data was analysed, using PLS-SEM. Findings: The tapestry of motivations that weave through these online football communities is as diverse as the fans themselves. It becomes apparent that fans are propelled by a spectrum of incentives. They seek education, yearn for information, revel in entertainment, embrace socialization, and fortify their self-esteem through their interactions within these digital spaces. Yet, it is the nuanced distinction in these motivations that shapes the trajectory of brand antagonism and engagement. Surprisingly, the study reveals a remarkable pattern. Football fans, despite their fierce rivalries, do not engage in brand antagonism based on educational pursuits, information-seeking endeavors, or socialization. Instead, it is motivations rooted in entertainment and self-esteem that serve as the fertile grounds for brand antagonism. Paradoxically, it is these very motivations coupled with the desire for socialization that nurture brand engagement, manifesting as active support and advocacy for their chosen club brand. Originality: Our research charters new waters by extending the boundaries of existing theories in the field. The Technology Acceptance Uses and Gratifications Theory, and Social Identity Theory all find new dimensions within the context of online brand community engagement. This not only deepens our understanding of the multifaceted world of online football fandom but also invites us to explore the implications these insights carry within the digital realm. Contribution to Practice: For marketers, our findings offer a treasure trove of actionable insights. They beckon the development of targeted content strategies that resonate with fan motivations. The implementation of brand advocacy programs, fostering opportunities for socialization, and the effective management of brand antagonism emerge as pivotal strategies. Furthermore, the utilization of data-driven insights is poised to refine consumer engagement strategies and strengthen brand affinity. Future Studies: For future studies, we advocate for longitudinal, cross-cultural, and qualitative studies that could shed further light on this topic. Comparative analyses across different types of online brand communities, an exploration of the role of brand community leaders, and inquiries into the factors that contribute to brand community dissolution all beckon the research community. Furthermore, understanding motivation-specific antagonistic behaviors and the intricate relationship between information-seeking and engagement present exciting avenues for further exploration. This study unfurls a vibrant tapestry of fan motivations, brand activism, and rivalry within online football communities. It extends a hand to scholars and marketers alike, inviting them to embark on a journey through this captivating digital realm, where passion, rivalry, and engagement harmonize to shape the world of sports fandom as we know it.

Keywords: online brand engagement, football fans, brand antagonism, motivations

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Authors: Rocio Murad, Marcela Sanchez, Mariana Calderon Jaramillo, Danny Rivera, Angela Cifuentes, Daniela Roldán, Juan Carlos Rivillas

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Women and girls have specific health needs, but during health pandemics such as COVID19 they are less likely to have access to quality essential health information, commodities and services, or insurance coverage for routine and catastrophic health expenses, especially in rural and marginalized communities. This is compounded by multiple or intersecting inequalities, such as ethnicity, socioeconomic status, disability, age, geographic location, and sexual orientation, among others. Despite concerted collective action, there is a lack of information on the situation of women, adolescents and youth, including gender inequalities exacerbated by the pandemic. Much more needs to be done to amplify the lived realities of women and adolescents in global and national advocacy and policy responses. The COVID 19 pandemic reflects the need for systematic advocacy policies based on the lived experiences of women and adolescents, underpinned by human rights. This research is part of the initiative of Profamilia Association (Solidarity Study), and its objective is twofold: i) to analyze the behavioral changes and immediate expectations of Colombians during the stage of relaxation of the confinement measures decreed by the national government; and ii) to identify the needs, experiences and resilient practices of adolescents and young women during the COVID-19 crisis in Colombia. Descriptive analysis of data collected by Profamilia through the Solidaridad study, an exploratory cross-sectional descriptive study that used subnational level data from a nonprobabilistic sample survey conducted to 1735 adults, between September 01 and 11, 2020. Interviews were conducted with key stakeholders about their experiences during COVID19, under three key axes: i) main challenges for adolescents and young women; ii) examples of what has worked well in responding to the challenge; and iii) how/what services are/should be provided during COVID-19 (and beyond) to address the challenge. Interviewees were selected based on prior mapping of social groups of interest. In total, 23 adolescents and young women participated in the interviews. The results show that people adopted behavioral changes such as wearing masks, avoiding people with symptoms, and reducing mobility, but there was also a doubling of concerns for many reasons, from effects on mental health, sexual health, and unattended reproductive health to the burden of care and working at home. The favorable perception that people had at the beginning of the quarantine about the response and actions of the national and local government to control Covid-19 decreased over the course of the quarantine. The challenges and needs of adolescents and young women were highlighted during the most restrictive measures to contain the COVID-19 pandemic, which resulted in disruptions to daily activities, education and work, as well as restrictions to mobility and social interaction. Concerns raised by participants included: impact on mental health and wellbeing due to disruption of daily life; limitations in access to formal and informal education; food insecurity; migration; loss of livelihoods; lack of access to health information and services; limitations to sexual and reproductive health and rights; insecurity problems; and problems in communication and treatment among household members.

Keywords: COVID-19, changes in behavior, adolescents, women

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Authors: Elena Bellini, Daniele Mugnaini, Michele Boschetto

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People with an Autistic Spectrum Disorder and an Intellectual Disability who need to attend a Hospital Emergency Waiting Room frequently present high levels of discomfort and challenging behaviors due to stress-related hyperarousal, sensory sensitivity, novelty-anxiety, communication and self-regulation difficulties. Increased agitation and acting out also disturb the diagnostic and therapeutic processes, and the emergency room climate. Architectural design disciplines aimed at reducing distress in hospitals or creating autism-friendly environments are called for to find effective answers to this particular need. A growing number of researchers are considering the physical environment as an important point of intervention for people with autism. It has been shown that providing the right setting can help enhance confidence and self-esteem and can have a profound impact on their health and wellbeing. Environmental psychology has evaluated the perceived quality of care, looking at the design of hospital rooms, paths and circulation, waiting rooms, services and devices. Furthermore, many studies have investigated the influence of the hospital environment on patients, in terms of stress-reduction and therapeutic intervention’ speed, but also on health professionals and their work. Several services around the world are organizing autism-friendly hospital environments which involve the architecture and the specific staff training. In Italy, the association Spes contra spem has promoted and published, in 2013, the ‘Chart of disabled people in the hospital’. It stipulates that disabled people should have equal rights to accessible and high-quality care. There are a few Italian examples of therapeutic programmes for autistic people as the Dama project in Milan and the recent experience of Children and Autism Foundation in Pordenone. Careggi’s Emergency Waiting Room in Florence has been built to satisfy this challenge. This project of research comes from a collaboration between the technical staff of Careggi Hospital, the Center for autism PAMAPI and some architects expert in the sensory environment. The methodology of focus group involved architects, psychologists and professionals through a transdisciplinary research, centered on the links between the spatial characteristics and clinical state of people with ASD. The relationship between architectural space and quality of life is studied to pay maximum attention to users’ needs and to support the medical staff in their work by a specific program of training. The result of this research is a sum of criteria used to design the emergency waiting room, that will be illustrated. A protected room, with a clear space design, maximizes comprehension and predictability. The multisensory environment is thought to help sensory integration and relaxation. Visual communication through Ipad allows an anticipated understanding of medical procedures, and a specific technological system supports requests, choices and self-determination in order to fit sensory stimulation to personal preferences, especially for hypo and hypersensitive people. All these characteristics should ensure a better regulation of the arousal, less behavior problems, improving treatment accessibility, safety, and effectiveness. First results about patient-satisfaction levels will be presented.

Keywords: accessibility of care, autism-friendly architecture, personalized therapeutic process, sensory environment

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Authors: Sigrid James

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Purpose and Background: Despite a global policy push for deinstitutionalization, residential care for children and youth remains a relevant and highly utilized out-of-home care option in many countries, fulfilling functions of care and accommodation as well as education and treatment. While many youths are placed in residential care programs temporarily or during times of transition, some still spend years in programs that range from small group homes to large institutions. How residential care is used and what function it plays in child welfare systems is influenced by a range of factors. Among them are sociocultural and historical developments, available resources for child welfare, cultural notions about family, a lack of family-based placement alternatives as well as a belief that residential care can be beneficial to children. As part of a larger study that examined differences in residential care across 16 countries along a range of dimensions, this paper reports findings on utilization rates of residential care, i.e., the proportion of out out-of-home care dedicated to residential care relative to forms of family-based foster care. Method: Using an embedded multiple-case design study approach where a country represents a case, residential care in 16 countries was studied and compared. The comparison was focused on countries with developed social welfare systems and included Spain, Denmark, Germany, Ireland, the Netherlands, England, Scotland, Australia, Italy, Israel, Argentina, Portugal, Finland, France, the United States and Canada. Experts from each country systematically collected data on residential care based on a common matrix developed by the author. A range of sources were accessed depending on the information sought, including administrative data, government reports, research studies, etc. Utilization rates were mostly drawn from administrative data or government reports. While denominators may slightly differ, available data allowed for meaningful comparisons. Beyond descriptive data on utilization rates, analysis allowed to also capture trends in utilization (increasing, decreasing, stable) as well as the rate change. Results: Results indicate high variability in the utilization of residential care, covering the entire spectrum from a low of 7% to a high of 97%, with most countries falling somewhere in between. Three utilization categories were identified: high-users of residential care (Portugal, Argentina and Israel), medium-users (Denmark, France, Italy, Finland, Spain, Netherlands, Germany), and low-users (England, Scotland, Ireland, Canada, Australia, the United States). A number of countries experienced drastic reductions in residential care during the past few years (e.g. US), while others have seen stable rates (e.g., Portugal) or even increasing rates (e.g., Spain). Conclusions: Multiple contextual factors have to be considered when interpreting findings. For instance, countries with low residential care rates have, in most cases, undergone recent legislative changes to drastically reduce residential care. In medium-utilization countries, residential care reforms seem to be primarily focused on improving standards and, thus, the quality of care. High utilization countries generally face serious obstacles to implementing alternative family-based forms of out-of-home care. Cultural acceptance of residential or foster care and notions of professionalism also appear to play an important role in explaining variability in utilization.

Keywords: residential youth care, child welfare, case study, cross-national comparative research

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Authors: Loreta Serniene, Dalia Sekmokiene, Justina Tomkeviciute, Lina Lauciene, Vaida Andruleviciute, Ingrida Sinkeviciene, Kristina Kondrotiene, Neringa Kasetiene, Mindaugas Malakauskas

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One of the most important areas of product development and research in the dairy industry is the product enrichment with active ingredients as well as leading to increased product safety and sustainability. The most expanding field of the active ingredients is the various plants' CO₂ extracts with aromatic, antioxidant and antimicrobial properties. In this study, 15 plant extracts were evaluated based on their antioxidant, antimicrobial properties as well as sensory acceptance indicators for the development of new dairy products. In order to increase the total antioxidant capacity of the milk products, it was important to determine the content of phenolic compounds and antioxidant activity of CO₂ extract. The total phenolic content of fifteen different commercial CO₂ extracts was determined by the Folin-Ciocalteu reagent and expressed as milligrams of the Gallic acid equivalents (GAE) in gram of extract. The antioxidant activities were determined by 2.2′-azinobis-(3-ethylbenzthiazoline)-6-sulfonate (ABTS) methods. The study revealed that the antioxidant activities of investigated CO₂ extract vary from 4.478-62.035 µmole Trolox/g, while the total phenolic content was in the range of 2.021-38.906 mg GAE/g of extract. For the example, the estimated antioxidant activity of Chinese cinnamon (Cinammonum aromaticum) CO₂ extract was 62.023 ± 0.15 µmole Trolox/g and the total flavonoid content reached 17.962 ± 0.35 mg GAE/g. These two parameters suggest that cinnamon could be a promising supplement for the development of new cheese. The inhibitory effects of these essential oils were tested by using agar disc diffusion method against pathogenic bacteria, most commonly found in dairy products. The obtained results showed that essential oil of lemon myrtle (Backhousia citriodora) and cinnamon (Cinnamomum cassia) has antimicrobial activity against E. coli, S. aureus, B. cereus, P. florescens, L. monocytogenes, Br. thermosphacta, P. aeruginosa and S. typhimurium with the diameter of inhibition zones variation from 10 to 52 mm. The sensory taste acceptability of plant extracts in combination with a dairy product was evaluated by a group of sensory evaluation experts (31 individuals) by the criteria of overall taste acceptability in the scale of 0 (not acceptable) to 10 (very acceptable). Each of the tested samples included 200g grams of natural unsweetened greek yogurt without additives and 1 drop of single plant extract (essential oil). The highest average of overall taste acceptability was defined for the samples with essential oils of orange (Citrus sinensis) - average score 6.67, lemon myrtle (Backhousia citriodora) – 6.62, elderberry flower (Sambucus nigra flos.) – 6.61, lemon (Citrus limon) – 5.75 and cinnamon (Cinnamomum cassia) – 5.41, respectively. The results of this study indicate plant extracts of Cinnamomum cassia and Backhousia citriodora as a promising additive not only to increase the total antioxidant capacity of the milk products and as alternative antibacterial agent to combat pathogenic bacteria commonly found in dairy products but also as a desirable flavour for the taste pallet of the consumers with expressed need for safe, sustainable and innovative dairy products. Acknowledgment: This research was funded by the European Regional Development Fund according to the supported activity 'Research Projects Implemented by World-class Researcher Groups' under Measure No. 01.2.2-LMT-K-718.

Keywords: antioxidant properties, antimicrobial properties, cinnamon, CO₂ plant extracts, dairy products, essential oils, lemon myrtle

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Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi

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Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.

Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation

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Authors: Hsing-Hua Stella Chang, Mong-Ching Lin, Cher-Min Fong

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There has recently been a notable rise in the number of emerging-market industrial small and medium-sized enterprises (SMEs) that have managed to upgrade their operations. Evolving from original equipment manufacturing (OEM) into value-added original or own brand manufacturing (OBM) in such firms represents a specific process of internationalization. The OEM-OBM upgrade requires development of a firm’s own brand. In this respect, the extant literature points out that emerging-market industrial marketers (latecomers) have developed some marketing capabilities, of which branding has been identified as one of the most important. In specific, an industrial non-brand marketer (OEM) marks the division of labor between manufacturing and branding (as part of marketing). In light of this discussion, this research argues that branding capability plays a critical role in supporting the evolution of manufacture upgrade. This is because a smooth transformation from OEM to OBM entails the establishment of strong brands through which branding capability is developed. Accordingly, branding capability can be exemplified as a series of processes and practices in relation to mobilizing branding resources and orchestrating branding activities, which will result in the establishment of business relationships, greater acceptance of business partners (channels, suppliers), and increased industrial brand equity in the firm as key resource advantages). For the study purpose, Taiwan was chosen as the research context, representing a typical case that exemplifies the industrial development path of more-established emerging markets, namely, transformation from OEM to OBM. This research adopted a two-phase research design comprising exploratory (a qualitative study) and confirmatory approaches (a survey study) The findings show that: Country-specific advantage is positively related to branding capability for internationalizing SMEs. Firm-specific advantage is positively related to branding capability for internationalizing SMEs. Hsing-Hua Stella Chang is Assistant Professor with National Taichung University of Education, International Master of Business Administration, (Yingcai Campus) No.227, Minsheng Rd., West Dist., Taichung City 40359, Taiwan, R.O.C. (phone: 886-22183612; e-mail: [email protected]). Mong-Ching Lin is PhD candidate with National Sun Yat-Sen University, Department of Business Management, 70 Lien-hai Rd., Kaohsiung 804, Taiwan, R.O.C. (e-mail: [email protected]). Cher-Min Fong is Full Professor with National Sun Yat-Sen University, Department of Business Management, 70 Lien-hai Rd., Kaohsiung 804, Taiwan, R.O.C. (e-mail: [email protected]). Branding capability is positively related to international performance for internationalizing SMEs. This study presents a pioneering effort to distinguish industrial brand marketers from non-brand marketers in exploring the role of branding capability in the internationalizing small and medium-sized industrial brand marketers from emerging markets. Specifically, when industrial non-brand marketers (OEMs) enter into a more advanced stage of internationalization (i.e., OBM), they must overcome disadvantages (liabilities of smallness, foreignness, outsidership) that do not apply in the case of incumbent developed-country MNEs with leading brands. Such critical differences mark the urgency and significance of distinguishing industrial brand marketers from non-brand marketers on issues relating to their value-adding branding and marketing practices in international markets. This research thus makes important contributions to the international marketing, industrial branding, and SME internationalization literature.

Keywords: brand marketers, branding capability, emerging markets, SME internationalization

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Authors: Ghulam Mustafa Halepota, Zaib Dahar

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Background: Low acceptance of FP services, particularly in hard to reach areas where geographic, economic, or social barriers limit-service uptake. Moreover, limited resources appeared to be a reflection of dismal contraceptive use in Pakistan. People’s Primary Health Care Initiative (PPHI) is a Public Private Partnership Program of Government of Sindh which aims to improve maternal child health through accessible family planning services in far flung areas. In 2015 PPHI launched special family planning camps to have achieved a rapid improvement in CPR. On quarterly basis, these camps focus on Long Acting Reversible Contraceptives (LARC). These camps are arranged at 250 BHU Plus (24/7 MCHCs). The Organization manages 1140 primary health care facilities all over Sindh province and focuses on maternal, newborn and child health which includes antenatal care, labor/delivery, postnatal care, family planning, immunization, nutrition, BEmONC, CEmONC, diagnostic laboratories, ambulance services. Under the FPRH program, the organization launched special family planning camps in far flung areas to achieve a rapid improvement in CPR-committed to FP 2020 goal. Objective: To assess the performance of special FP camps for the improvement of long acting reversible contraceptive in hard to reach areas. Methodology: Outreach camps are organized on quarterly basis in 250 BHUs and maternal and child health centers (available-24/7). Using observational study design, the study reports 2 years data of special FP camps conducted in 23 various districts of Sindh during April 2015-April 2017. These special camps served a range of modern contraceptive methods including IUCDs, implants, condoms, pills, and injections. Moreover, 125 male medical officers are trained across Sindh in LARC and 554 female have been trained in implants and IUCD insertions. MSI Impact calculator was used to determine health and demographic impact of services. Results: This intervention has brought exceptional results, and the response has been overwhelming in time. Total 2048 special camps during 2015 till April 2017 have been carried out. 231796 MWRAs visited camps 91% opted modern FP, of which 45% opted Implants, 6% selected IUCDs from LARC (long term reversible contraceptive) from short term, 17% opted injectable 18% choose pills, and 12% used condoms. This intervention created a high contraceptive impact in rural Sindh an estimated 125048 FP users have been created, of this 111846 LARC users and 13498 are SARC users, through this intervention an estimated 55774 unintended pregnancies, 36299 live births, 9394, 80 maternal deaths, 926 and 6077 unsafe abortion have been averted. Moreover, the intervention created an economic impact and saved 2,409,563 direct health expenditure on each woman with reproductive age. Conclusion: Special FP Camps along with routine services is an effective and acceptable model for increase in provision of long-acting and permanent methods in hard to reach areas. This innovative approach by PHHI-Sindh has also been adopted in other provinces of Pakistan.

Keywords: inequalities, special camps, family planning services, hard to reach areas

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Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

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Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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Authors: Alexandria Carey, Angela Starkweather, Ann Horgas, Hwayoung Cho, Jason Beneciuk

Abstract:

Background/Significance: Over 3.4 million acute axial low back pain (aLBP) cases are treated annually in the United States (US) emergency departments (ED). ED patients with aLBP receive varying verbal and written discharge routine care (RC), leading to ineffective patient self-management. Ineffective self-management increase chronic low back pain (cLPB) transition risks, a chief cause of worldwide disability, with associated costs >$60 million annually. This research addresses this significant problem by evaluating an ED digital pain self-management intervention (EDPSI) focused on improving self-management through improved knowledge retainment, skills, and self-efficacy (confidence) (KSC) thus reducing aLBP to cLBP transition in ED patients discharged with aLBP. The research has significant potential to increase self-efficacy, one of the most potent mechanisms of behavior change and improve health outcomes. Focusing on accessibility and usability, the intervention may reduce discharge disparities in aLBP self-management, especially with low health literacy. Study Questions: This research will answer the following questions: 1) Will an EDPSI focused on improving KSC progress patient self-management behaviors and health status?; 2) Is the EDPSI sustainable to improve pain severity, interference, and pain recurrence?; 3) Will an EDPSI reduce aLBP to cLBP transition in patients discharged with aLBP? Aims: The pilot randomized-controlled trial (RCT) study’s objectives assess the effects of a 12-week digital self-management discharge tool in patients with aLBP. We aim to 1) Primarily assess the feasibility [recruitment, enrollment, and retention], and [intervention] acceptability, and sustainability of EDPSI on participant’s pain self-management; 2) Determine the effectiveness and sustainability of EDPSI on pain severity/interference among participants. 3) Explore patient preferences, health literacy, and changes among participants experiencing the transition to cLBP. We anticipate that EDPSI intervention will increase likelihood of achieving self-management milestones and significantly improve pain-related symptoms in aLBP. Methods: The study uses a two-group pilot RCT to enroll 30 individuals who have been seen in the ED with aLBP. Participants are randomized into RC (n=15) or RC + EDPSI (n=15) and receive follow-up surveys for 12-weeks post-intervention. EDPSI innovative content focuses on 1) highlighting discharge education; 2) provides self-management treatment options; 3) actor demonstration of ergonomics, range of motion movements, safety, and sleep; 4) complementary alternative medicine (CAM) options including acupuncture, yoga, and Pilates; 5) combination therapies including thermal application, spinal manipulation, and PT treatments. The intervention group receives Booster sessions via Zoom to assess and reinforce their knowledge retention of techniques and provide return demonstration reinforcing ergonomics, in weeks two and eight. Outcome Measures: All participants are followed for 12-weeks, assessing pain severity/ interference using the Brief Pain Inventory short-form (BPI-sf) survey, self-management (measuring KSC) using the short 13-item Patient Activation Measure (PAM), and self-efficacy using the Pain Self-Efficacy Questionnaire (PSEQ) weeks 1, 6, and 12. Feasibility is measured by recruitment, enrollment, and retention percentages. Acceptability and education satisfaction are measured using the Education-Preference and Satisfaction Questionnaire (EPSQ) post-intervention. Self-management sustainment is measured including PSEQ, PAM, and patient satisfaction and healthcare utilization (PSHU) requesting patient overall satisfaction, additional healthcare utilization, and pain management related to continued back pain or complications post-injury.

Keywords: digital, pain self-management, education, tool

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Authors: Nino Kupatadze, Tamar Memanishvili, Natia Ochkhikidze, David Tugushi, Zaal Kokaia, Ramaz Katsarava

Abstract:

Amino acid-based Biodegradable poly(ester-amide)s (PEAs) have gained considerable interest as a promising materials for numerous biomedical applications. These polymers reveal a high biocompatibility and easily form small particles suitable for delivery various biological, as well as elastic bio-erodible films serving as matrices for constructing antibacterial coatings. In the present work we have demonstrated a potential of the PEAs for two applications: 1. cell therapy for stroke as vehicles for delivery and sustained release of growth factors, 2. bactericidal coating as prevention biofilm and applicable in infected wound management. Stroke remains the main cause of adult disability with limited treatment options. Although stem cell therapy is a promising strategy, it still requires improvement of cell survival, differentiation and tissue modulation. .Recently, microspheres (MPs) made of biodegradable polymers have gained significant attention for providing necessary support of transplanted cells. To investigate this strategy in the cell therapy of stroke, MPs loaded with transcription factors Wnt3A/BMP4 were prepared. These proteins have been shown to mediate the maturation of the cortical neurons. We have suggested that implantation of these materials could create a suitable microenvironment for implanted cells. Particles with spherical shape, porous surface, and 5-40 m in size (monitored by scanning electron microscopy) were made on the basis of the original PEA composed of adipic acid, L-phenylalanine and 1,4-butanediol. After 4 months transplantation of MPs in rodent brain, no inflammation was observed. Additionally, factors were successfully released from MPs and affected neuronal cell differentiation in in vitro. The in vivo study using loaded MPs is in progress. Another severe problem in biomedicine is prevention of surgical devices from biofilm formation. Antimicrobial polymeric coatings are most effective “shields” to protect surfaces/devices from biofilm formation. Among matrices for constructing the coatings preference should be given to bio-erodible polymers. Such types of coatings will play a role of “unstable seating” that will not allow bacteria to occupy the surface. In other words, bio-erodible coatings would be discomfort shelter for bacteria that along with releasing “killers of bacteria” should prevent the formation of biofilm. For this purpose, we selected an original biodegradable PEA composed of L-leucine, 1,6-hexanediol and sebacic acid as a bio-erodible matrix, and nanosilver (AgNPs) as a bactericidal agent (“killer of bacteria”). Such nanocomposite material is also promising in treatment of superficial wound and ulcer. The solubility of the PEA in ethanol allows to reduce AgNO3 to NPs directly in the solution, where the solvent served as a reductive agent, and the PEA served as NPs stabilizer. The photochemical reduction was selected as a basic method to form NPs. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscope (TEM), and dynamic light scattering (DLS). According to the UV-data and TEM data the photochemical reduction resulted in spherical AgNPs with wide particle size distribution with a high contribution of the particles below 10 nm that are known as responsible for bactericidal activity of AgNPs. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within ca. 50 nm.

Keywords: biodegradable polymers, microparticles, nanocomposites, stem cell therapy, stroke

Procedia PDF Downloads 384

Authors: Z. S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

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Authors: Suparna Bagchi

Abstract:

Education as a discipline will probably be shaped by the importance it places on a conceptual, curricular, and pedagogical need to shift the emphasis toward transformative classrooms working for positive change through cultural diversity. Awareness of cultural diversity and race equality has heightened following George Floyd’s killing in the USA in 2020. This increasing awareness is particularly relevant in areas of historically low ethnic diversity which have lately experienced a rise in ethnic minority populations and where inclusive growth is a challenge. This research study aims to explore the perspectives of practitioners, students, and parents towards multiculturalism in four South West England primary schools. A qualitative case study methodology has been adopted framed by sociocultural theory. Data were collected through virtually conducted semi-structured interviews with school practitioners and parents, observation of students’ classroom activities, and documentary analysis of classroom displays. Although one-third of the school population includes ethnically diverse children, BAME (Black, Asian, and Minority Ethnic) characters featured in children's books published in Britain in 2019 were almost invisible, let alone a BAME main character. The Office for Standards in Education, Children's Services and Skills (Ofsted) are vocal about extending the Curriculum beyond the academic and technical arenas for pupils’ broader development and creation of an understanding and appreciation of cultural diversity. However, race equality and community cohesion which could help in the students’ broader development are not Ofsted’s school inspection criteria. The absence of culturally diverse content in the school curriculum highlighted by the 1985 Swann Report and 2007 Ajegbo Report makes England’s National Curriculum look like a Brexit policy three decades before Brexit. A revised National Curriculum may be the starting point with the teachers as curriculum framers playing a significant part. The task design is crucial where teachers can place equal importance on the interwoven elements of “how”, “what” and “why” the task is taught. Teachers need to build confidence in encouraging difficult conversations around racism, fear, indifference, and ignorance breaking the stereotypical barriers, thus helping to create students’ conception of a multicultural Britain. Research showed that trainee teachers in predominantly White areas often exhibit confined perspectives while educating children. Irrespective of the geographical location, school teachers can be equipped with culturally responsive initial and continuous professional development necessary to impart multicultural education. This may aid in the reduction of employees’ unconscious bias. This becomes distinctly pertinent to avoid horrific cases in the future like the recent one in Hackney where a Black teenager was strip-searched during period wrongly suspected of cannabis possession. Early research findings show participants’ eagerness for more ethnic diversity content incorporated in teaching and learning. However, schools are considerably dependent on the knowledge-focused Primary National Curriculum in England. Moreover, they handle issues around the intersectionality of disability, poverty, and gender. Teachers were trained in times when foregrounding ethnicity matters was not happening. Therefore, preoccupied with Curriculum requirements, intersectionality issues, and teacher preparations, schools exhibit an incapacity due to which keeping momentum on ethnic diversity is somewhat endangered.

Keywords: case study, curriculum decolonisation, inclusive education, multiculturalism, qualitative research in Covid19 times

Procedia PDF Downloads 100

Authors: Ziyad S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

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Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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