Search results for: unmet need

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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Authors: Saradiya Mukherjee

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Background: Indian Muslims, compared to their counterparts in other religions, generally do not fare well on many yardsticks related to socio-economic progress and the same is true with maternal health care utilization. Due to low age at marriage a major percentage of child birth is ascribed to young (15-24 years) Muslim mothers in, which pose serious concerns on the maternal health care of Young Married Muslim women (YMMW). A thorough search of past literature on Muslim women’s health and health care reveals that studies in India have mainly focused on religious differences in fertility levels and contraceptive use while the research on the determinants of maternal health care utilization among Muslim women are lacking in India. Data and Methods: Retrieving data from the National Family Health Survey -3 (2005-06) this study attempts to assess the level of utilization and factors effecting three key maternal health indicators (full ANC, safe delivery and PNC) among YMMW (15-24 years) in India. The key socio-economic and demographic variables taken as independent or predictor variables in the study was guided by existing literature particularly for India. Bi-variate analysis and chi square test was applied and variables which were found to be significant were further included in binary logistic regression. Results: The findings of the study reveal abysmally low levels of utilization for all three indicators i.e. full ANC, safe delivery and PNC of maternal health care included in the study. Mother’s education, mass media exposure, women’s autonomy, birth order, economic status wanted status of child and region of residence were found to be significant variables effecting maternal health care utilization among YMMW. Multivariate analysis reveals that no mass media exposure, lower autonomy, education, poor economic background, higher birth order and unintended pregnancy are some of the reasons behind low maternal health care utilization. Conclusion: Considering the low level of safe maternal health care utilization and its proximate determinants among YMMW the study suggests educating Muslim girls, promoting family planning use, involving media and collaboration between religious leader and health care system could be some important policy level interventions to address the unmet need of maternity services among YMMW.

Keywords: young Muslim women, religion, socio-economic condition, antenatal care, delivery, post natal care

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Authors: Kristen Emory, Jerry Flores

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Purpose: We explore the unique and underrepresented experiences of Indigenous women living in Toronto, Canada, during the first year of the COVID-19 pandemic. The purpose of this study is to better document the impacts of COVID-19 on the mental health and well-being of Indigenous women in Toronto, Canada, in order to better understand unmet needs, as well as lay the groundwork for more targeted research and potential interventions based on these needs. Background: It has been fairly well documented that the COVID-19 pandemic has increased mental health concerns among various populations globally. There have also been numerous studies indicating increases in substance use and abuse in response to the stress of the pandemic. There is also evidence that the COVID-19 pandemic has disproportionately impacted a variety of historically marginalized populations in Canada, the US, and globally, including Indigenous populations. While these studies provide some insight into how the COVID-19 pandemic is impacting the global population, much less is known about the lived experiences of Indigenous populations during the time of COVID-19. Better understanding these experiences will allow public health professionals, governments, and non-governmental organizations better combat health inequities related to the pandemic. Methods: In-depth qualitative semi-structured virtual (due to COVID-19) interviews with 13 Indigenous women were conducted during the first year of the COVID-19 pandemic (2020). Interviews were recorded, transcribed, and analyzed by team members using Dedoose qualitative analysis software. Findings: COVID-19 negatively affected Indigenous females identifying participants’ mental health and corresponding reported increases in substance use. In addition to the daily stress of the unpredictability of life in the time of the COVID-19 pandemic, participants cited job loss, economic concerns, homeschooling, and lack of access to medical resources as primary factors in increasing their stress and decreasing mental health and wellbeing. In response to these stressors, a majority of participants cited coping mechanisms such as increased substance use to help deal with the uncertainty. In particular, alcohol and tobacco emerged as coping mechanisms to help participants cope with stress related to the pandemic (as well as its social and economic toll on respondents' lives). We will present qualitative data to be presented, including participant direct quotes, explaining their experiences with COVID-19, mental health, and increased substance use, as well as analysis and synthesis with the existing scientific evidence base. Conclusion: This research is among the good studies to our knowledge that scientifically explore the impact of COVID-19 on mental health and well-being and corresponding increases in reported substance use.

Keywords: mental health, covid-19, indigenous, inequity, anxiety, depression, stress

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Authors: Muhammad Naveed Babur, Maria Liaqat

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Background & Objective: People with disabilities especially neurological disabilities have many unmet health and rehabilitation needs, face barriers in accessing mainstream health-care services, and consequently have poor health. There are not sufficient epidemiological studies from Pakistan which assess barriers to neurorehabilitation and ways to counter it. Objectives: The objective of the study was to determine the challenges and to evaluate the barriers for neuro-rehabilitation services in developing countries. Methods: This is Exploratory sequential qualitative study based on the Panel discussion forum in International rehabilitation sciences congress and national rehabilitation conference 2017. Panel group discussion has been conducted in February 2017 with a sample size of eight professionals including Rehabilitation medicine Physician, Physical Therapist, Speech Language therapist, Occupational Therapist, Clinical Psychologist and rehabilitation nurse working in multidisciplinary/Interdisciplinary team. A comprehensive audio-videography have been developed, recorded, transcripted and documented. Data was transcribed and thematic analysis along with characteristics was drawn manually. Data verification was done with the help of two separate coders. Results: After extraction of two separate coders following results are emerged. General category themes are disease profile, demographic profile, training and education, research, barriers, governance, global funding, informal care, resources and cultural beliefs and public awareness. Barriers identified at the level are high cost, stigma, lengthy course of recovery. Hospital related barriers are lack of social support and individually tailored goal setting processes. Organizational barriers identified are lack of basic diagnostic facilities, lack of funding and human resources. Recommendations given by panelists were investment in education, capacity building, infrastructure, governance support, strategies to promote communication and realistic goals. Conclusion: It is concluded that neurorehabilitation in developing countries need attention in following categories i.e. disease profile, demographic profile, training and education, research, barriers, governance, global funding, informal care, resources and cultural beliefs and public awareness. This study also revealed barriers at the level of patient, hospital, organization. Recommendations were also given by panelists.

Keywords: disability, neurorehabilitation, telerehabilitation, disability

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Authors: Meng Xu, Alexis K. H. Lau, Ming Xu, Bill Barron, Narges Shahraki

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As an emerging unconventional energy, shale gas has been an economically viable step towards a cleaner energy future in U.S. China also has shale resources that are estimated to be potentially the largest in the world. In addition, China has enormous unmet for a clean alternative to substitute coal. Nonetheless, the geological complexity of China’s shale basins and issues of water scarcity potentially impose serious constraints on shale gas development in China. Further, even if China could replicate to a significant degree the U.S. shale gas boom, China faces the problem of transporting the gas efficiently overland with its limited pipeline network throughput capacity and coverage. The aim of this study is to identify the potential bottlenecks in China’s gas transmission network, as well as to examine the shale gas development affecting particular supply locations and demand centers. We examine this through application of three scenarios with projecting domestic shale gas supply by 2020: optimistic, medium and conservative shale gas supply, taking references from the International Energy Agency’s (IEA’s) projections and China’s shale gas development plans. Separately we project the gas demand at provincial level, since shale gas will have more significant impact regionally than nationally. To quantitatively assess each shale gas development scenario, we formulated a gas pipeline optimization model. We used ArcGIS to generate the connectivity parameters and pipeline segment length. Other parameters are collected from provincial “twelfth-five year” plans and “China Oil and Gas Pipeline Atlas”. The multi-objective optimization model uses GAMs and Matlab. It aims to minimize the demands that are unable to be met, while simultaneously seeking to minimize total gas supply and transmission costs. The results indicate that, even if the primary objective is to meet the projected gas demand rather than cost minimization, there’s a shortfall of 9% in meeting total demand under the medium scenario. Comparing the results between the optimistic and medium supply of shale gas scenarios, almost half of the shale gas produced in Sichuan province and Chongqing won’t be able to be transmitted out by pipeline. On the demand side, the Henan province and Shanghai gas demand gap could be filled as much as 82% and 39% respectively, with increased shale gas supply. To conclude, the pipeline network in China is currently not sufficient in meeting the projected natural gas demand in 2020 under medium and optimistic scenarios, indicating the need for substantial pipeline capacity expansion for some of the existing network, and the importance of constructing new pipelines from particular supply to demand sites. If the pipeline constraint is overcame, Beijing, Shanghai, Jiangsu and Henan’s gas demand gap could potentially be filled, and China could thereby reduce almost 25% its dependency on LNG imports under the optimistic scenario.

Keywords: energy policy, energy systematic analysis, scenario analysis, shale gas in China

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Authors: Seydou Drabo

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This paper examines how traditional contraceptives and abortion practices challenges the use of modern contraceptives in Burkina Faso. It demonstrates how fears and ‘superstitions’ interact with knowledge about modern contraceptives methods to determine use in a context where other way of controlling fertility (traditional contraceptives, abortion) are available to women in the public, private and traditional health sectors. Furthermore, these issues come at the time when Burkina Faso is among countries with a high fertility rate which (6.0 in 2010) and a very low used of contraceptives as only 16% of married women of childbearing age were using a contraceptive method in 2010. The country also has a young population since 33 % of the population is between 10-24 years old and this number is expected to increase by 2050, generating fears that a growing population of youth will put excessive pressure on available resources, including access to education, health services, and employment. Despite over two decades of dedicated policy attention, 24% of women of reproductive age (15-49) was estimated to have an unmet need for contraception in 2010. This paper draws on ethnographic fieldwork conducted since march 2016 (The research is still in progress) in Burkina Faso. Data were collected from 25 women (users and non-users of modern contraceptives and /or traditional contraceptives, post abortion care patients), 4 street drugs vendors and 3 traditional healers through formal and informal interviews, as well as direct observation. The findings show that a variety of contraceptives methods and abortion drugs or methods, both traditional and modern circulate and are available to women. Traditional contraceptives called African contraceptives by some of our participants refer to several birth control method including plants decoction, magical ring, waist necklace, a ritual done with a mixture of lay coming from termite mound and menses. Abortion is a practice that is done in secret through the use of abortion drugs or through intra uterine manoeuvres. Modern contraceptives include Oral contraceptive, implants, injectable. Stereotypes about modern contraceptives, having regular menstrual cycles and adopt of natural birth control methods, bad experience with modern contraceptives methods, the side effect of modern contraceptives, irregularity of sexual activities and the availability of emergency contraceptives are among factors that limit their use among women. In addition, a negative perception is built around modern contraceptives seen as the drug of ‘white people’. In general, the information on these drugs circulates in women’s social network (first line of information on contraceptive). Some women prefer using what they call African contraceptives or inducing an abortion over modern contraceptives because of their side effect. Furthermore, the findings show that women practices and attitudes in controlling birth varies throughout different phases of their lives. Beyond global discourses and technical solution, the issue of Family planning is all about social practices.

Keywords: abortion, Burkina Faso, contraception, culture, women

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Authors: Mohammed Fayez Al Rez

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Nowadays, there is an unmet clinical need for new small-diameter vascular grafts to overcome the drawbacks of traditional methods used for treatment of widespread cardiovascular diseases. Vascular tissue engineering (VTE) is a promising approach that can be utilized to develop viable vascular grafts by in vitro seeding of functional cells onto a scaffold allowing them to attach, proliferate and differentiate. To achieve this purpose, the scaffold should provide cells with the initial necessary extracellular matrix environment and structure until being able to reconstruct the required vascular tissue. Therefore, producing scaffolds with suitable features is crucial for guiding cells properly to develop the desired tissue-engineered vascular grafts for clinical applications. The main objective of this work is fabrication and characterization of tubular small-diameter ( < 6 mm) bilayered scaffolds for VTE. The scaffolds were prepared via mixing electrospinning approach of biodegradable poly(ε-caprolactone) (PCL) polymer – due to its favorable physicochemical properties – to mimic the natural environment-extracellular matrix. Firstly, tubular nanofibrous construct with inner diameter of 3, 4 or 5 mm was electrospun as inner layer, and secondly, microfibrous construct was electrospun as outer layer directly on the first produced inner layer. To improve the biological properties of PCL, a group of the electrospun scaffolds was immersed in type-1 collagen solution. The morphology and structure of the resulting fibrous scaffolds were investigated by scanning electron microscope. The electrospun nanofibrous inner layer contained fibers measuring 219±35 nm in diameter, while the electrospun microfibrous outer layer contained fibers measuring 1011 ± 150 nm. Furthermore, mechanical, thermal and physical tests were conducted with both electrospun bilayered scaffold types where revealed improved properties. Biological investigations using endothelial, smooth muscle and fibroblast cell line showed good biocompatibility of both tested electrospun scaffolds. Better attachment and proliferation were obviously found when cells were cultured on the scaffolds immersed with collagen due to increasing the hydrophilicity of the PCL. The easy, inexpensive and versatile electrospinning approach used in this work was able to successfully produce double layered tubular elastic structures containing both nanofibers and microfibers to imitate the native vascular structure. The PCL – as a suitable and approved biomaterial for many biomedical and tissue engineering applications – can ensure favorable mechanical properties of scaffolds used for VTE. The VTE approach using electrospun bilayered scaffolds offers optimal solutions and holds significant promises for treatment of many cardiovascular diseases.

Keywords: electrospinning, poly(ε-caprolactone) (PCL), tissue-engineered vascular graft, tubular bilayered scaffolds, vascular cells

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Authors: Antonio Ruiz Gonzalez, Kwang-Leong Choy

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The measurement of electrolytes has a high value in the clinical routine. Ions are present in all body fluids with variable concentrations and are involved in multiple pathologies such as heart failures and chronic kidney disease. In the case of dissolved potassium, although a high concentration in the blood (hyperkalemia) is relatively uncommon in the general population, it is one of the most frequent acute electrolyte abnormalities. In recent years, the integration of thin films technologies in this field has allowed the development of highly sensitive biosensors with ultra-low limits of detection for the assessment of metals in liquid samples. However, despite the current efforts in the miniaturization of sensitive devices and their integration into portable systems, only a limited number of successful examples used commercially can be found. This fact can be attributed to a high cost involved in their production and the sustained degradation of the electrodes over time, which causes a signal drift in the measurements. Thus, there is an unmet necessity for the development of low-cost and robust sensors for the real-time monitoring of analyte concentrations in patients to allow the early detection and diagnosis of diseases. This paper reports a thin film ion-selective sensor for the evaluation of potassium ions in aqueous samples. As an alternative for this fabrication method, aerosol assisted chemical vapor deposition (AACVD), was applied due to cost-effectivity and fine control over the film deposition. Such a technique does not require vacuum and is suitable for the coating of large surface areas and structures with complex geometries. This approach allowed the fabrication of highly homogeneous surfaces with well-defined microstructures onto 50 nm thin gold layers. The degradative processes of the ubiquitously employed poly (vinyl chloride) membranes in contact with an electrolyte solution were studied, including the polymer leaching process, mechanical desorption of nanoparticles and chemical degradation over time. Rational design of a protective coating based on an organosilicon material in combination with cellulose to improve the long-term stability of the sensors was then carried out, showing an improvement in the performance after 5 weeks. The antifouling properties of such coating were assessed using a cutting-edge quartz microbalance sensor, allowing the quantification of the adsorbed proteins in the nanogram range. A correlation between the microstructural properties of the films with the surface energy and biomolecules adhesion was then found and used to optimize the protective film.

Keywords: hyperkalemia, drift, AACVD, organosilicon

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Authors: Rocio Murad, Juan Carlos Rivillas, Nury Alejandra Rodriguez, Daniela Roldán

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In Colombia, around 5 million women have suffered forced displacement and all forms of gender-based violence, mostly adolescents and young women, single mothers, or widows with children affected by the war. After the signing of the peace agreements, the department of Antioquia has been one of the most affected by the armed conflict, from a territorial and gender perspective in the period. The objective of the research was to analyze the situation of sexual and reproductive rights in the department of Antioquia from a territorial and gender perspective in the period after the signing of the Peace Agreement. A mixed methodology was developed. The quantitative component conducted a cross-sectional descriptive study of barriers to access to contraceptive methods, safe abortion and gender-based violence based on microdata from the 2015 National Demographic and Health Survey. In the qualitative component, a case study was developed in Dabeiba, a municipality of Antioquia prioritized in order to deepen the experiences before, during and after the armed conflict in sexual and reproductive rights; using three research techniques: Focused observation, Semi-structured interviews, and Documentary review. The results showed that there is a gradient of greater vulnerability to greater effects of the conflict and that the subregion of Urabá Antioqueño, to which Dabeiba belongs, has the highest levels of vulnerability in relation to departmental data. In this subregion, the percentage of women with an unmet need for contraceptive methods (9%), women with unintended pregnancies (31%), of women between 15 and 19 years of age who are already mothers or are pregnant with their first child (32%) and the percentage of women victims of physical violence (42%) and sexual violence (13%) by their partners are significantly higher. Women, particularly rural and indigenous women, were doubly affected due to the existence of violence that is specifically directed at them or that has a greater impact on their life projects. There was evidence of insufficient, fragmented and disjointed social and institutional action in relation to women's rights and the existence of androcentric and patriarchal social imaginaries through which women and the feminine are undervalued. These results provide evidence of violations of sexual and reproductive rights in contexts of armed conflict and make it possible to identify mechanisms to guarantee the re-establishment of the rights of the victims, particularly women and girls. Among the mechanisms evidenced are: working for the elimination of gender stereotypes; supporting the formation and strengthening of women's social organizations; working for the concerted definition and articulated implementation of actions necessary to respond to sexual and reproductive health needs; and working for the recognition of reproductive violence as specific and different from sexual violence in the context of armed conflict. Also, it was evidenced that it is necessary to implement prevention, attention and reparation actions.

Keywords: sexual and reproductive rights, Colombia, armed conflict, violence against women

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Authors: Natasha Bhate

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Contraception is important in helping to reduce maternal and infant mortality rates by allowing women to control the number and spacing in-between their children. It also reduces the need for unsafe abortions. Women worldwide use contraception; however, the contraceptive prevalence rate is still relatively low in Central American countries like Guatemala. There is also an unmet need for contraception in Guatemala, which is more significant in rural, indigenous women due to barriers preventing contraceptive use. The study objective was to investigate and analyse the current barriers women face, in Guatemala, Panajachel and the surrounding areas, in using contraception, with a view of identifying ways to overcome these barriers. This included exploring the contraceptive barriers women believe exist and the influence of males in contraceptive decision making. The study took place at a charity in Panajachel, Guatemala, and had a cross-sectional, qualitative design to allow an in-depth understanding of information gathered. This particular study design was also chosen to help inform the charity with qualitative research analysis, in view of their intent to create a local reproductive health programme. A semi-structured interview design, including photo facilitation to improve cross-cultural communication, with interpreter assistance, was utilized. A pilot interview was initially conducted with small improvements required. Participants were recruited through purposive and convenience sampling. The study host at the charity acted as a gatekeeper; participants were identified through attendance of the charity’s women’s-initiative programme workshops. 20 participants were selected and agreed to study participation with two not attending; a total of 18 participants were interviewed in June 2017. Interviews were audio-recorded and data were stored on encrypted memory sticks. Framework analysis was used to analyse the data using NVivo11 software. The University of Leeds granted ethical approval for the research. Religion, language, the community, and fear of sickness were examples of existing contraceptive barrier themes recognized by many participants. The influence of men was also an important barrier identified, with themes of machismo and abuse preventing contraceptive use in some women. Women from more rural areas were believed to still face barriers which some participants did not encounter anymore, such as distance and affordability of contraceptives. Participants believed that informative workshops in various settings were an ideal method of overcoming existing contraceptive barriers and allowing women to be more empowered. The involvement of men in such workshops was also deemed important by participants to help reduce their negative influence in contraceptive usage. Overall, four recommendations following this study were made, including contraceptive educational courses, a gender equality campaign, couple-focused contraceptive workshops, and further qualitative research to gain a better insight into men’s opinions regarding women using contraception.

Keywords: barrier, contraception, machismo, religion

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Authors: Enrico Gugliandolo, Salvatore Cuzzocrea, Rosalia Crupi

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Osteoarthritis (OA) is one of the most common chronic pain conditions in dogs and cats. OA pain is currently viewed as a mixed phenomenon involving both inflammatory and neuropathic mechanisms at the peripheral (joint) and central (spinal and supraspinal) levels. Oxidative stress has been implicated in OA pain. Although nonsteroidal anti-inflammatory drugs are commonly prescribed for OA pain, they should be used with caution in pets because of adverse effects in the long term and controversial efficacy on neuropathic pain. An unmet need remains for safe and effective long-term treatments for OA pain. Palmitoyl-glucosamine (PGA) is an analogue of the ALIAamide palmitoylethanolamide, i.e., a body’s own endocannabinoid-like compound playing a sentinel role in nociception. PGA, especially in the micronized formulation, was shown safe and effective in OA pain. The aim of this study was to investigate the effect of a co-micronized formulation of PGA with the natural antioxidant curcumin (PGA-cur) on OA pain. Ten Sprague-Dawley male rats were used for each treatment group. The University of Messina Review Board for the care and use of animals authorized the study. On day 0, rats were anesthetized (5.0% isoflurane in 100% O2) and received intra-articular injection of MIA (3 mg in 25 μl saline) in the right knee joint, with the left being injected an equal volume of saline. Starting the third day after MIA injection, treatments were administered orally three times per week for 21 days, at the following doses: PGA 20 mg/kg, curcumin 10 mg/kg, PGA-cur (2:1 ratio) 30 mg/kg. On day 0 and 3, 7, 14 and 21 days post-injection, mechanical allodynia was measured using a dynamic plantar Von Frey hair aesthesiometer and expressed as paw withdrawal threshold (PWT) and latency (PWL). Motor functional recovery of the rear limb was evaluated on the same time points by walking track analysis using the sciatic functional index. On day 21 post-MIA injection, the concentration of the following inflammatory and nociceptive mediators was measured in serum using commercial ELISA kits: tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nerve growth factor (NGF) and matrix metalloproteinase-1-3-9 (MMP-1, MMP-3, MMP-9). The results were analyzed by ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Micronized PGA reduced neuropathic pain, as shown by the significant higher PWT and PWL values compared to vehicle group (p < 0.0001 for all the evaluated time points). The effect of PGA-cur was superior at all time points (p < 0.005). PGA-cur restored motor function already on day 14 (p < 0.005), while micronized PGA was effective a week later (D21). MIA-induced increase in the serum levels of all the investigated mediators was inhibited by PGA-cur (p < 0.01). PGA was also effective, except on IL-1 and MMP-3. Curcumin alone was inactive in all the experiments at any time point. The encouraging results suggest that PGA-cur may represent a valuable option in OA pain management and warrant further confirmation in well-powered clinical trials.

Keywords: ALIAmides, curcumin, osteoarthritis, palmitoyl-glucosamine

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Authors: D. M. Koers, A. J. Groen, P. D. Englis, R. Harms

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We are witnessing the largest level of displacement of people since World War II. Refugees want to become independent as quickly as possible and build a new, safe future; however, access to the labor market is difficult and they face many problems that are not easily solved. This makes self-employment including social entrepreneurship a valuable alternative. Our research studied refugee-based entrepreneurship and examined whether prior knowledge, unmet personal needs and contextual factors influence how refugees recognize opportunities and if this influences their social orientation. In addition, we examine the barriers refugees face when starting up a company in the Netherlands. We use a case study design with a mixed-method approach, combining in-depth interviews and survey data. Data was collected from two Dutch entrepreneurial training programs in the Netherlands. We have a sample size of 27 latent refugee entrepreneurs. Our results show that refugees score high on the social entrepreneurial measures. They perceive themselves as having a strong social vision and are determined to defend a social need. They also score high on sustainability and state that their business ideas improve the quality of life on the long run. Based on these findings, we did not expect that only 5 participants had business ideas with a social orientation. In this group, 37,5% started a company before and 77.8% used their personal experience to come up with this business idea. Another 70,3% had the higher professional education or academic education. In the interviews, we found that they often copy and paste their gained experience from a previous profession on their new context and expect that it would work well. The social aspect lies in their cultural values and personal beliefs but is not reflected in their business models. One of the reasons could be that the context in which the refugee operates as a moderator suppressing the social mission and social value creation opportunities. Refugees are first and foremost focused on their survival. They do not want to be on social welfare and feel a strong need to be independent. Since they cannot access the labor market easily and face labor market discrimination they want to start a company. Another factor that explains lack of the social orientation in their business ideas is that social entrepreneurship is not a known concept in their home countries. Their idea of entrepreneurship differs substantially. We found that a huge barrier for refugees is their expectations about setting up a business, which are often not realistic because they have little knowledge about the system, institutions and corresponding red tape. In those instances, can the institutional configuration of a country, cultural differences, and perspective on entrepreneurship hinders social entrepreneurship. In conclusion, there might be latent potential for social entrepreneurship in refugees but there are many barriers to overcome. Overcoming these barriers can enhance local communities and enhance integration. In addition it has a positive financial impact on the host country because it reduces the pressure on the social system and stimulate the economy.

Keywords: immigrant entrepreneurship, refugee entrepreneurship, social entrepreneurship, prior experience, opportunity recognition

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Authors: Garima Singh

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Objectives: Behavioral Crisis Center (BCC) is a community solution to a community problem. There has been an exponential increase in the incidence and prevalence of mental health crises around the world. The effects of the crisis negatively impact our patients and their families and strain the law enforcement and emergency room. The goal of the multi-disciplinary care model is to break the crisis cycle and provide 24-7 rapid access to an acre and crisis stabilization. We initiated our first BCC care center in 2020 in the midst of the COVID pandemic and have seen a remarkable improvement in patient ‘care and positive financial outcome. Background: Mental illnesses are common in the United States. Nearly one in five U.S. adults live with a mental illness (52.9 million in 2020). This number represented 21.0% of all U.S. adults. To address some of these challenges and help our community, In May 2020, we opened our first Behavioral crisis center (BCC). Since then, we have served more than 2500 patients and is the first southwest Missouri’s first 24/7 facility for crisis–level behavioral health and substance use needs. It has been proven to be a more effective place than emergency departments, jails, or local law enforcement. Methods: BCC was started in 2020 to serve the unmet need of the community and provide access to behavioral health and substance use services identified in the community. Funding was possible with significant investment from the county and Missouri Foundation for Health, with contributions from medical partners. It is a multi-disciplinary care center consisting of Physicians, nurse practitioners, nurses, behavioral technicians, peer support specialists, clinical intake specialists, and clinical coordinators and hospitality specialists. The center provides services including psychiatry care, outpatient therapy, community support services, primary care, peer support and engagement. It is connected to a residential treatment facility for substance use treatment for continuity of care and bridging the gap, which has resulted in the completion of treatment and better outcomes. Results: BCC has proven to be a great resource to the community and the Missouri Health Coalition is providing funding to replicate the model in other regions and work on a similar model for children and adolescents. Overall, 29% of the patients seen at BCC are stabilized and discharged with outpatient care. 50% needed acute stabilization in a hospital setting and 21% required long-term admission, mostly for substance use treatment. The local emergency room had a 42% reduction in behavioral health encounters compared to the previous 3 years. Also, by a quick transfer to BCC, the average stay in ER was reduced by 10 hours and time to follow up behavioral health assessment decreased by an average of 4 hours. Uninsured patients are also provided Medicaid application assistance which has benefited 55% of individuals receiving care at BCC. Conclusions: BCC is impacting community health and improving access to quality care and substance use treatment. It is a great investment for our patients and families.

Keywords: BCC, behvaioral health, community health care, addiction treatment

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Authors: Neha Joshi, Srikanth Jois, Hector J. Peughero, Poornima Jayakrishna, Moulya R., Purnima Madivanan, Kiran Kumar K. Salagame

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Transgenders are a marginalized section of the community, who are at high risk of mental health problems due to their stigmatization, abandonment by family, prejudice, discrimination by society at large, and the physical, emotional, and sexual abuse from both within and outside their community. Their mental healthcare needs remain largely unaddressed due to lack of access, discrimination by healthcare professions, and lack of resources, including time and money, to seek conventional medical and psychotherapeutic treatments. Meditation is increasingly receiving acceptance as a tool for managing stress and anxiety by the patients as well as mental healthcare professionals. “Meditation on Twin Hearts” is a no cost, self-administered intervention that a person can practice anywhere and at any time of the day. This pilot study evaluates the need for alternate traditional and ingenious interventions like “Meditation of Twin Hearts” to address the mental healthcare needs of the transgender community and acceptance of such an intervention by the community. Thirteen individuals identifying themselves as transgender were invited to participate in one (Hunsur Taluk) of the five scheduled free meditation camps in Mysore. After obtaining informed consent for participation in the study, their mental health status is captured using an anonymous survey using standard, validated, self-reported questionnaires Generalised Anxiety Disorders (GAD)-7 for anxiety, Patient Health Questionnaire (PHQ-9) for depression, and Suicidal Behavior Questionnaire-Revised for suicidality. Then, they were requested to attend a session on “Meditation on Twin Hearts.” After the session, their feedback on willingness to further explore the meditation technique for managing their mental healthcare need was assessed through another survey form. Out of the 13 participants, 92% scored for anxiety (4 mild, and 8 moderate anxiety). In the depression scale, 5 scored for mild and 5 for moderate depression, with a total of 77% (10/13) scoring positively on depression scale. Nearly 70% of participants (9/13), scored greater than the clinical cutoff for the need for clinical intervention. The proportion of individuals at risk for suicide was particularly high in this group, with 8/ 13 (61.5%) participants scoring the clinical cutoff score of ≥ 7. Surprisingly, none of the participants had ever consulted a mental healthcare professional. All the participants (13/13; 100%) responded in affirmative to the question, “Will you be willing to continue meditation for management of your anxiety?” Six out of 13 participants described their experience of meditation as “happy” and 3 described it as “peaceful”. None of the participants reported any negative beliefs or experience regarding the meditation. The study provides evidence for the urgent yet unmet mental healthcare need of the transgender community. The findings of the study also supports the rationale of conducting future systematic research to evaluate and explore ingenious and traditional practices, such as meditation, to meet the healthcare needs, especially in marginalized populations in a low income setting such as Lower and Middle Income countries. Based on these preliminary findings, the Principal Investigator (PI) is planning to cover 4 more areas of Mysore district.

Keywords: anxiety, depression, meditation on twin heart, suicidality, transgender

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Authors: Lilah Inzelberg, David Rand, Stanislav Steinberg, Moshe David Pur, Yael Hanein

Abstract:

Human facial expressions carry important psychological and neurological information. Facial expressions involve the co-activation of diverse muscles. They depend strongly on personal affective interpretation and on social context and vary between spontaneous and voluntary activations. Smiling, as a special case, is among the most complex facial emotional expressions, involving no fewer than 7 different unilateral muscles. Despite their ubiquitous nature, smiles remain an elusive and debated topic. Smiles are associated with happiness and greeting on one hand and anger or disgust-masking on the other. Accordingly, while high-resolution recording of muscle activation patterns, in a non-interfering setting, offers exciting opportunities, it remains an unmet challenge, as contemporary surface facial electromyography (EMG) methodologies are cumbersome, restricted to the laboratory settings, and are limited in time and resolution. Here we present a wearable and non-invasive method for objective mapping of facial muscle activation and demonstrate its application in a natural setting. The technology is based on a recently developed dry and soft electrode array, specially designed for surface facial EMG technique. Eighteen healthy volunteers (31.58 ± 3.41 years, 13 females), participated in the study. Surface EMG arrays were adhered to participant left and right cheeks. Participants were instructed to imitate three facial expressions: closing the eyes, wrinkling the nose and smiling voluntary and to watch a funny video while their EMG signal is recorded. We focused on muscles associated with 'enjoyment', 'social' and 'masked' smiles; three categories with distinct social meanings. We developed a customized independent component analysis algorithm to construct the desired facial musculature mapping. First, identification of the Orbicularis oculi and the Levator labii superioris muscles was demonstrated from voluntary expressions. Second, recordings of voluntary and spontaneous smiles were used to locate the Zygomaticus major muscle activated in Duchenne and non-Duchenne smiles. Finally, recording with a wireless device in an unmodified natural work setting revealed expressions of neutral, positive and negative emotions in face-to-face interaction. The algorithm outlined here identifies the activation sources in a subject-specific manner, insensitive to electrode placement and anatomical diversity. Our high-resolution and cross-talk free mapping performances, along with excellent user convenience, open new opportunities for affective processing and objective evaluation of facial expressivity, objective psychological and neurological assessment as well as gaming, virtual reality, bio-feedback and brain-machine interface applications.

Keywords: affective expressions, affective processing, facial EMG, high-resolution electromyography, independent component analysis, wireless electrodes

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Authors: Alaa Abdellatif, Gabrièle Breda

Abstract:

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

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

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

Abstract:

Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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

Abstract:

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: Subhash Nerella, Ziyuan Guan, Azra Bihorac, Parisa Rashidi

Abstract:

Intensive care units (ICUs) provide care to critically ill patients in severe and life-threatening conditions. However, patient monitoring in the ICU is limited by the time and resource constraints imposed on healthcare providers. Many critical care indices such as mobility are still manually assessed, which can be subjective, prone to human errors, and lack granularity. Other important aspects, such as environmental factors, are not monitored at all. For example, critically ill patients often experience circadian disruptions due to the absence of effective environmental “timekeepers” such as the light/dark cycle and the systemic effect of acute illness on chronobiologic markers. Although the occurrence of delirium is associated with circadian disruption risk factors, these factors are not routinely monitored in the ICU. Hence, there is a critical unmet need to develop systems for precise and real-time assessment through novel enabling technologies. We have developed the mobility and circadian disruption quantification system (Mobi-DiQ) by augmenting biomarker and clinical data with pervasive sensing data to generate mobility and circadian cues related to mobility, nightly disruptions, and light and noise exposure. We hypothesize that Mobi-DiQ can provide accurate mobility and circadian cues that correlate with bedside clinical mobility assessments and circadian biomarkers, ultimately important for delirium risk assessment and prevention. The collected multimodal dataset consists of depth images, Electromyography (EMG) data, patient extremity movement captured by accelerometers, ambient light levels, Sound Pressure Level (SPL), and indoor air quality measured by volatile organic compounds, and the equivalent CO₂ concentration. For delirium risk assessment, the system recognizes mobility cues (axial body movement features and body key points) and circadian cues, including nightly disruptions, ambient SPL, and light intensity, as well as other environmental factors such as indoor air quality. The Mobi-DiQ system consists of three major components: the pervasive sensing system, a data storage and analysis server, and a data annotation system. For data collection, six local pervasive sensing systems were deployed, including a local computer and sensors. A video recording tool with graphical user interface (GUI) developed in python was used to capture depth image frames for analyzing patient mobility. All sensor data is encrypted, then automatically uploaded to the Mobi-DiQ server through a secured VPN connection. Several data pipelines are developed to automate the data transfer, curation, and data preparation for annotation and model training. The data curation and post-processing are performed on the server. A custom secure annotation tool with GUI was developed to annotate depth activity data. The annotation tool is linked to the MongoDB database to record the data annotation and to provide summarization. Docker containers are also utilized to manage services and pipelines running on the server in an isolated manner. The processed clinical data and annotations are used to train and develop real-time pervasive sensing systems to augment clinical decision-making and promote targeted interventions. In the future, we intend to evaluate our system as a clinical implementation trial, as well as to refine and validate it by using other data sources, including neurological data obtained through continuous electroencephalography (EEG).

Keywords: deep learning, delirium, healthcare, pervasive sensing

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Authors: Sitira Williams, Georgina Cherry, Andrea Wright, Kevin Wells, Taran Rai, Richard Brown, Travis Street, Alasdair Cook

Abstract:

Social media sources (50) were identified, keywords defined by veterinarians and organised into 6 topics known to be indicative of feline pruritus: body areas, behaviors, symptoms, diagnosis, and treatments. These were augmented using academic literature, a cat owner survey, synonyms, and Google Trends. The content was collected using a social intelligence solution, with keywords tagged and filtered. Data were aggregated and de-duplicated. SL content matching body areas, behaviors and symptoms were reviewed manually, and posts were marked relevant if: posted by a pet owner, identifying an itchy cat and not duplicated. A sub-set of 493 posts published from 2009-2022 was used for reflexive thematic analysis in NVIVO (Burlington, MA) to identify themes. Five themes were identified: allergy, pruritus, additional behaviors, unusual or undesirable behaviors, diagnosis, and treatment. Most (258) posts reported the cat was excessively licking, itching, and scratching. The majority were indoor cats and were less playful and friendly when itchy. Half of these posts did not indicate a known cause of pruritus. Bald spots and scabs (123) were reported, often causing swelling and fur loss, and 56 reported bumps, lumps, and dry patches. Other impacts on the cat’s quality of life were ear mites, cat self-trauma and stress. Seven posts reported their cats’ symptoms caused them ongoing anxiety and depression. Cats with food allergies to poultry (often chicken and beef) causing bald spots featured in 23 posts. Veterinarians advised switching to a raw food diet and/or changing their bowls. Some cats got worse after switching, leaving owners’ needs unmet. Allergic reactions to flea bites causing excessive itching, red spots, scabs, and fur loss were reported in 13 posts. Some (3) posts indicated allergic reactions to medication. Cats with seasonal and skin allergies, causing sneezing, scratching, headshaking, watery eyes, and nasal discharge, were reported 17 times. Eighty-five posts identified additional behaviors. Of these, 13 reported their cat’s burst pimple or insect bite. Common behaviors were headshaking, rubbing, pawing at their ears, and aggressively chewing. In some cases, bites or pimples triggered previously unseen itchiness, making the cat irritable. Twenty-four reported their cat had anxiety: overgrooming, itching, losing fur, hiding, freaking out, breathing quickly, sleeplessness, hissing and vocalising. Most reported these cats as having itchy skin, fleas, and bumps. Cats were commonly diagnosed with an ear infection, ringworm, acne, or kidney disease. Acne was diagnosed in cats with an allergy flare-up or overgrooming. Ear infections were diagnosed in itchy cats with mites or other parasites. Of the treatments mentioned, steroids were most frequently used, then anti-parasitics, including flea treatments and oral medication (steroids, antibiotics). Forty-six posts reported distress following poor outcomes after medication or additional vet consultations. SL provides veterinarians with unique insights. Verbatim comments highlight the detrimental effects of pruritus on pets and owner quality of life. This study demonstrates the need for veterinarians to communicate management and treatment options more effectively to relieve owner frustrations. Data analysis could be scaled up using machine learning for topic modeling.

Keywords: content analysis, feline, itch, pruritus, social media, thematic analysis, veterinary dermatology

Procedia PDF Downloads 153