Search results for: Peggy Richter
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 36

Search results for: Peggy Richter

6 Oncolytic H-1 Parvovirus Entry in Cancer Cells through Clathrin-Mediated Endocytosis

Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini

Abstract:

H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.

Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry

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5 Advancing Early Intervention Strategies for United States Adolescents and Young Adults with Schizophrenia in the Post-COVID-19 Era

Authors: Peggy M. Randon, Lisa Randon

Abstract:

Introduction: The post-COVID-19 era has presented unique challenges for addressing complex mental health issues, particularly due to exacerbated stress, increased social isolation, and disrupted continuity of care. This article outlines relevant health disparities and policy implications within the context of the United States while maintaining international relevance. Methods: A comprehensive literature review (including studies, reports, and policy documents) was conducted to examine concerns related to childhood-onset schizophrenia and the impact on patients and their families. Qualitative and quantitative data were synthesized to provide insights into the complex etiology of schizophrenia, the effects of the pandemic, and the challenges faced by socioeconomically disadvantaged populations. Case studies were employed to illustrate real-world examples and areas requiring policy reform. Results: Early intervention in childhood is crucial for preventing or mitigating the long-term impact of complex psychotic disorders, particularly schizophrenia. A comprehensive understanding of the genetic, environmental, and physiological factors contributing to the development of schizophrenia is essential. The COVID-19 pandemic worsened symptoms and disrupted treatment for many adolescent patients with schizophrenia, emphasizing the need for adaptive interventions and the utilization of virtual platforms. Health disparities, including stigma, financial constraints, and language or cultural barriers, further limit access to care, especially for socioeconomically disadvantaged populations. Policy implications: Current US health policies inadequately support patients with schizophrenia. The limited availability of longitudinal care, insufficient resources for families, and stigmatization represent ongoing policy challenges. Addressing these issues necessitates increased research funding, improved access to affordable treatment plans, and cultural competency training for healthcare providers. Public awareness campaigns are crucial to promote knowledge, awareness, and acceptance of mental health disorders. Conclusion: The unique challenges faced by children and families in the US affected by schizophrenia and other psychotic disorders have yet to be adequately addressed on institutional and systemic levels. The relevance of findings to an international audience is emphasized by examining the complex factors contributing to the onset of psychotic disorders and their global policy implications. The broad impact of the COVID-19 pandemic on mental health underscores the need for adaptive interventions and global responses. Addressing policy challenges, improving access to care, and reducing the stigma associated with mental health disorders are crucial steps toward enhancing the lives of adolescents and young adults with schizophrenia and their family members. The implementation of virtual platforms can help overcome barriers and ensure equitable access to support and resources for all patients, enabling them to lead healthy and fulfilling lives.

Keywords: childhood, schizophrenia, policy, United, States, health, disparities

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4 Teen Insights into Drugs, Alcohol, and Nicotine: A National Survey of Adolescent Attitudes toward Addictive Substances

Authors: Linda Richter

Abstract:

Background and Significance: The influence of parents on their children’s attitudes and behaviors is immense, even as children grow out of what one might assume to be their most impressionable years and into teenagers. This study specifically examines the potential that parents have to prevent or reduce the risk of adolescent substance use, even in the face of considerable environmental influences to use nicotine, alcohol, or drugs. Methodology: The findings presented are based on a nationally representative survey of 1,014 teens aged 12-17 living in the United States. Data were collected using an online platform in early 2018. About half the sample was female (51%), 49% was aged 12-14, and 51% was aged 15-17. The margin of error was +/- 3.5%. Demographic data on the teens and their families were available through the survey platform. Survey items explored adolescent respondents’ exposure to addictive substances; the extent to which their sources of information about these substances are reliable or credible; friends’ and peers’ substance use; their own intentions to try substances in the future; and their relationship with their parents. Key Findings: Exposure to nicotine, alcohol, or other drugs and misinformation about these substances were associated with a greater likelihood that adolescents have friends who use drugs and that they have intentions to try substances in the future, which are known to directly predict actual teen substance use. In addition, teens who reported a positive relationship with their parents and having parents who are involved in their lives had a lower likelihood of having friends who use drugs and of having intentions to try substances in the future. This relationship appears to be mediated by parents’ ability to reduce the extent to which their children are exposed to substances in their environment and to misinformation about them. Indeed, the findings indicated that teens who reported a good relationship with their parents and those who reported higher levels of parental monitoring had significantly higher odds of reporting a lower number of risk factors than teens with a less positive relationship with parents or less monitoring. There also were significantly greater risk factors associated with substance use among older teens relative to younger teens. This shift appears to coincide directly with the tendency of parents to pull back in their monitoring and their involvement in their adolescent children’s lives. Conclusion: The survey findings underscore the importance of resisting the urge to completely pull back as teens age and demand more independence since that is exactly when the risks for teen substance use spike and young people need their parents and other trusted adults to be involved more than ever. Particularly through the cultivation of a healthy, positive, and open relationship, parents can help teens receive accurate and credible information about substance use and also monitor their whereabouts and exposure to addictive substances. These findings, which come directly from teens themselves, demonstrate the importance of continued parental engagement throughout children’s lives, regardless of their age and the disincentives to remaining involved and connected.

Keywords: adolescent, parental monitoring, prevention, substance use

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3 Linkages between Innovation Policies and SMEs' Innovation Activities: Empirical Evidence from 15 Transition Countries

Authors: Anita Richter

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Innovation is one of the key foundations of competitive advantage, generating growth and welfare worldwide. Consequently, all firms should innovate to bring new ideas to the market. Innovation is a vital growth driver, particularly for transition countries to move towards knowledge-based, high-income economies. However, numerous barriers, such as financial, regulatory or infrastructural constraints prevent, in particular, new and small firms in transition countries from innovating. Thus SMEs’ innovation output may benefit substantially from government support. This research paper aims to assess the effect of government interventions on innovation activities in SMEs in emerging countries. Until now academic research related to the innovation policies focused either on single country and/or high-income countries assessments and less on cross-country and/or low and middle-income countries. Therefore the paper seeks to close the research gap by providing empirical evidence from 8,500 firms in 15 transition countries (Eastern Europe, South Caucasus, South East Europe, Middle East and North Africa). Using firm-level data from the Business Environment and Enterprise Performance Survey of the World Bank and EBRD and policy data from the SME Policy Index of the OECD, the paper investigates how government interventions affect SME’s likelihood of investing in any technological and non-technological innovation. Using the Standard Linear Regression, the impact of government interventions on SMEs’ innovation output and R&D activities is measured. The empirical analysis suggests that a firm’s decision to invest into innovative activities is sensitive to government interventions. A firm’s likelihood to invest into innovative activities increases by 3% to 8%, if the innovation eco-system noticeably improves (measured by an increase of 1 level in the SME Policy Index). At the same time, a better eco-system encourages SMEs to invest more in R&D. Government reforms in establishing a dedicated policy framework (IP legislation), institutional infrastructure (science and technology parks, incubators) and financial support (public R&D grants, innovation vouchers) are particularly relevant to stimulate innovation performance in SMEs. Particular segments of the SME population, namely micro and manufacturing firms, are more likely to benefit from an increased innovation framework conditions. The marginal effects are particularly strong on product innovation, process innovation, and marketing innovation, but less on management innovation. In conclusion, government interventions supporting innovation will likely lead to higher innovation performance of SMEs. They increase productivity at both firm and country level, which is a vital step in transitioning towards knowledge-based market economies.

Keywords: innovation, research and development, government interventions, economic development, small and medium-sized enterprises, transition countries

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2 Prospects of Agroforestry Products in the Emergency Situation: A Case Study of Earthquake of 2015 in Central Nepal

Authors: Raju Chhetri

Abstract:

Agroforestry is one of the main sources of livelihood among the people of Nepal. In particular, this is the only one mode of livelihood among the Chepangs. The monster earthquake (7.3 MW) that hit the country on the 25th of April in 2015 and many of its aftershocks had devastating effects. As a result, not only the big structures collapsed, it incurred great losses on fabrication, collection centers, schools, markets and other necessary service centers. Although there were a large number of aftershocks after the monster earthquake, the most devastating aftershock took place on 12th May, 2015, which measured 6.3 richter scale. Consequently, it caused more destruction of houses, further calamity to the lives of people, and public life got further perdition. This study was mainly carried out to find out the food security and market situation of Agroforestry product of the Chepang community in Raksirang VDC (one of the severely affected VDCs of Makwanpur district) due to the earthquake. A total of 40 households (12 percent) were randomly selected as a sample in ward number 7 only. Questionnaires and focus groups were used to gather primary data. Additional, two Focus Group Discussions (FGD) were convened in the study area to get some descriptive information on this study. Estimated 370 hectares of land, which was full of Agroforestry plantation, ruptured by the earthquake. It caused severe damages to the households, and a serious loss of food-stock, up to 60-80 percent (maize, millet, and rice). Instead of regular cereal intake, banana (Muas Paradisca) consumption was found ‘high scale’ in the emergency period. The market price of rice (37-44 NRS/Kg) increased by 18.9 percent. Some difference in the income range before and after the earthquake was observed. Before earthquake, sale of Agroforestry, and livestock products were continuing, but after the earthquake, Agroforestry product sale is the only one means of livelihood among Chepangs. Nearly 50-60 percent Agroforestry production of banana (Mass Paradisca), citrus (Citrus Lemon), pineapple (Ananus comosus) and broom grass (Thysanolaena maxima) declined, excepting for cash income from the residual. Heavy demands of Agroforestry product mentioned above lay high farm gate prices (50-100 percent) helps surveyed the community to continue livelihood from its sale. Out of the survey samples, 30 households (75 percent) respondents migrated to safe location due to land rupture, ongoing aftershocks, and landslides. Overall food security situation in this community is acute and challenging for the days to come. Immediate and long term both response from a relief agency concerning food, shelter and safe stocking of Agroforestry product is required to keep secured livelihood in Chepang community.

Keywords: earthquake, rupture, agroforestry, livelihood, indigenous, food security

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1 Smart Architecture and Sustainability in the Built Environment for the Hatay Refugee Camp

Authors: Ali Mohammed Ali Lmbash

Abstract:

The global refugee crisis points to the vital need for sustainable and resistant solutions to different kinds of problems for displaced persons all over the world. Among the myriads of sustainable concerns, however, there are diverse considerations including energy consumption, waste management, water access, and resiliency of structures. Our research aims to develop distinct ideas for sustainable architecture given the exigent problems in disaster-threatened areas starting with the Hatay Refugee camp in Turkey where the majority of the camp dwellers are Syrian refugees. Commencing community-based participatory research which focuses on the socio-environmental issues of displaced populations, this study will apply two approaches with a specific focus on the Hatay region. The initial experiment uses Richter's predictive model and simulations to forecast earthquake outcomes in refugee campers. The result could be useful in implementing architectural design tactics that enhance structural reliability and ensure the security and safety of shelters through earthquakes. In the second experiment a model is generated which helps us in predicting the quality of the existing water sources and since we understand how greatly water is vital for the well-being of humans, we do it. This research aims to enable camp administrators to employ forward-looking practices while managing water resources and thus minimizing health risks as well as building resilience of the refugees in the Hatay area. On the other side, this research assesses other sustainability problems of Hatay Refugee Camp as well. As energy consumption becomes the major issue, housing developers are required to consider energy-efficient designs as well as feasible integration of renewable energy technologies to minimize the environmental impact and improve the long-term sustainability of housing projects. Waste management is given special attention in this case by imposing recycling initiatives and waste reduction measures to reduce the pace of environmental degradation in the camp's land area. As well, study gives an insight into the social and economic reality of the camp, investigating the contribution of initiatives such as urban agriculture or vocational training to the enhancement of livelihood and community empowerment. In a similar fashion, this study combines the latest research with practical experience in order to contribute to the continuing discussion on sustainable architecture during disaster relief, providing recommendations and info that can be adapted on every scale worldwide. Through collaborative efforts and a dedicated sustainability approach, we can jointly get to the root of the cause and work towards a far more robust and equitable society.

Keywords: smart architecture, Hatay Camp, sustainability, machine learning.

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