Over the past decades, major efforts were undertaken to develop devices on a nanoscale level for the efficient and nontoxic delivery of molecules to tissues and cells, for the purpose of either diagnosis or treatment of disease. The application of such devices in drug delivery has proven to be beneficial for matters as diverse as drug solubility, drug targeting, controlled drug release, and transport of drugs across cellular barriers. Multiple nanotherapeutics have been approved for clinical treatment, and more products are being evaluated in preclinical and clinical trials. However, many biological barriers hinder the medical application of nanocarriers. There are two main classes of barriers that need to be overcome by drug nanocarriers: extracellular and intracellular barriers, both of which may capture and/or destroy therapeutics before they reach their target site. This Account discusses major biological barriers that are confronted by nanotherapeutics, following their systemic administration, focusing on cellular entry and endosomal escape of gene delivery vectors. The use of pH-responsive materials to overcome the endosomal barrier is addressed. Historically, cell biologists have studied the interaction between cells and pathogens in order to unveil the mechanisms of endocytosis and cell signaling. Meanwhile, it is becoming clear that cells may respond in similar ways to artificial drug delivery systems and, consequently, that knowledge on the cellular response against both pathogens and nanoparticulate systems will aid in the design of improved nanomedicine. A close collaboration between bioengineers and cell biologists will promote this development. At the same time, we have come to realize that tools that we use to study fundamental cellular processes, including metabolic inhibitors of endocytosis and overexpression/downregulation of proteins, may cause changes in cellular physiology. This calls for the implementation of refined methods to study nanocarrier-cell interactions, as is discussed in this Account. Finally, recent papers on the dynamics of cargo release from endosomes by means of live cell imaging have significantly advanced our understanding of the transfection process. They have initiated discussion (among others) on the limited number of endosomal escape events in transfection, and on the endosomal stage at which genetic cargo is most efficiently released. Advancements in imaging techniques, including super-resolution microscopy, in concert with techniques to label endogenous proteins and/or label proteins with synthetic fluorophores, will contribute to a more detailed understanding of nanocarrier-cell dynamics, which is imperative for the development of safe and efficient nanomedicine.

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Carriers Break Barriers in Drug Delivery: Endocytosis and Endosomal Escape of Gene Delivery Vectors

Theories of gentrification represent gentrifiers as social groups at early- to mid- phases of their lifecourse. In urban contexts, this encompasses young, childless and upwardly mobile professionals and family gentrifiers with children. The latter are also prominent figures within representations of idyllic, gentrified rural places for raising children, family life and neighbourly relations; although in early rural gentrification studies there was reference to retirement migration. Such issues, however, are under-explored and mature populations have been absent from gentrification scholarship, despite the recognition of affluent households within ageing societies. At the same time, the ageing of gentrified populations is overlooked within cross-sectional analyses of gentrification. Our aim is to widen the lens on gentrifier populations, and to consider the effects of ageing in gentrified villages. Drawing on 2011 census data for England and Wales and findings from a household questionnaire, we identify populations of ageing gentrifiers who in-migrated before and at retirement, and have ‘stayed-put’ for considerable lengths of time. Through three vignettes, we highlight how these staying rural gentrifiers may create displacement pressures impacting on younger residents and potentially influence the supply of housing for subsequent waves of gentrification, although they may also come to be displaced by such waves.

https://dialnet.unirioja.es/descarga/articulo/7272035.pdf

The dynamics of rural gentrification and the effects of ageing on gentrified rural places

With rapid urbanization and industry development, China has witnessed substantial land acquisition. Using the rural household survey data, this paper examines the impact of land expropriation on land-lost farmers’ self-reported health with the ordered probit model and investigates the possible mechanisms. The results show that the land expropriation puts higher health risks over those land-lost farmers and the health status of land-lost farmers is significantly worse than that of those with land. Land expropriation has a negative impact on the land-lost farmer’s health through income effects and psychological effects. The health status of land-lost farmers can be enhanced through amending current land requisition policies, increasing the amount of compensation, improving the earning capacity of land-lost farmers and strengthening mental health education.

Effect of Land Expropriation on Land-Lost Farmers’ Health: Empirical Evidence from Rural China

Background The ongoing negative health effects of colonization have disproportionately affected Indigenous women, who are disproportionately affected by diabetes, food insecurity, and undernutrition. Indigenous women also perceive their health less positively than men do. This article draws theoretically from the socio-ecological model to explore health inequalities experienced by Indigenous women associated with the intergenerational effects of the residential school legacy, specifically related to food practices. Objectives Study objectives were to describe and compare the historical context of present-day urban and rural food environments, and explore the hypothesis that food insecurity may be associated with cultural loss resulting from the intergenerational trauma of residential schools in this region of southwestern Ontario, Canada. Methods Framed by a larger community-based participatory study, life history interviews took place with 18 Elder women living on- and off-reserve in southwestern Ontario, Canada. Results Women discussed painful circumstances of displacement from the land and social disconnection from families and communities. The 10 participants who were residential school survivors conveyed the intergenerational effects of loss, responsibility, lack of support, and an altered sense of identity as narratives of survival. Six women had moved away from their home communities, which created challenges to fully engage in local food procurement and sharing practices. These altered geographies present practical limitations, along with apparent mechanisms of social and cultural exclusion. Conclusions Research on Indigenous Peoples' food systems requires further analysis of the root causes of disparities in the context of societal and gender relations. Food sovereignty has been the domain of women, who have led movements aimed at both social and environmental justice. Unraveling the historical, social, and environmental determinants of Indigenous food knowledge will support and guide community and policy recommendations, highlighting the ongoing effects of residential schooling and other indirect examples of environmental dispossession that have disproportionately affected Indigenous women.

Exploring First Nation Elder Women's Relationships with Food from Social, Ecological, and Historical Perspectives.

For many Indigenous communities, decreased participation in traditional land-based activities has led to higher rates of chronic disease and a decrease in well-being. This systematic review explores how traditional land-based activities impact self-reported health and well-being of Indigenous adults, using Indigenous and Western perspectives. A search of three electronic databases (PubMed, Scopus, and Web of Science) identified nine studies which explored the experiences and perspectives of Indigenous adults taking part in land-based subsistence and ceremonial activities. A thematic analysis of these studies identified many interconnected physical, spiritual, mental, emotional, and community benefits. Community engagement throughout all stages of the interventions was an important factor in effectively addressing challenges and barriers stemming from colonization, decreased knowledge transfer, and increased use of technology. Participants reported developing more effective stress management techniques, a greater awareness of modifiable risk factors along with increased engagement with Elders. Ultimately, land-based subsistence and ceremonial activities were identified as playing an influential role in the lives of Indigenous adults. The involvement of community members allowed for the development of more culturally relevant interventions. Future community-specific research is needed to increase engagement in traditional physical-activities, improve well-being and overall reduce the risk of chronic disease.

https://www.mdpi.com/1660-4601/18/13/7099/pdf

The Impact of Land-Based Physical Activity Interventions on Self-Reported Health and Well-Being of Indigenous Adults: A Systematic Review.

Social determinants of self-reported health for Canada's indigenous peoples: a public health approach.

Purpose Achieving successful gene therapy requires delivery of a gene vector specifically to the targeted tissue with efficient expression and a good safety profile. The objective of this work was to develop, characterize and determine if a novel gemini surfactant-based lipoplex systems, modified with a cancer-targeting peptide p18-4, could serve this role. Methods The targeting peptide p18-4 was either chemically coupled to a gemini surfactant backbone or physically co-formulated with the lipoplexes. The influence of targeting ligand and formulation strategies on essential physicochemical properties of the lipoplexes was evaluated by dynamic light scattering and small angle X-ray scattering techniques. In vitro transfection activity and cellular toxicity of lipoplexes were assessed in a model human melanoma cell line. Results All lipoplexes zeta potential and particle size were optimal for cellular uptake and physical stability of the system. The lipoplexes adopted an inverted-hexagonal lipid arrangement. The lipoplexes modified with the peptide showed no significant changes in physicochemical properties or lipoplex assembly. The modification of the lipoplexes with the targeting peptide significantly enhanced protein expression 2-6 fold compared to non-modified lipoplexes. In addition, p18-4 modified lipoplexes significantly improved the safety of the lipoplexes. The ability of the p18-4 modified lipoplexes to selectively express the model protein was confirmed by using healthy human epidermal keratinocytes (HEKa). Conclusion The gemini surfactant-based lipoplexes modified with p18-4 peptide showed significantly higher efficiency and safety compared to the system that did not contain a cancer targeting peptide and provided evidence for their potential application to achieve targeted melanoma gene therapy.

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Design and Evaluation of Gemini Surfactant-Based Lipoplexes Modified with Cell-Binding Peptide for Targeted Gene Therapy in Melanoma Model.

Misuse of alcohol, including single risky occasion drinking (RSOD) is associated with a number of health, social and economic consequences. While research demonstrates that many factors contribute to individuals’ drinking practices, little is known about risk factors that contribute to RSOD in the Canadian population. The objectives of this study are to examine the patterns of RSOD in Canada, to identify factors associated with RSOD, and to explore policy implications. The Canadian Community Health Survey (CCHS) 2009–2010 annual component was used to conduct all the analyses in this paper. We used two models: (1) a binary logistic regression model, and (2) a multinomial logistic regression model, to identify factors that were significantly associated with our dependent variables, RSOD engagement and frequency of RSOD, respectively. Daily smokers were 6.20 times more likely to engage in frequent RSOD than those who never smoke. Males were 4.69 times more likely to engage in risky RSOD. We also found significant associations between the frequency of RSOD and Province/Territory of residence, income and education, marital status and perceived health status. Finally, stress was associated with engaging in infrequent RSOD. Our finding associating daily smoking with risk alcohol intake specifically suggests the possibility of combining public health interventions for both. The study findings also indicate that education is a protective factor, further supporting the role of education as a major determinant of health. The significant provincial variation we found also point to the need to study this issue further and understand the links between provincial level policies and RSOD.

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Richa Tikoo

Papers

Social determinants of self-reported health for Canada's indigenous peoples: a public health approach.

Design and Evaluation of Gemini Surfactant-Based Lipoplexes Modified with Cell-Binding Peptide for Targeted Gene Therapy in Melanoma Model.

Factors influencing risky single occasion drinking in Canada and policy implications