Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization

UNLABELLED: PHOSPHO1 is a phosphatase highly expressed in bone. We studied its functional involvement in mineralization through the use of novel small molecule inhibitors. PHOSPHO1 expression was present within matrix vesicles, and inhibition of enzyme action caused a decrease in the ability of matrix vesicles to calcify. INTRODUCTION: The novel phosphatase, PHOSPHO1, belongs to the haloacid dehalogenase superfamily of hydrolases and is capable of cleaving phosphoethanolamine (PEA) and phosphocholine to generate inorganic phosphate. Our aims in this study were to examine the expression of PHOSPHO1 in murine mineralizing cells and matrix vesicles (MV) and to screen a series of small-molecule PHOSPHO1-specific inhibitors for their ability to pharmacologically inhibit the first step of MV-mediated mineralization. MATERIALS AND METHODS: q-PCR and immunohistochemistry were used to study the expression and localization profiles of PHOSPHO1. Inhibitors of PHOSPHO1's PEA hydrolase activity were discovered using high-throughput screening of commercially available chemical libraries. To asses the efficacy of these inhibitors to inhibit MV mineralization, MVs were isolated from TNAP-deficient (Akp2(-/-)) osteoblasts and induced to calcify in their presence. RESULTS: q-PCR revealed a 120-fold higher level of PHOSPHO1 expression in bone compared with a range of soft tissues. The enzyme was immunolocalized to the early hypertrophic chondrocytes of the growth plate and to osteoblasts of trabecular surfaces and infilling primary osteons of cortical bone. Isolated MVs also contained PHOSPHO1. PEA hydrolase activity was observed in sonicated MVs from Akp2(-/-) osteoblasts but not intact MVs. Inhibitors to PHOSPHO1 were identified and characterized. Lansoprazole and SCH202676 inhibited the mineralization of MVs from Akp2(-/-) osteoblasts by 56.8% and 70.7%, respectively. CONCLUSIONS: The results show that PHOSPHO1 localization is restricted to mineralizing regions of bone and growth plate and that the enzyme present within MVs is in an active state, inhibition of which decreases the capacity of MVs to mineralize. These data further support our hypothesis that PHOSPHO1 plays a role in the initiation of matrix mineralization

WNT-3A modulates articular chondrocyte phenotype by activating both canonical and noncanonical pathways

Peer reviewedPublisher PD

An Emancipatory Approach to Cultural Competency: The Application of Critical Race, Postcolonial, and Intersectionality Theories

Nurses teach, work, and conduct research in an increasingly hostile sociopolitical climate where health inequities persist among marginalized communities. Current approaches to cultural competency do not adequately equip nurses to address these complex factors and risk perpetuating stereotypes and discrimination. A theory-driven emancipatory approach to cultural competency will instead lead to lasting change and uphold the core nursing value of commitment to social justice. This article explicates key tenets of critical race, postcolonial feminist, and intersectionality theories and then applies them, using an emancipatory approach to cultural competency that can reshape nursing education, research, and practice

Promoting the health of refugee women: a scoping literature review incorporating the social ecological model

The health of refugee women after settlement in a new country, can be adversely or positively affected by individual, interpersonal, community, and organizational factors. While much of the previous literature highlights these factors individually, there is a lack of comprehensive synthesis regarding how the factors interact to influence the health of refugee women. We conducted a thematic analysis in our literature review to elucidate how providers can work with refugee women to prevent adverse health outcomes and intervene at multiple levels to improve their health outcomes after resettlement. We reviewed peer-reviewed literature from 2009 to 2019 from Google Scholar, JSTOR, Global Health, PubMed, CINAHL, Sociological Abstracts, and Social Service Abstracts, and also used citation chaining, to identify relevant information pertaining to refugee women’s health. The key terms used for our literature review were, health care, violence, social support, and mental health. In total, we included 52 articles, 3 books, and 8 other sources. We found that refugee women are vulnerable to violence during migration and typically have high rates of post-traumatic stress disorder. There were also concerns of secondary victimization by providers after resettlement. We also found that social support is an important factor for reducing isolation, and improving access to health care, as well as improving mental health outcomes. However, social support was often difficult to maintain, and was moderated by factors such as English language fluency. Health care was influenced by health literacy, cultural difference, communication concerns, and access issues. The findings suggest that at the individual and interpersonal levels there is a need to address language barriers, improve provider-patient communication, and provide appropriate medical and mental health screenings. At the organizational level, interorganizational communication and awareness are vital. At the community level, providers can work with community leaders, to educate, create dialogue and collaboration, to help facilitate understanding and bolster community social support. Improved communication and knowledge about the unique needs and concerns of refugee women through an integrated, multi-system approach is necessary to improve their health outcomes

An analysis of reflections on researcher positionality

Reflexivity is a central tenet of qualitative research. Engaging in self-reflexive praxis allows researchers to identify areas of tension in the research process that need to be further deconstructed. In this paper, we draw on our collective self-reflective experiences as qualitative health researchers whose scholarship is informed by critical and postcolonial feminist epistemologies to offer some guidance on how to approach the concept of insider versus outsider in the research process. Specifically, we analyze recurring methodological tensions related to positionality and outline how they were addressed. The lessons learned from our studies can be instructive to other qualitative researchers.http://nsuworks.nova.edu/tqrpm2022Agricultural Economics, Extension and Rural Developmen

A qualitative assessment of gender roles in child nutrition in Central Malawi

This study was part of a baseline study conducted in 2017 as part of the CARE Southern Africa Nutrition Initiative (SANI), a project undertaken with the financial support of the Government of Canada through Global Affairs Canada.BACKGROUND : Child malnutrition persists globally with men and women playing distinct roles to support children’s nutrition. Women frequently carry the bulk of the workload related to food, care, and health, all of which are critical factors in child nutrition. For this reason, development efforts have emphasised women ignoring the potential role of men in supporting children’s nutrition. This study sought to understand the different roles that Malawian men and women play in children’s nutrition. METHODS : This qualitative was conducted in rural Central Malawi as part of a baseline study in 2017 for the CARE Southern Africa Nutrition Initiative. Seventy-six participants were interviewed, including 19 men and 57 women, using focus group discussions and in-depth interviews. We sought to understand the gender distribution of men’s and women’s roles and how these roles influence child nutrition. RESULTS : We found that both men and women were involved in productive, reproductive, and community work. However, consistent with the literature, women carried a disproportionate workload in supporting child nutrition compared to men. Women’s heavier workloads often prevented them from being able to meet children’s food needs. Nevertheless, shifts in gender roles were observed in some of the sampled communities, with men taking up responsibilities that have been typically associated with women. These changes in gender roles, however, did not necessarily increase women’s power within the household. CONCLUSIONS : Traditional gender roles remain prevalent in the sampled communities. Women continue to be primarily responsible for the food, care, and health of the household. Women’s heavy workloads prevent them from providing optimal care and nutrition for children. While efforts to advance gender equality by encouraging men to participate in child care and other household responsibilities appear to have had marginal success, the extent to which these efforts have successfully encouraged men to share power remains unclear. Improving gender equality and child nutrition will require efforts to redistribute gendered work and encourage men to move towards shared power with women over household decision-making and control over income.CARE Malawi.http://www.biomedcentral.com/bmcpublichealtham2023Agricultural Economics, Extension and Rural Developmen

Extraordinary exposed in early motherhood - a qualitative study exploring experiences of mothers with type 1 diabetes

<p>Abstract</p> <p>Background</p> <p>Women with type 1 diabetes face several challenges during pregnancy, childbirth and in relation to breastfeeding. It is therefore of utmost importance to consider their need for specific support, early postpartum as well as in daily life after discharge from maternity care. Few studies have investigated these aspects of healthcare. The aim of this study was to explore experiences after childbirth regarding breastfeeding, glycemic control, support and well-being in women with type 1 diabetes.</p> <p>Methods</p> <p>A hermeneutic reflective life world research approach was used in this qualitative study. Data was gathered through audio-recorded focus group discussions and individual interviews with 23 women with type 1 diabetes, 6-24 months after childbirth. After verbatim transcription, the text was analyzed in order to identify themes of meaning and a conclusive interpretation of the explored phenomenon.</p> <p>Results</p> <p>Experiences of extraordinary exposure challenged the women with type 1 diabetes in their transition to early motherhood. The exposure included a struggle with breastfeeding, although with a driving force to succeed. Everyday life was filled with uncertainty and unpredictability related to one's own unstable glycemic control and the women down-prioritized their own needs in favor of the child. A feeling of being disconnected from professional care further contributed to the experiences of extraordinary exposure.</p> <p>Conclusion</p> <p>In early motherhood women with type 1 diabetes have a great need for support in managing daily life postpartum, which requires contemporary approaches to overlap insufficient linkage between health care professionals in maternity and child health care, and diabetes care.</p

Prediction of the in vivo mechanical behavior of biointegrable acrylic macroporous scaffolds

[EN] This study examines a biocompatible scaffold series of random copolymer networks P(EA-HEA) made of Ethyl Acrylate, EA, and 2-Hydroxyl Ethyl Acrylate, HEA. The P(EA-HEA) scaffolds have been synthesized with varying crosslinking density and filled with a Poly(Vinyl Alcohol), PVA, to mimic the growing cartilaginous tissue during tissue repair. In cartilage regeneration the scaffold needs to have sufficient mechanical properties to sustain the compression in the joint and, at the same time, transmit mechanical signals to the cells for chondrogenic differentiation. Mechanical tests show that the elastic modulus increases with increasing crosslinking density of P(EA-HEA) scaffolds. The water plays an important role in the mechanical behavior of the scaffold, but highly depends on the crosslinking density of the proper polymer. Furthermore, when the scaffold with hydrogel is tested it can be seen that the modulus increases with increasing hydrogel density. Even so, the mechanical properties are inferior than those of the scaffolds with water filling the pores. The hydrogel inside the pores of the scaffolds facilitates the expulsion of water during compression and lowers the mechanical modulus of the scaffold. The P(EA-HEA) with PVA shows to be a good artificial cartilage model with mechanical properties close to native articular cartilage.This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through the project MAT2013-46467-C4-1-R (including the FEDER financial support). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors acknowledge the assistance and advice of Electron Microscopy Service of the UPV.Vikingsson, L.; Antolinos Turpín, CM.; Gómez-Tejedor, JA.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2016). Prediction of the in vivo mechanical behavior of biointegrable acrylic macroporous scaffolds. Materials Science and Engineering: C. 61:651-658. https://doi.org/10.1016/j.msec.2015.12.068S6516586

Local deformation in a hydrogel induced by an external magnetic field

The aim of this study is to prove the feasibility of a system able to apply local mechanical loading on cells seeded in a hydrogel for tissue engineering applications. This experimental study is based on a previously developed artificial cartilage model with different concentrations of poly(vinyl alcohol) (PVA) that simulates the cartilage extracellular matrix (ECM). Poly(l-lactic acid) (PLLA) microspheres with dispersed magnetic nanoparticles (MNPs) were produced with an emulsion method. These microspheres were embedded in aqueous PVA solutions with varying concentration to resemble increased viscosity of growing tissue during regeneration. The ability to induce a local deformation in the ECM was assessed by applying a steady or an oscillatory magnetic field gradient to different PVA solutions containing the magnetic microparticles, similarly as in ferrogels. PLLA microparticle motion was recorded, and the images were analyzed. Besides, PVA gels and PLLA microparticles were introduced into the pores of a polycaprolactone scaffold, and the microparticle distribution and the mechanical properties of the construct were evaluated. The results of this experimental model show that the dispersion of PLLA microparticles containing MNPs, together with cells in a supporting gel, will allow applying local mechanical stimuli to cells during tissue regeneration. This local stimulation can have a positive effect on the differentiation of seeded cells and improve tissue regeneration.The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the MAT2013-46467-C4-1-R project, including the Feder funds. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors thank "Servicio de Microscopia Electronica" of Universitat Politecnica de Valencia for their invaluable help. The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain.Vikingsson, L.; Vinals Guitart, Á.; Valera Martínez, A.; Riera Guasp, J.; Vidaurre Garayo, AJ.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2016). Local deformation in a hydrogel induced by an external magnetic field. Journal of Materials Science. 51(22):9979-9990. https://doi.org/10.1007/s10853-016-0226-8S997999905122Eyre D (2002) Collagen of articular cartilage. Arthritis Res 4:30–35Roughley PJ, Lee ER (1994) Cartilage proteoglycans: structure and potential functions. Microsc Res Tech 28:385–397Gillard GC, Reilly HC, Bell-Booth PG, Flint MH (1979) The influence of mechanical forces on the glycosaminoglycan content of the rabbit flexor digitorum profundus tendon. 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What explains gender inequalities in HIV/AIDS prevalence in sub-Saharan Africa? Evidence from the demographic and health surveys

Abstract Background Women are disproportionally affected by human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa (SSA). The determinants of gender inequality in HIV/AIDS may vary across countries and require country-specific interventions to address them. This study aimed to identify the socio-demographic and behavioral characteristics underlying gender inequalities in HIV/AIDS in 21 SSA countries. Methods We applied an extension of the Blinder-Oaxaca decomposition approach to data from Demographic and Health Surveys and AIDS Indicator Surveys to quantify the differences in HIV/AIDS prevalence between women and men attributable to socio-demographic factors, sexual behaviours, and awareness of HIV/AIDS. We decomposed gender inequalities into two components: the percentage attributable to different levels of the risk factors between women and men (the “composition effect”) and the percentage attributable to risk factors having differential effects on HIV/AIDS prevalence in women and men (the “response effect”). Results Descriptive analyses showed that the difference between women and men in HIV/AIDS prevalence varied from a low of 0.68 % (P = 0.008) in Liberia to a high of 11.5 % (P < 0.001) in Swaziland. The decomposition analysis showed that 84 % (P < 0.001) and 92 % (P < 0.001) of the higher prevalence of HIV/AIDS among women in Uganda and Ghana, respectively, was explained by the different distributions of HIV/AIDS risk factors, particularly age at first sex between women and men. In the majority of countries, however, observed gender inequalities in HIV/AIDS were chiefly explained by differences in the responses to risk factors; the differential effects of age, marital status and occupation on prevalence of HIV/AIDS for women and men were among the significant contributors to this component. In Cameroon, Guinea, Malawi and Swaziland, a combination of the composition and response effects explained gender inequalities in HIV/AIDS prevalence. Conclusions The factors that explain gender inequality in HIV/AIDS in SSA vary by country, suggesting that country-specific interventions are needed. Unmeasured factors also contributed substantially to the difference in HIV/AIDS prevalence between women and men, highlighting the need for further study