Targeting TGF-ß for treatment of osteogenesis imperfecta.

BACKGROUNDCurrently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-ß signaling is a pathogenic mechanism in OI. Here, we evaluated TGF-ß signaling in children with OI and conducted a phase I clinical trial of TGF-ß inhibition in adults with OI.METHODSHistology and RNA-Seq were performed on bones obtained from children. Gene Ontology (GO) enrichment assay, gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) were used to identify dysregulated pathways. Reverse-phase protein array, Western blot, and IHC were performed to evaluate protein expression. A phase I study of fresolimumab, a TGF-ß neutralizing antibody, was conducted in 8 adults with OI. Safety and effects on bone remodeling markers and lumbar spine areal bone mineral density (LS aBMD) were assessed.RESULTSOI bone demonstrated woven structure, increased osteocytes, high turnover, and reduced maturation. SMAD phosphorylation was the most significantly upregulated GO molecular event. GSEA identified the TGF-ß pathway as the top activated signaling pathway, and IPA showed that TGF-ß1 was the most significant activated upstream regulator mediating the global changes identified in OI bone. Treatment with fresolimumab was well-tolerated and associated with increases in LS aBMD in participants with OI type IV, whereas participants with OI type III and VIII had unchanged or decreased LS aBMD.CONCLUSIONIncreased TGF-ß signaling is a driver pathogenic mechanism in OI. Anti-TGF-ß therapy could be a potential disease-specific therapy, with dose-dependent effects on bone mass and turnover.TRIAL REGISTRATIONClinicalTrials.gov NCT03064074.FUNDINGBrittle Bone Disorders Consortium (U54AR068069), Clinical Translational Core of Baylor College of Medicine Intellectual and Developmental Disabilities Research Center (P50HD103555) from National Institute of Child Health and Human Development, USDA/ARS (cooperative agreement 58-6250-6-001), and Sanofi Genzyme.

Borders, centers, and margins: critical landscapes for migrant health.

Nurses in North America have a distinguished history of involvement in immigrant health due to the immigrant character of this region. The Western Hemisphere is a region composed of recent migrants from nearly every corner of the globe. Complicated economic, environmental, and social dynamics contribute to these various migration patterns and commensurate health-related issues-physical, psychological, and spiritual. Nurses attuned to health issues of newer immigrants' lives use newfound knowledge to shape the care they provide, and political advocacy. This article updates our understandings of migration, utilizing critical perspectives to analyze contemporary dynamics of migration and respective health issues.

Of migrants and metaphors: disrupting discourses to welcome the stranger.

An increasing vitriolic anti-immigrant discourse has grown in media venues in the last several years, creating a climate of fear and hatred of immigrants that has spawned violence against some of them at individual and systemic levels. Historically, metaphors have been used to create a public acceptance of policies of discrimination, racism, and even genocide of targeted social groups, including immigrants. This article examines the use of such metaphors, juxtaposing an analysis of nursing journal articles regarding immigrant health, and of major nursing organizations for policy statements that might support immigrant healthcare.

The elephant in the room: critical reflections on militarism, war, and their health contingencies.

This philosophical analysis critically explores an archeology of militarism as an underpinning to multiple forms of violence, especially war. Deconstructing militarism and its discourses reveal it as a pervasive geographical, cultural, political, and psychological presence. New war technologies, related health and environmental problems, injuries, social suffering, and disproportionality in military spending as a threat to health are uncovered. Continuing the dialogue in formal nursing associations, critiquing media complicity in securing consent for war, and reconstructing a nonviolent, healthier world through nonviolent resistance are advocated.

Fractured migrant families: paradoxes of hope and devastation.

The increasing feminization of migration from Oaxaca, Mexico, in a context of economic globalization has profound implications for the emotional and psychological health of indigenous transnational immigrant women, who often arrive in the United States (US), having left family members or their children behind in the care of relatives. Simultaneously, indigenous women who are left behind on the migration trail also grapple with the suffering of separation and persistent undercurrents of sorrow because of an increasingly dangerous and intransigent US-Mexico border that makes family reunifications so difficult. The public policy discourses surrounding unauthorized immigration across the US-Mexico border tend to neglect attention to the mental and social health effects on families and communities. This article describes their experiences by sharing their voices, and challenges us both to shape new clinical responses, international connections, and solidarity in efforts humanize immigration policy, and to transform the dynamics of economic globalization that contribute to these conditions.

Cross-cultural reliability of the Health Perception Index and the Health Control and Competence Index.

PURPOSE: To test the reliability of two Spanish instruments to measure (a) health perceptions, and (b) health control and competence. DESIGN: Triangulated methodology used with two different Latino populations. METHODS: Preliminary qualitative data were collected in Mexico. Based on themes from Mexico, data were collected from 44 men (Dominican Republic, n=24 ; Peru, n=20) with two instruments, the Health Competence and Control Index and the Health Perception Index. Alpha reliability estimates were obtained. FINDINGS: Results of the study confirmed reliability of the instruments in one of the Latino populations, consistent with understanding of the constructs found in the Mexican study. Reliability was low in the second Latino population. CONCLUSIONS: Although results from this study are useful, further translation and research procedures are needed to address the many differences among ethnically similar groups and to further strengthen internal and external validity of instruments designed to assess Latino men's perceptions of health and their control over health.

Undocumentedness and liminality as health variables.

The growing exodus of indigenous people from Mexico into the United States, especially from the multiethnic state of Oaxaca, is used as an exemplar of the global phenomenon of transnational migration and its effects on health. Lately, indigenous Oaxacan women have become a predominant part of this diaspora in the United States. Driven by economic desperation most arrive across the border as undocumented persons that configure them into multiple liminal spaces inimical to health and well-being. This article provides a venue for some of their voices to be heard, some major concerns understood, and for proposing links between postcolonial Mexico, neoliberal globalization, and immigration border policy as driving forces that undergird these conditions. An emancipatory praxis of nursing to promote health and reduce suffering within transnational migrants is proposed as a starting place for future nursing scholarship.