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This paper describes a poverty reduction approach to addressing an important determinant of health and well-being among Canada’s First Nations. The Poverty Action Research Project (PARP) has its origins in the Make Poverty History Committee established by the Assembly of First Nations (AFN) in 2008. Academic members of the Committee in cooperation with the AFN subsequently applied for an action research grant to the Canadian Institutes of Health Research (CIHR). The project selected five volunteer First Nations from different parts of Canada, hiring a coordinator in each, undertaking background research, developing a profile and working with First Nation representatives in the development of a strategy to address upstream determinants of health and well-being. Subsequently, project team members within each region assisted where needed with plan implementation, supporting some initiatives with small grants. This paper provides insights from the project in several key areas, including First Nation rejection of the concept of poverty as usually defined, the importance of taking action to strengthen collectivities as well as individuals, the feasibility of assisting First Nations who are at different points in their development journey, the strengths of the leadership within the First Nations, and finding the appropriate balance between the elected and business leadership. These insights emerged from dialogue and reflection among project team members and community participants over the life of the project. We also describe what we have learned about how to engage effectively and with mutual respect with First Nations in this kind of project. The paper concludes with a review of our experiences with the policies and practices of the national research granting councils and the universities, which have not fully adjusted to the requirements of action research involving First Nations.

Successful daily self-management of diabetes is essential to the achievement of positive health outcomes. Basic to successful self-management of any disease is a sense of self-efficacy, or the feeling of confidence in one's self-management abilities. This study examined the association of these variables on the achievement of glycemic control, specifically A1C levels. This study used a retrospective cohort design to evaluate the predictive relationship of self-efficacy and self-care behaviors on A1C level. After Institutional Review Board approval was obtained, 60 medical records were accessed of people ≥ 18 years of age with type 1 or type 2 diabetes who were seen consecutively in a primary care practice located in an urban setting. Data analysis revealed no statistically significant relationships between global measures of self-efficacy and self-care and A1C levels. However, there were two questions from the Stanford Diabetes Self-Efficacy for Diabetes Scale found to be significantly related to A1C (P < 0.009). Those whose diabetes was well controlled were confident in selecting appropriate foods when hungry and in their ability to exercise for 15–30 minutes, four to five times per week. These findings, if replicated in future studies, may provide clinicians an opportunity to develop and test targeted self-management interventions yielding the highest probability of improved glycemic control.

Matrix metalloprotease (MMP)-9 is an elastolytic endopeptidase produced by activated macrophages that may be involved in the development of human pulmonary emphysema and could be inhibited with existing compounds. Mouse models have demonstrated that excess MMP-9 production can result in permanent alveolar destruction.To determine if MMP-9 causes cigarette smoke-induced emphysema using MMP-9 knockout mice and human samples.Mouse lungs were analyzed for inflammation and airspace enlargement using a mainstream smoke-exposure model. Human macrophage mRNA was isolated from subjects with emphysema by laser capture microdissection. Human blood monocyte mRNA was isolated from subjects with greater than 30 pack-year smoking history. Human gene expression was determined by quantitative polymerase chain reaction and compared with emphysema severity determined by automated computed tomography analysis. Plasma Clara cell secretory protein and surfactant protein-D were quantified to measure ongoing lung injury.Mice deficient in MMP-9 develop the same degree of cigarette smoke-induced inflammation and airspace enlargement as strain-matched controls. Macrophages are the predominant source of MMP-9 production in human emphysema specimens and similar quantities of macrophage MMP-9 mRNA is present in areas of lung with and without emphysema. Circulating monocytes produce more MMP-9 in individuals with advanced emphysema severity despite no correlation of MMP-9 with markers of ongoing lung damage.These results suggest that MMP-9 in humans who smoke is similar to smoke-exposed mice, where MMP-9 is present in emphysematous lung but not correlated with the emphysema. To the degree that the mechanisms of emphysema in humans who smoke resemble the mouse model, these data suggest specific inhibition of MMP-9 is unlikely to be an effective therapy for cigarette smoke-induced emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT 00757120).

Cross-species analysis of microarray data has shown improved discriminating power between healthy and diseased states. Computational approaches have proven effective in deciphering the complexity of human disease by identifying upstream regulatory elements and the transcription factors that interact with them. Here we used both methods to identify highly conserved transcriptional responses during mechanical ventilation, an important therapeutic treatment that has injurious side effects. We generated control and ventilated whole lung samples from the premature baboon model of bronchopulmonary dysplasia (BPD), processed them for microarray, and combined them with existing whole lung oligonucleotide microarray data from 85 additional control samples from mouse, rat, and human and 19 additional ventilated samples from mouse and rat. Of the 2,531 orthologs shared by all 114 samples, 60 were modulated by mechanical ventilation [false discovery rate (FDR)-adjusted q value ( qFDR) = 0.005, ANOVA]. These included transcripts encoding the transcription factors ATF3 and FOS. Because of compelling known roles for these transcription factors, we used computational methods to predict their targets in the premature baboon model of BPD, which included elastin (ELN), gastrin-releasing polypeptide (GRP), and connective tissue growth factor (CTGF). This approach identified highly conserved transcriptional responses to mechanical ventilation and may facilitate identification of therapeutic targets to reduce the side effects of this valuable treatment.

Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs.Thirteen human severe emphysematous lungs, including five with alpha(1)-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA and RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed.Nucleic acid oxidation was increased in alveolar wall cells in emphysematous lungs compared to non-COPD and donor lungs (p0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm,0.5 mm; p0.05) and CT scan (-950 Hounsfield units; p0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p0.05) and airway epithelial cells (p0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells.We demonstrated for the first time that nucleic acids, especially RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.

Retinoids regulate elastin synthesis by alveolar myofibroblasts and affect angiogenesis pathways, both of which are processes critical for alveolar development. Retinoids accelerate alveolarization in rodents and are now used therapeutically in premature infants at risk of bronchopulmonary dysplasia (BPD). This study examined the effects of retinoid supplementation on alveolar elastin expression and deposition and angiogenesis-related signaling in a primate model of BPD. Premature baboons delivered at 125 d of gestation after maternal steroid treatment were given surfactant and ventilated with minimal supplemental oxygen for 14 d with (n = 5) and without (n = 5) supplemental vitamin A (5000 U/kg/d) and compared with 140-d unventilated controls. Ventilatory efficiency index (VEI) and oxygenation index (OI) were not statistically different between ventilated treatment groups. Expression of vascular endothelial growth factor A (VEGF-A), fms-related tyrosine kinase 1 (Flt-1), and tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE-1) was repressed by premature delivery and mechanical ventilation and was not altered by retinoid supplementation. Retinoid supplementation did not enhance alveolar angiogenesis. Elastin expression was repressed by premature delivery and extended ventilation, and retinoid supplementation increased elastin expression specifically in alveolar myofibroblasts within alveolar walls. These results suggest that the small decrease in mortality among premature infants receiving retinoid supplementation may not be mediated through enhanced alveolar development.

Objetivos: Determinar la prevalencia de leucemias agudas, por inmunofenotipo. Diseño: Descriptivo transversal. Institución: Instituto de Investigaciones Clínicas, Facultad de Medicina, UNMSM, y Hospital Nacional Dos de Mayo (HNDM). Participantes: Pacientes con neoplasias hematológicas atendidos en el HNDM en el periodo 2011-julio 2012. Intervenciones: A todos los pacientes se realizó hemograma, mielograma, citometría de flujo (sangre medular). Principales medidas de resultados: Prevalencia de neoplasias hematológicas y leucemias agudas, características inmunofenotípicas. Resultados: Se encontró 80 neoplasias hematológicas: 42 (52,5%) leucemias agudas, 21(26,3%) mieloma múltiple, 8 (10%), linfomas, 5 (6,3%) síndromes mieloproliferativos crónicos, 4 (5%) mielodisplasias. Las leucemias agudas con citometría, en 12 (41,4%) mujeres y 17 (58,6%) varones se encontró lla 17 (40,5%), 12 (28,6%) lma, 13 (30,9%) no tipificada. Características inmunofenotipicas de las lla: 2 fueron t y 15 b. Orden de frecuencia: lla común pura (10), lla pre b (02), lla pro b (02) lla bifenotípica (01). En lma: (12) lma–m2 (08), lma-m0 (1), lma-m1 (1), lma–m3 (1), lma-m5 (1). Conclusiones: 52% de las neoplasias en el HNDM fueron leucemias agudas. La lla b común fue la más frecuente (58,8% respecto a lla y 34,5% a todas las leucemias agudas con citometría), prevalencia similar a otros estudios internacionales.

Oxidative stress is widely proposed as a pathogenic mechanism for chronic obstructive pulmonary disease (COPD), but the molecular pathway connecting oxidative damage to tissue destruction remains to be fully defined. We suggest that reactive oxygen species (ROS) oxidatively damage nucleic acids, and this effect requires multiple repair mechanisms, particularly base excision pathway components 8-oxoguanine-DNA glycosylase (OGG1), endonuclease III homologue 1 (NTH1), and single-strand–selective monofunctional uracil-DNA glycosylase 1 (SMUG1), as well as the nucleic acid-binding protein, Y-box binding protein 1 (YB1). This study was therefore designed to define the levels of nucleic-acid oxidation and expression of genes involved in the repair of COPD and in corresponding models of this disease. We found significant oxidation of nucleic acids localized to alveolar lung fibroblasts, increased levels of OGG1 mRNA expression, and decreased concentrations of NTH1, SMUG1, and YB1 mRNA in lung samples from subjects with very severe COPD compared with little or no COPD. Mice exposed to cigarette smoke exhibited a time-dependent accumulation of nucleic-acid oxidation in alveolar fibroblasts, which was associated with an increase in OGG1 and YB1 mRNA concentrations. Similarly, human lung fibroblasts exposed to cigarette smoke extract exhibited ROS-dependent nucleic-acid oxidation. The short interfering RNA (siRNA)-dependent knockdown of OGG1 and YB1 expression increased nucleic-acid oxidation at the basal state and after exposure to cigarette smoke. Together, our results demonstrate ROS-dependent, cigarette smoke-induced nucleic-acid oxidation in alveolar fibroblasts, which may play a role in the pathogenesis of emphysema.

Research on marine geological and lake sediment benefits from community repository facilities that are supported by the U.S. National Science Foundation (NSF) at eight U.S. institutions. These facilities house sediment cores, sediment trap samples, and sea floor rocks, and distribute data and materials for national and international scientific use. For more than 30 years, in partnership with participating universities, NSF has provided support for these community service facilities, recognizing that storage and distribution of these unique materials leverage the best and most cost-effective science for the global community. Curators representing the participating institutions meet semi-annually to coordinate repository activities, to set standards for archival, and to maintain policies that maximize research use of materials. These planning meetings began in 1977, when lack of coordination among institutions limited access to the broader community. The inaugural meeting of 18 interested repositories yielded a preliminary sediment description scheme and a first community data base, which opened in 1979 with records on 5000 sediment cores hosted by the National Oceanic and Atmospheric Administration's National Geophysical Data Center (NGDC) and World Data Center for Marine Geology and Geophysics in Boulder, Colorado.