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BACKGROUND: Group medical visits (GMV) effectively improve patient care and outcomes through interactive education, increased patient contact, and facilitated social support. This quality improvement research examined if patient activation and quality of life correlate with weight, blood pressure (BP), and hemoglobin A1c (A1C) through GMV interventions. METHODS: Participants were enrolled in GMV Lighten Up for weight management or GMV Diabetes. At pre- and post-intervention, patients completed the Patient Activation Measure (PAM) and the health-related quality of life measure, the SF-12; and were assessed for weight, blood pressure (BP), and hemoglobin A1c (A1C). RESULTS: Weight and PAM scores significantly improved regardless of group. For patients in GMV Diabetes, A1C significantly decreased. GMV Lighten Up participants had statistically significant declines in diastolic BP. Both groups improved patient activation, but statistically significantly so only in GMV Diabetes participants. SF-12 scores did not statistically significantly improve. There were no predictors of A1C and PAM score change for the Diabetes GMV. However, age, SBP and SF-12 scores predicted PAM score changes in GMV Lighten up participants. CONCLUSIONS: Participants in this study showed overall improvement in biomarkers and patient activation. Thus, GMV continue to be a viable method for healthcare delivery.
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Diabetes Mellitus , Participación del Paciente , Humanos , Calidad de Vida , Hemoglobina Glucada , Diabetes Mellitus/terapiaRESUMEN
The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE: Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses.
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Infecciones por Bifidobacteriales/inmunología , Bifidobacterium longum/inmunología , Polisacáridos Bacterianos/inmunología , Células Th17/inmunología , Animales , Infecciones por Bifidobacteriales/microbiología , Bifidobacterium longum/genética , Citocinas/inmunología , Femenino , Humanos , Interleucina-17/inmunología , Ratones , Ratones Endogámicos BALB CRESUMEN
The Bifibobacterium longum subsp. longum 35624™ strain (formerly named Bifidobacterium longum subsp. infantis) is a well described probiotic with clinical efficacy in Irritable Bowel Syndrome clinical trials and induces immunoregulatory effects in mice and in humans. This paper presents (a) the genome sequence of the organism allowing the assignment to its correct subspeciation longum; (b) a comparative genome assessment with other B. longum strains and (c) the molecular structure of the 35624 exopolysaccharide (EPS624). Comparative genome analysis of the 35624 strain with other B. longum strains determined that the sub-speciation of the strain is longum and revealed the presence of a 35624-specific gene cluster, predicted to encode the biosynthetic machinery for EPS624. Following isolation and acid treatment of the EPS, its chemical structure was determined using gas and liquid chromatography for sugar constituent and linkage analysis, electrospray and matrix assisted laser desorption ionization mass spectrometry for sequencing and NMR. The EPS consists of a branched hexasaccharide repeating unit containing two galactose and two glucose moieties, galacturonic acid and the unusual sugar 6-deoxy-L-talose. These data demonstrate that the B. longum 35624 strain has specific genetic features, one of which leads to the generation of a characteristic exopolysaccharide.
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BACKGROUND: The Wnt/ß-catenin pathway regulates intestinal development, homeostasis, and regeneration after injury. Wnt/ß-catenin signaling drives intestinal proliferation by activating expression of the c-Myc proto-oncogene (Myc) through the Myc 3' Wnt responsive DNA element (Myc 3' WRE). In a previous study, we found that deletion of the Myc 3' WRE in mice caused increased MYC expression and increased cellular proliferation in the colon. When damaged by dextran sodium sulfate (DSS), the increased proliferative capacity of Myc 3' WRE(-/-) colonocytes resulted in a more rapid recovery compared with wild-type (WT) mice. In that study, we did not examine involvement of the immune system in colonic regeneration. PURPOSE: To characterize the innate immune response in Myc 3' WRE(-/-) and WT mice during and after DSS-induced colonic injury. METHODS: Mice were fed 2.5 % DSS in their drinking water for five days to induce colonic damage and were then returned to normal water for two or four days to recover. Colonic sections were prepared and neutrophils and macrophages were analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by probing a cytokine array with colonic lysates. RESULTS: In comparison with WT mice, there was enhanced leukocyte infiltration into the colonic mucosal and submucosal layers of Myc 3' WRE(-/-) mice after DSS damage. Levels of activated neutrophils were substantially increased in damaged Myc 3' WRE(-/-) colons as were levels of the neutrophil chemoattractants C5/C5a, CXCL1, and CXCL2. CONCLUSION: The Myc 3' WRE regulates neutrophil infiltration into DSS-damaged colons.
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Movimiento Celular/fisiología , Enfermedades del Colon/fisiopatología , Neutrófilos/fisiología , Proteínas Proto-Oncogénicas c-myc/fisiología , Elementos de Respuesta/fisiología , Transducción de Señal/fisiología , Proteínas Wnt/fisiología , Animales , Proliferación Celular , Quimiocinas/metabolismo , Colon/metabolismo , Colon/fisiopatología , Enfermedades del Colon/inducido químicamente , Enfermedades del Colon/patología , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Inmunidad Innata/genética , Inmunidad Innata/fisiología , Ratones , Ratones Noqueados , Neutrófilos/patología , Proteínas Proto-Oncogénicas c-myc/genética , Regeneración/genética , Regeneración/fisiología , Elementos de Respuesta/genética , Transducción de Señal/genética , Proteínas Wnt/genéticaRESUMEN
Ferrochelatase is the terminal enzyme of haem biosynthesis, catalysing the insertion of ferrous iron into the macrocycle of protoporphyrin IX, the last common intermediate of haem and chlorophyll synthesis. Its activity has been reported in both plastids and mitochondria of higher plants, but the relative amounts of the enzyme in the two organelles are unknown. Ferrochelatase is difficult to assay since ferrous iron requires strict anaerobic conditions to prevent oxidation, and in photosynthetic tissues chlorophyll interferes with the quantification of the product. Accordingly, we developed a sensitive fluorimetric assay for ferrochelatase that employs Co(2+) and deuteroporphyrin in place of the natural substrates, and measures the decrease in deuteroporphyrin fluorescence. A hexane-extraction step to remove chlorophyll is included for green tissue. The assay is linear over a range of chloroplast protein concentrations, with an average specific activity of 0.68 nmol x min(-1) x mg of protein(-1), the highest yet reported. The corresponding value for mitochondria is 0.19 nmol x min(-1) x mg of protein(-1). The enzyme is inhibited by N-methylprotoporphyrin, with an estimated IC(50) value of approximately 1 nM. Using this assay we have quantified ferrochelatase activity in plastids and mitochondria from green pea leaves, etiolated pea leaves and pea roots to determine the relative amounts in the two organelles. We found that, in all three tissues, greater than 90% of the activity was associated with plastids, but ferrochelatase was reproducibly detected in mitochondria, at levels greater than the contaminating plastid marker enzyme, and was latent. Our results indicate that plastids are the major site of haem biosynthesis in higher plant cells, but that mitochondria also have the capacity for haem production.