Relationship between subjective fall risk assessment and falls and fall-related fractures in frail elderly people

<p>Abstract</p> <p>Background</p> <p>Objective measurements can be used to identify people with risks of falls, but many frail elderly adults cannot complete physical performance tests. The study examined the relationship between a subjective risk rating of specific tasks (SRRST) to screen for fall risks and falls and fall-related fractures in frail elderly people.</p> <p>Methods</p> <p>The SRRST was investigated in 5,062 individuals aged 65 years or older who were utilized day-care services. The SRRST comprised 7 dichotomous questions to screen for fall risks during movements and behaviours such as walking, transferring, and wandering. The history of falls and fall-related fractures during the previous year was reported by participants or determined from an interview with the participant's family and care staff.</p> <p>Results</p> <p>All SRRST items showed significant differences between the participants with and without falls and fall-related fractures. In multiple logistic regression analysis adjusted for age, sex, diseases, and behavioural variables, the SRRST score was independently associated with history of falls and fractures. Odds ratios for those in the high-risk SRRST group (≥ 5 points) compared with the no risk SRRST group (0 point) were 6.15 (p < 0.01) for a single fall, 15.04 (p < 0.01) for recurrent falls, and 5.05 (p < 0.01) for fall-related fractures. The results remained essentially unchanged in subgroup analysis accounting for locomotion status.</p> <p>Conclusion</p> <p>These results suggest that subjective ratings by care staff can be utilized to determine the risks of falls and fall-related fractures in the frail elderly, however, these preliminary results require confirmation in further prospective research.</p

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Mitochondrial Localized STAT3 Is Involved in NGF Induced Neurite Outgrowth

Background: Signal transducer and activator of transcription 3 (STAT3) plays critical roles in neural development and is increasingly recognized as a major mediator of injury response in the nervous system. Cytokines and growth factors are known to phosphorylate STAT3 at tyrosine 705 with or without the concomitant phosphorylation at serine 727, resulting in the nuclear localization of STAT3 and subsequent transcriptional activation of genes. Recent evidence suggests that STAT3 may control cell function via alternative mechanisms independent of its transcriptional activity. Currently, the involvement of STAT3 mono-phosphorylated at residue serine 727 (P-Ser-STAT3) in neurite outgrowth and the underlying mechanism is largely unknown. Principal Findings: In this study, we investigated the role of nerve growth factor (NGF) induced P-Ser-STAT3 in mediating neurite outgrowth. NGF induced the phosphorylation of residue serine 727 but not tyrosine 705 of STAT3 in PC12 and primary cortical neuronal cells. In PC12 cells, serine but not tyrosine dominant negative mutant of STAT3 was found to impair NGF induced neurite outgrowth. Unexpectedly, NGF induced P-Ser-STAT3 was localized to the mitochondria but not in the nucleus. Mitochondrial STAT3 was further found to be intimately involved in NGF induced neurite outgrowth and the production of reactive oxygen species (ROS). Conclusion: Taken together, the findings herein demonstrated a hitherto unrecognized novel transcription independen

IL-33 Is Produced by Mast Cells and Regulates IgE-Dependent Inflammation

Background: IL-33 is a recently characterized IL-1 family cytokine and found to be expressed in inflammatory diseases, including severe asthma and inflammatory bowl disease. Recombinant IL-33 has been shown to enhance Th2-associated immune responses and potently increase mast cell proliferation and cytokine production. While IL-33 is constitutively expressed in endothelial and epithelial cells, where it may function as a transcriptional regulator, cellular sources of IL-33 and its role in inflammation remain unclear. Methodology/Principal Findings: Here, we identify mast cells as IL-33 producing cells. IgE/antigen activation of bone marrow-derived mast cells or a murine mast cell line (MC/9) significantly enhanced IL-33. Conversely, recombinant IL-33 directly activated mast cells to produce several cytokines including IL-4, IL-5 and IL-6 but not IL-33. We show that expression of IL-33 in response to IgE-activation required calcium and that ionomycin was sufficient to induce IL-33. In vivo, peritoneal mast cells expressed IL-33 and IL-33 levels were significantly lower within the skin of mast cell deficient mice, compared to littermate controls. Local activation of mast cells promotes edema, followed by the recruitment of inflammatory cells. We demonstrate using passive cutaneous anaphylaxis, a mast cell-dependent model, that deficiency in ST2 or antibody blockage of ST2 or IL-33 ablated the late phase inflammatory response but that the immediate phase response was unaffected. IL-33 levels in the skin were significantly elevated only during the late phase

Paracrine IL-33 Stimulation Enhances Lipopolysaccharide-Mediated Macrophage Activation

BACKGROUND: IL-33, a member of the IL-1 family of cytokines, provokes Th2-type inflammation accompanied by accumulation of eosinophils through IL-33R, which consists of ST2 and IL-1RAcP. We previously demonstrated that macrophages produce IL-33 in response to LPS. Some immune responses were shown to differ between ST2-deficient mice and soluble ST2-Fc fusion protein-treated mice. Even in anti-ST2 antibody (Ab)-treated mice, the phenotypes differed between distinct Ab clones, because the characterization of such Abs (i.e., depletion, agonistic or blocking Abs) was unclear in some cases. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the precise role of IL-33, we newly generated neutralizing monoclonal Abs for IL-33. Exogenous IL-33 potentiated LPS-mediated cytokine production by macrophages. That LPS-mediated cytokine production by macrophages was suppressed by inhibition of endogenous IL-33 by the anti-IL-33 neutralizing mAbs. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that LPS-mediated macrophage activation is accelerated by macrophage-derived paracrine IL-33 stimulation