The associations of adipokines with selected markers of the renin-angiotensinogen-aldosterone system: the multi-ethnic study of atherosclerosis.

Among obese individuals, increased sympathetic nervous system (SNS) activity results in increased renin and aldosterone production, as well as renal tubular sodium reabsorption. This study determined the associations between adipokines and selected measures of the renin-angiotensinogen-aldosterone system (RAAS). The sample consisted of 1970 men and women from the Multi-Ethnic Study of Atherosclerosis who were free of clinical cardiovascular disease at baseline and had blood assayed for adiponectin, leptin, plasma renin activity (PRA) and aldosterone. The mean age was 64.7 years and 50% were female. The mean (s.d.) PRA and aldosterone were 1.45 (0.56) ng ml(-1) and 150.1 (130.5) pg ml(-1), respectively. After multivariable adjustment, a 1-s.d. increment of leptin was associated with a 0.55 ng ml(-1) higher PRA and 8.4 pg ml(-1) higher aldosterone (P<0.01 for both). Although adiponectin was not significantly associated with PRA levels, the same increment in this adipokine was associated with lower aldosterone levels (-5.5 pg ml(-1), P=0.01). Notably, the associations between aldosterone and both leptin and adiponectin were not materially changed with additional adjustment for PRA. Exclusion of those taking antihypertensive medications modestly attenuated the associations. The associations between leptin and both PRA and aldosterone were not different by gender but were significantly stronger among non-Hispanic Whites and Chinese Americans than African and Hispanic Americans (P<0.01). The findings suggest that both adiponectin and leptin may be relevant to blood pressure regulation via the RAAS, in that the associations appear to be robust to antihypertension medication use and that the associations are likely different by ethnicity

The PULSE Project: A Case of Use of Big Data Uses Toward a Cohomprensive Health Vision of City Well Being

Despite the silent effects sometimes hidden to the major audience, air pollution is becoming one of the most impactful threat to global health. Cities are the places where deaths due to air pollution are concentrated most

Intuitive and Informal Knowledge in Preschoolers’ Development of Probabilistic Thinking

Preschoolers develop a wide range of mathematical informal knowledge and intuitive thinking before they enter formal, goal-oriented education. In their everyday activities young children get engaged with situations that enhance them to develop skills, concepts, strategies, representations, attitudes, constructs and operations concerning a wide range of mathematical notions. Recently there is scientific interest in linking children’s informal and formal knowledge in order to provide them with opportunities to avoid biases aiming at formulating, perceiving, reflecting on and exercising probabilistic notions. The current study investigates preschoolers’ (N=90) intuitive understanding of the likelihood of events in a probabilistic task with spinners. Participants, at the age of 4 to 6, are tested on their predictions of the most probable outcome prior to and after an instructive session of reasoning. The probabilistic task, based on constructivist principles, includes methodological alterations concerning the sample space and the themes of the stimuli. Educational implications are further discussed under the general point of view that in order to link informal to formal mathematical learning in preschool classroom, the subject content and the cognitive capacity of children are important to match

Pentraxin-3 as a Marker of Advanced Atherosclerosis Results from the Bruneck, ARMY and ARFY Studies

PubMed ID: 22319633This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Cigarette smoke induces PTX3 expression in pulmonary veins of mice in an IL-1 dependent manner

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammatory responses and structural alterations of the airways, lung parenchyma and pulmonary vasculature. Since Pentraxin-3 (PTX3) is a tuner of inflammatory responses and is produced by endothelial and inflammatory cells upon stimuli such as interleukin-1β (IL-1β), we hypothesized that PTX3 is involved in COPD pathogenesis.</p> <p>Methods and Results</p> <p>We evaluated whether cigarette smoke (CS) triggers pulmonary and systemic PTX3 expression <it>in vivo </it>in a murine model of COPD. Using immunohistochemical (IHC) staining, we observed PTX3 expression in endothelial cells of lung venules and veins but not in lung arteries, airways and parenchyma. Moreover, ELISA on lung homogenates and semi-quantitative scoring of IHC-stained sections revealed a significant upregulation of PTX3 upon subacute and chronic CS exposure. Interestingly, PTX3 expression was not enhanced upon subacute CS exposure in IL-1RI KO mice, suggesting that the IL-1 pathway is implicated in CS-induced expression of vascular PTX3. Serum PTX3 levels increased rapidly but transiently after acute CS exposure.</p> <p>To elucidate the functional role of PTX3 in CS-induced responses, we examined pulmonary inflammation, protease/antiprotease balance, emphysema and body weight changes in WT and Ptx3 KO mice. CS-induced pulmonary inflammation, peribronchial lymphoid aggregates, increase in MMP-12/TIMP-1 mRNA ratio, emphysema and failure to gain weight were not significantly different in Ptx3 KO mice compared to WT mice. In addition, Ptx3 deficiency did not affect the CS-induced alterations in the pulmonary (mRNA and protein) expression of VEGF-A and FGF-2, which are crucial regulators of angiogenesis.</p> <p>Conclusions</p> <p>CS increases pulmonary PTX3 expression in an IL-1 dependent manner. However, our results suggest that either PTX3 is not critical in CS-induced pulmonary inflammation, emphysema and body weight changes, or that its role can be fulfilled by other mediators with overlapping activities.</p

A critical realist evaluation of a music therapy intervention in palliative care

BACKGROUND: Music therapy is increasingly used as an adjunct therapy to support symptom management in palliative care. However, studies to date have paid little attention to the processes that lead to changes in patient outcomes. To fill this gap, we examined the processes and experiences involved in the introduction of music therapy as an adjunct complementary therapy to palliative care in a hospice setting in the United Kingdom (UK). METHODS: Using a realistic evaluation approach, we conducted a qualitative study using a variety of approaches. These consisted of open text answers from patients (n = 16) on how music therapy helped meet their needs within one hospice in Northern Ireland, UK. We also conducted three focus groups with a range of palliative care practitioners (seven physicians, seven nursing staff, two social workers and three allied health professionals) to help understand their perspectives on music therapy's impact on their work setting, and what influences its successful implementation. This was supplemented with an interview with the music therapist delivering the intervention. RESULTS: Music therapy contains multiple mechanisms that can provide physical, psychological, emotional, expressive, existential and social support. There is also evidence that the hospice context, animated by a holistic approach to healthcare, is an important facilitator of the effects of music therapy. Examination of patients' responses helped identify specific benefits for different types of patients. CONCLUSIONS: There is a synergy between the therapeutic aims of music therapy and those of palliative care, which appealed to a significant proportion of participants, who perceived it as effective

C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older.

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation

Histone Deacetylase Inhibitors Downregulate Checkpoint Kinase 1 Expression to Induce Cell Death in Non-Small Cell Lung Cancer Cells

Background: Histone deacetylase inhibitors (HDACis) are promising anticancer drugs; however, the molecular mechanisms leading to HDACi-induced cell death have not been well understood and no clear mechanism of resistance has been elucidated to explain limited efficacy of HDACis in clinical trials. Methods and Findings: Here, we show that protein levels of checkpoint kinase 1 (Chk1), which has a major role in G2 cell cycle checkpoint regulation, was markedly reduced at the protein and transcriptional levels in lung cancer cells treated with pan-and selective HDACis LBH589, scriptaid, valproic acid, apicidin, and MS-275. In HDACi treated cells Chk1 function was impaired as determined by decreased inhibitory phosphorylation of cdc25c and its downstream target cdc2 and increased expression of cdc25A and phosphorylated histone H3, a marker of mitotic entry. In time course experiments, Chk1 downregulation occurred after HDACi treatment, preceding apoptosis. Ectopic expression of Chk1 overcame HDACiinduced cell death, and pretreating cells with the cdc2 inhibitor purvalanol A blocked entry into mitosis and prevented cell death by HDACis. Finally, pharmacological inhibition of Chk1 showed strong synergistic effect with LBH589 in lung cancer cells. Conclusions: These results define a pathway through which Chk1 inhibition can mediate HDACi-induced mitotic entry and cell death and suggest that Chk1 could be an early pharmacodynamic marker to assess HDACi efficacy in clinical samples

A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection

10.1186/1471-2334-4-34BMC Infectious Diseases4-BIDM