Overweight and Class I Obesity Are Associated with Lower 10-Year Risk of Mortality in Brazilian Older Adults: The Bambuí Cohort Study of Ageing

Background: Prospective studies mostly with European and North-American populations have shown inconsistent results r

C-Reactive Protein and B-Type Natriuretic Peptide Yield Either a Non-Significant or a Modest Incremental Value to Traditional Risk Factors in Predicting Long-Term Overall Mortality in Older Adults

Background:New biomarkers may aid in preventive and end-of-life decisions in older adults if they enhance the prognostic ability of traditional risk factors. We investigated whether C-reactive protein (CRP) and/or B-type natriuretic peptide (BNP) improve the ability to predict overall mortality among the elderly of the Bambuí, Brazil Study of Aging when added to traditional risk factors.Methods:From 1997 to 2007, 1,470 community-dwelling individuals (≥60 years) were followed-up. Death was ascertained by continuous verification of death certificates. We calculated hazard ratios per 1 standard deviation change (HR) of death for traditional risk factors only (old model), and traditional risk factors plus CRP and/or BNP (new models) and assessed calibration of the models. Subsequently, we compared c-statistic of each of the new models to the old one, and calculated integrated discriminative improvement (IDI) and net reclassification improvement (NRI).Results:544 (37.0%) participants died in a mean follow-up time of 9.0 years. CRP (HR 1.28, 95% CI 1.17-1.40), BNP (HR 1.31 95% CI 1.19-1.45), and CRP plus BNP (HR 1.26, 95% CI 1.15-1.38, and HR 1.29, 95% CI 1.16-1.42, respectively) were independent determinants of mortality. All models were well-calibrated. Discrimination was similar among the old (c-statistic 0.78 [0.78-0.81]) and new models (p=0.43 for CRP; p=0.57 for BNP; and p=0.31 for CRP plus BNP). Compared to the old model, CRP, BNP, and CRP plus BNP models led to an IDI of 0.009 (p<0.001), -0.005 (p<0.001) and -0.003 (p=0.84), and a NRI of 0.04 (p=0.24), 0.07 (p=0.08) and 0.06 (p=0.10), respectively.Conclusions:Despite being independent predictors of long-term risk of death, compared to traditional risk factors CRP and/or BNP led to either a modest or non-significant improvement in the ability of predicting all-cause mortality in older adults

Role of 5-HT1A and 5-HT2C receptors of the dorsal periaqueductal gray in the anxiety- and panic-modulating effects of antidepressants in rats

Antidepressant drugs are first-line treatment for panic disorder. Facilitation of 5-HT1A receptor-mediated neurotransmission in the dorsal periaqueductal gray (dPAG), a key panic-associated area, has been implicated in the panicolytic effect of the selective serotonin reuptake inhibitor fluoxetine. However, it is still unknown whether this mechanism accounts for the antipanic effect of other classes of antidepressants drugs (ADs) and whether the 5-HT interaction with 5-HT2C receptors in this midbrain area (which increases anxiety) is implicated in the anxiogenic effect caused by short-term treatment with ADs. The results showed that previous injection of the 5-HT1A receptor antagonist WAY-100635 in the dPAG blocked the panicolytic-like effect caused by chronic systemic administration of the tricyclic AD imipramine in male Wistar rats tested in the elevated T-maze. Neither chronic treatment with imipramine nor fluoxetine changed the expression of 5-HT1A receptors in the dPAG. Treatment with these ADs also failed to significantly change ERK1/2 (extracellular-signal regulated kinase) phosphorylation level in this midbrain area. Blockade of 5-HT2C receptors in the dPAG with the 5-HT2C receptor antagonist SB-242084 did not change the anxiogenic effect caused by a single acute injection of fluoxetine or imipramine in the Vogel conflict test. These results reinforce the view that the facilitation of 5-HT1A receptor mediated neurotransmission in the dPAG is a common mechanism involved in the panicolytic effect caused by chronic administration of ADs. On the other hand, the anxiogenic effect observed after short-term treatment with these drugs does not depend on 5-HT2C receptors located in the dPAG.Peer reviewe

Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells

BACKGROUND: Breastfed human infants are predominantly colonized by bifidobacteria that thrive on human milk oligosaccharides (HMO). Two predominant species of bifidobacteria in infant feces are Bifidobacterium breve (B. breve) and Bifidobacterium longum subsp. infantis (B. infantis), both of which include avid HMO-consumer strains. Our laboratory has previously shown that B. infantis, when grown on HMO, increases adhesion to intestinal cells and increases the expression of the anti-inflammatory cytokine interleukin-10. The purpose of the current study was to investigate the effects of carbon source—glucose, lactose, or HMO—on the ability of B. breve and B. infantis to adhere to and affect the transcription of intestinal epithelial cells on a genome-wide basis. RESULTS: HMO-grown B. infantis had higher percent binding to Caco-2 cell monolayers compared to B. infantis grown on glucose or lactose. B. breve had low adhesive ability regardless of carbon source. Despite differential binding ability, both HMO-grown strains significantly differentially affected the Caco-2 transcriptome compared to their glucose or lactose grown controls. HMO-grown B. breve and B. infantis both downregulated genes in Caco-2 cells associated with chemokine activity. CONCLUSION: The choice of carbon source affects the interaction of bifidobacteria with intestinal epithelial cells. HMO-grown bifidobacteria reduce markers of inflammation, compared to glucose or lactose-grown bifidobacteria. In the future, the design of preventative or therapeutic probiotic supplements may need to include appropriately chosen prebiotics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-015-0508-3) contains supplementary material, which is available to authorized users

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

10-year cumulative incidence of death per BMI unit at baseline according to age groups.

<p>10-year cumulative incidence of death per BMI unit at baseline according to age groups.</p