•Caffeic, rosmarinic and salvianolic acids were identified in Salvia hispanica L.•Ferulic acid was identified in hydrolyzed extracts of the Salvia hispanica L.•Danshensu, caffeic, rosmarinic and ...ferulic acids showed electrochemical activity.•The total phenolic content from chia seeds and fiber flour extracts were similar.
The consumption of chia seeds products has increased recently and it has been suggested that the inclusion of this functional food in a daily human diet could contribute to improve consumers’ health. However, a better knowledge about the composition of these products is mandatory. In this work, the phenolic compounds from commercial samples of chia seed, fiber flour and oil were extracted using an ultrasound-assisted methodology and were separated and identified by high-performance liquid chromatography coupled to a mass spectrometer. Methanol:water extracts were prepared and submitted to an acidic hydrolysis. Crude and hydrolyzed extracts were analyzed and phenolic compounds found were mainly caffeic acid and danshensu and its derivatives, such as rosmarinic and salvianolic acids. TPC was higher in the hydrolyzed extracts. These results supply new information about the main phenolic compounds presents in chia, which are important dietary sources of natural antioxidants for prevention of diseases caused by oxidative stress.
Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) trials showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular ...death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes. However, neither trial was powered to assess effects on cardiovascular death or all-cause death or to characterise effects in clinically important subgroups. Using study-level published data from DAPA-HF and patient-level data from EMPEROR-Reduced, we aimed to estimate the effect of SGLT2 inhibition on fatal and non-fatal heart failure events and renal outcomes in all randomly assigned patients with HFrEF and in relevant subgroups from DAPA-HF and EMPEROR-Reduced trials.
We did a prespecified meta-analysis of the two single large-scale trials assessing the effects of SGLT2 inhibitors on cardiovascular outcomes in patients with HFrEF with or without diabetes: DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin). The primary endpoint was time to all-cause death. Additionally, we assessed the effects of treatment in prespecified subgroups on the combined risk of cardiovascular death or hospitalisation for heart failure. These subgroups were based on type 2 diabetes status, age, sex, angiotensin receptor neprilysin inhibitor (ARNI) treatment, New York Heart Association (NYHA) functional class, race, history of hospitalisation for heart failure, estimated glomerular filtration rate (eGFR), body-mass index, and region (post-hoc). We used hazard ratios (HRs) derived from Cox proportional hazard models for time-to-first event endpoints and Cochran's Q test for treatment interactions; the analysis of recurrent events was based on rate ratios derived from the Lin-Wei-Yang-Ying model.
Among 8474 patients combined from both trials, the estimated treatment effect was a 13% reduction in all-cause death (pooled HR 0·87, 95% CI 0·77–0·98; p=0·018) and 14% reduction in cardiovascular death (0·86, 0·76–0·98; p=0·027). SGLT2 inhibition was accompanied by a 26% relative reduction in the combined risk of cardiovascular death or first hospitalisation for heart failure (0·74, 0·68–0·82; p<0·0001), and by a 25% decrease in the composite of recurrent hospitalisations for heart failure or cardiovascular death (0·75, 0·68–0·84; p<0·0001). The risk of the composite renal endpoint was also reduced (0·62, 0·43–0·90; p=0·013). All tests for heterogeneity of effect size between trials were not significant. The pooled treatment effects showed consistent benefits for subgroups based on age, sex, diabetes, treatment with an ARNI and baseline eGFR, but suggested treatment-by-subgroup interactions for subgroups based on NYHA functional class and race.
The effects of empagliflozin and dapagliflozin on hospitalisations for heart failure were consistent in the two independent trials and suggest that these agents also improve renal outcomes and reduce all-cause and cardiovascular death in patients with HFrEF.
Boehringer Ingelheim.
This article aims to identify the existence of a laughter community in Portugal in the late eighteenth and early nineteenth centuries. Based on research into the beginnings of humour in periodicals ...published in Portugal, a corpus consisting of newspapers published between 1797 and 1835 was analysed, from the first in which humour was used systematically as a resource (Almocreve de Petas) until the establishment of the Constitutional Monarchy. With the concept of laughter community in mind, evidence was sought that it was present in the period that covers the political, social and economic transition from the Ancien Régime to modern society, having as main players writers, editors, printers, readers and listeners, in a process of production, reception, circulation and appropriation of ideas and meanings. This process, which developed in the public sphere, also played a part in forming incipient public opinion. To detect evidence of this community, clichés, jocular expressions and comic stories conveyed by the periodicals were identified. Very often they were found to have kept the same meaning they had at the time, while some expressions have survived with slight changes, and others simply no longer make people laugh.
An unresolved question for the understanding of Alzheimer's disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not ...develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (n = 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast
). Cross-sectional and longitudinal tau-positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aβ only in CU Ast
individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aβ with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
Astrocytes can adopt multiple molecular phenotypes in the brain of Alzheimer's disease (AD) patients. Here, we studied the associations of cerebrospinal fluid (CSF) glial fibrillary acidic protein ...(GFAP) and chitinase-3-like protein 1 (YKL-40) levels with brain amyloid-β (Aβ) and tau pathologies. We assessed 121 individuals across the aging and AD clinical spectrum with positron emission tomography (PET) brain imaging for Aβ (
FAZD4694) and tau (
FMK-6240), as well as CSF GFAP and YKL-40 measures. We observed that higher CSF GFAP levels were associated with elevated Aβ-PET but not tau-PET load. By contrast, higher CSF YKL-40 levels were associated with elevated tau-PET but not Aβ-PET burden. Structural equation modeling revealed that CSF GFAP and YKL-40 mediate the effects of Aβ and tau, respectively, on hippocampal atrophy, which was further associated with cognitive impairment. Our results suggest the existence of distinct astrocyte biomarker signatures in response to brain Aβ and tau accumulation, which may contribute to our understanding of the complex link between reactive astrogliosis heterogeneity and AD progression.
Background Identifying the mechanistic pathways potentially associated with incident heart failure (HF) may provide a basis for novel preventive strategies. Methods and Results To identify proteomic ...biomarkers and the potential underlying mechanistic pathways that may be associated with incident HF defined as the first hospitalization for HF, a nested-matched case-control design was used with cases (incident HF) and controls (without HF) selected from 3 cohorts (>20 000 individuals). Controls were matched on cohort, follow-up time, age, and sex. Two independent sample sets (a discovery set with 286 cases and 591 controls and a replication set with 276 cases and 280 controls) were used to discover and replicate the findings. Two hundred fifty-two circulating proteins in the plasma were studied. Adjusting for the matching variables age, sex, and follow-up time (and correcting for multiplicity of tests), 89 proteins were found to be associated with incident HF in the discovery phase, of which 38 were also associated with incident HF in the replication phase. These 38 proteins pointed to 4 main network clusters underlying incident HF: (1) inflammation and apoptosis, indicated by the expression of the TNF (tumor necrosis factor)-family members; (2) extracellular matrix remodeling, angiogenesis and growth, indicated by the expression of proteins associated with collagen metabolism, endothelial function, and vascular homeostasis; (3) blood pressure regulation, indicated by the expression of natriuretic peptides and proteins related to the renin-angiotensin-aldosterone system; and (4) metabolism, associated with cholesterol and atherosclerosis. Conclusions Clusters of biomarkers associated with mechanistic pathways leading to HF were identified linking inflammation, apoptosis, vascular function, matrix remodeling, blood pressure control, and metabolism. These findings provide important insight on the pathophysiological mechanisms leading to HF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02556450.
Aims
Estimated plasma volume status (ePVS) predicts prognosis in patients with heart failure (HF). It remains unclear whether admission, discharge or change ePVS best predicts post-discharge outcome ...in patients with acute decompensated heart failure (ADHF).
Methods
We retrospectively analyzed three cohort studies: 383 patients admitted at the Tokyo Medical University hospital, 165 patients admitted at the Centro Hospitalar do Porto and 164 patients admitted at the Nancy University Hospital (ICALOR study). ePVS at admission and at discharge as well as its change thereof were, respectively, calculated using the Duarte and Strauss formulas, both derived from hemoglobin and hematocrit ratios. Clinical variables including physical assessment, biological and echocardiographic parameters were recorded. The clinical outcome was a composite of re-hospitalization for worsening HF or all-cause mortality.
Results
The primary outcomes occurred in 27.2% at 1 year (in the Tokyo cohort), 45.3% at 6 months (in the Porto cohort) and 53.9% at median terms of 298.3 days (in the ICALOR study). After adjusting for potential confounders including natriuretic peptide, discharge ePVS remained significantly associated with increased rates of composite outcome in the Tokyo and Porto cohorts and ICALOR study hazard ratio (HR) 1.21 (1.01–1.44),
p
= 0.04; HR 1.45 (1.16–1.81),
p
< 0.01; HR 1.45 (1.16–1.81),
p
< 0.01, respectively. In addition, a pooled analysis yielded a significant improvement in reclassification with discharge ePVS net reclassification index 13.6% (5.9–22.7),
p
= 0.004.
Conclusions
As validated in three independent ADHF cohorts, ePVS at discharge was independently associated with post-discharge clinical outcomes and improved the risk stratification of patients admitted for ADHF on top of well-established prognostic markers.
Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 ...(COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes.
The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio IRR) and the intention-to-treat principle.
Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients’ mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 standard deviation SD 6.3 vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 95% CI 1.06-2.62; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016).
RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.
Pulmonary congestion is associated with poor prognosis following hospitalization for worsening heart failure (HF), although its quantification and optimal timing during HF hospitalization remains ...challenging. The aim of this study was to assess the prognostic value of radiographic pulmonary congestion at admission and discharge in patients with worsening HF.
Clinical, echocardiographic, laboratory and chest X-ray data of 292 acute decompensated HF patients were retrospectively studied (follow-up 1 year). Lung congestion was blindly scored on chest X-ray performed at admission and discharge using a systematic 6-zone approach. Primary clinical outcome was a composite outcome of re-hospitalization for worsening HF or all cause death.
Patients were stratified according to the median of congestion score index (CSI) at both admission (median CSI(A) = 1.33) and discharge (median CSI(D) = 0.33). BNP levels, LVEF and eGFR did not differ between CSI categories. In multivariable Cox regression analysis, discharge CSI (HR for 1-point increase = 1.83 1.02 to 3.27 p = 0.04) and discharge BNP were significantly associated with the composite outcome whereas NYHA class, physical signs, admission CSI and echocardiographic data were not. Furthermore, discharge CSI significantly increased reclassification on top of clinical covariates (continuous NRI = 19.6% 4.0 to 30.0 p = 0.03 and IDI = 2.2% 0.0 to 7.6 p = 0.046) while discharge BNP did not significantly improve risk reclassification.
Residual pulmonary congestion assessed by radiographic scoring predicts poor prognosis beyond physical assessment, echocardiographic parameters and BNP. These findings further support the capital prognostic value of radiographic pulmonary congestion in patients hospitalized for worsening HF.
•Congestion score index is a semi-quantitative method to quantify congestion (ranging from 0 to 3) on chest X-rays•Both discharge and change in lung congestion assessed by chest X-ray had a prognostic value for post-discharge outcomes•Residual congestion using chest X-ray appears as a useful tool which could help risk-stratification in routine care for HF
Originally described in 1990 as a protein secreted by pancreatic acinar cells to inhibit growth and nucleation of calcium carbonate crystals in the pancreatic juice, subsequent preclinical studies ...have shown that PSP is actually a damage-associated molecular patterns (DAMPs) produced as a response to sepsis. Overall, comparing to routine biomarkers, namely C-reactive protein (CRP) and procalcitonin (PCT), PSP has shown to be more specific and sensitive on infection and sepsis diagnosis in different clinical settings (adults, pediatrics, post-operative, trauma, emergency and intensive care departments). ...knowing that early recognition of sepsis is essential and a major determinant of the outcome, point-of-care testing as the one available for PSP is very appealing, as it provides results at bedside in less than 10 min.
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