Prognostic value of geriatric and cardiac parameters for one-year mortality in older heart failure patients. A multicentre, observational, prospective study.

PURPOSE: Heart failure is prevalent among older people and has a poor prognosis. The aim of this study is to identify potential prognostic, geriatric, and cardiac parameters which could help clinicians identify older heart failure patients at high risk for one-year mortality. METHODS: The multicentre, observational cohort study which included 147 heart failure patients aged ≥75 years, hospitalized in the cardiac or geriatric department in two hospitals. One-year survival was the outcome measure. For univariate analysis Chi-square test and independent sample T-test were used; for multivariate analysis Logistic regression and Cox regression for time-dependent analysis. RESULTS: One-year mortality was 28% (41/147). One-year survivors and non-survivors did not differ in the following characteristics: age, gender, sodium level at hospital discharge, ejection fraction, NYHA Class, basic and instrumental activities of daily living, and the presence of a geriatric risk profile. There was a significant lower systolic blood pressure at discharge in non-survivors compared to one-year-survivors (mean 125.26 mmHg vs. 137.59 mmHg). Non-survivors had more severe underlying comorbidities according to the age adjusted Charlson Comorbidity index (CCI) (mean 8.80 vs. 7.40).Both logistic and Cox regression showed a higher risk and rate of mortality with decreasing systolic blood pressure at discharge (OR 0.963, p=0.001 and HR 0.970, p<0.001) and with increasing CCI (OR 1.344, p=0.002 and HR 1.269, p=0.001); the other variables were not significantly related. CONCLUSION: Lower blood pressure and more severe comorbidities, but not functionality nor the presence of a geriatric risk profile, are related to one-year mortality in older, in-hospital heart failure patients.

Inflammation at the Crossroads: the Combined Effects of COVID-19, Ageing, and Air Pollution.

The global COVID-19 pandemic has highlighted different vulnerability profiles among individuals. With the highest mortality rate, the elderly are a very sensitive group. With regard to the main symptoms, a failure of the respiratory system, associated with deregulation of the immune system, has been observed. These symptoms may also be encountered in chronic exposure of susceptible populations to air pollution, including exacerbation of the inflammatory response. Is there a relationship between age, pollution exposure and the severity of COVID-19? Although it is unclear how these parameters are related, the same pathways can be activated and appear to find a common mechanism of action in inflammation.

Gingival fibroblasts resist apoptosis in response to oxidative stress in a model of periodontal diseases.

Periodontal diseases are classified as inflammation affecting the supporting tissue of teeth, which eventually leads to tooth loss. Mild reversible gingivitis and severe irreversible periodontitis are the most common periodontal diseases. Periodontal pathogens initiate the diseases. The bacterial toxin, lipopolysaccharide (LPS), triggers the inflammatory response and leads to oxidative stress. However, the progress of oxidative stress in periodontal diseases is unknown. The purpose of this study is to examine oxidative stress and cell damage in gingivitis and periodontitis. Our results showed that LPS increases reactive oxygen species (ROS) accumulation in gingival fibroblast (GF). However, oxidative stress resulting from excessive ROS did not influence DNA damage and cell apoptosis within 24 h. The mechanism may be related to the increased expression of DNA repair genes, Ogg1, Neil1 and Rad50. Detection of apoptosis-related proteins also showed anti-apoptotic effects and pro-apoptotic effects were balanced. The earliest damage appeared in DNA when increased γH2AX, an early biomarker for DNA damage, was detected in the LPS group after 48 h. Later, when recurrent inflammation persisted, 8-OHdG, a biomarker for oxidative stress was much higher in periodontitis model compared to the control in vivo. Staining of 8-OHdG in human periodontitis specimens confirmed the results. Furthermore, TUNEL staining of apoptotic cells indicated that the periodontitis model induced more cell apoptosis in gingival tissue. This suggested GF could resist early and acute inflammation (gingivitis), which was regarded as reversible, but recurrent and chronic inflammation (periodontitis) led to permanent cell damage and death.

Mutagenicity and clastogenicity of native airborne particulate matter samples collected under industrial, urban or rural influence.

Airborne particulate matter has recently been classified by the IARC as carcinogenic to humans (group 1). However, the link between PM chemical composition and its carcinogenicity is still unclear. The aim of the present study was to evaluate and to compare genotoxic potencies of 6 native PM samples collected in spring-summer or autumn-winter, either in industrial, urban or rural area. We evaluated their mutagenicity through Ames test on YG1041, TA98, and TA102 tester strains, and their clastogenicity on human bronchial epithelial BEAS-2B cells using comet assay, γ-H2AX quantification, and micronucleus assay. Ames test results showed a strong positive response, presumably associated with nitro-aromatics content. In addition, at least 2 positive responses were observed out of the 3 genotoxicity assays for each of the 6 samples, demonstrating their clastogenicity. Our data suggest that PM samples collected in autumn-winter season are more genotoxic than those collected in spring-summer, potentially because of higher concentrations of adsorbed organic compounds. Taken together, our results showed the mutagenicity and clastogenicity of native PM2.5 samples from different origins, and bring additional elements to explain the newly recognized carcinogenicity of outdoor air pollution.

Mutagenicity and genotoxicity of PM2.5 issued from an urbano-industrialized area of Dunkerque (France).

Epidemiological studies have demonstrated the link between chronic exposure to particulate matter (PM), especially particles with an aerodynamic diameter lesser than 2.5 µm (PM(2.5) ), and lung cancer. Mechanistic investigations focus on the contribution of the various genotoxicants adsorbed onto the particles, and more particularly on polycyclic aromatic hydrocarbons or nitroaromatics. Most of the previous studies dealing with genotoxic and/or mutagenic measurements were performed on organic extracts obtained from PM(2.5) collected in polluted areas. In contrast, we have evaluated genotoxic and mutagenic properties of urbano-industrial PM(2.5) (PM) collected in Dunkerque (France). Thermally desorbed PM(2.5) (dPM) was also comparatively studied. Suspensions of PM and dPM (5-50 µg per plate) were tested in Salmonella tester strains TA98, TA102 and YG1041 ± S9mix. Significant mutagenicity was observed for PM in YG1041 ± S9 mix. In strain TA102 - S9mix, a slight, but not significant dose-response increase was observed, for both PM and dPM. Genotoxic properties of PM and dPM were evaluated by the measurement of (1) 8-OHdG in A549 cells and (2) bulky DNA adducts on A549 cells and on human alveolar macrophages (AMs) in primary culture. A dose-dependant formation of 8-OHdG adducts was observed on A549 cells for PM and dPM, probably mainly attributed to the core of the particles. Bulky DNA adducts were observed only in AMs after exposure to PM and dPM. In conclusion, using relevant exposure models, suspension of PM(2.5) induces a combination of DNA-interaction mechanisms, which could contribute to the induction of lung cancer in exposed populations.

Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity.

Inflammation causes the induction of cyclooxygenase-2 (Cox-2), leading to the release of prostanoids, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity. Peripheral inflammation also generates pain hypersensitivity in neighbouring uninjured tissue (secondary hyperalgesia), because of increased neuronal excitability in the spinal cord (central sensitization), and a syndrome comprising diffuse muscle and joint pain, fever, lethargy and anorexia. Here we show that Cox-2 may be involved in these central nervous system (CNS) responses, by finding a widespread induction of Cox-2 expression in spinal cord neurons and in other regions of the CNS, elevating prostaglandin E2 (PGE2) levels in the cerebrospinal fluid. The major inducer of central Cox-2 upregulation is interleukin-1beta in the CNS, and as basal phospholipase A2 activity in the CNS does not change with peripheral inflammation, Cox-2 levels must regulate central prostanoid production. Intraspinal administration of an interleukin-converting enzyme or Cox-2 inhibitor decreases inflammation-induced central PGE2 levels and mechanical hyperalgesia. Thus, preventing central prostanoid production by inhibiting the interleukin-1beta-mediated induction of Cox-2 in neurons or by inhibiting central Cox-2 activity reduces centrally generated inflammatory pain hypersensitivity.

Cholinergic projections to the visual thalamus and superior colliculus.

The parabrachial region of the brainstem reticular formation projects to the dorsal lateral geniculate nucleus of the thalamus and to the intermediate gray layer of the superior colliculus. We used the retrograde axonal transport of two fluorescent labels to demonstrate that individual parabrachial cells project to both structures. The results suggest that cholinergic cells of the parabrachial region may coordinate the relay of visuosensory information to the cortex with the onset of orienting movements.