Impaired chemoreflex sensitivity in adult patients with multiple organ dysfunction syndrome—the potential role of disease severity

Objective The cardiac chemoreflex sensitivity is a powerful predictor of autonomic dysfunction in chronic heart failure and after myocardial infarction. The objective of the present study was to characterize cardiac chemoreflex sensitivity in patients with multiple organ dysfunction syndrome (MODS). We also aimed to elucidate the effect of the severity of MODS on the assessment of cardiac chemoreflex sensitivity.Design Prospective cohort study.Setting Twelve-bed medical intensive care unit in a university center.Patients Forty consecutively admitted patients with MODS during a 7-month period. Patients with MODS were identified by an APACHE II score of 20 or more. Sepsis was defined as a Sepsis Score, according to Elebute and Stoner, of 12 or more.Interventions The cardiac chemoreflex sensitivity was assessed using the regression of heart interval (ms) versus arterial oxygen pressure (mmHg).Measurements and results First, we established a new method to assess cardiac chemoreflex sensitivity and applied it to healthy controls and patients. Second, we found that cardiac chemoreflex sensitivity correlated with the severity of MODS as calculated by the APACHE II score (r²=0.34, p=0.001). This relation was best fitted by a model including minimum heart rate and standard bicarbonate in 24 h (r²=0.5, p<0.001) and Glasgow Coma Scale (r²=0.5, p=0.005). Age, however, did not significantly contribute (r²=0.001, p=0.8).Conclusions The calculation of cardiac chemoreflex sensitivity enabled us to quantify an important component of the cardiorespiratory interactions in patients with MODS. Severity of illness was a more pronounced determinant of impaired cardiac chemoreflex sensitivity than age. The quantification of the cardiorespiratory interactions by measuring the cardiac chemoreflex sensitivity has potential to identify a subgroup of patients with worse prognosis.     

Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12Rβ1

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Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction,Memory and Life Span in C57BL/6J Mice

Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer’s disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19–22 months old) compared to young mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding partly enhanced brain mitochondrial respiration with only minor beneficial effect on brain ATP levels and memory of aged mice. Life-long PGE feeding led to a transient but significant shift of survival curve toward higher survival rates but without effect on the overall survival. The moderate effects of PGE were associated with elevated SIRT1 but not SIRT3 mRNA expressions in brain and liver tissue. The beneficial effects of the grape extract may have been influenced by the profile of bioavailable polyphenols and the starting point of interventions.     

The influence of comorbid oppositional defiant disorder on white matter microstructure in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are highly comorbid disorders. ADHD has been associated with altered white matter (WM) microstructure, though the literature is inconsistent, which may be due to differences in the in- or exclusion of participants with comorbid ODD. WM abnormalities in ODD are still poorly understood, and it is unclear whether comorbid ODD in ADHD may have confounded the current ADHD literature. Diffusion Tensor Imaging (DTI) was used to compare fractional anisotropy (FA) and mean diffusivity (MD) between ADHD patients with (n = 42) and without (n = 117) comorbid ODD. All participants were between 8–25 years and groups did not differ in mean age or gender. Follow-up analyses were conducted to examine the role of antisocial behaviour (conduct problems) on FA and MD values in both groups. Comorbid ODD in ADHD was associated with lower FA in left frontotemporal WM, which appeared independent of ADHD symptoms. FA was negatively associated with antisocial behaviour in ADHD + ODD, but not in ADHD-only. Comorbid ODD is associated with WM abnormalities in individuals with ADHD, which appears to be independent of ADHD symptoms. Altered WM microstructure in comorbid ODD may play a role in inconsistencies in the current DTI literature in ADHD. Altered development of these tracts may contribute to social-emotional and cognitive problems in children with oppositional and antisocial behaviour.