Lack of interleukin-6 expression is not protective against focal central nervous system ischemia

BACKGROUND AND PURPOSE: Interleukin-6 (IL-6) appears to be involved in the inflammatory response associated with central nervous system (CNS) ischemia. Although IL-6 levels increase after stroke, it is not known whether IL-6 directly influences CNS ischemic injury. In this study, we used a focal reversible stroke model to investigate whether mice lacking IL-6 were protected against acute ischemic injury. METHODS: We bred IL-6-deficient C57 black mice (I-129 IL-6 KO back-crossed with C57), including homozygous knockouts (IL-6 -/-), heterozygous littermates (IL-6 +/-), and normal littermates (IL-6 +/+). The status of all animals was confirmed by DNA sampling and polymerase chain reaction analysis. Reversible middle cerebral artery occlusion was produced by advancing a silicone-coated 8-0 filament into the internal carotid artery for 2 hours (experiment 1) or 45 minutes (experiment 2). At 24 hours, animals were evaluated on a 28-point clinical scale, blood and cerebrospinal fluid were obtained, and the brains were evaluated for infarct volume and IL-6 mRNA levels. RESULTS: In experiment 1 (severe ischemia), no differences were seen in lesion size or neurological function between the groups: lesion volume was IL-6 -/- (n=15), 57+/-13 mm(3); IL-6 +/- (n=15), 58+/-23 mm(3); and IL-6 +/+ (n=15), 58+/-18 mm(3) (P=NS). ELISA testing confirmed very low to absent levels of IL-6 in the serum and cerebrospinal fluid of knockout animals. Brain mRNA levels of the other proinflammatory cytokines, including tumor necrosis factor-alpha, IL-1beta, and IL-1 receptor antagonist, were 50% lower in IL-6-deficient ischemic animals than in normal animals. In experiment 2 (mild ischemia), no differences were seen in lesion size or neurological function between the groups: lesion volume was IL-6 -/- (n=10), 16+/-8 mm(3); IL-6 +/- (n=10), 14+/-4 mm(3); and IL-6 +/+ (n=10), 19+/-12 mm(3) (P=NS). CONCLUSIONS: In this study, infarct size and neurological function at 24 hours were not different in animals deficient in IL-6 after transient CNS ischemia. This suggests that IL-6 does not have a direct influence on acute ischemic injury. Further study investigating the role of IL-6 on long-term recovery after stroke is in progress.     

Accountability in integrated working: Meaning and implications for cancer care teams

This article presents a critical evaluation of the concepts of accountability and delegated authority and how this impacts on integrated working in cancer care teams. It looks at the difficulties experienced by radiographers in establishing their roles in integrated teams through an analysis of how professional teams have developed from a sociological and historical perspective. The paper highlights the contestability of the terms and contends that many non-medical professional practitioners experience problems with assuming full accountability. The article acknowledges and advocates that the wishes of patients and clients must be prioritised in the decision making process, thus requiring professionals to embrace accountability fully and differentiate and manage risk. The importance of leadership in furthering the achievement of integrated working is recognised. In conclusion, the article proposes that shared accountability among teams is challenging for radiographers and others, and that education providers should take this into account when designing curricula.     

Relationship between arterial dysfunction and extra-articular features in patients with rheumatoid arthritis

Systemic inflammation may be a common process that underpins both atherosclerosis and extra-articular features (ExRA) of rheumatoid arthritis (RA). We evaluated the relationship between ExRA and arterial dysfunction in 114 consecutive patients with RA (82% women) without overt arterial disease aged 40–65?years. A trained research nurse undertook ‘SphygmoCor’ pulse wave analysis (PWA) using radial applanation tonometry to measure the extent (augmentation index, AIX%) and timing (reflected wave transit time, RWT, msec) of aortic wave reflection. Assessment included fasting blood sample, patient questionnaire and medical record review. Mean differences were adjusted for age, sex, mean blood pressure, smoking pack-years, fasting cholesterol, Stanford HAQ score and erythrocyte sedimentation rate. Mean age was 54 (SD 7) and median RA duration 10 (IQR 4–17) years. There was a trend for arterial dysfunction (higher AIX%; lower RWT) to increase as the number of ExRA features rose, but no difference in AIX% (?0.5, 95%CI ?2.8 to 1.8, P?=?0.65) or RWT (0.3?ms, 95%CI ?3.6 to 4.2, P?=?0.86) between ‘any ExRA’ and ‘no ExRA’. Arterial dysfunction was not associated with the presence of rheumatoid nodules, Sjogren’s syndrome or carpal tunnel syndrome. Our study was too small to determine whether severe (‘Malmo’) ExRA (vasculitis, pericarditis, episcleritis) was truly associated with a higher AIX% (3.8, 95%CI ?2.3 to 9.9, P?=?0.22) and lower RWT (?5.5?ms 95%CI ?13.1 to 2.1, P?=?0.16). While arterial dysfunction may be associated with the number of ExRA features and severe ExRA, it does not appear to be associated with other ExRA features.     

Risk and protective factors for wellbeing in older veterans in New Zealand

Objectives: To compare indicators relating to aging and health among veterans and non-veterans, and identify factors associated with subjective wellbeing (SWB) of older New Zealand veterans.

Methods: Self-reported data were obtained from participants in a longitudinal cohort study of New Zealand older adults. Responses from 352 veterans and 1500 non-veterans (age range of 55–86 and gender matched) were selected as a comparison group on indicators related to health and aging. The association of these indicators with veterans’ SWB were assessed using hierarchical regression.

Results: Apart from being older, smoking more, and having more chronic conditions, veterans did not differ from non-veterans on indicators of health and wellbeing. Mental health, physical health, purpose in life, housing satisfaction, and capabilities (choice and freedom) accounted for a significant amount of variance in veterans’ SWB.

Conclusion: Our results suggest that older veterans do not differ greatly on indices of health and aging from their non-veteran peers. Results support previous findings that lower mental and physical health is associated with lower SWB for veterans. Building upon prior findings, the current results demonstrate that interventions focusing on enhancing a sense of purpose in life, supporting one's capability to achieve, and strengthening social and physical environment through social connectedness, may serve as protective factors for SWB in veterans.     

Sleep and resting‐state functional magnetic resonance imaging connectivity in middle‐aged adults and the elderly: A population‐based study

Sleep problems increase with ageing. Increasing evidence suggests that sleep problems are not only a consequence of age‐related processes, but may independently contribute to developing vascular or neurodegenerative brain disease. Yet, it remains unclear what mechanisms underlie the impact sleep problems may have on brain health in the general middle‐aged and elderly population. Here, we studied sleep's relation to brain functioning in 621 participants (median age 62 years, 55% women) from the population‐based Rotterdam Study. We investigated cross‐sectional associations of polysomnographic and subjectively measured aspects of sleep with intrinsic neural activity measured with resting‐state functional magnetic resonance imaging on a different day. We investigated both functional connectivity between regions and brain activity (blood‐oxygen‐level‐dependent signal amplitude) within regions, hierarchically towards smaller topographical levels. We found that longer polysomnographic total sleep time is associated with lower blood‐oxygen‐level‐dependent signal amplitude in (pre)frontal regions. No objective or subjective sleep parameters were associated with functional connectivity between or within resting‐state networks. The findings may indicate a pathway through which sleep, in a ‘real‐life’ population setting, impacts brain activity or regional brain activity determines total sleep time.