Is enough oxygen too much?

Human cells require O2 for their energy supply, and critical illness can threaten the efficient delivery of O2 in accordance with tissue metabolic needs. In the accompanying article, Martin and colleagues point out that hypoxia is a normal and well-tolerated stress during embryonic development. A better understanding of how fetal cells survive these conditions and how adult cells adapt to high altitude exposure may provide insight into how these mechanisms might be engaged in the treatment of hypoxemic patients. They suggest that 'permissive hypoxia' represents a therapeutic possibility. But before we turn down the inspired O2 levels we should consider the broader effects of hypoxia on tissue repair in critical illness

Disruption of mitochondrial complex I induces progressive parkinsonism

Loss of functional mitochondrial complex I (MCI) in the dopaminergic neurons of the substantia nigra is a hallmark of Parkinson’s disease1. Yet, whether this change contributes to Parkinson’s disease pathogenesis is unclear2. Here we used intersectional genetics to disrupt the function of MCI in mouse dopaminergic neurons. Disruption of MCI induced a Warburg-like shift in metabolism that enabled neuronal survival, but triggered a progressive loss of the dopaminergic phenotype that was first evident in nigrostriatal axons. This axonal deficit was accompanied by motor learning and fine motor deficits, but not by clear levodopa-responsive parkinsonism—which emerged only after the later loss of dopamine release in the substantia nigra. Thus, MCI dysfunction alone is sufficient to cause progressive, human-like parkinsonism in which the loss of nigral dopamine release makes a critical contribution to motor dysfunction, contrary to the current Parkinson’s disease paradigm.Electron microscopy tissue processing and imaging was performed at the Northwestern University Center for Advanced Microscopy, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. This study was supported by grants from the Michael J. Fox Foundation (to D.J.S.), the JPB Foundation (to D.J.S.), the IDP Foundation (to D.J.S.), the Flanagan Fellowship (to P.G.-R.) and the European Research Council ERC Advanced Grant PRJ201502629 (to J.L.-B.)

Effect of caffeine ingestion on fluid balance during exercise in the heat and during recovery

Background. The effect of ingestion of a common stimulant, caffeine, on fluid balance during exercise and recovery is not fully known. Objectives. To determine the effect of caffeine on fluid balance during exercise in the heat and during a 3-hour recovery period thereafter. Methods. In a randomised, controlled design, caffeine-naive participants (N=8) pedalled on a bike to achieve 2.5% baseline body mass loss in a hot environment in four separate conditions: with (C+) or without (C–) caffeine ingestion (6 mg/kg of body mass) prior to exercise, followed by (W+) or without (W–) 100% fluid replenishment (water) of the body mass loss during a 3-hour recovery period (yielding C+W+, C+W–, C–W+ and C–W–, respectively). Results. Mean (standard deviation) urine production was not different (p>0.05) regardless of rehydration status: 230 (162) mL (C+W–) v. 168 (77) mL (C–W–); and 713 (201) mL (C+W+) v. 634 (185) mL (C–W+). For the 3-hour recovery, caffeine ingestion caused higher hypohydration during rehydration conditions (p=0.02), but practically the mean difference in the loss of body mass was only 0.2 kg. Conclusion. In practical terms, there was no evidence that caffeine ingestion in moderation would impair fluid balance during prolonged exercise in the heat or during 3 hours of recovery

Information security collaboration formation in organisations

This is an accepted manuscript of an article published by The Institution of Engineering and Technology in IET Information Security, available online: https://doi.org/10.1049/iet-ifs.2017.0257 The accepted version of the publication may differ from the final published version.Collaboration between employees in the domain of information security efficiently mitigates the effect of information security attacks on organisations. Collaboration means working together to do or to fulfil a shared goal, the target of which in this paper is the protection of the information assets in organisations. Information Security Collaboration (ISC) aims to aggregate the employees’ contribution against information security threats. This study clarifies how ISC is to be developed and how it helps to reduce the effect of attacks. The socialisation of collaboration in the domain of information security applies two essential theories: Social Bond Theory (SBT) and the Theory of Planned Behaviour (TPB). The results of the data analysis revealed that personal norms, involvement, and commitment significantly influence the employees’ attitude towards ISC intention. However, contrary to our expectation, attachment does not influence the attitude of employees towards ISC. In addition, attitudes towards ISC, perceived behavioural control, and personal norms significantly affect the intention towards ISC. The findings also show that the intention for ISC and organisational support positively influence ISC, but that trust does not significantly affect ISC behaviour.Published versio

Assessment of Chronic Illness-Related Cognitive Fusion: Preliminary Development and Validation of a New Scale with an IBD Sample

Although research recognizes the advantages of creating specific content measures, no specific measure of chronic illness-related cognitive fusion had been developed to date. The current study presents the development and validation of the Cognitive Fusion Questionnaire-Chronic Illness (CFQ-CI) in a sample of inflammatory bowel disease (IBD) patients and the analysis of the role of this construct in the psychological health of those patients. Results indicated that the 7-item CFQ-CI was a unidimensional measure of cognitive fusion in patients with chronic illnesses, and that scores had adequate/good internal consistency and construct, convergent, and discriminant validity. This study also showed that chronic illness-related cognitive fusion as assessed by the CFQ-CI acted as a mediator in the association between both IBD-related symptoms and shame with quality of life. The development of the CFQ-CI may thus contribute to a better understanding of the mechanisms influencing functional outcomes in chronic illness

The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats

To study the role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats. Rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 6), a group in which LPS administration was followed by immediate fluid resuscitation which prevented the drop of renal blood flow (EARLY group) (n = 6), and a group in which LPS administration was followed by delayed (i.e., a 2-h delay) fluid resuscitation (LATE group) (n = 6). Renal blood flow was measured using a transit-time ultrasound flow probe. Microvascular perfusion and oxygenation distributions in the renal cortex were assessed using laser speckle imaging and phosphorimetry, respectively. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were measured as markers of systemic inflammation. Furthermore, renal tissue samples were stained for leukocyte infiltration and inducible nitric oxide synthase (iNOS) expression in the kidney. LPS infusion worsened both microvascular perfusion and oxygenation distributions. Fluid resuscitation improved perfusion histograms but not oxygenation histograms. Improvement of microvascular perfusion was more pronounced in the EARLY group compared with the LATE group. Serum cytokine levels decreased in the resuscitated groups, with no difference between the EARLY and LATE groups. However, iNOS expression and leukocyte infiltration in glomeruli were lower in the EARLY group compared with the LATE group. In our model, prevention of endotoxemia-induced systemic hypotension by immediate fluid resuscitation (EARLY group) did not prevent systemic inflammatory activation (IL-6, IL-10, TNF-α) but did reduce renal inflammation (iNOS expression and glomerular leukocyte infiltration). However, it could not prevent reduced renal microvascular oxygenatio