A sore red eye with systemic involvement

The study of happiness has long been a playground for philosophical speculation. By lack of empirical measures of happiness, it was not possible to check propositions about the matter. In the late 20th century, survey-research methods introduced by the social sciences have brought a break-through. Dependable measures of happiness have developed, by means of which a significant body of knowledge has evolved

Eye care in the intensive care unit

Ocular surface disease is common in the intensive care population with 20–42% of patients developing corneal epithelial defects. The ocular surface is normally protected by the ability to produce tears, to blink and to close the eyes with rest or sleep. All of these mechanisms can be disrupted in the intensive care population, increasing the risk of developing ocular surface disease. Despite the scale of the problem, eye-care protocols are commonly not instigated and documentation of eye care is often poor. This review details the risk factors for developing ocular surface disease. It also provides evidence-based guidance on protecting the eyes in vulnerable patients, identifying diseases affecting the eye in intensive care patients and delivering the best treatment to the eye. There is growing evidence that adherence to a correctly performed eye-care guideline prevents the majority of corneal problems encountered in the intensive care unit

Reply

Refers to: Koushik Tripathy, Re: Niederer et al.: Predictors of long-term visual outcome, in: intermediate uveitis (Ophthalmology. 2017;124:393-398) Ophthalmology, Volume 124, Issue 7, July 2017, Pages e59. https://doi.org/10.1016/j.ophtha.2017.02.01

Continuous Free Cortisol Profiles – Circadian Rhythms in Healthy Men

The pituitary-adrenal axis had historically been considered a representative model for circadian rhythms. A recently developed portable collection device provided the opportunity to evaluate free cortisol profiles using the microdialysis approach in individuals free to conduct their day-to-day activities in their own surroundings. Methods Two separate experiments were conducted in healthy male volunteers – ten-minutely total and subcutaneous free cortisol were measured for 24-hour period in one and twenty-minutely subcutaneous free cortisol for 72 consecutive hours in free-living individuals in the other experiment. Results The characteristic circadian rhythm was evident in both serum total and subcutaneous free cortisol with the lowest levels being achieved and maintained in the hours surrounding sleep onset with peak levels occurring in every individual around waking. In all free-living individuals, the circadian rhythm was consistent across 72-hours despite a wide range of activities. All participants also showed increased cortisol following the consumption of lunch. The lowest levels during all 24 hour periods were observed during the hours following lights switch-off, at the onset of sleep Conclusions This is the first study to show up to three consecutive 24-hour measurements of subcutaneous free cortisol in healthy individuals. This, we believe is a landmark study that paves the way for ambulatory monitoring of free cortisol profiles continuously up to a period of 72 hours in a free-living individual going about their day to day activities whether in health or in diseases involving the HPA axis

Continuous Free Cortisol Profiles in Healthy Men - Validation of Microdialysis Method

Abstract Context In humans, approximately 95% of circulating cortisol is bound to corticosteroid-binding globulin and albumin. It is only the free fraction that is biologically active and can activate signalling pathways via glucocorticoid hormone receptors in cells. Microdialysis is a well-established technique that enables the sampling of molecules in different compartments of the body, including extracellular fluid. This is the first study validating a rapid sampling microdialysis method measuring free cortisol in the subcutaneous and blood compartments of healthy volunteers. Methods Healthy non-smoking volunteers (42 men; age 18-24 years; BMI 18-25 kg/m2) received placebo (saline), 250 µg Synacthen or 1 mg dexamethasone with ten minutely sampling to measure total and free cortisol (subcutaneous, intravenous and saliva) for an hour before and 4 hours after administration. Results Following stimulation by Synacthen, total serum cortisol and free cortisol in both compartments rose significantly, achieving and maintaining maximum levels between 2 and 3 hours following the stimulus. A decline in cortisol levels was evident after the administration of dexamethasone or placebo, but there was a clear pulsatile activity around lunchtime in the latter group which was prominent in the blood compartment (total and free cortisol). There was good correlation between serum total and free cortisol (SC and intravenous) in the Synacthen and dexamethasone groups with no significant delay (less than 5 minutes) between total and free cortisol. Conclusions This seminal study demonstrated the dynamic responses of total blood cortisol and microdialysis derived free cortisol in blood, subcutaneous tissue and saliva in man. </jats:sec

Ultradian Cortisol Pulsatility Encodes a Distinct, Biologically Important Signal

Cortisol is released in ultradian pulses. The biological relevance of the resulting fluctuating cortisol concentration has not been explored.Determination of the biological consequences of ultradian cortisol pulsatility.A novel flow through cell culture system was developed to deliver ultradian pulsed or continuous cortisol to cells. The effects of cortisol dynamics on cell proliferation and survival, and on gene expression were determined. In addition, effects on glucocorticoid receptor (GR) expression levels and phosphorylation, as a potential mediator, were measured.Pulsatile cortisol caused a significant reduction in cell survival compared to continuous exposure of the same cumulative dose, due to increased apoptosis. Comprehensive analysis of the transcriptome response by microarray identified genes with a differential response to pulsatile versus continuous glucocorticoid delivery. These were confirmed with qRT-PCR. Several transcription factor binding sites were enriched in these differentially regulated target genes, including CCAAT-displacement protein (CDP). A CDP regulated reporter gene (MMTV-luc) was, as predicted, also differentially regulated by pulsatile compared to continuous cortisol delivery. Importantly there was no effect of cortisol delivery kinetics on either GR expression, or activation (GR phosphoSer(211)).Cortisol oscillations exert important effects on target cell gene expression, and phenotype. This is not due to differences in cumulative cortisol exposure, or either expression, or activation of the GR. This suggests a novel means to regulate GR function

Circadian distribution of epileptiform discharges in epilepsy: Candidate mechanisms of variability

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: All code used to produce the results presented in this manuscript are available on GitHub at https://github.com/imarinelli/Marinelli_PLOSCB2022Epilepsy is a serious neurological disorder characterised by a tendency to have recurrent, spontaneous, seizures. Classically, seizures are assumed to occur at random. However, recent research has uncovered underlying rhythms both in seizures and in key signatures of epilepsy-so-called interictal epileptiform activity-with timescales that vary from hours and days through to months. Understanding the physiological mechanisms that determine these rhythmic patterns of epileptiform discharges remains an open question. Many people with epilepsy identify precipitants of their seizures, the most common of which include stress, sleep deprivation and fatigue. To quantify the impact of these physiological factors, we analysed 24-hour EEG recordings from a cohort of 107 people with idiopathic generalized epilepsy. We found two subgroups with distinct distributions of epileptiform discharges: one with highest incidence during sleep and the other during day-time. We interrogated these data using a mathematical model that describes the transitions between background and epileptiform activity in large-scale brain networks. This model was extended to include a time-dependent forcing term, where the excitability of nodes within the network could be modulated by other factors. We calibrated this forcing term using independently-collected human cortisol (the primary stress-responsive hormone characterised by circadian and ultradian patterns of secretion) data and sleep-staged EEG from healthy human participants. We found that either the dynamics of cortisol or sleep stage transition, or a combination of both, could explain most of the observed distributions of epileptiform discharges. Our findings provide conceptual evidence for the existence of underlying physiological drivers of rhythms of epileptiform discharges. These findings should motivate future research to explore these mechanisms in carefully designed experiments using animal models or people with epilepsy.University of Birmingham Dynamic Investment FundEpilepsy Research UKEngineering and Physical Sciences Research Council (EPSRC)National Institute for Health and Care Research (NIHR)Medical Research Council (MRC

Association between infection early in life and mental disorders among youth in the community: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to examine the association between infection early in life and mental disorders among youth in the community.</p> <p>Methods</p> <p>Data were drawn from the MECA (Methods in Epidemiology of Child and Adolescent psychopathology), a community-based study of 1,285 youth in the United States conducted in 1992. Multiple logistic regression analyses were used to investigate the association between parent/caregiver-reported infection early in life and DSM/DISC diagnoses of mental disorders at ages 9-17.</p> <p>Results</p> <p>Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9), social phobia (OR = 5.8), overanxious disorder (OR = 6.1), panic disorder (OR = 12.1), and oppositional defiant disorder (OR = 3.7).</p> <p>Conclusions</p> <p>These findings are consistent with and extend previous results by providing new evidence suggesting a link between infection early in life and increased risk of depression and anxiety disorders among youth. These results should be considered preliminary. Replication of these findings with longitudinal epidemiologic data is needed. Possible mechanisms are discussed.</p