Differential gene expression patterns related to lipid metabolism in response to ocean acidification in larvae and juveniles of Atlantic cod.

Elevated environmental carbon dioxide (pCO2) levels have been found to cause organ damage in the early life stages of different commercial fish species, including Atlantic cod (Gadus morhua). To illuminate the underlying mechanisms causing pathologies in the intestines, the kidney, the pancreas and the liver in response to elevated pCO2, we examined related gene expression patterns in Atlantic cod reared for two months under three different pCO2 regimes: 380 µatm (control), 1800 µatm (medium) and 4200 µatm (high). We extracted RNA from whole fish sampled during the larval (32 dph) and early juvenile stage (46 dph) for relative expression analysis of 18 different genes related to essential metabolic pathways. At 32 dph, larvae subjected to the medium treatment displayed an up-regulation of genes mainly associated with fatty acid and glycogen synthesis (GYS2, 6PGL, ACoA, CPTA1, FAS and PPAR1b). Larvae exposed to the high pCO2 treatment upregulated fewer but similar genes (6PGL, ACoA and PPAR1b,). These data suggest stress-induced alterations in the lipid and fatty acid metabolism and a disrupted lipid homeostasis in larvae, providing a mechanistic link to the findings of lipid droplet overload in the liver and organ pathologies. At 46 dph, no significant differences in gene expression were detected, confirming a higher resilience of juveniles in comparison to larvae when exposed to elevated pCO2 up to 4200 µatm.

The Peripheral Perfusion Index tracks systemic haemodynamics during general anaesthesia.

Stable intraoperative haemodynamics are associated with improved outcome and even short periods of instability are associated with an increased risk of complications. During anaesthesia intermittent non-invasive blood pressure and heart rate remains the cornerstone of haemodynamic monitoring. Continuous monitoring of systemic blood pressure or even -flow requires invasive or advanced modalities creating a barrier for obtaining important real-time haemodynamic insight. The Peripheral Perfusion Index (PPI) is obtained continuously and non-invasively by standard photoplethysmography. We hypothesized that changes in indices of systemic blood flow during general anaesthesia would be reflected in the PPI. PPI, stroke volume (SV), cardiac output (CO) and mean arterial pressure (MAP) were evaluated in 20 patients. During general anaesthesia but before start of surgery relative changes of SV, CO and MAP were compared to the relative changes of PPI induced by head-up (HUT) and head-down tilt (HDT). Furthermore, the effect of phenylephrine (PE) during HUT on these parameters was investigated. ∆PPI correlated significantly (p < 0.001) with ∆SV (r = 0.9), ∆CO (r = 0.9), and ∆MAP (r = 0.9). HUT following induction of anaesthesia resulted in a decrease in PPI of 41% (25-52) [median (IQR)], SV 27% (23-31), CO 27% (25-35), and MAP 28% (22-35). HDT led to an increase in PPI of 203% (120-375), SV of 29% (21-41), CO 22% (16-34), and MAP 47% (42-60). After stabilizing a second HUT decreased PPI 59% (49-76), SV 33% (28-37), CO 31% (28-36), and MAP 34% (26-38). Restoration of preload with PE increased PPI by 607% (218-1078), SV by 96% (82-116), CO by 65% (56-99), and MAP by 114% (83-147). During general anaesthesia changes in PPI tracked changes in systemic haemodynamics.

Transcriptome profiling reveals exposure to predicted end-of-century ocean acidification as a stealth stressor for Atlantic cod larvae.

Ocean acidification (OA), a direct consequence of increasing atmospheric CO2 concentration dissolving in ocean waters, is impacting many fish species. Little is known about the molecular mechanisms underlying the observed physiological impacts in fish. We used RNAseq to characterize the transcriptome of 3 different larval stages of Atlantic cod (Gadus morhua) exposed to simulated OA at levels (1179 µatm CO2) representing end-of-century predictions compared to controls (503 µatm CO2), which were shown to induce tissue damage and elevated mortality in G. morhua. Only few genes were differentially expressed in 6 and 13 days-post-hatching (dph) (3 and 16 genes, respectively), during a period when maximal mortality as a response to elevated pCO2 occurred. At 36 dph, 1413 genes were differentially expressed, most likely caused by developmental asynchrony between the treatment groups, with individuals under OA growing faster. A target gene analysis revealed only few genes of the universal and well-defined cellular stress response to be differentially expressed. We thus suggest that predicted ocean acidification levels constitute a "stealth stress" for early Atlantic cod larvae, with a rapid breakdown of cellular homeostasis leading to organismal death that was missed even with an 8-fold replication implemented in this study.

Effect of a single pre-operative 125 mg dose of methylprednisolone on postoperative delirium in hip fracture patients; a randomised, double-blind, placebo-controlled trial.

Postoperative delirium is common after hip fracture surgery, and may have a neuro-inflammatory cause. We conducted a single-centre, randomised, double-blind, placebo-controlled trial of 117 older hip fracture patients to see if a single, pre-operative intravenous dose of 125 mg methylprednisolone could reduce the severity and/or incidence of postoperative delirium, assessed using the Confusion Assessment Method delirium severity score. Modified intention-to-treat analysis found no significant difference in our primary outcome, median (IQR [range]) cumulative Confusion Assessment Method delirium severity score over the first three postoperative days between the methylprednisolone and placebo groups (1 (0-6 [0-39]) vs. 2 (0-10 [0-32]), p = 0.294). Both the prevalence of postoperative delirium (Confusion Assessment Method delirium severity score ≥ 5, 10/59 vs. 19/58, p = 0.048) and the median (IQR [range]) cumulated postoperative (by day 3) fatigue scores (5 (2-6 [0-11]) vs. 6 (4-8 [0-16]), p = 0.008) were significantly lower in the methylprednisolone compared with the placebo group. There were no significant between-group differences in the rate of completing physiotherapy, postoperative pain, the administration of antipsychotic drugs, infection, length of inpatient stay or 30- and 90-day mortality. No major adverse reactions related to methylprednisolone were recorded. We conclude that a single, pre-operative dose of 125 mg methylprednisolone does not reduce the severity of postoperative delirium, but may reduce both the prevalence of delirium and the severity of fatigue after hip fracture surgery in older patients, enabling remobilisation and recovery.

Effects of parental acclimation and energy limitation in response to high CO2 exposure in Atlantic cod.

Ocean acidification (OA), the dissolution of excess anthropogenic carbon dioxide in ocean waters, is a potential stressor to many marine fish species. Whether species have the potential to acclimate and adapt to changes in the seawater carbonate chemistry is still largely unanswered. Simulation experiments across several generations are challenging for large commercially exploited species because of their long generation times. For Atlantic cod (Gadus morhua), we present first data on the effects of parental acclimation to elevated aquatic CO2 on larval survival, a fundamental parameter determining population recruitment. The parental generation in this study was exposed to either ambient or elevated aquatic CO2 levels simulating end-of-century OA levels (~1100 µatm CO2) for six weeks prior to spawning. Upon fully reciprocal exposure of the F1 generation, we quantified larval survival, combined with two larval feeding regimes in order to investigate the potential effect of energy limitation. We found a significant reduction in larval survival at elevated CO2 that was partly compensated by parental acclimation to the same CO2 exposure. Such compensation was only observed in the treatment with high food availability. This complex 3-way interaction indicates that surplus metabolic resources need to be available to allow a transgenerational alleviation response to ocean acidification.

Cerebral oximetry during preoperative resuscitation in elderly patients with hip fracture: a prospective observational study.

This study explores the association between postadmission and intraoperative cerebral oxygenation (ScO2), reflecting systemic perfusion, and postoperative mortality and delirium. Forty elderly (age > 65 years) patients with hip fractures were included in this prospective observational study. The ScO2 was determined using near-infrared spectroscopy at initial resuscitation after patients were admitted to the hospital and during surgery. Postoperative delirium was assessed up to seven days after surgery using the memorial delirium assessment scale and the confusion assessment method. Ten patients (25%) developed postoperative delirium within the first seven postoperative days. At initial resuscitation ScO2 was lower in patients that later developed delirium, but the difference was not significant (p = 0.331). Intraoperative ScO2 values remained similar in the two groups. Mortality regardless of cause was 10% (4 out of 40 patients) after 30 days. At initial resuscitation ScO2 was significant lower in the mortality group than in the surviving group (p = 0.042), and the ScO2 nadir values were also significant lower (p = 0.047). Low ScO2 during initial resuscitation (defined as ScO2 < 55 for a minimum of two consecutive minutes) was also significantly associated with 30-day mortality (p = 0.015). There were no associations between low blood pressure and postoperative delirium or 30-day mortality. We found that low preoperative ScO2 was better associated with 30-day all-cause mortality in elderly patients undergoing surgery for hip fracture than blood pressure measurements. Future studies in preoperative resuscitation of hip fracture patients should focus on perfusion measures as opposed to conventional haemodynamic.

Effects of egg size, parental origin and feeding conditions on growth of larval and juvenile cod Gadus morhua.

An experimental study was performed to disentangle parental and environmental effects on the growth of Atlantic cod Gadus morhua larvae and juveniles. Eggs were collected during the spawning season from spawning pairs (families) kept separately in specially designed spawning compartments. Newly hatched larvae were released simultaneously into two mesocosms of 2,500 and 4,400 m(3). Larval growth was monitored by sampling over a 10 week period, after which juveniles were transferred to on-growing tanks, where they were tagged and kept for up to 2 years. Maternal origin was determined by individual microsatellite genotyping of the larvae (n = 3949, 24 families) and juveniles (n = 600). The results showed significant positive correlations between egg size and larval size during the whole mesocosm period. Correlations, however, weakened with time and were no longer significant at the first tank-rearing sampling at an age of 9 months. Significant family-specific differences in growth were observed. The coefficient of variation (c.v.) was calculated in order to examine variation in standard length of larvae during the mesocosm period. Inter-family c.v. was on average 69% of intra-family c.v. Differences in zooplankton densities between the two mesocosms were reflected in larval growth, condition factor and c.v. Low food abundance appeared to reduce c.v. and favour growth of larvae that showed relatively slow growth at high food abundance. It is suggested that genetically determined variation in growth potential is maintained by environmental variability.