Generation of a reference transcriptome for evaluating rainbow trout responses to various stressors

<p>Abstract</p> <p>Background</p> <p>Fish under intensive culture conditions are exposed to a variety of acute and chronic stressors, including high rearing densities, sub-optimal water quality, and severe thermal fluctuations. Such stressors are inherent in aquaculture production and can induce physiological responses with adverse effects on traits important to producers and consumers, including those associated with growth, nutrition, reproduction, immune response, and fillet quality. Understanding and monitoring the biological mechanisms underlying stress responses will facilitate alleviating their negative effects through selective breeding and changes in management practices, resulting in improved animal welfare and production efficiency.</p> <p>Results</p> <p>Physiological responses to five treatments associated with stress were characterized by measuring plasma lysozyme activity, glucose, lactate, chloride, and cortisol concentrations, in addition to stress-associated transcripts by quantitative PCR. Results indicate that the fish had significant stressor-specific changes in their physiological conditions. Sequencing of a pooled normalized transcriptome library created from gill, brain, liver, spleen, kidney and muscle RNA of control and stressed fish produced 3,160,306 expressed sequence tags which were assembled and annotated. SNP discovery resulted in identification of ~58,000 putative single nucleotide polymorphisms including 24,479 which were predicted to fall within exons. Of these, 4907 were predicted to occupy the first position of a codon and 4110 the second, increasing the probability to impact amino acid sequence variation and potentially gene function.</p> <p>Conclusion</p> <p>We have generated and characterized a reference transcriptome for rainbow trout that represents multiple tissues responding to multiple stressors common to aquaculture production environments. This resource compliments existing public transcriptome data and will facilitate approaches aiming to evaluate gene expression associated with stress in this species.</p

Biased-corrected richness estimates for the Amazonian tree flora

Amazonian forests are extraordinarily diverse, but the estimated species richness is very much debated. Here, we apply an ensemble of parametric estimators and a novel technique that includes conspecific spatial aggregation to an extended database of forest plots with up-to-date taxonomy. We show that the species abundance distribution of Amazonia is best approximated by a logseries with aggregated individuals, where aggregation increases with rarity. By averaging several methods to estimate total richness, we confirm that over 15,000 tree species are expected to occur in Amazonia. We also show that using ten times the number of plots would result in an increase to just ~50% of those 15,000 estimated species. To get a more complete sample of all tree species, rigorous field campaigns may be needed but the number of trees in Amazonia will remain an estimate for years to come

Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury : A European Prospective and Multicenter Study

Background Although rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care. Objective Therefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI. Methods Data from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge. Results In the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24). Conclusions Based on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.Peer reviewe

Tracheal intubation in traumatic brain injury: a multicentre prospective observational study

Background We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. Methods Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. Results In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79–1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65–1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. Conclusion The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. Clinical trial registration NCT02210221

Health-related quality of life after traumatic brain injury : deriving value sets for the QOLIBRI-OS for Italy, The Netherlands and The United Kingdom

Purpose The Quality of Life after Brain Injury overall scale (QOLIBRI-OS) measures health-related quality of life (HRQoL) after traumatic brain injury (TBI). The aim of this study was to derive value sets for the QOLIBRI-OS in three European countries, which will allow calculation of utility scores for TBI health states. Methods A QOLIBRI-OS value set was derived by using discrete choice experiments (DCEs) and visual analogue scales (VAS) in general population samples from the Netherlands, United Kingdom and Italy. A three-stage procedure was used: (1) A selection of health states, covering the entire spectrum of severity, was defined; (2) General population samples performed the health state valuation task using a web-based survey with three VAS questions and an at random selection of sixteen DCEs; (3) DCEs were analysed using a conditional logistic regression and were then anchored on the VAS data. Utility scores for QOLIBRI-OS health states were generated resulting in estimates for all potential health states. Results The questionnaire was completed by 13,623 respondents. The biggest weight increase for all attributes is seen from "slightly" to "not at all satisfied", resulting in the largest impact on HRQoL. "Not at all satisfied with how brain is working" should receive the greatest weight in utility calculations in all three countries. Conclusion By transforming the QOLIBRI-OS into utility scores, we enabled the application in economic evaluations and in summary measures of population health, which may be used to inform decision-makers on the best interventions and strategies for TBI patients.Peer reviewe

Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase.

Metformin is a first-line drug for the treatment of individuals with type 2 diabetes, yet its precise mechanism of action remains unclear. Metformin exerts its antihyperglycemic action primarily through lowering hepatic glucose production (HGP). This suppression is thought to be mediated through inhibition of mitochondrial respiratory complex I, and thus elevation of 5'-adenosine monophosphate (AMP) levels and the activation of AMP-activated protein kinase (AMPK), though this proposition has been challenged given results in mice lacking hepatic AMPK. Here we report that the AMP-inhibited enzyme fructose-1,6-bisphosphatase-1 (FBP1), a rate-controlling enzyme in gluconeogenesis, functions as a major contributor to the therapeutic action of metformin. We identified a point mutation in FBP1 that renders it insensitive to AMP while sparing regulation by fructose-2,6-bisphosphate (F-2,6-P2), and knock-in (KI) of this mutant in mice significantly reduces their response to metformin treatment. We observe this during a metformin tolerance test and in a metformin-euglycemic clamp that we have developed. The antihyperglycemic effect of metformin in high-fat diet-fed diabetic FBP1-KI mice was also significantly blunted compared to wild-type controls. Collectively, we show a new mechanism of action for metformin and provide further evidence that molecular targeting of FBP1 can have antihyperglycemic effects

Frequency of fatigue and its changes in the first 6 months after traumatic brain injury: results from the CENTER-TBI study

Background Fatigue is one of the most commonly reported subjective symptoms following traumatic brain injury (TBI). The aims were to assess frequency of fatigue over the first 6 months after TBI, and examine whether fatigue changes could be predicted by demographic characteristics, injury severity and comorbidities. Methods Patients with acute TBI admitted to 65 trauma centers were enrolled in the study Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI). Subjective fatigue was measured by single item on the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), administered at baseline, three and 6 months postinjury. Patients were categorized by clinical care pathway: admitted to an emergency room (ER), a ward (ADM) or an intensive care unit (ICU). Injury severity, preinjury somatic- and psychiatric conditions, depressive and sleep problems were registered at baseline. For prediction of fatigue changes, descriptive statistics and mixed effect logistic regression analysis are reported. Results Fatigue was experienced by 47% of patients at baseline, 48% at 3 months and 46% at 6 months. Patients admitted to ICU had a higher probability of experiencing fatigue than those in ER and ADM strata. Females and individuals with lower age, higher education, more severe intracranial injury, preinjury somatic and psychiatric conditions, sleep disturbance and feeling depressed postinjury had a higher probability of fatigue. Conclusion A high and stable frequency of fatigue was found during the first 6 months after TBI. Specific socio-demographic factors, comorbidities and injury severity characteristics were predictors of fatigue in this study

Vibrational spectroscopy for the triage of traumatic brain injury computed tomography priority and hospital admissions

Computed tomography (CT) brain imaging is routinely used to support clinical decision-making in patients with traumatic brain injury (TBI). Only 7% of scans, however, demonstrate evidence of TBI. The other 93% of scans contribute a significant cost to the healthcare system and a radiation risk to patients. There may be better strategies to identify which patients, particularly those with mild TBI, are at risk of deterioration and require hospital admission. We introduce a blood serum liquid biopsy that utilizes attenuated total reflectance (ATR)-Fourier transform infrared (FTIR) spectroscopy with machine learning algorithms as a decision-making tool to identify which patients with mild TBI will most likely present with a positive CT scan. Serum samples were obtained from patients (n = 298) patients who had acquired a TBI and were enrolled in CENTER-TBI and from asymptomatic control patients (n = 87). Injury patients (all severities) were stratified against non-injury controls. The cohort with mild TBI was further examined by stratifying those who had at least one CT abnormality against those who had no CT abnormalities. The test performed exceptionally well in classifications of patients with mild injury versus non-injury controls (sensitivity = 96.4% and specificity = 98.0%) and also provided a sensitivity of 80.2% when stratifying mild patients with at least one CT abnormality against those without. The results provided illustrate the test ability to identify four of every five CT abnormalities and show great promise to be introduced as a triage tool for CT priority in patients with mild TBI