Complete Inactivation of Sebum-Producing Genes Parallels the Loss of Sebaceous Glands in Cetacea

Publisher's version (útgefin grein)Genomes are dynamic biological units, with processes of gene duplication and loss triggering evolutionary novelty. The mammalian skin provides a remarkable case study on the occurrence of adaptive morphological innovations. Skin sebaceous glands (SGs), for instance, emerged in the ancestor of mammals serving pivotal roles, such as lubrication, waterproofing, immunity, and thermoregulation, through the secretion of sebum, a complex mixture of various neutral lipids such as triacylglycerol, free fatty acids, wax esters, cholesterol, and squalene. Remarkably, SGs are absent in a few mammalian lineages, including the iconic Cetacea. We investigated the evolution of the key molecular components responsible for skin sebum production: Dgat2l6, Awat1, Awat2, Elovl3, Mogat3, and Fabp9. We show that all analyzed genes have been rendered nonfunctional in Cetacea species (toothed and baleen whales). Transcriptomic analysis, including a novel skin transcriptome from blue whale, supports gene inactivation. The conserved mutational pattern found in most analyzed genes, indicates that pseudogenization events took place prior to the diversification of modern Cetacea lineages. Genome and skin transcriptome analysis of the common hippopotamus highlighted the convergent loss of a subset of sebum-producing genes, notably Awat1 and Mogat3. Partial loss profiles were also detected in non-Cetacea aquatic mammals, such as the Florida manatee, and in terrestrial mammals displaying specialized skin phenotypes such as the African elephant, white rhinoceros and pig. Our findings reveal a unique landscape of “gene vestiges” in the Cetacea sebum-producing compartment, with limited gene loss observed in other mammalian lineages: suggestive of specific adaptations or specializations of skin lipids.This work was supported by Project No. 031342 cofinanced by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by Fundac¸a~o para a Cie^ncia e a Tecnologia through national funds. R.R.F. thanks the Danish National Research Foundation for its support of the Center for Macroecology, Evolution, and Climate (grant DNRF96). We acknowledge the various Cetacea genome consortiums for genome sequencing and assemblies. We also thank Gısli Vikingsson at the Marine and Freshwater Research Institute in Iceland for lending us the Larsen gun and to North Sailing whale watching for the use of their zodiac.Peer Reviewe

Rehabilitation Needs, Service Provision, and Costs in the First Year Following Traumatic Injuries: Protocol for a Prospective Cohort Study

Background: Traumatic injuries, defined as physical injuries with sudden onset, are a major public health problem worldwide. There is a paucity of knowledge regarding rehabilitation needs and service provision for patients with moderate and major trauma, even if rehabilitation research on a spectrum of specific injuries is available. Objective: This study aims to describe the prevalence of rehabilitation needs, the provided services, and functional outcomes across all age groups, levels of injury severity, and geographical regions in the first year after trauma. Direct and indirect costs of rehabilitation provision will also be assessed. The overarching aim is to better understand where to target future efforts. Methods: This is a population-based prospective follow-up study. It encompasses patients of all ages with moderate and severe acute traumatic injury (New Injury Severity Score >9) admitted to the regional trauma centers in southeastern and northern Norway over a 1-year period (2020). Sociodemographic and injury data will be collected. Upon hospital discharge, rehabilitation physicians estimate rehabilitation needs. Rehabilitation needs are assessed by the Rehabilitation Complexity Scale Extended–Trauma (RCS E–Trauma; specialized inpatient rehabilitation), Needs and Provision Complexity Scale (NPCS; community-based rehabilitation and health care service delivery), and Family Needs Questionnaire–Pediatric Version (FNQ-P). Patients, family caregivers, or both will complete questionnaires at 6- and 12-month follow-ups, which are supplemented by telephone interviews. Data on functioning and disability, mental health, health-related quality of life measured by the EuroQol Questionnaire (EQ-5D), and needs and provision of rehabilitation and health care services are collected by validated outcome measures. Unmet needs are represented by the discrepancies between the estimates of the RCS E–Trauma and NPCS at the time of a patient’s discharge and the rehabilitation services the patient has actually received. Formal service provision (including admission to inpatient- or outpatient-based rehabilitation), informal care, and associated costs will be collected. Results: The project was funded in December 2018 and approved by the Regional Committee for Medical and Health Research Ethics in October 2019. Inclusion of patients began at Oslo University Hospital on January 1, 2020, and at the University Hospital of North Norway on February 1, 2020. As of February 2021, we have enrolled 612 patients, and for 286 patients the 6-month follow-up has been completed. Papers will be drafted for publication throughout 2021 and 2022. Conclusions: This study will improve our understanding of existing service provision, the gaps between needs and services, and the associated costs for treating patients with moderate and major trauma. This may guide the improvement of rehabilitation and health care resource planning and allocation

Rehabilitation and outcomes after complicated vs uncomplicated mild TBI:results from the CENTER-TBI study

Background: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. Methods: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. Results: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. Conclusions: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. Trial registration: ClinicalTrials.gov NCT02210221.</p

Hydrothermal Liquefaction of Enzymatic Hydrolysis Lignin: Biomass Pretreatment Severity Affects Lignin Valorization

Alkaline hydrothermal liquefaction (HTL) of lignin-rich enzymatic hydrolysis residues (EnzHR) from wheat straw and Miscanthus x giganteus was performed at 255, 300, and 345 \ub0C to investigate valorization of this side-stream from second-generation bioethanol production. The EnzHR were from biomass hydrothermally pretreated at two different levels of severity (190 \ub0C, 10 min or 195 \ub0C, 15 min), and HTL at 300 \ub0C of these EnzHR showed the most effective lignin depolymerization of the low severity EnzHR for both wheat straw and Miscanthus. The degree of depolymerization during HTL was temperature dependent and was not complete after 20 min at 255 \ub0C, most distinctly for the Miscanthus EnzHR. The yields of 128 monomeric products quantified by gas chromatography-mass spectrometry were up to 15.4 wt % of dry matter. Principal component analysis of the quantified compounds showed that nonlignin HTL products are main contributors to the variance of the HTL products from the two biomasses. The chemically modified lignin polymer was found to have increased thermal stability after HTL. Analytical pyrolysis was applied to investigate the chemical composition of a larger fraction of the products. Analytical pyrolysis contributed with additional chemical information as well as confirming trends seen from quantified monomers. This work is relevant for future lignin valorization in biorefineries based on current second-generation bioethanol production

Hydrothermal Liquefaction of Enzymatic Hydrolysis Lignin: Biomass Pretreatment Severity Affects Lignin Valorization

Alkaline hydrothermal liquefaction (HTL) of lignin-rich enzymatic hydrolysis residues (EnzHR) from wheat straw and Miscanthus x giganteus was performed at 255, 300, and 345 °C to investigate valorization of this side-stream from second-generation bioethanol production. The EnzHR were from biomass hydrothermally pretreated at two different levels of severity (190 °C, 10 min or 195 °C, 15 min), and HTL at 300 °C of these EnzHR showed the most effective lignin depolymerization of the low severity EnzHR for both wheat straw and Miscanthus. The degree of depolymerization during HTL was temperature dependent and was not complete after 20 min at 255 °C, most distinctly for the Miscanthus EnzHR. The yields of 128 monomeric products quantified by gas chromatography–mass spectrometry were up to 15.4 wt % of dry matter. Principal component analysis of the quantified compounds showed that nonlignin HTL products are main contributors to the variance of the HTL products from the two biomasses. The chemically modified lignin polymer was found to have increased thermal stability after HTL. Analytical pyrolysis was applied to investigate the chemical composition of a larger fraction of the products. Analytical pyrolysis contributed with additional chemical information as well as confirming trends seen from quantified monomers. This work is relevant for future lignin valorization in biorefineries based on current second-generation bioethanol production

Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study.

BACKGROUND: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. METHODS: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale - Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury - Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. RESULTS: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. CONCLUSIONS: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT02210221

Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study

Background: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury.Methods: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles.Results: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL.Conclusions: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach.Trial registration: ClinicalTrials.gov NCT02210221