A comprehensive coding and microRNA transcriptome of vertebral bone in postlarvae and juveniles of Senegalese sole (Solea senegalensis).

Understanding vertebral bone development is essential to prevent skeletal malformations in farmed fish related to genetic and environmental factors. This is an important issue in Solea senegalensis, with special impact of spinal anomalies in postlarval and juvenile stages. Vertebral bone transcriptomics in farmed fish mainly comes from coding genes, and barely on miRNA expression. Here, we used RNA-seq of spinal samples to obtain the first comprehensive coding and miRNA transcriptomic repertoire for postlarval and juvenile vertebral bone, covering different vertebral phenotypes and egg-incubation temperatures related to skeleton health in S. senegalensis. Coding genes, miRNA and pathways regulating bone development and growth were identified. Differential transcriptomic profiles and suggestive mRNA-miRNA interactions were found between postlarvae and juveniles. Bone-related genes and functions were associated with the extracellular matrix, development and regulatory processes, calcium binding, retinol and lipid metabolism or response to stimulus, including those revealed by the miRNA targets related to signaling, cellular and metabolic processes, growth, cell proliferation and biological adhesion. Pathway enrichment associated with fish skeleton were identified when comparing postlarvae and juveniles: growth and bone development functions in postlarvae, while actin cytoskeleton, focal adhesion and proteasome related to bone remodeling in juveniles. The transcriptome data disclosed candidate coding and miRNA gene markers related to bone cell processes, references for functional studies of the anosteocytic bone of S. senegalensis. This study establishes a broad transcriptomic foundation to study healthy and anomalous spines under early thermal conditions across life-stages in S. senegalensis, and for comparative analysis of skeleton homeostasis and pathology in fish and vertebrates.

Heterogeneous microgeographic genetic structure of the common cockle (Cerastoderma edule) in the Northeast Atlantic Ocean: biogeographic barriers and environmental factors.

Knowledge of genetic structure at the finest level is essential for the conservation of genetic resources. Despite no visible barriers limiting gene flow, significant genetic structure has been shown in marine species. The common cockle (Cerastoderma edule) is a bivalve of great commercial and ecological value inhabiting the Northeast Atlantic Ocean. Previous population genomics studies demonstrated significant structure both across the Northeast Atlantic, but also within small geographic areas, highlighting the need to investigate fine-scale structuring. Here, we analysed two geographic areas that could represent opposite models of structure for the species: (1) the SW British Isles region, highly fragmented due to biogeographic barriers, and (2) Galicia (NW Spain), a putative homogeneous region. A total of 9250 SNPs genotyped by 2b-RAD on 599 individuals from 22 natural beds were used for the analysis. The entire SNP dataset mostly confirmed previous observations related to genetic diversity and differentiation; however, neutral and divergent SNP outlier datasets enabled disentangling physical barriers from abiotic environmental factors structuring both regions. While Galicia showed a homogeneous structure, the SW British Isles region was split into four reliable genetic regions related to oceanographic features and abiotic factors, such as sea surface salinity and temperature. The information gathered supports specific management policies of cockle resources in SW British and Galician regions also considering their particular socio-economic characteristics; further, these new data will be added to those recently reported in the Northeast Atlantic to define sustainable management actions across the whole distribution range of the species.

Non-synonymous variation and protein structure of candidate genes associated with selection in farm and wild populations of turbot (Scophthalmus maximus).

Non-synonymous variation (NSV) of protein coding genes represents raw material for selection to improve adaptation to the diverse environmental scenarios in wild and livestock populations. Many aquatic species face variations in temperature, salinity and biological factors throughout their distribution range that is reflected by the presence of allelic clines or local adaptation. The turbot (Scophthalmus maximus) is a flatfish of great commercial value with a flourishing aquaculture which has promoted the development of genomic resources. In this study, we developed the first atlas of NSVs in the turbot genome by resequencing 10 individuals from Northeast Atlantic Ocean. More than 50,000 NSVs where detected in the ~ 21,500 coding genes of the turbot genome, and we selected 18 NSVs to be genotyped using a single Mass ARRAY multiplex on 13 wild populations and three turbot farms. We detected signals of divergent selection on several genes related to growth, circadian rhythms, osmoregulation and oxygen binding in the different scenarios evaluated. Furthermore, we explored the impact of NSVs identified on the 3D structure and functional relationship of the correspondent proteins. In summary, our study provides a strategy to identify NSVs in species with consistently annotated and assembled genomes to ascertain their role in adaptation.

A chromosome-level genome assembly enables the identification of the follicule stimulating hormone receptor as the master sex-determining gene in the flatfish Solea senegalensis.

Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis.

Genomic survey of edible cockle (Cerastoderma edule) in the Northeast Atlantic: A baseline for sustainable management of its wild resources.

Knowledge on correlations between environmental factors and genome divergence between populations of marine species is crucial for sustainable management of fisheries and wild populations. The edible cockle (Cerastoderma edule) is a marine bivalve distributed along the Northeast Atlantic coast of Europe and is an important resource from both commercial and ecological perspectives. We performed a population genomics screening using 2b-RAD genotyping on 9309 SNPs localized in the cockle's genome on a sample of 536 specimens pertaining to 14 beds in the Northeast Atlantic Ocean to analyse the genetic structure with regard to environmental variables. Larval dispersal modelling considering species behaviour and interannual/interseasonal variation in ocean conditions was carried out as an essential background to which compare genetic information. Cockle populations in the Northeast Atlantic displayed low but significant geographical differentiation between populations (F ST = 0.0240; p < 0.001), albeit not across generations. We identified 742 and 36 outlier SNPs related to divergent and balancing selection in all the geographical scenarios inspected, and sea temperature and salinity were the main environmental correlates suggested. Highly significant linkage disequilibrium was detected at specific genomic regions against the very low values observed across the whole genome. Two main genetic groups were identified, northwards and southwards of French Brittany. Larval dispersal modelling suggested a barrier for larval dispersal linked to the Ushant front that could explain these two genetic clusters. Further genetic subdivision was observed using outlier loci and considering larval advection. The northern group was divided into the Irish/Celtic Seas and the English Channel/North Sea, while the southern group was divided into three subgroups. This information represents the baseline for the management of cockles, designing conservation strategies, founding broodstock for depleted beds and producing suitable seed for aquaculture production.

Genomic Hatchery Introgression in Brown Trout (Salmo trutta L.): Development of a Diagnostic SNP Panel for Monitoring the Impacted Mediterranean Rivers.

Brown trout (Salmo trutta L.) populations have been restocked during recent decades to satisfy angling demand and counterbalance the decline of wild populations. Millions of fertile brown trout individuals were released into Mediterranean and Atlantic rivers from hatcheries with homogeneous central European stocks. Consequently, many native gene pools have become endangered by introgressive hybridization with those hatchery stocks. Different genetic tools have been used to identify and evaluate the degree of introgression starting from pure native and restocking reference populations (e.g., LDH-C* locus, microsatellites). However, due to the high genetic structuring of brown trout, the definition of the "native pool" is hard to achieve. Additionally, although the LDH-C* locus is useful for determining the introgression degree at the population level, its consistency at individual level is far from being accurate, especially after several generations were since releases. Accordingly, the development of a more powerful and cost-effective tool is essential for an appropriate monitoring to recover brown-trout-native gene pools. Here, we used the 2b restriction site-associated DNA sequencing (2b-RADseq) and Stacks 2 with a reference genome to identify single-nucleotide polymorphisms (SNPs) diagnostic for hatchery-native fish discrimination in the Atlantic and Mediterranean drainages of the Iberian Peninsula. A final set of 20 SNPs was validated in a MassARRAY® System genotyping by contrasting data with the whole SNP dataset using samples with different degree of introgression from those previously recorded. Heterogeneous introgression impact was confirmed among and within river basins, and was the highest in the Mediterranean Slope. The SNP tool reported here should be assessed in a broader sample scenario in Southern Europe considering its potential for monitoring recovery plans.

A genome-wide association study, supported by a new chromosome-level genome assembly, suggests sox2 as a main driver of the undifferentiatiated ZZ/ZW sex determination of turbot (Scophthalmus maximus).

BACKGROUND: Understanding sex determination (SD) across taxa is a major challenge for evolutionary biology. The new genomic tools are paving the way to identify genomic features underlying SD in fish, a group frequently showing limited sex chromosome differentiation and high SD evolutionary turnover. Turbot (Scophthalmus maximus) is a commercially important flatfish with an undifferentiated ZW/ZZ SD system and remarkable sexual dimorphism. Here we describe a new long-read turbot genome assembly used to disentangle the genetic architecture of turbot SD by combining genomics and classical genetics approaches. RESULTS: The new turbot genome assembly consists of 145 contigs (N50 = 22.9 Mb), 27 of them representing >95% of its estimated genome size. A genome wide association study (GWAS) identified a ~ 6.8 Mb region on chromosome 12 associated with sex in 69.4% of the 36 families analyzed. The highest associated markers flanked sox2, the only gene in the region showing differential expression between sexes before gonad differentiation. A single SNP showed consistent differences between Z and W chromosomes. The analysis of a broad sample of families suggested the presence of additional genetic and/or environmental factors on turbot SD. CONCLUSIONS: The new chromosome-level turbot genome assembly, one of the most contiguous fish assemblies to date, facilitated the identification of sox2 as a consistent candidate gene putatively driving SD in this species. This chromosome SD system barely showed any signs of differentiation, and other factors beyond the main QTL seem to control SD in a certain proportion of families.

Recent trends of invasive mechanical ventilation in older adults: a nationwide population-based study.

BACKGROUND: Critical care demand for older people is increasing. However, there is scarce population-based information about the use of life-support measures such as invasive mechanical ventilation (IMV) in this population segment. OBJECTIVE: To examine the characteristics and recent trends of IMV for older adults. METHODS: Retrospective cohort study on IMV in adults ≥65 years using the 2004-15 Spanish national hospital discharge database. Primary outcomes were incidence, inhospital mortality and resource utilization. Trends were assessed for average annual percentage change in rates using joinpoint regression models. RESULTS: 233,038 cases were identified representing 1.27% of all-cause hospitalizations and a crude incidence of 248 cases/100,000 older adult population. Mean age was 75 years, 62% were men and 70% had comorbidities. Inhospital mortality was 48%. Across all ages, about 80% of survivors were discharged home. Incidence rates of IMV remained roughly unchanged over time with an average annual change of -0.2% (95% confidence interval (CI): -0.9, 0.6). Inhospital mortality decreased an annual average of -0.7% (95% CI: -0.5, -1.0), a trend detected across age groups and most clinical strata. Further, there was a 3.4% (95% CI: 3.0, 3.8) annual increase in the proportion of adults aged ≥80 years, an age group that showed higher mortality risk, lower frequency of prolonged IMV, shorter hospital stays and lower costs. CONCLUSIONS: Overall rates of IMV remained roughly stable among older adults, while inhospital mortality showed a decreasing trend. There was a notable increase in adults aged ≥80 years, a group with high mortality and lower associated hospital resource use.

Low impact of different SNP panels from two building-loci pipelines on RAD-Seq population genomic metrics: case study on five diverse aquatic species.

BACKGROUND: The irruption of Next-generation sequencing (NGS) and restriction site-associated DNA sequencing (RAD-seq) in the last decade has led to the identification of thousands of molecular markers and their genotyping for refined genomic screening. This approach has been especially useful for non-model organisms with limited genomic resources. Many building-loci pipelines have been developed to obtain robust single nucleotide polymorphism (SNPs) genotyping datasets using a de novo RAD-seq approach, i.e. without reference genomes. Here, the performances of two building-loci pipelines, STACKS 2 and Meyer's 2b-RAD v2.1 pipeline, were compared using a diverse set of aquatic species representing different genomic and/or population structure scenarios. Two bivalve species (Manila clam and common edible cockle) and three fish species (brown trout, silver catfish and small-spotted catshark) were studied. Four SNP panels were evaluated in each species to test both different building-loci pipelines and criteria for SNP selection. Furthermore, for Manila clam and brown trout, a reference genome approach was used as control. RESULTS: Despite different outcomes were observed between pipelines and species with the diverse SNP calling and filtering steps tested, no remarkable differences were found on genetic diversity and differentiation within species with the SNP panels obtained with a de novo approach. The main differences were found in brown trout between the de novo and reference genome approaches. Genotyped vs missing data mismatches were the main genotyping difference detected between the two building-loci pipelines or between the de novo and reference genome comparisons. CONCLUSIONS: Tested building-loci pipelines for selection of SNP panels seem to have low influence on population genetics inference across the diverse case-study scenarios here studied. However, preliminary trials with different bioinformatic pipelines are suggested to evaluate their influence on population parameters according with the specific goals of each study.

A multidisciplinary approach to identify priority areas for the monitoring of a vulnerable family of fishes in Spanish Marine National Parks.

BACKGROUND: Syngnathid fishes (Actinopterygii, Syngnathidae) are flagship species strongly associated with seaweed and seagrass habitats. Seahorses and pipefishes are highly vulnerable to anthropogenic and environmental disturbances, but most species are currently Data Deficient according to the IUCN (2019), requiring more biological and ecological research. This study provides the first insights into syngnathid populations in the two marine Spanish National Parks (PNIA-Atlantic- and PNAC-Mediterranean). Fishes were collected periodically, marked, morphologically identified, analysed for size, weight, sex and sexual maturity, and sampled for stable isotope and genetic identification. Due the scarcity of previous information, habitat characteristics were also assessed in PNIA. RESULTS: Syngnathid diversity and abundance were low, with two species identified in PNIA (Hippocampus guttulatus and Syngnathus acus) and four in PNAC (S. abaster, S. acus, S. typhle and Nerophis maculatus). Syngnathids from both National Parks (NP) differed isotopically, with much lower δ15N in PNAC than in PNIA. The dominant species were S. abaster in PNAC and S. acus in PNIA. Syngnathids preferred less exposed sites in macroalgal assemblages in PNIA and Cymodocea meadows in PNAC. The occurrence of very large specimens, the absence of small-medium sizes and the isotopic comparison with a nearby population suggest that the population of Syngnathus acus (the dominant syngnathid in PNIA) mainly comprised breeders that migrate seasonally. Mitochondrial cytochrome b sequence variants were detected for H. guttulatus, S. acus, and S. abaster, and a novel 16S rDNA haplotype was obtained in N. maculatus. Our data suggest the presence of a cryptic divergent mitochondrial lineage of Syngnathus abaster species in PNAC. CONCLUSIONS: This is the first multidisciplinary approach to the study of syngnathids in Spanish marine NPs. Habitat preferences and population characteristics in both NPs differed. Further studies are needed to assess the occurrence of a species complex for S. abaster, discarding potential misidentifications of genus Syngnathus in PNAC, and evaluate migratory events in PNIA. We propose several preferential sites in both NPs for future monitoring of syngnathid populations and some recommendations for their conservation.

Use and outcomes of mechanical ventilation for people with severe mental disorders admitted due to natural causes: A nationwide population-based study.

OBJECTIVE: To characterize temporal trends and outcomes of invasive mechanical ventilation (MV) for people with severe mental disorders (SMD) admitted due to natural causes. METHODS: We identified all 224,507 hospitalizations of patients aged 15-69 who underwent MV in Spain between 2000 and 2015, excluding poisonings and injuries, and divided them by presence of an SMD diagnosis. We compared the two study groups regarding demographic and clinical characteristics and examined time trends in the incidence of MV and in-hospital mortality. RESULTS: SMD patients were younger and had fewer comorbidities and lower in-hospital mortality than the non-SMD group. However, among patients admitted due to circulatory diseases, SMD patients had higher mortality risk (OR = 1.39; 95%CI = 1.22-1.59). In the SMD group, the increase in MV use quadrupled that of non-SMD patients (Average Annual Percent Change = 6.9%; 95%CI = 5.5-8.3 vs. 1.5%; 0.9-2.0, respectively). Overall in-hospital mortality declined similarly in both study groups. While the SMD group's circulatory-specific mortality also decreased, by 2015 it remained elevated in comparison to non-SMD patients (44% vs. 38%, respectively). CONCLUSION: The increase in MV use due to natural causes among people with SMD outpaced that of non-SMD patients, with comparable decreasing trends in mortality. Although declining, SMD patients' higher circulatory-specific mortality risk requires further investigation.

Genomic Signatures After Five Generations of Intensive Selective Breeding: Runs of Homozygosity and Genetic Diversity in Representative Domestic and Wild Populations of Turbot (Scophthalmus maximus).

Massive genotyping of single nucleotide polymorphisms (SNP) has opened opportunities for analyzing the way in which selection shapes genomes. Artificial or natural selection usually leaves genomic signatures associated with selective sweeps around the responsible locus. Strong selective sweeps are most often identified either by lower genetic diversity than the genomic average and/or islands of runs of homozygosity (ROHi). Here, we conducted an analysis of selective sweeps in turbot (Scophthalmus maximus) using two SNP datasets from a Northeastern Atlantic population (36 individuals) and a domestic broodstock (46 individuals). Twenty-six families (∼ 40 offspring per family) from this broodstock and three SNP datasets applying differing filtering criteria were used to adjust ROH calling parameters. The best-fitted genomic inbreeding estimate (FROH) was obtained by the sum of ROH longer than 1 Mb, called using a 21,615 SNP panel, a sliding window of 37 SNPs and one heterozygous SNP per window allowed. These parameters were used to obtain the ROHi distribution in the domestic and wild populations (49 and 0 ROHi, respectively). Regions with higher and lower genetic diversity within each population were obtained using sliding windows of 37 SNPs. Furthermore, those regions were mapped in the turbot genome against previously reported genetic markers associated with QTL (Quantitative Trait Loci) and outlier loci for domestic or natural selection to identify putative selective sweeps. Out of the 319 and 278 windows surpassing the suggestive pooled heterozygosity thresholds (ZHp) in the wild and domestic population, respectively, 78 and 54 were retained under more restrictive ZHp criteria. A total of 116 suggestive windows (representing 19 genomic regions) were linked to either QTL for production traits, or outliers for divergent or balancing selection. Twenty-four of them (representing 3 genomic regions) were retained under stricter ZHp thresholds. Eleven QTL/outlier markers were exclusively found in suggestive regions of the domestic broodstock, 7 in the wild population and one in both populations; one (broodstock) and two (wild) of those were found in significant regions retained under more restrictive ZHp criteria in the broodstock and the wild population, respectively. Genome mining and functional enrichment within regions associated with selective sweeps disclosed relevant genes and pathways related to aquaculture target traits, including growth and immune-related pathways, metabolism and response to hypoxia, which showcases how this genome atlas of genetic diversity can be a valuable resource to look for candidate genes related to natural or artificial selection in turbot populations.

Population Genomics in Rhamdia quelen (Heptapteridae, Siluriformes) Reveals Deep Divergence and Adaptation in the Neotropical Region.

Rhamdia quelen, a Neotropical fish with hybridization between highly divergent mitochondrial DNA (mtDNA) lineages, represents an interesting evolutionary model. Previous studies suggested that there might be demographic differences between coastal lagoons and riverine environments, as well as divergent populations that could be reproductively isolated. Here, we investigated the genetic diversity pattern of this taxon in the Southern Neotropical Basin system that includes the La Plata Basin, Patos-Merin lagoon basin and the coastal lagoons draining to the SW Atlantic Ocean, through a population genomics approach using 2b-RAD-sequencing-derived single nucleotide polymorphisms (SNPs). The genomic scan identified selection footprints associated with divergence and suggested local adaptation environmental drivers. Two major genomic clusters latitudinally distributed in the Northern and Southern basins were identified, along with consistent signatures of divergent selection between them. Population structure based on the whole set of loci and on the presumptive neutral vs. adaptive loci showed deep genomic divergence between the two major clusters. Annotation of the most consistent SNPs under divergent selection revealed some interesting candidate genes for further functional studies. Moreover, signals of adaptation to a coastal lagoon environment mediated by purifying selection were found. These new insights provide a better understanding of the complex evolutionary history of R. quelen in the southernmost basin of the Neotropical region.

Effect of dementia on the incidence, short-term outcomes, and resource utilization of invasive mechanical ventilation in the elderly: a nationwide population-based study.

BACKGROUND: Though the prevalence of dementia among hospitalized patients is increasing, there is limited population data in Europe about the use of life-support measures such as invasive mechanical ventilation in these patients. Our objective is to assess whether dementia influences the incidence, outcomes, and hospital resource use in elderly patients undergoing mechanical ventilation. METHODS: Using ICD-9-CM codes, all hospitalizations involving invasive mechanical ventilation in adults aged ≥ 65 years were identified in the Spanish national hospital discharge database covering the period 2000-2013. The cases identified were stratified into two cohorts (patients with or without dementia) in which main outcome measures were compared. The impact of dementia on in-hospital mortality and hospital resource use were assessed through multivariable models. Trends were assessed through joinpoint regression analysis and results expressed as average annual percentage change. RESULTS: Of the 259,623 cases identified, 5770 (2.2%) had been assigned codes for dementia. Cases with dementia were older, had a lower Charlson comorbidity score, and less frequently received prolonged mechanical ventilation or were assigned a surgical DRG. Circulatory disease was the most common main diagnosis in both cohorts. No significant impact of dementia was observed on in-hospital mortality (adjusted OR 1.04, [95% CI] 0.98, 1.09). In the cohort with dementia, the incidence of mechanical ventilation underwent an average annual increase over time of 5.39% (95% CI 4.0, 6.7) while this rate was 1.62% (95% CI 0.9, 2.4) in cases without dementia. However, unlike this cohort, mortality in cases with dementia did not significantly decline over time. Geometric mean hospital cost and stay were lower among cases with than without dementia (- 14% [95% CI - 12%, - 15%] and - 12% [95% CI, - 9%, - 14%], respectively), and these differences increased over time. CONCLUSION: This nationwide population-based study suggests no impact of dementia on in-hospital mortality in elderly patients undergoing invasive mechanical ventilation. However, dementia is significantly associated with shorter stay and hospital costs. Our data also identifies a recent marked increase in the use of this life-support measure in elderly patients with dementia and that this increase is much greater than that observed in elderly individuals without dementia.

Parallel pattern of differentiation at a genomic island shared between clinal and mosaic hybrid zones in a complex of cryptic seahorse lineages.

Diverging semi-isolated lineages either meet in narrow clinal hybrid zones, or have a mosaic distribution associated with environmental variation. Intrinsic reproductive isolation is often emphasized in the former and local adaptation in the latter, although both reduce gene flow between groups. Rarely are these two patterns of spatial distribution reported in the same study system. Here, we report that the long-snouted seahorse Hippocampus guttulatus is subdivided into discrete panmictic entities by both types of hybrid zones. Along the European Atlantic coasts, a northern and a southern lineage meet in the southwest of France where they coexist in sympatry-i.e., in the same geographical zone-with little hybridization. In the Mediterranean Sea, two lineages have a mosaic distribution, associated with lagoon-like and marine habitats. A fifth lineage was identified in the Black Sea. Genetic homogeneity over large spatial scales contrasts with isolation maintained in sympatry or close parapatry at a fine scale. A high variation in locus-specific introgression rates provides additional evidence that partial reproductive isolation must be maintaining the divergence. We find that fixed differences between lagoon and marine populations in the Mediterranean Sea belong to the most differentiated SNPs between the two Atlantic lineages, against the genome-wide pattern of structure that mostly follow geography. These parallel outlier SNPs cluster on a single chromosome-wide island of differentiation. Since Atlantic lineages do not map to lagoon-sea habitat variation, genetic parallelism at the genomic island suggests a shared genetic barrier contributes to reproductive isolation in contrasting contexts-i.e., spatial versus ecological. We discuss how a genomic hotspot of parallel differentiation could have evolved and become associated both with space and with a patchy environment in a single study system.

The impact of dementia on hospital outcomes for elderly patients with sepsis: A population-based study.

BACKGROUND: Prior studies have suggested that dementia adversely influences clinical outcomes and increases resource utilization in patients hospitalized for acute diseases. However, there is limited population-data information on the impact of dementia among elderly hospitalized patients with sepsis. METHODS: From the 2009-2011 National Hospital Discharge Database we identified hospitalizations in adults aged ≥65 years. Using ICD9-CM codes, we selected sepsis cases, divided them into two cohorts (with and without dementia) and compared both groups with respect to organ dysfunction, in-hospital mortality and the use of hospital resources. We estimated the impact of dementia on these primary endpoints through multivariate regression models. RESULTS: Of the 148 293 episodes of sepsis identified, 16 829 (11.3%) had diagnoses of dementia. Compared to their dementia-free counterparts, they were more predominantly female and older, had a lower burden of comorbidities and were more frequently admitted due to a principal diagnosis of sepsis. The dementia cohort showed a lower risk of organ dysfunction (adjusted OR: 0.84, 95% Confidence Interval [CI]: 0.81, 0.87) but higher in-hospital mortality (adjusted OR: 1.32, 95% [CI]: 1.27, 1.37). The impact of dementia on mortality was higher in the cases of younger age, without comorbidities and without organ dysfunction. The cases with dementia also had a lower length of stay (-3.87 days, 95% [CI]: -4.21, -3.54) and lower mean hospital costs (-3040€, 95% [CI]: -3279, -2800). CONCLUSIONS: This nationwide population-based study shows that dementia is present in a substantial proportion of adults ≥65s hospitalized with sepsis, and while the condition does seem to come with a lower risk of organ dysfunction, it exerts a negative influence on in-hospital mortality and acts as an independent mortality predictor. Furthermore, it is significantly associated with shorter length of stay and lower hospital costs.

Epidemiology and Trends of Sepsis in Young Adults Aged 20-44 Years: A Nationwide Population-Based Study.

BACKGROUND: While sepsis may have especially marked impacts in young adults, there is limited population-based information on its epidemiology and trends. METHODS: Population-based longitudinal study on sepsis in adults aged 20-44 years using the 2006-2015 Spanish national hospital discharge database. Cases are identified by an ICD-9-CM coding strategy. Primary endpoints are incidence and in-hospital mortality. Trends are assessed for annual percentage change (AAPC) in rates using Joinpoint regression models. RESULTS: 28,351 cases are identified, representing 3.06‱ of all-cause hospitalisations and a crude incidence of 16.4 cases/100,000 population aged 20-44. The mean age is 36 years, 58% of cases are men, and around 60% have associated comorbidities. Seen in one third of cases, the source of infection is respiratory. Single organ dysfunction is recorded in 45% of cases. In-hospital mortality is 24% and associated with age, comorbidity and extent of organ dysfunction. Incidence rates increase over time in women (AAPC: 3.8% (95% CI: 2.1, 5.5)), whereas case-fatality decline with an overall AAPC of -5.9% (95% CI -6.6, -5.2). Our results indicate that sepsis is common in young adults and associated with high in-hospital mortality, though it shows a decreasing trend. The substantial increase in incidence rates in women needs further research.

Parallel evolution and adaptation to environmental factors in a marine flatfish: Implications for fisheries and aquaculture management of the turbot (Scophthalmus maximus).

Unraveling adaptive genetic variation represents, in addition to the estimate of population demographic parameters, a cornerstone for the management of aquatic natural living resources, which, in turn, represent the raw material for breeding programs. The turbot (Scophthalmus maximus) is a marine flatfish of high commercial value living on the European continental shelf. While wild populations are declining, aquaculture is flourishing in southern Europe. We evaluated the genetic structure of turbot throughout its natural distribution range (672 individuals; 20 populations) by analyzing allele frequency data from 755 single nucleotide polymorphism discovered and genotyped by double-digest RAD sequencing. The species was structured into four main regions: Baltic Sea, Atlantic Ocean, Adriatic Sea, and Black Sea, with subtle differentiation apparent at the distribution margins of the Atlantic region. Genetic diversity and effective population size estimates were highest in the Atlantic populations, the area of greatest occurrence, while turbot from other regions showed lower levels, reflecting geographical isolation and reduced abundance. Divergent selection was detected within and between the Atlantic Ocean and Baltic Sea regions, and also when comparing these two regions with the Black Sea. Evidence of parallel evolution was detected between the two low salinity regions, the Baltic and Black seas. Correlation between genetic and environmental variation indicated that temperature and salinity were probably the main environmental drivers of selection. Mining around the four genomic regions consistently inferred to be under selection identified candidate genes related to osmoregulation, growth, and resistance to diseases. The new insights are useful for the management of turbot fisheries and aquaculture by providing the baseline for evaluating the consequences of turbot releases from restocking and farming.

Nutritional supplements for patients being treated for active visceral leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL) is a disease caused by a parasite, which can lead to death if untreated. Poor nutritional status hastens the progression of VL infection, and VL worsens malnutrition status. Malnutrition is one of the poor prognostic factors identified for leishmaniasis. However, the effects of nutritional supplementation in people treated for VL are not known. OBJECTIVES: To assess the effects of oral nutritional supplements in people being treated with anti-leishmanial drug therapy for VL. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and two trial registers up to 12 September 2017. We checked conference proceedings and WHO consultative meeting reports, the reference lists of key documents and existing reviews, and contacted experts and nutritional supplement companies. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-randomized controlled trials (quasi-RCTs), and non-randomized controlled trials (NRCTs) of any oral nutritional supplement, compared to no nutritional intervention, placebo, or dietary advice alone, in people being treated for VL. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature search results for studies that met the inclusion criteria. We had planned for two review authors to independently extract data and assess the risk of bias of the included studies. We planned to follow the Cochrane standard methodological procedures for assessing risk of bias and analysing the data. MAIN RESULTS: We identified no eligible studies for this review, either completed or ongoing. AUTHORS' CONCLUSIONS: We found no studies, either completed or ongoing, that assessed the effects of oral nutritional supplements in people with VL who were being treated with anti-leishmanial drug therapy. Thus, we could not draw any conclusions on the impact of these interventions on primary cure of VL, definitive cure of VL, treatment completion, self-reported recovery from illness or resolution of symptoms, weight gain, increased skinfold thickness, other measures of lean or total mass, or growth in children.This absence of evidence should not be interpreted as evidence of no effect for nutritional supplements in people under VL treatment. It means that we did not identify research that fulfilled our review inclusion criteria.The effects of oral nutritional supplements in people with VL who are being treated with anti-leishmanial drug therapy have yet to be determined by rigorous experimental studies, such as cluster-randomized trials, that focus on outcomes relevant for patients.