Prevalence and Predictors of Cerebral Microangiopathy Determined by Pulsatility Index in an Asymptomatic Population From the ILERVAS Project

Background: Little is known about the prevalence of cerebral microangiopathy (CM), which is related to cognitive impairment, in an asymptomatic population. Pulsatility index (PI) is an easily measurable parameter of cerebral vascular resistance in transcranial duplex of the middle cerebral artery (MCA) study. We aimed to determine the prevalence of CM measured by PI of MCA in low to moderate vascular risk subjects. Methods: We included 3,721 subjects between 45 and 70 years without previous history of vascular disease or diabetes mellitus and with at least one other vascular risk factor from the cross-sectional study ILERVAS (Lleida, Spain). Patients underwent transcranial duplex to determine MCA-PI. Possible CM was defined by MCA-PI >1.1. Carotid and femoral arteries ultrasound registration was done to determine the presence, the number, and the area of atheromatous plaques. Body mass index (BMI), pulse pressure (PP) and laboratory data were also recorded. Results: 439 (11.8%) subjects were excluded due to the low quality of transcranial duplex images. Median age was 57 [IQR 52, 62] years. Possible CM was found in 424 (12.9%) subjects. CM patients had higher prevalence of plaques than non-CM (77.4 vs. 66.4%, p < 0.001). PI showed a positive linear correlation with the number of territories with plaques (r = 0.130, p < 0.001), and the total plaque area (r = 0.082, p < 0.001). The predictors of possible CM were the age, male gender, and PP. Conclusions: In low-to-moderate vascular risk asymptomatic population, the proportion of abnormal brain microvascular bed determined by MCA-PI is not negligible. The planned 10-year follow-up will describe the clinical relevance of these findings.This work was supported by grants from the Diputacio de Lleida, Instituto de Salud Carlos III (RETIC RD16/0009/0011) and Ministerio de Ciencia, Inovación y Universidades (IJC2018-037792-I). FP was supported by the Catalan Autonomous Government’s Agència de Gestió d’Ajuts Universitaris i de Recerca (2017 suport a les activitats dels grups de recerca 1628). RP was supported by the Spanish Ministry of Science, Innovation, and Universities (grant RTI2018-099200-B-I00), and the Generalitat of Catalonia: Agency for Management of University and Research Grants (2017SGR696). This study was co-financed by FEDER funds from the European Union (A way to build Europe). IRBLleida is a CERCA Programme/Generalitat of Catalonia

Behavioral characterization of a mouse model overexpressing DSCR1/ RCAN1

DSCR1/ RCAN1 is a chromosome 21 gene found to be overexpressed in the brains of Down syndrome (DS) and postulated as a good candidate to contribute to mental disability. However, even though Rcan1 knockout mice have pronounced spatial learning and memory deficits, the possible deleterious effects of its overexpression in DS are not well understood. We have generated a transgenic mouse model overexpressing DSCR1/RCAN1 in the brain and analyzed the effect of RCAN1 overexpression on cognitive function. TgRCAN1 mice present a marked disruption of the learning process in a visuo-spatial learning task. However, no significant differences were observed in the performance of the memory phase of the test (removal session) nor in a step-down passive avoidance task, thus suggesting that once learning has been established, the animals are able to consolidate the information in the longer term

Quantitative trait loci for fatness at growing and reproductive stages in Iberian × Meishan F2 sows

A considerable number of fatness QTL have been identified in growing pigs, but there is a lack of knowledge about the genetic architecture of this trait in gilts and sows. We have performed a genome scan, in 255 Iberian × Meishan F2 sows, for backfat thickness (BF) at 150 (BF150) and 210 (BF210) days of age, 30 days after conception (BF30) and 7–10 days before farrowing (BFbf). We have found one BF150 QTL in SSC6 (120 cM) that was highly significant (P < 0.001) at the chromosome-wide level and suggestive at the genome-wide level (P < 0.1). Ten additional chromosome-wide significant QTL were found for sow BF150 (SSC1, SSC13), BF210 (SSC6, SSC8, SSC15), BF30 (SSC5, SSC6) and BFbf (SSC1, SSC6, SSC13). The location of several of the BF QTL varied depending on the growing and reproductive status of the sow, suggesting that part of these genetic effects may have a temporal pattern of phenotypic expression.Financial support was provided by Ministerio de Educación y Ciencia, Spain (Grant AGL2004-08368-C03/GAN).Peer reviewe

Value migration: digitalization of shipping as a mechanism of industry dethronement

In this conceptual paper, we review latest developments related to unmanned vessels and sketch potential scenarios that implicate with the existing maritime industry structure. On the one hand, we isolate a range of challenges that make the imminent realization of unmanned vessels seem like a rather utopian pursuit. On the other hand, we explain the reasons that may catalyse their emergence. Inspired by these opposing tensions, we highlight that the digital transformation of the shipping industry has the potential to enhance value within the industry’s ecosystem. However, we also contend that unmanned vessels -if realized- pose a very particular threat to the identity of the shipping industry as we know it. In particular, we build upon the concept of value migration and we highlight the drastic existential changes that may likely stem from a shift to non-seafarer-centric shipping. We conclude with questions that matter for industry dethronement purposes i.e., the possibility that existing industry structures may be substantially reconfigured following a removal of the seafarer as the nucleus of value creation in shipping

Effects of Neonatal Neural Progenitor Cell Implantation on Adult Neuroanatomy and Cognition in the Ts65Dn Model of Down Syndrome

As much of the aberrant neural development in Down syndrome (DS) occurs postnatally, an early opportunity exists to intervene and influence life-long cognitive development. Recent success using neural progenitor cells (NPC) in models of adult neurodegeneration indicate such therapy may be a viable option in diseases such as DS. Murine NPC (mNPC, C17.2 cell line) or saline were implanted bilaterally into the dorsal hippocampus of postnatal day 2 (PND 2) Ts65Dn pups to explore the feasibility of early postnatal treatment in this mouse model of DS. Disomic littermates provided karyotype controls for trisomic pups. Pups were monitored for developmental milestone achievement, and then underwent adult behavior testing at 14 weeks of age. We found that implanted mNPC survived into adulthood and migrated beyond the implant site in both karyotypes. The implantation of mNPC resulted in a significant increase in the density of dentate granule cells. However, mNPC implantation did not elicit cognitive changes in trisomic mice either neonatally or in adulthood. To the best of our knowledge, these results constitute the first assessment of mNPC as an early intervention on cognitive ability in a DS model

Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: possible role in Down syndrome

Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system

QTL mapping for teat number in an Iberian-by-Meishan pig intercross

The aim of this study was to investigate chromosomal regions affecting the number of teats in pigs and possible epistatic interactions between the identified quantitative trait loci (QTL). An experimental F2 cross between Iberian and Chinese Meishan lines was used for this purpose. A genomic scan was conducted with 117 markers covering the 18 porcine autosomes. Linkage analyses were performed by interval mapping using an animal model to estimate QTL and additive polygenic effects. Complementary analyses with models fitting two QTL were also carried out. The results showed three genomewide significant QTL mapping on chromosomes 5, 10 and 12, whose joint action control up to 30% of the phenotypic variance of the trait. Meishan alleles had a positive additive effect on teat number, and a positive-additive x additive-epistatic interaction was detected between QTL on chromosomes 10 and 12. © 2005 International Society for Animal Genetics