Implementation of different relationship estimate methodologies in breeding value prediction in kiwiberry (Actinidia arguta).

In dioecious crops such as Actinidia arguta (kiwiberries), some of the main challenges when breeding for fruit characteristics are the selection of potential male parents and the long juvenile period. Currently, breeding values of male parents are estimated through progeny tests, which makes the breeding of new kiwiberry cultivars time-consuming and costly. The application of best linear unbiased prediction (BLUP) would allow direct estimation of sex-related traits and speed up kiwiberry breeding. In this study, we used a linear mixed model approach to estimate narrow sense heritability for one vine-related trait and five fruit-related traits for two incomplete factorial crossing designs. We obtained BLUPs for all genotypes, taking into consideration whether the relationship was pedigree-based or marker-based. Owing to the high cost of genome sequencing, it is important to understand the effects of different sources of relationship matrices on estimating breeding values across a breeding population. Because of the increasing implementation of genomic selection in crop breeding, we compared the effects of incorporating different sources of information in building relationship matrices and ploidy levels on the accuracy of BLUPs' heritability and predictive ability. As kiwiberries are autotetraploids, multivalent chromosome formation and occasionally double reduction can occur during meiosis, and this can affect the accuracy of prediction. This study innovates the breeding programme of autotetraploid kiwiberries. We demonstrate that the accuracy of BLUPs of male siblings, without phenotypic observations, strongly improved when a tetraploid marker-based relationship matrix was used rather than parental BLUPs and female siblings with phenotypic observations. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01419-8.

Investigating the genetic components of tuber bruising in a breeding population of tetraploid potatoes.

BACKGROUND: Tuber bruising in tetraploid potatoes (Solanum tuberosum) is a trait of economic importance, as it affects tubers' fitness for sale. Understanding the genetic components affecting tuber bruising is a key step in developing potato lines with increased resistance to bruising. As the tetraploid setting renders genetic analyses more complex, there is still much to learn about this complex phenotype. Here, we used capture sequencing data on a panel of half-sibling populations from a breeding programme to perform a genome-wide association analysis (GWAS) for tuber bruising. In addition, we collected transcriptomic data to enrich the GWAS results. However, there is currently no satisfactory method to represent both GWAS and transcriptomics analysis results in a single visualisation and to compare them with existing knowledge about the biological system under study. RESULTS: When investigating population structure, we found that the STRUCTURE algorithm yielded greater insights than discriminant analysis of principal components (DAPC). Importantly, we found that markers with the highest (though non-significant) association scores were consistent with previous findings on tuber bruising. In addition, new genomic regions were found to be associated with tuber bruising. The GWAS results were backed by the transcriptomics differential expression analysis. The differential expression notably highlighted for the first time the role of two genes involved in cellular strength and mechanical force sensing in tuber resistance to bruising. We proposed a new visualisation, the HIDECAN plot, to integrate the results from the genomics and transcriptomics analyses, along with previous knowledge about genomic regions and candidate genes associated with the trait. CONCLUSION: This study offers a unique genome-wide exploration of the genetic components of tuber bruising. The role of genetic components affecting cellular strength and resistance to physical force, as well as mechanosensing mechanisms, was highlighted for the first time in the context of tuber bruising. We showcase the usefulness of genomic data from breeding programmes in identifying genomic regions whose association with the trait of interest merit further investigation. We demonstrate how confidence in these discoveries and their biological relevance can be increased by integrating results from transcriptomics analyses. The newly proposed visualisation provides a clear framework to summarise of both genomics and transcriptomics analyses, and places them in the context of previous knowledge on the trait of interest.

High-density linkage map construction in an autotetraploid blueberry population and detection of quantitative trait loci for anthocyanin content.

Highbush blueberry (Vaccinium corymbosum, 2n = 4x = 48) is the most cultivated type of blueberry, both in New Zealand and overseas. Its perceived nutritional value is conferred by phytonutrients, particularly anthocyanins. Identifying the genetic mechanisms that control the biosynthesis of these metabolites would enable faster development of cultivars with improved fruit qualities. Here, we used recently released tools for genetic mapping in autotetraploids to build a high-density linkage map in highbush blueberry and to detect quantitative trait loci (QTLs) for fruit anthocyanin content. Genotyping was performed by target sequencing, with ∼18,000 single nucleotide polymorphism (SNP) markers being mapped into 12 phased linkage groups (LGs). Fruits were harvested when ripe for two seasons and analyzed with high-performance liquid chromatography-mass spectrometry (HPLC-MS): 25 different anthocyanin compounds were identified and quantified. Two major QTLs that were stable across years were discovered, one on LG2 and one on LG4, and the underlying candidate genes were identified. Interestingly, the presence of anthocyanins containing acylated sugars appeared to be under strong genetic control. Information gained in this study will enable the design of molecular markers for marker-assisted selection and will help build a better understanding of the genetic control of anthocyanin biosynthesis in this crop.

Understanding suicide clusters through exploring self-harm: Semi-structured interviews with individuals presenting with near-fatal self-harm during a suicide cluster.

There was a highly publicised cluster of at least ten suicides in South Wales, United Kingdom, in 2007-2008. We carried out a qualitative descriptive study using cross-case thematic analysis to investigate the experiences and narratives of eight individuals who lived in the area where the cluster occurred and who survived an episode of near-fatal self-harm at the time of the cluster. Interviews were conducted from 01.01.2015 to 31.12.2015. All interviewees denied that the other deaths in the area had affected their own suicidal behaviour. However, in other sections of the interviews they spoke about the cluster contributing to difficulties they were experiencing at the time, including damage to social relationships, feelings of loss and being out of control. When asked about support, the interviewees emphasized the importance of counselling, which they would have found helpful but in most cases did not receive, even in the case of close contacts of individuals who had died. The findings suggest that effective prevention messaging must be subtle, since those affected may not be explicitly aware of or acknowledge the imitative aspects of their behaviour. This could be related to stigma attached to suicidal behaviour in a cluster context. Lessons for prevention include changing the message from asking if people 'have been affected by' the suicide deaths to emphasising the preventability of suicide, and directly reaching out to individuals rather than relying on people to come forward.

Construction of a high-density genetic map for hexaploid kiwifruit (Actinidia chinensis var. deliciosa) using genotyping by sequencing.

Commercially grown kiwifruit (genus Actinidia) are generally of two sub-species which have a base haploid genome of 29 chromosomes. The yellow-fleshed Actinidia chinensis var. chinensis, is either diploid (2n = 2x = 58) or tetraploid (2n = 4x = 116) and the green-fleshed cultivar A. chinensis var. deliciosa "Hayward," is hexaploid (2n = 6x = 174). Advances in breeding green kiwifruit could be greatly sped up by the use of molecular resources for more efficient and faster selection, for example using marker-assisted selection (MAS). The key genetic marker that has been implemented for MAS in hexaploid kiwifruit is for gender testing. The limited marker-trait association has been reported for other polyploid kiwifruit for fruit and production traits. We have constructed a high-density linkage map for hexaploid green kiwifruit using genotyping-by-sequence (GBS). The linkage map obtained consists of 3686 and 3940 markers organized in 183 and 176 linkage groups for the female and male parents, respectively. Both parental linkage maps are co-linear with the A. chinensis "Red5" reference genome of kiwifruit. The linkage map was then used for quantitative trait locus (QTL) mapping, and successfully identified QTLs for king flower number, fruit number and weight, dry matter accumulation, and storage firmness. These are the first QTLs to be reported and discovered for complex traits in hexaploid kiwifruit.

Microthin Descemet Stripping Automated Endothelial Keratoplasty Versus Descemet Membrane Endothelial Keratoplasty: A Randomized Clinical Trial.

PURPOSE: To compare visual outcomes, complications, and vision-related quality of life (QoL) after microthin Descemet stripping automated endothelial keratoplasty (MT-DSAEK) versus Descemet membrane endothelial keratoplasty (DMEK) for the management of corneal endothelial dysfunction in Fuchs dystrophy. METHODS: This is a prospective, double-blinded randomized controlled clinical trial. Patients with visually significant endothelial decompensation from Fuchs dystrophy were prospectively randomized to receive MT-DSAEK or DMEK surgery. The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 12 months. Secondary outcomes included refraction, keratometry, endothelial cell count, complications, and vision-related QoL at 6 and 12 months postoperatively. RESULTS: A total of 56 eyes of 56 patients were enrolled, 28 in each group. Postoperatively, LogMAR mean BSCVA in the MT-DSAEK group was 0.17 ± 0.08 and 0.11 ± 0.09 at 6 and 12 months compared with 0.09 ± 0.13 and 0.04 ± 0.13 after DMEK (P = 0.03, P = 0.002 respectively) with the DMEK cohort achieving 3.5 logarithm of the minimum angle of resolution letters better BSCVA at 1 year compared with MT-DSAEK. Complication rates were similar with 3.5% rebubbling rate in both groups, 1 primary graft failure in DMEK and a single endothelial rejection in the MT-DSAEK arm. Vision-related QoL was comparable at 6 and 12 months postoperatively, and no eyes demonstrated loss of vision from preoperative BSCVA. CONCLUSIONS: DMEK surgery resulted in significantly better BSCVA at 1, 3, 6, and 12 months postoperatively compared with MT-DSAEK. Patient satisfaction was similar with no differences reported in vision-related QoL scores, as was the complications profile between groups. Thus, our results favor DMEK as the better choice procedure for eyes with Fuchs-related corneal decompensation without ocular comorbidities.

Validation of a hospital clinical pharmacy workforce calculator: A methodology for pharmacy?

BACKGROUND: The benefits of clinical pharmacy services are established within hospital practice but staff numbers required for service delivery are not well described and staffing levels vary. The need for a consistent, objective method of determining staffing levels was recognised at a UK University Hospital and a Clinical Pharmacy Workforce Calculator (CPWC) was developed. OBJECTIVE: To develop the Activity Standard (AS) for pharmaceutical care and establish the reliability of the CPWC across acute hospital settings in UK. SETTING: Acute hospital in-patient clinical pharmacy services on medical and surgical wards. METHOD: Using the World Health Organisation's Workload Indicators of Staffing Need (WISN) methodology, a two-round Delphi study was undertaken. This developed the Activity Standard for pharmaceutical care and identified the staff-time unavailable for clinical work. Consenting panel members then tested the CPWC, calculating the staff required for three scenarios to determine whether it could be reliably used by different operators. RESULTS: Thirty-six participants consented to participate. Data were returned from 22 (61%) of whom 20 (56%) supplied analysable data. Consensus was achieved on the tasks required for pharmaceutical care delivery, the mean time each takes, how frequently they should be completed and the time unavailable for clinical work for each grade of staff. The CPWC calculates staffing requirements using these data. Eleven participants (55%) tested the CPWC and analysis of responses demonstrated that 30 of 33 (91%) calculations were accurately completed. DISCUSSION: This study defined the WISN Activity Standard for UK pharmaceutical care delivery to hospital inpatients and showed content validity for the CPWC in acute medical and surgical hospital settings. Different operators used the CPWC reliably and applied it to local sites. CONCLUSION: The CPWC offers hospital pharmacy managers a useful tool to negotiate adequate staffing to deliver pharmaceutical care. Its development methodology could be applied widely in pharmacy practice.

QTL Mapping for Resistance to Cankers Induced by Pseudomonas syringae pv. actinidiae (Psa) in a Tetraploid Actinidia chinensis Kiwifruit Population.

Polyploidy is a key driver of significant evolutionary changes in plant species. The genus Actinidia (kiwifruit) exhibits multiple ploidy levels, which contribute to novel fruit traits, high yields and resistance to the canker-causing dieback disease incited by Pseudomonas syringae pv. actinidiae (Psa) biovar 3. However, the genetic mechanism for resistance to Psa observed in polyploid kiwifruit is not yet known. In this study we performed detailed genetic analysis of a tetraploid Actinidia chinensis var. chinensis population derived from a cross between a female parent that exhibits weak tolerance to Psa and a highly Psa-resistant male parent. We used the capture-sequencing approach across the whole kiwifruit genome and generated the first ultra-dense maps in a tetraploid kiwifruit population. We located quantitative trait loci (QTLs) for Psa resistance on these maps. Our approach to QTL mapping is based on the use of identity-by-descent trait mapping, which allowed us to relate the contribution of specific alleles from their respective homologues in the male and female parent, to the control of Psa resistance in the progeny. We identified genes in the diploid reference genome whose function is suggested to be involved in plant defense, which underly the QTLs, including receptor-like kinases. Our study is the first to cast light on the genetics of a polyploid kiwifruit and suggest a plausible mechanism for Psa resistance in this species.

CRISPR-Cas9 enrichment and long read sequencing for fine mapping in plants.

BACKGROUND: Genomic methods for identifying causative variants for trait loci applicable to a wide range of germplasm are required for plant biologists and breeders to understand the genetic control of trait variation. RESULTS: We implemented Cas9-targeted sequencing for fine-mapping in apple, a method combining CRISPR-Cas9 targeted cleavage of a region of interest, followed by enrichment and long-read sequencing using the Oxford Nanopore Technology (ONT). We demonstrated the capability of this methodology to specifically cleave and enrich a plant genomic locus spanning 8 kb. The repeated mini-satellite motif located upstream of the Malus × domestica (apple) MYB10 transcription factor gene, causing red fruit colouration when present in a heterozygous state, was our exemplar to demonstrate the efficiency of this method: it contains a genomic region with a long structural variant normally ignored by short-read sequencing technologiesCleavage specificity of the guide RNAs was demonstrated using polymerase chain reaction products, before using them to specify cleavage of high molecular weight apple DNA. An enriched library was subsequently prepared and sequenced using an ONT MinION flow cell (R.9.4.1). Of the 7,056 ONT reads base-called using both Albacore2 (v2.3.4) and Guppy (v3.2.4), with a median length of 9.78 and 9.89 kb, respectively, 85.35 and 91.38%, aligned to the reference apple genome. Of the aligned reads, 2.98 and 3.04% were on-target with read depths of 180 × and 196 × for Albacore2 and Guppy, respectively, and only five genomic loci were off-target with read depth greater than 25 × , which demonstrated the efficiency of the enrichment method and specificity of the CRISPR-Cas9 cleavage. CONCLUSIONS: We demonstrated that this method can isolate and resolve single-nucleotide and structural variants at the haplotype level in plant genomic regions. The combination of CRISPR-Cas9 target enrichment and ONT sequencing provides a more efficient technology for fine-mapping loci than genome-walking approaches.

sismonr: simulation of in silico multi-omic networks with adjustable ploidy and post-transcriptional regulation in R.

SUMMARY: We present sismonr, an R package for an integral generation and simulation of in silico biological systems. The package generates gene regulatory networks, which include protein-coding and non-coding genes along with different transcriptional and post-transcriptional regulations. The effect of genetic mutations on the system behaviour is accounted for via the simulation of genetically different in silico individuals. The ploidy of the system is not restricted to the usual haploid or diploid situations but can be defined by the user to higher ploidies. A choice of stochastic simulation algorithms allows us to simulate the expression profiles of the genes in the in silico system. We illustrate the use of sismonr by simulating the anthocyanin biosynthesis regulation pathway for three genetically distinct in silico plants. AVAILABILITY AND IMPLEMENTATION: The sismonr package is implemented in R and Julia and is publicly available on the CRAN repository (https://CRAN.R-project.org/package=sismonr). A detailed tutorial is available from GitHub at https://oliviaab.github.io/sismonr/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Tuber transcriptome profiling of eight potato cultivars with different cold-induced sweetening responses to cold storage.

Tubers are vegetative reproduction organs formed from underground extensions of the plant stem. Potato tubers are harvested and stored for months. Storage under cold temperatures of 2-4 °C is advantageous for supressing sprouting and diseases. However, development of reducing sugars can occur with cold storage through a process called cold-induced sweetening (CIS). CIS is undesirable as it leads to darkened color with fry processing. The purpose of the current study was to find differences in biological responses in eight cultivars with variation in CIS resistance. Transcriptome sequencing was done on tubers before and after cold storage and three approaches were taken for gene expression analysis: 1. Gene expression correlated with end-point glucose after cold storage, 2. Gene expression correlated with increased glucose after cold storage (after-before), and 3. Differential gene expression before and after cold storage. Cultivars with high CIS resistance (low glucose after cold) were found to increase expression of an invertase inhibitor gene and genes involved in DNA replication and repair after cold storage. The cultivars with low CIS resistance (high glucose after cold) showed increased expression of genes involved in abiotic stress response, gene expression, protein turnover and the mitochondria. There was a small number of genes with similar expression patterns for all cultivars including genes involved in cell wall strengthening and phospholipases. It is proposed that the pattern of gene expression is related to chilling-induced DNA damage repair and cold acclimation and that genetic variation in these processes are related to CIS.

Molecular Characterisation of a Supergene Conditioning Super-High Vitamin C in Kiwifruit Hybrids.

During analysis of kiwifruit derived from hybrids between the high vitamin C (ascorbic acid; AsA) species Actinidia eriantha and A. chinensis, we observed bimodal segregation of fruit AsA concentration suggesting major gene segregation. To test this hypothesis, we performed whole-genome sequencing on pools of hybrid genotypes with either high or low AsA fruit. Pool-GWAS (genome-wide association study) revealed a single Quantitative Trait Locus (QTL) spanning more than 5 Mbp on chromosome 26, which we denote as qAsA26.1. A co-dominant PCR marker was used to validate this association in four diploid (A. chinensis × A. eriantha) × A. chinensis backcross families, showing that the A. eriantha allele at this locus increases fruit AsA levels by 250 mg/100 g fresh weight. Inspection of genome composition and recombination in other A. chinensis genetic maps confirmed that the qAsA26.1 region bears hallmarks of suppressed recombination. The molecular fingerprint of this locus was examined in leaves of backcross validation families by RNA sequencing (RNASEQ). This confirmed strong allelic expression bias across this region as well as differential expression of transcripts on other chromosomes. This evidence suggests that the region harbouring qAsA26.1 constitutes a supergene, which may condition multiple pleiotropic effects on metabolism.

TriPoly: haplotype estimation for polyploids using sequencing data of related individuals.

Motivation: Knowledge of haplotypes, i.e. phased and ordered marker alleles on a chromosome, is essential to answer many questions in genetics and genomics. By generating short pieces of DNA sequence, high-throughput modern sequencing technologies make estimation of haplotypes possible for single individuals. In polyploids, however, haplotype estimation methods usually require deep coverage to achieve sufficient accuracy. This often renders sequencing-based approaches too costly to be applied to large populations needed in studies of Quantitative Trait Loci. Results: We propose a novel haplotype estimation method for polyploids, TriPoly, that combines sequencing data with Mendelian inheritance rules to infer haplotypes in parent-offspring trios. Using realistic simulations of both short and long-read sequencing data for banana (Musa acuminata) and potato (Solanum tuberosum) trios, we show that TriPoly yields more accurate progeny haplotypes at low coverages compared to existing methods that work on single individuals. We also apply TriPoly to phase Single Nucleotide Polymorphisms on chromosome 5 for a family of tetraploid potato with 2 parents and 37 offspring sequenced with an RNA capture approach. We show that TriPoly haplotype estimates differ from those of the other methods mainly in regions with imperfect sequencing or mapping difficulties, as it does not rely solely on sequence reads and aims to avoid phasings that are not likely to have been passed from the parents to the offspring. Availability and implementation: TriPoly has been implemented in Python 3.5.2 (also compatible with Python 2.7.3 and higher) and can be freely downloaded at https://github.com/EhsanMotazedi/TriPoly. Supplementary information: Supplementary data are available at Bioinformatics online.

Genomic Selection for Ascochyta Blight Resistance in Pea.

Genomic selection (GS) is a breeding tool, which is rapidly gaining popularity for plant breeding, particularly for traits that are difficult to measure. One such trait is ascochyta blight resistance in pea (Pisum sativum L.), which is difficult to assay because it is strongly influenced by the environment and depends on the natural occurrence of multiple pathogens. Here we report a study of the efficacy of GS for predicting ascochyta blight resistance in pea, as represented by ascochyta blight disease score (ASC), and using nucleotide polymorphism data acquired through genotyping-by-sequencing. The effects on prediction accuracy of different GS models and different thresholds for missing genotypic data (which modified the number of single nucleotide polymorphisms used in the analysis) were compared using cross-validation. Additionally, the inclusion of marker × environment interactions in a genomic best linear unbiased prediction (GBLUP) model was evaluated. Finally, different ways of combining trait data from two field trials using bivariate, spatial, and single-stage analyses were compared to results obtained using a mean value. The best prediction accuracy achieved for ASC was 0.56, obtained using GBLUP analysis with a mean value for ASC and data quality threshold of 70% (i.e., missing SNP data in <30% of lines). GBLUP and Bayesian Reproducing kernel Hilbert spaces regression (RKHS) performed slightly better than the other models trialed, whereas different missing data thresholds made minimal differences to prediction accuracy. The prediction accuracies of individual, randomly selected, testing/training partitions were highly variable, highlighting the effect that the choice of training population has on prediction accuracy. The inclusion of marker × environment interactions did not increase the prediction accuracy for lines which had not been phenotyped, but did improve the results of prediction across environments. GS is potentially useful for pea breeding programs pursuing ascochyta blight resistance, both for predicting breeding values for lines that have not been phenotyped, and for providing enhanced estimated breeding values for lines for which trait data is available.

Kiwifruit SVP2 controls developmental and drought-stress pathways.

KEY MESSAGE: Genome-wide targets of Actinidia chinensis SVP2 confirm roles in ABA- and dehydration-mediated growth repression and reveal a conservation in mechanism of action between SVP genes of taxonomically distant Arabidopsis and a woody perennial kiwifruit. The molecular mechanisms underlying growth and dormancy in woody perennials are largely unknown. In Arabidopsis, the MADS-box transcription factor SHORT VEGETATIVE PHASE (SVP) plays a key role in the progression from vegetative to floral development, and in woody perennials SVP-like genes are also proposed to be involved in controlling dormancy. During kiwifruit development SVP2 has a role in growth inhibition, with high-chill kiwifruit Actinidia deliciosa transgenic lines overexpressing SVP2 showing suppressed bud outgrowth. Transcriptomic analyses of these plants suggests that SVP2 mimics the well-documented abscisic acid (ABA) effect on the plant dehydration response. To corroborate the growth inhibition role of SVP2 in kiwifruit development at the molecular level, we analysed the genome-wide direct targets of SVP2 using chromatin immunoprecipitation followed by high-throughput sequencing in kiwifruit A. chinensis. SVP2 was found to bind to at least 297 target sites in the kiwifruit genome, and potentially modulates 252 genes that function in a range of biological processes, especially those involved in repressing meristem activity and ABA-mediated dehydration pathways. In addition, our ChIP-seq analysis reveals remarkable conservation in mechanism of action between SVP genes of taxonomically distant plant species.

When Men Grieve: Widowers' Stories of Coping With Their Wives' Deaths.

To increase our understanding of the role gender plays in spousal loss, this qualitative study analyzes bereavement narratives of 33 recent widowers, aged 45-89 years, all of whom accessed the National Widowers' Organization website. In particular, we look at how these widowers' lives changed, the impact of changing gender norms, and coping strategies. To illuminate the temporal process evident in these narratives, we utilize Silverman's nonlinear characteristics of bereavement and the anthropological concept of liminality. In contrast to studies of widowers in earlier decades, our analysis reveals questioning and rejection of stereotypical masculine gender norms, a wide variety of creative responses to spousal loss, and the need for individualized support.

Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats.

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.

Cerebral Small Vessel Disease Burden Is Increased in Systemic Lupus Erythematosus.

BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) increases stroke risk, but the mechanism is uncertain. This study aimed to determine the association between SLE and features on neuroimaging of cerebral small vessel disease (SVD), a risk factor for stroke. METHODS: Consecutive patients attending a clinic for SLE were recruited. All patients underwent brain magnetic resonance imaging; had blood samples taken for markers of inflammation, endothelial dysfunction, cholesterol, and autoantibodies; and underwent cognitive and psychiatric testing. The data were compared with sex- and age-matched healthy controls and patients with minor stroke. Features of SVD were measured, a total SVD score calculated, and associations sought with vascular risk factors, cognition, SLE activity, and disease duration. RESULTS: Fifty-one SLE patients (age: 48.8 years; SD: 14.3 years) had a greater total SVD score compared with healthy controls (1 versus 0; P<0.0001) and stroke patients (1 versus 0; P=0.02). There were higher perivascular spaces and deep white matter hyperintensity scores and more superficial brain atrophy in SLE patients versus healthy controls. Despite fewer vascular risk factors than similarly aged stroke patients, SLE patients had similar or more of some SVD features. The total SVD score was not associated with SLE activity, cognition, disease duration, or any blood measure. CONCLUSIONS: In this data set, SLE patients had a high burden of SVD features on magnetic resonance imaging, particularly perivascular spaces. A larger longitudinal study is warranted to determine the causes of SVD features in SLE and clinical implications.

Drag-Reducing Polymer Enhances Microvascular Perfusion in the Traumatized Brain with Intracranial Hypertension.

Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood-soluble, nontoxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and ischemic limb, but have not yet been studied in the brain. We recently demonstrated that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using in vivo two-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow, and, as a result, reduced tissue hypoxia in both nontraumatized and traumatized rat brains at high intracranial pressure. Our study suggests that DRP could constitute an effective treatment for improving microvascular flow in brain ischemia caused by high intracranial pressure after TBI.