Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

Background The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. Methods This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. Results A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with <70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and <20% in 84 patients. Conclusion Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone. Copyright © 2010 by the Society for Vascular Surgery

The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke

Objective: To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. Methods: A JBA was defined as an area of pixels with a grayscale value &lt;25 adjacent to the lumen without a visible echogenic cap after image normalization. The size of a JBA was measured in the carotid plaque images of 1121 patients with asymptomatic carotid stenosis 50% to 99% in relation to the bulb (Asymptomatic Carotid Stenosis and Risk of Stroke study); the patients were followed for up to 8 years. Results: The JBA had a linear association with future stroke rate. The area under the receiver-operating characteristic curve was 0.816. Using Kaplan-Meier curves, the mean annual stroke rate was 0.4% in 706 patients with a JBA &lt;4 mm 2, 1.4% in 171 patients with a JBA 4 to 8 mm2, 3.2% in 46 patients with a JBA 8 to 10 mm2, and 5% in 198 patients with a JBA &gt;10 mm2 (P &lt;.001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (&lt;4 mm2, 4-8 mm2, &gt;8 mm2) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was &lt;1% in 734 patients, 1% to 1.9% in 94 patients, 2% to 3.9% in 134 patients, 4% to 5.9% in 125 patients, and 6% to 10% in 34 patients. Conclusions: The size of a JBA is linearly related to the risk of stroke and can be used in risk stratification models. These findings need to be confirmed in future prospective studies or in the medical arm of randomized controlled studies in the presence of optimal medical therapy. In the meantime, the JBA may be used to select asymptomatic patients at high stroke risk for carotid endarterectomy and spare patients at low risk from an unnecessary operation

Preferential Occupancy of R2 Retroelements on the B Chromosomes of the Grasshopper Eyprepocnemis plorans

R2 non-LTR retrotransposons exclusively insert into the 28S rRNA genes of their host, and are expressed by co-transcription with the rDNA unit. The grasshopper Eyprepocnemis plorans contains transcribed rDNA clusters on most of its A chromosomes, as well as non-transcribed rDNA clusters on the parasitic B chromosomes found in many populations. Here the structure of the E. plorans R2 element, its abundance relative to the number of rDNA units and its retrotransposition activity were determined. Animals screened from five populations contained on average over 12,000 rDNA units on their A chromosomes, but surprisingly only about 100 R2 elements. Monitoring the patterns of R2 insertions in individuals from these populations revealed only low levels of retrotransposition. The low rates of R2 insertion observed in E. plorans differ from the high levels of R2 insertion previously observed in insect species that have many fewer rDNA units. It is proposed that high levels of R2 are strongly selected against in E. plorans, because the rDNA transcription machinery in this species is unable to differentiate between R2-inserted and uninserted units. The B chromosomes of E. plorans contain an additional 7,000 to 15,000 rDNA units, but in contrast to the A chromosomes, from 150 to over 1,500 R2 elements. The higher concentration of R2 in the inactive B chromosomes rDNA clusters suggests these chromosomes can act as a sink for R2 insertions thus further reducing the level of insertions on the A chromosomes. These studies suggest an interesting evolutionary relationship between the parasitic B chromosomes and R2 elements.This study was supported by grants from the Spanish Ministerio de Ciencia y Tecnología (CGL2009-11917) and Plan Andaluz de Investigacion (CVI-6649), and was partially performed by FEDER funds and a grant from the National Institutes of Health (GM42790)

28S junctions and chimeric elements of the rDNA targeting non-LTR retrotransposon R2 in crustacean living fossils (Branchiopoda, Notostraca).

The 28S rRNA genes of several metazoans are interrupted by site-specific targeting non-LTR retrotransposons, such as R2. R2 elements have been deeply analyzed but aspects of their retrotransposition mechanism and the origin of the wide diversity observed are still debated. We characterized six new R2 lineages in four tadpole shrimp species (Notostraca), samples deriving from a parthenogenetic population of Triops cancriformis (R2Tc_it) and from bisexual Lepidurus populations of L. lubbocki (R2Ll), L. couesii (R2LcA, R2LcB, R2LcC) and L. arcticus (R2La). All elements fit the canonical R2 structure but R2Ll which turned out to be a chimera with an additional ORF originating from another R2. Consistently with data on LINEs, R2Ll could be the result of recombination due to reverse transcriptase template jump. The analysis of 28S/R2 5' end junctions further suggests aberrant homologous recombination, as observed in RNA viruses

R2 dynamics in Triops cancriformis (Bosc, 1801) (Crustacea, Branchiopoda, Notostraca): turnover rate and 28S concerted evolution

The R2 retrotransposon is here characterized in bisexual populations of the European crustacean Triops cancriformis. The isolated element matches well with the general aspects of the R2 family and it is highly differentiated from that of the congeneric North American Triops longicaudatus. The analysis of 5′ truncations indicates that R2 dynamics in T. cancriformis populations show a high turnover rate as observed in Drosophila simulans. For the first time in the literature, though, individuals harboring truncation variants, but lacking the complete element, are found. Present results suggest that transposition-mediated deletion mechanisms, possibly involving genomic turnover processes acting on rDNAs, can dramatically decrease the copy number or even delete R2 from the ribosomal locus. The presence of R2 does not seem to impact on the nucleotide variation of inserted 28S rDNA with respect to the uninserted genes. On the other hand, a low level of polymorphism characterizes rDNA units because new 28S variants continuously spread across the ribosomal array. Again, the interplay between transposition-mediated deletion and molecular drive may explain this pattern

Genome-wide study on intramuscular fat in Italian Large White pig breed using the 4 PorcineSNP60 BeadChip

Genome-wide association study results are presented for intramuscular fat in Italian Large White pig breed. 886 individuals were genotyped with PorcineSNP60 BeadChip. After quality control performed with Plink software and in R environment, 49,208 markers remained for the association 22 analysis. The GWAS was conducted using linear mixed model implemented in GenABEL. We detected 7 new SNPs of genes till now not found associated to IMF. Three markers map in a wide intergenic region rich of QTL linked to fat traits, one map 388 kb upstream gene SDK1, one map inside PPP3CA gene, one inside SCPEP1 gene and the last is not mapped in the porcine genome yet. Associations here presented indicate a moderate effect of these genes on IMF. In particular PPP3CA, that is involved in the oxidative metabolism of skeletal muscle, could be considerate as an interesting candidate gene for IMF content in pigs. However further studies are needed to clarify the role of these genes on the physiological processes involved in IMF regulation. These results may be useful to control this trait that is important in terms of nutritional, technological and organoleptic characteristics of fresh meat and processed products

Evaluation of CD44 variant 6 expression and clinicopathological factors in pulmonary metastases from colon carcinoma.

Although relatively little is known about the molecular mechanisms underlying tumor progression, recently CD44 glycoproteins and the c-Met receptor tyrosine kinase have been identified as potentially important components of the metastatic cascade. CD44 is a family of transmembrane receptors generated from a single gene by alternative splicing and differential glycosylation. Important biological processes involving CD44 glycoproteins include cell adhesion, lymphocyte homing, hematopoiesis, tumor progression and metastasis. The precise mechanism via which CD44 promotes tumorigenesis have not yet been elucidated. We evaluated the expression of adhesion molecule CD44 variant 6 in pulmonary metastases from colorectal carcinomas and its correlation with clinicopathological parameters. Twenty patients were randomly selected from the patients who had undergone a resection of pulmonary metastasis from colorectal cancer. Formalin-fixed, paraffin-embedded archival specimens of tumor tissues and adjacent normal mucosa from these patients were the subjects of the present study. Immunoreactivity for CD44 was quantified. Specimens were considered positive if almost 25% of the neoplastic cells were stained. CD44 v6 expression was related to the interval between colon resection and metastases diagnosis, the number of pulmonary metastases, and the survival after lung resection. No statistical correlation was found between CD44 v6 positivity and disease-free interval after colon resection, number of metastases or 2-year survival after lung resection. Probably CD44 v6 is necessary and sufficient to confer metastatic potential to carcinoma cells increasing the migration capacity and participating in invasion via changes in adhesion to the extracellular ligands, but is not necessary to modify the clinical history of the metastases. Therefore the evaluation of CD44 v6 expression in lung metastases does not influence the therapeutic scheme

Ectopic liver encountered during laparoscopic cholecystectomy: importance of this rare entity.

The ectopic liver (or choristoma) is a rare condition found during autopsy or abdominal exploration for various indications. The authors report two cases of ectopic liver found during laparoscopic cholecystectomy for acute cholestytis. The ectopic liver tissue has been reported to develop in several sites as thoracic cavity, gastrohepatic ligament, adrenal glands, pancreas, esophagus and, above all, gallbladder. The Authors review the literature and report their experience as a contribution to the knowledge of this rare pathological entity