Diagnostic value of d-dimer in patients with a moderate pretest probability of deep venous thrombosis

The negative predictive value (NPV) of d-dimer (DD) for the exclusion of venous thromboembolism is, overall, high and tends to increase as clinical pretest probability decreases. We have assessed the accuracy of a diagnostic protocol including clinical evaluation and DD in 134 outpatients presenting with a moderate pretest probability of proximal deep venous thrombosis (DVT). In these patients, a negative DD value safely excluded DVT (NPV 100%, 95% CI 85-100) In our experience, these results are equivalent to those found for low-pretest probability patients and therefore the same diagnostic strategy can be used for both risk groups.     

Serum uric acid correlates with extracellular superoxide dismutase activity in patients with chronic heart failure

Increased serum uric acid has been identified as an independent risk factor for cardiovascular disease. However, because of its antioxidant capacity, uric acid may play a beneficial role in endothelial function. This paradoxical relationship between uric acid and endothelial function in chronic heart failure patients remains poorly understood. Thirty-eight chronic heart failure patients (New York Heart Association functional class II-III, mean age 58+/-10 years and mean left ventricular ejection fraction 25+/-8%) and twelve age-and-sex-matched healthy controls were studied. Chronic heart failure patients showed higher uric acid levels (7.3+/-2.3 mg/dL vs. 6.1+/-0.2 mg/dL, p<0.05) and lower extracellular superoxide dismutase activity (136+/-36 U ml(-1) min(-1) vs. 203+/-61 U ml(-1) min(-1), p<0.01) and endothelium-dependent vasodilatation (4.0+/-1.6% v. 9.1+/-3.0%, p<0.01) when compared with control subjects. In chronic heart failure patients, correlations between both uric acid levels and extracellular superoxide dismutase activity (r=0.45; p<0.01), and uric acid and endothelium-dependent vasodilatation (r=0.35; p=0.03) were detected. These correlations were not observed in healthy individuals, suggesting a positive effect of uric acid on endothelial function partially mediated by modulation of extracellular superoxide dismutase activity in chronic heart failure.     

Limited Variation in BK Virus T-Cell Epitopes Revealed by Next-Generation Sequencing

BK virus (BKV) infection causing end-organ disease remains a formidable challenge to the hematopoietic cell transplant (HCT) and kidney transplant fields. As BKV-specific treatments are limited, immunologic-based therapies may be a promising and novel therapeutic option for transplant recipients with persistent BKV infection. Here, we describe a whole-genome, deep-sequencing methodology and bioinformatics pipeline that identify BKV variants across the genome and at BKV-specific HLA-A2-, HLA-B0702-, and HLA-B08-restricted CD8 T-cell epitopes. BKV whole genomes were amplified using long-range PCR with four inverse primer sets, and fragmentation libraries were sequenced on the Ion Torrent Personal Genome Machine (PGM). An error model and variant-calling algorithm were developed to accurately identify rare variants. A total of 65 samples from 18 pediatric HCT and kidney recipients with quantifiable BKV DNAemia underwent whole-genome sequencing. Limited genetic variation was observed. The median number of amino acid variants identified per sample was 8 (range, 2 to 37; interquartile range, 10), with the majority of variants (77%) detected at a frequency of <5%. When normalized for length, there was no statistical difference in the median number of variants across all genes. Similarly, the predominant virus population within samples harbored T-cell epitopes similar to the reference BKV strain that was matched for the BKV genotype. Despite the conservation of epitopes, low-level variants in T-cell epitopes were detected in 77.7% (14/18) of patients. Understanding epitope variation across the whole genome provides insight into the virus-immune interface and may help guide the development of protocols for novel immunologic-based therapies.     

Factors That Contribute or Impede the Physical Health Recovery of Women Exposed to Intimate Partner Violence: A Longitudinal Study

BackgroundSeveral cross-sectional studies have demonstrated the negative impact that intimate partner violence (IPV) has on the physical health of women. However, longitudinal studies are needed to establish the time course of this effect. This study assessed the physical health course of female IPV victims and established the factors that enhance or impede their recovery.MethodsWomen (n = 91) who participated in a previous cross-sectional study (T-1) and were either victims of physical/psychological IPV (n = 33) or psychological IPV (n = 23) were evaluated 3 years later (T-2). A control group of women (n = 35) was included for comparison. Structured interviews provided information regarding IPV characteristics, physical health, and lifestyle.FindingsPhysical symptoms decreased over time for both groups of abused women. Factors that contributed to this improvement were perception of social support and the cessation of physical IPV. Factors that impaired recovery included cohabitation with the aggressor, victimization experiences at T-2, negative perceptions of life events, and continuing psychological IPV.ConclusionsThis study shows that physical health improvement is possible in female victims of IPV, but that continuing psychological IPV hinders recovery. Additional longitudinal studies are needed to investigate the factors that best predict health recovery in female IPV victims to design effective intervention programs.     

Development and Use of an Evaluation Tool for Taste-Testing Activities by School-Aged Children

We describe the development and application of a teacher-administered tool for routine program evaluation of food-tasting activities among low-income children and adolescents in a classroom or afterschool setting. This six-item evaluation tool is intended to capture student willingness to try new foods and ask for them at home. Phase 1 involved one-on-one interviews to determine the feasibility of the taste test tool among nine elementary school teachers in 2009 (168 students) and a validation pilot study in 2010 among 114 school-aged students participating in a University of California Supplemental Nutrition Assistance Program Nutrition Education (UC SNAP-Ed) summer program. Phase 2 determined instrument reliability and compared student response by grade level and food category in a convenience sample of 514 UC SNAP-Ed classrooms in 2010-2011. The mean proportion of the classroom ever having tried the foods before was 0.62±0.33, and 0.77±0.27 were willing to ask for the foods at home (P<0.0001). Compared with younger students (preschool through sixth grade), older students (seventh through 12th grade) were less likely to try the foods in class and less willing to try them again or ask for them at home (P<0.05). Students reported significantly greater previous exposure and willingness to try the food again for fruits than for vegetables (P<0.0001). A teacher-administered taste test tool is feasible to use in a group setting and capable of yielding valid, reliable information to evaluate student response and to guide SNAP-Ed program delivery.     

The ketogenic diet increases mitochondrial uncoupling protein levels and activity

Fatty acids are known to enhance mitochondrial uncoupling protein (UCP) activity. We asked whether a high-fat ketogenic diet (KD) increases UCP levels and activity in hippocampi of juvenile mice. Maximum mitochondrial respiration rates were significantly (p < 0.001) higher in KD- versus standard diet (SD)-treated animals, indicating increased UCP-mediated proton conductance that can reduce reactive oxygen species (ROS) production. Western blots showed significant (p < 0.05) or borderline significant increases in UCP2, UCP4, and UCP5 protein levels, and increased immunoreactivity to these three UCP isoforms was most prominently seen in the dentate gyrus of KD-fed mice. Finally, we found that oligomycin-induced ROS production was significantly (p < 0.05) lower in KD-fed mice than in SD controls. Collectively, our data suggest that a KD may exert neuroprotective effects by diminishing ROS production through activation of mitochondrial UCPs.     

Epidural morphine provides postoperative pain relief in peripheral vascular and orthopedic surgical patients: a dose-response study

A randomized double-blind study compared the dose-response relationship of epidural morphine for postoperative pain relief in two groups of patients whose surgical procedures would result in either moderate (femoral-popliteal bypass) or severe (total knee replacement) postoperative pain. Preservative-free morphine sulphate in doses of 0, 2, 5, or 10 mg in a volume of 10 ml saline were administered via lumbar epidural catheters. The epidural morphine was administered 1 hr after the last dose of intraoperative local epidural anesthetic in an effort to achieve a pain-free postoperative course. A significant relationship existed between the dose of epidural morphine and both time to first required pain medication and 24-hr weighted pain score. Five mg epidural morphine provided significant improvement in postoperative analgesia compared with the control in both groups. Further enhancement of analgesia occurred with 10 mg; however, late respiratory depression, demonstrated by an increased resting PaCO2 10 hr after administration, was seen only with the 10-mg dose in both surgical groups. Minor complications such as nausea, vomiting, pruritus, and urinary retention were uncommon and did not appear to be related to dose. We found that 5 mg epidural morphine provided long-lasting postoperative analgesia without serious adverse effects after peripheral vascular and orthopedic surgery.     

Dissecting genetic heterogeneity in autoimmune thyroid diseases by subset analysis

Abundant epidemiological data point to a strong genetic susceptibility to the development of autoimmune thyroid diseases (AITD), Graves' disease (GD) and Hashimoto's thyroiditis (HT). However, identifying the AITD susceptibility genes has been confounded by significant genetic heterogeneity that exists in AITD. The goals of the present study were to dissect the genetic heterogeneity in AITD in order to identify novel AITD genes. We studied a dataset of 102 multiplex Caucasian AITD families (540 individuals) and divided them into three subsets: (1) families with young age of onset (AO< or =30), (2) families with females-only affected, and (3) Italian families. These subsets were analyzed separately for linkage with AITD in a whole genome screen. Four subset-specific loci were mapped: analyzing the families with AO< or =30, we identified a locus on 10q (linked with AITD) and a locus on Xp containing the FOXP3 gene (linked with GD); analysis of markers flanking the FOXP3 gene demonstrated association of one of the FOXP3 markers with juvenile GD in females (p=0.02); in the subset of families with females-only affected the thyroglobulin (Tg) gene locus was linked with AITD; and in the Italian subset, a novel locus on 3q was linked with GD. Finally, applying the predivided-sample test confirmed that all four loci were specific to the subsets. We conclude that distinct genes predispose to AITD in different subsets of patients. We have identified four subset-specific AITD loci, and two putative subset-specific AITD susceptibility genes; the FOXP3 gene in juvenile GD and the thyroglobulin gene in females with AITD. In view of the significant genetic heterogeneity observed in AITD, analyzing subsets is an efficient way to resolve heterogeneity and identify novel genes.