A structural basis for selection and cross-species reactivity of the semi-invariant NKT cell receptor in CD1d/glycolipid recognition

Little is known regarding the basis for selection of the semi-invariant alphabeta T cell receptor (TCR) expressed by natural killer T (NKT) cells or how this mediates recognition of CD1d-glycolipid complexes. We have determined the structures of two human NKT TCRs that differ in their CDR3beta composition and length. Both TCRs contain a conserved, positively charged pocket at the ligand interface that is lined by residues from the invariant TCR alpha- and semi-invariant beta-chains. The cavity is centrally located and ideally suited to interact with the exposed glycosyl head group of glycolipid antigens. Sequences common to mouse and human invariant NKT TCRs reveal a contiguous conserved "hot spot" that provides a basis for the reactivity of NKT cells across species. Structural and functional data suggest that the CDR3beta loop provides a plasticity mechanism that accommodates recognition of a variety of glycolipid antigens presented by CD1d. We propose a model of NKT TCR-CD1d-glycolipid interaction in which the invariant CDR3alpha loop is predicted to play a major role in determining the inherent bias toward CD1d. The findings define a structural basis for the selection of the semi-invariant alphabeta TCR and the unique antigen specificity of NKT cells.     

Exit interview-consultation for research validation and dissemination

Dissemination of research findings to practice and maintenance of rigor and validity in qualitative research are continuing challenges for nurse researchers. Using three nursing home case studies as examples, this article describes how exit interview-consultation was used as (a) a validation strategy and (b) a rapid research dissemination tool that is particularly useful for nursing systems research. Through an exit interview-consultation method, researchers validated inferences made from qualitative and quantitative data collected in three comprehensive nursing home case studies that examined nursing management practices. This exit interview-consultation strategy extends the traditional member-check approach by providing confirmation at the individual and organizational level. The study examined how using the exit interview-consultation strategy can potentially assist nursing home organizations to increase their capacity for improving operations. Benefits from research participation are often indirect; this study's results suggest that exit interview-consultation can provide direct and immediate benefits to organizations and individuals.     

Genital findings of women after consensual and nonconsensual intercourse

After a sexual assault, forensic nurses, nurse practitioners, and physicians are called on to collect evidence, document any genital injuries, and testify about the significance of injuries. Recently, the scientific rigor of the research has been challenged in the courts.     

Comparison of effectiveness and safety of drug-eluting stents versus vascular brachytherapy for saphenous vein graft in-stent restenosis

We investigated the safety and efficacy of drug-eluting stents (DESs) for the treatment of patients who presented with in-stent restenosis (ISR) of saphenous vein grafts (SVGs) and compared the in-hospital and 6-month clinical outcomes of DESs with those of intravascular brachytherapy and balloon angioplasty alone. Records of 187 patients who presented with ISR of SVGs were analyzed. Of these, 34 consecutive patients were treated with DES implantation, 93 were treated with intravascular brachytherapy (n = 60 with gamma-radiation, n = 33 with beta-radiation), and 60 patients underwent conventional treatment with balloon angioplasty alone. Clinical and angiographic characteristics at baseline were comparable between groups. The DES group had less non-Q-wave myocardial infarction than did the intravascular brachytherapy and balloon angioplasty groups (0%, 20%, and 26%, p = 0.003 and <0.001, respectively). At 6 months, death occurred in 0% of the DES group, 2% of the intravascular brachytherapy group, and 5% of the balloon angioplasty group (p = 0.36 and <0.18, respectively). Target lesion revascularization/major adverse cardiac events were similar in the intravascular brachytherapy and DES groups (12% and 3%, p = 0.13) and significantly decreased compared with patients who were treated with balloon angioplasty alone (55%, p <0.001 for the 2 comparisons). The results of this retrospective analysis suggest that DES implantation is at least as effective and safe as intravascular brachytherapy for the treatment of SVG ISR and that these treatment modalities are superior to balloon angioplasty alone.     

Lipid profile of patients with increased risk for cardiovascular events in daily clinical practice

Although there are specific guidelines regarding the treatment of dyslipidemia in highly risk patients, these recommendations are usually inadequately followed. The aim of this study is to investigate risk factors in patients with increased cardiovascular risk currently treated in Brazil and Venezuela. Medical charts of 412 patients were selected in 4 institutions. Patients were divided into groups according to the use of lipid-lowering drugs (LLD), particularly statins. Patients who did not use LLD showed higher levels of total cholesterol (p< 0.001), LDL cholesterol (p< 0,001) and HDL cholesterol (p< 0.001), besides lower levels of triglycerides (p< 0.001). The use of statins was associated with a decrease in levels of total cholesterol (from 251.0 +/- 40.0 to 196.0 +/- 46.0), LDL cholesterol (from 168.0 +/- 36.0 to 116.0 +/- 39.0), HDL cholesterol (from 51.0 +/- 46.0 to 46.0 +/- 12.0) and triglycerides (from 181.0 +/- 120.0 to 160.0 +/-79.0). Finally, only a small percentage of patients, even those under treatment with LLD, showed cholesterol levels according to currently available guidelines. Therefore, although the guidelines for the treatment of dyslipidemia are widely known, only a small percentage of patients achieve adequate levels of cholesterol. It is necessary to decrease lipid levels of these patients by increasing the dose of the statins or using a second drug.     

Genetic variation in myosin IXB is associated with ulcerative colitis

BACKGROUND & AIMS: Common germline genetic variation in the 3' region of myosin IXB (MYO9B) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease. METHODS: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3' region of MYO9B. These included the strongest celiac disease-associated variants reported in a Dutch cohort. These SNPs were studied in 3 independently collected and genotyped case-control cohorts of European descent (UK, Dutch, and Canadian/Italian), comprising in total 2717 inflammatory bowel disease patients (1197 with Crohn's disease, 1520 with ulcerative colitis) and 4440 controls. RESULTS: Common variation in MYO9B was associated with susceptibility to inflammatory bowel disease in all 3 cohorts examined (most associated SNP, rs1545620; meta-analysis P = 1.9 x 10(-6); odds ratio, 1.2), with the same alleles showing association as reported for celiac disease. CONCLUSIONS: MYO9B genetic variants predispose to inflammatory bowel disease. Interestingly, rs1545620 is a nonsynonymous variant leading to an amino acid change (Ala1011Ser) in the third calmodulin binding IQ domain of MYO9B. Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MYO9B was considerably stronger with ulcerative colitis, although weaker association with Crohn's disease also was observed. These data imply shared causal mechanisms underlying intestinal inflammatory diseases.     

Mechanism of the Frank-Starling law--a simulation study with a novel cardiac muscle contraction model that includes titin and troponin I

A stretch-induced increase of active tension is one of the most important properties of the heart, known as the Frank-Starling law. Although a variation of myofilament Ca(2+) sensitivity with sarcomere length (SL) change was found to be involved, the underlying molecular mechanisms are not fully clarified. Some recent experimental studies indicate that a reduction of the lattice spacing between thin and thick filaments, through the increase of passive tension caused by the sarcomeric protein titin with an increase in SL within the physiological range, promotes formation of force-generating crossbridges (Xbs). However, the mechanism by which the Xb concentration determines the degree of cooperativity for a given SL has so far evaded experimental elucidation. In this simulation study, a novel, rather simple molecular-based cardiac contraction model, appropriate for integration into a ventricular cell model, was designed, being the first model to introduce experimental data on titin-based radial tension to account for the SL-dependent modulation of the interfilament lattice spacing and to include a conformational change of troponin I (TnI). Simulation results for the isometric twitch contraction time course, the length-tension and the force-[Ca(2+)] relationships are comparable to experimental data. A complete potential Frank-Starling mechanism was analyzed by this simulation study. The SL-dependent modulation of the myosin binding rate through titin's passive tension determines the Xb concentration which then alters the degree of positive cooperativity affecting the rate of the TnI conformation change and causing the Hill coefficient to be SL-dependent.     

Performance of drug-drug interaction software for personal digital assistants

BACKGROUND: Personal digital assistants (PDAs) allow healthcare professionals to check for potential drug-drug interactions (DDIs) at the point of care, reducing the need to consult traditional references. However, PDAs can only be as effective as the software programs they use. OBJECTIVE: To examine the ability of DDI software programs manufactured for Palm OS-compatible PDAs in detecting clinically important DDIs. METHODS: Eight PDA software programs were assessed for sensitivity, specificity, and positive and negative predictive values for 16 well-documented DDIs contained within 6 simulated patient profiles. RESULTS: Sensitivity of the software programs ranged from 0.81 to 1.0, specificity ranged from 0.52 to 1.0, positive predictive values ranged from 0.62 to 1.0, and negative predictive values ranged from 0.88 to 1.0. Five programs scored perfect sensitivity scores: DrugIx, ePocrates Rx, ePocrates Rx Pro, Lexi-Interact, and the Tarascon pocket Pharmacopoeia. Of these, the ePocrates programs scored the highest in specificity (0.9), while Lexi-Interact and the Tarascon pocket Pharmacopoeia scored considerably lower (0.52). MosbyIx was the only program to score a 1.0 in specificity; however, its sensitivity was just 0.81. CONCLUSIONS: ePocrates Rx and ePocrates Rx Pro scored greater than or equal to 90% in regard to both sensitivity and specificity, making them the most reliable in detecting the clinically relevant interactions studied without the distraction of detecting those of no clinical significance. In addition, ePocrates Rx is updated regularly and is easily accessible on the Internet at no cost.     

The relationship between patella position and length of the iliotibial band as assessed using Ober's test

The purpose of the study was to investigate the relationship between length of the iliotibial band (ITB) and the medio-lateral position patella. Eighty subjects (37 male, 43 female) were examined for patella position and ITB length. All subjects were physically active, asymptomatic and aged between 18 and 34 years (mean 21.5 years). ITB length was assessed using the Ober's test and modified Ober's test, with hip adduction angle being measured using a fluid goniometer. Patella position was assessed using the method first described by McConnell [The management of chondromalacia patellae: a long term solution. Australian Journal of Physiotherapy 1986;32:215-22]. Patella position had a weak correlation (r=0.28) with modified Ober's (extended knee) test and a poor correlation with Ober's (knee flexed) test (r=0.1). In the group of 47 subjects with laterally displaced patellae, patella position had a moderate statistically significant correlation to ITB length measured by modified Ober's test (r=0.34, P=0.012). Only a poor relationship existed between Ober's test and patella position in the laterally displaced group. The results of this study only partially support the hypothesis that there is a relationship between ITB length and lateral patella displacement. The relationship was not strong enough to confirm ITB length as the only cause of lateral patella displacement.