Early diagnosis of acute coronary syndrome.

The diagnostic evaluation of acute chest pain has been augmented in recent years by advances in the sensitivity and precision of cardiac troponin assays, new biomarkers, improvements in imaging modalities, and release of new clinical decision algorithms. This progress has enabled physicians to diagnose or rule-out acute myocardial infarction earlier after the initial patient presentation, usually in emergency department settings, which may facilitate prompt initiation of evidence-based treatments, investigation of alternative diagnoses for chest pain, or discharge, and permit better utilization of healthcare resources. A non-trivial proportion of patients fall in an indeterminate category according to rule-out algorithms, and minimal evidence-based guidance exists for the optimal evaluation, monitoring, and treatment of these patients. The Cardiovascular Round Table of the ESC proposes approaches for the optimal application of early strategies in clinical practice to improve patient care following the review of recent advances in the early diagnosis of acute coronary syndrome. The following specific 'indeterminate' patient categories were considered: (i) patients with symptoms and high-sensitivity cardiac troponin 99th percentile but without dynamic change; and (iv) patients with symptoms and high-sensitivity troponin >99th percentile and dynamic change but without coronary plaque rupture/erosion/dissection. Definitive evidence is currently lacking to manage these patients whose early diagnosis is 'indeterminate' and these areas of uncertainty should be assigned a high priority for research

Increased blood product use among coronary artery bypass patients prescribed preoperative aspirin and clopidogrel

BACKGROUND: The administration of antiplatelet drugs before coronary artery bypass graft surgery (CABG) is associated with an increased risk of major hemorrhage and related surgical reexploration. Little is known about the relative effect of combined clopidogrel and aspirin on blood product use around the time of CABG. We evaluated the associated risk between the combined use of aspirin and clopidogrel and the transfusion of blood products perioperatively. METHODS: We retrospectively studied a cohort of 659 individuals who underwent a first CABG, without concomitant valvular or aortic surgery, at a single large Canadian cardiac surgical centre between January 2000 and April 2002. The four study exposure groups were those prescribed aspirin (n = 105), clopidogrel (n = 11), the combination of both (n = 46), or neither drug (n = 497), within 7 days prior to CABG. The primary study outcome was the excessive transfusion of blood products during CABG and up to the second post-operative day, defined as ≥ 2 units of packed red blood cells (PRBC), ≥ 2 units of fresh frozen plasma, ≥ 5 units of cryoprecipitate or ≥ 5 units of platelets. Secondary outcomes included the mean number of transfused units of each type of blood product. RESULTS: A greater mean number of units of PRBC were transfused among those who received clopidogrel alone (2.9) or in combination with aspirin (2.4), compared to those on aspirin alone (1.9) or neither antiplatelet drug (1.4) (P = 0.001). A similar trend was seen for the respective mean number of transfused units of platelets (3.6, 3.7, 1.3 and 1.0; P < 0.001) and fresh frozen plasma (2.5, 3.1, 2.3, 1.6; P = 0.01). Compared to non-users, the associated risk of excessive blood product transfusion was highest among recipients of aspirin and clopidogrel together (adjusted OR 2.2, 95% CI 1.1–4.3). No significant association was seen among lone users of aspirin (adjusted OR 1.0, 95% CI 0.6–1.6) or clopidogrel (adjusted OR 0.7, 95% CI 0.2–2.5), compared to non-users. CONCLUSIONS: While combined use of aspirin and clopidogrel shortly before CABG surgery may increase the associated risk of excess transfusion of blood products perioperatively, several study limitations prevent any confident conclusions from being drawn. Beyond challenging these findings, future research might focus on the value of both intraoperative monitoring of platelet function, and the effectiveness of antifibrinolytic agents, at reducing the risk of postoperative bleeding

Phylogeny and Classification of the Trapdoor Spider Genus Myrmekiaphila: An Integrative Approach to Evaluating Taxonomic Hypotheses

Background: Revised by Bond and Platnick in 2007, the trapdoor spider genus Myrmekiaphila comprises 11 species. Species delimitation and placement within one of three species groups was based on modifications of the male copulatory device. Because a phylogeny of the group was not available these species groups might not represent monophyletic lineages; species definitions likewise were untested hypotheses. The purpose of this study is to reconstruct the phylogeny of Myrmekiaphila species using molecular data to formally test the delimitation of species and species-groups. We seek to refine a set of established systematic hypotheses by integrating across molecular and morphological data sets. Methods and Findings: Phylogenetic analyses comprising Bayesian searches were conducted for a mtDNA matrix composed of contiguous 12S rRNA, tRNA-val, and 16S rRNA genes and a nuclear DNA matrix comprising the glutamyl and prolyl tRNA synthetase gene each consisting of 1348 and 481 bp, respectively. Separate analyses of the mitochondrial and nuclear genome data and a concatenated data set yield M. torreya and M. millerae paraphyletic with respect to M. coreyi and M. howelli and polyphyletic fluviatilis and foliata species groups. Conclusions: Despite the perception that molecular data present a solution to a crisis in taxonomy, studies like this demonstrate the efficacy of an approach that considers data from multiple sources. A DNA barcoding approach during the species discovery process would fail to recognize at least two species (M. coreyi and M. howelli) whereas a combine

Search for High Mass Photon Pairs in p-pbar --> gamma-gamma-jet-jet Events at sqrt(s)=1.8 TeV

A search has been carried out for events in the channel p-barp --> gamma gamma jet jet. Such a signature can characterize the production of a non-standard Higgs boson together with a W or Z boson. We refer to this non-standard Higgs, having standard model couplings to vector bosons but no coupling to fermions, as a "bosonic Higgs." With the requirement of two high transverse energy photons and two jets, the diphoton mass (m(gamma gamma)) distribution is consistent with expected background. A 90(95)% C.L. upper limit on the cross section as a function of mass is calculated, ranging from 0.60(0.80) pb for m(gamma gamma) = 65 GeV/c^2 to 0.26(0.34) pb for m(gamma gamma) = 150 GeV/c^2, corresponding to a 95% C.L. lower limit on the mass of a bosonic Higgs of 78.5 GeV/c^2.Comment: 9 pages, 3 figures. Replacement has new H->gamma gamma branching ratios and corresponding new mass limit

Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Despite extensive research, the five-year survival rate of oral squamous cell carcinoma (OSCC) patients has not improved. Effective treatment of OSCC requires the identification of molecular targets and signaling pathways to design appropriate therapeutic strategies. Several genes from the mTOR signaling pathway are known to be dysregulated in a wide spectrum of cancers. However, not much is known about the involvement of this pathway in tumorigenesis of OSCC. We therefore investigated the role of the tumor suppressor genes, <it>TSC1 </it>and <it>TSC2</it>, and other members of this pathway in tumorigenesis of OSCC.</p> <p>Methods</p> <p>Expression of genes at the RNA and protein levels was examined by semi-quantitative RT-PCR and western blot analyses, respectively. Loss of heterozygosity was studied using matched blood and tumor DNA samples and microsatellite markers from the <it>TSC1</it>, <it>TSC2 </it>and <it>PTEN </it>candidate regions. The effect of promoter methylation on TSC gene expression was studied by treating cells with methyltransferase inhibitor 5-azacytidine. Methylation status of the <it>TSC2 </it>promoter in tissue samples was examined by combined bisulfite restriction analysis (COBRA).</p> <p>Results</p> <p>The semi-quantitative RT-PCR analysis showed downregulation of <it>TSC1</it>, <it>TSC2</it>, <it>EIF4EBP1 </it>and <it>PTEN</it>, and upregulation of <it>PIK3C2A</it>, <it>AKT1</it>, <it>PDPK1</it>, <it>RHEB</it>, <it>FRAP1</it>, <it>RPS6KB1</it>, <it>EIF4E </it>and <it>RPS6 </it>in tumors. A similar observation was made for AKT1 and RPS6KB1 expression in tumors at the protein level. Investigation of the mechanism of downregulation of TSC genes identified LOH in 36.96% and 39.13% of the tumors at the TSC1 and TSC2 loci, respectively. No mutation was found in TSC genes. A low LOH rate of 13% was observed at the PTEN locus. Treatment of an OSCC cell line with the methyltransferase inhibitor 5-azacytidine showed a significant increase in the expression of TSC genes, suggesting methylation of their promoters. However, the 5-azacytidine treatment of non-OSCC HeLa cells showed a significant increase in the expression of the <it>TSC2 </it>gene only. In order to confirm the results in patient tumor samples, the methylation status of the <it>TSC2 </it>gene promoter was examined by COBRA. The results suggested promoter hypermethylation as an important mechanism for its downregulation. No correlation was found between the presence or absence of LOH at the TSC1 and TSC2 loci in 50 primary tumors to their clinicopathological variables such as age, sex, T classification, stage, grade, histology, tobacco habits and lymph node metastasis.</p> <p>Conclusion</p> <p>Our study suggests the involvement of TSC genes and other members of the mTOR signaling pathway in the pathogenesis of OSCC. LOH and promoter methylation are two important mechanisms for downregulation of TSC genes. We suggest that known inhibitors of this pathway could be evaluated for the treatment of OSCC.</p

Meditation on the Soles of the Feet Practice Provides Some Control of Aggression for Individuals with Alzheimer’s Disease

Alzheimer’s disease is a progressive neurodegenerative condition that affects cognition, mental and physical health, and functionality of older people. As the disease progresses from the mild to moderate stage, there is a concomitant increase in several behavioral variables, chiefly agitation, anger, and aggression. Currently, there are no evidence-based treatments for these behaviors in this population. Three individuals with moderate Alzheimer’s disease were taught an informal mindfulness practice, meditation on the Soles of the Feet (SoF), as a self-management strategy within a multiple-baseline design across participants. All three were able to learn and use the SoF practice to manage their verbal and physical aggression. Their use of the SoF practice was correlated with decreased perceived psychological stress for their spouses and caregivers, as well as for the participants, but to a much smaller degree. In terms of social validity, the participants, their spouses, and caregivers rated the SoF practice as acceptable, effective, with no unintended effects, and indicated that they would recommend the practice to others. However, they also rated SoF as effortful for the participants because it involves the participants remembering to use the practice with rising anger, a requirement particularly challenging for those with memory problems. The SoF practice may enable individuals in the early stages of dementia to manage their anger and aggression. The data were derived from an internally valid experimental design, suggestive of initial proof-of-concept, but needs to be replicated before any clinical implications can be imputed from this study

MicroRNA Expression Profiling of the Porcine Developing Brain

BACKGROUND: MicroRNAs are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level and play an important role in the control of developmental and physiological processes. In particular, the developing brain contains an impressive diversity of microRNAs. Most microRNA expression profiling studies have been performed in human or rodents and relatively limited knowledge exists in other mammalian species. The domestic pig is considered to be an excellent, alternate, large mammal model for human-related neurological studies, due to its similarity in both brain development and the growth curve when compared to humans. Considering these similarities, studies examining microRNA expression during porcine brain development could potentially be used to predict the expression profile and role of microRNAs in the human brain. METHODOLOGY/PRINCIPAL FINDINGS: MicroRNA expression profiling by use of microRNA microarrays and qPCR was performed on the porcine developing brain. Our results show that microRNA expression is regulated in a developmentally stage-specific, as well as a tissue-specific manner. Numerous developmental stage or tissue-specific microRNAs including, miR-17, miR-18a, miR-29c, miR-106a, miR-135a and b, miR-221 and miR-222 were found by microarray analysis. Expression profiles of selected candidates were confirmed by qPCR. CONCLUSIONS/SIGNIFICANCE: The differential expression of specific microRNAs in fetal versus postnatal samples suggests that they likely play an important role in the regulation of developmental and physiological processes during brain development. The data presented here supports the notion that microRNAs act as post-transcriptional switches which may regulate gene expression when required

No association between the common calcium-sensing receptor polymorphism rs1801725 and irritable bowel syndrome

Background The calcium-sensing receptor (CaSR) is a calcium (Ca2+) sensitive G protein-coupled receptor implicated in various biological processes. In particular, it regulates Ca2+/Mg2+- homeostasis and senses interstitial Ca2+ levels and thereby controls downstream signalling cascades. Due to its expression in the gut epithelium, the enteric nervous system and smooth muscles and its key function in regulation and coordination of muscular contraction and secretion, it represents an excellent candidate gene to be investigated in the pathophysiology of irritable bowel syndrome (IBS). Disturbed CaSR structure and function may impact gastrointestinal regulation of muscular contraction, neuronal excitation and secretion and consequently contribute to symptoms seen in IBS, such as disordered defecation as well as disturbed gut motility and visceral sensitivity. Methods We have therefore genotyped the functional CASR SNP rs1801725 in three case control samples from the UK, Belgium and the USA. Results Genotype frequencies showed no association in the three genotyped case–control samples, neither with IBS nor with IBS subtypes. Conclusions Although we could not associate the SNP to any of the established bowel symptom based IBS subtypes we cannot rule out association to altered Ca2+ levels and disturbed secretion and gut motility which were unfortunately not assessed in the patients genotyped. This underlines the necessity of a more detailed phenotyping of IBS patients and control individuals in future studies

Program design features that can improve participation in health education interventions

<p>Abstract</p> <p>Background</p> <p>Although there have been reported benefits of health education interventions across various health issues, the key to program effectiveness is participation and retention. Unfortunately, not everyone is willing to participate in health interventions upon invitation. In fact, health education interventions are vulnerable to low participation rates. The objective of this study was to identify design features that may increase participation in health education interventions and evaluation surveys, and to maximize recruitment and retention efforts in a general ambulatory population.</p> <p>Methods</p> <p>A cross-sectional questionnaire was administered to 175 individuals in waiting rooms of two hospitals diagnostic centres in Toronto, Canada. Subjects were asked about their willingness to participate, in principle, and the extent of their participation (frequency and duration) in health education interventions under various settings and in intervention evaluation surveys using various survey methods.</p> <p>Results</p> <p>The majority of respondents preferred to participate in one 30–60 minutes education intervention session a year, in hospital either with a group or one-on-one with an educator. Also, the majority of respondents preferred to spend 20–30 minutes each time, completing one to two evaluation surveys per year in hospital or by mail.</p> <p>Conclusion</p> <p>When designing interventions and their evaluation surveys, it is important to consider the preferences for setting, length of participation and survey method of your target population, in order to maximize recruitment and retention efforts. Study respondents preferred short and convenient health education interventions and surveys. Therefore, brevity, convenience and choice appear to be important when designing education interventions and evaluation surveys from the perspective of our target population.</p