Risk prediction for type 2 diabetes (T2D) and cardiovascular disease (CVD) remains suboptimal even after the introduction of global risk assessment by various scores. This has prompted the search for ...additional biomarkers. A variety of blood biomarkers representing various pathophysiological pathways of insulin resistance and atherosclerosis, as well as markers of subclinical disease and genetic markers, have been investigated. This review provides an overview of studies assessing the clinical utility of various biomarkers on the basis of hypothesis‐driven selection as well as hypothesis‐free approaches from novel “‐omics” technologies. So far, the assessment of genotypes and of several candidate biomarkers from blood has resulted in only small improvements in the accuracy of prediction of CVD and T2D over and above that predicted on the basis of established risk factors. Integrated approaches, combining biomarkers from genomics, transcriptomics, proteomics, and metabolomics, as well as serial measurements of biomarkers, are required to make a complete assessment of the potential clinical usefulness of biomarkers for risk prediction of cardiometabolic disease.
Clinical Pharmacology & Therapeutics (2011) 90 1, 52–66. doi:10.1038/clpt.2011.93
Homophobic teasing is often long-term, systematic, and perpetrated by groups of students (Rivers, 2001); it places targets at risk for greater suicidal ideation, depression, and isolation (Elliot & ...Kilpatrick, 1994). This study fills a gap in the literature by examining buffering influences of positive parental relations and positive school climate on mental health outcomes for high school students who are questioning their sexual orientation. Participants were 13,921 high school students from a Midwestern U.S. public school district. Students completed a survey consisting of a wide range of questions related to their school experiences (bullying, homophobia, school climate), parental support, mood, and drug-alcohol use. Students were categorized into three groups: (a) youth who identified as heterosexual, (b) youth who questioned their sexual orientation, and (c) youth who identified as lesbian, gay, or bisexual (LGB). As hypothesized, sexual minority youth were more likely to report high levels of depression-suicide feelings and alcohol-marijuana use; students who were questioning their sexual orientation reported more teasing, greater drug use, and more feelings of depression and suicide than either heterosexual or LGB students. Sexually questioning students who experienced homophobic teasing were also more likely than LGB students to use drugs-alcohol and rate their school climate as negative. Finally, positive school climate and parental support protected LGB and questioning students against depression and drug use.
Methods to intercept bacterial quorum sensing (QS) have attracted significant attention as potential anti-infective therapies. Staphylococcus aureus is a major human pathogen that utilizes ...autoinducing peptide (AIP) signals to mediate QS and thereby regulate virulence. S. aureus strains are categorized into four groups (I–IV) according to their AIP signal and cognate extracellular receptor, AgrC. Each group is associated with a certain disease profile, and S. aureus group-III strains are responsible for toxic shock syndrome and have been underestimated in other infections to date. A limited set of non-native AIP analogs have been shown to inhibit AgrC receptors; such compounds represent promising tools to study QS pathways in S. aureus. We seek to expand this set of chemical probes and report herein the first design, synthesis, and biological testing of AIP-III mimetics. A set of non-native peptides was identified that can inhibit all four of the AgrC receptors (I–IV) with picomolar IC50 values in reporter strains. These analogs also blocked hemolysis by wild-type S. aureus group I–IV strainsa virulence trait under the control of QSat picomolar concentrations. Moreover, four of the lead AgrC inhibitors were capable of attenuating the production of toxic shock syndrome toxin-1 (also under the control of QS) by over 80% at nanomolar concentrations in a wild-type S. aureus group-III strain. These peptides represent, to our knowledge, the most potent synthetic inhibitors of QS in S. aureus known, and constitute new and readily accessible chemical tools for the study of the AgrC system and virulence in this deadly pathogen.
The release of cardiomyocyte components, i.e. biomarkers, into the bloodstream in higher than usual quantities indicates an ongoing pathological process. Thus, detection of elevated concentrations of ...cardiac biomarkers in blood is a sign of cardiac injury which could be due to supply–demand imbalance, toxic effects, or haemodynamic stress. It is up to the clinician to determine the most probable aetiology, the proper therapeutic measures, and the subsequent risk implied by the process. For this reason, the measurement of biomarkers always must be applied in relation to the clinical context and never in isolation. There are a large number of cardiac biomarkers, but they can be subdivided into four broad categories, those related to necrosis, inflammation, haemodynamic stress, and/or thrombosis. Their usefulness is dependent on the accuracy and reproducibility of the measurements, the discriminatory limits separating pathology from physiology, and their sensitivity and specificity for specific organ damage and/or disease processes. In recent years, cardiac biomarkers have become important adjuncts to the delivery of acute cardiac care. Therefore, the Working Group on Acute Cardiac Care of the European Society of Cardiology established a committee to deal with ongoing and newly developing issues related to cardiac biomarkers. The intention of the group is to outline the principles for the application of various biomarkers by clinicians in the setting of acute cardiac care in a series of expert consensus documents. The first of these will focus on cardiac troponin, a pivotal marker of cardiac injury/necrosis.
Molecular dynamics plays an important role for the biological function of proteins. For protein ligand interactions, changes of conformational entropy of protein and hydration layer are relevant for ...the binding process. Quasielastic neutron scattering (QENS) was used to investigate differences in protein dynamics and conformational entropy of ligand-bound and ligand-free streptavidin. Protein dynamics were probed both on the fast picosecond time scale using neutron time-of-flight spectroscopy and on the slower nanosecond time scale using high-resolution neutron backscattering spectroscopy. We found the internal equilibrium motions of streptavidin and the corresponding mean square displacements (MSDs) to be greatly reduced upon biotin binding. On the basis of the observed MSDs, we calculated the difference of conformational entropy ΔS conf of the protein component between ligand-bound and ligand-free streptavidin. The rather large negative ΔS conf value (−2 kJ mol–1 K–1 on the nanosecond time scale) obtained for the streptavidin tetramer seems to be counterintuitive, given the exceptionally high affinity of streptavidin–biotin binding. Literature data on the total entropy change ΔS observed upon biotin binding to streptavidin, which includes contributions from both the protein and the hydration water, suggest partial compensation of the unfavorable ΔS conf by a large positive entropy gain of the surrounding hydration layer and water molecules that are displaced during ligand binding.
Ecological variables often fluctuate synchronously over wide geographical areas, a phenomenon known as spatial autocorrelation or spatial synchrony. Development of statistical approaches designed to ...test for spatial autocorrelation combined with the increasing accessibility of long-term, large-scale ecological datasets are now making it possible to document the patterns and understand the causes of spatial synchrony at scales that were previously intractable. These developments promise to foster significant future advances in understanding population regulation, metapopulation dynamics and other areas of population ecology.
Clin Microbiol Infect 2012; 18: E49–E51
Of 109 clinical Escherichia coli isolates from two major tertiary hospitals in Lagos (University Teaching Hospital and the National Orthopaedic Hospital ...Igbobi), 14 (12.8%) extended‐spectrum beta‐lactamse (ESBL) producers were characterized using PCR and sequencing, ERIC‐PCR and multilocus sequence typing. All ESBL‐producing isolates encoded only the CTX‐M‐15 gene. Clonal group ST131 (35.7%) was the predominant ST, followed by ST617 (28.6%). Isolated cases of other sequence types were also observed. Plasmid‐mediated quinolone resistance genes qnrA, qnrB1 and aac‐(6′)‐lb‐cr were detected among these ESBL isolates of different clonal groups. This is the first description of the clonality of CTX‐M‐15‐producing E. coli from Nigeria. The presence of diverse clonal lineages shows the continuing potential for genetic diversification and emergence of new epidemic strains.
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