Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

Effect of an EBM course in combination with case method learning sessions: an RCT on professional performance, job satisfaction, and self-efficacy of occupational physicians

Objective An intervention existing of an evidence-based medicine (EBM) course in combination with case method learning sessions (CMLSs) was designed to enhance the professional performance, self-efficacy and job satisfaction of occupational physicians. Methods A cluster randomized controlled trial was set up and data were collected through questionnaires at baseline (T0), directly after the intervention (T1) and 7 months after baseline (T2). The data of the intervention group [T0 (n = 49), T1 (n = 31), T2 (n = 29)] and control group [T0 (n = 49), T1 (n = 28), T2 (n = 28)] were analysed in mixed model analyses. Mean scores of the perceived value of the CMLS were calculated in the intervention group. Results The overall effect of the intervention over time comparing the intervention with the control group was statistically significant for professional performance (p <0.001). Job satisfaction and self-efficacy changes were small and not statistically significant between the groups. The perceived value of the CMLS to gain new insights and to improve the quality of their performance increased with the number of sessions followed. Conclusion An EBM course in combination with case method learning sessions is perceived as valuable and offers evidence to enhance the professional performance of occupational physicians. However, it does not seem to influence their self-efficacy and job satisfactio

Do Physicians Know When Their Diagnoses Are Correct?

This study explores the alignment between physicians' confidence in their diagnoses and the “correctness” of these diagnoses, as a function of clinical experience, and whether subjects were prone to over-or underconfidence. Design : Prospective, counterbalanced experimental design. Setting : Laboratory study conducted under controlled conditions at three academic medical centers. Participants : Seventy-two senior medical students, 72 senior medical residents, and 72 faculty internists. Intervention : We created highly detailed, 2-to 4-page synopses of 36 diagnostically challenging medical cases, each with a definitive correct diagnosis. Subjects generated a differential diagnosis for each of 9 assigned cases, and indicated their level of confidence in each diagnosis. Measurements And Main Results : A differential was considered “correct” if the clinically true diagnosis was listed in that subject's hypothesis list. To assess confidence, subjects rated the likelihood that they would, at the time they generated the differential, seek assistance in reaching a diagnosis. Subjects' confidence and correctness were “mildly” aligned (Κ=.314 for all subjects, .285 for faculty, .227 for residents, and .349 for students). Residents were overconfident in 41% of cases where their confidence and correctness were not aligned, whereas faculty were overconfident in 36% of such cases and students in 25%. Conclusions : Even experienced clinicians may be unaware of the correctness of their diagnoses at the time they make them. Medical decision support systems, and other interventions designed to reduce medical errors, cannot rely exclusively on clinicians' perceptions of their needs for such support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74850/1/j.1525-1497.2005.30145.x.pd

Non-detection of Chlamydia species in carotid atheroma using generic primers by nested PCR in a population with a high prevalence of Chlamydia pneumoniae antibody

BACKGROUND: The association of Chlamydia pneumoniae with atherosclerosis is controversial. We investigated the presence of C. pneumoniae and other Chlamydia spp. in atheromatous carotid artery tissue. METHODS: Forty elective carotid endarterectomy patients were recruited (27 males, mean age 65 and 13 females mean age 68), 4 had bilateral carotid endarterectomies (n= 44 endarterectomy specimens). Control specimens were taken from macroscopically normal carotid artery adjacent to the atheromatous lesions (internal controls), except in 8 cases where normal carotid arteries from post mortem (external controls) were used. Three case-control pairs were excluded when the HLA DRB gene failed to amplify from the DNA. Genus specific primers to the major outer membrane protein (MOMP) gene were used in a nested polymerase chain reaction (nPCR) in 41 atheromatous carotid specimens and paired controls. PCR inhibition was monitored by spiking with target C. trachomatis. Atheroma severity was graded histologically. Plasma samples were tested by microimmunofluorescence (MIF) for antibodies to C. pneumoniae, C. trachomatis and C. psittaci and the corresponding white cells were tested for Chlamydia spp. by nPCR. RESULTS: C. pneumoniae was not detected in any carotid specimen. Twenty-five of 38 (66%) plasma specimens were positive for C. pneumoniae IgG, 2/38 (5%) for C. trachomatis IgG and 1/38 (3%) for C. psittaci IgG. CONCLUSIONS: We were unable to show an association between the presence of Chlamydia spp. and atheroma in carotid arteries in the presence of a high seroprevalence of C. pneumoniae antibodies in Northern Ireland

Dialetheism in Action: A New Strategy for Solving the Equal Validity Paradox

This paper starts from the Equal Validity Paradox, a paradoxical argument connected to the so-called phenomenon of faultless disagreement. It is argued that there are at least six strategies for solving the paradox. After presenting the first five strategies and their main problems, the paper focuses on the sixth strategy which rejects the assumption that every proposition cannot be both true a false. Dialetheism is the natural candidate for developing strategy six. After presenting strategy six in detail, we formulate a normative problem for the dialetheist and offer a tentative solution to it. We then elaborate further considerations connecting strategy six to pluralism about truth and logic. Even if strategy six is a hard path to take, its scrutiny highlights some important points on truth, logic and the norms for acceptance and rejection

Application of biomedical informatics to chronic pediatric diseases: a systematic review

<p>Abstract</p> <p>Background</p> <p>Chronic diseases affect millions of children worldwide leading to substantial disease burden to the children and their families as well as escalating health care costs. The increasing trend in the prevalence of complex pediatric chronic diseases requires innovative and optimal delivery of care. Biomedical informatics applications play an important role in improving health outcomes while being cost-effective. However, their utility in pediatric chronic diseases has not been studied in a comprehensive and systematic way. The objective of this study was to conduct a systematic review of the effects of biomedical informatics applications in pediatric chronic diseases.</p> <p>Methods</p> <p>A comprehensive literature search was conducted using MEDLINE, the Cochrane Library and EMBASE databases from inception of each database to September 2008. We included studies of any methodological type and any language that applied biomedical informatics to chronic conditions in children and adolescents 18 years of age or younger. Two independent reviewers carried out study selection and data extraction. Quality assessment was performed using a study design evaluation instrument to appraise the strength of the studies and their methodological adequacy. Because of heterogeneity in the conditions and outcomes we studied, a formal meta-analysis was not performed.</p> <p>Results</p> <p>Based on our search strategy, 655 titles and abstracts were reviewed. From this set we identified 27 relevant articles that met our inclusion criteria. The results from these studies indicated that biomedical informatics applications have favourable clinical and patient outcomes including, but not limited to, reduced number of emergency room visits, improved knowledge on disease management, and enhanced satisfaction. Seventy percent of reviewed papers were published after year 2000, 89% of users were patients and 11% were either providers or caregivers. The majority (96%) of the selected studies reported improved outcomes.</p> <p>Conclusion</p> <p>Published studies suggested positive impacts of informatics predominantly in pediatric asthma. As electronic tools become more widely adopted, there will be opportunities to improve patient care in a wide range of chronic illnesses through informatics solutions.</p

Are isomeric alkenes used in species recognition among neo-tropical stingless bees (Melipona spp)

The majority of our understanding of the role of cuticular hydrocarbons (CHC) in recognition is based largely on temperate ant species and honey bees. The stingless bees remain relatively poorly studied, despite being the largest group of eusocial bees, comprising more than 400 species in some 60 genera. The Meliponini and Apini diverged between 80-130 Myr B.P. so the evolutionary trajectories that shaped the chemical communication systems in ants, honeybees and stingless bees may be very different. Therefore, the main aim of this study was to study if a unique species CHC signal existed in Neotropical stingless bees, as shown for many temperate species, and if so what compounds are involved. This was achieved by collecting CHC data from 24 colonies belonging to six species of Melipona from North-eastern Brazil and comparing this new data with all previously published CHC studies on Melipona. We found that each of the eleven Melipona species studied so far each produced a unique species CHC signal based around their alkene isomer production. A remarkable number of alkene isomers, up to 25 in M. asilvai, indicated the diversification of alkene positional isomers among the stingless bees. The only other group to have really diversified in alkene isomer production are the primitively eusocial Bumblebees (Bombus spp), which are the sister group of the stingless bees. Furthermore, among the eleven Neotropical Melipona species we could detect no effect of the environment on the proportion of alkane production as has been suggested for some other species

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV