Evidence for Shear Stress-Mediated Dilation of the Internal Carotid Artery in Humans.

Increases in arterial carbon dioxide tension (hypercapnia) elicit potent vasodilation of cerebral arterioles. Recent studies have also reported vasodilation of the internal carotid artery during hypercapnia, but the mechanism(s) mediating this extracranial vasoreactivity are unknown. Hypercapnia increases carotid shear stress, a known stimulus to vasodilation in other conduit arteries. To explore the hypothesis that shear stress contributes to hypercapnic internal carotid dilation in humans, temporal changes in internal and common carotid shear rate and diameter, along with changes in middle cerebral artery velocity, were simultaneously assessed in 18 subjects at rest and during hypercapnia (6% carbon dioxide). Middle cerebral artery velocity increased significantly (69±10-103±17 cm/s; P<0.01) along with shear in both the internal (316±52-518±105 1/s; P<0.01) and common (188±40-275±61 1/s; P<0.01) carotids. Diameter also increased (P<0.01) in both carotid arteries (internal: +6.3±2.9%; common: +5.8±3.0%). Following hypercapnia onset, there was a significant delay between the onset of internal carotid shear (22±12 seconds) and diameter change (85±51 seconds). This time course is associated with shear-mediated dilation of larger conduit arteries in humans. There was a strong association between change in shear and diameter of the internal carotid (r=0.68; P<0.01). These data indicate, for the first time in humans, that shear stress is an important stimulus for hypercapnic vasodilation of the internal carotid artery. The combination of a hypercapnic stimulus and continuous noninvasive, high-resolution assessment of internal carotid shear and dilation may provide novel insights into the function and health of the clinically important extracranial arteries in humans

Decision for reconstructive interventions of the upper limb in individuals with tetraplegia: the effect of treatment characteristics

Objective: To determine the effect of treatment characteristics on the\ud decision for reconstructive interventions for the upper extremities (UE) in\ud subjects with tetraplegia. - \ud Setting: Seven specialized spinal cord injury centres in the Netherlands. - \ud Method: Treatment characteristics for UE reconstructive interventions were\ud determined. Conjoint analysis (CA) was used to determine the contribution\ud and the relative importance of the treatment characteristics on the decision\ud for therapy. Therefore, a number of different treatment scenarios using these\ud characteristics were established. Different pairs of scenarios were presented\ud to subjects who were asked to choose the preferred scenario of each set. - \ud Results: forty nine subjects with tetraplegia with a stable C5, C6 or C7\ud lesion were selected. All treatment characteristics significantly influenced\ud the choice for treatment. Relative importance of treatment characteristics\ud were: intervention type (surgery or surgery with FES implant) 13%, number\ud of operations 15%, in patient rehabilitation period 22%, ambulant\ud rehabilitation period 9%, complication rate 15%, improvement of elbow\ud function 10%, improvement of hand function 15%. In deciding for therapy\ud 40% of the subjects focused on one characteristic. - \ud Conclusion: CA is applicable in Spinal Cord Injury medicine to study the\ud effect of health outcomes and non-health outcomes on the decision for\ud treatment. Non-health outcomes which relate to the intensity of treatment\ud are equally important or even more important than functional outcome in the\ud decision for reconstructive UE surgery in subjects with tetraplegia

Biochemical applications of surface-enhanced infrared absorption spectroscopy

An overview is presented on the application of surface-enhanced infrared absorption (SEIRA) spectroscopy to biochemical problems. Use of SEIRA results in high surface sensitivity by enhancing the signal of the adsorbed molecule by approximately two orders of magnitude and has the potential to enable new studies, from fundamental aspects to applied sciences. This report surveys studies of DNA and nucleic acid adsorption to gold surfaces, development of immunoassays, electron transfer between metal electrodes and proteins, and protein–protein interactions. Because signal enhancement in SEIRA uses surface properties of the nano-structured metal, the biomaterial must be tethered to the metal without hampering its functionality. Because many biochemical reactions proceed vectorially, their functionality depends on proper orientation of the biomaterial. Thus, surface-modification techniques are addressed that enable control of the proper orientation of proteins on the metal surface. [Figure: see text

α1Proteinase Inhibitor Regulates CD4+ Lymphocyte Levels and Is Rate Limiting in HIV-1 Disease

Background: The regulation of adult stem cell migration through human hematopoietic tissue involves the chemokine CXCL12 (SDF-1) and its receptor CXCR4 (CD184). In addition, human leukocyte elastase (HLE) plays a key role. When HLE is located on the cell surface (HLE CS), it acts not as a proteinase, but as a receptor for a 1proteinase inhibitor (a 1PI, a 1antitrypsin, SerpinA1). Binding of a1PI to HLECS forms a motogenic complex. We previously demonstrated that a1PI deficiency attends HIV-1 disease and that a1PI augmentation produces increased numbers of immunocompetent circulating CD4 + lymphocytes. Herein we investigated the mechanism underlying the a 1PI deficiency that attends HIV-1 infection. Methods and Findings: Active a 1PI in HIV-1 subjects (median 17 mM, n = 35) was significantly below normal (median 36 mM, p,0.001, n = 30). In HIV-1 uninfected subjects, CD4 + lymphocytes were correlated with the combined factors a1PI, HLECS + lymphocytes, and CXCR4 + lymphocytes (r 2 = 0.91, p,0.001, n = 30), but not CXCL12. In contrast, in HIV-1 subjects with.220 CD4 cells/ml, CD4 + lymphocytes were correlated solely with active a 1PI (r 2 =0.93,p,0.0001, n = 26). The monoclonal anti-HIV-1 gp120 antibody 3F5 present in HIV-1 patient blood is shown to bind and inactivate human a 1PI. Chimpanzee a 1PI differs from human a1PI by a single amino acid within the 3F5-binding epitope. Unlike human a1PI, chimpanzee a1PI did not bind 3F5 or become depleted following HIV-1 challenge, consistent with the normal CD4 + lymphocyte levels and benign syndrome of HIV-1 infected chimpanzees. The presence of IgG-a 1PI immune complexes correlated with decreased CD4 + lymphocytes in HIV-1 subjects

Patterns of impact resulting from a 'sit less, move more' web-based program in sedentary office employees.

PURPOSE: Encouraging office workers to 'sit less and move more' encompasses two public health priorities. However, there is little evidence on the effectiveness of workplace interventions for reducing sitting, even less about the longer term effects of such interventions and still less on dual-focused interventions. This study assessed the short and mid-term impacts of a workplace web-based intervention (Walk@WorkSpain, W@WS; 2010-11) on self-reported sitting time, step counts and physical risk factors (waist circumference, BMI, blood pressure) for chronic disease. METHODS: Employees at six Spanish university campuses (n=264; 42±10 years; 171 female) were randomly assigned by worksite and campus to an Intervention (used W@WS; n=129; 87 female) or a Comparison group (maintained normal behavior; n=135; 84 female). This phased, 19-week program aimed to decrease occupational sitting time through increased incidental movement and short walks. A linear mixed model assessed changes in outcome measures between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for Intervention versus Comparison groups. RESULTS: A significant 2 (group) × 2 (program phases) interaction was found for self-reported occupational sitting (F[3]=7.97, p=0.046), daily step counts (F[3]=15.68, p=0.0013) and waist circumference (F[3]=11.67, p=0.0086). The Intervention group decreased minutes of daily occupational sitting while also increasing step counts from baseline (446±126; 8,862±2,475) through ramping (+425±120; 9,345±2,435), maintenance (+422±123; 9,638±3,131) and follow-up (+414±129; 9,786±3,205). In the Comparison group, compared to baseline (404±106), sitting time remained unchanged through ramping and maintenance, but decreased at follow-up (-388±120), while step counts diminished across all phases. The Intervention group significantly reduced waist circumference by 2.1cms from baseline to follow-up while the Comparison group reduced waist circumference by 1.3cms over the same period. CONCLUSIONS: W@WS is a feasible and effective evidence-based intervention that can be successfully deployed with sedentary employees to elicit sustained changes on "sitting less and moving more"

Compliance and persistence with osteoporosis medications: A critical review of the literature

It is widely acknowledged that compliance and persistence with oral osteoporosis medications, particularly with bisphosphonates, is poor. Several excellent reviews have been written on compliance and persistence with osteoporosis medications and have discussed improvements seen with extended dosing intervals. This review begins with studies on extended dosing intervals to examine the limitations of administrative claims data. It also looks at compliance and persistence across multiple medical conditions, examining the importance of prescription fulfillment, intentional choice, causation and possible interventions

A systematic review of techniques and interventions for improving adherence to inclusion and exclusion criteria during enrolment into randomised controlled trials

<p>Abstract</p> <p>Background</p> <p>Enrolment of patients into a randomised controlled trial (RCT) in violation of key inclusion or exclusion criteria, may lead to excess avoidable harm. The purpose of this paper was to systematically identify and review techniques and interventions proven to prevent or avoid inappropriate enrolment of patients into RCTs.</p> <p>Methods</p> <p>EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, online abstract repositories, and conference websites were searched. Experts were contacted and bibliographies of retrieved papers hand-searched. The search cut-off date was 31 August 2009.</p> <p>Results</p> <p>No primary publications were found. We identified one study in the grey literature (conference abstracts and presentations) reporting the results of an evaluation of the effectiveness of an intervention designed to prevent or avoid inappropriate enrolment of patients into an RCT. In the context of a multicentre trial, use of a dummy enrolment run-in phase was shown to reduce enrolment errors significantly (<it>P </it>< 0.001), from 16.1% during the run-in phase to < 1% after trial initiation.</p> <p>Conclusions</p> <p>Our systematic search yielded only one technique or intervention shown to improve adherence to eligibility criteria during enrolment into RCTs. Given the potential harm involved in recruiting patients into a clinical trial in violation of key eligibility criteria, future research is needed to better inform those conducting clinical trials of how best to prevent enrolment errors</p

Health promotion services for lifestyle development within a UK hospital – Patients' experiences and views

<p>Abstract</p> <p>Background</p> <p>UK public health policy requires hospitals to have in place health promotion services which enable patients to improve their health through adopting healthy behaviours, i.e. health education. This study investigated hospitalised patients' experiences of health education for smoking, alcohol use, diet, physical activity, and weight, and their views concerning the appropriateness of hospitals as a setting for the delivery of health education services.</p> <p>Methods</p> <p>Recently discharged adult hospital patients (n = 322) were sent a questionnaire asking about their smoking, alcohol use, diet, physical activity, and weight. For each of these risk factors, participants were asked whether they agreed with screening for the risk factor, whether they received health education, whether it was "helpful", and if they wanted to change their behaviour. Participants were also asked a set of general questions concerning health education within hospitals.</p> <p>Results</p> <p>190 patients responded (59%). Over 80% agreed with screening for all risk factors. 80% of smokers, 52% consuming alcohol above recommended limits, 86% of obese, 66% consuming less than five fruit and vegetables a day, and 61% of physically inactive participants wanted to change their respective behaviour. However only a third reported receiving health education. While over 60% of patients wanted health education around discharge, the majority of those receiving health education did so at admission. The majority agreed that "hospital is a good place for patients to receive" health education (87%) and that "the hospital should provide patients with details of community organisations that provide" health education (83%). Only a minority (31%) reported a preference for health education from their GP instead of hospital.</p> <p>Conclusion</p> <p>While the delivery of health education to patients within hospital was poor, hospitals are viewed by patients as an appropriate, and in some cases preferred setting for the screening of risk factors and delivery of health education.</p

Nonthermal Emission from Star-Forming Galaxies

The detections of high-energy gamma-ray emission from the nearby starburst galaxies M82 & NGC253, and other local group galaxies, broaden our knowledge of star-driven nonthermal processes and phenomena in non-AGN star-forming galaxies. We review basic aspects of the related processes and their modeling in starburst galaxies. Since these processes involve both energetic electrons and protons accelerated by SN shocks, their respective radiative yields can be used to explore the SN-particle-radiation connection. Specifically, the relation between SN activity, energetic particles, and their radiative yields, is assessed through respective measures of the particle energy density in several star-forming galaxies. The deduced energy densities range from O(0.1) eV/cm^3 in very quiet environments to O(100) eV/cm^3 in regions with very high star-formation rates.Comment: 17 pages, 5 figures, to be published in Astrophysics and Space Science Proceeding

Trends in postpartum hemorrhage in high resource countries: a review and recommendations from the International Postpartum Hemorrhage Collaborative Group

<p>Abstract</p> <p>Background</p> <p>Postpartum hemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. Several recent publications have noted an increasing trend in incidence over time. The international PPH collaboration was convened to explore the observed trends and to set out actions to address the factors identified.</p> <p>Methods</p> <p>We reviewed available data sources on the incidence of PPH over time in Australia, Belgium, Canada, France, the United Kingdom and the USA. Where information was available, the incidence of PPH was stratified by cause.</p> <p>Results</p> <p>We observed an increasing trend in PPH, using heterogeneous definitions, in Australia, Canada, the UK and the USA. The observed increase in PPH in Australia, Canada and the USA was limited solely to immediate/atonic PPH. We noted increasing rates of severe adverse outcomes due to hemorrhage in Australia, Canada, the UK and the USA.</p> <p>Conclusion</p> <p><it>Key Recommendations</it></p> <p indent="1">1. Future revisions of the International Classification of Diseases should include separate codes for atonic PPH and PPH immediately following childbirth that is due to other causes. Also, additional codes are required for placenta accreta/percreta/increta.</p> <p indent="1">2. Definitions of PPH should be unified; further research is required to investigate how definitions are applied in practice to the coding of data.</p> <p indent="1">3. Additional improvement in the collection of data concerning PPH is required, specifically including a measure of severity.</p> <p indent="1">4. Further research is required to determine whether an increased rate of reported PPH is also observed in other countries, and to further investigate potential risk factors including increased duration of labor, obesity and changes in second and third stage management practice.</p> <p indent="1">5. Training should be provided to all staff involved in maternity care concerning assessment of blood loss and the monitoring of women after childbirth. This is key to reducing the severity of PPH and preventing any adverse outcomes.</p> <p indent="1">6. Clinicians should be more vigilant given the possibility that the frequency and severity of PPH has in fact increased. This applies particularly to small hospitals with relatively few deliveries where management protocols may not be defined adequately and drugs or equipment may not be on hand to deal with unexpected severe PPH.</p