Effects of cuff width on arterial occlusion: implications for blood flow restricted exercise

The purpose of this study was to determine the difference in cuff pressure which occludes arterial blood flow for two different types of cuffs which are commonly used in blood flow restriction (BFR) research. Another purpose of the study was to determine what factors (i.e., leg size, blood pressure, and limb composition) should be accounted for when prescribing the restriction cuff pressure for this technique. One hundred and sixteen (53 males, 63 females) subjects visited the laboratory for one session of testing. Mid-thigh muscle (mCSA) and fat (fCSA) cross-sectional area of the right thigh were assessed using peripheral quantitative computed tomography. Following the mid-thigh scan, measurements of leg circumference, ankle brachial index, and brachial blood pressure were obtained. Finally, in a randomized order, arterial occlusion pressure was determined using both narrow and wide restriction cuffs applied to the most proximal portion of each leg. Significant differences were observed between cuff type and arterial occlusion (narrow: 235 (42)?mmHg vs. wide: 144 (17)?mmHg; p?=?0.001, Cohen's D?=?2.52). Thigh circumference or mCSA/fCSA with ankle blood pressure, and diastolic blood pressure, explained the most variance in the cuff pressure required to occlude arterial flow. Wide BFR cuffs restrict arterial blood flow at a lower pressure than narrow BFR cuffs, suggesting that future studies account for the width of the cuff used. In addition, we have outlined models which indicate that restrictive cuff pressures should be largely based on thigh circumference and not on pressures previously used in the literature.     

Health care services utilization stratified by virological and immunological markers of HIV: evidence from a universal health care setting

Objective

The aim of the study was to determine rates of utilization of in‐patient, out‐patient and laboratory services stratified by virological and immunological markers of HIV disease among patients on antiretroviral treatment in British Columbia, Canada.

Methods

We estimated resource utilization for in‐patient visits, out‐patient visits, and laboratory tests among patients initiating antiretroviral treatment between 1 April 1994 and 31 December 2000, with follow‐up to 31 March 2001. Resource use was stratified by CD4 cell count and plasma HIV viral load (pVL) at the time of utilization and rates per 100 patient‐years were calculated for each health care resource.

Results

A total of 2718 patients were included in our analyses. The overall rates of in‐patient visits, out‐patient visits, and laboratory tests were 902, 3001 and 840 per 100 patient‐years, respectively. Utilization was higher for patients with low CD4 cell counts and high pVLs when compared with patients with high CD4 cell counts and low pVLs.

Conclusions

Patients with low CD4 cell counts and high pVLs had the highest use of health care services. Regular follow‐up with health care providers in an out‐patient setting, allowing for proper monitoring and maintenance of HIV care, is important in minimizing unnecessary and potentially costly in‐patient care.     

Local delivery of sirolimus nanoparticles for the treatment of in‐stent restenosis

Transcatheter aortic valve implantation is a possible, although off‐label, alternative to conventional aortic valve replacement for high‐surgical‐risk patients with severe, non‐calcified aortic regurgitation (AR). To date, feasibility has only been demonstrated with the Medtronic CoreValve prosthesis (MCV). This prosthesis needs the aortic sinuses to have enough width to avoid coronary obstruction. We report a case of MCV implantation for severe AR where the narrow aortic root theoretically precluded the technique. Good procedural outcome was achieved thanks to a strategy of implantation with planned positioning of the prosthesis leaflets away from the coronary arteries. © 2013 Wiley Periodicals, Inc.     

The vertical stability of the cervical spine

The concept of the three-column cervical spine and load transmission through each column was experimentally tested. Material consisted of five cervical columns removed from cadavers. The experiment was conducted on an Instron load testing machine. Load was applied on superior articular surfaces of the axis vertebra and was recorded below from each column separately at the level of the sixth cervical vertebra. It was found that 36% of the total load applied on the top of the specimen is transmitted through the anterior column formed by bodies and intervertebral discs and 32% each through the two posterior cervical columns formed by the articular processes. The experiment very strongly supported the role of neural arch in transmission of vertebral compressive forces.     

Accurate visual guidance despite severe neglect

Unilateral inactivation of the superior colliculus causes profound neglect. In cats, this neglect has been studied previously using tasks that require gaze orientation to, or detection of, a stimulus appearing somewhere in the visual field of an attentive animal. We investigated how neglect affects a completely different kind of task, visually guided foot placement while walking across a cluttered surface. We made muscimol injections into one superior colliculus, and performed perimetry to gauge the extent of the cat's neglect. Cats then walked repeatedly through a cluttered test alley. Most of the time, their gaze was deviated towards the side of the injection, so that they saw the alley floor ahead of them in their neglected hemifield. Surprisingly, they accurately avoided stepping on the densely scattered objects, just as they normally do. We surmise that cats process 'neglected' visual stimuli to guide foot placement even when they are unable to consciously perceive these stimuli.     

Mortality is influenced by locality in a major HIV/AIDS epidemic

Objectives

The aim of the study was to compare the risks of death among HIV‐infected patients on highly active antiretroviral therapy (HAART) in two proximate, yet distinct neighbourhoods: a neighbourhood with a high concentration of gay men, and a neighbourhood with a high concentration of injecting drug users.

Methods

We compared the clinical and socioeconomic characteristics of HIV‐infected patients from the two neighbourhoods entering the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program from 1 September 1997 to 30 November 2005, using contingency table statistics. Cox survival models and Kaplan–Meier methods were used to estimate the cumulative mortality rates. Results We found significant differences between patients from the two neighbourhoods for all socioeconomic variables. Patients in the neighbourhood with a high concentration of injecting drug users were more likely to be female, have a history of injecting drug use, have a less HIV‐experienced physician and be less adherent. Patients in the neighbourhood with a high concentration of gay men were more likely to have AIDS. Mortality was significantly higher for patients in the neighbourhood with a high concentration of injecting drug users [hazard ratio (HR) 3.01; 95% confidence interval (CI) 1.73, 5.24].

Conclusions

A threefold increase was observed in the risk of death among HIV‐infected individuals on HAART in the neighbourhood with a high concentration of injecting drug users relative to the neighbourhood with a high concentration of gay men. The implications of this study should be assessed in similar HIV/AIDS epicentres.     

Estimating the public health impact of disbanding a government alcohol monopoly: application of new methods to the case of Sweden

Background

Government alcohol monopolies were created in North America and Scandinavia to limit health and social problems. The Swedish monopoly, Systembolaget, reports to a health ministry and controls the sale of all alcoholic beverages with >?3.5% alcohol/volume for off-premise consumption, within a public health mandate. Elsewhere, alcohol monopolies are being dismantled with evidence of increased consumption and harms. We describe innovative modelling techniques to estimate health outcomes in scenarios involving Systembolaget being replaced by 1) privately owned liquor stores, or 2) alcohol sales in grocery stores. The methods employed can be applied in other jurisdictions and for other policy changes.

Methods

Impacts of the privatisation scenarios on pricing, outlet density, trading hours, advertising and marketing were estimated based on Swedish expert opinion and published evidence. Systematic reviews were conducted to estimate impacts on alcohol consumption in each scenario. Two methods were applied to estimate harm impacts: (i) alcohol attributable morbidity and mortality were estimated utilising the International Model of Alcohol Harms and Policies (InterMAHP); (ii) ARIMA methods to estimate the relationship between per capita alcohol consumption and specific types of alcohol-related mortality and crime.

Results

Replacing government stores with private liquor stores (Scenario 1) led to a 20.0% (95% CI, 15.3–24.7) increase in per capita consumption. Replacement with grocery stores (Scenario 2) led to a 31.2% (25.1–37.3%) increase. With InterMAHP there were 763 or?+?47% (35–59%) and 1234 or?+?76% (60–92%) more deaths per year, for Scenarios 1 and 2 respectively. With ARIMA, there were 850 (334–1444) more deaths per year in Scenario 1 and 1418 more in Scenario 2 (543–2505). InterMAHP also estimated 10,859 or?+?29% (22–34%) and 16,118 or?+?42% (35–49%) additional hospital stays per year respectively.

Conclusions

There would be substantial adverse consequences for public health and safety were Systembolaget to be privatised. We demonstrate a new combined approach for estimating the impact of alcohol policies on consumption and, using two alternative methods, alcohol-attributable harm. This approach could be readily adapted to other policies and settings. We note the limitation that some significant sources of uncertainty in the estimates of harm impacts were not modelled.

     

Synthesis and biological evaluation of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of cyclin-dependent kinases

Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.     

Location and connections of visual cortical areas in the cat's suprasylvian sulcus

The initial aim of the experiments described here was to identify and quantify the cortical and thalamic connections of visual cortical areas located in the vicinity of the suprasylvian sulcus. Inputs to various sites in this region were studied by making small injections of wheat germ agglutinin (conjugated to horseradish peroxidase) at physiologically identified locations. Retrogradely labeled cells were counted in each identifiable area of cortex and in thalamic nuclei. Some injections yielded quantitatively similar distributions of labeled cells, and it is suggested that such evidence provides a useful way of dividing the cortex into areas. By this criterion, a single, relatively large, cortical area was identified that occupied most of the medial bank of the suprasylvian sulcus, all or most of its posterior bank, and a small segment of its lateral bank. It was referred to as the Clare-Bishop area. Because neighboring visual areas were found to lack input from area 17, while the Clare-Bishop area received a strong striate input, its boundaries were investigated by labeling afferents from area 17. Together with the results of retrograde tracer injections, these data suggested that the Clare-Bishop area cuts across several of the visual areas defined physiologically by Tusa et al. ('81). As a consequence, its retinotopic organization must be relatively complex, with duplications of some parts of the visual field. Three other visual areas were tentatively identified on the basis of their distinctive connections. One was situated on the lateral bank of the suprasylvian sulcus and appeared to border the Clare-Bishop area laterally. Another, referred to as area 21, lay adjacent to area 19, and, for part of its length, also appeared to bound the Clare-Bishop area. The third, corresponding approximately to Heath and Jones's ('71) posterior suprasylvian region, lay lateral and anterior to the Clare-Bishop area in the depths of the posterior suprasylvian sulcus.