Under-the-Mango-Tree: a theatre-based male EMTCT engagement intervention in post-conflict northern Uganda.

Male involvement in human immunodeficiency virus (HIV) care cascades is identified as a critical prerequisite for the successful elimination of mother-to-child transfer of HIV. Scant evidence exists on efficacious culturally appropriate and male-inclusive elimination of mother-to-child transfer interventions. This reflection-in-action paper highlights field notes and observations of the development of Under-the- Mango-Tree, a theatre-based male-inclusive intervention pilot tested in northern Uganda. The intervention included: (a) traditional drama, dances and songs and (b) expert testimonies and group dialogue. Observations in this pilot showed that a theatre-based intervention was suitable for social persuasion; role modelling and moderating mastery of experience through effectively combining simple songs, dances and drama; testimonies of successful adherence by expert clients; and through reflective group discussions. These observations have implications for male-inclusive elimination of mother-to-child transfer intervention development.

A Study of the Role of Small Ethnic Retail Grocery Stores in Urban Renewal in a Social Housing Project, Toronto, Canada.

Urban renewal often drives away the original residents, replacing them with higher income residents who can afford the new spaces, leading to gentrification. Urban renewal that takes place over many years can create uncertainties for retailers and residents, exacerbating the gentrification process. This qualitative study explored how the urban renewal process in a multi-cultural social housing neighborhood in Toronto (Regent Park) affected the small ethnic retail grocery stores (SERGS) that supplied ethnic foods and items to the ethnic populations living there. Interviews were conducted with ten SERGS store owners/managers and 16 ethnic residents who lived in Regent Park before renewal and were displaced, or who were displaced and returned. The SERGS stated that they provided culturally familiar items and offered a social credit scheme that recognized existing social relationships and allowed low-income residents to afford food and other amenities in a dignified manner and pay later, without penalty or interest. At the same time, the SERGS were unsupported during the renewal, were excluded from the civic planning processes, could not compete for space in the new buildings, and experienced declining sales and loss of business. The residents stated that the SERGS were trusted, provided a valued cultural social spaces for ethnic identity formation, and ethnic food security but they faced many uncertainties about the role of SERGS in a renewed neighborhood. Based on this study, it is recommended that ethnic retailers be recognized for the role they play in formulating ethnic identities and food security in mixed-use mixed-income communities and that they be included in planning processes during urban renewal. Such recognition may enable more former residents to return and lessen the gentrification.

Key innovation or adaptive change? A test of leaf traits using Triodiinae in Australia.

The evolution of novel traits ("key innovations") allows some lineages to move into new environments or adapt to changing climates, whereas other lineages may track suitable habitat or go extinct. We test whether, and how, trait shifts are linked to environmental change using Triodiinae, C4 grasses that form the dominant understory over about 30% of Australia. Using phylogenetic and relaxed molecular clock estimates, we assess the Australian biogeographic origins of Triodiinae and reconstruct the evolution of stomatal and vascular bundle positioning. Triodiinae diversified from the mid-Miocene, coincident with the aridification of Australia. Subsequent niche shifts have been mostly from the Eremaean biome to the savannah, coincident with the expansion of the latter. Biome shifts are correlated with changes in leaf anatomy and radiations within Triodiinae are largely regional. Symplectrodia and Monodia are nested within Triodia. Rather than enabling biome shifts, convergent changes in leaf anatomy have probably occurred after taxa moved into the savannah biome-they are likely to have been subsequent adaptions rather than key innovations. Our study highlights the importance of testing the timing and origin of traits assumed to be phenotypic innovations that enabled ecological shifts.

A dose-response study of thymosin ß4 for the treatment of acute stroke.

BACKGROUND: Thymosin ß4 (Tß4) is a 5K actin binding peptide. Tß4 improves neurological outcome in a rat model of embolic stroke and research is now focused on optimizing its dose for clinical trials. The purpose of this study was to perform a dose-response study of Tß4 to determine the optimal dose of neurological improvement in a rat model of embolic stroke. METHODS: Male Wistar rats were subjected to embolic middle cerebral artery occlusion (MCAo). Rats were divided into 4 groups of 10 animals/group: control, 2, 12 and 18 mg/kg. Tß4 was administered intraperitoneally 24h after MCAo and then every 3 days for 4 additional doses in a randomized controlled fashion. Neurological tests were performed after MCAo and before treatment and up to 8 weeks after treatment. The rats were sacrificed 56 days after MCAo and lesion volumes measured. Generalized estimating equation was used to compare the treatment effect on long term functional recovery at day 56. A quartic regression model was used for an optimal dose determination. RESULTS: Tß4 significantly improved neurological outcome at dose of 2 and 12 mg/kg at day 14 and extended to day 56 (p-values <0.05). The higher dose of 18 mg/kg did not show significant improvement. The estimated optimal dose of 3.75 mg/kg would provide optimal neurological improvement. CONCLUSIONS: This study shown that Tß4 significantly improved the long term neurological functional recovery at day 56 after MCAo with an optimal dose of 3.75 mg/kg. These results provide preclinical data for human clinical trials.

Intravascular embolisation and surgical resection of a giant neurofibroma with intratumoural haemorrhage.

The use of pre-operative embolisation has been described for small neurofibromas, but not for giant lesions. Advances in embolisation techniques are extending the indications for this procedure, in particular to assist with operative intervention on a range of lesions. This case report describes a 45-year-old male with a giant neurofibroma who underwent embolisation to stabilise intratumoural haemorrhage and to assist with haemostasis during the subsequent surgical resection. Minimal transfusion was required and the patient has made a good recovery. This case demonstrates that pre-operative embolisation of these large and challenging lesions is technically feasible and appears to be beneficial in reducing perioperative blood loss and morbidity.

Thymosin beta4 improves functional neurological outcome in a rat model of embolic stroke.

UNLABELLED: Thymosin beta4 (Tbeta4) is a developmentally expressed 43-amino acid peptide that inhibits organization of the actin-cytoskeleton by sequestration of G-actin monomers. Tbeta4 improves cardiac function after myocardial infarction in adult mice and promotes healing properties in both dermal and corneal wounds. We tested the hypothesis that Tbeta4 improves functional neurological outcome in a rat model of embolic stroke. EXPERIMENTAL PROCEDURES: Male Wistar rats (n=18) were subjected to embolic middle cerebral artery occlusion (MCAo). Tbeta4 (6 mg/kg, IP) was administered 24 h after MCAo and then every 3 days for four additional doses (n=9). Rats treated with saline were used as a control (n=9). The adhesive-removal test (ART) and modified Neurological Severity Score (mNSS) were performed to measure functional outcome. Rats were sacrificed 56 days after MCAo. Immunostaining was performed with antibodies against NG-2 (chondroitin sulfate proteoglycan), CNPase (2", 3"-cyclic nucleotide 3'-phosphodiesterase) to detect immature and mature oligodendrocytes. Neurofilament-H (NF-H) antibodies were used to detect axons while myelinated axons were identified with Bielschowsky/Luxol (B/L) Blue staining. EBA (endothelial barrier antigen) was used for detection of mature vessels. RESULTS: Ischemic rats treated with Tbeta4 demonstrated a significant overall improvement (P<0.01) in the ART and the mNSS when compared to controls. Significant improvement was observed beginning at 14 and 35 days, respectively. Lesion volumes showed no significant differences between the two groups. Treatment with Tbeta4 increased myelinated axons and increased vessel density in the ischemic boundary (P<0.05) and augmented remyelination which was associated with an increase of oligodendrocyte progenitor cells (OPCs) and myelinating oligodendrocytes (P<0.05). CONCLUSIONS: The present study suggests that Tbeta4 improves neurological functional outcome after embolic stroke in rats. Axonal remodeling from mobilization of OPCs is proposed as contributing to Tbeta4 induced functional improvement.

The Notch pathway mediates expansion of a progenitor pool and neuronal differentiation in adult neural progenitor cells after stroke.

Molecular mechanisms by which stroke increases neurogenesis have not been fully investigated. Using neural progenitor cells isolated from the subventricular zone (SVZ) of the adult rat subjected to focal cerebral ischemia, we investigated the Notch pathway in regulating proliferation and differentiation of adult neural progenitor cells after stroke. During proliferation of neural progenitor cells, ischemic neural progenitor cells exhibited substantially increased levels of Notch, Notch intracellular domain (NICD), and hairy enhancer of split (Hes) 1, which was associated with a significant increase of proliferating cells. Blockage of the Notch pathway by short interfering ribonucleic acid (siRNA) against Notch or a gamma secretase inhibitor significantly reduced Notch, NICD and Hes1 expression and cell proliferation induced by stroke. During differentiation of neural progenitor cells, Notch and Hes1 expression was downregulated in ischemic neural progenitor cells, which was coincident with a significant increase of neuronal population. Inhibition of the Notch pathway with a gamma secretase inhibitor further substantially increased neurons, but did not alter astrocyte population in ischemic neural progenitor cells. These data suggest that the Notch signaling pathway mediates adult SVZ neural progenitor cell proliferation and differentiation after stroke.

Bright x-ray flares in gamma-ray burst afterglows.

Gamma-ray burst (GRB) afterglows have provided important clues to the nature of these massive explosive events, providing direct information on the nearby environment and indirect information on the central engine that powers the burst. We report the discovery of two bright x-ray flares in GRB afterglows, including a giant flare comparable in total energy to the burst itself, each peaking minutes after the burst. These strong, rapid x-ray flares imply that the central engines of the bursts have long periods of activity, with strong internal shocks continuing for hundreds of seconds after the gamma-ray emission has ended.

An unexpectedly rapid decline in the X-ray afterglow emission of long gamma-ray bursts.

'Long' gamma-ray bursts (GRBs) are commonly accepted to originate in the explosion of particularly massive stars, which give rise to highly relativistic jets. Inhomogeneities in the expanding flow result in internal shock waves that are believed to produce the gamma-rays we see. As the jet travels further outward into the surrounding circumstellar medium, 'external' shocks create the afterglow emission seen in the X-ray, optical and radio bands. Here we report observations of the early phases of the X-ray emission of five GRBs. Their X-ray light curves are characterised by a surprisingly rapid fall-off for the first few hundred seconds, followed by a less rapid decline lasting several hours. This steep decline, together with detailed spectral properties of two particular bursts, shows that violent shock interactions take place in the early jet outflows.

Extension of the therapeutic window for recombinant tissue plasminogen activator with argatroban in a rat model of embolic stroke.

BACKGROUND AND PURPOSE: Argatroban, a specific thrombin inhibitor, has been shown to reduce ischemic lesion size after focal cerebral ischemia in rats. In addition, recombinant tissue plasminogen activator (rtPA) has been shown to reduce ischemic lesion size in both rats and humans if given within 3 hours of symptom onset. We tested the hypothesis that the administration of argatroban with rtPA could extend the treatment window of stroke to 4 hours without increasing gross cerebral hemorrhage rates or reducing efficacy. METHODS: Male Wistar rats were subjected to middle cerebral artery (MCA) occlusion by a single fibrin-rich clot. After embolization, rats were administered argatroban at the following dose levels: 2.08, 6.25, and 18.75 microgram . kg(-1). min(-1). In a second experiment, rats received argatroban (6.25 microgram . kg(-1). min(-1)) or argatroban in combination with rtPA 4 hours after MCA occlusion. Tissue sections were then analyzed for lesion volume, gross hemorrhage and fibrin deposition. RESULTS: The 6.25 microgram. kg(-1). min(-1) dose demonstrated a significant reduction (P<0.05) in lesion volume after 48 hours (27.2+/-6.3%) compared with controls (35.3+/-3.7%). A significant reduction (P<0.05) in lesion volume was observed in the argatroban-plus-rtPA group (17.1+/-10.4%) compared with controls (35.3+/-3.7%). No increase in hemorrhagic transformation was observed. Fibrin deposition in the ipsilateral cortical microvasculature was significantly decreased in the 4-hour combination argatroban-plus-rtPA group compared with the controls (P<0.05). CONCLUSIONS: This study demonstrates that the combination of argatroban and rtPA extends the window of opportunity for treatment of stroke to 4 hours without increasing hemorrhagic transformation.

Pseudoaneurysm of the uterine artery after abdominal hysterectomy: radiologic diagnosis and management.

Uterine artery pseudoaneurysm is a rare but serious complication of pelvic surgery. Radiology has an important role in its diagnosis and primary management. We believe that this complication and its management are of importance to those assessing for complications following pelvic surgery.

Trends in outcome and costs of coronary intervention in the 1990s.

Our objective was to examine trends in outcome and cost of percutaneous coronary intervention (PCI) between 1990 and 1999. PCI has become the most common form of myocardial revascularization in recent years, rivaling the more established coronary artery bypass surgery. There has been increasing interest in improving outcome of PCI while also seeking to minimize cost. A total of 21,755 patients undergoing PCI were evaluated. Clinical data were gathered from the Emory Cardiovascular Database and financial data from the UB92 formulation of the hospital bill. Charges were reduced to cost using departmental cost-to-charge ratios. Costs were inflated to 1999 dollars using medical care inflation rates. Mortality varied without a significant trend from 0.63% to 0.44% (p = 0.64). The Q-wave myocardial infarction rate decreased from 0.68% to 0.40% (p = 0.0003). Emergent coronary surgery decreased from 3.50% to 1.25% (p <0.0001). Mean hospital inflation-adjusted cost decreased from $10,478 to $8,367 (p <0.0001). Length of stay after the procedure decreased from 2.8 to 1.8 days (p <0.0001). Outcome of PCI continues to improve, with a decrease in coronary surgery and Q-wave myocardial infarction but with no significant change in mortality. This was accomplished while also decreasing costs and length of stay. Whether these favorable trends will continue remains to be seen.

MR spectroscopy study of dichloroacetate treatment after ischemic stroke.

In a double-blind, placebo-controlled study, we used 1H MR spectroscopy to assess the effect of a single infusion of sodium dichloroacetate on lesion lactate 1 to 5 days after ischemic stroke. Apparent trends toward a reduction in lactate/N-acetyl compound ratios were seen at the higher drug doses employed, and in patients treated in the first 2 days following infarction. Use of spectroscopic measures as endpoints is feasible in acute stroke clinical trials.

Measurement of cerebral microvessel diameters after embolic stroke in rat using quantitative laser scanning confocal microscopy.

Perfusion of the microcirculation after stroke is central to preserving neuronal function and improving functional outcome. Using laser scanning confocal microscopy (LSCM) and a novel computer software program, MIRAGE, we measured a reduction in cerebral microvessel diameter after 1 and 4 h of embolic middle cerebral artery (MCA) occlusion. The methodology used by MIRAGE for measurement of blood vessel diameter involves a linearly applied spherical inflation technique. Three-dimensional quantitative analysis revealed a significant (P<0.05) mean 10-12% reduction in vessel diameter in the ipsilateral cortex when compared to the homologous region in the contralateral hemisphere. This reduction was seen only in the cortex and not the striatum. A larger reduction in mean vessel diameter in the ipsilateral cortex, 16-30% (P<0.05) was observed when compared to sham control rats. These results are in strong agreement with other studies using different stroke models and imaging techniques. Our work represents a novel application of LSCM technology to the three dimensional investigation of microvessel diameter changes in acute stroke and identifies its potential as an important tool for investigation of cerebral pathology.

The use of intrastent peripheral stent in large coronary arteries: report of three cases.

We report three cases of coronary angioplasty using the IntraTherapeutics Intrastent biliary stent. We describe a technique utilizing routine coronary angioplasty equipment including 8 Fr guiding catheters and 0.014" guidewires. This technique can be easily performed in large-diameter coronary arteries.

Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators.

BACKGROUND: Ventricular septal defect (VSD) complicating acute myocardial infarction has been studied primarily in small, prethrombolytic-era trials. Our goal was to determine clinical predictors and angiographic and clinical outcomes of this complication in the thrombolytic era. METHODS AND RESULTS: We compared enrollment characteristics, angiographic patterns, and outcomes (30-day and 1-year mortality) of patients enrolled in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial with and without a confirmed diagnosis of VSD. Univariable and multivariable analyses were used to assess relations between enrollment factors and the development of VSD. In all, 84 of the 41 021 patients (0.2%) developed VSD, a smaller percentage than reported in the prethrombolytic era. The median time from symptom onset to VSD diagnosis was 1 day. Enrollment factors most associated with this complication were advanced age, anterior infarction, female sex, and no previous smoking. The infarct artery was more often the left anterior descending and more likely to be totally occluded in patients who developed VSD. Mortality at 30 days was higher in patients with VSDs than in those without this complication (73.8% versus 6.8%, P<0.001). Patients with VSDs selected for surgical repair (n=34) had better outcomes than patients treated medically (n=35; 30-day mortality, 47% versus 94%). CONCLUSIONS: Compared with historical control subjects, patients who undergo thrombolysis within 6 hours of infarction onset may have a reduced risk of later VSD. If patients develop this mechanical complication, however, it typically occurs sooner than described in the prethrombolytic era. Despite improvements in medical therapy and percutaneous and surgical techniques, mortality with this complication remains extremely high.

High resolution quantitation of microvascular plasma perfusion in non-ischemic and ischemic rat brain by laser-scanning confocal microscopy.

Laser-scanning confocal microscopy (LSCM) was used to measure at high resolution cerebral plasma volumes (perfusion) using two fluorescent plasma markers in a rat model of embolic stroke. This application of LSCM to study the microvascular circulation in embolic stroke was developed as an alternative to autoradiography to measure cerebral perfusion. An additional benefit of LSCM is that it quantitates with great accuracy the structural relationships of the microcirculation to cells and the pathological alterations of the ischemic brain. Autoradiography allows only a quantitative analysis of cerebral perfusion. For example, in order to study the microcirculation and its relationship to blood brain barrier damage, the volume of perfused cerebral capillaries was measured by administering two fluorescent plasma markers (FITC-dextran and Evans blue) intravenously to a rat. Evans blue was administered before cerebral ischemia and FITC-dextran administered post-ischemia 1 min before sacrifice. Volumes of plasma perfusion were analyzed by means of a system developed for 3D analysis of fixed and stained serial brain histologies. Plasma volumes for the non-ischemic cerebral cortex were 1.00%+/-0.38% while plasma volumes in the caudate/putamen were 0.69%+/-0.17% in good agreement with the previously published values using the autoradiography method. The architecture of the capillaries in the ischemic core showed perfusion of Evans blue but there was no flow of FITC dextran. Our work represents a novel application of this technology to investigation of cerebral vascular disease and identifies its potential to become an important tool for investigation of cerebral pathology.

Can cardiovascular clinical characteristics be identified and outcome models be developed from an in-patient claims database?

The objective of this study was to assess whether administrative (claims) databases can be used to assess clinical variables and predict outcome. Although administrative databases are useful for assessing resource utilization, their utility for assessing clinical information is less certain. Prospectively gathered clinical databases, however, are expensive and not widely available. The UB92 formulation of the hospital bill was used as an administrative source of data and compared with the clinical cardiovascular database at Emory University. The claims database was compared with the clinical database for 11 variables. Outcome models were developed with multivariate methods. A total of 11,883 patients who underwent catheterization (5,255 underwent percutaneous transluminal coronary angioplasty [PTCA] and 3,794 underwent coronary artery bypass surgery [CABG]) between 1991 and 1995 were included. For some variables, the claims database correlated well (diabetes, sensitivity 87%, specificity 99%), whereas for others the claims database was less accurate (peripheral vascular disease, sensitivity 20%, specificity 99%). Uncertain coding in the claims database, which can result in the same code being used for co-morbid states and severity of disease, as well as complications, limited the ability of claims to predict outcome. Clinical databases may also be limited by lack of objectivity and missing data. The utility of claims databases to assess severity of disease and co-morbid states is limited, and outcome modeling and risk assessment from claims databases may be inappropriate and spurious. Developing better data standards and less expensive methods for acquisition of clinical data is necessary for improved outcome assessment.