Cerebrovascular carbon dioxide reactivity and flow-mediated dilation in young healthy South Asian and Caucasian European men.

South Asians living in the United Kingdom have a 1.5-fold greater risk of ischemic stroke than the general population. Impaired cerebrovascular carbon dioxide (CO2) reactivity is an independent predictor of ischemic stroke and cardiovascular mortality. We sought to test the hypothesis that cerebrovascular CO2 reactivity is reduced in South Asians. Middle cerebral artery blood velocity (MCA Vm) was measured at rest and during stepwise changes in end-tidal partial pressure of CO2 (PETCO2) in South Asian (n = 16) and Caucasian European (n = 18) men who were young (~20 yr), healthy, and living in the United Kingdom. Incremental hypercapnia was delivered via the open-circuit steady-state method, with stages of 4 and 7% CO2 (≈21% oxygen, nitrogen balanced). Cerebrovascular CO2 reactivity was calculated as the change in MCA Vm relative to the change in PETCO2. MCA Vm was not different in South Asians [59 (9) cm/s, mean (standard deviation)] and Caucasian Europeans [61 (12) cm/s; P > 0.05]. Similarly, cerebrovascular CO2 reactivity was not different between the groups [South Asian 2.53 (0.76) vs. Caucasian European 2.61 (0.81) cm·s-1·mmHg-1; P > 0.05]. Brachial artery flow-mediated dilation was lower in South Asians [5.48 (2.94)%] compared with Caucasian Europeans [7.41 (2.28)%; P < 0.05]; however, when corrected for shear rate no between-group differences in flow-mediated dilation were observed (P > 0.05). Flow-mediated dilation was not correlated with cerebrovascular CO2 reactivity measures. In summary, cerebrovascular CO2 reactivity and flow-mediated dilation corrected for shear rate are preserved in young healthy South Asian men living in the United Kingdom.NEW & NOTEWORTHY Previous reports have identified an increased risk of ischemic stroke and peripheral endothelial dysfunction in South Asians compared with Caucasian Europeans. The main finding of this study is that cerebrovascular carbon dioxide reactivity (an independent predictor of ischemic stroke) is not different in healthy young South Asian and Caucasian European men.

Suitability of loci for multiple-locus variable-number of tandem-repeats analysis of Cryptosporidium parvum for inter-laboratory surveillance and outbreak investigations.

Cryptosporidium parvum is the major cause of livestock and zoonotically-acquired human cryptosporidiosis. The ability to track sources of contamination and routes of transmission by further differentiation of isolates would assist risk assessment and outbreak investigations. Multiple-locus variable-number of tandem-repeats (VNTR) analysis provides a means for rapid characterization by fragment sizing and estimation of copy numbers, but structured, harmonized development has been lacking for Cryptosporidium spp. To investigate potential for application in C. parvum surveillance and outbreak investigations, we studied nine commonly used VNTR loci (MSA, MSD, MSF, MM5, MM18, MM19, MS9-Mallon, GP60 and TP14) for chromosome distribution, repeat unit length and heterogeneity, and flanking region proximity and conservation. To investigate performance in vitro, we compared these loci in 14 C. parvum samples by capillary electrophoresis in three laboratories. We found that many loci did not contain simple repeat units but were more complex, hindering calculations of repeat unit copy number for standardized reporting nomenclature. However, sequenced reference DNA enabled reproducible fragment sizing and inter-laboratory allele assignation based on size normalized to that of the sequenced fragments by both single round and nested polymerase chain reactions. Additional Cryptosporidium loci need to be identified and validated for robust inter-laboratory surveillance and outbreak investigations.

The Trypanosoma brucei AIR9-like protein is cytoskeleton-associated and is required for nucleus positioning and accurate cleavage furrow placement.

AIR9 is a cytoskeleton-associated protein in Arabidopsis thaliana with roles in cytokinesis and cross wall maturation, and reported homologues in land plants and excavate protists, including trypanosomatids. We show that the Trypanosoma brucei AIR9-like protein, TbAIR9, is also cytoskeleton-associated and colocalizes with the subpellicular microtubules. We find it to be expressed in all life cycle stages and show that it is essential for normal proliferation of trypanosomes in vitro. Depletion of TbAIR9 from procyclic trypanosomes resulted in increased cell length due to increased microtubule extension at the cell posterior. Additionally, the nucleus was re-positioned to a location posterior to the kinetoplast, leading to defects in cytokinesis and the generation of aberrant progeny. In contrast, in bloodstream trypanosomes, depletion of TbAIR9 had little effect on nucleus positioning, but resulted in aberrant cleavage furrow placement and the generation of non-equivalent daughter cells following cytokinesis. Our data provide insight into the control of nucleus positioning in this important pathogen and emphasize differences in the cytoskeleton and cell cycle control between two life cycle stages of the T. brucei parasite.

A comparison of the outcome of aneurysmal subarachnoid haemorrhage before and after the introduction of an endovascular service.

There has been a rapid change from predominantly surgical to endovascular treatment of ruptured intracranial aneurysms giving the opportunity to assess change in patient outcome during this transition. We identified and followed 139 patients with subarachnoid haemorrhage (SAH) treated in the year prior to (group 1) and following (group 2) the introduction of an endovascular service in a retrospective, cross-sectional study. A total of 78.7% of patients in group 1 underwent surgical treatment, 10.7% underwent endovascular treatment and 10.7% received no treatment, whereas patients in group 2 received 29.7%, 65.7% and 4.7%, respectively. MRS scores were obtained in 91% of patients in group 1 and in 89% of patients in group 2. A total of 30.7% and 24.0% of patients had a poor outcome in groups 1 and 2 respectively (p=0.34). The overall change in the management of ruptured cerebral aneurysms in the post-International Subarachnoid Aneurysm Trial (ISAT) era has not significantly changed cross-sectional outcome, although absolute differences appear to reflect difference in outcome noted in the ISAT.