Gold catalysed synthesis of 3-alkoxyfurans at room temperature

Synthetically important 3-alkoxyfurans can be prepared efficiently via treatment of acetal-containing propargylic alcohols (obtained from the addition of 3,3-diethoxypropyne to aldehydes) with 2 mol% gold catalyst in an alcohol solvent at room temperature. The resulting furans show useful reactivity in a variety of subsequent transformations

GridIMAGE: A Novel Use of Grid Computing to Support Interactive Human and Computer-Assisted Detection Decision Support

This paper describes a Grid-aware image reviewing system (GridIMAGE) that allows practitioners to (a) select images from multiple geographically distributed digital imaging and communication in medicine (DICOM) servers, (b) send those images to a specified group of human readers and computer-assisted detection (CAD) algorithms, and (c) obtain and compare interpretations from human readers and CAD algorithms. The currently implemented system was developed using the National Cancer Institute caGrid infrastructure and is designed to support the identification of lung nodules on thoracic computed tomography. However, the infrastructure is general and can support any type of distributed review. caGrid data and analytical services are used to link DICOM image databases and CAD systems and to interact with human readers. Moreover, the service-oriented and distributed structure of the GridIMAGE framework enables a flexible system, which can be deployed in an institution (linking multiple DICOM servers and CAD algorithms) and in a Grid environment (linking the resources of collaborating research groups). GridIMAGE provides a framework that allows practitioners to obtain interpretations from one or more human readers or CAD algorithms. It also provides a mechanism to allow cooperative imaging groups to systematically perform image interpretation tasks associated with research protocols

Hypertension Management Using Mobile Technology and Home Blood Pressure Monitoring: Results of a Randomized Trial in Two Low/Middle-Income Countries

Abstract Objective: Hypertension and other noncommunicable diseases represent a growing threat to low/middle-income countries (LMICs). Mobile health technologies may improve noncommunicable disease outcomes, but LMICs lack resources to provide these services. We evaluated the efficacy of a cloud computing model using automated self-management calls plus home blood pressure (BP) monitoring as a strategy for improving systolic BPs (SBPs) and other outcomes of hypertensive patients in two LMICs. Subjects and Methods: This was a randomized trial with a 6-week follow-up. Participants with high SBPs (≥140?mm Hg if nondiabetic and ≥130?mm Hg if diabetic) were enrolled from clinics in Honduras and Mexico. Intervention patients received weekly automated monitoring and behavior change telephone calls sent from a server in the United States, plus a home BP monitor. At baseline, control patients received BP results, hypertension information, and usual healthcare. The primary outcome, SBP, was examined for all patients in addition to a preplanned subgroup with low literacy or high hypertension information needs. Secondary outcomes included perceived health status and medication-related problems. Results: Of the 200 patients recruited, 181 (90%) completed follow-up, and 117 of 181 had low literacy or high hypertension information needs. The median annual income was $2,900 USD, and average educational attainment was 6.5 years. At follow-up intervention patients' SBPs decreased 4.2?mm Hg relative to controls (95% confidence interval ?9.1, 0.7; p=0.09). In the subgroup with high information needs, intervention patients' average SBPs decreased 8.8?mm Hg (?14.2, ?3.4, p=0.002). Compared with controls, intervention patients at follow-up reported fewer depressive symptoms (p=0.004), fewer medication problems (p<0.0001), better general health (p<0.0001), and greater satisfaction with care (p≤0.004). Conclusions: Automated telephone care management plus home BP monitors can improve outcomes for hypertensive patients in LMICs. A cloud computing model within regional telecommunication centers could make these services available in areas with limited infrastructure for patient-focused informatics support.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98494/1/tmj%2E2011%2E0271.pd

Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia

White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP + astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehydedehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP + cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by 42-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P50.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP + astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood–brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1–28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP + astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood–brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia

Alpha-particle-induced complex chromosome exchanges transmitted through extra-thymic lymphopoiesis in vitro show evidence of emerging genomic instability

Human exposure to high-linear energy transfer α-particles includes environmental (e.g. radon gas and its decay progeny), medical (e.g. radiopharmaceuticals) and occupational (nuclear industry) sources. The associated health risks of α-particle exposure for lung cancer are well documented however the risk estimates for leukaemia remain uncertain. To further our understanding of α-particle effects in target cells for leukaemogenesis and also to seek general markers of individual exposure to α-particles, this study assessed the transmission of chromosomal damage initially-induced in human haemopoietic stem and progenitor cells after exposure to high-LET α-particles. Cells surviving exposure were differentiated into mature T-cells by extra-thymic T-cell differentiation in vitro. Multiplex fluorescence in situ hybridisation (M-FISH) analysis of naïve T-cell populations showed the occurrence of stable (clonal) complex chromosome aberrations consistent with those that are characteristically induced in spherical cells by the traversal of a single α-particle track. Additionally, complex chromosome exchanges were observed in the progeny of irradiated mature T-cell populations. In addition to this, newly arising de novo chromosome aberrations were detected in cells which possessed clonal markers of α-particle exposure and also in cells which did not show any evidence of previous exposure, suggesting ongoing genomic instability in these populations. Our findings support the usefulness and reliability of employing complex chromosome exchanges as indicators of past or ongoing exposure to high-LET radiation and demonstrate the potential applicability to evaluate health risks associated with α-particle exposure.This work was supported by the Department of Health, UK. Contract RRX95 (RMA NSDTG)

Informing the design of a national screening and treatment programme for chronic viral hepatitis in primary care: qualitative study of at-risk immigrant communities and healthcare professionals

n Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedThis paper presents independent research funded by the National Institute for Health Research (NIHR) under the Programme Grants for Applied Research programme (RP-PG-1209-10038).

QPRT: a potential marker for follicular thyroid carcinoma including minimal invasive variant; a gene expression, RNA and immunohistochemical study

Background The differential diagnosis between follicular thyroid adenoma and minimal invasive follicular thyroid carcinoma is often difficult for several reasons. One major aspect is the lack of typical cytological criteria in well differentiated specimens. New marker molecules, shown by poly- or monoclonal antibodies proved helpful. Methods We performed global gene expression analysis of 12 follicular thyroid tumours (4 follicular adenomas, 4 minimal invasive follicular carcinomas and 4 widely invasive follicular carcinomas), followed by immunohistochemical staining of 149 cases. The specificity of the antibody was validated by western blot analysis Results In gene expression analysis QPRT was detected as differently expressed between follicular thyroid adenoma and follicular thyroid carcinoma. QPRT protein could be detected by immunohistochemistry in 65% of follicular thyroid carcinomas including minimal invasive variant and only 22% of follicular adenomas. Conclusion Consequently, QPRT is a potential new marker for the immunohistochemical screening of follicular thyroid nodules