Proximal ischemia is a frequent cause of exercise-induced pain in patients with a normal ankle to brachial index at rest

BACKGROUND: Excluding a vascular origin of exercise-related pain is often difficult in clinical practice. Recent papers have underlined the frequent association of concurrent lumbar spine degenerative disease and peripheral arterial disease. Furthermore, even when suspected, isolated exercise-induced proximal ischemia is difficult to diagnose. Measurement of transcutaneous oxygen pressure (tcpO2) is an interesting and accurate method to differentiate proximal (buttock) from distal (calf) regional blood flow impairment (RBFI) during exercise. OBJECTIVES: We searched for isolated proximal-without-distal RBFI as a possible cause of claudication, in patients with borderline (ABI-b: 0.91 - 0.99) or normal (ABI-n: 1.00 to 1.40) ankle to brachial index at rest. STUDY DESIGN: Retrospective cohort design study. We analyzed patients referred to our laboratory with symptom limiting claudication and an ankle brachial index within normal limits. SETTING: University-based exercise-investigation center. METHODS: Over a 12-year period, we identified 463 patients referred to our laboratory that had their lowest resting ABI between 0.90 and 1.40. The tcpO2 on chest, buttocks, and calves were recorded during treadmill walking tests (3.2 km/h, 10% slope) in 220 ABI-b and 243 ABI-n unique consecutive patients complaining of limiting claudication (each patient\u27s ABI was the lowest of the 2 legs). Limiting claudication was defined as the reported inability to walk 1 kilometer without stopping. A DROP index (limb tcpO2-changes minus chest tcpO2-changes from rest) below -15 mmHg was used to indicate a positive result (i.e. exercise-induced RBFI). RESULTS: Treadmill exercise showed evidence for proximal or distal RBFI, of at least one side, in 128 out of 220 patients (58.2%) and in 86 out of 243 (35.4%) patients with ABI-b and ABI-n, respectively. Isolated proximal-without-distal RBFI was found in 32 out of the 128 (25.0 %) positive tests in ABI-b and 32 out of the 86 (37.2%) positive tests in ABI-n patients. LIMITATIONS: Study limitations include the absence of systematic follow-up of diagnosed patients and absence of systematic search for cardio-respiratory co-morbid conditions. CONCLUSION: Isolated proximal-without distal RBFI is found in approximately one out of 7 patients complaining of symptom limiting claudication with a borderline or normal resting ABI. Exercise-tcpO2 may help to discriminate patients with arterial claudication that could benefit from invasive vascular investigations and procedures

Finite Theories and the SUSY Flavor Problem

We study a finite SU(5) grand unified model based on the non-Abelian discrete symmetry A_4. This model leads to the democratic structure of the mass matrices for the quarks and leptons. In the soft supersymmetry breaking sector, the scalar trilinear couplings are aligned and the soft scalar masses are degenerate, thus solving the SUSY flavor problem.Comment: 17 pages, LaTeX, 1 figur

The histone binding capacity of SPT2 controls chromatin structure and function in Metazoa

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response. Genome-wide profiling showed that CeSPT-2 binds to a range of highly expressed genes, and we find that spt-2 mutants have increased chromatin accessibility at a subset of these loci. We also show that SPT2 influences chromatin structure and controls the levels of soluble and chromatin-bound H3.3 in human cells. Our work reveals roles for SPT2 in controlling chromatin structure and function in Metazoa.</p

Corporate political activity in less developed countries:The Volta River Project in Ghana, 1958-66

The article expands existing categorisations of political and economic governance by including literature on less developed countries (LDCs). In four consecutive negotiations between the US multinational Kaisers and the US and Ghana governments in the early 1960s, it is argued that the company reached levels of influence that are at odds with existing explanations. In order to understand corporate political activities in LDCs, analysis needs to go beyond static factors (political risk) and include dynamic factors such as diplomatic relations and 'arenas of power', and consider the role of the investor's home country relative to the host economy

Could climate change benefit invasive snakes? Modelling the potential distribution of the California Kingsnake in the Canary Islands

The interaction between climate change and biological invasions is a global conservation challenge with major consequences for invasive species management. However, our understanding of this interaction has substantial knowledge gaps; this is particularly relevant for invasive snakes on islands because they can be a serious threat to island ecosystems. Here we evaluated the potential influence of climate change on the distribution of invasive snakes on islands, using the invasion of the California kingsnake (Lampropeltis californiae) in Gran Canaria. We analysed the potential distribution of L. californiae under current and future climatic conditions in the Canary Islands, with the underlying hypothesis that the archipelago might be suitable for the species under these climate scenarios. Our results indicate that the Canary Islands are currently highly suitable for the invasive snake, with increased suitability under the climate change scenarios tested here. This study supports the idea that invasive reptiles represent a substantial threat to near-tropical regions, and builds on previous studies suggesting that the menace of invasive reptiles may persist or even be exacerbated by climate change. We suggest future research should continue to fill the knowledge gap regarding invasive reptiles, in particular snakes, to clarify their potential future impacts on global biodiversity

3640 Unique EST Clusters from the Medaka Testis and Their Potential Use for Identifying Conserved Testicular Gene Expression in Fish and Mammals

BACKGROUND: The fish medaka is the first vertebrate capable of full spermatogenesis in vitro from self-renewing spermatogonial stem cells to motile test-tube sperm. Precise staging and molecular dissection of this process has been hampered by the lack of suitable molecular markers. METHODOLOGY AND PRINCIPAL FINDINGS: We have generated a normalized medaka testis cDNA library and obtained 7040 high quality sequences representing 3641 unique gene clusters. Among these, 1197 unique clusters are homologous to known genes, and 2444 appear to be novel genes. Ontology analysis shows that the 1197 gene products are implicated in diverse molecular and cellular processes. These genes include markers for all major types of testicular somatic and germ cells. Furthermore, markers were identified for major spermatogenic stages ranging from spermatogonial stem cell self-renewal to meiosis entry, progression and completion. Intriguingly, the medaka testis expresses at least 13 homologs of the 33 mouse X-chromosomal genes that are enriched in the testis. More importantly, we show that key components of several signaling pathways known to be important for testicular function in mammals are well represented in the medaka testicular EST collection. CONCLUSIONS/SIGNIFICANCE: Medaka exhibits a considerable similarity in testicular gene expression to mammals. The medaka testicular EST collection we obtained has wide range coverage and will not only consolidate our knowledge on the comparative analysis of known genes' functions in the testis but also provide a rich resource to dissect molecular events and mechanism of spermatogenesis in vivo and in vitro in medaka as an excellent vertebrate model

Potent Antioxidant and Genoprotective Effects of Boeravinone G, a Rotenoid Isolated from Boerhaavia diffusa

Background and Aims: Free radicals are implicated in the aetiology of some gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. In the present study we investigated the antioxidant and genoprotective activity of some rotenoids (i.e. boeravinones) isolated from the roots of Boerhaavia diffusa, a plant used in the Ayurvedic medicine for the treatment of diseases affecting the gastrointestinal tract. Methods/Principal Findings: Antioxidant activity has been evaluated using both chemical (Electron Spin Resonance spectroscopy, ESR) and Caco-2 cells-based (TBARS and ROS) assays. DNA damage was evaluated by Comet assay, while pERK 1/2 and phospho-NF-kB p65 levels were estimated by western blot. Boeravinones G, D and H significantly reduced the signal intensity of ESR induced by hydroxyl radicals, suggesting a scavenging activity. Among rotenoids tested, boeravinone G exerted the most potent effect. Boeravinone G inhibited both TBARS and ROS formation induced by Fenton's reagent, increased SOD activity and reduced H 2O 2-induced DNA damage. Finally, boeravinone G reduced the levels of pERK 1 and phospho-NF-kB p65 (but not of pERK 2) increased by Fenton's reagent. Conclusions: It is concluded that boeravinone G exhibits an extraordinary potent antioxidant activity (significant effect in the nanomolar range). The MAP kinase and NF-kB pathways seem to be involved in the antioxidant effect of boeravinone G. Boeravinone G might be considered as lead compound for the development of drugs potentially useful against those pathologies whose aetiology is related to ROS-mediated injuries

Organizational innovation in the multinational enterprise: internalization theory and business history

This article engages in a methodological experiment by using historical evidence to challenge a common misperception about internalization theory. The theory has often been criticized for maintaining that it assumes a hierarchically organized MNE based on knowledge flowing from the home country. This is not an accurate description of how global firms operate in recent decades, but this article shows it has never been true historically. Using longitudinal data on individual firms from the nineteenth century onwards, it reveals evidence of how entrepreneurs and firms with multinational activity faced with market imperfections changed the design of their headquarters and their organizational structures