Renal artery stenosis-when to screen, what to stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed

Spherical perspective

We survey the present state of spherical perspective, regarding both mathematical structure and drawing practice, with a view to applications in the visual arts. We define a spherical perspective as the entailment of a conical anamorphosis with a compact flattening of the visual sphere. We examine a general framework for solving spherical perspectives, exemplified with the azimuthal equidistant (“fisheye”) and equirectangular cases. We consider the relation between spherical and curvilinear perspectives. We briefly discuss computer renderings but focus on methods adapted to freehand sketching or technical drawing with simple instruments such as ruler and compass. We discuss how handmade spherical perspective drawings can generate immersive anamorphoses, which can be rendered as virtual reality panoramas, leading to hybrid visual creations that bridge the gap between traditional drawing and digital environments.info:eu-repo/semantics/publishedVersio

Evolutionary, ecological and biotechnological perspectives on plasmids resident in the human gut mobile metagenome

Numerous mobile genetic elements (MGE) are associated with the human gut microbiota and collectively referred to as the gut mobile metagenome. The role of this flexible gene pool in development and functioning of the gut microbial community remains largely unexplored, yet recent evidence suggests that at least some MGE comprising this fraction of the gut microbiome reflect the co-evolution of host and microbe in the gastro-intestinal tract. In conjunction, the high level of novel gene content typical of MGE coupled with their predicted high diversity, suggests that the mobile metagenome constitutes an immense and largely unexplored gene-space likely to encode many novel activities with potential biotechnological or pharmaceutical value, as well as being important to the development and functioning of the gut microbiota. Of the various types of MGE that comprise the gut mobile metagenome, plasmids are of particular importance since these elements are often capable of autonomous transfer between disparate bacterial species, and are known to encode accessory functions that increase bacterial fitness in a given environment facilitating bacterial adaptation. In this article current knowledge regarding plasmids resident in the human gut mobile metagenome is reviewed, and available strategies to access and characterize this portion of the gut microbiome are described. The relative merits of these methods and their present as well as prospective impact on our understanding of the human gut microbiota is discussed

Impact of mediastinal, liver and lung 123I-metaiodobenzylguanidine (123I-MIBG) washout on calculated 123I-MIBG myocardial washout

PURPOSE: In planar (123)I-metaiodobenzylguanidine ((123)I-MIBG) myocardial imaging mediastinum (M) activity is often used as a background correction in calculating "washout" (WO). However, the most likely sources for counts that might produce errors in estimating myocardial (Myo) activity are lung (Lu) and liver (Li), which typically have higher counts/pixel (cpp) than M. The present study investigated the relationship between changes in Lu, Li and Myo activity between early and late planar (123)I-MIBG images, with comparison to M as the best estimator of non-specific background activity. METHODS: Studies on 98 subjects with both early (e) and late (l) planar (123)I-MIBG images were analysed. There were 68 subjects with chronic heart failure (CHF), 14 with hypertension (HTN) but no known heart disease and 16 controls (C). For each image, regions of interest (ROIs) were drawn: an irregular whole Myo, Lu, upper M and Li. For each ROI, WO was calculated as [(cpp(e)-cpp(l:decay corrected))/cpp(e)]x100%. RESULTS: Multivariable forward stepwise regression analysis showed that overall a significant proportion of the variation in Myo WO could be explained by a model containing M WO and Lu WO (37%, p < 0.001). Only in controls was M WO the sole variable explaining a significant proportion of the variation in Myo WO (27%, p = 0.023). CONCLUSION: Although increased Myo WO in CHF subjects reflects disease severity, part of the count differences measured on planar (123)I-MIBG myocardial images likely reflects changes in the adjacent and surrounding Lu tissue. The results for the controls suggest that this is the only group where a mediastinum correction alone may be appropriate for cardiac WO calculation

Are the pneumococcal polysaccharide vaccines effective? Meta-analysis of the prospective trials

The objective was to review the evidence of effectiveness of the polyvalent polysaccharide pneumococcal vaccine from prospective properly randomised controlled trials comparing pneumococcal vaccines with placebo in subjects who are immunocompetent and those likely to have an impaired immune system. Databases searched included the Cochrane Library, (issue 2, 2000), MEDLINE (1966-August 2000), PubMed (to August 2000) and EMBASE ( to August 2000). Reference lists of reports and reviews were also searched. To be included in the analysis, a study had to have been a prospective randomised comparison of a polysaccharide pneumococcal vaccine (any valency) and to have a placebo or no treatment comparison group. Papers had to report important clinical outcomes, such as rates of pneumonia, pneumococcal pneumonia, lower respiratory tract infections, pneumonia deaths or bacteraemia. Serological outcomes were not sought. Thirteen randomised comparisons with over 45,000 subjects were identified in an extensive literature review. Eight studies had a quality score of 3 or more on a scale of 1 to 5. In three comparisons with 21,152 immunocompetent subjects (South African gold miners, New Guinea highlanders) pneumococcal vaccination was effective in reducing the incidence of all-cause pneumonia (relative risk 0.56, 95% confidence interval 0.47 to 0.66), pneumococcal pneumonia (0.16; 0.11 to 0.23), pneumonia deaths (0.70; 0.50 to 0.96) and bacteraemia (0.18; 0.09 to 0.34). In ten comparisons in over 24,000 people who were elderly or likely to have impaired immune systems, pneumococcal vaccination was without effect for any outcome. Present guidelines recommend pneumococcal vaccination for "high-risk" groups. There is no evidence from randomised trials that this is of any benefit

Effects of L1-ORF2 fragments on green fluorescent protein gene expression

The retrotransposon known as long interspersed nuclear element-1 (L1) is 6 kb long, although most L1s in mammalian and other eukaryotic cells are truncated. L1 contains two open reading frames, ORF1 and ORF2, that code for an RNA-binding protein and a protein with endonuclease and reverse transcriptase activities, respectively. In this work, we examined the effects of full length L1-ORF2 and ORF2 fragments on green fluorescent protein gene (GFP) expression when inserted into the pEGFP-C1 vector downstream of GFP. All of the ORF2 fragments in sense orientation inhibited GFP expression more than when in antisense orientation, which suggests that small ORF2 fragments contribute to the distinct inhibitory effects of this ORF on gene expression. These results provide the first evidence that different 280-bp fragments have distinct effects on the termination of gene transcription, and that when inserted in the antisense direction, fragment 280-9 (the 3' end fragment of ORF2) induces premature termination of transcription that is consistent with the effect of ORF2

Mitochondrial Pseudogenes in the Nuclear Genomes of Drosophila

Mitochondrial pseudogenes in nuclear chromosomes (numts) have been detected in the genomes of a diverse range of eukaryotic species. However, the numt content of different genomes and their properties is not uniform, and study of these differences provides insight into the mechanisms and dynamics of genome evolution in different organisms. In the genus Drosophila, numts have previously only been identified on a genome-wide scale in the melanogaster subgroup. The present study extends the identification to 11 species of the Drosophila genus. We identify a total of 302 numts and show that the numt complement is highly variable in Drosophilids, ranging from just 4 in D. melanogaster to 67 in D. willistoni, broadly correlating with genome size. Many numts have undergone large-scale rearrangements in the nucleus, including interruptions, inversions, deletions and duplications of sequence of variable size. Estimating the age of the numts in the nucleus by phylogenetic tree reconstruction reveals the vast majority of numts to be recent gains, 90% having arisen on terminal branches of the species tree. By identifying paralogs and counting duplications among the extant numts we estimate that 23% of extant numts arose through post-insertion duplications. We estimate genus average rates of insertion of 0.75 per million years, and a duplication rate of 0.010 duplications per numt per million years

Migration of Th1 Lymphocytes Is Regulated by CD152 (CTLA-4)-Mediated Signaling via PI3 Kinase-Dependent Akt Activation

Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response

African herbal medicines in the treatment of HIV: Hypoxis and Sutherlandia. An overview of evidence and pharmacology

In Africa, herbal medicines are often used as primary treatment for HIV/AIDS and for HIV-related problems. In general, traditional medicines are not well researched, and are poorly regulated. We review the evidence and safety concerns related to the use of two specific African herbals, which are currently recommended by the Ministry of Health in South Africa and member states for use in HIV: African Potato and Sutherlandia. We review the pharmacology, toxicology and pharmacokinetics of these herbal medicines. Despite the popularity of their use and the support of Ministries of Health and NGOs in some African countries, no clinical trials of efficacy exist, and low-level evidence of harm identifies the potential for drug interactions with antiretroviral drugs. Efforts should be made by mainstream health professionals to provide validated information to traditional healers and patients on the judicious use of herbal remedies. This may reduce harm through failed expectations, pharmacologic adverse events including possible drug/herb interactions and unnecessary added therapeutic costs. Efforts should also be directed at evaluating the possible benefits of natural products in HIV/AIDS treatment

Nursing home care for people with dementia and residents' quality of life, quality of care and staff well-being: Design of the Living Arrangements for people with Dementia (LAD) - study

<p>Abstract</p> <p>Background</p> <p>There is limited information available on how characteristics of the organization of nursing home care and especially group living home care and staff ratio contribute to care staff well being, quality of care and residents' quality of life. Furthermore, it is unknown what the consequences of the increasingly small scale organization of care are for the amount of care staff required in 2030 when there will be much more older people with dementia.</p> <p>Methods/Design</p> <p>This manuscript describes the design of the 'Living Arrangements for people with Dementia study' (LAD-study). The aim of this study is to include living arrangements from every part of this spectrum, ranging from large scale nursing homes to small group living homes. The LAD-study exists of quantitative and qualitative research. Primary outcomes of the quantitative study are wellbeing of care staff, quality of care and quality of life of residents. Furthermore, data concerning staff ratio and characteristics of the living arrangements such as group living home care characteristics are assessed. To get more in-depth insight into the barriers and facilitators in living arrangements for people with dementia to provide good care, focus groups and Dementia Care Mapping are carried out.</p> <p>Discussion</p> <p>Results of this study are important for policymakers, directors and staff of living arrangements providing nursing home care to people with dementia and essential for the development of methods to improve quality of care, residents' and staff well-being. Data collection will be repeated every two years, to generate knowledge on the results of changing policies in this field.</p