Acute effects of nicotine on visual search tasks in young adult smokers

Rationale Nicotine is known to improve performance on tests involving sustained attention and recent research suggests that nicotine may also improve performance on tests involving the strategic allocation of attention and working memory. Objectives We used measures of accuracy and response latency combined with eye-tracking techniques to examine the effects of nicotine on visual search tasks. Methods In experiment 1 smokers and non-smokers performed pop-out and serial search tasks. In experiment 2, we used a within-subject design and a more demanding search task for multiple targets. In both studies, 2-h abstinent smokers were asked to smoke one of their own cigarettes between baseline and tests. Results In experiment 1, pop-out search times were faster after nicotine, without a loss in accuracy. Similar effects were observed for serial searches, but these were significant only at a trend level. In experiment 2, nicotine facilitated a strategic change in eye movements resulting in a higher proportion of fixations on target letters. If the cigarette was smoked on the first trial (when the task was novel), nicotine additionally reduced the total number of fixations and refixations on all letters in the display. Conclusions Nicotine improves visual search performance by speeding up search time and enabling a better focus of attention on task relevant items. This appears to reflect more efficient inhibition of eye movements towards task irrelevant stimuli, and better active maintenance of task goals. When the task is novel, and therefore more difficult, nicotine lessens the need to refixate previously seen letters, suggesting an improvement in working memory

State of the art: refinement of multiple sequence alignments

BACKGROUND: Accurate multiple sequence alignments of proteins are very important in computational biology today. Despite the numerous efforts made in this field, all alignment strategies have certain shortcomings resulting in alignments that are not always correct. Refinement of existing alignment can prove to be an intelligent choice considering the increasing importance of high quality alignments in large scale high-throughput analysis. RESULTS: We provide an extensive comparison of the performance of the alignment refinement algorithms. The accuracy and efficiency of the refinement programs are compared using the 3D structure-based alignments in the BAliBASE benchmark database as well as manually curated high quality alignments from Conserved Domain Database (CDD). CONCLUSION: Comparison of performance for refined alignments revealed that despite the absence of dramatic improvements, our refinement method, REFINER, which uses conserved regions as constraints performs better in improving the alignments generated by different alignment algorithms. In most cases REFINER produces a higher-scoring, modestly improved alignment that does not deteriorate the well-conserved regions of the original alignment

Multi-parametric flow cytometric and genetic investigation of the peripheral B cell compartment in human type 1 diabetes.

The appearance of circulating islet-specific autoantibodies before disease diagnosis is a hallmark of human type 1 diabetes (T1D), and suggests a role for B cells in the pathogenesis of the disease. Alterations in the peripheral B cell compartment have been reported in T1D patients; however, to date, such studies have produced conflicting results and have been limited by sample size. In this study, we have performed a detailed characterization of the B cell compartment in T1D patients (n = 45) and healthy controls (n = 46), and assessed the secretion of the anti-inflammatory cytokine interleukin (IL)-10 in purified B cells from the same donors. Overall, we found no evidence for a profound alteration of the B cell compartment or in the production of IL-10 in peripheral blood of T1D patients. We also investigated age-related changes in peripheral B cell subsets and confirmed the sharp decrease with age of transitional CD19(+) CD27(-) CD24(hi) CD38(hi) B cells, a subset that has recently been ascribed a putative regulatory function. Genetic analysis of the B cell compartment revealed evidence for association of the IL2-IL21 T1D locus with IL-10 production by both memory B cells (P = 6·4 × 10(-4) ) and islet-specific CD4(+) T cells (P = 2·9 × 10(-3) ). In contrast to previous reports, we found no evidence for an alteration of the B cell compartment in healthy individuals homozygous for the non-synonymous PTPN22 Trp(620) T1D risk allele (rs2476601; Arg(620) Trp). The IL2-IL21 association we have identified, if confirmed, suggests a novel role for B cells in T1D pathogenesis through the production of IL-10, and reinforces the importance of IL-10 production by autoreactive CD4(+) T cells

Diversity of floral visitors to sympatric Lithophragma species differing in floral morphology

Most coevolving relationships between pairs of species are embedded in a broader multispecific interaction network. The mutualistic interaction between Lithophragma parviflorum (Saxifragaceae) and its pollinating floral parasite Greya politella (Lepidoptera, Prodoxidae) occurs in some communities as a pairwise set apart from most other interactions in those communities. In other communities, however, this pair of species occurs with congeners and with other floral visitors to Lithophragma. We analyzed local and geographic differences in the network formed by interactions between Lithophragma plants and Greya moths in communities containing two Lithophragma species, two Greya species, and floral visitors other than Greya that visit Lithophragma flowers. Our goal was to evaluate if non-Greya visitors were common, if visitor assembly differs between Lithophragma species and populations and if these visitors act as effective pollinators. Sympatric populations of L. heterophyllum and L. parviflorum differ in floral traits that may affect assemblies of floral visitors. Visitation rates by non-Greya floral visitors were low, and the asymptotic number of visitor species was less than 20 species in all populations. Lithophragma species shared some of the visitors, with visitor assemblages differing between sites more for L. heterophyllum than for L. parviflorum. Pollination efficacy experiments showed that most visitors were poor pollinators. Single visits to flowers by this assemblage of species resulted in significantly higher seed set in Lithophragma heterophyllum (30.6 ± 3.9 SE) than in L. parviflorum (4.7 ± 3.4 SE). This difference was consistent between sites, suggesting that these visitors provide a better fit to the floral morphology of L. heterophyllum. Overall, none of the non-Greya visitors appears to be either sufficiently common or efficient as a pollinator to impose strong selection on any of these four Lithophragma populations in comparison with Greya, which occurs within almost all populations of these species throughout their geographic ranges

Carotid axillary bypass in a patient with blocked subclavian stents: a case report

<p>Abstract</p> <p>Introduction</p> <p>Surgical treatment of symptomatic occlusive lesions of the proximal subclavian artery is infrequently necessary. Carotid subclavian bypass has gained popularity and is now considered standard treatment when stenting is not possible. Exposure of the subclavian artery and bypass grafting onto it is difficult, as the vessel is delicate, thin-walled and located deep in the supraclavicular fossa. The thoracic duct and brachial plexus are in close proximity to the left subclavian artery and are therefore susceptible to damage. Distal grafting to the axillary artery instead of the subclavian artery has the potential of avoiding some of these risks. Infraclavicular exposure of the axillary artery is more straightforward. The vessel wall is thicker and is easier to handle. In this case report, we describe a patient with a left proximal subclavian occlusion which was stented twice and blocked on both occasions. The patient underwent a carotid axillary bypass, as grafting onto the subclavian artery was impossible because of the two occluded metal stents.</p> <p>Case presentation</p> <p>A 56-year-old Caucasian woman, a heavy smoker, presented acutely with left arm numbness and pain and blood pressure discrepancies in both arms. A diagnosis of subclavian stenosis was confirmed on the basis of a computed tomographic scan and a magnetic resonance angiogram. The patient had undergone subclavian artery stenting twice, and unfortunately the stents blocked on both occasions. The patient underwent carotid axillary bypass surgery. She had an uneventful recovery and was able to return to a full, normal life.</p> <p>Conclusion</p> <p>Carotid axillary bypass appears to be a good alternative to carotid subclavian bypass in the treatment of symptomatic proximal stenosis or occlusion of the subclavian artery.</p

Risk stratification by pre-operative cardiopulmonary exercise testing improves outcomes following elective abdominal aortic aneurysm surgery : a cohort study

Background: In 2009, the NHS evidence adoption center and National Institute for Health and Care Excellence (NICE) published a review of the use of endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs). They recommended the development of a risk-assessment tool to help identify AAA patients with greater or lesser risk of operative mortality and to contribute to mortality prediction. A low anaerobic threshold (AT), which is a reliable, objective measure of pre-operative cardiorespiratory fitness, as determined by pre-operative cardiopulmonary exercise testing (CPET) is associated with poor surgical outcomes for major abdominal surgery. We aimed to assess the impact of a CPET-based risk-stratification strategy upon perioperative mortality, length of stay and non-operative costs for elective (open and endovascular) infra-renal AAA patients. Methods: A retrospective cohort study was undertaken. Pre-operative CPET-based selection for elective surgical intervention was introduced in 2007. An anonymized cohort of 230 consecutive infra-renal AAA patients (2007 to 2011) was studied. A historical control group of 128 consecutive infra-renal AAA patients (2003 to 2007) was identified for comparison. Comparative analysis of demographic and outcome data for CPET-pass (AT ≥ 11 ml/kg/min), CPET-fail (AT < 11 ml/kg/min) and CPET-submaximal (no AT generated) subgroups with control subjects was performed. Primary outcomes included 30-day mortality, survival and length of stay (LOS); secondary outcomes were non-operative inpatient costs. Results: Of 230 subjects, 188 underwent CPET: CPET-pass n = 131, CPET-fail n = 35 and CPET-submaximal n = 22. When compared to the controls, CPET-pass patients exhibited reduced median total LOS (10 vs 13 days for open surgery, n = 74, P < 0.01 and 4 vs 6 days for EVAR, n = 29, P < 0.05), intensive therapy unit requirement (3 vs 4 days for open repair only, P < 0.001), non-operative costs (£5,387 vs £9,634 for open repair, P < 0.001) and perioperative mortality (2.7% vs 12.6% (odds ratio: 0.19) for open repair only, P < 0.05). CPET-stratified (open/endovascular) patients exhibited a mid-term survival benefit (P < 0.05). Conclusion: In this retrospective cohort study, a pre-operative AT > 11 ml/kg/min was associated with reduced perioperative mortality (open cases only), LOS, survival and inpatient costs (open and endovascular repair) for elective infra-renal AAA surgery

ATP release from the human ureter on distension and P2X3 receptor expression on suburothelial sensory nerves

It is not clear how the increase in intraluminal pressure behind an obstructing ureteric calculus causes an increase in action potential frequency in ureteric sensory nerves so the pain messages are transmitted to the brain. It has been proposed that ureteric distension causes urothelial release of ATP, which activates purinoceptors on suburothelial nociceptive sensory nerves. The purpose of this study was to determine whether distension of the human ureter results in the release of ATP and whether the nociceptive P2 receptor, P2X3, is expressed on suburothelial sensory nerves in the human ureter. Human ureter segments were perfused with Krebs solution and intermittently distended to a range of pressures. Samples of perfusate were collected throughout and the ATP concentration ([ATP]) was determined using a luciferin-luciferase assay. Sections of ureter were stained using antibodies against P2X3 and capsaicin receptors (TRPV1). [ATP] rose to more than 10 times baseline levels after distension beyond a threshold of 25–30 cmH2O. Immunofluorescence studies on consecutive frozen sections showed that suburothelial nerves stained positively for P2X3 and capsaicin receptors, with no staining in controls. These findings are consistent with the hypothesis that purinergic signalling is involved in human ureteric mechanosensory transduction, leading to nociception

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

The Role of Robotics in the Invasive Management of Bladder Cancer

Robot-assisted radical cystectomy (RARC) has been adopted widely in many centres, owed largely to the success of robot-assisted laparoscopic prostatectomy (RALP). It aims to replicate the oncological outcomes of open radical cystectomy (ORC), while providing a shorter recovery period. Despite this, previous RCTs have failed to show a benefit for RARC over ORC. These trials have compared extracorporeal RARC (eRARC) with ORC, which requires a further incision to mobilise the bowel for urinary reconstruction with an open technique. For intracorporeal RARC (iRARC), this urinary reconstruction is performed robotically without further incisions. There are theoretical benefits to this approach such as reduced recovery time for the bowel and reduced ileus rates, but no level 1 evidence currently exists to support this. While there has been an improvement in patient outcomes since the adoption of RARC, various other factors, such as enhanced recovery programmes and surgical learning curve, have made it difficult to attribute this solely to the robotic approach as many centres performing ORC have also shown similar improvements. In this review, we will discuss implementation of RARC as well as perioperative measures that have helped improve outcomes, offer a comparison of outcomes between ORC and RARC and highlight upcoming RCTs that may offer new evidence for or against a paradigm shift in the future of bladder cancer surgery

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed