Transcriptional changes in the aphid species Myzus cerasi under different host and environmental conditions.

Aphids feature complex life cycles, which in the case of many agriculturally important species involve primary and secondary host plant species. Whilst host alternation between primary and secondary host can occur in the field depending on host availability and the environment, aphid populations maintained as laboratory stocks generally are kept under conditions that allow asexual reproduction by parthenogenesis on secondary hosts. We used Myzus cerasi (black cherry aphid) to assess aphid transcriptional differences between populations collected from primary hosts in the field and those adapted to secondary hosts under controlled environment conditions. Transfer of M. cerasi collected from local cherry trees to reported secondary host species resulted in low survival rates. Moreover, aphids were unable to survive on the secondary host land cress, unless first adapted to another secondary host, cleavers. Transcriptome analyses of the different aphid populations (field collected and adapted) revealed extensive transcriptional plasticity to a change in environment, with predominantly genes involved in redox reactions differentially regulated. Most of the differentially expressed genes were duplicated and we found evidence for differential exon usage. Our data suggest that aphid adaptation to different environments may pose a major hurdle and leads to extensive gene expression changes.

Efficacy of Computed Tomography Venography (CTV) Screening Compared to Duplex Ultrasound (DU), Multiplanar Venography (MV), and Intravascular Ultrasound (IVUS) in Iliac Vein Compression Syndrome (IVCS)

No prior study has prospectively evaluated the efficacyof CTV for identifying IVCS in chronic venous disease (CVD). It has neverbeen compared to DU, MV, and IVUS before. The purpose of this studywas to describe CTV findings and the ability to detect and classify the degreeof IVCS when compared to DU, MV, and IVUS...

Phosphatidylserine exposure on the surface of Leishmania amazonensis amastigotes modulates in vivo infection and dendritic cell function.

Leishmania amazonensis parasites can cause diverse forms of leishmaniasis in humans and persistent lesions in most inbred strains of mice. In both cases, the infection is characterized by a marked immunosuppression of the host. We previously showed that amastigote forms of the parasite make use of surface-exposed phosphatidylserine (PS) molecules to infect host cells and promote alternative macrophage activation, leading to uncontrolled intracellular proliferation of the parasites. In this study, we demonstrated that treatment of infected mice with a PS-targeting monoclonal antibody ameliorated parasite loads and lesion development, which correlated with increased proliferative responses by lymphocytes. In addition, we observed an enhanced dendritic cell (DC) activation and antigen presentation in vitro. Our data imply that the recognition of PS exposed on the surface of amastigotes plays a role in down-modulating DC functions, in a matter similar to that of apoptotic cell clearance. This study provides new information regarding the mechanism of immune suppression in Leishmania infection.

Investigations of mechanical vibrations for beamlines at the Canadian Light Source.

Vibration is often a problem causing poor quality of photon beams at synchrotron radiation facilities, since beamlines are quite sensitive to vibrations. Therefore, vibration analysis and control at synchrotron radiation facilities is crucial. This paper presents investigations on mechanical vibrations at four beamlines and endstations at the Canadian Light Source, i.e. the Canadian Macromolecular Crystallography Facility 08ID-1 beamline, the Hard X-ray MicroAnalysis 06ID-1 beamline, the Resonant Elastic and Inelastic Soft X-ray Scattering 10ID-2 beamline, and the Scanning Transmission X-ray Microscope endstation at the Spectromicroscopy 10ID-1 beamline. This study identifies vibration sources and investigates the influence of mechanical vibrations on beamline performance. The results show that vibrations caused by movable mechanical equipment significantly affect the data acquired from beamlines.

Retargeting adenoviral vectors to improve gene transfer into tumors.

Gene targeting to tumors using adenoviral (Ad) vectors holds great potential for cancer imaging and therapy, but the limited efficacy of current methods used to improve delivery to target tissues and reduce unwanted interactions remain substantial barriers to further development. Progress in characterizing the set of molecular interactions used by Ad vectors to infect particular tissues has aided the development of novel strategies for retargeting vectors to tumor cells. One method is chemical retargeting of adenovirus using bispecific antibodies (bsAbs) against both viral capsid proteins and tumor-specific cell surface molecules. This approach can be combined either with competitive inhibitors designed to reduce viral tropism in undesired tissues, or with traditional therapeutics to increase the expression of surface molecules for improved tumor targeting. Ablating liver cell-specific interactions through mutation of capsid proteins or chemical means are promising strategies for reducing adenovirus-induced liver toxicity. The nature of tumor neovasculature also influences Ad delivery, and the use of vascular disrupting agents (VDAs) such as combretastatin can help elucidate these contributions. In this investigation, we evaluate a variety of these methods for retargeting Ad vectors to tumor cells in vitro and in vivo, and assess the contributions of specific molecular and tissue interactions that affect Ad transgene delivery.

Multimodality imaging of hypoxia in preclinical settings.

Hypoxia has long been recognized to influence solid tumor response to therapy. Increasingly, hypoxia has also been implicated in tumor aggressiveness, including growth, development and metastatic potential. Thus, there is a fundamental, as well as a clinical interest, in assessing in situ tumor hypoxia. This review will examine diverse approaches focusing on the preclinical setting, particularly, in rodents. The strategies are inevitably a compromise in terms of sensitivity, precision, temporal and spatial resolution, as well as cost, feasibility, ease and robustness of implementation. We will review capabilities of multiple modalities and examine what makes them particularly suitable for investigating specific aspects of tumor pathophysiology. Current approaches range from nuclear imaging to magnetic resonance and optical, with varying degrees of invasiveness and ability to examine spatial heterogeneity, as well as dynamic response to interventions. Ideally, measurements would be non-invasive, exploiting endogenous reporters to reveal quantitatively local oxygen tension dynamics. A primary focus of this review is magnetic resonance imaging (MRI) based techniques, such as ¹9F MRI oximetry, which reveals not only hypoxia in vivo, but more significantly, spatial distribution of pO2 quantitatively, with a precision relevant to radiobiology. It should be noted that preclinical methods may have very different criteria for acceptance, as compared with potential investigations for prognostic radiology or predictive biomarkers suitable for use in patients.

Endovascular stents for intermittent claudication.

BACKGROUND: Endovascular stents have been suggested as a means to improve the patency of arteries after angioplasty in patients with intermittent claudication. This is an update of a Cochrane review published in 2002. OBJECTIVES: The null hypothesis to be tested by this review is that for individuals with claudication the use of an endovascular stent, in addition to percutaneous transluminal angioplasty, does not improve symptoms of life-style limiting claudication when compared to percutaneous angioplasty alone. SEARCH STRATEGY: For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched August 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched 2009, Issue 3). SELECTION CRITERIA: Randomised trials comparing angioplasty alone versus angioplasty with endovascular stents in patients with intermittent claudication. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted the data. Only published trial data were used but unpublished data were sought for the update. Effectiveness was measured by the pre-defined primary outcome measures restenosis or reocclusion rates and maximum walking distance. MAIN RESULTS: Two studies were included involving a total of 104 participants. Both studies included only individuals with femoro-popliteal disease. They compared angioplasty and stenting with the Palmaz stent against angioplasty alone. Although one study showed a slight statistical advantage in arterial patency after angioplasty alone, this was not found when the two studies were combined. No differences in the secondary outcomes were detected in either study. AUTHORS' CONCLUSIONS: The small number of relevant studies identified together with the small sample sizes and methodological weaknesses severely limit the usefulness of this review in guiding practice. The results from larger multicentre trials are needed.

Clinical trial: the treatment of gastro-oesophageal reflux disease in primary care--prospective randomized comparison of rabeprazole 20 mg with esomeprazole 20 and 40 mg.

BACKGROUND: A trial of empirical PPI therapy is usual practice for most patients with symptoms of gastro-oesophageal reflux disease (GERD) in primary care. AIM: To determine if the 4-week efficacy of rabeprazole 20 mg for resolving heartburn and regurgitation symptoms is non-inferior to esomeprazole 40 mg or 20 mg. METHODS: In all, 1392 patients were randomized to rabeprazole 20 mg, esomeprazole 20 mg or 40 mg once daily. Patients, doctors and assessors were blinded. Symptom resolution data were collected on days 0-7 and day-28 using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index with a shortened version used on days 8-27. RESULTS: Rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete resolution of regurgitation and satisfactory resolution of heartburn and regurgitation. For complete heartburn resolution, the efficacy of rabeprazole 20 mg and esomeprazole 40 mg was statistically indistinguishable, although the non-inferiority test was inconclusive. Rabeprazole 20 mg was non-inferior to esomeprazole 20 mg for all outcomes. CONCLUSIONS: In uninvestigated GERD patients, rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete and satisfactory relief of regurgitation and satisfactory relief of heartburn, and not different for complete resolution of heartburn.

The role of subintimal angioplasty in the management of arterial disease of the lower limb: the North-East of Scotland experience.

INTRODUCTION: The management of occlusive femoropopliteal disease continues to evolve and a definitive strategy remains to be defined. We examine the utility ofsubintimal angioplasty (SIA) in our institution. METHODS: A retrospective study with predefined end-points, including technical success and primary patency. RESULTS: 61 consecutive cases were identified (claudicants n=29 and critical ischaemia n=32). Sixty-four percent of occlusions were greater than 10 cm with poor run-off (60% with two vessels or less). Technical and physiological success was 95% and 79% respectively, with clinical improvement reported by 72%. At a mean follow-up of 20 months twelve-month primary patency (assessed clinically, with ABPI and selective duplex scanning) was 67% (subgroup analysis: claudicants 83%, criticals 53%, p=0.02) and morbidity 8% with no limb loss or procedure related mortality. CONCLUSION: SIA is an effective procedure for chronic lower limb ischaemia with acceptable outcome. Our experience correlates well with evidence in the current literature.

Modeling stem cell asymmetry in yeast.

For adult stem cells to both self-renew and give rise to differentiating progenitors, they must undergo an inherently asymmetric division. This defining model of asymmetric cell division requires either that stem cells preferentially distribute internal factors, thereby maintaining a stem cell phenotype in one lineage, or that extrinsic signals determine the fate of daughter cells, allowing the maintenance of one stem cell lineage. Although microbial systems are often used to model asymmetry, lineage-specific asymmetry has not been characterized in these organisms. Recently, we identified a stem-cell-like lineage-specific pattern of kinetochore asymmetry in postmeiotic yeast spores. Because the function of the kinetochore is to segregate chromosomes, this asymmetry has the potential to segregate sister chromatids nonrandomly. This may be relevant to stem cells because more than 30 years ago, it was proposed that stem cells selectively segregate one strand of their chromosomes into the self-renewing stem cell lineage (Cairns 1975). Although advanced labeling methods have provided evidence to both support and refute this hypothesis, it remains unclear how nonrandom sister-chromatid segregation might be achieved in a stem cell lineage. We have identified a kinetochore-specific mechanism in yeast that could support lineage-specific nonrandom sister-chromatid segregation and we discuss the implications of this observation.

CT-based classification of long spinal allograft fusion.

Anterior column reconstruction of the thoracolumbar spine by structural allograft has an increased potential for biological fusion when compared to synthetic reconstructive options. Estimation of cortical union and trabecular in-growth is, however, traditionally based on plain radiography, a technique lacking in sensitivity. A new assessment method of bony union using high-speed spiral CT imaging is proposed which reflects the gradually increasing biological stability of the construct. Grade I (complete fusion) implies cortical union of the allograft and central trabecular continuity. Grade II (partial fusion) implies cortical union of the structural allograft with partial trabecular incorporation. Grade III (unipolar pseudarthrosis) denotes superior or inferior cortical non-union of the central allograft with partial trabecular discontinuity centrally and Grade IV (bipolar pseudarthrosis) suggests both superior and inferior cortical non-union with a complete lack of central trabecular continuity. Twenty-five patients underwent anterior spinal reconstruction for a single level burst fracture between T4 and L5. At a minimum of two years follow up the subjects underwent high-speed spiral CT scanning through the reconstructed region of the thoracolumbar spine. The classification showed satisfactory interobserver (kappa score = 0.91) and intraobserver (kappa score = 0.95) reliability. The use of high-speed CT imaging in the assessment of structural allograft union may allow a more accurate assessment of union. The classification system presented allows a reproducible categorization of allograft incorporation with implications for treatment.

TAT-BH4 counteracts Abeta toxicity on capillary endothelium.

Oxidative stress is one of the factor contributing to blood brain barrier degeneration. This phenomenon is observed during pathological conditions such as Alzheimer's disease or cerebral amyloid angiopathy in which brain haemorrhages are very frequent. Both diseases are characterized by beta amyloid peptide deposition either in neurons or in vessels. Oxidative stress leads to impairment of mitochondrial functions and apoptotic cell death subsequent to caspases activation. In this paper we demonstrate that BH4 domain of Bcl-xl administrated to endothelial cells as the conjugated form with TAT peptide, reverts Abeta-induced apoptotic cell death by activating a survival programme which is Akt/endothelial nitric oxide synthase dependent.

Therapeutic transarterial embolisation in the management of benign and malignant renal conditions.

PURPOSE: The aim of this study was to critically appraise the efficacy and complications of Therapeutic Transarterial Embolisation (TAE) in various benign and malignant renal conditions. MATERIAL AND METHODS: The records of all patients who underwent renal embolisation procedures, at a single institution, between March 1992 and March 2004, were reviewed. The patients were identified from hospital records via the procedure coding system and the radiology department procedures book and were analysed retrospectively. Twenty-nine patients were analysed, looking at indications, clinical outcome, complications and long-term results. RESULTS: Twenty-nine patients underwent 35 embolisation procedures during this period. Fourteen patients with benign diseases underwent 17 embolisation procedures for haematuria or intractable pain. In the haematuria group, selective embolisation was used to treat bleeding post percutaneous nephrolithotomy (PCNL) (n=4), angiomyolipoma (n=2), arteriovenous (AV) malformation (n=l1), renal artery aneurysm (n=1) and renal trauma (n=2). In the renal pain group (n=3), non-selective embolisation was done. Two of these patients had recurrence of pain despite repeat embolisation and subsequently underwent nephrectomy. Fifteen patients with advanced renal malignancy, who were deemed unfit for surgery, underwent 18 embolisation procedures for symptomatic haematuria. Twelve of the 15 patients had successful outcomes with cessation of haematuria. Three patients required repeat embolisation procedures for continuing haematuria with success. There were no major embolisation-related complications. Minor complications were self-limiting and settled with conservative management. CONCLUSION: Renal artery embolisation is effective in managing haematuria in benign and malignant renal conditions where indicated, with minor and easily treatable adverse effects

The outcome of direct current cardioversion (DCC) for the treatment of atrial fibrillation (AF) in a district general hospital in Ireland.

BACKGROUND: Direct current cardioversion (DCC) is a method to control persistent AF, to facilitate a reduction in stroke risk. Although this is a frequently performed procedure, there are no available published data regarding its outcome in an Irish setting. AIMS: To determine the short- and long-term outcome of DCC, factors predicting a successful outcome, and its safety. METHODS: Data relating to each DCC were collected retrospectively from patient notes over a 6.3 year-period, and subsequently entered into a Microsoft Access database before subsequent statistical analysis. RESULTS: Forty-five consecutive unselected patients were identified, in which 59 DCCs were performed. Sinus rhythm (SR) was achieved immediately after DCC in 54/59 (91%) patients. There was a significant positive correlation between patient body weight and the energy level required to achieve SR (p=0.0001). No thromboembolic complications were noted. After a mean follow-up time of 12 +/- 13.7months, 30/45 (67%) had maintained SR. After univariate analysis, a number of important factors predictive of maintenance of SR at follow-up were identified. CONCLUSION: DCC was found to be an effective method for short- and long-term control of AF, without thromboembolic complications, and patients with a favourable long-term outcome after DCC could conceivably be predicted on the basis of a methodical history, careful examination, simple investigations and pharmacological variables.

Spontaneous life-threatening perirenal haemorrhage: an uncommon urological emergency.

Spontaneous perirenal haemorrhage is a rare but potentially life-threatening condition and requires urgent management. Diagnosis is based on clinical assessment combined with radiological investigations, as reported by Belville et al. (Radiology 172:733, 1989) and Zagoria et al. (J Urol 145:468, 1991). Reported is a case of spontaneous perirenal haemorrhage diagnosed on computed tomography scan and then successfully embolized using coils.

A new method for radiochemical separation of arsenic from irradiated germanium oxide.

Radioarsenic labelled radiopharmaceuticals could be a valuable asset to Positron Emission Tomography (PET). In particular, the long half-lives of (72)As (T(1/2)=26 h) and (74)As (T(1/2)=17.8 d) allow to investigate slow physiological or metabolical processes, like the enrichment and distribution of antibodies in tumor tissue. This work describes the direct production of no-carrier-added (nca) arsenic isotopes *As, with *=71, 72, 73, 74 or 77, the reaction to [*As]AsI(3) and its radiochemical separation from the irradiated solid germanium oxide via polystyrene-based solid-phase extraction. The germanium oxide target, irradiated at a cyclotron or a nuclear reactor, is dissolved in concentrated HF and Ge is separated almost quantitatively (99.97%) as [GeF(6)](2-). [*As]AsI(3) is formed by addition of potassium iodide. The radiochemical separation yield for arsenic is >90%. [*As]AsI(3) is a versatile radioarsenic labelling synthon.