International Collaborative Partnership for the Study of Atrial Fibrillation (INTERAF): Rationale, Design, and Initial Descriptives.

published_or_final_versio

Biology of a new virus isolated from Lupinus nootkatensis plants in Alaska

A new virus named Nootka lupine vein-clearing virus (NLVCV) was isolated from Lupinus nootkatensis plants that were confined to a relatively small area in the Talkeetna mountains of south-central Alaska. Annual surveys (2000–03) consistently found leaf symptoms of pronounced vein clearing and mosaic on 3- to 4-week-old plants in late June. Spherical particles ≈ 30 nm in diameter were isolated from these leaves. Virions contained a single-stranded RNA of ≈ 4·0–4·2 kb and one species of capsid protein estimated to be ≈ 40 kDa. The double-stranded RNA profile from naturally infected leaves consisted of three major bands ≈ 4·2, 1·9 and 1·5 kbp. Protein extractions from either sap or virions of diseased plants reacted to polyclonal antiserum made against the virions in Western blot assays. A predicted PCR product ≈ 500 bp was synthesized from virion RNA using primers specific to the carmovirus RNA-dependent RNA polymerase (RDRP) gene. The nucleotide sequence of the amplified DNA did not match any known virus, but contained short regions of identity to several carmoviruses. Only species belonging to the Fabaceae were susceptible to NLVCV by mechanical inoculation. Based on dsRNA profile, size of virion RNA genome and capsid protein, and similarity of the RDRP gene to that of other carmoviruses, it is suggested that NLVCV is a member of the family Tombusviridae , and tentatively of the genus Carmovirus . As the host range, RDRP gene and dsRNA profile of NLVCV are different from those of known viruses, this is a newly described plant virus

The inhibition of Bid expression by Akt leads to resistance to TRAIL-induced apoptosis in ovarian cancer cells

Epithelial ovarian cancer (EOC) cells often show increased activity of the PI3K/Akt pathway. In addition, we have previously shown that EOC ascites induce Akt activation in the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-sensitive EOC cell line, CaOV3, leading to TRAIL-mediated apoptosis inhibition. In this study, we investigated the role of Akt in intrinsic resistance to TRAIL, which is common in EOC cells. We report that Akt activation reduces the sensitivity of EOC cells to TRAIL. TRAIL-resistant SKOV3ip1 and COV2 cells were sensitized to TRAIL-induced apoptosis by PI3K or Akt inhibitors although inhibition of PI3K/Akt signaling pathway did not interfere with the recruitment and processing of caspase-8 to the death-inducing signaling complex. Conversely, overexpression of Akt1 in TRAIL-sensitive cells promoted resistance to TRAIL. Although the fact that TRAIL-induced caspase-8 activation was observed in both sensitive and resistant cell lines, Bid cleavage occurred only in sensitive cells or in SKOV3ip1 cells treated with LY294002. Bid expression was low in resistant cells and Akt activation downregulated its expression. Depletion of Bid by siRNA in OVCAR3 cells was associated with a decrease in TRAIL-mediated apoptosis. Overexpression of Bid only in SKOV3ip1 cells enhanced TRAIL-induced apoptosis. Simultaneous blockade of Akt pathway further increased TRAIL-induced apoptosis. Thus, Akt acts upstream of mitochondria and inhibits TRAIL-induced apoptosis by decreasing Bid protein levels and possibly inhibiting its cleavage

Mercury in Nelson's Sparrow Subspecies at Breeding Sites

Background: Mercury is a persistent, biomagnifying contaminant that can cause negative effects on ecosystems. Marshes are often areas of relatively high mercury methylation and bioaccumulation. Nelson’s Sparrows (Ammodramus nelsoni) use marsh habitats year-round and have been documented to exhibit tissue mercury concentrations that exceed negative effects thresholds. We sought to further characterize the potential risk of Nelson’s Sparrows to mercury exposure by sampling individuals from sites within the range of each of its subspecies

The Expanding Fireball of Nova Delphini 2013

A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting from one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 +/- 0.59 kpc from the Sun.Comment: Published in Nature. 32 pages. Final version available at http://www.nature.com/nature/journal/v515/n7526/full/nature13834.htm

Usefulness of an accelerated transoesophageal stress echocardiography in the preoperative evaluation of high risk severely obese subjects awaiting bariatric surgery

<p>Abstract</p> <p>Background</p> <p>Severe obesity is associated with an increased risk of coronary artery disease (CAD). Bariatric surgery is an effective procedure for long term weight management as well as reduction of comorbidities. Preoperative evaluation of cardiac operative risk may often be necessary but unfortunately standard imaging techniques are often suboptimal in these subjects. The purpose of this study was to demonstrate the feasibility, safety and utility of transesophageal dobutamine stress echocardiography (TE-DSE) using an adapted accelerated dobutamine infusion protocol in severely obese subjects with comorbidities being evaluated for bariatric surgery for assessing the presence of myocardial ischemia.</p> <p>Methods</p> <p>Subjects with severe obesity [body mass index (BMI) >40 kg/m²] with known or suspected CAD and being evaluated for bariatric surgery were recruited.</p> <p>Results</p> <p>Twenty subjects (9M/11F), aged 50 ± 8 years (mean ± SD), weighing 141 ± 21 kg and with a BMI of 50 ± 5 kg/m²were enrolled in the study and underwent a TE-DSE. The accelerated dobutamine infusion protocol used was well tolerated. Eighteen (90%) subjects reached their target heart rate with a mean intubation time of 13 ± 4 minutes. Mean dobutamine dose was 31.5 ± 9.9 ug/kg/min while mean atropine dose was 0.5 ± 0.3 mg. TE-DSE was well tolerated by all subjects without complications including no significant arrhythmia, hypotension or reduction in blood arterial saturation. Two subjects had abnormal TE-DSE suggestive of myocardial ischemia. All patients underwent bariatric surgery with no documented cardiovascular complications.</p> <p>Conclusions</p> <p>TE-DSE using an accelerated infusion protocol is a safe and well tolerated imaging technique for the evaluation of suspected myocardial ischemia and cardiac operative risk in severely obese patients awaiting bariatric surgery. Moreover, the absence of myocardial ischemia on TE-DSE correlates well with a low operative risk of cardiac event.</p

Evidence for handheld electronic medical records in improving care: a systematic review

BACKGROUND: Handheld electronic medical records are expected to improve physician performance and patient care. To confirm this, we performed a systematic review of the evidence assessing the effects of handheld electronic medical records on clinical care. METHODS: To conduct the systematic review, we searched MEDLINE, EMBASE, CINAHL, and the Cochrane library from 1966 through September 2005. We included randomized controlled trials that evaluated effects on practitioner performance or patient outcomes of handheld electronic medical records compared to either paper medical records or desktop electronic medical records. Two reviewers independently reviewed citations, assessed full text articles and abstracted data from the studies. RESULTS: Two studies met our inclusion criteria. No other randomized controlled studies or non-randomized controlled trials were found that met our inclusion criteria. Both studies were methodologically strong. The studies examined changes in documentation in orthopedic patients with handheld electronic medical records compared to paper charts, and both found an increase in documentation. Other effects noted with handheld electronic medical records were an increase in time to document and an increase in wrong or redundant diagnoses. CONCLUSION: Handheld electronic medical records may improve documentation, but as yet, the number of studies is small and the data is restricted to one group of patients and a small group of practitioners. Further study is required to determine the benefits with handheld electronic medical records especially in assessing clinical outcomes

Lateral wedge insoles for reducing biomechanical risk factors for medial knee osteoarthritis progression : a systematic review and meta-analysis

Objective Lateral wedge insoles are intended to reduce biomechanical risk factors of medial knee osteoarthritis (OA) progression, such as increased knee joint load; however, there has been no definitive consensus on this topic. The aim of this systematic review and meta-analysis was to establish the within-subject effects of lateral wedge insoles on knee joint load in people with medial knee OA during walking. Methods Six databases were searched from inception until February 13th 2015. Included studies reported on the acute biomechanical effects of lateral wedge insoles in people with medial knee osteoarthritis during walking. Primary outcomes of interest relating to the biomechanical risk of disease progression were the 1st and 2nd peak external knee adduction moment (EKAM) and knee adduction angular impulse (KAAI). Eligible studies were pooled using random-effects meta-analysis. Results Eighteen studies were included with a total of 534 participants. Lateral wedge insoles resulted in a small but statistically significant reduction in the 1st peak EKAM (SMD: -0.19; 95% CI -0.23 − -0.15) and 2nd peak EKAM (SMD: -0.25; 95% CI -0.32 − -0.19) with a low level of heterogeneity (I2 = 5% and 30%, respectively). There was a favourable but small reduction in the KAAI with lateral wedge insoles (SMD: -0.14; 95% CI -0.21 − -0.07, I2 =31%). Risk of methodological bias scores (Quality Index) ranged from 8 to 13 out of 16. Conclusions Lateral wedge insoles cause small reductions in the EKAM and KAAI in people with medial knee OA during walking. At present, they appear ineffective at attenuating structural changes in people with medial knee OA as a whole and may be better suited to targeted use in biomechanical phenotypes associated with larger reductions in knee load

Increased sensitivity to TRAIL-induced apoptosis occurs during the adenoma to carcinoma transition of colorectal carcinogenesis

The death ligand TRAIL (Apo2L) has potential for cancer therapy, since tumour cells are thought to be more sensitive than normal cells. We investigated whether sensitivity to TRAIL increases during the adenoma to carcinoma transition of colorectal carcinogenesis. Under the same culture conditions, we compared the extent of TRAIL-induced apoptosis in four premalignant adenoma and three carcinoma cell lines. Although TRAIL induced some apoptosis in adenoma cultures, the carcinoma cell lines were significantly more sensitive (P<0.001). This finding was recapitulated in an in vitro model of tumour progression in which conversion of the adenoma cell line AA/C1 to a tumorigenic phenotype was associated with increased TRAIL sensitivity (P<0.001). Increased TRAIL sensitivity during colorectal carcinogenesis has been previously attributed to changes in the balance between TRAIL receptors TRAIL-R1 and -R2 and ‘decoy' receptors TRAIL-R3 and -R4 during malignant progression. To address this, cell surface receptor expression was measured by flow cytometry. In summary, during colorectal carcinogenesis, there is a marked increase in sensitivity to TRAIL-induced apoptosis associated with progression from benign to malignant tumour that could be exploited for colon cancer therapy, but alterations in cell surface TRAIL receptor expression may not be the primary reason for this change