Bedside Interactions from the Other Side of the Bedrail

To assess the importance to patients of various aspects of bedside interactions with physician teams. Design : Cross-sectional survey. Setting : VA hospital. Patients : Ninety-seven medical inpatients. Intervention : Survey of 44 questions including short answer, multiple choice, and Likert-type questions. Measurements and Main Results : Data analysis included descriptive statistics. The sample was predominantly male, with a mean age of 62. Overall satisfaction with the hospital experience and with the team of doctors were both high (95% and 96% reported being very or mostly satisfied, respectively). Patients reported learning about several issues during their interactions with the teams; the 3 most highly rated areas were new problems, tests that will be done, and treatments that will be done. Most patients (76%) felt that their teams cared about them very much. Patients were made comfortable when the team showed that they cared, listened, and appeared relaxed (reported by 63%, 57%, and 54%, respectively). Patients were made uncomfortable by the team using language they did not understand (22%) and when several people examined them at once (13%). Many (58%) patients felt personally involved in teaching. The majority of patients liked having medical students and residents involved in their care (69% and 64%, respectively). Conclusions : Patients have much to teach about what is important about interacting with physician teams. Although patients' reactions to team interactions are generally positive, patients are different with respect to what makes them comfortable and uncomfortable. Taking their preferences into account could improve the experience of being in a teaching hospital.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75456/1/j.1525-1497.2005.40192.x.pd

Chloramphenicol Selection of IS10 Transposition in the cat Promoter Region of Widely Used Cloning Vectors

The widely used pSU8 family of cloning vectors is based on a p15A replicon and a chloramphenicol acetyltransferase (cat) gene conferring chloramphenicol resistance. We frequently observed an increase in the size of plasmids derived from these vectors. Analysis of the bigger molecular species shows that they have an IS10 copy inserted at a specific site between the promoter and the cat open reading frame. Promoter activity from both ends of IS10 has been reported, suggesting that the insertion events could lead to higher CAT production. Insertions were observed in certain constructions containing inserts that could lead to plasmid instability. To test the possibility that IS10 insertions were selected as a response to chloramphenicol selection, we have grown these constructs in the presence of different amounts of antibiotic and we observed that insertions arise promptly under higher chloramphenicol selective pressure. IS10 is present in many E. coli laboratory strains, so the possibility of insertion in constructions involving cat-containing vectors should be taken into account. Using lower chloramphenicol concentrations could solve this problem

The Sigma-trial protocol: a prospective double-blind multi-centre comparison of laparoscopic versus open elective sigmoid resection in patients with symptomatic diverticulitis

BACKGROUND: Diverticulosis is a common disease in the western society with an incidence of 33-66%. 10-25% of these patients will develop diverticulitis. In order to prevent a high-risk acute operation it is advised to perform elective sigmoid resection after two episodes of diverticulitis in the elderly patient or after one episode in the younger ( 50 years or in case of progressive abdominal complaints due to strictures caused by a previous episode of diverticulits. The diagnosis is confirmed by CT-scan, barium enema and/or coloscopy.It is required that the participating surgeons have performed at least 15 laparoscopic and open sigmoid resections. Open resection is performed by median laparotomy, laparoscopic resection is approached by 4 or 5 cannula. Sigmoid and colon which contain serosal changes or induration are removed and a tension free anastomosis is created. After completion of either surgical procedure an opaque dressing will be used, covering from 10 cm above the umbilicus to the pubic bone. Surgery details will be kept separate from the patient's notes.Primary endpoints are the postoperative morbidity and mortality. We divided morbidity in minor (e.g. wound infection), major (e.g. anastomotic leakage) and late (e.g. incisional hernias) complications, data will be collected during hospital stay and after six weeks and six months postoperative. Secondary endpoints are the operative and the postoperative recovery data. Operative data include duration of the operation, blood loss and conversion to laparotomy. Post operative recovery consists of return to normal diet, pain, analgesics, general health (SF-36 questionnaire) and duration of hospital stay. DISCUSSION: The Sigma-trial is a prospective, multi-center, double-blind, randomized study to define the role of laparoscopic sigmoid resection in patients with symptomatic diverticuliti

Efficient Cellular Release of Rift Valley Fever Virus Requires Genomic RNA

The Rift Valley fever virus is responsible for periodic, explosive epizootics throughout sub-Saharan Africa. The development of therapeutics targeting this virus is difficult due to a limited understanding of the viral replicative cycle. Utilizing a virus-like particle system, we have established roles for each of the viral structural components in assembly, release, and virus infectivity. The envelope glycoprotein, Gn, was discovered to be necessary and sufficient for packaging of the genome, nucleocapsid protein and the RNA-dependent RNA polymerase into virus particles. Additionally, packaging of the genome was found to be necessary for the efficient release of particles, revealing a novel mechanism for the efficient generation of infectious virus. Our results identify possible conserved targets for development of anti-phlebovirus therapies

A Predictive Model of Intein Insertion Site for Use in the Engineering of Molecular Switches

Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch

Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience

Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

Background: Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms. Design: The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about 1200 patients are needed to detect a 24% reduction in primary outcome. Implications: The GROUND study will provide insight into the question whether non-invasive cardiac imaging reduces the risk of cardiovascular events in patients with peripheral arterial disease, but without symptoms of coronary artery disease. Trial registration: Clinicaltrials.gov NCT0018911

Forest Plant and Bird Communities in the Lau Group, Fiji

We examined species composition of forest and bird communities in relation to environmental and human disturbance gradients on Lakeba (55.9 km²), Nayau (18.4 km²), and Aiwa Levu (1.2 km²), islands in the Lau Group of Fiji, West Polynesia. The unique avifauna of West Polynesia (Fiji, Tonga, Samoa) has been subjected to prehistoric human-caused extinctions but little was previously known about this topic in the Lau Group. We expected that the degree of human disturbance would be a strong determinant of tree species composition and habitat quality for surviving landbirds, while island area would be unrelated to bird diversity.All trees > 5 cm diameter were measured and identified in 23 forest plots of 500 m² each. We recognized four forest species assemblages differentiated by composition and structure: coastal forest, dominated by widely distributed species, and three forest types with differences related more to disturbance history (stages of secondary succession following clearing or selective logging) than to environmental gradients (elevation, slope, rockiness). Our point counts (73 locations in 1 or 2 seasons) recorded 18 of the 24 species of landbirds that exist on the three islands. The relative abundance and species richness of birds were greatest in the forested habitats least disturbed by people. These differences were due mostly to increased numbers of columbid frugivores and passerine insectivores in forests on Lakeba and Aiwa Levu. Considering only forested habitats, the relative abundance and species richness of birds were greater on the small but completely forested (and uninhabited) island of Aiwa Levu than on the much larger island of Lakeba.Forest disturbance history is more important than island area in structuring both tree and landbird communities on remote Pacific islands. Even very small islands may be suitable for conservation reserves if they are protected from human disturbance

Secretion of Novel SEL1L Endogenous Variants Is Promoted by ER Stress/UPR via Endosomes and Shed Vesicles in Human Cancer Cells

We describe here two novel endogenous variants of the human endoplasmic reticulum (ER) cargo receptor SEL1LA, designated p38 and p28. Biochemical and RNA interference studies in tumorigenic and non-tumorigenic cells indicate that p38 and p28 are N-terminal, ER-anchorless and more stable relative to the canonical transmembrane SEL1LA. P38 is expressed and constitutively secreted, with increase after ER stress, in the KMS11 myeloma line and in the breast cancer lines MCF7 and SKBr3, but not in the non-tumorigenic breast epithelial MCF10A line. P28 is detected only in the poorly differentiated SKBr3 cell line, where it is secreted after ER stress. Consistently with the presence of p38 and p28 in culture media, morphological studies of SKBr3 and KMS11 cells detect N-terminal SEL1L immunolabeling in secretory/degradative compartments and extracellularly-released membrane vesicles. Our findings suggest that the two new SEL1L variants are engaged in endosomal trafficking and secretion via vesicles, which could contribute to relieve ER stress in tumorigenic cells. P38 and p28 could therefore be relevant as diagnostic markers and/or therapeutic targets in cancer

A haplotype map of allohexaploid wheat reveals distinct patterns of selection on homoeologous genomes

BACKGROUND: Bread wheat is an allopolyploid species with a large, highly repetitive genome. To investigate the impact of selection on variants distributed among homoeologous wheat genomes and to build a foundation for understanding genotype-phenotype relationships, we performed population-scale re-sequencing of a diverse panel of wheat lines. RESULTS: A sample of 62 diverse lines was re-sequenced using the whole exome capture and genotyping-by-sequencing approaches. We describe the allele frequency, functional significance, and chromosomal distribution of 1.57 million single nucleotide polymorphisms and 161,719 small indels. Our results suggest that duplicated homoeologous genes are under purifying selection. We find contrasting patterns of variation and inter-variant associations among wheat genomes; this, in addition to demographic factors, could be explained by differences in the effect of directional selection on duplicated homoeologs. Only a small fraction of the homoeologous regions harboring selected variants overlapped among the wheat genomes in any given wheat line. These selected regions are enriched for loci associated with agronomic traits detected in genome-wide association studies. CONCLUSIONS: Evidence suggests that directional selection in allopolyploids rarely acted on multiple parallel advantageous mutations across homoeologous regions, likely indicating that a fitness benefit could be obtained by a mutation at any one of the homoeologs. Additional advantageous variants in other homoelogs probably either contributed little benefit, or were unavailable in populations subjected to directional selection. We hypothesize that allopolyploidy may have increased the likelihood of beneficial allele recovery by broadening the set of possible selection targets