Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xq2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites

Epibiotic pressure contributes to biofouling invader success

Reduced competition is a frequent explanation for the success of many introduced species. In benthic marine biofouling communities, space limitation leads to high rates of overgrowth competition. Some species can utilise other living organisms as substrate (epibiosis), proffering a competitive advantage for the epibiont. Additionally, some species can prevent or reduce epibiotic settlement on their surfaces and avoid being basibionts. To test whether epibiotic pressure differs between native and introduced species, we undertook ex situ experiments comparing bryozoan larval settlement to determine if introduced species demonstrate a greater propensity to settle as epibionts, and a reduced propensity to be basibionts, than native species. Here we report that introduced species opportunistically settle on any space (bare, native, or introduced), whereas native species exhibit a strong tendency to settle on and near other natives, but avoid settling on or near introduced basibionts. In addition, larvae of native species experience greater larval wastage (mortality) than introduced species, both in the presence and absence of living substrates. Introduced species’ ability to settle on natives as epibionts, and in turn avoid epibiosis as basibionts, combined with significantly enhanced native larval wastage, provides a comprehensive suite of competitive advantages contributing to the invasion success of these biofouling species

The Crystal Structure of PPIL1 Bound to Cyclosporine A Suggests a Binding Mode for a Linear Epitope of the SKIP Protein

BACKGROUND: The removal of introns from pre-mRNA is carried out by a large macromolecular machine called the spliceosome. The peptidyl-prolyl cis/trans isomerase PPIL1 is a component of the human spliceosome and binds to the spliceosomal SKIP protein via a binding site distinct from its active site. PRINCIPAL FINDINGS: Here, we have studied the PPIL1 protein and its interaction with SKIP biochemically and by X-ray crystallography. A minimal linear binding epitope derived from the SKIP protein could be determined using a peptide array. A 36-residue region of SKIP centred on an eight-residue epitope suffices to bind PPIL1 in pull-down experiments. The crystal structure of PPIL1 in complex with the inhibitor cyclosporine A (CsA) was obtained at a resolution of 1.15 A and exhibited two bound Cd(2+) ions that enabled SAD phasing. PPIL1 residues that have previously been implicated in binding of SKIP are involved in the coordination of Cd(2+) ions in the present crystal structure. Employing the present crystal structure, the determined minimal binding epitope and previously published NMR data, a molecular docking study was performed. In the docked model of the PPIL1.SKIP interaction, a proline residue of SKIP is buried in a hydrophobic pocket of PPIL1. This hydrophobic contact is encircled by several hydrogen bonds between the SKIP peptide and PPIL1. CONCLUSION: We characterized a short, linear epitope of SKIP that is sufficient to bind the PPIL1 protein. Our data indicate that this SKIP peptide could function in recruiting PPIL1 into the core of the spliceosome. We present a molecular model for the binding mode of SKIP to PPIL1 which emphasizes the versatility of cyclophilin-type PPIases to engage in additional interactions with other proteins apart from active site contacts despite their limited surface area

Two-year changes in quality of life in elderly patients with low-energy hip fractures. A case-control study

<p>Abstract</p> <p>Background</p> <p>The long-term effect of hip fracture on health-related quality of life (HRQOL) and global quality of life (GQOL) has not been thoroughly studied in prospective case-control studies.</p> <p>Aims</p> <p>a) to explore whether patients with low-energy hip fracture regain their pre-fracture levels in HRQOL and GQOL compared with changes in age- and sex-matched controls over a two year period; b) to identify predictors of changes in HRQOL and GQOL after two years.</p> <p>Methods</p> <p>We examined 61 patients (mean age = 74 years, <it>SD </it>= 10) and 61 matched controls (mean age = 73 years, <it>SD </it>= 8). The Short Form 36 assessed HRQOL and the Quality of Life Scale assessed GQOL. Paired samples <it>t </it>tests and multiple linear regression analyses were applied.</p> <p>Results</p> <p>HRQOL decreased significantly between baseline and one-year follow-up in patients with hip fractures, within all the SF-36 domains (<it>p </it>< 0.04), except for social functioning (<it>p </it>= 0.091). There were no significant decreases within the SF-36 domains in the controls. Significantly decreased GQOL scores (<it>p </it>< 0.001) were observed both within patients and within controls between baseline and one-year follow-up. The same pattern persisted between baseline and two-year follow-up, except for the HRQOL domain mental health (<it>p </it>= 0.193). The patients with hip fractures did not regain their HRQOL and GQOL. Worsened physical health after two years was predicted by being a patient with hip fracture (B = -5.8, <it>p </it>< 0.001) and old age (B = -1.0, <it>p </it>= 0.015), while worsened mental health was predicted by co-morbidity (B = -2.2, <it>p </it>= 0.029). No significant predictors of differential changes in GQOL were identified.</p> <p>Conclusion</p> <p>A hip fracture has a long-term impact on HRQOL and is a strong predictor of worsened physical health. Our data emphasize the importance of preventing hip fracture in the elderly to maintain physical health. This knowledge should be included in decision-making and health care plans.</p

Integrating Flux Balance Analysis into Kinetic Models to Decipher the Dynamic Metabolism of Shewanella oneidensis MR-1

Shewanella oneidensis MR-1 sequentially utilizes lactate and its waste products (pyruvate and acetate) during batch culture. To decipher MR-1 metabolism, we integrated genome-scale flux balance analysis (FBA) into a multiple-substrate Monod model to perform the dynamic flux balance analysis (dFBA). The dFBA employed a static optimization approach (SOA) by dividing the batch time into small intervals (i.e., ∼400 mini-FBAs), then the Monod model provided time-dependent inflow/outflow fluxes to constrain the mini-FBAs to profile the pseudo-steady-state fluxes in each time interval. The mini-FBAs used a dual-objective function (a weighted combination of “maximizing growth rate” and “minimizing overall flux”) to capture trade-offs between optimal growth and minimal enzyme usage. By fitting the experimental data, a bi-level optimization of dFBA revealed that the optimal weight in the dual-objective function was time-dependent: the objective function was constant in the early growth stage, while the functional weight of minimal enzyme usage increased significantly when lactate became scarce. The dFBA profiled biologically meaningful dynamic MR-1 metabolisms: 1. the oxidative TCA cycle fluxes increased initially and then decreased in the late growth stage; 2. fluxes in the pentose phosphate pathway and gluconeogenesis were stable in the exponential growth period; and 3. the glyoxylate shunt was up-regulated when acetate became the main carbon source for MR-1 growth

No long-term impact of low-energy distal radius fracture on health-related quality of life and global quality of life: a case-control study

<p>Abstract</p> <p>Background</p> <p>Changes in patient-reported outcomes like health related quality of life (HRQOL) and global quality of life (GQOL) in patients with low-energy distal radius fracture might be related to fracture, or be within the normal range of variation in an elderly population. Hence, the present study aims to examine: Whether patients with low-energy distal radius fracture attain their pre-fracture levels in HRQOL and GQOL one year after the fracture and compare these levels with age- and sex-matched controls; and whether objective factors predict changes in HRQOL and GQOL during the same one year period.</p> <p>Methods</p> <p>We examined 160 patients and 169 age- and sex matched controls, respectively (mean ± SD) 67 ± 9 and 66 ± 9 years of age. HRQOL was assessed by the Modified Health Assessment Questionnaire (MHAQ) and the Short–Form 36 (SF-36). The Quality of Life Scale (QOLS) assessed GQOL. Paired sample t-tests and multiple linear regression analyses were applied.</p> <p>Results</p> <p>After one year no differences were found in HRQOL (assessed as arm functions, physical health and mental health) compared to pre-fracture level in the patient group. Both patients with distal radius fracture and controls reported a reduced GQOL after one year (p < 0.001). Low-energy distal radius fracture did not predict worsened HRQOL or GQOL one year after inclusion, and few predictors of changes were identified. Worsened arm function was predicted by low BMI (B = -0.20, p = 0.019) at baseline, worsened physical health was predicted by low education (B = 1.37, p = 0.017) at baseline, and living with someone predicted worsened mental health (B = 2.85, p = 0.009)</p> <p>Conclusion</p> <p>Patients with a distal radius fracture seem to manage well despite the fracture, and distal radius fracture is not an independent predictor of worsened HRQOL and GQOL.</p

250 labels used to stigmatise people with mental illness

<p>Abstract</p> <p>Background</p> <p>The stigma against people with mental illness is a major barrier to help-seeking in young people for mental health problems. The objective of this study was to investigate the extent of stigma in relation to treatment avoidance in 14 year-old school students in England in relation to how they refer to people with mental illness.</p> <p>Methods</p> <p>This is a qualitative, cross-sectional study. The data were gathered as part of the baseline assessment for an intervention study intended to reduce stigma among 14 year old school students. The participating schools were two grammar (selective) schools and three comprehensive (non-selective) schools. At the start of the lesson, the students were asked 'What sorts of words or phrases might you use to describe someone who experiences mental health problems?' Words and terms used to refer to mental illness were enumerated. Using the grounded theory approach, words and terms were grouped in terms of their denotative and connotative meanings. Labels were then derived to capture the key themes attached by the students to the concepts of mental illness. The frequencies of occurrence for each word were also tabulated.</p> <p>Results</p> <p>400 of the 472 participating students (85%) provided 250 words and terms to describe a person with mental illness. Five themes were identified from the data. The first theme called 'popular derogatory terms' (116 items) accounted for nearly half of the words examined. The second theme occurred less often and was described as 'negative emotional state' (61 items). The third theme demonstrated the confusion of young people between physical disabilities, learning difficulties and mental health problems (38 items). The use of psychiatric diagnoses (15 items) and terms related to violence (9 items) were unexpectedly uncommon.</p> <p>Conclusion</p> <p>Our findings suggest the hypothesis that help-seeking by mentally ill young people may be improved by interventions that address both their lack of factual information about mental illness, and those which reduce their strong negative emotional reactions towards people with mental illness.</p

Abdominal Wound Dehiscence in Adults: Development and Validation of a Risk Model

Background: Several studies have been performed to identify risk factors for abdominal wound dehiscence. No risk model had yet been developed for the general surgical population. The objective of the present study was to identify independent risk factors for abdominal wound dehiscence and to develop a risk model to recognize high-risk patients. Identification of high-risk patients offers opportunities for intervention strategies. Methods: Medical registers from January 1985 to December 2005 were searched. Patients who had primarily undergone appendectomies or nonsurgical (e.g., urological) operations were excluded. Each patient with abdominal wound dehiscence was matched with three controls by systematic random sampling. Putative relevant patient-related, operation-related, and postoperative variables were evaluated in univariate analysis and subsequently entered in multivariate stepwise logistic regression models to delineate major independent predictors of abdominal wound dehiscence. A risk model was developed, which was validated in a population of patients who had undergone operation between January and December 2006. Results: A total of 363 cases and 1,089 controls were analyzed. Major independent risk factors were age, gender, chronic pulmonary disease, ascites, jaundice, anemia, emergency surgery, type of surgery, postoperative coughing, and wound infection. In the validation population, risk scores were significantly higher (P < 0.001) for patients with abdominal wound dehiscence (n = 19) compared to those without (n = 677). Resulting scores ranged from 0 to 8.5, and the risk for abdominal wound dehiscence over this range increased exponentially from 0.02% to 70.1%. Conclusions: The validated risk model shows high predictive value for abdominal wound dehiscence and may help to identify patients at increased risk

Hospital variation in transfusion and infection after cardiac surgery: a cohort study

<p>Abstract</p> <p>Background</p> <p>Transfusion practices in hospitalised patients are being re-evaluated, in part due to studies indicating adverse effects in patients receiving large quantities of stored blood. Concomitant with this re-examination have been reports showing variability in the use of specific blood components. This investigation was designed to assess hospital variation in blood use and outcomes in cardiac surgery patients.</p> <p>Methods</p> <p>We evaluated outcomes in 24,789 Medicare beneficiaries in the state of Michigan, USA who received coronary artery bypass graft surgery from 2003 to 2006. Using a cohort design, patients were followed from hospital admission to assess transfusions, in-hospital infection and mortality, as well as hospital readmission and mortality 30 days after discharge. Multilevel mixed-effects logistic regression was used to calculate the intrahospital correlation coefficient (for 40 hospitals) and compare outcomes by transfusion status.</p> <p>Results</p> <p>Overall, 30% (95 CI, 20% to 42%) of the variance in transfusion practices was attributable to hospital site. Allogeneic blood use by hospital ranged from 72.5% to 100% in women and 49.7% to 100% in men. Allogeneic, but not autologous, blood transfusion increased the odds of in-hospital infection 2.0-fold (95% CI 1.6 to 2.5), in-hospital mortality 4.7-fold (95% CI 2.4 to 9.2), 30-day readmission 1.4-fold (95% CI 1.2 to 1.6), and 30-day mortality 2.9-fold (95% CI 1.4 to 6.0) in elective surgeries. Allogeneic transfusion was associated with infections of the genitourinary system, respiratory tract, bloodstream, digestive tract and skin, as well as infection with <it>Clostridium difficile</it>. For each 1% increase in hospital transfusion rates, there was a 0.13% increase in predicted infection rates.</p> <p>Conclusion</p> <p>Allogeneic blood transfusion was associated with an increased risk of infection at multiple sites, suggesting a system-wide immune response. Hospital variation in transfusion practices after coronary artery bypass grafting was considerable, indicating that quality efforts may be able to influence practice and improve outcomes.</p