Clostridium: Transmission difficile?

Stephan Harbarth and Matthew Samore discuss the implications, and the limitations, of new research that might indicate that most Clostridium difficile cases are imported into hospitals

Role of cardiac mitofusins in cardiac conduction following simulated ischemia–reperfusion

Mitochondrial dysfunction induced by acute cardiac ischemia–reperfusion (IR), may increase susceptibility to arrhythmias by perturbing energetics, oxidative stress production and calcium homeostasis. Although changes in mitochondrial morphology are known to impact on mitochondrial function, their role in cardiac arrhythmogenesis is not known. To assess action potential duration (APD) in cardiomyocytes from the Mitofusins-1/2 (Mfn1/Mfn2)-double-knockout (Mfn-DKO) compared to wild-type (WT) mice, optical-electrophysiology was conducted. To measure conduction velocity (CV) in atrial and ventricular tissue from the Mfn-DKO and WT mice, at both baseline and following simulated acute IR, multi-electrode array (MEA) was employed. Intracellular localization of connexin-43 (Cx43) at baseline was evaluated by immunohistochemistry, while Cx-43 phosphorylation was assessed by Western-blotting. Mfn-DKO cardiomyocytes demonstrated an increased APD. At baseline, CV was significantly lower in the left ventricle of the Mfn-DKO mice. CV decreased with simulated-ischemia and returned to baseline levels during simulated-reperfusion in WT but not in atria of Mfn-DKO mice. Mfn-DKO hearts displayed increased Cx43 lateralization, although phosphorylation of Cx43 at Ser-368 did not differ. In summary, Mfn-DKO mice have increased APD and reduced CV at baseline and impaired alterations in CV following cardiac IR. These findings were associated with increased Cx43 lateralization, suggesting that the mitofusins may impact on post-MI cardiac-arrhythmogenesis

Removal of gaseous toluene using immobilized Candida tropicalis in a fluidized bed bioreactor

A pure yeast strain Candida tropicalis was immobilized on the matrix of powdered activated carbon, sodium alginate, and polyethylene glycol (PSP beads). The immobilized beads were used as fluidized material in a bioreactor to remove toluene from gaseous stream. Applied toluene loadings were 15.4 and 29.8 g/m3 h in Step 1 and Step 2, respectively, and toluene removal was found above 95% during the entire operation. A continuous pH decline was observed and pH of the suspension was just above 6 in Step 2 but no adverse effects on treatment efficiency were observed. The CO2 yield values were found to be 0.57 and 0.62 g-\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$C_{{{\text{CO}}_{2} }} /{\text{g-}}C_{\text{toluene}}$$\end{document} in Step 1 and Step 2, respectively. These values indicate that a major portion of toluene-carbon was channeled to yeast respiration even at higher toluene loading. In conclusion, immobilized C. tropicalis can be used as a fluidized material for enhanced degradation of gaseous toluene

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Unmet needs of patients with chronic obstructive pulmonary disease (COPD): A qualitative study on patients and doctors

Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease with repeated exacerbations resulting in gradual debilitation. The quality of life has been shown to be poor in patients with COPD despite efforts to improve self-management. However, the evidence on the benefit of self-management in COPD is conflicting. Whether this could be due to other unmet needs of patients have not been investigated. Therefore, we aimed to explore unmet needs of patients from both patients and doctors managing COPD. Methods: We conducted a qualitative study with doctors and patients in Malaysia. We used convenience sampling to recruit patients until data saturation. Eighteen patients and eighteen doctors consented and were interviewed using a semi-structured interview guide. The interviews were audio-recorded, transcribed verbatim and checked by the interviewers. Data were analysed using a thematic approach. Results: The themes were similar for both the patients and doctors. Three main themes emerged: knowledge and awareness of COPD, psychosocial and physical impact of COPD and the utility of self-management. Knowledge about COPD was generally poor. Patients were not familiar with the term chronic obstructive pulmonary disease or COPD. The word ‘asthma’ was used synonymously with COPD by both patients and doctors. Most patients experienced difficulties in their psychosocial and physical functions such as breathlessness, fear and helplessness. Most patients were not confident in self-managing their illness and prefer a more passive role with doctors directing their care. Conclusions: In conclusion, our study showed that knowledge of COPD is generally poor. There was mislabelling of COPD as asthma by both patients and physicians. This could have resulted in the lack of understanding of treatment options, outcomes, and prognosis of COPD. The misconception that cough due to COPD was contagious, and breathlessness that resulted from COPD, had important physical and psychosocial impact, and could lead to social isolation. Most patients and physicians did not favour self-management approaches, suggesting innovations based on self-management may be of limited benefit

Noninvasive assessment of asthma severity using pulse oximeter plethysmograph estimate of pulsus paradoxus physiology

<p>Abstract</p> <p>Background</p> <p>Pulsus paradoxus estimated by dynamic change in area under the oximeter plethysmograph waveform (PEP) might provide a measure of acute asthma severity. Our primary objective was to determine how well PEP correlates with forced expiratory volume in 1-second (%FEV₁) (criterion validity) and change of %FEV₁(responsiveness) during treatment in pediatric patients with acute asthma exacerbations.</p> <p>Methods</p> <p>We prospectively studied subjects 5 to 17 years of age with asthma exacerbations. PEP, %FEV₁, airway resistance and accessory muscle use were recorded at baseline and at 2 and 4 hours after initiation of corticosteroid and bronchodilator treatments. Statistical associations were tested with Pearson or Spearman rank correlations, logistic regression using generalized estimating equations, or Wilcoxon rank sum tests.</p> <p>Results</p> <p>We studied 219 subjects (median age 9 years; male 62%; African-American 56%). Correlation of PEP with %FEV₁demonstrated criterion validity (r = - 0.44, 95% confidence interval [CI], - 0.56 to - 0.30) and responsiveness at 2 hours (r = - 0.31, 95% CI, - 0.50 to - 0.09) and 4 hours (r = - 0.38, 95% CI, - 0.62 to - 0.07). PEP also correlated with airway resistance at baseline (r = 0.28 for ages 5 to 10; r = 0.45 for ages 10 to 17), but not with change over time. PEP was associated with accessory muscle use (OR 1.16, 95% CI, 1.11 to 1.21, P < 0.0001).</p> <p>Conclusions</p> <p>PEP demonstrates criterion validity and responsiveness in correlations with %FEV₁. PEP correlates with airway resistance at baseline and is associated with accessory muscle use at baseline and at 2 and 4 hours after initiation of treatment. Incorporation of this technology into contemporary pulse oximeters may provide clinicians improved parameters with which to make clinical assessments of asthma severity and response to treatment, particularly in patients who cannot perform spirometry because of young age or severity of illness. It might also allow for earlier recognition and improved management of other disorders leading to elevated pulsus paradoxus.</p

Co-expression of vascular endothelial growth factor (VEGF) and its receptors (flk-1 and flt-1) in hormone-induced mammary cancer in the Noble rat

Vascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis. The action of VEGF is mediated by two high-affinity receptors with ligand-stimulated tyrosine kinase activity: VEGFR-1/flt-1 and VEGFR-2/flk-1, which are expressed mainly in vascular endothelial cells. To the best of our knowledge, no previous studies on the expression of these receptors in breast cancer cells has been made. We have established a new animal model for breast cancer, using a combination of 17β-oestradiol and testosterone as ‘carcinogens’. Taking advantage of the animal model, we have demonstrated that mammary cancer cells expressed not only high levels of VEGF but also, surprisingly, its receptors (flt-1 and flk-1) in mammary cancer cells. Intense reactivities to VEGF, flt-1 and flk-1 were observed in mammary cancer cells, especially in invasive mammary carcinoma. Western blot analysis confirmed the increase in flk-1 and flt-1 proteins in induced mammary cancers. Based on these observations, we hypothesize that in mammary cancer, VEGF regulates, in addition to endothelial proliferation and angiogenesis, also growth of cancer cells by an autocrine mechanism mediated through its receptors. To further verify this hypothesis, we investigated the correlation between cellular proliferation and the expression of VEGF, flt-1 and flk-1. Using double-labelling immunocytochemistry, we have shown a correlation between high VEGF activity and Ki-67 expression. The Ki-67 indices in the areas of strong and weak VEGF reactivities were 58.3% and 3.7% respectively. Similarly, there was also a correlation of strong flk-1 and Ki-67 reactivity. The Ki-67 indices for areas of strong and weak flk-1 reactivities were 53.9% and 3.1% respectively. On the other hand, there was a reverse correlation between flt-1 and Ki-67 activities. These results indicate that overexpression of VEGF and flk-1 is correlated with high Ki-67 index. The data, therefore, suggest that VEGF may act as an autocrine growth factor for mammary cancer cells in vivo and this autocrine regulatory role may be mediated through flk-1. The present study is the first report showing that VEGF may act as a growth stimulator for mammary cancer cells. © 1999 Cancer Research Campaig

Group support systems features and their contribution to technology strategy decision-making: A review and analysis

Collective decision-making processes require careful design considerations in organizations. On one hand, the inclusion of a greater number of actors contribute to a wider knowledge base, on the other, it can become a diffuse process and be distorted from the principles initially established. This paper observes a specific collective decision making process in organizations—technology strategy formulation—and, through a critical review of the literature, analyzes how the advances in features of group support systems support improvements in different stages of this process. This paper also discusses the implications of GSS appropriation in group dynamics.This research was supported by Fundação para a Ciência e Tecnologia (SFRH/ BD/ 33727/ 2009), within the framework of the MIT Portugal Program.info:eu-repo/semantics/publishedVersio