Spores of Clostridium difficile Clinical Isolates Display a Diverse Germination Response to Bile Salts

Clostridium difficile spores play a pivotal role in the transmission of infectious diarrhoea, but in order to cause disease spores must complete germination and return to vegetative cell growth. While the mechanisms of spore germination are well understood in Bacillus, knowledge of C. difficile germination remains limited. Previous studies have shown that bile salts and amino acids play an important role in regulating the germination response of C. difficile spores. Taurocholate, in combination with glycine, can stimulate germination, whereas chenodeoxycholate has been shown to inhibit spore germination in a C. difficile clinical isolate. Our recent studies of C. difficile sporulation characteristics have since pointed to substantial diversity among different clinical isolates. Consequently, in this study we investigated how the germination characteristics of different C. difficile isolates vary in response to bile salts. By analysing 29 isolates, including 16 belonging to the BI/NAP1/027 type, we show that considerable diversity exists in both the rate and extent of C. difficile germination in response to rich medium containing both taurocholate and glycine. Strikingly, we also show that although a potent inhibitor of germination for some isolates, chenodeoxycholate does not inhibit the germination, or outgrowth, of all C. difficile strains. Finally, we provide evidence that components of rich media may induce the germination of C. difficile spores, even in the absence of taurocholate. Taken together, these data suggest that the mechanisms of C. difficile spore germination in response to bile salts are complex and require further study. Furthermore, we stress the importance of studying multiple isolates in the future when analysing the nutrients or chemicals that either stimulate or inhibit C. difficile spore germination

Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study):study protocol for a randomized, controlled, multicenter, international clinical trial

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017

Normative values for the Foot Posture Index

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Absence of Inhibin Alpha and Retinoblastoma Protein Leads to Early Sertoli Cell Dysfunction

Sertoli cells, the support cells of mammalian spermatogenesis, are regulated by a number of nuclear factors and express retinoblastoma (RB) tumor suppressor protein. We hypothesized that RB is an important mediator of Sertoli cell tumorigenesis in inhibin α knockout (Inha KO) mice. In our previous mouse studies, we found that conditional knockout (cKO) of Rb in Sertoli cells caused progressive Sertoli cell dysfunction. Initially, loss of RB had no gross effect on Sertoli cell function as the mice were fertile with normal testis weights at 6 weeks of age, but by 10–14 weeks of age, mutant mice demonstrated severe Sertoli cell dysfunction and infertility. Although double knockout (dKO) of Rb and Inha did not result in exacerbation of the tumorigenic phenotype of Inha-null mice, we found that the dKO mice demonstrate an acceleration of Sertoli cell dysfunction compared to Rb cKO mice. Specifically, in contrast to Rb cKO mice, Inha/Rb dKO mice showed signs of Sertoli cell dysfunction as early as 4 weeks of age. These results demonstrate that RB is not essential for Sertoli cell tumorigenesis in Inha KO mice but that loss of Inha accelerates the infertility phenotype of Rb cKO mice

All Effects of Psychophysical Variables on Color Attributes: A Classification System

This paper reports the research and structuring of a classification system for the effects of psychophysical variables on the color attributes. A basic role of color science is to psychophysically specify color appearance. An early stage is to specify the effects of the psychophysical variables (as singles, pairs, etc) on the color attributes (as singles, pairs, etc), for example to model color appearance. Current data on effects are often scarce or conflicting. Few effects are well understood, and the practice of naming effects after their discoverer(s) is inadequate and can be confusing. The number and types of possible effects have never been systematically analyzed and categorized. We propose a simple and rigorous system of classification including nomenclature. The total range of effects is computed from the possible combinations of three psychophysical variables (luminance, dominant wavelength, purity) and six color attributes (lightness, brightness, hue, chroma, colorfulness, saturation) in all modes of appearance. Omitting those effects that are normally impossible to perceive at any one time (such as four- or five-dimensional colors), the total number perceivable is 161 types of effects for all modes of appearance. The type of effect is named after the psychophysical stimulus (or stimuli) and the relevant color attribute(s), e.g., Luminance-on-hue effect (traditionally known as Bezold-Brucke effect). Each type of effect may include slightly different effects with infinite variations depending on experimental parameters.M. Melgosa was supported by the Ministry of Economy and Competitiveness of the Government of Spain, research project FIS2013-40661-P, with the European Research Development Fund

Systematic evaluation of implementation fidelity of complex interventions in health and social care

<p>Abstract</p> <p>Background</p> <p>Evaluation of an implementation process and its fidelity can give insight into the 'black box' of interventions. However, a lack of standardized methods for studying fidelity and implementation process have been reported, which might be one reason for the fact that few prior studies in the field of health service research have systematically evaluated interventions' implementation processes.</p> <p>The aim of this project is to systematically evaluate implementation fidelity and possible factors influencing fidelity of complex interventions in health and social care.</p> <p>Methods</p> <p>A modified version of The Conceptual Framework for Implementation Fidelity will be used as a conceptual model for the evaluation. The modification implies two additional moderating factors: context and recruitment. A systematic evaluation process was developed. Multiple case study method is used to investigate implementation of three complex health service interventions. Each case will be investigated in depth and longitudinally, using both quantitative and qualitative methods.</p> <p>Discussion</p> <p>This study is the first attempt to empirically test The Conceptual Framework for Implementation Fidelity. The study can highlight mechanism and factors of importance when implementing complex interventions. Especially the role of the moderating factors on implementation fidelity can be clarified.</p> <p>Trial Registration</p> <p>Supported Employment, SE, among people with severe mental illness -- a randomized controlled trial: NCT00960024.</p

Temporal trends in serum concentrations of polychlorinated dioxins, furans, and PCBs among adult women living in Chapaevsk, Russia: a longitudinal study from 2000 to 2009

<p>Abstract</p> <p>Background</p> <p>The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-<it>p</it>-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.</p> <p>Methods</p> <p>Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.</p> <p>Results</p> <p>The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the sum of PCBs decreased for six of eight women. During this nine year period, larger decreases in serum TEQs and PCBs were found in women with greater increases in body mass index.</p> <p>Conclusions</p> <p>This study provides suggestive evidence that average serum concentrations of dioxins, furans, and PCBs are decreasing over time among residents of this town.</p

Expert Premier League soccer managers’ use of transformational leadership behaviours and attitude towards sport integrity: An intrinsic case study

The present study is the first to examine transformational leadership behaviours and integrity attitudes of expert, Premier League and International level football managers. To provide a rich, detailed exploration of the expert managers’ experiences, a qualitative approach was adopted utilising holistic content analysis. Constructed narratives revealed that the key behaviours demonstrated were inspirational messages or team talks (i.e. inspirational motivation), empathy (i.e. individualised consideration), introducing new training methods (i.e. intellectual stimulation), using exemplar players (i.e. appropriate role modelling), and goal setting (i.e. high performance expectations). However, the use and effect of such behaviours varied greatly between managers. Each of the managers also claimed to have been willing to “bend the rules” as a player and frequently used euphemistic labels to describe such behaviour. However, upon entering management, all three managers claimed to have adjusted such attitudes without providing an explanation for this

Synthesis and Characterization of Tin Disulfide (SnS2) Nanowires

The ordered tin disulfide (SnS2) nanowire arrays were first fabricated by sulfurizing the Sn nanowires, which are embedded in the nanochannels of anodic aluminum oxide (AAO) template. SnS2nanowire arrays are highly ordered and highly dense. X-ray diffraction (XRD) and corresponding selected area electron diffraction (SAED) patterns demonstrate the SnS2nanowire is hexagonal polycrystalline. The study of UV/Visible/NIR absorption shows the SnS2nanowire is a wide-band semiconductor with three band gap energies (3.3, 4.4, and 5.8 eV)

The Impact of Changing Medicaid Enrollments on New Mexico's Immunization Program

Background: Immunizations are an important component to pediatric primary care. New Mexico is a relatively poor and rural state which has sometimes struggled to achieve and maintain its childhood immunization rates. We evaluated New Mexico’s immunization rates between 1996 and 2006. Specifically, we examined the increase in immunization rates between 2002 and 2004, and how this increase may have been associated with Medicaid enrollment levels, as opposed to changes in government policies concerning immunization practices. Methods and Findings: This study examines trends in childhood immunization coverage rates relative to Medicaid enrollment among those receiving Temporary Assistance for Needy Families (TANF) in New Mexico. Information on health policy changes and immunization coverage was obtained from state governmental sources and the National Immunization Survey. We found statistically significant correlations varying from 0.86 to 0.93 between immunization rates and Medicaid enrollment. Conclusions: New Mexico’s improvement and subsequent deterioration in immunization rates corresponded with changing Medicaid coverage, rather than the state’s efforts to change immunization practices. Maintaining high Medicaid enrollmen