Evaluation of bioluminescent imaging for noninvasive monitoring of colorectal cancer progression in the liver and its response to immunogene therapy

<p>Abstract</p> <p>Background</p> <p>Bioluminescent imaging (BLI) is based on the detection of light emitted by living cells expressing a luciferase gene. Stable transfection of luciferase in cancer cells and their inoculation into permissive animals allows the noninvasive monitorization of tumor progression inside internal organs. We have applied this technology for the development of a murine model of colorectal cancer involving the liver, with the aim of improving the pre-clinical evaluation of new anticancer therapies.</p> <p>Results</p> <p>A murine colon cancer cell line stably transfected with the luciferase gene (MC38Luc1) retains tumorigenicity in immunocompetent C57BL/6 animals. Intrahepatic inoculation of MC38Luc1 causes progressive liver infiltration that can be monitored by BLI. Compared with ultrasonography (US), BLI is more sensitive, but accurate estimation of tumor mass is impaired in advanced stages. We applied BLI to evaluate the efficacy of an immunogene therapy approach based on the liver-specific expression of the proinflammatory cytokine interleukin-12 (IL-12). Individualized quantification of light emission was able to determine the extent and duration of antitumor responses and to predict long-term disease-free survival.</p> <p>Conclusion</p> <p>We show that BLI is a rapid, convenient and safe technique for the individual monitorization of tumor progression in the liver. Evaluation of experimental treatments with complex mechanisms of action such as immunotherapy is possible using this technology.</p

Mental Toughness in Talented Youth Tennis Players:A Comparison Between on-Court Observations and a Self-Reported Measure

In tennis, mental toughness is often considered highly important in achieving the elite level. The current study is the first to examine behavioural expressions of mental toughness on the court and their relationships with selfreported measures. Based on the input of five experienced tennis coaches of junior tennis players and behaviours used in previous studies, we developed a taxonomy consisting of six positive behaviours and ten negative ones. To investigate the relationship between these on-court behaviours of mental toughness and how the players rated their own mental toughness, emotional control in particular, six talented tennis players (aged 10-13) were recorded during tennis matches and filled out the self-reported measure of mental toughness (MTQ48). The intra-and inter-rater reliability of the taxonomy was high. With regard to the relationships between on-court behaviours and self-reported mental toughness (total score and subscale emotional control), results revealed no significant correlations between the ratios of positive and negative behaviours (range r = -0.49 -0.11, p > 0.05) or between the variability of negative behaviours (r = 0.54 & r = 0.10, p > 0.05) and the self-reported measure. However, interestingly, we found negative correlations between the variability of positive behaviours and self-reported mental toughness (r = -0.93 & r = -0.84, p <0.05). These results indicate that variability in on-court behaviours provides interesting information about tennis players' mental toughness, more specifically on the (in) stability of their psychological state during a match

Naar een integraal alcoholbeleid in België

The omnipresence and social acceptance of alcohol in Belgium in many cases masks the harmful effects of alcohol. In order to reduce the negative consequences of harmful alcohol consumption, much research has been done in recent years into the effectiveness of possible policy measures. Despite the recommendations of these studies and of several health organizations, there is still no national alcohol policy plan in force in Belgium. Measures in the areas of prevention, care, price, supply and marketing are necessary to effectively reduce the harmful effects of alcohol.De alomtegenwoordigheid en sociale aanvaarding van alcohol in België verbloemt in vele gevallen de schadelijke gevolgen die alcohol heeft. Om die gevolgen te reduceren, is er de afgelopen jaar veel onderzoek gedaan naar de effectiviteit van mogelijke overheidsmaatregelen. Onder andere de Wereldgezondheidsorganisatie adviseert landen over effectieve beleidsmaatregelen op basis van wetenschappelijke inzichten. Ondanks de aanbevelingen van de Wereldgezondheidsorganisatie en uit wetenschappelijke onderzoeken is er in België nog altijd geen sprake van een nationaal alcoholbeleidsplan waarin deze maatregelen integraal zijn opgenomen. Maatregelen op het vlak van preventie, hulpverlening, prijs, aanbod en marketing zijn noodzakelijk om de schadelijke gevolgen van alcohol effectief te reduceren

Single-molecule manipulation reveals supercoiling-dependent modulation of lac repressor-mediated DNA looping

Gene expression regulation is a fundamental biological process which deploys specific sets of genomic information depending on physiological or environmental conditions. Several transcription factors (including lac repressor, LacI) are present in the cell at very low copy number and increase their local concentration by binding to multiple sites on DNA and looping the intervening sequence. In this work, we employ single-molecule manipulation to experimentally address the role of DNA supercoiling in the dynamics and stability of LacI-mediated DNA looping. We performed measurements over a range of degrees of supercoiling between −0.026 and +0.026, in the absence of axial stretching forces. A supercoiling-dependent modulation of the lifetimes of both the looped and unlooped states was observed. Our experiments also provide evidence for multiple structural conformations of the LacI–DNA complex, depending on torsional constraints. The supercoiling-dependent modulation demonstrated here adds an important element to the model of the lac operon. In fact, the complex network of proteins acting on the DNA in a living cell constantly modifies its topological and mechanical properties: our observations demonstrate the possibility of establishing a signaling pathway from factors affecting DNA supercoiling to transcription factors responsible for the regulation of specific sets of genes

Cost-effectiveness of a vocational enablement protocol for employees with hearing impairment; design of a randomized controlled trial

Background: Hearing impairment at the workplace, and the resulting psychosocial problems are a major health problem with substantial costs for employees, companies, and society. Therefore, it is important to develop interventions to support hearing impaired employees. The objective of this article is to describe the design of a randomized controlled trial evaluating the (cost-) effectiveness of a Vocational Enablement Protocol (VEP) compared with usual care. Methods/Design. Participants will be selected with the 'Hearing and Distress Screener'. The study population will consist of 160 hearing impaired employees. The VEP intervention group will be compared with usual care. The VEP integrated care programme consists of a multidisciplinary assessment of auditory function, work demands, and personal characteristics. The goal of the intervention is to facilitate participation in work. The primary outcome measure of the study is 'need for recovery after work'. Secondary outcome measures are coping with hearing impairment, distress, self-efficacy, psychosocial workload, job control, general health status, sick leave, work productivity, and health care use. Outcome measures will be assessed by questionnaires at baseline, and 3, 6, 9, and 12 months after baseline. The economic evaluation will be performed from both a societal and a company perspective. A process evaluation will also be performed. Discussion. Interventions addressing occupational difficulties of hearing impaired employees are rare but highly needed. If the VEP integrated care programme proves to be (cost-) effective, the intervention can have an impact on the well-being of hearing impaired employees, and thereby, on the costs for the company as well for the society. Trial registration. Netherlands Trial Register (NTR): NTR2782. © 2012 Gussenhoven et al; BioMed Central Ltd

U.S. medical resident familiarity with national tuberculosis guidelines

<p>Abstract</p> <p>Background</p> <p>The ability of medical residents training at U.S. urban medical centers to diagnose and manage tuberculosis cases has important public health implications. We assessed medical resident knowledge about tuberculosis diagnosis and early management based on American Thoracic Society guidelines.</p> <p>Methods</p> <p>A 20-question tuberculosis knowledge survey was administered to 131 medical residents during a single routinely scheduled teaching conference at four different urban medical centers in Baltimore and Philadelphia. Survey questions were divided into 5 different subject categories. Data was collected pertaining to institution, year of residency training, and self-reported number of patients managed for tuberculosis within the previous year. The Kruskal-Wallis test was used to detect differences in median percent of questions answered correctly based on these variables.</p> <p>Results</p> <p>The median percent of survey questions answered correctly for all participating residents was 55%. Medical resident knowledge about tuberculosis did not improve with increasing post-graduate year of training or greater number of patients managed for tuberculosis within the previous year. Common areas of knowledge deficiency included the diagnosis and management of latent tuberculosis infection (median percent correct, 40.7%), as well as the interpretation of negative acid-fast sputum smear samples.</p> <p>Conclusion</p> <p>Many medical residents lack adequate knowledge of recommended guidelines for the management of tuberculosis. Since experience during training influences future practice pattterns, education of medical residents on guidelines for detection and early management of tuberculosis may be important for future improvements in national tuberculosis control strategies.</p

Recognizing and Resolving Social Dilemmas in Supply Chain Public–Private Partnerships

The public-private partnership is a popular strategy for creating global sustainable value. However, many public-private partnerships struggle to realize their value-added potential. Why do some public-private partnerships succeed while others fail, and how may those struggling succeed? Combining supply-chain integration and social dilemma perspectives into the conversation of public-private partnerships, we examine the dynamics and psychology ofcooperation necessary for public-private partnership success. Addressing the first part of our research question, we recognize three social dilemmas that can manifest while managing public-private partnership supply chains: a give-some dilemma, a take-some dilemma, and a give-or-take-some dilemma. To address the second part of our research question, we present a taxonomy of strategies resolving these public-private partnership social dilemmas through the enhancement of trust, self-efficacy, and/or social responsibility. We discuss implications for public-private partnerships, supply-chain, and social dilemma literatures

FRET studies of a landscape of Lac repressor-mediated DNA loops

DNA looping mediated by the Lac repressor is an archetypal test case for modeling protein and DNA flexibility. Understanding looping is fundamental to quantitative descriptions of gene expression. Systematic analysis of LacI•DNA looping was carried out using a landscape of DNA constructs with lac operators bracketing an A-tract bend, produced by varying helical phasings between operators and the bend. Fluorophores positioned on either side of both operators allowed direct Förster resonance energy transfer (FRET) detection of parallel (P1) and antiparallel (A1, A2) DNA looping topologies anchored by V-shaped LacI. Combining fluorophore position variant landscapes allows calculation of the P1, A1 and A2 populations from FRET efficiencies and also reveals extended low-FRET loops proposed to form via LacI opening. The addition of isopropyl-β-d-thio-galactoside (IPTG) destabilizes but does not eliminate the loops, and IPTG does not redistribute loops among high-FRET topologies. In some cases, subsequent addition of excess LacI does not reduce FRET further, suggesting that IPTG stabilizes extended or other low-FRET loops. The data align well with rod mechanics models for the energetics of DNA looping topologies. At the peaks of the predicted energy landscape for V-shaped loops, the proposed extended loops are more stable and are observed instead, showing that future models must consider protein flexibility

First M87 Event Horizon Telescope Results and the Role of ALMA

In April 2019, the Event Horizon Telescope (EHT) collaboration revealed the first image of the candidate super-massive black hole (SMBH) at the centre of the giant elliptical galaxy Messier 87 (M87). This event-horizon-scale image shows a ring of glowing plasma with a dark patch at the centre, which is interpreted as the shadow of the black hole. This breakthrough result, which represents a powerful confirmation of Einstein's theory of gravity, or general relativity, was made possible by assembling a global network of radio telescopes operating at millimetre wavelengths that for the first time included the Atacama Large Millimeter/ submillimeter Array (ALMA). The addition of ALMA as an anchor station has enabled a giant leap forward by increasing the sensitivity limits of the EHT by an order of magnitude, effectively turning it into an imaging array. The published image demonstrates that it is now possible to directly study the event horizon shadows of SMBHs via electromagnetic radiation, thereby transforming this elusive frontier from a mathematical concept into an astrophysical reality. The expansion of the array over the next few years will include new stations on different continents - and eventually satellites in space. This will provide progressively sharper and higher-fidelity images of SMBH candidates, and potentially even movies of the hot plasma orbiting around SMBHs. These improvements will shed light on the processes of black hole accretion and jet formation on event-horizon scales, thereby enabling more precise tests of general relativity in the truly strong field regime.Comment: 11 pages + cover page, 6 figure