Maternal TLR4 and NOD2 Gene Variants, Pro-Inflammatory Phenotype and Susceptibility to Early-Onset Preeclampsia and HELLP Syndrome

Background: Altered maternal inflammatory responses play a role in the development of preeclampsia and the hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. We examined whether allelic variants of the innate immune receptors toli-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain (NOD2), that impair the inflammatory response to endotexin are related to preeclampsia and HELLP syndrome. Methods and Finding: We determined five common mutations in TLR4 (D299G and T399I and NOD2 (R70W, G908R and L1007fs) in 340 primiparous women with a histo

Perception of Relative Depth Interval: Systematic Biases in Perceived Depth

Given an estimate of the binocular disparity between a pair of points and an estimate of the viewing distance, or knowledge of eye position, it should be possible to obtain an estimate of their depth separation. Here we show that, when points are arranged in different vertical geometric configurations across two intervals, many observers find this task difficult. Those who can do the task tend to perceive the depth interval in one configuration as very different from depth in the other configuration. We explore two plausible explanations for this effect. The first is the tilt of the empirical vertical horopter: Points perceived along an apparently vertical line correspond to a physical line of points tilted backwards in space. Second, the eyes can rotate in response to a particular stimulus. Without compensation for this rotation, biases in depth perception would result. We measured cyclovergence indirectly, using a standard psychophysical task, while observers viewed our depth configuration. Biases predicted from error due either to cyclovergence or to the tilted vertical horopter were not consistent with the depth configuration results. Our data suggest that, even for the simplest scenes, we do not have ready access to metric depth from binocular disparity.</jats:p

Two Novel Point Mutations in Clinical Staphylococcus aureus Reduce Linezolid Susceptibility and Switch on the Stringent Response to Promote Persistent Infection

Staphylococcus aureus frequently invades the human bloodstream, leading to life threatening bacteremia and often secondary foci of infection. Failure of antibiotic therapy to eradicate infection is frequently described; in some cases associated with altered S. aureus antimicrobial resistance or the small colony variant (SCV) phenotype. Newer antimicrobials, such as linezolid, remain the last available therapy for some patients with multi-resistant S. aureus infections. Using comparative and functional genomics we investigated the molecular determinants of resistance and SCV formation in sequential S. aureus isolates from a patient who had a persistent and recurrent S. aureus infection, after failed therapy with multiple antimicrobials, including linezolid. Two point mutations in key staphylococcal genes dramatically affected clinical behaviour of the bacterium, altering virulence and antimicrobial resistance. Most strikingly, a single nucleotide substitution in relA (SACOL1689) reduced RelA hydrolase activity and caused accumulation of the intracellular signalling molecule guanosine 3′, 5′-bis(diphosphate) (ppGpp) and permanent activation of the stringent response, which has not previously been reported in S. aureus. Using the clinical isolate and a defined mutant with an identical relA mutation, we demonstrate for the first time the impact of an active stringent response in S. aureus, which was associated with reduced growth, and attenuated virulence in the Galleria mellonella model. In addition, a mutation in rlmN (SACOL1230), encoding a ribosomal methyltransferase that methylates 23S rRNA at position A2503, caused a reduction in linezolid susceptibility. These results reinforce the exquisite adaptability of S. aureus and show how subtle molecular changes cause major alterations in bacterial behaviour, as well as highlighting potential weaknesses of current antibiotic treatment regimens

Quality Indicators for Colonoscopy Procedures: A Prospective Multicentre Method for Endoscopy Units

BACKGROUND AND AIMS: Healthcare professionals are required to conduct quality control of endoscopy procedures, and yet there is no standardised method for assessing quality. The topic of the present study was to validate the applicability of the procedure in daily practice, giving physicians the ability to define areas for continuous quality improvement. METHODS: In ten endoscopy units in France, 200 patients per centre undergoing colonoscopy were enrolled in the study. An evaluation was carried out based on a prospectively developed checklist of 10 quality-control indicators including five dependent upon and five independent of the colonoscopy procedure. RESULTS: Of the 2000 procedures, 30% were done at general hospitals, 20% at university hospitals, and 50% in private practices. The colonoscopies were carried out for a valid indication for 95.9% (range 92.5-100). Colon preparation was insufficient in 3.7% (range 1-10.5). Colonoscopies were successful in 95.3% (range 81-99). Adenoma detection rate was 0.31 (range 0.17-0.45) in successful colonoscopies. CONCLUSION: This tool for evaluating the quality of colonoscopy procedures in healthcare units is based on standard endoscopy and patient criteria. It is an easy and feasible procedure giving the ability to detect suboptimal practice and differences between endoscopy-units. It will enable individual units to assess the quality of their colonoscopy techniques

VIP in construction: systematic development and evaluation of a multifaceted health programme aiming to improve physical activity levels and dietary patterns among construction workers

<p>Abstract</p> <p>Background</p> <p>The prevalence of both overweight and musculoskeletal disorders (MSD) in the construction industry is high. Many interventions in the occupational setting aim at the prevention and reduction of these health problems, but it is still unclear how these programmes should be designed. To determine the effectiveness of interventions on these health outcomes randomised controlled trials (RCTs) are needed. The aim of this study is to systematically develop a tailored intervention for prevention and reduction of overweight and MSD among construction workers and to describe the evaluation study regarding its (cost-)effectiveness.</p> <p>Methods/Design</p> <p>The Intervention Mapping (IM) protocol was applied to develop and implement a tailored programme aimed at the prevention and reduction of overweight and MSD. The (cost-) effectiveness of the intervention programme will be evaluated using an RCT. Furthermore, a process evaluation will be conducted. The research population will consist of blue collar workers of a large construction company in the Netherlands.</p> <p>Intervention</p> <p>The intervention programme will be aimed at improving (vigorous) physical activity levels and healthy dietary behaviour and will consist of tailored information, face-to-face and telephone counselling, training instruction (a fitness "card" to be used for exercises), and materials designed for the intervention (overview of the company health promoting facilities, waist circumference measuring tape, pedometer, BMI card, calorie guide, recipes, and knowledge test).</p> <p>Main study parameters/endpoints</p> <p>The intervention effect on body weight and waist circumference (primary outcome measures), as well as on lifestyle behaviour, MSD, fitness, CVD risk indicators, and work-related outcomes (i.e. productivity, sick leave) (secondary outcome measures) will be assessed.</p> <p>Discussion</p> <p>The development of the VIP in construction intervention led to a health programme tailored to the needs of construction workers. This programme, if proven effective, can be directly implemented.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2095">NTR2095</a></p

Vertical Heterophoria and Postural Control in Nonspecific Chronic Low Back Pain

The purpose of this study was to test postural control during quiet standing in nonspecific chronic low back pain (LBP) subjects with vertical heterophoria (VH) before and after cancellation of VH; also to compare with healthy subjects with, and without VH. Fourteen subjects with LBP took part in this study. The postural performance was measured through the center of pressure displacements with a force platform while the subjects fixated on a target placed at either 40 or 200 cm, before and after VH cancellation with an appropriate prism. Their postural performance was compared to that of 14 healthy subjects with VH and 12 without VH (i.e. vertical orthophoria) studied previously in similar conditions. For LBP subjects, cancellation of VH with a prism improved postural performance. With respect to control subjects (with or without VH), the variance of speed of the center of pressure was higher, suggesting more energy was needed to stabilize their posture in quiet upright stance. Similarly to controls, LBP subjects showed higher postural sway when they were looking at a target at a far distance than at a close distance. The most important finding is that LBP subjects with VH can improve their performance after prism-cancellation of their VH. We suggest that VH reflects mild conflict between sensory and motor inputs involved in postural control i.e. a non optimal integration of the various signals. This could affect the performance of postural control and perhaps lead to pain. Nonspecific chronic back pain may results from such prolonged conflict

Does CT colonography have a role for population-based colorectal cancer screening?

Colorectal cancer (CRC) is the second most common cancer and second most common cause of cancer-related deaths in Europe. CRC screening has been proven to reduce disease-specific mortality and several European countries employ national screening programmes. These almost exclusively rely on stool tests, with endoscopy used as an adjunct in some countries. Computed tomographic colonography (CTC) is a potential screening test, with an estimated sensitivity of 88 % for advanced neoplasia ≥10 mm. Recent randomised studies have shown that CTC and colonoscopy have similar yields of advanced neoplasia per screened invitee, indicating that CTC is potentially viable as a primary screening test. However, the evidence is not fully elaborated. It is unclear whether CTC screening is cost-effective and the impact of extracolonic findings, both medical and economic, remains unknown. Furthermore, the effect of CTC screening on CRC-related mortality is unknown, as it is also unknown for colonoscopy. It is plausible that both techniques could lead to decreased mortality, as for sigmoidoscopy and gFOBT. Although radiation exposure is a drawback, this disadvantage may be over-emphasised. In conclusion, the detection characteristics and acceptability of CTC suggest it is a viable screening investigation. Implementation will depend on detection of extracolonic disease and health-economic impact

Anxiety Levels in Children with Autism Spectrum Disorder:A Meta-Analysis

The aim of the current study was to meta-analytically examine whether anxiety levels in children with autism spectrum disorders (ASD) are elevated. A total of 83 articles were selected from a systematic literature search and were included in the meta-analyses. Results demonstrated that children with ASD had higher anxiety levels compared to typically developing children, and this difference increased with IQ. Youth with ASD also tended to have higher anxiety levels compared to clinically referred children, and this difference increased with age. Children with ASD had higher anxiety levels compared to youth with externalizing or developmental problems, but not when compared to youth with internalizing problems. The study findings highlight the importance of more research in order to fully understand the nature and development of anxiety in children with ASD. More specifically, the results suggest that especially high-functioning adolescents with ASD may be at risk for developing anxiety disorders. Therefore, it seems important to carefully follow and monitor children with ASD transcending to adolescenc

Addressing food and nutrition insecurity in the Caribbean through domestic smallholder farming system innovation

Structural conditions underlying the development of CARICOM’s two-tiered agricultural innovation system depict diverse drivers of change over time, versus institutional inertia of export-oriented formal institutions and the neglect of informal domestic markets. Key principles of taking an agroecological approach would include: supporting diversity and redundancy, building connectivity, managing slow variables and feedbacks, improving understanding of socioecological systems as complex adaptive systems, and encouraging polycentric governance systems. In this paper, we review the conditions that have been undermining sustainable food and nutrition security in the Caribbean, focusing on issues of history, economy, and innovation