DeloRes trial: study protocol for a randomized trial comparing two standardized surgical approaches in rectal prolapse - Delorme¿s procedure versus resection rectopexy

ABSTRACT: BACKGROUND: More than 100 surgical approaches to treat rectal prolapse have been described. These can be done through the perineum or transabdominally. Delorme's procedure is the most frequently used perineal, resection rectopexy the most commonly used abdominal procedure. Recurrences seem more common after perineal compared to abdominal techniques, but the latter may carry a higher risk of peri- and postoperative morbidity and mortality. METHODS: DeloRes is a randomized, controlled, observer-blinded multicenter trial with two parallel groups. Patients with a full-thickness rectal prolapse (third degree prolapse), considered eligible for both operative methods are included.The primary outcome is time to recurrence of full-thickness rectal prolapse during the 24 months following primary surgery. Secondary endpoints are time to and incidence of recurrence of full-thickness rectal prolapse during the 5-year follow-up, duration of surgery, morbidity, hospital stay, quality of life, constipation, and fecal incontinence.A meta-analysis was done on the basis of the available data on recurrence rates from 17 publications comprising 1,140 patients. Based on the results of a meta-analysis it is assumed that the recurrence rate after 2 years is 20% for Delorme's procedure and 5% for resection rectopexy. Considering a rate of lost to follow-up without recurrence of 30% a total of 130 patients (2 x 65 patients) was calculated as an adequate sample size to assure a power of 80% for the confirmatory analysis. DISCUSSION: The DeloRes Trial will clarify which procedure results in a smaller recurrence rate but also give information on how morbidity and functional results compare.Trial registrationGerman Clinical Trial Number DRKS00000482.     

The impact of intraspecific variation in a fish predator on the evolution of phenotypic plasticity and investment in sex in Daphnia ambigua

Theory predicts that the evolution of phenotypic plasticity depends upon cues that indicate environmental change. Predators typically induce plastic responses in prey. However, variation among populations of predators alters the frequency of predation and, possibly, the evolution of plasticity. We compared responses to predator cues in Daphnia ambigua from lakes where alewife (Alosa pseudoharengus) either do (anadromous) or do not (landlocked) migrate between marine and freshwater. In 'anadromous' lakes, Daphnia are abundant each spring but eliminated by alewives in summer, whereas Daphnia are constantly under the threat of predation in 'landlocked' lakes. Daphnia from 'anadromous' lakes grew faster, matured earlier and larger, produced more offspring and invested more in sex than Daphnia from landlocked lakes. We observed several significant lake type-by-predator treatment interactions. These interactions, whereby the differences between lakes were greater in predator-conditioned water, agree with theory and argue that Daphnia plasticity has been influenced by variation in alewives.     

Laboratory cryo soft X-ray microscopy

Lens-based water-window X-ray microscopy allows two- and three-dimensional (2D and 3D) imaging of intact unstained cells in their near-native state with unprecedented contrast and resolution. Cryofixation is essential to avoid radiation damage to the sample. Present cryo X-ray microscopes rely on synchrotron radiation sources, thereby limiting the accessibility for a wider community of biologists. In the present paper we demonstrate water-window cryo X-ray microscopy with a laboratory-source-based arrangement. The microscope relies on a λ=2.48-nm liquid-jet high-brightness laser-plasma source, normal-incidence multilayer condenser optics, 30-nm zone-plate optics, and a cryo sample chamber. We demonstrate 2D imaging of test patterns, and intact unstained yeast, protozoan parasites and mammalian cells. Overview 3D information is obtained by stereo imaging while complete 3D microscopy is provided by full tomographic reconstruction. The laboratory microscope image quality approaches that of the synchrotron microscopes, but with longer exposure times. The experimental image quality is analyzed from a numerical wave-propagation model of the imaging system and a path to reach synchrotron-like exposure times in laboratory microscopy is outlined.     

D-CAT: Density and Clustering Annotation Tool for three dimensional electron microscopic volumes

Three dimensional (3D) electron microscopy techniques have become valuable tools for investigating cellular architecture and the processes that govern it. A vast amount of information is available in every 3D tomogram but the options for presenting this information in a clear and visually appealing way are limited. To address this, we developed D-CAT; a MatLab-application to accurately visualize the distribution of membrane proteins and/or membrane-bound structures. Presence (density) and distribution (clustering, depletion) are presented as color-coded areas on membranes. By using IMOD models both as input and output format, we ensure that the application fits within workflows common in the field of 3D electron microscopy.     

Fetal Mesenchymal Stromal Cells Differentiating towards Chondrocytes Acquire a Gene Expression Profile Resembling Human Growth Plate Cartilage

We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFβ3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development.     

Down-Regulation of Small Rubber Particle Protein Expression Affects Integrity of Rubber Particles and Rubber Content in Taraxacum brevicorniculatum

The biosynthesis of rubber is thought to take place on the surface of rubber particles in laticifers, highly specialized cells that are present in more than 40 plant families. The small rubber particle protein (SRPP) has been supposed to be involved in rubber biosynthesis, and recently five SRPPs (TbSRPP1-5) were identified in the rubber-producing dandelion species Taraxacum brevicorniculatum. Here, we demonstrate by immunogold labeling that TbSRPPs are localized to rubber particles, and that rubber particles mainly consist of TbSRPP3, 4 and 5 as shown by high-resolution two-dimensional gel electrophoresis and mass spectrometric analysis. We also carried out an RNA-interference approach in transgenic plants to address the function of TbSRPPs in rubber biosynthesis as well as rubber particle morphology and stability. TbSRPP-RNAi transgenic T. brevicorniculatum plants showed a 40-50% reduction in the dry rubber content, but neither the rubber weight average molecular mass nor the polydispersity of the rubber were affected. Although no phenotypical differences to wild-type particles could be observed in vivo, rubber particles from the TbSRPP-RNAi transgenic lines were less stable and tend to rapidly aggregate in expelling latex after wounding of laticifers. Our results prove that TbSRPPs are very crucial for rubber production in T. brevicorniculatum, probably by contributing to a most favourable and stable rubber particle architecture for efficient rubber biosynthesis and eventually storage.     

Cost-Effectiveness Analysis of Three Leprosy Case Detection Methods in Northern Nigeria

Background

Despite several leprosy control measures in Nigeria, child proportion and disability grade 2 cases remain high while new cases have not significantly reduced, suggesting continuous spread of the disease. Hence, there is the need to review detection methods to enhance identification of early cases for effective control and prevention of permanent disability. This study evaluated the cost-effectiveness of three leprosy case detection methods in Northern Nigeria to identify the most cost-effective approach for detection of leprosy.

Methods

A cross-sectional study was carried out to evaluate the additional benefits of using several case detection methods in addition to routine practice in two north-eastern states of Nigeria. Primary and secondary data were collected from routine practice records and the Nigerian Tuberculosis and Leprosy Control Programme of 2009. The methods evaluated were Rapid Village Survey (RVS), Household Contact Examination (HCE) and Traditional Healers incentive method (TH). Effectiveness was measured as number of new leprosy cases detected and cost-effectiveness was expressed as cost per case detected. Costs were measured from both providers'' and patients'' perspectives. Additional costs and effects of each method were estimated by comparing each method against routine practise and expressed as incremental cost-effectiveness ratio (ICER). All costs were converted to the U.S. dollar at the 2010 exchange rate. Univariate sensitivity analysis was used to evaluate uncertainties around the ICER.

Results

The ICER for HCE was $142 per additional case detected at all contact levels and it was the most cost-effective method. At ICER of $194 per additional case detected, THs method detected more cases at a lower cost than the RVS, which was not cost-effective at $313 per additional case detected. Sensitivity analysis showed that varying the proportion of shared costs and subsistent wage for valuing unpaid time did not significantly change the results.

Conclusion

Complementing routine practice with household contact examination is the most cost-effective approach to identify new leprosy cases and we recommend that, depending on acceptability and feasibility, this intervention is introduced for improved case detection in Northern Nigeria.     

Arginine Consumption by the Intestinal Parasite Giardia intestinalis Reduces Proliferation of Intestinal Epithelial Cells

In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the host´s production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/citrulline-complemented medium, as well as in interaction with different G. intestinalis isolates, were used to study effects on host cell replication by MTT assay. IEC proliferation was further analyzed by DNA content analysis, polyamine measurements and expressional analysis of cell cycle regulatory genes. IEC proliferation was reduced upon arginine-withdrawal and also in an arginine-dependent manner upon interaction with G. intestinalis or addition of Giardia ADI. We show that arginine-withdrawal by intestinal pathogens leads to a halt in the cell cycle in IECs through reduced polyamine levels and upregulated cell cycle inhibitory genes. This is of importance with regards to intestinal tissue homeostasis that is affected through reduced cell proliferation. Thus, the slower epithelial cell turnover helps the pathogen to maintain a more stable niche for colonization. This study also shows why supplementation therapy of diarrhea patients with arginine/citrulline is helpful and that citrulline especially should gain further attention in future treatment strategies.     

Effects of productivity, disturbance, and ecosystem size on food-chain length: insights from a metacommunity model of intraguild predation

Traditionally, productivity and disturbance have been hypothesized as important determinants of food-chain length. More recently, growing empirical evidence suggests a strong role of ecosystem size. To theoretically explore the effects of basal productivity, disturbance, and ecosystem size on food-chain length, we develop and analyze a metacommunity model of intraguild predation (IGP). The model finds that, when local IGP is weak, increasing basal productivity, weakening disturbance, and increasing ecosystem size will generally increase food-chain length. When local IGP is strong, by contrast, increasing basal productivity or weakening disturbance favors intraguild predators and hinders the coexistence of intraguild predators and intraguild prey, limiting food-chain length. In contrast, increasing ecosystem size can promote coexistence even when local IGP is strong, increasing food-chain length through inserting intraguild prey and changing the degree of omnivory by intraguild predators. Intraguild prey needs to be the superior colonizer to intraguild predators for this to occur. We discuss that these theoretical predictions appear consistent with empirical patterns.