Therapeutic approaches of diametaphyseal radius fractures in children.

BACKGROUND: There are clear standards for when to operate on both distal epiphyseal and diaphyseal forearm fractures in children. However, paediatric surgeons are often faced with fractures in the transition zone between metaphysis and diaphysis. This aim of the study is to compare different treatment approaches for diametaphyseal forearm fractures, to classify different types of these fractures, and to define further assessment parameters and treatment recommendations. METHODS: This retrospective study included all patients with diametaphyseal radial fractures who were seen at a paediatric surgery clinic between 01.01.2010 and 31.12.2013. Patients were treated either non-surgically (C) or surgically using bicortical Kirschner wire (BC-KW), intramedullary K-wire (IM-KW), elastic stable intramedullary nailing (ESIN), or combined bicortical and intramedullary K-wire (BCIM-KW). RESULTS: During the study period, 547 patients presented with forearm fractures of which 88 patients (16%) had a fracture in the diametaphyseal region. The majority of diametaphyseal fractures were greenstick fractures (54.4%) followed by transverse fractures (44.3%). Distal fractures were predominantly treated with bicortical K-wiring (BC-KW, 40.5%) or non-surgically (C, 26.2%). Proximal fractures were treated by ESIN osteosynthesis (50%), followed by IM-KW (30%). Intermediate fractures were just as likely to be treated with one out of the 5 above-mentioned techniques. The ulna was involved in 64 of 88 cases. Depending on the type of fracture, it was treated either by ESIN osteosynthesis or non-surgically. No superior operative technique was identified. CONCLUSIONS: The description of diametaphyseal fractures as a separate entity is important, because the therapy of these fractures is heterogeneous and challenging. A classification into proximal, intermediate, and distal may be useful in clinical decision-making. Despite the retrospective nature of this study, our data suggest that the use of a K-wire or combined technique BCIM-KW-technique, whenever technically feasible, achieves better radiological results without secondary dislocation. Further prospective studies are needed to provide better guidance to trauma surgeons.

Linking dendroecology and association genetics in natural populations: Stress responses archived in tree rings associate with SNP genotypes in silver fir (Abies alba Mill.).

Genetic association studies in forest trees would greatly benefit from information on the response of trees to environmental stressors over time, which can be provided by dendroecological analysis. Here, we jointly analysed dendroecological and genetic data of surviving silver fir trees to explore the genetic basis of their response to the iconic stress episode of the 1970s and 1980s that led to large-scale forest dieback in Central Europe and has been attributed to air pollution. Specifically, we derived dendrophenotypic measures from 190 trees in the Bavarian Forest that characterize the resistance, resilience and recovery during this growth depression, and in the drought year in 1976. By focusing on relative growth changes of trees and by standardizing the dendrophenotypes within stands, we accounted for variation introduced by micro- and macroscale environmental differences. We associated the dendrophenotypes with single nucleotide polymorphisms (SNPs) in candidate genes using general linear models (GLMs) and the machine learning algorithm random forest with subsequent feature selection. Most trees at our study sites experienced a severe growth decline from 1974 until the mid-1980s with minimum values during the drought year. Fifteen genes were associated with the dendrophenotypes, including genes linked to photosynthesis and drought stress. With our study, we show that dendrophenotypes can be a powerful resource for genetic association studies that permit to account for micro- and macroenvironmental variation when data are derived from natural populations. We call for a wider collaboration of dendroecologists and forest geneticists to integrate individual tree-level dendrophenotypes in genetic association studies.

Influence of concomitant medications on the total clearance and the risk for supra-therapeutic plasma concentrations of Citalopram. A population-based cohort study.

INTRODUCTION: The main objective of this study was to investigate the influence of the use of multiple medications and other risk factors on citalopram plasma concentrations. METHODS: A retrospective cohort study with a naturalistic population of 957 patients for whom routine therapeutic drug monitoring (TDM) of citalopram had been requested between 2006 and 2013 was conducted. RESULTS: Concomitant drugs inhibiting at least 2 different CYP subtypes involved in the metabolism of citalopram decreased statistically significantly the total clearance (Clt). Compared to younger patients over 64-year-old patients had on average a 4.5 times higher risk rate of supra-therapeutic plasma concentrations. However, binary logistic regression showed that age, sex and co-medication accounted only for 26% of the inter-individual variability of citalopram plasma concentrations. DISCUSSION: Due to pharmacokinetic interactions, citalopram plasma concentrations are often higher than expected with a given dose. Especially in geriatric and often multimorbid patients who are usually prescribed high numbers of concomitant drugs and are at higher risk for adverse drug reactions (ADR), restriction of the maximal dose of citalopram is not sufficient to prevent supra-therapeutic plasma concentrations.

DNA barcodes for species identification in the hyperdiverse ant genus Pheidole (Formicidae: Myrmicinae).

DNA sequencing is increasingly being used to assist in species identification in order to overcome taxonomic impediment. However, few studies attempt to compare the results of these molecular studies with a more traditional species delineation approach based on morphological characters. Mitochondrial DNA Cytochrome oxidase subunit 1 (CO1) gene was sequenced, measuring 636 base pairs, from 47 ants of the genus Pheidole (Formicidae: Myrmicinae) collected in the Brazilian Atlantic Forest to test whether the morphology-based assignment of individuals into species is supported by DNA-based species delimitation. Twenty morphospecies were identified, whereas the barcoding analysis identified 19 Molecular Operational Taxonomic Units (MOTUs). Fifteen out of the 19 DNA-based clusters allocated, using sequence divergence thresholds of 2% and 3%, matched with morphospecies. Both thresholds yielded the same number of MOTUs. Only one MOTU was successfully identified to species level using the CO1 sequences of Pheidole species already in the Genbank. The average pairwise sequence divergence for all 47 sequences was 19%, ranging between 0-25%. In some cases, however, morphology and molecular based methods differed in their assignment of individuals to morphospecies or MOTUs. The occurrence of distinct mitochondrial lineages within morphological species highlights groups for further detailed genetic and morphological studies, and therefore a pluralistic approach using several methods to understand the taxonomy of difficult lineages is advocated.

Spinning a laser web: predicting spider distributions using LiDAR.

LiDAR remote sensing has been used to examine relationships between vertebrate diversity and environmental characteristics, but its application to invertebrates has been limited. Our objectives were to determine whether LiDAR-derived variables could be used to accurately describe single-species distributions and community characteristics of spiders in remote forested and mountainous terrain. We collected over 5300 spiders across multiple transects in the Bavarian National Park (Germany) using pitfall traps. We examined spider community characteristics (species richness, the Shannon index, the Simpson index, community composition, mean body size, and abundance) and single-species distribution and abundance with LiDAR variables and ground-based measurements. We used the R2 and partial R2 provided by variance partitioning to evaluate the predictive power of LiDAR-derived variables compared to ground measurements for each of the community characteristics. The total adjusted R2 for species richness, the Shannon index, community species composition, and body size had a range of 25-57%. LiDAR variables and ground measurements both contributed >80% to the total predictive power. For species composition, the explained variance was approximately 32%, which was significantly greater than expected by chance. The predictive power of LiDAR-derived variables was comparable or superior to that of the ground-based variables for examinations of single-species distributions, and it explained up to 55% of the variance. The predictability of species distributions was higher for species that had strong associations with shade in open-forest habitats, and this niche position has been well documented across the European continent for spider species. The similar statistical performance between LiDAR and ground-based measures at our field sites indicated that deriving spider community and species distribution information using LiDAR data can provide not only high predictive power at relatively low cost, but may also allow unprecedented mapping of community- and species-level spider information at scales ranging from stands to landscapes. Therefore, LiDAR is a viable tool to assist species-specific conservation as well as broader biodiversity planning efforts not only for a growing list of vertebrates, but for invertebrates as well.

Shallow phylogeographic structuring of Vimba vimba across Europe suggests two distinct refugia during the last glaciation.

Genetic variation and geographical structuring of vimba Vimba vimba were analysed across 26 sites (80 individuals) by means of mtDNA sequences (cyt b gene, mitochondrial control region) to localize hypothesized glacial refugia and to reconstruct postglacial recoloniation routes. Although genetic diversity among sequenced individuals was low, a combined analysis of the two sequenced fragments revealed a western (central and northern Europe: Danube, Elbe and lakes of Sweden) and an eastern clade (eastern Europe: Dnieper-South Bug, Don, Neman). Furthermore, a number of divergent ancestral haplotypes distributed around the Black and Caspian Seas became apparent. Mismatch analyses supported a sudden expansion model for the populations of the western clade between 50 and 10 000 bp. Overall, the study provides strong evidence for a northward and westward expansion of V. vimba from two refugial regions located in the Danubian drainage and the northern Pontic regions respectively.

[Chronic relapsing compartment syndrome]. / Das chronische rezidivierende Kompartmentsyndrom.

Chronic relapsing exertional compartment syndrome is not only found in young athletic subjects. Non-athletic patients can also suffer from exercise dependent pain in the lower limb. The syndrome is defined by increased tissue pressure in between a closed osteo-fibrous space resulting in disturbed microcirculation and finally irreversible neuroischemic damage. Pain increases during running and disappears gradually at rest. The diagnosis is based on the typical symptoms and so far on the pre-, 1 and 5 min post exercise intramuscular pressure measurement. We first describe sonographic criteria induced by increased compartment pressure, especially for the most frequent anterior compartment syndrome with compression of the deep veins, increased movement of arterial wall and finally enddiastolic closure of the anterior tibial artery. Duplex ultrasound also provides pathogenetic factors like popliteal and anterior entrapment, stenosis or hypoplasia of the anterior tibial artery or thrombosis of the deep muscle veins. Many patients are reporting a pain history over years, resulting in complete reduction of their sporting activity. The knowledge about pathogenesis, symptoms, diagnosis and therapy should help shorten the negative impact of the syndrome on their quality of life.

Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion.

Nuclear factor-kappa B (NF-kappaB)/Rel transcription factors play an important role in the inducible regulation of a variety of genes involved in the inflammatory and proliferative responses of cells. The present study was designed to elucidate the implication of NF-kappaB/Rel in the pathogenesis of atherosclerosis. Activation of the dimeric NF-kappaB complex is regulated at a posttranslational level and requires the release of the inhibitor protein IkappaB. The newly developed mAb alpha-p65mAb recognizes the IkappaB binding region on the p65 (RelA) DNA binding subunit and therefore selectively reacts with p65 in activated NF-kappaB. Using immunofluorescence and immunohistochemical techniques, activated NF-kappaB was detected in the fibrotic-thickened intima/media and atheromatous areas of the atherosclerotic lesion. Activation of NF-kappaB was identified in smooth muscle cells, macrophages, and endothelial cells. Little or no activated NF-kappaB was detected in vessels lacking atherosclerosis. Electrophoretic mobility shift assays and colocalization of activated NF-kappaB with NF-kappaB target gene expression suggest functional implications for this transcription factor in the atherosclerotic lesion. This study demonstrates the presence of activated NF-kappaB in human atherosclerotic tissue for the first time. Atherosclerosis, characterized by features of chronic inflammation and proliferative processes, may be a paradigm for the involvement of NF-kappaB/Rel in chronic inflammatory disease.

Gene expression profiling of human stent-induced neointima by cDNA array analysis of microscopic specimens retrieved by helix cutter atherectomy: Detection of FK506-binding protein 12 upregulation.

BACKGROUND: Restenosis due to neointima formation is the major limitation of stent-supported balloon angioplasty. Despite abundant animal data, molecular mechanisms of neointima formation have been investigated on only a limited basis in patients. This study sought to establish a method for profiling gene expression in human in-stent neointima and to identify differentially expressed genes that may serve as novel therapeutic targets. METHODS AND RESULTS: We retrieved tissue specimens from patients with symptomatic in-stent restenosis using a novel helix cutter atherectomy device. cDNA samples prepared from neointima (n=10) and, as a control, from the media of normal arteries (n=14) were amplified using a novel polymerase chain reaction protocol and hybridized to cDNA arrays. Immunohistochemistry characterized the atherectomy material as neointima. cDNA arrays readily identified differentially expressed genes. Some of the differentially expressed genes complied with expected gene expression patterns of neointima, including downregulation of desmin and upregulation of thrombospondin-1, cyclooxygenase-1, and the 70-kDa heat shock protein B. Additionally, we discovered previously unknown gene expression patterns, such as downregulation of mammary-derived growth inhibitor and upregulation of FK506-binding protein 12 (FKBP12). Upregulation of FKBP12 was confirmed at the protein level in neointimal smooth muscle cells. CONCLUSIONS: Gene expression patterns of human neointima retrieved by helix-cutter atherectomy can be reliably analyzed by cDNA array technology. This technique can identify therapeutic targets in patients, as exemplified by the findings regarding FKBP12. FKBP12 is the receptor for Rapamycin (sirolimus), which in animal models reduced neointima formation. Our study thus yields a rationale for the use of Rapamycin to prevent restenosis in patients.

The niche of higher plants: evidence for phylogenetic conservatism.

A species' ecological niche depends on the species' adaptations to its present habitat, but also on the legacy from its ancestors. Most authors argue that such a phylogenetic niche conservatism is of minor importance, although no quantitative analyses across a major taxon is available. Higher plants from central Europe offer a unique opportunity for such an exercise, as the niche positions along various environmental gradients are available for most species. We quantified niche conservatism by two approaches. First, we used a phylogenetic tree and quantified the degree of retention of niches across the tree. Depending on the gradient, the values ranged from 0.43 to 0.22. This was significantly greater than the null expectation. Second, we used a taxonomy and quantified the amount of variance among species that could be explained at higher taxonomic levels. The values ranged from 25 to 72%. Again, this was significantly higher than the null expectation. Thus, both approaches indicated a clear niche conservatism. The distribution of conservatism across taxonomic levels differed considerably among environmental gradients. The differences among environmental gradients could be correlated with the palaeoenvironmental conditions during the radiation of the phylogenetic lineages. Thus, niche conservatism among extant plant species may reflect the opportunities of their ancestors during their diversification.

Pattern formation triggered by rare events: lessons from the spread of rabies.

Understanding of large-scale spatial pattern formation is a key to successful management in ecology and epidemiology. Neighbourhood interactions between local units are known to contribute to large-scale patterns, but how much do they contribute and what is the role of regional interactions caused by long-distance processes? How much long-distance dispersal do we need to explain the patterns that we observe in nature? There seems to be no way to answer these questions empirically. Therefore, we present a modelling approach that is a combination of a grid-based model describing local interactions and an individual-based model describing dispersal. Applying our approach to the spread of rabies, we show that in addition to local rabies dynamics, one long-distance infection per 14000 km2 per year is sufficient to reproduce the wave-like spread of this disease. We conclude that even rare ecological events that couple local dynamics on a regional scale may have profound impacts on large-scale patterns and, in turn, dynamics. Furthermore, the following results emerge: (i) Both neighbourhood infection and long-distance infection are needed to generate the wave-like dispersal pattern of rabies; (ii) randomly walking rabid foxes are not sufficient to generate the wave pattern; and (iii) on a scale of less than 100 km x 100 km, temporal oscillations emerge that are independent from long-distance dispersal.

Niches and size relationships in Coleoptera associated with Cardueae host plants: adaptations to resource gradients.

The ecological meaning of size relationships within guilds is still a matter of debate. We analyzed the niches and size relationships in Coleoptera associated with Cardueae host plants. Species were grouped into guilds using distributional data, host records and feeding strategies: a) The species of the genus Larinus are inhabitants of flower heads within the Cynaroideae. Two types of Larinus species were distinguished: one type attacks immature flower heads, the other exploits the floer heads in a more advanced stage. The females of the first group have elongated rostres adapted to piercing through the bracts of closed flower heads, the other group possesses blunt, short rostres. For an oligophagous group of four Larinus species we are able to show that the distribution of average female rostre length is non-random. b) In southern France four stem boring species of the genera Agapanthia and Lixus coexist within the same hosts. The frequency distributions of body length from these species are clearly overdispersed. c) Coexisting species of the folivorous genus Cassida show no differences in body sizes. We conclude that morphometric differences within the investigated guild of endophytic species (Larinus and Agapanthia/Lixus) evolved in response to size of the used plant structures and the size of potentially competing species, a pattern not evident in ectophytic species. We suggest that these differences are part of a general pattern as the evolution of herbivorous guild may strongly depend on the way how the host resource is exploited (endophagy vs ectophagy). So current differences in statements on the organization of herbivore communities could perhaps be reconciled.

How to live in colonies: spatial foraging strategies of the black-headed gull.

This paper describes some spatial foraging strategies observed in the course of the breeding season in five adult radio-tagged black-headed gulss (Larus ridibundus). 1. Individual foraging distances increased continuously during the nesting period. 2. The maximum foraging distance observed was 18.5 km. 3. All birds showed nearly constant flight directions over the whole breeding period. 4. It is suggested that the continuous increase in foraging distances reduces intraspecific competition around the colony. 5. Because of long foraging distances it seems to be advantageous to use only a small constant foraging sector. This behaviour can probably optimize spatial memory and enhance energetic and temporal efficiency.

Diversity and composition of phytophagous insect guilds on Brassicaceae.

We investigated the guild structure of phytophagous insects on Brassicaceae in Poland and the influence of host-plant parameters (e.g. sampling effort, geographical distribution, taxonomic isolation, nitrogen indicator values) on the species richness of these guilds. The data were extracted from a study published by Lipa et al. The overall number of recorded ectophagous species is about twice the number of endophagous species. Irrespective of the feeding niche, species are predominantly oligophagous, feeding on more than two Brassicaceae genera. The relative importance of endophagous species within the fauna decreases with increasing host range. The sampling effort predicts a high proportion of the variance of alpha-diversity in oligo- and polyphagous insects, but only a low proportion in specialized species. After correction for sampling effort, most of the plant parameters do not explain an additional proportion of the variance in species richness. We hypothesize that the uniform chemical defence system across genera in Brassicaceae is an important factor triggering host range and diversity patterns in phytophagous insects on crucifers.

Dietary niche breadth in a local community of passerine birds: an analysis using phylogenetic contrasts.

The analysis of a local community of forest passerines (13 species) using phylogenetic contrasts shows a correlation between body size of bird species and mean prey size, minimum prey size, maximum prey size and the size range of dietary items. This suggests that larger birds drop small prey taxa from their prey list, because of the difficulty of capturing very small prey, for energetic reasons or because of microhabitat usage. We find some support for the third hypothesis. Dietary niche breadth calculated across prey taxa is not related to body size. Dietary niche breadth, however, is correlated with size-corrected measurements of the bill and locomotor apparatus. Long and slender bills increase the dietary niche breadth. Thus subtle differences constrain foraging and the techniques of extracting certain prey taxa form crevices. Dietary niche breadth and foraging diversity are positively correlated with population density: at least locally dietary generalists occur at higher breeding densities than specialists.

[Spiral CT of the abdomen: weight-adjusted dose reduction]. / Spiral-CT des Abdomens: Gewichtsadaptierte Dosisreduktion.

AIM OF THE STUDY: The influence of weight-adjusted current application in spiral CT of the abdomen on noise was investigated in a clinical study. PATIENTS AND METHODS: In 77 routine abdominal CT investigations (120 kV, 8 mm, pitch 1.5) the patients were divided into three body-weight groups A (< 60 kg), B (60-80 kg), and C (> 80 kg). The tube current was randomized prospectively in low weight group A, either 125 mA or 150 mA, in middle and high weight groups B and C, 150, 175 or 200 mA, with a tube revolution time of one second. The noise was measured in liver, skeleton muscle, fat tissue, and bladder content for evaluation of image quality. RESULTS: The bodyweight groups differ significantly in noise, e.g., in the liver (150 mA): group A: 15.8 HU, group B: 18.9 HU, group C: 21.5 HU. The increase of tube current (150, 175, 200 mA) within a body weight group resulted in a minor decrease of noise (18.9 HU, 17.6 HU, 17.5 HU, respectively, in group B). There is a good correlation of noise with body weight, body mass index and body cross section, but not with body size. CONCLUSION: A body weight adjusted reduction of tube current is possible without an increase of noise.

[Studies on image quality, high contrast resolution and dose for the axial skeleton and limbs with a new, dedicated CT system (ISO-C-3 D)]. / Untersuchungen zur Bildqualität, Hochkontrastauflösung und Dosis am Stamm- und Gliedmassenskelett mit einem neuen dedizierten CT-System (ISO-C-3D).

PURPOSE: Evaluation of 3D-CT imaging of the axial skeleton and different joints of the lower and upper extremities with a new dedicated CT system (ISO-C-3D) based on a mobile isocentric C-arm image amplifier. MATERIAL AND METHODS: 27 cadaveric specimes of different joints of the lower and upper extremities and of the spinal column were examined with 3D-CT imaging (ISO-C-3D). All images were evaluated by 3 radiologists for image quality using a semiquantitative score (score value 1: poor quality; score value 4: excellent quality). In addition, dose measurements and measurements of high contrast resolution were performed in comparison to conventional and low-dose spiral CT using a high contrast phantom (Catphan, Phantom Laboratories). RESULTS: Adequate image quality (mean score values 3 - 4) could be achieved with an applied dose comparable to low-dose CT in smaller joints such as wrist, elbow, ankle and knee. A remarkably inferior image quality resulted in imaging of the hip, lumbar and thoracic spine (mean score values 2 - 3) in spite of almost doubling the dose (dose increased by 85 percent). The image quality of shoulder examinations was insufficient (mean score value 1). Phantom studies showed a high-contrast resolution comparable to helical CT in the xy-axis (9 lp/cm). CONCLUSION: Preliminary results show, that image quality of C-arm-based CT-imaging (ISO-C-3D) seems to be adequate in smaller joints. ISO-C-3D images of the hip and axial skeleton show a decreased image quality, which does not seem to be sufficient for diagnosing subtle fractures.

[Detection of tibial condylar fractures using 3D imaging with a mobile image amplifier (Siemens ISO-C-3D): Comparison with plain films and spiral CT]. / Frakturdiagnostik am Kniegelenk mit einem neuen mobilen CT-System (ISO-C-3D): Vergleich mit konventionellem Röntgen und Spiral-CT.

PURPOSE: To analyze a prototype mobile C-arm 3D image amplifier in the detection and classification of experimental tibial condylar fractures with multiplanar reconstructions (MPR). METHOD: Human knee specimens (n = 22) with tibial condylar fractures were examined with a prototype C-arm (ISO-C-3D, Siemens AG), plain films (CR) and spiral CT (CT). The motorized C-arm provides fluoroscopic images during a 190 degrees orbital rotation computing a 119 mm data cube. From these 3D data sets MP reconstructions were obtained. All images were evaluated by four independent readers for the detection and assessment of fracture lines. All fractures were classified according to the Müller AO classification. To confirm the results, the specimens were finally surgically dissected. RESULTS: 97 % of the tibial condylar fractures were easily seen and correctly classified according to the Müller AO classification on MP reconstruction of the ISO-C-3D. There is no significant difference between ISO-C and CT in detection and correct classification of fractures, but ISO-CD-3D is significant by better than CR. CONCLUSION: The evaluation of fractures with the ISO-C is better than with plain films alone and comparable to CT scans. The three-dimensional reconstruction of the ISO-C can provide important information which cannot be obtained from plain films. The ISO-C-3D may be useful in planning operative reconstructions and evaluating surgical results in orthopaedic surgery of the limbs.

Migration behavior of human smooth muscle cells cultivated from restenotic and primary lesions.

Subintimal smooth muscle cell (SMC) migration is considered an essential determinant of arteriosclerosis and neointimal formation. In this study, a cell culture model was established to characterize migration activity of SMCs originating from restenotic and primary lesions. Plaques from symptomatic stenoses of 32 patients (19 men, 13 women; 4 carotid, 17 peripheral, 11 coronary lesions) were removed by percutaneous atherectomy or direct operative approach. Ten patients suffered from recurrent stenosis. Cell cultures were established by explantation of tissue samples. By indirect immunofluorescence microscopy, SMCs were shown to be the predominant cell type of all advanced lesions irrespective of their origin. The spontaneous cellular motility of SMCs was analyzed in vitro by means of a computer-assisted observation system. Cells of all groups exhibited random motility. SMC migratory velocity was found to be significantly (P < 0.001) greater in cells from restenotic lesions than in those from primary plaques. In conclusion, migration behavior of human SMCs originating from arteriosclerotic lesions may be quantified in vitro as a functional determinant characterizing restenotic versus primary lesions.