Functional limitations in children and adolescents suffering from chronic pain: validation and psychometric properties of the German Functional Disability Inventory (FDI-G)

Our objective was to translate the Functional Disability Inventory (FDI) into German, to evaluate its validity and to assess functional limitation in a large cohort of children and adolescents with juvenile fibromyalgia syndrome (jFMS). We administered several questions (e.g., sociodemographics, school-related issues) and questionnaires to 329 patients and one parent. The questionnaires included, among others, a German version of the FDI, the CHAQ (parent report), KIDSCREEN, tender point score (TPS), Depression Inventory for Children and Adolescents (DIKJ) and others. Patients were asked about the severity of pain today (NRS = numerical rating scale) and other symptoms. Internal consistency was evaluated with Cronbach’s alpha. Construct validity of the FDI was evaluated by correlating the FDI with the questionnaires as well as with the pain and other variables, e.g., days missed school. An exploratory factor analysis (EFA) was also performed. Mean age was 13.9 years (SD ±2.48). Means were for pain today 5.37 (±2.39) and for the TPS 39.71 (±21.56). Internal consistency was α = .90. Low-to-moderate correlations were obtained between the FDI and the CHAQ (ρ = .51**), KIDSCREEN (e.g., physical well-being ρ = ?.62**; peers and social support ρ = ?.28**) as well as the pain variables (NRS ρ = .24**; TPS ρ = .38**). Psychological variables were also correlated with the FDI (e.g., DIJK ρ = .28**). An EFA suggested a two-factor solution. The FDI is a valid instrument for measuring functional limitations in German children and adolescents with jFMS.     

Comparison of the osteogenic capacity of minipig and human bone marrow‐derived mesenchymal stem cells

Minipigs are a recommended large animal model for preclinical testing of human orthopedic implants. Mesenchymal stem cells (MSCs) are the key repair cells in bone healing and implant osseointegration, but the osteogenic capacity of minipig MSCs is incompletely known. The aim of this study was to isolate and characterize minipig bone marrow (BM) and peripheral blood (PB) MSCs in comparison to human BM‐MSCs. BM sample was aspirated from posterior iliac crest of five male Göttingen minipigs (age 15 ± 1 months). PB sample was drawn for isolation of circulating MSCs. MSCs were selected by plastic‐adherence as originally described by Friedenstein. Cell morphology, colony formation, proliferation, surface marker expression, and differentiation were examined. Human BM‐MSCs were isolated and cultured from adult fracture patients (n = 13, age 19–60 years) using identical techniques. MSCs were found in all minipig BM samples, but no circulating MSCs could be detected. Minipig BM‐MSCs had similar morphology, proliferation, and colony formation capacities as human BM‐MSCs. Unexpectedly, minipig BM‐MSCs had a significantly lower ability than human BM‐MSCs to form differentiated and functional osteoblasts. This observation emphasizes the need for species‐specific optimization of MSC culture protocol before direct systematic comparison of MSCs between human and various preclinical large animal models can be made. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1019–1025, 2012     

Neue Behandlungskonzepte von Symptomen des unteren Harntraktes beim Mann

For patients with lower urinary tract symptoms (LUTS), ??1-adrenoreceptor inhibitors and 5-alpha reductase inhibitors as well as their combination are considered the gold standard. In addition, anticholinergic agents are being introduced as monotherapy or in combination with ??1-adrenocepetor inhibitors for patients with predominant storage disorders. Phosphodiesterase 5 (PDE5) inhibitors are often the best option for patients with LUTS who also suffer from erectile dysfunction. Recently, novel treatment options have been presented and intraprostatic injection of various agents, such as botulinum toxin A, NX-1207 and PRX302 has shown promising initial results. In addition, innovative minimally invasive treatment options, such as UroLift? appear to be efficacious and safe in this patient cohort. Particular emphasis should be laid on patients with LUTS and concomitant sexual disorders.     

Behandlungsverfahren der Blase bei Querschnittl?hmung und Myelomeningozele

The established treatment of neurogenic lower urinary tract dysfunction (NLUTD) in patients with spinal cord injury (SCI) or meningomyelocele (MMC) is mainly conservative and is aimed at the lower urinary tract. For example, oral antimuscarinic medication is the standard treatment of neurogenic detrusor overactivity. Recently, however, treatment aiming directly or indirectly at the innervation of the urinary tract has gained increasing attention. Current evidence does not justify the use of nerve rerouting but the existing preliminary data are more promising for MMC patients than for those with SCI. Sacral neuromodulation is already a therapeutic option for incomplete SCI patients. Initial data from a pilot study indicate that in patients with complete SCI implementation in the spinal shock phase may prevent the development of NLUTD. Licensing of onabotulinum toxin A (Botox?) facilitated its clinical use for treating NLUTD but it is limited to the indication of neurogenic detrusor overactivity incontinence with a dosage of 200?IU. The mentioned unconventional treatments, although discussed controversially, are promising future treatment options for NLUTD.     

Maternal Mindfulness Is Associated With Lower Child Body Mass Index Z Score

BackgroundParental mindfulness may be a novel intervention target for child obesity prevention.ObjectiveTo examine associations between maternal mindfulness and child body mass index z-score (BMIz).MethodsIn a secondary data analysis of preintervention data from a randomized controlled trial, we assessed survey and anthropometric data from English-speaking mother/child dyads enrolled in Head Start in south central Michigan (n = 105). Surveys included demographic information, child dietary intake, family meal frequency, and the Philadelphia Mindfulness Questionnaire. Multivariable linear regression examined associations between maternal mindfulness and child BMIz, child intake of fruits and vegetables, and frequency of family meals.ResultsChildren were M = 53.7 (standard deviation [SD] 7.5) months old, and mothers were M = 31.6 (SD 8.3) years old. The sample of children was 39% white, 26% black, 14% Hispanic, and 35% of children were overweight or obese. Mean maternal BMI was 32.0 (SD 8.3). Greater mindfulness was associated with child BMIz (β = ?.02 (SE 0.01), P = .027) adjusting for child race/ethnicity, household food security, maternal education, maternal age, and maternal BMI. Mindfulness was not associated with child fruit intake, child vegetable intake or frequency of family meals. The results were consistent with alternative outcomes of BMI percentile (P = .016) and BMI at the trend level (P = .0595) at the trend level.ConclusionsGreater maternal mindfulness was associated with lower child BMIz. Future work should consider mechanisms of association. Pediatric providers might consider supporting maternal mindfulness as one element of multicomponent strategies for child obesity prevention.     

Insulin resistance and fasting plasma glucose in first degree relatives of patients with type 1 diabetes

BackgroundWe analyzed the relationship between fasting plasma glucose (FPG), the presence of autoantibodies, first phase of insulin secretion and insulin resistance in the first degree relatives of patients with type 1 diabetes.Materials and MethodsThe group studied consisted of 90 healthy relatives, divided into two groups: “high-normal” FPG group (≥ 88 mg/dl) and “low-normal” FPG group (< 88/mg/dl). All subjects underwent an intravenous glucose tolerance test, and the 1st phase insulin response (FPIR) and FPIR-to-HOMA-IR-ratio were calculated. Additionally, islet autoantibodies (GADA, IAA and IA-2A) were determined by radioimmunoassays.ResultsThe subjects with "high-normal" FPG were older (p = 0.0009), had higher BMI (p < 0.0001) and lower HOMA%B (p = 0.0004), FPIR (p = 0.006) and FPIR-to-HOMA-IR-ratio (p = 0.004) in comparison with the "low-normal" FPG group. Autoantibodies were present in 40.9% and in 21.7% of the subjects with "high-normal" and “low-normal” FPG, respectively. In the "high-normal" FPG group, FPG correlated positively with GADA (r = 0.31, p = 0.04), and HOMA-IR (r = 0.19, p = 0.02), and negatively with HOMA%B (r = ? 0.36, p = 0.001), whereas FPIR correlated positively with HOMA%B (r = 0.55, p = 0.0001) and BMI (r = 0.30, p = 0.04). After an adjustment for BMI, the difference in FPIR between the “high-normal” and “low-normal” FPG groups remained significant (p = 0.025), whereas the difference in FPIR-to-HOMA-IR-ratio became insignificant.ConclusionsOur results suggest that taking into account the impact of age and BMI on insulin sensitivity, it would be expected that the relatives of patients with type 1 diabetes with "high-normal" glucose levels would become gradually unable to compensate for increasing insulin resistance.     

A ridge-to-reef ecosystem microbial census reveals environmental reservoirs for animal and plant microbiomes

Microbes are found in nearly every habitat and organism on the planet, where they are critical to host health, fitness, and metabolism. In most organisms, few microbes are inherited at birth; instead, acquiring microbiomes generally involves complicated interactions between the environment, hosts, and symbionts. Despite the criticality of microbiome acquisition, we know little about where hosts’ microbes reside when not in or on hosts of interest. Because microbes span a continuum ranging from generalists associating with multiple hosts and habitats to specialists with narrower host ranges, identifying potential sources of microbial diversity that can contribute to the microbiomes of unrelated hosts is a gap in our understanding of microbiome assembly. Microbial dispersal attenuates with distance, so identifying sources and sinks requires data from microbiomes that are contemporary and near enough for potential microbial transmission. Here, we characterize microbiomes across adjacent terrestrial and aquatic hosts and habitats throughout an entire watershed, showing that the most species-poor microbiomes are partial subsets of the most species-rich and that microbiomes of plants and animals are nested within those of their environments. Furthermore, we show that the host and habitat range of a microbe within a single ecosystem predicts its global distribution, a relationship with implications for global microbial assembly processes. Thus, the tendency for microbes to occupy multiple habitats and unrelated hosts enables persistent microbiomes, even when host populations are disjunct. Our whole-watershed census demonstrates how a nested distribution of microbes, following the trophic hierarchies of hosts, can shape microbial acquisition.

Microbial partners metabolize our food, fight off disease, and run the machinery that sustains the air we breathe, water we drink, and soil under our feet. Despite their importance, most host-associated microbes are generally not present at birth and are instead acquired (1). Because microbial symbionts can influence host health and fitness, the processes that determine how different microbiomes assemble within different hosts is a matter of active and urgent inquiry. Microbial ecologists have made great progress in determining how factors such as abiotic conditions (2–4), host evolution (5, 6), and microbial traits (7–9) shape environmental microbiomes, but considerably less is known about how surrounding environments or different guilds of host organisms contribute to host-associated microbiome composition. Longitudinal studies show that microbial richness accumulates and community composition changes over time across a wide diversity of hosts and habitats (1), but we know comparatively little about from where these microbes originate. To better understand microbial transmission and its role in community composition, we propose a framework that relies on theory from foodweb and landscape ecology.The concept of a foodweb has had a place in the ecological lexicon since at least the time of Elton (1927; (10)), and others such as Lindeman (11) and Odum (12) significantly expanded upon this notion to include how macroorganisms interact within their environments, in addition to their feeding relationships. The units of study for foodwebs are ecosystems, which are spatially explicit and include all organisms along with their abiotic environments and their interactions within its bounds (13). This definition was born from the efforts of the founders of the Hubbard Brook Ecosystem Study (HBES; 1963), who recognized that a watershed naturally delineates the boundaries of an ecosystem, an idea that parallels the Hawaiian ahupuaʻa concept. Since then, the HBES and its framework have led to numerous milestones in our understanding of processes such as the effects of long-term changes in acidification (14) and ecosystem impacts of global warming (15). Here, we adopt the notion of the watershed as an entire discrete ecosystem to better understand the landscape ecology of microbes. Landscape ecology is a means to understand how spatial processes affect biodiversity (16). In classic landscape ecology theory, the structure (heterogeneity) and fragmentation of habitats (or patches) within a matrix of otherwise inhospitable areas affect species’ dispersal ability and establishment. This ultimately shapes species’ abundance and distributions across the landscape (17). Contemporary landscape ecology theory extends this idea to include the concept of a landscape continuum, where continuous environmental variables, as opposed to discrete habitat patches surrounded by a matrix, better describe species’ distributions. Connecting these concepts, foodwebs are embedded in landscapes, and watersheds constitute a useful unit of measure to better understand their interactions.To expand concepts from foodweb and landscape ecology to be inclusive of microbes, we must first consider the following: a landscape for microbes can be both structural (e.g., different land covers or hydrology) and biotic (e.g., variation in the distribution of host populations). Also, microbes might better fit a continuous landscape model rather than a patch model if their distributions are not governed merely by the presence of a compatible host or habitat, but rather, if they exist among multiple hosts across a gradient of environmental conditions. This requires microbes to be generalists to some degree and/or a matrix that is at least partially hospitable (18). These considerations are important because while microbial transmission among related hosts is one obvious means of microbiome assembly, this model, in and of itself, is insufficient to sustain microbiomes (defined here as communities of bacteria and archaea) across a dynamic landscape. For example, many plants and animals are either sparse, seasonal, or ephemeral, requiring that their symbiotic microbes be capable of residing, at times, in alternate nearby hosts or environments. This potential for a microbe to persist in, and disperse among, hosts of different kingdoms and guilds, or even between liquid and land, is a trait with the potential to add an additional dimension to microbiome assembly theory (19). Where, then, might a host’s microbes reside when not inside that host? In addition, what factors might predict microbiome distributions among potentially interacting hosts and environments?Variability in matrix suitability and host specialization may result in differing microbial communities reflected in one of three nonmutually exclusive patterns, each of which leaves a diagnostic imprint on microbiome structure. If any host or environment has an equal likelihood of harboring microbes that are present in any other host or environment, we might expect host–microbe interaction networks that are randomly structured. Alternatively, if microbes are more likely to co-occur among related hosts or guilds, we might expect these to contain unique and specific consortia of microbes (modules) that are not found elsewhere in the interaction network. Finally, host–microbe interactions might be best characterized as stratified, resulting in a network topology in which microbial diversity is nested such that taxa-poor microbiomes are subsets of those that are taxa-rich. In this scenario, nonhost environmental matrices (e.g., soil, sediment, water) serve as reservoirs of broad microbial diversity that is subsequently, and hierarchically, partitioned into simpler microbiomes. While this concept is fairly intuitive, there are actually few, if any, studies that demonstrate transmission among environmental microbiomes and multiple hosts at ecosystem scales. Instead, many of the insights gleaned into assembly processes of microbiomes are owed to studies of single hosts, tractable model systems, or global syntheses (20). We address this gap by sampling microbiomes from aquatic, marine, and terrestrial foodwebs within a single watershed to examine the dynamics of sources and sinks of microbial diversity.Here, we present a microbial census of a model ecosystem metacommunity in which continental-scale environmental heterogeneity is recapitulated within a comparatively small watershed. Because of this, we can surmise the distribution limits of microbiomes across land, stream, and sea, a feat that would not be plausible in most other landscapes of similar size or environmental variability. From ridge to reef, our compact watershed spans a roughly 3.5 m rainfall differential, ∼27 times that encountered along the Mississippi, the largest watershed in continental North America. Also, our model ecosystem is located on the most isolated archipelago on the planet, making exogenous microbial inputs infrequent, if not unlikely. Furthermore, owing to parallels in environmental heterogeneity and foodweb structure across this compact watershed compared to others, our findings are potentially relevant for highly connected ecosystems that span substantially larger geographic areas.For example, a long-standing question in biogeography is the relationship between organisms’ local distributions and those at larger scales. Many factors influence the distributions of microbes, including their physiology, size, population density, and dispersal abilities (21–23). A common assumption is that niche breadth should also predict the range size of an organism, since the ability to survive in broader environments, and to use a greater array of resources, should indicate the ability to occupy more habitats that occur over greater distances (24, 25). This is an important component of source and sink dynamics, because it suggests that local occupancy should predict global distributions. This relationship is seldom tested empirically, however, because small areas rarely contain, or are sampled for, broad climatic variability and host diversity. In the absence of phenotypic, genomic, or even well-resolved taxonomic information about the majority of the earth’s microbial biodiversity, geographic range is one of the few traits that can be directly inferred from short environmental DNA sequence reads. By examining our ecosystem-wide microbiome census within the context of the global survey of the Earth Microbiome Project (26), we assess the relationship between global and local microbial distributions.     

Application of intensity-modulated radiation therapy for pediatric malignancies

Novel radiation therapy delivery techniques have moved very slowly in the field of pediatric oncology. Some collaborative groups allow new radiation therapy delivery techniques in their trials. In many instances, the option of using these techniques is not addressed. These newer techniques of radiation delivery have the potential to reduce the probability of the common late effects of radiation and at the same time, potentially improve upon control and survival. The purpose of this study is to show the feasibility of IMRT in pediatric patients. No treatment results or toxicities will be presented. Five patients with a variety of pediatric malignancies received intensity-modulated radiation therapy (IMRT) at our institution as part of their disease management. A rigid immobilization device was developed for each patient and a computed tomography (CT) simulation was performed in the treatment position. In 3 of the patients, magnetic resonance imaging (MRI) scans were coregistered with the planning CT to facilitate target and critical structure delineation. In all but 1 patient, coplanar beam arrangements were used in the IMRT planning process. All IMRT plans exhibited a high degree of conformality. Dose homogeneity inside the tumor and rapid dose falloff outside the target volume is characteristic of IMRT plans, which allows for improved normal tissue sparing. Dose distributions were obtained for all plans, as well as dose and volume relationship histograms, to evaluate the fitness of the plans. IMRT is a viable alternative to conventional treatment techniques for pediatric cancer patients. The improved dose distributions coupled with the ease of delivery of the IMRT fields make this technique very attractive, especially in view of the potential to increase local control and possibly improve on survival.     

The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients.

BACKGROUND: Uraemic pruritus (UP) is still one of the most vexing and disabling symptoms in chronic renal failure. The pathogenesis of UP is obscure and effective therapeutic strategies are elusive. Deduced from partial successful treatment modalities, there is evidence that an alteration of the immune system with a pro-inflammatory pattern along with a deranged T-helper-cell differentiation may be involved in the pathogenesis of UP. We, therefore, investigated whether UP is related to an augmented Th1-differentiation as measured by determination of intracytoplasmatic (i.c.) cytokines and expression of chemokine receptors. Additionally, pro-inflammatory cytokines were determined in serum. METHODS: In a multicentre study, 171 patients on haemodialysis (HD) were screened for UP. Finally, 13 HD patients with and 13 HD patients without UP, as well as 15 healthy controls were enrolled in the study. Peripheral blood mononuclear cells were isolated and the proportion of Th1- and Th2-cells was determined by flow cytometry. The expression of chemokine receptors on CD4 cells (CXCR3 preferentially on Th1 and CCR4 on Th2) and i.c. cytokines (IFNgamma for Th1 and IL4 for Th2) were measured after in vitro stimulation. Serum cytokine levels (IL6 and TNFalpha) and CRP were measured by ELISA. RESULTS: Compared to HD patients without UP, those complaining of UP showed a significantly enhanced proportion of Th1-cells as measured by both techniques. Additionally, serum CRP and IL6 levels were significantly higher in HD patients with UP, compared to HD patients without UP. CONCLUSIONS: These results point to a central role of inflammation in the pathogenesis of UP in HD patients.