Growth hormone treatment in growth-retarded adolescents after renal transplant

Growth failure is a psychosocial problem for many patients who have undergone renal transplantation. 18 adolescents (mean age 15 6, range 11·3-19 5) with severe growth retardation after renal transplantation were treated with biosynthetic growth hormone (GH) for 2 years. All received prednisone, administered daily or on alternate days, with azathioprine and/or cyclosporin A. 16 were blindly assigned to one of two GH doses (4 vs 8 IU per m2 per day). Growth, bone maturation, renal graft function, plasma insulin-like growth factors, serum binding proteins, and other biochemical parameters were checked regularly. Glomerular filtration rate and effective renal plasma flow were tested with 125I-Thalamate and 131I-Hippuran. Data on growth and glomerular filtration rate during GH treatment were also compared with those of matched non-GH-treated controls. Mean (standard deviation) increment in height after 2 years of GH was 15·7 (5·1) cm, significantly greater (p25% reduction in glomerular filtration rate over 2 years was not significantly higher in GH-treated patients than in non-GH-treated controls (39% vs 32%, p=0·97). Although a few patients had deterioration of graft function, we could not find a relation with GH treatment. Our results show that sustained improvement of height can be achieved with GH in severely growth-retarded adolescents after renal transplantation

A randomized controlled trial of nonoperative treatment versus open reduction and internal fixation for stable, displaced, partial articular fractures of the radial head: The RAMBO trial

Background: The choice between operative or nonoperative treatment is questioned for partial articular fractures of the radial head that have at least 2 millimeters of articular step-off on at least one radiograph (defined as displaced), but less than 2 millimeter of gap between the fragments (defined as stable) and that are not associated with an elbow dislocation, interosseous ligament injury, or other fractures. These kinds of fractures are often classified as Mason type-2 fractures. Retrospective comparative studies suggest that operative treatment might be better than nonoperative treatment, but the long-term results of nonoperative treatment are very good. Most experts agree that problems like reduced range of motion, painful crepitation, nonunion or bony ankylosis are infrequent with both nonoperative and operative treatment of an isolated displaced partial articular fracture of the radial head, but determining which patients will have problems is difficult. A prospective, randomized comparison would help minimize bias and determine the balance between operative and nonoperative risks and benefits. Methods/Design. The RAMBO trial (Radial Head - Amsterdam - Amphia - Boston - Others) is an international prospective, randomized, multicenter trial. The primary objective of this study is to compare patient related outcome defined by the \u27Disabilities of Arm, Shoulder and Hand (DASH) score\u27 twelve months after injury between operative and nonoperative treated patients. Adult patients with partial articular fractures of the radial head that comprise at least 1/3rd of the articular surface, have ≥ 2 millimeters of articular step-off but less than 2 millimeter of gap between the fragments will be enrolled. Secondary outcome measures will be the Mayo Elbow Performance Index (MEPI), the Oxford Elbow Score (OES), pain intensity through the \u27Numeric Rating Scale\u27, range of motion (flexion arc and rotational arc), radiographic appearance of the fracture (heterotopic ossification, radiocapitellar and ulnohumeral arthrosis, fracture healing, and signs of implant loosening or breakage) and adverse events (infection, nerve injury, secondary interventions) after one year. Discussion. The successful completion of this trial will provide evidence on the best treatment for stable, displaced, partial articular fractures of the radial head. Trial registration. The trial is registered at the Dutch Trial Register: NTR3413. © 2014Bruinsma et al.; licensee BioMed Central Ltd

Low Urinary Iodine Excretion during Early Pregnancy Is Associated with Alterations in Executive Functioning in Children 1-3

Abstract The rare but deleterious effects of severe iodine deficiency during pregnancy on cognitive functioning of children are well known. Reports on possible associations between mild-to-moderate maternal iodine deficiency and child development, however, are scarce. In a population-based cohort we examined the association between maternal urinary iodine during early pregnancy and executive functioning in children at 4 y of age. In addition, we investigated the modification of this association by maternal diet and thyroid function. During pregnancy, we measured urinary iodine and thyroid hormone concentrations in associated with higher urinary iodine. Thus, low maternal urinary iodine during pregnancy is associated with impaired executive functioning in children. Because these symptoms were subclinical and occurred at an early age, future studies are needed to show whether these children are more vulnerable to develop later clinical disorders

Low Urinary Iodine Excretion during Early Pregnancy Is Associated with Alterations in Executive Functioning in Children 1-3

Abstract The rare but deleterious effects of severe iodine deficiency during pregnancy on cognitive functioning of children are well known. Reports on possible associations between mild-to-moderate maternal iodine deficiency and child development, however, are scarce. In a population-based cohort we examined the association between maternal urinary iodine during early pregnancy and executive functioning in children at 4 y of age. In addition, we investigated the modification of this association by maternal diet and thyroid function. During pregnancy, we measured urinary iodine and thyroid hormone concentrations in associated with higher urinary iodine. Thus, low maternal urinary iodine during pregnancy is associated with impaired executive functioning in children. Because these symptoms were subclinical and occurred at an early age, future studies are needed to show whether these children are more vulnerable to develop later clinical disorders

A randomized controlled trial of nonoperative treatment versus open reduction and internal fixation for stable, displaced, partial articular fractures of the radial head: The RAMBO trial

Background: The choice between operative or nonoperative treatment is questioned for partial articular fractures of the radial head that have at least 2 millimeters of articular step-off on at least one radiograph (defined as displaced), but less than 2 millimeter of gap between the fragments (defined as stable) and that are not associated with an elbow dislocation, interosseous ligament injury, or other fractures. These kinds of fractures are often classified as Mason type-2 fractures. Retrospective comparative studies suggest that operative treatment might be better than nonoperative treatment, but the long-term results of nonoperative treatment are very good. Most experts agree that problems like reduced range of motion, painful crepitation, nonunion or bony ankylosis are infrequent with both nonoperative and operative treatment of an isolated displaced partial articular fracture of the radial head, but determining which patients will have problems is difficult. A prospective, randomized comparison would help minimize bias and determine the balance between operative and nonoperative risks and benefits. Methods/Design. The RAMBO trial (Radial Head - Amsterdam - Amphia - Boston - Others) is an international prospective, randomized, multicenter trial. The primary objective of this study is to compare patient related outcome defined by the 'Disabilities of Arm, Shoulder and Hand (DASH) score' twelve months after injury between operative and nonoperative treated patients. Adult patients with partial articular fractures of the radial head that comprise at least 1/3rd of the articular surface, have ≥ 2 millimeters of articular step-off but less than 2 millimeter of gap between the fragments will be enrolled. Secondary outcome measures will be the Mayo Elbow Performance Index (MEPI), the Oxford Elbow Score (OES), pain intensity through the 'Numeric Rating Scale', range of motion (flexion arc and rotational arc), radiographic appearance of the fracture (heterotopic ossification, radiocapitellar and ulnohumeral arthrosis, fracture healing, and signs of implant loosening or breakage) and adverse events (infection, nerve injury, secondary interventions) after one year. Discussion. The successful completion of this trial will provide evidence on the best treatment for stable, displaced, partial articular fractures of the radial head. Trial registration. The trial is registered at the Dutch Trial Register: NTR3413

Ecology of bacteria in the human gastrointestinal tract—identification of keystone and foundation taxa

Background Determining ecological roles of community members and the impact of specific taxa on overall biodiversity in the gastrointestinal (GI) microbiota is of fundamental importance. A step towards a systems-level understanding of the GI microbiota is characterization of biotic interactions. Community time series analysis, an approach based on statistical analysis of changing population abundances within a single system over time, is needed in order to say with confidence that one population is affecting the dynamics of another. Results Here, we characterize biotic interaction structures and define ecological roles of major bacterial groups in four healthy individuals by analysing high-resolution, long-term (>180 days) GI bacterial community time series. Actinobacteria fit the description of a keystone taxon since they are relatively rare, but have a high degree of ecological connectedness, and are positively correlated with diversity both within and between individuals. Bacteriodetes were found to be a foundation taxon in that they are numerically dominant and interact extensively, in particular through positive interactions, with other taxa. Although community structure, diversity and biotic interaction patterns were specific to each individual, we observed a strong tendency towards more intense competition within than between phyla. This is in agreement with Darwin’s limiting similarity hypothesis as well as a published biotic interaction model of the GI microbiota based on reverse ecology. Finally, we link temporal enterotype switching to a reciprocal positive interaction between two key genera. Conclusions In this study, we identified ecological roles of key taxa in the human GI microbiota and compared our time series analysis results with those obtained through a reverse ecology approach, providing further evidence in favour of the limiting similarity hypothesis first put forth by Darwin. Larger longitudinal studies are warranted in order to evaluate the generality of basic ecological concepts as applied to the GI microbiota, but our results provide a starting point for achieving a more profound understanding of the GI microbiota as an ecological system

A novel ultra high-throughput 16S rRNA gene amplicon sequencing library preparation method for the Illumina HiSeq platform

Background Advances in sequencing technologies and bioinformatics have made the analysis of microbial communities almost routine. Nonetheless, the need remains to improve on the techniques used for gathering such data, including increasing throughput while lowering cost and benchmarking the techniques so that potential sources of bias can be better characterized. Methods We present a triple-index amplicon sequencing strategy to sequence large numbers of samples at significantly lower c ost and in a shorter timeframe compared to existing methods. The design employs a two-stage PCR protocol, incorpo rating three barcodes to each sample, with the possibility to add a fourth-index. It also includes heterogeneity spacers to overcome low complexity issues faced when sequencing amplicons on Illumina platforms. Results The library preparation method was extensively benchmarked through analysis of a mock community in order to assess biases introduced by sample indexing, number of PCR cycles, and template concentration. We further evaluated the method through re-sequencing of a standardized environmental sample. Finally, we evaluated our protocol on a set of fecal samples from a small cohort of healthy adults, demonstrating good performance in a realistic experimental setting. Between-sample variation was mainly related to batch effects, such as DNA extraction, while sample indexing was also a significant source of bias. PCR cycle number strongly influenced chimera formation and affected relative abundance estimates of species with high GC content. Libraries were sequenced using the Illumina HiSeq and MiSeq platforms to demonstrate that this protocol is highly scalable to sequence thousands of samples at a very low cost. Conclusions Here, we provide the most comprehensive study of performance and bias inherent to a 16S rRNA gene amplicon sequencing method to date. Triple-indexing greatly reduces the number of long custom DNA oligos required for library preparation, while the inclusion of variable length heterogeneity spacers minimizes the need for PhiX spike-in. This design results in a significant cost reduction of highly multiplexed amplicon sequencing. The biases we characterize highlight the need for highly standardized protocols. Reassuringly, we find that the biological signal is a far stronger structuring factor than the various sources of bias