Does Early Conversion to Below-elbow Casting for Pediatric Diaphyseal Both-bone Forearm Fractures Adversely Affect Patient-reported Outcomes and ROM?

BACKGROUND: For distal forearm fractures in children, it has been shown that a below-elbow cast is an adequate treatment that overcomes the discomfort of an above-elbow cast and unnecessary immobilization of the elbow. For reduced diaphyseal both-bone forearm fractures, our previous randomized controlled trial (RCT)-which compared an above-elbow cast with early conversion to a below-elbow cast-revealed no differences in the risk of redisplacement or functional outcomes at short-term follow-up. Although studies with a longer follow-up after diaphyseal both-bone forearm fractures in children are scarce, they are essential, as growth might affect the outcome. QUESTIONS/PURPOSES: In this secondary analysis of an earlier RCT, we asked: (1) Does early conversion from an above-elbow to a below-elbow cast in children with reduced, stable diaphyseal forearm fractures result in worse clinical and radiological outcome? (2) Does a malunion result in inferior clinical outcomes at 7.5 years of follow-up? METHODS: In this study, we evaluated children at a minimum of 5 years of follow-up who were included in a previous RCT. The median (range) duration of follow-up was 7.5 years (5.2 to 9.9). The patients for this RCT were included from the emergency departments of four different urban hospitals. Between January 2006 and August 2010, we treated 128 patients for reduced diaphyseal both-bone forearm fractures. All 128 patients were eligible; 24% (31) were excluded because they were lost before the minimum study follow-up or had incomplete datasets, leaving 76% (97) for secondary analysis. The loss in the follow-up group was comparable to the included population. Eligible patients were invited for secondary functional and radiographic assessment. The primary outcome was the difference in forearm rotation compared with the uninjured contralateral arm. Secondary outcomes were the ABILHAND-kids and QuickDASH questionnaire, loss of flexion and extension of the elbow and wrist compared with the contralateral forearm, JAMAR grip strength ratio, and radiological assessment of residual deformity. The study was not blinded regarding the children, parents, and clinicians. RESULTS: At 7.5-year follow-up, there were no differences in ABILHAND-kids questionnaire score (above-elbow cast: 41 ± 2.4 versus above/below-elbow cast: 41.7 ± 0.7, mean difference -0.7 [95% confidence interval (CI) -1.4 to 0.04]; p = 0.06), QuickDASH (above-elbow cast: 5.8 ± 9.6 versus 2.9 ± 6.0 for above-/below-elbow cast, mean difference 2.9 [95% CI -0.5 to 6.2]; p = 0.92), and grip strength (0.9 ± 0.2 for above-elbow cast versus 1 ± 0.2 for above/below-elbow cast, mean difference -0.04 [95% CI -1 to 0.03]; p = 0.24). Functional outcomes showed no difference (loss of forearm rotation: above-elbow cast 7.9 ± 17.7 versus 4.1 ± 6.9 for above-/below-elbow cast, mean difference 3.8 [95% CI -1.7 to 9.4]; p = 0.47; arc of motion: above-elbow cast 152° ± 21° versus 155° ± 11° for the above/below-elbow cast group, mean difference -2.5 [95% CI -9.3 to -4.4]; p = 0.17; loss of wrist flexion-extension: above-elbow cast group 1.0° ± 5.0° versus 0.6° ± 4.2° for above/below-elbow cast, mean difference 0.4° [95% CI -1.5° to 2.2°]; p = 0.69). The secondary follow-up showed improvement in forearm rotation in both groups compared with the rotation at 7 months. For radiographical analysis, the only difference was in AP ulna (above-elbow cast: 6° ± 3° versus above/below-elbow cast: 5° ± 2°, mean difference 1.8° [0.7° to 3°]; p = 0.003), although this is likely not clinically relevant. There were no differences in the other parameters. Thirteen patients with persistent malunion at 7-month follow-up showed no clinically relevant differences in functional outcomes at 7.5-year follow-up compared with children without malunion. The loss of forearm rotation was 5.5ׄ° ± 9.1° for the malunion group compared with 6.0° ± 13.9° in the no malunion group, with a mean difference of 0.4 (95% CI of -7.5 to 8.4; p = 0.92). CONCLUSION: In light of these results, we suggest that surgeons perform an early conversion to a below-elbow cast for reduced diaphyseal both-bone forearm fractures in children. This study shows that even in patients with secondary fracture displacement, remodeling occurred. And even in persistent malunion, these patients mostly showed good-to-excellent final results. Future studies, such as a meta-analysis or a large, prospective observational study, would help to establish the influence of skeletal age, sex, and the severity and direction of malunion angulation of both the radius and ulna on clinical result. Furthermore, a similar systematic review could prove beneficial in clarifying the acceptable angulation for pediatric lower extremity fractures. LEVEL OF EVIDENCE: Level I, therapeutic study.

Improved forearm rotation even after early conversion to below-elbow cast for non-reduced diaphyseal both-bones forearm fractures in children: a secondary 7.5-year follow up of a randomized trial.

BACKGROUND AND PURPOSE: previous RCT compared short-term results of above-elbow cast (AEC) with early conversion to below-elbow cast (BEC) in children with non-reduced diaphyseal both-bone forearm fractures. After 7 months both groups had comparable function. Our primary aim was to investigate whether forearm rotation improves or worsens over time. Secondary aims were loss of flexion and extension of the elbow and wrist, patient-reported outcomes measures, grip strength ratio, and radiographic assessment. PATIENTS AND METHODS: We performed long-term follow-up (FU) of a previous RCT. All patients were invited again for the long-term FU measurements. Primary outcome was limitation of forearm rotation. Secondary outcomes were loss of flexion and extension of the elbow and wrist compared with the contralateral forearm, the ABILHAND-Kids questionnaire and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, grip strength ratio, and radiographic assessment. RESULTS: The mean FU was 7.5 (4.4-9.6) years. Of the initial 47 children, 38 (81%) participated. Rotation improved in both groups over time, with no significant difference in the final forearm rotation: 8° (SD 22) for the AEC group and 8° (SD 15) for the BEC group with a mean difference of 0° (95% confidence interval -13 to 12). Secondary outcomes showed no statistically significant differences. Finally, children < 9 years almost all have full recovery of function. CONCLUSION: Long-term follow-up showed that loss of forearm rotation after a non-reduced diaphyseal both-bone forearm fracture improved significantly compared with that at 7 months, independent of the initial treatment and children aged < 9 will have almost full recovery of function. This substantiates that the remaining growth behaves like a "friend" at long-term follow-up.

Do We Need to Stabilize All Reduced Metaphyseal Both-bone Forearm Fractures in Children with K-wires?

BACKGROUND: Short-term follow-up studies have shown that reduced metaphyseal both-bone forearm fractures in children should be treated with K-wires to prevent redisplacement and inferior functional results. Minimum 5-year follow-up studies are limited. Range of motion, patient-reported outcome measures, and radiographic parameters at minimum 5-year follow-up should be evaluated because they could change insights into how to treat pediatric metaphyseal forearm fractures. QUESTIONS/PURPOSES: (1) Does K-wire stabilization of reduced metaphyseal both-bone forearm fractures in children provide better forearm rotation at minimum 5-year follow-up? (2) Do malunions (untreated redisplaced fractures) of reduced metaphyseal both-bone forearm fractures in children induce worse functional results? (3) Which factors lead to limited forearm rotation at minimum 5-year follow-up? METHODS: We analyzed the extended minimum 5-year follow-up of a randomized controlled trial in which children with a reduced metaphyseal both-bone forearm fracture were randomized to either an above-elbow cast (casting group) or fixation with K-wires and an above-elbow cast (K-wire group). Between January 2006 and December 2010, 128 patients were included in the original randomized controlled trial: 67 in the casting group and 61 in the K-wire group. For the current study, based on an a priori calculation, it was determined that, with an anticipated mean limitation in prosupination (forearm rotation) of 7° ± 7° in the casting group and 3° ± 5° in the K-wire group, a power of 80% and a significance of 0.05, the two groups should consist of 50 patients each. Between January 2014 and May 2016, 82% (105 of 128) of patients were included, with a mean follow-up of 6.8 ± 1.4 years: 54 in the casting group and 51 in the K-wire group. At trauma, patients had a mean age of 9 ± 3 years and had mean angulations of the radius and ulna of 25° ± 14° and 23° ± 18°, respectively. The primary result was limitation in forearm rotation. Secondary outcome measures were radiologic assessment, patient-reported outcome measures (QuickDASH and ABILHAND-kids), handgrip strength, and VAS score for cosmetic appearance. Assessments were performed by the first author (unblinded). Multivariable logistic regression analysis was performed to analyze which factors led to a clinically relevant limitation in forearm rotation. RESULTS: There was a mean limitation in forearm rotation of 5° ± 11° in the casting group and 5° ± 8° in the K-wire group, with a mean difference of 0.3° (95% CI -3° to 4°; p = 0.86). Malunions occurred more often in the casting group than in the K-wire group: 19% (13 of 67) versus 7% (4 of 61) with an odds ratio of 0.22 for K-wiring (95% CI 0.06 to 0.80; p = 0.02). In patients in whom a malunion occurred (malunion group), there was a mean limitation in forearm rotation of 6° ± 16° versus 5° ± 9° in patients who did not have a malunion (acceptable alignment group), with a mean difference 0.8° (95% CI -5° to 7°; p = 0.87). Factors associated with a limited forearm rotation ≥ 20° were a malunion after above-elbow casting (OR 5.2 [95% CI 1.0 to 27]; p = 0.045) and a refracture (OR 7.1 [95% CI 1.4 to 37]; p = 0.02). CONCLUSION: At a minimum of 5 years after injury, in children with a reduced metaphyseal both-bone forearm fracture, there were no differences in forearm rotation, patient-reported outcome measures, or radiographic parameters between patients treated with only an above-elbow cast compared with those treated with additional K-wire fixation. Redisplacements occurred more often if treated by an above-elbow cast alone. If fracture redisplacement is not treated promptly, this leads to a malunion, which is a risk factor for a clinically relevant (≥ 20°) limitation in forearm rotation at minimum 5-year follow-up. Children with metaphyseal both-bone forearm fractures can be treated with closed reduction and casting without additional K-wire fixation. Nevertheless, a clinician should inform parents and patient about the high risk of fracture redisplacement (and therefore malunion), with risk for limited forearm rotation if left untreated. Weekly radiographic monitoring is essential. If redisplacement occurs, remanipulation and fixation with K-wires should be considered based on gender, age, and direction of angulation. Future research is required to establish the influence of (skeletal) age, gender, and the direction of malunion angulation on clinical outcome. LEVEL OF EVIDENCE: Level I, therapeutic study.

Gold Coast diagnostic criteria: Implications for ALS diagnosis and clinical trial enrollment.

Diagnostic criteria for amyotrophic lateral sclerosis (ALS) are complex, incorporating multiple levels of certainty from possible through to definite, and are thereby prone to error. Specifically, interrater variability was previously established to be poor, thereby limiting utility as diagnostic enrollment criteria for clinical trials. In addition, the different levels of diagnostic certainty do not necessarily reflect disease progression, adding confusion to the diagnostic algorithm. Realizing these inherent limitations, the World Federation of Neurology, the International Federation of Clinical Neurophysiology, the International Alliance of ALS/MND Associations, the ALS Association (United States), and the Motor Neuron Disease Association convened a consensus meeting (Gold Coast, Australia, 2019) to consider the development of simpler criteria that better reflect clinical practice, and that could merge diagnostic categories into a single entity. The diagnostic accuracy of the novel Gold Coast criteria was subsequently interrogated through a large cross-sectional study, which established an increased sensitivity for ALS diagnosis when compared with previous criteria. Diagnostic accuracy was maintained irrespective of disease duration, functional status, or site of disease onset. Importantly, the Gold Coast criteria differentiated atypical phenotypes, such as primary lateral sclerosis, from the more typical ALS phenotype. It is proposed that the Gold Coast criteria should be incorporated into routine practice and clinical trial settings.

Below-elbow cast sufficient for treatment of minimally displaced metaphyseal both-bone fractures of the distal forearm in children: long-term results of a randomized controlled multicenter trial.

Background and purpose - We have previously shown that children with minimally displaced metaphyseal both-bone forearm fractures, who were treated with a below-elbow cast (BEC) instead of an above-elbow cast (AEC), experienced more comfort, less interference in daily activities, and similar functional outcomes at 7 months' follow-up (FU). This study evaluates outcomes at 7 years' follow-up.Patients and methods - A secondary analysis was performed of the 7 years' follow-up data from our RCT. Primary outcome was loss of forearm rotation compared with the contralateral forearm. Secondary outcomes were patient-reported outcome measures (PROMs) consisting of the ABILHAND-kids and the DASH questionnaire, grip strength, radiological assessment, and cosmetic appearance.Results - The mean length of FU was 7.3 years (5.9-8.7). Of the initial 66 children who were included in the RCT, 51 children were evaluated at long-term FU. Loss of forearm rotation and secondary outcomes were similar in the 2 treatment groups.Interpretation - We suggest that children with minimally displaced metaphyseal both-bone forearm fractures should be treated with a below-elbow cast.

Three-Dimensional Proton Beam Writing of Optically Active Coherent Vacancy Spins in Silicon Carbide.

Constructing quantum devices comprises various challenging tasks, especially when concerning their nanoscale geometry. For quantum color centers, the traditional approach is to fabricate the device structure after the nondeterministic placement of the centers. Reversing this approach, we present the controlled generation of quantum centers in silicon carbide (SiC) by focused proton beam in a noncomplex manner without need for pre- or postirradiation treatment. The generation depth and resolution can be predicted by matching the proton energy to the material's stopping power, and the amount of quantum centers at one specific sample volume is tunable from ensembles of millions to discernible single photon emitters. We identify the generated centers as silicon vacancies through their characteristic magnetic resonance signatures and demonstrate that they possess a long spin-echo coherence time of 42 ± 20 µs at room temperature. Our approach hence enables the fabrication of quantum hybrid nanodevices based on SiC platform, where spin centers are integrated into p-i-n diodes, photonic cavities, and mechanical resonators.

A multilevel screening strategy defines a molecular fingerprint of proregenerative olfactory ensheathing cells and identifies SCARB2, a protein that improves regenerative sprouting of injured sensory spinal axons.

Olfactory ensheathing cells (OECs) have neuro-restorative properties in animal models for spinal cord injury, stroke, and amyotrophic lateral sclerosis. Here we used a multistep screening approach to discover genes specifically contributing to the regeneration-promoting properties of OECs. Microarray screening of the injured olfactory pathway and of cultured OECs identified 102 genes that were subsequently functionally characterized in cocultures of OECs and primary dorsal root ganglion (DRG) neurons. Selective siRNA-mediated knockdown of 16 genes in OECs (ADAMTS1, BM385941, FZD1, GFRA1, LEPRE1, NCAM1, NID2, NRP1, MSLN, RND1, S100A9, SCARB2, SERPINI1, SERPINF1, TGFB2, and VAV1) significantly reduced outgrowth of cocultured DRG neurons, indicating that endogenous expression of these genes in OECs supports neurite extension of DRG neurons. In a gain-of-function screen for 18 genes, six (CX3CL1, FZD1, LEPRE1, S100A9, SCARB2, and SERPINI1) enhanced and one (TIMP2) inhibited neurite growth. The most potent hit in both the loss- and gain-of-function screens was SCARB2, a protein that promotes cholesterol secretion. Transplants of fibroblasts that were genetically modified to overexpress SCARB2 significantly increased the number of regenerating DRG axons that grew toward the center of a spinal cord lesion in rats. We conclude that expression of SCARB2 enhances regenerative sprouting and that SCARB2 contributes to OEC-mediated neuronal repair.

Think twice before re-manipulating distal metaphyseal forearm fractures in children.

BACKGROUND: Treatment of displaced paediatric distal forearm fractures is not always successful. Re-occurrence of angular deformity is a frequent complication. No consensus exists when to perform secondary manipulations. The purpose of this study was to analyse the long-term outcome of re-angulated paediatric forearm fractures to determine if re-manipulations can be avoided. METHODS: Children who underwent closed reduction for distal forearm fractures and presented with re-angulation at follow-up were included in this retrospective cohort study. We compared those that were re-manipulated to those managed conservatively. Re-angulation was defined as ≥15° of angulation on either the AP or lateral view. Children were reviewed after 1-8 years post injury. Outcome measures were residual angulation on radiographs, active range of motion, grip strength, Visual Analogue Scales (satisfaction, cosmetics and pain) and the ABILHANDS-kids questionnaire. RESULTS: Sixty-six children (mean age of 9.6 years) were included. Twenty-four fractures were re-manipulated and 42 fractures had been left to heal in angulated position. At time of re-angulation, children <12 years in the conservative group had similar angulations to those re-manipulated. Children ≥12 years in the re-manipulation group had significantly greater angulations than children in the conservative group. At final follow-up, after a mean of 4.0 years, near anatomical alignment was seen on radiographs in all patients. Functional outcome was predominantly excellent. There was no significant difference in functional, subjective or radiological outcomes between treatment groups. CONCLUSION: Re-manipulation of distal forearm fractures in children <12 years did not improve outcomes, deeming re-manipulations unnecessary. Children ≥12 years in the conservative group achieved satisfactory outcomes despite re-angulations exceeding current guidelines. Based on observed remodelling, we now accept up to 30° angulation in children <9 years; 25° angulation in children aged 9-<12; 20° angulation in children ≥12 years, when re-angulation occurs. We conclude that clinicians should be more reluctant to perform re-manipulations.

Animal board invited review: Heritability of nitrogen use efficiency in fattening pigs: Current state and possible directions.

Pork, an important component of human nutrition worldwide, contributes considerably to anthropogenic nitrogen and greenhouse gas emissions. Reducing the environmental impact of pig production is therefore essential. This can be achieved through system-level strategies, such as optimising resource use, improving manure management and recycling leftovers from human food production, and at the individual animal level by maintaining pig health and fine-tuning dietary protein levels to individual requirements. Breeding, coupled with nutritional strategies, offers a lasting solution to improve nitrogen use efficiency (NUE) - the ratio of nitrogen retained in the body to nitrogen ingested. With a heritability as high as 0.54, incorporating NUE into breeding programmes appears promising. Nitrogen use efficiency involves multiple tissues and metabolic processes, and is influenced by the environment and individual animal characteristics, including its genetic background. Heritable genetic variation in NUE may therefore occur in many different processes, including the central nervous regulation of feed intake, the endocrine system, the gastrointestinal tract where digestion and absorption take place, and the composition of the gut microbiome. An animal's postabsorptive protein metabolism might also harbour important genetic variation, especially in the maintenance requirements of tissues and organs. Precise phenotyping, although challenging and costly, is essential for successful breeding. Various measurement techniques, such as imaging techniques and mechanistic models, are being explored for their potential in genetic analysis. Despite the difficulties in phenotyping, some studies have estimated the heritability and genetic correlations of NUE. These studies suggest that direct selection for NUE is more effective than indirect methods through feed efficiency. The complexity of NUE indicates a polygenic trait architecture, which has been confirmed by genome-wide association studies that have been unable to identify significant quantitative trait loci. Building sufficiently large reference populations to train genomic prediction models is an important next step. However, this will require the development of truly high-throughput phenotyping methods. In conclusion, breeding pigs with higher NUE is both feasible and necessary but will require increased efforts in high-throughput phenotyping and improved genome annotation.

Outcomes of 3-D corrective osteotomies for paediatric malunited both-bone forearm fractures.

Closed treatment of paediatric diaphyseal forearm fractures carries the risk of re-displacement, which can lead to symptomatic malunions. This is because growth will not correct angulation deformity as it does in metaphyseal fractures. The purpose of this prospective cohort study was to evaluate the outcomes after 3-D-planned corrective osteotomy with patient-specific surgical guides for paediatric malunited forearm fractures causing impaired pro-supination. Our primary outcome measure was the gain in pro-supination at 12 months follow-up. Fifteen patients with a mean age at trauma of 9.6 years and time until osteotomy of 5.9 years were included. Preoperatively, patients displayed a mean pro-supination of 67° corresponding to 44% of the contralateral forearm. At final follow-up, this improved to 128°, achieving 85% of the contralateral side. Multivariate linear regression analysis revealed that predictors of greater functional gain after 3-D corrective osteotomy are severe preoperative impairment in pro-supination, shorter interval until 3-D corrective osteotomy and greater angulation of the radius.Level of evidence: III.

A multiparametric activity profiling platform for neuron disease phenotyping and drug screening.

Patient stem cell-derived models enable imaging of complex disease phenotypes and the development of scalable drug discovery platforms. Current preclinical methods for assessing cellular activity do not, however, capture the full intricacies of disease-induced disturbances and instead typically focus on a single parameter, which impairs both the understanding of disease and the discovery of effective therapeutics. Here, we describe a cloud-based image processing and analysis platform that captures the intricate activity profile revealed by GCaMP fluorescence recordings of intracellular calcium changes and enables the discovery of molecules that correct 153 parameters that define the amyotrophic lateral sclerosis motor neuron disease phenotype. In a high-throughput screen, we identified compounds that revert the multiparametric disease profile to that found in healthy cells, a novel and robust measure of therapeutic potential quite distinct from unidimensional screening. This platform can guide the development of therapeutics that counteract the multifaceted pathological features of diseased cellular activity.

Haemophilia management: time to get personal?

The possibility of alloimmunization in patients receiving protein replacement therapy depends on (at least) three risk factors, which are necessary concomitantly but insufficient alone. The first is the degree of structural difference between the therapeutic protein and the patient's own endogenous protein, if expressed. Such differences depend on the nature of the disease mutation and the pre-mutation endogenous protein structure as well as on post-translational changes and sequence-engineered alterations in the therapeutic protein. Genetic variations in the recipients' immune systems comprise the second set of risk determinants for deleterious immune responses. For example, the limited repertoire of MHC class II isomers encoded by a given person's collection of HLA genes may or may not be able to present a 'foreign' peptide(s) produced from the therapeutic protein - following its internalization and proteolytic processing - on the surface of their antigen-presenting cells (APCs). The third (and least characterized) variable is the presence or absence of immunologic 'danger signals' during the display of foreign-peptide/MHC-complexes on APCs. A choice between existing therapeutic products or the manufacture of new proteins, which may be less immunogenic in some patients or patient populations, may require prior definition of the first two of these variables. This leads then to the possibility of developing personalized therapies for disorders due to genetic deficiencies in endogenous proteins, such as haemophilia A and B. [Correction made after online publication 11 July 2011: several critical corrections have been made to the abstract].

Voice handicap index and voice-related quality of life in small laryngeal carcinoma.

Laryngeal cancer can affect the patients' voice. For assessment of the patients' self-perception of their voice, several tools were introduced into clinical routine. The voice handicap index questionnaire (VHI) is regarded as the "gold standard". However, in benign laryngeal pathologies and in functional dysphonia, the shorter voice-related quality of life questionnaire (V-RQOL) proved to be equivalent. This study examines the correlation of both questionnaires in patients who had been treated for small (T1 and T2) laryngeal cancer. It was performed during regular outclinic examinations. In total, 65 patients aged 62.1 ± 10.0 years completed the German versions of the VHI and V-RQOL. Their average VHI total score was 38.9 ± 26.0 points and the average V-RQOL score was 70.1 ± 24.4%. The total scores correlated with |ρ| = 0.92 and p < 0.01. Both questionnaires give quasi identical results, the shorter V-RQOL may be favoured for clinical application.

Evaluation of feeding behaviour traits to predict efficiency traits in pigs using partial least square regression.

The improvement of efficiency traits, such as protein efficiency (PE), digestible energy efficiency (EnE) and lipid gain (LipG), are relevant given their associations with environmental pollution, cost of production, and the quality of meat. However, these traits are difficult to measure and usually require slaughtering of pigs. Efficiency traits are complex, and several factors, such as genetic predisposition, feed composition, but also individual feeding behaviour may contribute to efficiency. The objective of this study was therefore to evaluate the potential of using feeding behaviour traits to predict efficiency traits under dietary protein restriction. A total of 587 Swiss Large White pigs, consisting of 312 females and 275 castrated males, had ad libitum access to feed and water, and were fed a protein-reduced diet (80% of recommended digestible protein and essential amino acids) from 22.5 ± 1.6 to 106.6 ± 4.6 kg BW. Individual feed intake was monitored and carcass composition (lean and fat mass) at slaughter was determined by dual-energy X-ray absorptiometry. The PE and EnE were calculated as the ratio of protein or energy in the carcass (estimated by dual-energy X-ray absorptiometry) to the total protein or energy consumed. Feeding behaviour traits monitored were daily feed intake, feed intake per meal, number of daily meals, duration per meal, feeding rate, and feeder occupation. A partial least square (PLS) regression was used to predict PE, EnE and LipG from feeding behaviour traits, while including farrowing series (for PE only), age at slaughter and BW at slaughter. Accuracy of PLS regression was assessed based on RMSE and R2 for calibration and validation sets, and on concordance correlation coefficient, which were estimated over 100 replicates of calibration and validation sets. Models with a number of latent variables of 5, 2 and 3 were identified as optimal for PE, EnE, and LipG, which explained 34.64%, 55.42% and 82.68% of the total variation in PE, EnE, and LipG, respectively. Significant concordance correlation coefficient was found between predicted and observed values for PE (0.50), EnE (0.70), and LipG (0.90). In conclusion, individual feeding behaviour traits can better predict EnE and LipG than for PE under dietary protein restriction when fed ad libitum.

Accuracy of predicting chemical body composition of growing pigs using dual-energy X-ray absorptiometry.

Studies in animal science assessing nutrient and energy efficiency or determining nutrient requirements benefit from gathering exact measurements of body composition or body nutrient contents. Those are acquired by standardized dissection or by grinding the body followed by wet chemical analysis, respectively. The two methods do not result in the same type of information, but both are destructive. Harnessing human medical imaging techniques for animal science can enable repeated measurements of individuals over time and reduce the number of individuals required for research. Among imaging techniques, dual-energy X-ray absorptiometry (DXA) is particularly promising. However, the measurements obtained with DXA do not perfectly match dissections or chemical analyses, requiring the adjustment of the DXA via calibration equations. Several calibration regressions have been published, but comparative studies of those regression equations and whether they are applicable to different data sets are pending. Thus, it is currently not clear whether existing regression equations can be directly used to convert DXA measurements into chemical values or whether each individual DXA device will require its own calibration. Our study builds prediction equations that relate body composition to the content of single nutrients in growing entire male pigs (BW range 20-100 kg) as determined by both DXA and chemical analyses, with R2 ranging between 0.89 for ash and 0.99 for water and CP. Moreover, we show that the chemical composition of the empty body can be satisfactorily determined by DXA scans of carcasses, with the prediction error ranging between 4.3% for CP and 12.6% for ash. Finally, we compare existing prediction equations for pigs of a similar range of BWs with the equations derived from our DXA measurements and evaluate their fit with our chemical analysis data. We found that existing equations for absolute contents that were built using the same DXA beam technology predicted our data more precisely than equations based on different technologies and percentages of fat and lean mass. This indicates that the creation of generic regression equations that yield reliable estimates of body composition in pigs of different growth stages, sexes and genetic breeds could be achievable in the near future. DXA may be a promising tool for high-throughput phenotyping for genetic studies, because it efficiently measures body composition in a large number and wide array of animals.

Human amyotrophic lateral sclerosis excitability phenotype screen: Target discovery and validation.

Drug development is hampered by poor target selection. Phenotypic screens using neurons differentiated from patient stem cells offer the possibility to validate known and discover novel disease targets in an unbiased fashion. To identify targets for managing hyperexcitability, a pathological feature of amyotrophic lateral sclerosis (ALS), we design a multi-step screening funnel using patient-derived motor neurons. High-content live cell imaging is used to evaluate neuronal excitability, and from a screen against a chemogenomic library of 2,899 target-annotated compounds, 67 reduce the hyperexcitability of ALS motor neurons carrying the SOD1(A4V) mutation, without cytotoxicity. Bioinformatic deconvolution identifies 13 targets that modulate motor neuron excitability, including two known ALS excitability modulators, AMPA receptors and Kv7.2/3 ion channels, constituting target validation. We also identify D2 dopamine receptors as modulators of ALS motor neuron excitability. This screen demonstrates the power of human disease cell-based phenotypic screens for identifying clinically relevant targets for neurological disorders.

Olfactory ensheathing glia and Schwann cells exhibit a distinct interaction behavior with meningeal cells.

Schwann cells (SCs) and olfactory ensheathing glia (OEG) have both been used as cellular transplants to promote spinal cord repair. Both cell types support axonal regeneration and have beneficial effects on functional recovery. A significant difference between SCs and OEG is the effect of these cell types on astrocytes (ACs) present in the neural scar. In contrast to OEG, which associate and intermingle with ACs, SCs and ACs form separate cellular territories. Here, we show that OEG and SCs also interact differently with meningeal cells (MCs), another major cellular component of the neural scar. Whereas OEG intermingle with MCs in cocultures, SCs aggregate into well-defined cell clusters. Our data suggest that (a) soluble factor(s) as well as direct cellular contact are involved in the MC-induced SC clustering. Furthermore, the cluster formation of SCs in coculture with MCs is different from the previously reported segregation of SCs and ACs in coculture. The present results help to understand the differential behavior of both cell types after transplantation in the injured spinal cord and will be important to either determine which cell has optimal capacities to render the scar more permissive for regeneration, or to exploit the transplantation of both cell types in combination.

Mosaicism and haemophilia.

Mosaicism may affect the haemophilia phenotype. Well-known instances include chromosomal mosaicism due to aneuploidy and pseudo-mosaicism due to varying patterns of X-chromosome inactivation. Chromosomal mosaicism in a chimera is a potential source of phenotypic variation. Gene mosaicism is commonplace. Its pattern and effect depend on the stage of development at which a mutation occurs. Proven or possible genetic mosaicism is an important consideration when predicting the likelihood of transmission of haemophilia to a future generation.

Mosaics and haemophilia.

Some mosaic conditions may affect the haemophilia phenotype. Well-known instances include chromosomal mosaicism because of aneuploidy and pseudo-mosaicism because of varying patterns of X-chromosome inactivation. Chromosomal mosaicism in a chimera is a potential source of phenotypic variation. Gene mosaicism is commonplace. Its pattern and effect depend on the stage of development at which a mutation occurs. Proven or possible genetic mosaicism is an important consideration when predicting the likelihood of transmission of haemophilia to a future generation. A mosaic is an individual who has two or more cell lines, genetically different with regard to chromosomes or genes. As techniques improve and studies accumulate, mosaics are being found to be more common than hitherto believed. Some mosaic conditions may affect the phenotype of haemophilia in males and of the carrier state in females. Cells may be mosaic with regard to chromosomes, as in some instances of aneuploidy, and in chimeras, and in females owing to the pattern of X-chromosome inactivation. Cells may be mosaic with regard to new gene mutations. The pattern of mosaicism depends upon the stage in embryogenesis or in germ-cell formation in which the mutation arose.

Carcinogen and microsomal membrane interactions: changes in membrane density and ability to bind nucleic acids.

DNA and synthetic copolymer polyribocytidylic-polyriboguanylic acid bind to microsomal membrane. The nucleic acid-membrane complex may be detected by centrifugation in cesium chloride density gradients. The density of the nucleic acid-membrane complex and, in certain cases, the amount of nucleic acid associated with the membrane was changed in the presence of various carcinogenic chemicals.