Do obstetric risk factors truly influence the etiopathogenesis of congenital muscular torticollis?

BACKGROUND: Congenital muscular torticollis (CMT) is seen in childhood and presents within months after birth. The etiology remains unknown; however, medical textbooks suggest trauma at birth as a main reason. The aim of this study was to systematically describe obstetric and perinatal outcomes in a population of children with a confirmed congenital muscular torticollis diagnosis. MATERIALS AND METHODS: Children with a validated diagnosis of congenital muscular torticollis born at Aarhus University Hospital from 2000 to 2014 were included in the study. Information on perinatal, intrapartum and neonatal characteristics were obtained from databases and from medical records, and systematically described. RESULTS: In this study, there were no differences in birth characteristics in children with left- and right-sided torticollis, between boys and girls or between the conservatively treated and the children who needed surgery. Most of the children with congenital muscular torticollis in this study were delivered at term without signs of birth complications or trauma. None experienced moderate or severe asphyxia. CONCLUSIONS: The results of the present study suggests that complicated birth or birth trauma may not be the main cause of congenital muscular torticollis and point towards intrauterine and prenatal reasons for its development. LEVEL OF EVIDENCE ACCORDING TO OCEBM LEVELS OF EVIDENCE WORKING GROUP: 3.

Physeal histological morphology after thermal epiphysiodesis using radiofrequency ablation.

BACKGROUND: Several treatments have been described for leg length discrepancy. Epiphysiodesis is the most commonly used because of its effectiveness. Thermal epiphysiodesis using radiofrequency ablation (RFA) alters the growth plate morphology without damaging the adjacent articular cartilage; it is a minimally invasive method that has shown excellent results in animal models. This study describes the macro and micro morphology after the procedure. MATERIALS AND METHODS: Epiphysiodesis using RFA was performed in vivo for 8 min (92-98 °C) at two ablation sites (medial and lateral) in one randomly-selected tibia in eight growing pigs. The contralateral tibia was used as control. After 12 weeks, the pigs were killed and the tibiae harvested. The specimens were studied macroscopically and histology samples were obtained. Physeal morphology, thickness and characteristics were then described. RESULTS: Macroscopically, the articular cartilage was normal in all the treated tibiae. Microscopically, the physis was detected as a discontinuous line on the treated tibiae while it was continuous in all controls. In the control specimens, the mean thickness of the physis was 625 µm (606-639, SD = 14). All the physeal layers were organized. In the ablated specimens, disorganized layers in a heterogeneous line were observed. Bone bridges were identified at the ablation sites. The central part of the physis looked normal. Next to the bone bridge, the physis was thicker and presented fibrosis. The mean thickness was 820 µm (628-949, SD = 130). No abnormalities in the articular cartilage were observed. CONCLUSIONS: Thermal epiphysiodesis with RFA disrupts the physeal morphology and causes the formation of bone bridges at the ablation sites. This procedure does not damage the adjacent articular cartilage. The damaged tissue, next to the bone bridges, is characterized by disorganization and fibrosis.

Systematized water content calculation in cartilage using T1-mapping MR estimations: design and validation of a mathematical model.

BACKGROUND: Up to 80 % of cartilage is water; the rest is collagen fibers and proteoglycans. Magnetic resonance (MR) T1-weighted measurements can be employed to calculate the water content of a tissue using T1 mapping. In this study, a method that translates T1 values into water content data was tested statistically. MATERIALS AND METHODS: To develop a predictive equation, T1 values were obtained for tissue-mimicking gelatin samples. 1.5 T MRI was performed using inverse angle phase and an inverse sequence at 37 (±0.5) °C. Regions of interest were manually delineated and the mean T1 value was estimated in arbitrary units. Data were collected and modeled using linear regression. To validate the method, articular cartilage from six healthy pigs was used. The experiment was conducted in accordance with the Danish Animal Experiment Committee. Double measurements were performed for each animal. Ex vivo, all water in the tissue was extracted by lyophilization, thus allowing the volume of water to be measured. This was then compared with the predicted water content via Lin's concordance correlation coefficient at the 95 % confidence level. RESULTS: The mathematical model was highly significant when compared to a null model (p < 0.0001). 97.3 % of the variation in water content can be explained by absolute T1 values. Percentage water content could be predicted as 0.476 + (T1 value) × 0.000193 × 100 %. We found that there was 98 % concordance between the actual and predicted water contents. CONCLUSION: The results of this study demonstrate that MR data can be used to predict percentage water contents of cartilage samples. LEVEL OF EVIDENCE: 3 (case-control study).

Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial.

AIMS: To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal variables in patients with type 2 diabetes. METHODS: The study was a placebo-controlled, double-blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included (51) Cr-EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI-based renal blood flow (RBF), tissue perfusion and oxygenation. RESULTS: Liraglutide had no effect on GFR [95% confidence interval (CI) -6.8 to 3.6 ml/min/1.73 m(2) ] or on RBF (95% CI -39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin-angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines. CONCLUSIONS: Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.

Water-content calculation in growth plate and cartilage using MR T1-mapping design and validation of a new method in a porcine model.

OBJECTIVE: There is a close relation between cartilage health and its hydration state. Current magnetic resonance methods allow visualizing this tissue. However, a quantitative analysis is more useful when studying disease. The purpose of this study was to quantify water content in cartilage using magnetic resonance without contrast agents. MATERIALS AND METHODS: Water-content estimations using T1 magnetic resonance mapping were done first in eight gelatin samples where the water content was previously known. The same method was used in the physeal areas of eight skeletally immature 30-kg pigs. To calculate accuracy, T1 calculations were compared to dry-freeze, which is considered the gold standard because it can remove the total water content form a tissue. Four fresh cartilage and seven gelatin samples were dry-frozen. Water content obtained from dry-freeze was compared to the one calculated from T1 map values. A mathematical model and statistical analysis were used to calculate the predictive value of the method and its significance. RESULTS: T1-map-based magnetic resonance method can calculate water content in cartilage with an accuracy of 97.3 %. We calculated a coefficient of variance for this method against dry-frozen sample of 3.68 (SD = 1.2) in gelatin samples, and 2.73 (SD = 1.3) in in vivo samples. Between two independent observers, the coefficient of variance was 0.053, which suggests it can be easily reproduced. CONCLUSIONS: Magnetic resonance was able to calculate, with high accuracy, the cartilage water content using T1 mapping sequences.

Virtual reality increases pressure pain threshold and lowers anxiety in children compared with control and non-immersive control-A randomized, crossover trial.

BACKGROUND: Virtual reality (VR) is a promising non-pharmacological pain intervention because it may not only distract but also modulate pain by immersing the user in a three-dimensional 360° alternate reality. In children, VR has been reported to reduce clinical pain and anxiety during medical procedures. However, the effect of immersive VR on pain and anxiety remains to be investigated in randomized controlled trials (RCT). The aim of the present crossover RCT was to assess the effect of VR on pressure pain threshold (PPT) and anxiety level measured with the modified Yale Preoperative Anxiety Scale (mYPAS) in children in a controlled experimental setting. METHODS: Seventy-two children (mean age 10.2 (6-14) years) were randomized to 24 sequences of four interventions (immersive VR Game, immersive VR video, tablet: 2D video and control: small talk). Outcome measures PPT, mYPAS and heart rate were assessed before and after each intervention. RESULTS: PPT increased significantly during VR game (PPTdiff): 136 kPa (CI 112; 161), p < 0.0001 and VR Video (PPTdiff): 122 kPa (CI 91; 153), p < 0.0001. Also, anxiety levels significantly decreased during both VR game (mYPASdiff: -7 points (-8 to -5), p < 0.0001) and VR video (mYPASdiff: -6 points (CI -7; -4), p < 0.0001). CONCLUSIONS: VR had a marked beneficial effect on PPT and anxiety compared with the control interventions: 2D video and small talk. Thus, immersive VR had a distinct modulatory effect on pain and anxiety in a well-controlled experimental setting. Immersive VR was effective and feasible in children and can act as a valid tool for non-pharmacological pain and anxiety management. SIGNIFICANCE: Paediatric immersive VR seems to be beneficial although well-controlled studies are pending. We investigated whether immersive VR can modulate children's threshold for pain and anxiety level in an experimental well-controlled setting. We document a modulatory pain threshold increase and anxiety level decrease compared with extensive control conditions. Paediatric immersive VR is effective, feasible and valid for non-pharmacological pain and anxiety management. All efforts to reach the goal that no child should experience pain or anxiety when exposed to medical procedures.

Fast-ion orbit sensitivity of neutron emission spectroscopy diagnostics.

Fast ions in fusion plasmas often leave characteristic signatures in the plasma neutron emission. Measurements of this emission are subject to the phase-space sensitivity of the diagnostic, which can be mapped using weight functions. In this paper, we present orbit weight functions for the TOFOR and NE213 neutron diagnostics at the Joint European Torus, mapping their phase-space sensitivity in 3D orbit space. Both diagnostics are highly sensitive to fast ions that spend a relatively large fraction of their orbit transit times inside the viewing cone of the diagnostic. For most neutron energies, TOFOR is found to be relatively sensitive to potato orbits and heavily localized counter-passing orbits, as well as trapped orbits whose "banana tips" are inside the viewing cone of TOFOR. For the NE213-scintillator, the sensitivity is found to be relatively high for stagnation orbits.

Carbon-13--rich diagenetic carbonates in miocene formations of california and Oregon.

Carbon unusually rich in C(13)(deltaC(13) = +5.4 to +19.0 per mil relative to the Peedee belemnite carbonate standard of the University of Chicago) is characteristic of certain diagenetic limestones and dolomites in the Miocene Monterey Shale of California and the Nye Mudstone of Oregon. This heavy carbon may have originated through low-temperature equilibration between CO(3)- - and CO(2) in migrating carbonated waters or between CH(4) and CO(2) in natural gas. Light carbon (deltaC(13) = -5.6 to -18.2 per mil) derived through nonequilibrium oxidation of organic matter also occurs in the carbonate of Monterey Shale in some localities, but at most places it is much less common than heavy carbon.

Voyager telecommunications: the broadcast from jupiter.

Sweeping past Jupiter, the Voyager 1 spacecraft presages a new era in the exploration of the solar system. Not since the TV return from Apollo has a spacecraft returned information of such volume and pictures of such startling clarity. Yet this feat was accomplished from a distance 1770 times as great as that of the lunar adventure. The communication system responsible for this remarkable achievement is a oompilation of elements ranging from tiny integrated circuits to enormous ground antennas. This article seeks to describe the way in which data are returned from these fascinating, faraway bodies and to convey the excitement of the engineering work that supports our scientific endeavors.

Velocity-space tomography using prior information at MAST.

Velocity-space tomography provides a way of diagnosing fast ions in a fusion plasma by combining measurements from multiple instruments. We use a toroidally viewing and a vertically viewing fast-ion D-alpha diagnostic installed on the mega-amp spherical tokamak (before the upgrade) to perform velocity-space tomography of the fast-ion distribution function. To make up for the scarce amount of data, prior information is included in the inversions. We impose a non-negativity constraint, suppress the distribution in the velocity-space region associated with null-measurements, and encode the belief that the distribution function does not extend to energies significantly higher than those expected neoclassically. This allows us to study the fast-ion velocity distributions and the derived fast-ion densities before and after a sawtooth crash.

Fast ion D-alpha measurements using a bandpass-filtered system on EAST.

Based on the charge exchange reaction between fast ions and a neutral beam, fast ion features can be inferred from the spectrum of Doppler-shifted Balmer-alpha light from energetic hydrogenic atoms. In order to study the interaction between instabilities and fast-ion transport, recently we extended the fast ion D-alpha (FIDA) measurements by using a combination of a bandpass filter and a photomultiplier tube (PMT) (f-FIDA). A bandpass filter selects the desired spectral band from 651 nm to 654 nm before detection by the PMT. Preliminary data from the EAST tokamak show that the active signals have been detected from reneutralized beam ions along the vertical and tangential viewing geometries. The details will be presented in this paper to primarily address the specifications and performance of f-FIDA hardware components and preliminary FIDA measurements.

Retinoic acid down-regulates the expression of the vasoactive intestinal polypeptide receptor type-1 in human breast carcinoma cell lines.

Four breast carcinoma cell lines (T47D, ZR-75-1, MDA-MB-231, and MCF-7) were tested for regulation of the expression of vasoactive intestinal polypeptide receptor type-1 (VIP-R1). In all four cell lines, retinoic acid (RA) treatment caused a fast and marked decrease in VIP-R1 mRNA level as examined by Northern blots. Cycloheximide pretreatment attenuated the effect from 3- to 2-fold, indicating that existing proteins can mediate the decreasing effect of RA, but to attain the maximal effect new protein synthesis might be needed. Transcriptional inhibition with Actinomyocin D showed that RA did not influence the VIP-R1 mRNA half-life, indicating that the decreasing effect of RA on the mRNA level is due to transcriptional inhibition. In agreement with the observations on mRNA level, we found that the VIP receptor number was reduced 3-fold from 88 to 32 fmol/10(6) cells in T47D cells and from 222 to 73 fmol/10(6) cells in MDA-MB-231 cells upon RA treatment for 72 h. The promoter and 5'-flanking region of the VIP-R1 gene were cloned from a human placental cosmid library, and 2.5 kb were sequenced to search for regulatory elements. Our results, therefore, imply that the regulation of VIP-R1 gene expression by RA could have a role in human mammary tumor biology.

Is structural hydroxyapatite tricalcium-phosphate graft or tricortical iliac crest autograft better for calcaneal lengthening osteotomy in childhood? interim results from a randomised, controlled non-inferiority study.

AIMS: To compare the structural durability of hydroxyapatite-tricalcium phosphate (HATCP) to autologous iliac crest bone graft in calcaneal lengthening osteotomy (CLO) for pes planovalgus in childhood. PATIENTS AND METHODS: We present the interim results of ten patients (HATCP, n = 6 and autograft, n = 5) with a mean age of 11.5 years (8.2 to 14.2) from a randomised controlled non-inferiority trial with six months follow-up. The primary outcome was the stability of the osteotomy as measured by radiostereometric analysis. A non-inferiority margin of ≤ 2 mm osteotomy compression was set. RESULTS: At six months the data showed that the osteotomy had been compressed by a mean 1.97 mm (99.8% confidence interval -1.65 to 5.60) more in the HATCP group than in the autograft group. Migration of the CLO grafted with HATCP stabilised at six months rather than at six weeks with autograft. CONCLUSION: This is the first randomised trial to compare the efficacy of HATCP graft with autograft in terms of stability of CLO in children. Because of problems with the HATCP the trial was stopped. We do not recommend HATCP graft in its current structure for use in unfixed CLOs. Cite this article: Bone Joint J 2016;98-B:1554-62.

Does radiofrequency ablation (RFA) epiphysiodesis affect adjacent joint cartilage?

PURPOSE: To test the hypothesis that epiphysiodesis made with radiofrequency ablation (RFA) is a safe procedure that disrupts the growth plate without damaging the adjacent joint articular cartilage. METHODS: RFA epiphysiodesis was done during 8 min in vivo in 40 growing pig tibia physis. In addition, three tibiae were ablated for 16 min and three more for 24 min. As a burned cartilage reference, six tibiae were ablated on the joint articular cartilage for 8 min. After the procedure, the animals were terminated and the tibiae were harvested. Magnetic resonance imaging (MRI) was done ex vivo to evaluate the joint articular cartilage in all samples. We used T1-weighted, T2-weighted, and water content sequences under a 1.5 T magnetic field. RESULTS: On the burned articular cartilage, intensity changes were observed at MRI. We found no evidence of articular cartilage damage on the 40 8-min RFA procedures. The tibiae ablated for 16 min and 24 min showed intact joint cartilage. CONCLUSIONS: Epiphysiodesis using RFA is safe for the adjacent articular cartilage. This study shows that RFA can be done safely in the growing physis of pigs, even with triple duration procedures.

International consensus on the most useful physical examination tests used by physiotherapists for patients with headache: A Delphi study.

BACKGROUND: A wide range of physical tests have been published for use in the assessment of musculoskeletal dysfunction in patients with headache. Which tests are used depends on a physiotherapist's clinical and scientific background as there is little guidance on the most clinically useful tests. OBJECTIVES: To identify which physical examination tests international experts in physiotherapy consider the most clinically useful for the assessment of patients with headache. DESIGN/METHODS: Delphi survey with pre-specified procedures based on a systematic search of the literature for physical examination tests proposed for the assessment of musculoskeletal dysfunction in patients with headache. RESULTS: Seventeen experts completed all three rounds of the survey. Fifteen tests were included in round one with eleven additional tests suggested by the experts. Finally eleven physical examination tests were considered clinically useful: manual joint palpation, the cranio-cervical flexion test, the cervical flexion-rotation test, active range of cervical movement, head forward position, trigger point palpation, muscle tests of the shoulder girdle, passive physiological intervertebral movements, reproduction and resolution of headache symptoms, screening of the thoracic spine, and combined movement tests. CONCLUSIONS: Eleven tests are suggested as a minimum standard for the physical examination of musculoskeletal dysfunctions in patients with headache.

Modulatory drug action in an allosteric Markov model of ion channel behaviour: biphasic effects with access-limited binding to either a stimulatory or an inhibitory site.

Concentration-dependent biphasic effects of drugs on ion channel activity have been reported in a variety of preparations, usually with stimulatory effects seen at low concentrations followed by increasingly dominant inhibition at higher levels. Such behaviour is often interpreted as evidence for the existence of separate modulatory drug binding sites. We demonstrate in this paper that it is possible for biphasic effects to be produced in an allosteric model of a ligand-activated ion channel, where diffusion-limited binding of the modulatory drug is restricted to either a stimulatory or an inhibitory site (but not both) because of steric overlap. The possibility of such an interaction mechanism should be kept in mind when interpreting experimental data if stoichiometric evidence from complementary techniques suggests that only one drug molecule is bound per receptor/ion channel complex.

Characterization of the inhibitory effect of growth hormone on primary preadipocyte differentiation.

GH exerts adipogenic activity in several preadipocyte cell lines, whereas in primary rat preadipocytes, GH has an antiadipogenic activity. To better understand the molecular mechanism involved in adipocyte differentiation, the expression of adipocyte-specific genes was analyzed in differentiating preadipocytes in response to GH. We found that the expression of both adipocyte determination and differentiation factor 1 (ADD1) and peroxisome proliferator activated receptor gamma(PPARgamma) was induced in preadipocytes during differentiation. In the presence of GH, which markedly inhibited triglyceride accumulation, no reduction in the expression level of ADD1 was observed in response to GH, whereas there was a 50% reduction in the expression of PPARgamma. The DNA binding activity of the PPARgamma/retinoid X receptor-alpha(RXRalpha) to the ARE7 element from the aP2 gene was also reduced by approximately 50% in response to GH. GH inhibited the expression of late markers of adipocyte differentiation, fatty acid synthase, aP2, and hormone-sensitive lipase by 70-80%. The antiadipogenic effect of GH was not affected by the mitogen-activated protein (MAP) kinase/ extracellular-regulated protein (ERK) kinase inhibitor PD 98059, indicating that the mitogen-activated protein kinase pathway was not involved in GH inhibition of preadipocyte differentiation. The expression of preadipocyte factor-1/fetal antigen 1 was decreased during differentiation, and GH treatment prevented this down-regulation of Pref1/FA1. A possible role for Pref-1/FA1 in mediating the antiadipogenic effect of GH was indicated by the observation that FA1 inhibited differentiation as effectively as GH. These data suggest that GH exerts its inhibitory activity in adipocyte differentiation at a step after the induction of ADD1 but before the induction of genes required for terminal differentiation.

Precise and feasible measurements of lateral calcaneal lengthening osteotomies by radiostereometric analysis in cadaver feet.

OBJECTIVES: Lengthening osteotomies of the calcaneus in children are in general grafted with bone from the iliac crest. Artificial bone grafts have been introduced, however, their structural and clinical durability has not been documented. Radiostereometric analysis (RSA) is a very accurate and precise method for measurements of rigid body movements including the evaluation of joint implant and fracture stability, however, RSA has not previously been used in clinical studies of calcaneal osteotomies. We assessed the precision of RSA as a measurement tool in a lateral calcaneal lengthening osteotomy (LCLO). METHODS: LCLO was performed in six fixed adult cadaver feet. Tantalum markers were inserted on each side of the osteotomy and in the cuboideum. Lengthening was done with a plexiglas wedge. A total of 24 radiological double examinations were obtained. Two feet were excluded due to loose and poorly dispersed markers. Precision was assessed as systematic bias and 95% repeatability limits. RESULTS: Systematic bias was generally below 0.10 mm for translations. Precision of migration measurements was below 0.2 mm for translations in the osteotomy. CONCLUSION: RSA is a precise tool for the evaluation of stability in LCLO. Cite this article: Bone Joint Res 2015;4:78-83.