Multiple Phases of Chondrocyte Enlargement Underlie Differences in Skeletal Proportions

Even a casual pass through the great halls of mammals in the world’s natural history museums highlights the wide diversity of skeletal proportions that allow us to distinguish between species even when reduced to their calcified components. Similarly each individual is comprised of a variety of bones of differing lengths. The largest contribution to the lengthening of a skeletal element, and to the differential elongation of elements, comes from a dramatic increase in the volume of hypertrophic chondrocytes in the growth plate as they undergo terminal differentiation1–7. Despite this recognized importance, the mechanisms of chondrocyte volume enlargement have remained a mystery8–11. Here we use quantitative phase microscopy12 to show that chondrocytes undergo three distinct phases of volume increase, including a phase of massive cell swelling in which the cellular dry mass is significantly diluted. In light of the tight fluid regulatory mechanisms known to control volume in many cell types13, this stands as a remarkable mechanism for increasing cell size and regulating growth rate. It is, however, the duration of the final phase of volume enlargement by proportional dry mass increase at low density that varies most between rapidly and slowly elongating growth plates. Moreover, we find that this third phase is locally regulated through an Insulin-like Growth Factor-dependent mechanism. This study provides a framework for understanding how skeletal size is regulated and for exploring how cells sense, modify, and establish a volume set point

Sodium intake and blood pressure in children and adolescents: protocol for a systematic review and meta-analysis.

Hypertension is a major risk factor for cardiovascular diseases. In adults, high sodium intake is associated with elevated blood pressure. In children, experimental studies have shown that reducing sodium intake can reduce blood pressure. However, their external validity is limited, notably because the sodium reduction was substantial and not applicable in a real-life setting. Observational studies, on the other hand, allow assess the association between blood pressure and sodium intake across usual levels of consumption. There is also evidence that the association differs between subgroups of children according to age and body weight. Our objective is to conduct a systematic review and meta-analysis of experimental and observational studies on the association between sodium intake and blood pressure in children and adolescents and to assess whether the association differs according to age and body weight. A systematic search of the MEDLINE, EMBASE, CINAHL and CENTRAL databases will be conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies involving children or adolescents between 0 and 18 years of age will be included. The exposure will be dietary sodium intake, estimated using different methods including urinary sodium excretion. The outcomes will be systolic and diastolic blood pressure, elevated blood pressure and hypertension. If appropriate, meta-analyses will be performed by pooling data across all studies together and separately for experimental and observational studies. Subgroup meta-analyses by age and body weight will be also conducted. Moreover, separate meta-analyses for different sodium intake levels will be conducted to investigate the dose-response relationship. This systematic review and meta-analysis will be published in a peer-reviewed journal. A report will be prepared for national authorities and other stakeholders in the domains of nutrition, public health, and child health in Switzerland. CRD42016038245

Adapting the "Chester step test" to predict peak oxygen uptake in children.

Maximal exercise testing may be difficult to perform in clinical practice, especially in obese children who have low cardiorespiratory fitness and exercise tolerance. We aimed to elaborate a model predicting peak oxygen consumption (VO2) in lean and obese children with use of the submaximal Chester step test. We performed a maximal step test, which consisted of 2-minute stages with increasing intensity to exhaustion, in 169 lean and obese children (age range: 7-16 years). VO2 was measured with indirect calorimetry. A statistical Tobit model was used to predict VO2 from age, gender, body mass index (BMI) z-score and intensity levels. Estimated VO2peak was then determined from the heart rate-VO2 linear relationship extrapolated to maximal heart rate (220 minus age, in beats.min-1). VO2 (ml/kg/min) can be predicted using the following equation: VO2 = 22.82 - [0.68*BMI z-score] - [0.46*age (years)] - [0.93*gender (male = 0; female = 1)] + [4.07*intensity level (stage 1, 2, 3 etc.)] - [0.24*BMI z-score *intensity level] - [0.34*gender*intensity level]. VO2 was lower in participants with high BMI z-scores and in female subjects. The Chester step test can assess cardiorespiratory fitness in lean and obese children in clinical settings. Our adapted equation allows the Chester step test to be used to estimate peak aerobic capacity in children

Urine Spot Samples Can Be Used to Estimate 24-Hour Urinary Sodium Excretion in Children.

The gold standard to assess salt intake is 24-h urine collections. Use of a urine spot sample can be a simpler alternative, especially when the goal is to assess sodium intake at the population level. Several equations to estimate 24-h urinary sodium excretion from urine spot samples have been tested in adults, but not in children. The objective of this study was to assess the ability of several equations and urine spot samples to estimate 24-h urinary sodium excretion in children. A cross-sectional study of children between 6 and 16 y of age was conducted. Each child collected one 24-h urine sample and 3 timed urine spot samples, i.e., evening (last void before going to bed), overnight (first void in the morning), and morning (second void in the morning). Eight equations (i.e., Kawasaki, Tanaka, Remer, Mage, Brown with and without potassium, Toft, and Meng) were used to estimate 24-h urinary sodium excretion. The estimates from the different spot samples and equations were compared with the measured excretion through the use of several statistics. Among the 101 children recruited, 86 had a complete 24-h urine collection and were included in the analysis (mean age: 10.5 y). The mean measured 24-h urinary sodium excretion was 2.5 g (range: 0.8-6.4 g). The different spot samples and equations provided highly heterogeneous estimates of the 24-h urinary sodium excretion. The overnight spot samples with the Tanaka and Brown equations provided the most accurate estimates (mean bias: -0.20 to -0.12 g; correlation: 0.48-0.53; precision: 69.7-76.5%; sensitivity: 76.9-81.6%; specificity: 66.7%; and misclassification: 23.0-27.7%). The other equations, irrespective of the timing of the spot, provided less accurate estimates. Urine spot samples, with selected equations, might provide accurate estimates of the 24-h sodium excretion in children at a population level. At an individual level, they could be used to identify children with high sodium excretion. This study was registered at clinicaltrials.gov as NCT02900261

Update of the European paediatric respiratory medicine syllabus

The 10-year-old European syllabus for paediatric respiratory medicine (PRM; also known as paediatric pulmonology) was updated by a consensus-based method using an expert task force for redrafting, and a subsequent Delphi process to achieve consensus. There was a high degree of consensus for the final syllabus, which has been streamlined and made more relevant to current practice. All modules are now mandatory apart from the undertaking of research projects, which is optional. Although there are still a number of countries in Europe which do not recognise PRM as a separate subspecialty, there are paediatric respiratory physicians practising in every country in Europe, and a current and harmonised European syllabus in the subspecialty remains important for defining the training and areas of practice of PRM practitioners

Cryptic Variation in Morphological Evolution: HSP90 as a Capacitor for Loss of Eyes in Cavefish

In the process of morphological evolution, the extent to which cryptic, preexisting variation provides a substrate for natural selection has been controversial. We provide evidence that heat shock protein 90 (HSP90) phenotypically masks standing eye-size variation in surface populations of the cavefish Astyanax mexicanus. This variation is exposed by HSP90 inhibition and can be selected for, ultimately yielding a reduced-eye phenotype even in the presence of full HSP90 activity. Raising surface fish under conditions found in caves taxes the HSP90 system, unmasking the same phenotypic variation as does direct inhibition of HSP90. These results suggest that cryptic variation played a role in the evolution of eye loss in cavefish and provide the first evidence for HSP90 as a capacitor for morphological evolution in a natural setting

Sodium intake and blood pressure in children with clinical conditions: A systematic review with meta-analysis.

Little is known on the effect of sodium intake on BP of children with clinical conditions. Our objective was therefore to review systematically studies that have assessed the association between sodium intake and BP in children with various clinical conditions. A systematic search of several databases was conducted and supplemented by a manual search of bibliographies and unpublished studies. Experimental and observational studies assessing the association between sodium intake and BP and involving children or adolescents between 0 and 18 years of age with any clinical condition were included. Out of the 6861 records identified, 51 full texts were reviewed, and 16 studies (10 experimental and 6 observational), involving overall 2902 children and adolescents, were included. Ten studies were conducted in children with elevated BP without identifiable cause, two in children with familial hypertension, one in children with at least one cardiovascular risk factor, one in children with chronic renal insufficiency, one in children with urolithiasis, and one in premature infants. A positive association between sodium intake and BP was found in all studies, except one. The meta-analysis of six studies among children with elevated BP without identifiable cause revealed a difference of 6.3 mm Hg (95% CI 2.9-9.6) and 3.5 mm Hg (95% CI 1.2-5.7) in systolic and diastolic BP, respectively, for every additional gram of sodium intake per day. In conclusion, our results indicate that the BP response to salt is greater in children with clinical conditions, mainly hypertension, than in those without associated clinical conditions

ERS syllabus for postgraduate training in respiratory infections:A guide for comprehensive training

ERS has developed a syllabus for postgraduate training in respiratory infections to guide programme designers http://ow.ly/xJ0R30m8CYB

Discrete cilia modelling with singularity distributions

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system