Flatfoot in children and adolescents. Analysis of imaging findings and therapeutic implications

SummaryIntroductionPes planovalgus (PPV) is a complex three-dimensional deformity of which routine radiographs provide only a two-dimensional analysis.HypothesisAngles and other radiographic parameters of the foot in children and adolescents, when studied on both the dorsoplantar and the lateral view, can be used to establish a radiographic classification system for PPV that provides useful therapeutic guidance in clinical practice.Materials and methodsA retrospective single-centre study was conducted on 65 feet in 35 patients aged 7 to 18 years and having adequate ossification. All patients had a clinical diagnosis of idiopathic or neurologic PPV and available weight-bearing dorsoplantar and strict lateral radiographs. We excluded pes planus due to tarsal coalition, congenital bone deformities, or overcorrection of talipes equinovarus (n=25). All possible axes were drawn and angles measured after an evaluation of interindividual agreement.ResultsWe identified four patterns of PPV: subtalar pes planus (n=16) with marked subtalar valgus and longitudinal sag predominating at the talonavicular joint, midtarsal pes planus (n=12) without subtalar valgus but with marked midtarsal abduction and sag predominating at the cuneonavicular joint, mixed pes planus (n=28) with subtalar valgus, midtarsal abduction, and sag at both the talonavicular and cuneonavicular joints, and pes planocavus (n=9) with sag of the medial arch and cavus deformity of the lateral arch.ConclusionThis original classification system provides therapeutic guidance by helping to match the surgical procedure to the nature and location of the deformities.Level of evidenceLevel IV

Electric-field tuning of the valley splitting in silicon corner dots

We perform an excited state spectroscopy analysis of a silicon corner dot in a nanowire field-effect transistor to assess the electric field tunability of the valley splitting. First, we demonstrate a back-gate-controlled transition between a single quantum dot and a double quantum dot in parallel that allows tuning the device in to corner dot formation. We find a linear dependence of the valley splitting on back-gate voltage, from $880~\mu \text{eV}$ to $610~\mu \text{eV}$ with a slope of $-45\pm 3~\mu \text{eV/V}$ (or equivalently a slope of $-48\pm 3~\mu \text{eV/(MV/m)}$ with respect to the effective field). The experimental results are backed up by tight-binding simulations that include the effect of surface roughness, remote charges in the gate stack and discrete dopants in the channel. Our results demonstrate a way to electrically tune the valley splitting in silicon-on-insulator-based quantum dots, a requirement to achieve all-electrical manipulation of silicon spin qubits.Comment: 5 pages, 3 figures. In this version: Discussion of model expanded; Fig. 3 updated; Refs. added (15, 22, 32, 34, 35, 36, 37

Nuclear mRNA Degradation Pathway(s) Are Implicated in Xist Regulation and X Chromosome Inactivation

A critical step in X-chromosome inactivation (XCI), which results in the dosage compensation of X-linked gene expression in mammals, is the coating of the presumptive inactive X chromosome by the large noncoding Xist RNA, which then leads to the recruitment of other factors essential for the heterochromatinisation of the inactive X and its transcriptional silencing. In an approach aimed at identifying genes implicated in the X-inactivation process by comparative transcriptional profiling of female and male mouse gastrula, we identified the Eif1 gene involved in translation initiation and RNA degradation. We show here that female embryonic stem cell lines, silenced by RNA interference for the Eif1 gene, are unable to form Xist RNA domains upon differentiation and fail to undergo X-inactivation. To probe further an effect involving RNA degradation pathways, the inhibition by RNA interference of Rent1, a factor essential for nonsense-mediated decay and Exosc10, a specific nuclear component of the exosome, was analysed and shown to similarly impair Xist upregulation and XCI. In Eif1-, Rent1-, and Exosc10-interfered clones, Xist spliced form(s) are strongly downregulated, while the levels of unspliced form(s) of Xist and the stability of Xist RNA remain comparable to that of the control cell lines. Our data suggests a role for mRNA nuclear degradation pathways in the critical regulation of spliced Xist mRNA levels and the onset of the X-inactivation process

Monitoring immune modulation by nutrition in the general population: identifying and substantiating effects on human health

Optimal functioning of the immune system is crucial to human health, and nutrition is one of the major exogenous factors modulating different aspects of immune function. Currently, no single marker is available to predict the effect of a dietary intervention on different aspects of immune function. To provide further guidance on the assessment and interpretation of the modulation of immune functions due to nutrition in the general population, International Life Sciences Institute Europe commissioned a group of experts from academia, government and the food industry to prepare a guidance document. A draft of this paper was refined at a workshop involving additional experts. First, the expert group defined criteria to evaluate the usefulness of immune function markers. Over seventy-five markers were scored within the context of three distinct immune system functions: defence against pathogens; avoidance or mitigation of allergy; control of low-grade (metabolic) inflammation. The most useful markers were subsequently classified depending on whether they by themselves signify clinical relevance and/or involvement of immune function. Next, five theoretical scenarios were drafted describing potential changes in the values of markers compared with a relevant reference range. Finally, all elements were combined, providing a framework to aid the design and interpretation of studies assessing the effects of nutrition on immune function. This stepwise approach offers a clear rationale for selecting markers for future trials and provides a framework for the interpretation of outcomes. A similar stepwise approach may also be useful to rationalise the selection and interpretation of markers for other physiological processes critical to the maintenance of health and well-bein

A Consideration of Biomarkers to be Used for Evaluation of Inflammation in Human Nutritional Studies

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammatio

Generation of amorphous carbon and crystallographic texture during low-temperature subseismic slip in calcite fault gouge

Identification of the nano-scale to micro-scale mechanochemical processes occurring during fault slip is of fundamental importance to understand earthquake nucleation and propagation. Here we explore the micromechanical processes occurring during fault nucleation and slip at subseismic rates (∼3 × 10−6 m s–1) in carbonate rocks. We experimentally sheared calcite-rich travertine blocks at simulated upper crustal conditions, producing a nano-grained fault gouge. Strain in the gouge is accommodated by cataclastic comminution of calcite grains and concurrent crystal-plastic deformation through twinning and dislocation glide, producing a crystallographic preferred orientation (CPO). Continued wear of fine-grained gouge particles results in the mechanical decomposition of calcite and production of amorphous carbon. We show that CPO and the production of amorphous carbon, previously attributed to frictional heating and weakening during seismic slip, can be produced at low temperature during stable slip at subseismic rates without slip weakening

GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors

Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-κB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-κB activation by H-Ala-D-γGlu-DAP (γTriDAP). GEF-H1 is essential for NF-κB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens