Art and Pediatric Orthopaedics: Repin and Inclusiveness.

A famous painting of the 19th century, by Ilia Repin, of a religious procession depicts the pageantry of the event but also draws the attention of the viewer to the exclusion of a disabled child from the festivities.

Piezoelectric micropump with integrated elastomeric check valves: design, performance characterization and primary application for 3D cell culture.

This paper reports on the study of a piezoelectric actuated micropump with integrated elastomeric check valves that can transport small amounts of fluid in a highly controllable manner. The proposed micropump consists of a piezoelectric actuated fluid chamber with two integrated elastomeric check valves for regulating input and output flow direction, while restricting backflows. The actuation, fluid dynamic response and fluid-structure interactions at various working cycles are studied through a fully coupled multiphysics simulation (solid mechanics, electrostatic and fluid flow). The pump bodies are manufactured by micromachining of PMMA sheets, while the middle elastomeric membrane and diaphragm are fabricated by spin-coating PDMS. The experimental results confirm that the micropump can provide sufficiently low-velocity outflow for biomedical applications between 3.4 - 41.8 µl/min. The performance of the micropump is improved significantly through a convenient geometric modification of an off-the-shelf piezoelectric brass disc. Furthermore, the combination of this micropump with the 3D cell-culture microfluidic chip realizes the dynamic culture of cells encapsulated in 3D hydrogels with a continuous flowing medium, which offers the potential for changing the traditional mode of 3D cell culture with a static supply of nutrition and factors.

Back to Carracci.

Annibale Carracci's sketch of a boy with a hunchback conveys the boy's emotions remarkably well. The possibilities of the underlying cause of the spinal deformity and its neurologic complications are discussed.

Art and Pediatric Orthopaedics: Cot and the Crutch.

Pierre Auguste Cot's painting, "Mireille giving alms at the door of Saint-Trophime," depicts a wealthy lady giving alms to a crippled beggar boy. The beautiful painting portrays the striking contrast between the rich and the poor. The painting also draws attention to the crude crutch the boy was using. This type of crutch was used over the centuries; improvements in the design of the axillary crutch occurred only in the 20th century.

Does Prolonged Weight Relief Increase the Chances of a Favourable Outcome After Containment for Perthes Disease?

We have been treating children with Legg-Calvé-Perthes disease (LCPD) with a femoral varus osteotomy (PFVO) and weight relief till the disease evolves to the latter part of the stage of reconstitution (Stage IIIb). This entails weight relief for 18 to 24 months. We undertook this case-control study to test if a shorter period of weight relief would compromise the chance of retaining the spherical shape of the femoral head when the disease healed. Forty-one children diagnosed in the early stages of LCPD (Stages Ia, Ib, and IIa), were treated by PFVO and non-weight-bearing for a period of 6 months following surgery (6m group). Eighty-two children with LCPD matched for age, sex, and stage at surgery, who resumed weight-bearing only once they reached Stage IIIb, served as the control group (3b group). Both groups were followed up till the disease healed. The sphericity deviation score was calculated, and the height and width of the epiphysis were measured on the first radiograph designated as Stage IV. The median sphericity deviation score value at healing was 3 in the 3b group and 11 in the 6m group (P<0.001). The frequency of spherical heads was 76% in the 3b group and 49% in the 6m group (P<0.003). The Odds Ratio of the disease healing with an aspherical head in 6-month group was 3.05 (CI: 1.28 to 7.22) compared with the 3b group. The percentage increase in width of the femoral epiphysis at healing was greater in the 6 group (111.5±8.5% vs. 106.5±7.2%; P<0.001). The study confirms that containment by PFVO performed early in the course of LCPD combined with weight relief till the disease has evolved to Stage IIIb is likely to result in spherical hips in 75% of children. Reducing the period of weight relief to 6 months may yield significantly poorer results with only 49% spherical femoral heads.

Art and Pediatric Orthopaedics: "Arm-twisting" by Wyspianski, the Poet, Actor, and Artist.

Stanislaw Wyspianski, a multifaceted Polish artist painted "A Girl with a Red Hat", which portrays a young girl with an obviously deformed right upper limb. The pattern of deformities is suggestive of either athetoid hemiplegic cerebral palsy or Erb's palsy.

Low Molecular Weight Inhibitors Targeting the RNA-Binding Protein HuR.

The RNA-binding protein human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. This protein has been progressively recognized as a relevant therapeutic target for several pathologies, like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here, we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatic approaches, high-throughput virtual screening, and RNA-protein pulldown assays, we demonstrate that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits a dose-dependent HuR inhibition effect in binding experiments. Importantly, the chemical scaffold is new with respect to the currently known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.

Copping Coping With the Braced Limbs.

Harold Copping illustrated an edition of Charles Dickens' classic, "A Christmas Carol." One of the paintings of Bob Cratchit and Tiny Tim in the book shows Tiny Tim wearing braces on his lower limbs. Several diagnoses of Tiny Tim's ailment have been suggested in the past but based on the details of Copping's painting we suggest that he had rickets. The above-knee braces with uprights only on the lateral side of the limbs may have been given to prevent genu valgum, a common deformity in childhood rickets.

Collins, Bruegel, and the Games They Play.

William Collins and Pieter Bruegel the Elder in their respective paintings, "Happy as a King" and "Children's Games" show children playing outdoors. The types of injuries these children could sustain in the 16th and 19th centuries are contrasted with sports related pediatric fractures in the present day.

Art and Paediatric Orthopaedics: A Sixteenth Century Lie-down Comedian.

This outstanding painting, by an unknown artist, of a man with multiple deformities compatible with a diagnosis of arthrogryposis multiplex congenita induces the viewer to think deeply about the artist's portrayal of the subject.

The "Discoid Epiphysis"-An Uncommon Presentation of Legg-Calvé-Perthes Disease.

BACKGROUND: Among a cohort of 402 children with Legg-Calvé-Perthes disease (LCPD), 32 children presented with sclerosis and severe collapse of the entire femoral epiphysis that closely resembled a discus.This study was undertaken to identify the characteristics of children with this form of a "discoid epiphysis," compare them with typical LCPD and ascertain the radiologic outcome of their hips when the disease healed. METHODS: Sequential radiographs of the children were studied to monitor disease evolution. Femoral epiphyseal extrusion was measured on the initial anteroposterior radiograph. Thirty-one of the 32 children were treated with a proximal femoral varus osteotomy and weight-bearing was deferred till the disease reached stage IIIb. The pattern of fragmentation of the epiphysis was noted and the Sphericity Deviation Score (SDS) was computed once the disease healed. RESULTS: The mean age of children with a discoid epiphysis was 6.81±1.57 years at onset of symptoms while that of children with the typical presentation was 7.54±1.64 years (P<0.017). Perfusion magnetic resonance imaging scans of three children with a discoid epiphysis done in stage Ib of the disease showed that over 95% of the epiphysis was avascular. Femoral head extrusion was frequently present on the initial radiographs (mean Reimer's migration index 27.08±8.7; range: 6.4 to 42.55).In operated children with a discoid epiphysis, the disease evolved typically with fragmentation of the epiphysis followed by reconstitution. The height of the epiphysis was never restored; when the disease healed the mean epiphyseal height was 51.31±10.44% of the normal contralateral epiphysis as compared with 82.46±11.24% in children with typical LCPD (P<0.001).The SDS at healing of operated children with a discoid epiphysis was 14.95±10.86 while the SDS for operated children without a discoid epiphysis was 9.77±11.7 (P<0.019). However, the SDS of children with typical onset LCPD who had Catterall IV involvement and Herring C collapse was 15.25±15.19 (P=0.49 NS). CONCLUSION: The outcome of treatment of children with a discoid epiphysis is comparable to that of children with typical onset LCPD with Catterall IV (whole-head involvement) and Herring C collapse of the lateral pillar. About a third of these children who undergo early surgical containment may have spherical heads when the disease heals.

Does the Deformity Index Reliably Predict the Shape of the Femoral Head at Healing of Legg-Calvé-Perthes Disease?

BACKGROUND: Treatment of Legg-Calvé-Perthes disease (LCPD) aims to preserve the spherical shape of the femoral head. The deformity index (DI) <0.3, measured 2 years from disease onset, is a surrogate measure that predicts that the femoral head will be Stulberg class I or II at skeletal maturity. There is no study that compares the predictive value of DI against a quantitative measure of the shape of the femoral head when the disease heals. We undertook this study to assess the reproducibility of a new method of measurement of DI and see if DI could predict the shape of the femoral head when the disease healed. METHODS: DI was measured 2 years after disease onset and the Sphericity Deviation Score (SDS) was measured at healing of LCPD on radiographs of 43 children. Reproducibility of measurement was tested. Each healed femoral head was classified as spherical or aspherical based on subjective visual assessment. The DI values were compared with SDS values. RESULTS: The reproducibility of measurement of SDS was excellent and superior to that of DI. The mean duration of disease was 3.97±0.96 years. Only 17 of 32 hips with DI values <0.3 at 2 years had spherical femoral heads at healing (SDS <10). Three hips with SDS values <10 had DI values >0.3. The positive and negative predictive values of a DI <0.3 in predicting if the femoral head will be spherical (SDS <10) when the disease healed were 53% and 73%, respectively. CONCLUSION: Though DI can be reproducibly measured the predictive value of a DI <0.3, to accurately identify hips that are likely to heal with spherical femoral heads, is not sufficiently high to justify its use as an outcome measure.

Art and Pediatric Orthopaedics: The Master of Alkmaar and an Act of Mercy.

The painting, "The First Act of Mercy" shows a subject with complex lower limb anomalies. The probable diagnosis is discussed.

Art and Pediatric Orthopaedics: Sorolla and a Sad Inheritance.

The Sad Inheritance painted by Sorolla depict children with polio. The clarity of the painting enables the viewer to identify gait abnormalities due to muscle paralysis.

Art and Pediatric Orthopaedics: Monet and a Twist in Time.

The work of art by Monet shows a young child sitting with the toes turned inwards. The cause is probably due to femoral anteversion.

Bruegel and the Cost of the Bended Knee.

In Pieter Bruegel's painting, "The Seven Acts of Charity" he portrays 2 subjects with flexed knees. One of them cannot walk while the other can walk but does so with excessive energy expenditure.

Art and Pediatric Orthopaedics: Velazquez, an Artist of Stature.

Diego Velazquez painted several dwarfs employed at the Royal Court of Spain and one of the best known among them is the painting of Sebastian de Morra, a court jester. The clarity of the painting enables the reader to make a diagnosis of achondroplasia.

Carry on With Raja Ravi Varma, Mary Cassatt, and Renoir.

Raja Ravi Varma's painting "There Comes Papa" depicts his daughter carrying her son astride her hip. The positive implication of the posture of the hips of the child while being carried in this manner on acetabular development is discussed.

Raphael at the Temple.

Raphael, in his painting "Healing of the Lame Man" shows one lame man encountering St. Peter and St. John while another lame man waits his turn. Children with unusually muscular bodies are also depicted in the painting. The possible causes of lameness in the men and muscle hypertrophy in the children are discussed.

Shedding Light on the Interactions of Hydrocarbon Ester Substituents upon Formation of Dimeric Titanium(IV) Triscatecholates in DMSO Solution.

The dissociation of hierarchically formed dimeric triple lithium bridged triscatecholate titanium(IV) helicates with hydrocarbyl esters as side groups is systematically investigated in DMSO. Primary alkyl, alkenyl, alkynyl as well as benzyl esters are studied in order to minimize steric effects close to the helicate core. The 1 H NMR dimerization constants for the monomer-dimer equilibrium show some solvent dependent influence of the side chains on the dimer stability. In the dimer, the ability of the hydrocarbyl ester groups to aggregate minimizes their contacts with the solvent molecules. Due to this, most solvophobic alkyl groups show the highest dimerization tendency followed by alkenyls, alkynyls and finally benzyls. Furthermore, trends within the different groups of compounds can be observed. For example, the dimer is destabilized by internal double or triple bonds due to π-π repulsion. A strong indication for solvent supported London dispersion interaction between the ester side groups is found by observation of an even/odd alternation of dimerization constants within the series of n-alkyls, n-Ω-alkenyls or n-Ω-alkynyls. This corresponds to the interaction of the parent hydrocarbons, as documented by an even/odd melting point alternation.