The effect of training in an interactive dynamic stander on ankle dorsiflexion and gross motor function in children with cerebral palsy

Objective: To study the effect of active stretching of ankle plantarflexors using an interactive dynamic stander in children with cerebral palsy (CP).

Methods: Six children in Gross Motor Function Classification System classes I–III, aged 4–10 years, trained intensive active dorsiflexion in an interactive dynamic stander using ankle movement to play custom computer games following a 10-week control period. Gross Motor Function Measure Item Set, gait performance and passive and active dorsiflexion with extended and flexed knee were chosen as outcome parameters.

Results: Median active and passive ankle dorsiflexion increased significantly (5 and 10 degrees, respectively) with extended knee. There was a small but clinically significant increase in gross motor function. The intervention had no effect on temporospatial gait parameters.

Conclusion: In spite of the low number of participants, these results may indicate that intensive active stretching in an interactive dynamic stander could be an effective new conservative clinical treatment of ankle plantarflexor contracture in children with CP.     

GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding,self-association and cellular degradation

GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C > T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (k_cat) and normal affinity for α-D-glucose, and resistance to limited proteolysis by trypsin comparable with wild-type. When stably expressed in HEK293 cells and MIN6 β-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY.     

Activated platelets promote increased monocyte expression of CXCR5 through prostaglandin E2-related mechanisms and enhance the anti-inflammatory effects of CXCL13

Background

We have previously shown that the homeostatic chemokine CXCL13 is up-regulated in monocytes in atherosclerosis, mediating anti-apoptotic and anti-inflammatory effects.

Objective

To investigate the regulation of CXCL13s receptor, CXCR5.

Methods/patients

In vitro studies in THP-1 and primary monocytes and studies of CXCR5 expression in thrombus material obtained at the site of plaque rupture during myocardial infarction (MI).

Results

Our major findings were: (i) toll-like receptor agonists and particularly β-adrenergic receptor activation and releasate from thrombin-activated platelets increased CXCR5 mRNA levels in monocytes. (ii) The platelet-mediated induction of CXCR5 involved prostaglandin E₂/cAMP/protein kinase A-dependent as well as RANTES-dependent pathways with NFκB activation as a potential common down-stream mediator. (iii) Releasate from thrombin-activated platelets augmented the anti-inflammatory effects of CXCL13 in monocytes at least partly by enhancing the effects of CXCL13 on CXCR5 expression. (iv) We found strong immunostaining of CXCR5 in thrombus material obtained at the site of plaque rupture in patients with ST elevation MI (STEMI) and in unstable carotid lesions, co-localized with platelets.

Conclusion

Our findings suggest that platelet-mediated signaling through CXCR5 may be active in vivo during plaque destabilization, potentially representing a counteracting mechanism to inflammation.     

Does skin-to-skin contact reduce stress during diaper change in preterm infants?

Background

Skin-to-skin contact reduces pain response in preterm infants subjected to minor painful procedures, such as heel lance. Diaper change is a procedure performed several times daily in hospitalized preterm infants. Routine care giving tasks such as diaper change may be stressful for the infant.

Aims

The purpose of this study was to investigate whether diaper change induces stress and if skin-to-skin contact could reduce such stress, measured by changes in skin conductance.

Study design

This was a randomized crossover pilot study in 19 preterm infants with gestational age between 28 and 34 weeks. The diaper change procedure was done twice in each infant, once during skin-to-skin contact, and once in incubator or bed with the mother present.

Outcome measures

During diaper change heart rate (HR), peripheral oxygen saturation (SpO₂), and changes in skin conductance (SC) peaks per sec, using the Skin Conductance Algesimeter (SCA), were registered.

Results

The mean SC peaks/sec increased/decreased significantly under/after change of diapers which thereby underpins that this is a stressful procedure for the preterm infant.Skin-to-skin contact (SSC) entails significantly lower stress levels (p < 0.05) compared to diaper changed in an incubator/bed measured by the SCA.

Conclusions

Diaper change is a stressful procedure for preterm infants and may be ameliorated by skin-to-skin contact.