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.     

Deoxygenation of the Baltic Sea during the last century

Deoxygenation is a global problem in coastal and open regions of the ocean, and has led to expanding areas of oxygen minimum zones and coastal hypoxia. The recent expansion of hypoxia in coastal ecosystems has been primarily attributed to global warming and enhanced nutrient input from land and atmosphere. The largest anthropogenically induced hypoxic area in the world is the Baltic Sea, where the relative importance of physical forcing versus eutrophication is still debated. We have analyzed water column oxygen and salinity profiles to reconstruct oxygen and stratification conditions over the last 115 y and compare the influence of both climate and anthropogenic forcing on hypoxia. We report a 10-fold increase of hypoxia in the Baltic Sea and show that this is primarily linked to increased inputs of nutrients from land, although increased respiration from higher temperatures during the last two decades has contributed to worsening oxygen conditions. Although shifts in climate and physical circulation are important factors modulating the extent of hypoxia, further nutrient reductions in the Baltic Sea will be necessary to reduce the ecosystems impacts of deoxygenation.Dead zones are hypoxic (low-oxygen) areas unable to support most marine life, and over the past 50 y they have spread rapidly in the open ocean (1) as well as in coastal ecosystems (2). Global warming is thought to be a major driver for these changes (3), although biogeochemical factors have also been recognized, especially in coastal marine ecosystems (4, 5). In the Baltic Sea, the present spread of hypoxia is the combined result of climate changes influencing deepwater oxygenation (6) and increased eutrophication (7, 8), resulting in a hypoxic area ranging between 12,000 and 70,000 km² with an average of 49,000 km² over the time period 1961–2000 (7). Here, we separate the effects of the two factors on oxygen conditions.Physical factors are an important consideration in whether an ecosystem will experience hypoxia. The Baltic Sea is naturally prone to hypoxia due to a restricted water exchange with the ocean and a long residence time above 30 y (9, 10). Saltier, denser water from the North Atlantic flows over a series of shallow sills in the Danish Straits to ventilate waters below the permanent halocline and are governed by meteorological-induced variations in sea levels (11), displaying variations at decadal scales (12, 13). The dense saltwater inflows bring new supplies of oxygen to bottom waters, but at the same time enhance stratification, creating larger bottom areas that experience hypoxia (14). In particular, the ventilation of the deeper waters is attributed to events of larger inflows of high-saline water (>17), termed Major Baltic Inflows (MBIs), that have been less frequent in the last three decades (6).Climate warming decreases oxygen solubility due to higher water temperature, increases stratification, and enhances respiration processes (15). Climate warming is likely to be accompanied by increased precipitation and inflows of freshwater and nutrients to coastal waters in many areas of the globe. Increasing nutrient inputs from land stimulates primary production and export of organic material to the deep waters, thereby disrupting the subtle natural balance between oxygen supply from physical processes and oxygen demand from consumption of organic material. However, the importance of decreasing oxygenation versus increasing nutrient inputs for explaining the recent spread of hypoxia is not known (6, 7).Water column measurements of dissolved oxygen concentrations began around 1900 with more regularly spaced measurements commencing in the 1960s (Fig. S1), allowing a more consistent assessment of the spatial extent of hypoxia (7, 14). The sparse temporal and spatial resolution of oxygen data before 1960 allowed only assessing hypoxia at specific locations (16) or specific years (17). To our knowledge, our study is the first to report basin-wide trends of stratification and oxygen conditions from 1898 to present, and here we will focus on the two basins that have perennial hypoxia—the Bornholm Basin and the Gotland Basin (Fig. S2). These two basins are connected via a channel with a sill depth of 60 m.     

Percutaneous Penetration ‐ Methodological Considerations

Studies on percutaneous penetration are needed to assess the hazards after unintended occupational skin exposures to industrial products as well as the efficacy after intended consumer exposure to topically applied medicinal or cosmetic products. During recent decades, a number of methods have been developed to replace methods involving experimental animals. The results obtained from these methods are decided not only by the chemical or product tested, but to a significant degree also by the experimental set‐up and decisions made by the investigator during the planning phase. The present MiniReview discusses some of the existing and well‐known experimental in vitro and in vivo methods for studies of percutaneous penetration together with some more recent and promising methods. After this, some considerations and recommendations about advantages and limitations of the different methods and their relevance for the prediction of percutaneous penetration are given. Which method to prefer will depend on the product to be tested and the question asked. Regulatory guidelines exist for studies on percutaneous penetration, but researchers as well as regulatory bodies need to pay specific attention to the vehicles and solvents used in donor and sampling fluids so that it reflects in‐use conditions as closely as possible. Based on available experimental data, mathematical models have been developed to aid predictions of skin penetration. The authors question the general use of the present mathematical models in hazard assessment, as they seem to ignore outliers among chemicals as well as the heterogeneity of skin barrier properties and skin conditions within the exposed populations.     

Systemic immunogenicity of para-Phenylenediamine and Diphenylcyclopropenone: two potent contact allergy-inducing haptens

p-Phenylenediamine (PPD) and Diphenylcyclopropenone (DPCP) are two potent haptens. Both haptens are known to cause delayed-type hypersensitivity, involving a cytokine response and local infiltration of T-cell subpopulations, resulting in contact dermatitis. We investigated the systemic immune effects of PPD and DPCP, two relatively unexplored skin allergens. The dorsal sides of the ears of BALB/c mice were exposed to PPD or DPCP (0.1 % w/v or 0.01 % w/v), or vehicle alone. Mice were treated once daily for 3 days (induction period) and subsequently twice per week for 8 weeks. Local and systemic immune responses in the auricular and pancreatic lymph nodes, spleen, liver, serum, and ears were analyzed with cytokine profiling MSD, flow cytometry, and qPCR. Ear swelling increased significantly in mice treated with 1 % PPD, 0.01 % DPCP or 0.1 % DPCP, compared with vehicle treatment, indicating that the mice were sensitized and that there was a local inflammation. Auricular lymph nodes, pancreatic lymph nodes, spleen, and liver showed changes in regulatory T-cell, B-cell, and NKT-cell frequencies, and increased activation of CD8⁺ T cells and B cells. Intracellular cytokine profiling revealed an increase in the IFN-γ- and IL-4-positive NKT cells present in the liver following treatment with both haptens. Moreover, we saw a tendency toward a systemic increase in IL-17A. We observed systemic immunological effects of PPD and DPCP. Furthermore, concentrations too low to increase ear thickness and cause clinical symptoms may still prime the immune system. These systemic immunological effects may potentially predispose individuals to certain diseases.     

Structure–property relations in linear viscoelasticity of supramolecular hydrogels

Extraordinary mechanical properties of supramolecular gels (fracture toughness, fatigue resistance, injectability and self-healing ability) are strongly affected by their viscoelastic response driven by rearrangement (association and dissociation) of physical bonds. The kinetics of rearrangement is traditionally studied in small-amplitude shear oscillatory tests by analyzing the effect of the frequency of oscillations ω on the storage G′ and loss G′′ moduli. Conventional Maxwell-type models describe observations rather poorly when the gels reveal a pronounced flattening of the graphs G′′(ω) at high frequencies. A simple model is derived in linear viscoelasticity of supramolecular gels. Its advantage is that the model reproduces experimental data correctly, on the one hand, and involves only four material constants, on the other. Based on the analysis of experimental data on gels cross-linked by coiled-coil complexes, covalent and ionic bonds, phenylboronic acid-diol complexes and metal–ligand coordination bonds, the model is applied to develop structure–property relations that describe the influence of chemical structure of supramolecular gels (concentration of polymer chains and type and molar fraction of temporary bonds) and environmental conditions (temperature, pH and ionic strength of buffer solutions) on their viscoelastic response.

A model is developed for the linear viscoelastic response of supramolecular gels and applied to the analysis of structure–property relations in gels with various supramolecular motifs.