Modified constraint-induced movement therapy or bimanual occupational therapy following injection of Botulinum toxin-A to improve bimanual performance in young children with hemiplegic cerebral palsy: a randomised controlled trial methods paper

<p>Abstract</p> <p>Background</p> <p>Use of Botulinum toxin-A (BoNT-A) for treatment of upper limb spasticity in children with cerebral palsy has become routine clinical practice in many paediatric treatment centres worldwide. There is now high-level evidence that upper limb BoNT-A injection, in combination with occupational therapy, improves outcomes in children with cerebral palsy at both the body function/structure and activity level domains of the International Classification of Functioning, Disability and Health. Investigation is now required to establish what amount and specific type of occupational therapy will further enhance functional outcomes and prolong the beneficial effects of BoNT-A.</p> <p>Methods/Design</p> <p>A randomised, controlled, evaluator blinded, prospective parallel-group trial. Eligible participants were children aged 18 months to 6 years, diagnosed with spastic hemiplegic cerebral palsy and who were able to demonstrate selective motor control of the affected upper limb. Both groups received upper limb injections of BoNT-A. Children were randomised to either the modified constraint-induced movement therapy group (experimental) or bimanual occupational therapy group (control). Outcome assessments were undertaken at pre-injection and 1, 3 and 6 months following injection of BoNT-A. The primary outcome measure was the Assisting Hand Assessment. Secondary outcomes included: the Quality of Upper Extremity Skills Test; Pediatric Evaluation of Disability Inventory; Canadian Occupational Performance Measure; Goal Attainment Scaling; Pediatric Motor Activity Log; modified Ashworth Scale and; the modified Tardieu Scale.</p> <p>Discussion</p> <p>The aim of this paper is to describe the methodology of a randomised controlled trial comparing the effects of modified constraint-induced movement therapy (a uni-manual therapy) versus bimanual occupational therapy (a bimanual therapy) on improving bimanual upper limb performance of children with hemiplegic cerebral palsy following upper limb injection of BoNT-A. The paper outlines the background to the study, the study hypotheses, outcome measures and trial methodology. It also provides a comprehensive description of the interventions provided.</p> <p>Trial Registration</p> <p>ACTRN12605000002684</p

Change of the Yb valence in Yb-TM-Al compounds

We present an investigation of Yb-TM-Al phase diagrams with TM = Pd, Ag and Au. Several new compounds have been characterized by measurements of the magnetic susceptibility, the electrical resistivity and, in some cases, the specific heat. It seems that the crossover from the stable-trivalent to the intermediate-valent behavior occurs much more abruptly in Yb- than in Ce-based compounds on changing the composition. A comparison of the Ce-TM-Al compounds with their Yb homologs suggests that replacement of Ce by Yb in an intermediate-valent Ce compound and in a trivalent Ce compound results in an Yb3+ and in an Yb2+ state, respectively

Yb₂Ni₂Al: A prototypical Yb-based heavy-fermion system

We have investigated the properties of Yb(2)Ni(2)Al by means of resistivity, susceptibility and specific heat measurements. Our results suggest that it is the first magnetically non-ordered Yb heavy-fermion system with a low characteristic energy and clear coherence effects in the resistivity. A logarithmic temperature dependence of CIT indicates that it is close to the transition to a magnetic ordered ground state. We further found a simple systematic for composition dependence of the Yb-valence in binary and ternary Yb-T-Al compounds (T:Ni, Pd, Pt)

Heavy fermions: Typical phenomena and recent developments

A survey is given of typical phenomena, new materials and recent developments in heavy-fermion physics. In particular, the following topics are addressed: (i) YbNiAl, a new heavy-fermion local-moment antiferromagnet (LMM) with Neel temperature T(N) = 3 K, (ii) ''non-Fermi-liquid'' behavior at the magnetic instability in two heavy-fermion systems with intact from sublattice, i.e. orthorhombic CePt(Si1-xGex) and tetragonal U(Cu4+xAl8-x), (iii) the low-temperature properties of the anisotropic ''Kondo insulator'' CeNiSn, and (iv) some of the most unusual observations made on ''low-carrier-density'' rare-earth systems like Sm3Te4 and Sm3Se4. While the ezotic symmetry-broken (superconducting and magnetic) ground states of heavy-fermion metals are discussed in several other contributions to this volume, we focus in the remainder of this paper on the relationship between LMM ordering and heavy-fermion superconductivity: Firstly, the LMM ordered compound CeCu2Ge2 (T(N) = 4.1 K) is addressed which was recently found to become a non-magnetic heavy-fermion superconductor under high hydrostatic pressure, p greater-than-or-equal-to 70 kbar (D. Jaccard et al., Phys. Lett. A 163,475 (1992)). Point-contact spectroscopy is used to investigate in more detail the high-pressure superconducting phase of CeCU2Ge2. Secondly, we summarize high-pressure results on UPd2Al3, the first compound to show homogeneous coexistence between LMM ordering and heavy-fermion superconductivity

YbNiAl: A new Yb-based heavy-fermion antiferromagnet

We have investigated the compound YbNiAl, which crystallizes in the same structure as the well-known mixed-valent system YbCuAl, and have found that it is the first example of a clear cut Yb-based heavy-fermion antiferromagnet. The resistivity increases logarithmically by 25% between 100 and 10 K, C/T extrapolates below 0.4 K to a gamma value of 350 mJ/K-2 mol and the entropy at the antiferromagnetic ordering temperature T-N = 3 K reaches only 0.45R In 2. We compare the properties of this compound with those of YbPtAl, where Yb is trivalent

4f-conduction electron hybridization in ternary CeTMAl compounds

We present an investigation of Ce-TM-Al phase diagrams with TM = Ru, Pd, Pt and Au. Several new compounds have been characterized by measurements of the electrical resistivity rho(T), the dc susceptibility chi(T) and, in some cases, the specific heat C(T). We find that in the compounds with TM=Ru, the hybridization strength between 4f and conduction electrons is strong, leading in most compounds to an intermediate valent (IV) state. By contrast, most of the investigated compounds with TM = Pd, Pt and Au order magnetically indicating a much weaker hybridization strength. However, some of the Pt and especially Pd compounds are very near to the crossover from the magnetic to the non-magnetic regime as deduced from a Kondo-type maximum in the resistivity and a large electronic specific heat at low temperatures

GPER1 influences cellular homeostasis and cytostatic drug resistance via influencing long chain ceramide synthesis in breast cancer cells

The G protein-coupled estrogen receptor 1 (GPER1) is involved in the regulation of physiological processes such as cellular growth and proliferation, but also in pathophysiological processes such as tumor development. The role of GPER1 in breast cancer is contradictory. Therefore, we investigated the influence of GPER1 overexpression on cellular processes in MCF-7 breast cancer cells. GPER1 overexpression leads to a cell cycle arrest in the G1 phase, induction of autophagy and reduced proliferation. Reduced proliferation was accompanied by a reduced basal respiration and reduced glycolysis rate in GPER1 overexpressing cells. This is presumably ascribable to mitophagy induction following GPER1 overexpression. However, GPER1 overexpressing cells were less sensitive against doxorubicin as compared to control cells. In previous work we showed the effect of transient GPER1 overexpression on the synthesis of several ceramide synthases (CerS) thereby influencing the sphingolipid pathway. Therefore, we investigated CerS expression and sphingolipid level in stable GPER1 overexpressing and control cells. Stable GPER1 overexpression strongly reduced CerS4, CerS5 and CerS6 promoter activity and CerS5 and CerS6 mRNA expression, whereas CerS2 mRNA expression was upregulated. The GPER1 effect on CerS5 promoter is mediated by GSK-3β signaling. In addition, other enzymes of the sphingolipid pathway were upregulated. Our study provides new insights into the role of GPER1 and the activated sphingolipid pathways and how GPER1 may influence cellular processes such as cancer cell survival following chemotherapy. Further studies are needed to investigate the molecular mechanisms leading to these cellular effects. Finding new therapeutic targets for modulating specifically GPER1 in breast tumors may improve endocrine breast cancer therapy