10 research outputs found
Unraveling micro- and nanoscale degradation processes during operation of high-temperature polymer-electrolyte-membrane fuel cells
C<sub>s</sub> corrected STEM analysis â operation related nanoscale degradation processes in high-temperature polymer-electrolyte-membrane fuel cells
Muscle activity and vibration transmissibility during wholeâbody vibration in chronic stroke
The acute effects of stretching with vibration on dynamic flexibility in young female gymnasts
Influence of a brisk walking program on isokinetic muscular capacities of knee in sedentary older women
Whole-body vibration as a treatment option for chronic lower back pain
Occupational exposure to vibration has long been seen as an important cause of chronic lower back pain (CLBP). However, research has also established that CLBP is associated with reduction or loss of spinal reflexes in the trunk musculature, and also with hampered lumbo-pelvic proprioception. It was therefore hoped that whole-body vibration (WBV), which has been shown to elicit muscle stretch and stretch reflexes, can help to re-establish functionality in the trunk musculature.
Studies into the acute spinal responses to vibration support this idea. Independent of this, vibration seems to also reduce the perception of pain in the trunk musculature and elsewhere. Today, a series of clinical studies with more than 300 patients effectively demonstrates the suitability of WBV as a treatment of CLBP, with improvements in pain sensation, in disability, in pelvic flexibility, in pelvic proprioception, in quality of life and in habitual physical activity levels. Thus, WBV lends itself for application in CLBP treatment on a larger scale.
Future research should also try to establish which types of vibration exposures (exercising vs. occupational) and which dosage (amplitude, frequency, shape, duration) determine whether vibration is helpful or detrimental
Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma
Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L-CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti-leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L-CTCL