Disrupting the CD95-PLCγ1 interaction prevents Th17-driven inflammation.

CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca2+ response via docking of PLCγ1 to the calcium-inducing domain (CID) within CD95. This signaling pathway induces accumulation of inflammatory Th17 cells in damaged organs of lupus patients, thereby aggravating disease pathology. A large-scale screen revealed that the HIV protease inhibitor ritonavir is a potent disruptor of the CD95-PLCγ1 interaction. A structure-activity relationship approach highlighted that ritonavir is a peptidomimetic that shares structural characteristics with CID with respect to docking to PLCγ1. Thus, we synthesized CID peptidomimetics abrogating both the CD95-driven Ca2+ response and transmigration of Th17 cells. Injection of ritonavir and the CID peptidomimetic into lupus mice alleviated clinical symptoms, opening a new avenue for the generation of drugs for lupus patients.

Home-based telehealth service for swallowing and nutrition management following head and neck cancer treatment.

Introduction Following (chemo)radiotherapy (C/RT) for head and neck cancer (HNC), patients return to hospital for regular outpatient reviews with speech pathology (SP) and nutrition and dietetics (ND) for acute symptom monitoring, nutritional management, and swallowing and communication rehabilitation. The aim of the current study was to determine the feasibility of a home-based telehealth model for delivering SP and ND reviews, to provide patients with more convenient access to these appointments. Methods Service outcomes, costs, and consumer satisfaction were examined across 30 matched participants: 15 supported via the standard model of care (SMOC), and 15 via the home-based telehealth model of care (TMOC). Results All patients were successfully managed via telehealth. The TMOC was more efficient, with a reduced number ( p < 0.003) and duration ( p < 0.01) of appointments required until discharge. Significant patient cost savings ( p = 0.002) were reported for the TMOC due to decreased travel requirements. While staff costs were reduced, additional telehealth equipment levies resulted in a lower but non-significant overall cost difference to the health service when using the TMOC. High satisfaction was reported by all participants attending the TMOC. Discussion The findings support the feasibility of a home-based telehealth model for conducting SP and ND reviews post C/RT for HNC.

Effects of approach-avoidance related motor behaviour on the startle response during emotional picture processing.

Motivational states may be induced by affective foreground stimulation or via proprioceptive feedback by certain postures or body movements. In the present study, we addressed the question of an interaction between basic motor actions and the valence of visual stimuli in an affective modulation of startle paradigm: is the potentiation for aversive and the attenuation for pleasant stimuli more pronounced when the muscles for a congruent approach or avoidance action are activated? Thirty-four volunteers (20 female) watched emotional pictures on a computer screen while simultaneously contracting the flexor vs. extensor muscles of the upper arm. After 3-4s, an acoustic startle stimulus (105dB, binaural, instantaneous rise time) was presented via headphones. Arm movement interacted with picture valence: flexion, compared to extension, increased affective startle modulation (F=4.32, p<0.05). This result suggests integration and not simple summation of postural and body movement effects on startle reflexivity.