Validity of Robot-based Assessments of Upper Extremity Function

Objective To examine the validity of 5 robot-based assessments of arm motor function post-stroke. Design Cross sectional. Setting Outpatient clinical research center. Participants Volunteer sample of 40 participants, age \u3e18 years, 3-6 months post-stroke, with arm motor deficits that had plateaued. Intervention None. Main Outcome Measures Clinical standards included the Fugl-Meyer Arm Motor Scale (FMA), and 5 secondary motor outcomes: hand/wrist subsection of the FMA; Action Research Arm Test (ART); Box & Blocks test (B/B); hand subscale of Stroke Impact Scale-2 (SIS); and the Barthel Index (BI). Robot-based assessments included: wrist targeting; finger targeting; finger movement speed; reaction time; and a robotic version of the (B/B) test. Anatomical measures included percentage injury to the corticospinal tract (CST) and primary motor cortex (M1, hand region) obtained from MRI . Results Subjects had moderate-severe impairment (arm FMA scores = 35.6±14.4, range 13.5-60). Performance on the robot-based tests, including speed (r=0.82, p\u3c0.0001), wrist targeting (r=0.72, p\u3c0.0001), and finger targeting (r=0.67, p\u3c0.0001) correlated significantly with the FMA scores. Wrist targeting (r=0.57 - 0.82) and finger targeting (r=0.49 - 0.68) correlated significantly with all 5 secondary motor outcomes and with percent CST injury. The robotic version of the B/B correlated significantly with the clinical B/B test but was less prone to floor effect. Robot-based assessments were comparable to FMA score in relation to percent CST injury and superior in relation to M1 hand injury. Conclusions The current findings support using a battery of robot-based methods for assessing the upper extremity motor function in subjects with chronic stroke

Validity of Robot-Based Assessments of Upper Extremity Function.

ObjectiveTo examine the validity of 5 robot-based assessments of arm motor function poststroke.DesignCross-sectional study.SettingOutpatient clinical research center.ParticipantsVolunteer sample of participants (N=40; age, >18y; 3-6mo poststroke) with arm motor deficits that had reached a stable plateau.InterventionsNot applicable.Main outcome measuresClinical standards included the arm motor domain of the Fugl-Meyer Assessment (FMA) and 5 secondary motor outcomes: hand/wrist subsection of the arm motor domain of the FMA, Action Research Arm Test, Box and Block test (BBT), hand motor subscale of the Stroke Impact Scale Version 2.0, and Barthel Index. Robot-based assessments included wrist targeting, finger targeting, finger movement speed, reaction time, and a robotic version of the BBT. Anatomical measures included percent injury to the corticospinal tract (CST) and extent of injury of the hand region of the primary motor cortex obtained from magnetic resonance imaging.ResultsParticipants had moderate to severe impairment (arm motor domain of the FMA scores, 35.6±14.4; range, 13.5-60). Performance on the robot-based tests, including speed (r=.82; P<.0001), wrist targeting (r=.72; P<.0001), and finger targeting (r=.67; P<.0001), correlated significantly with the arm motor domain of the FMA scores. Wrist targeting (r=.57-.82) and finger targeting (r=.49-.68) correlated significantly with all 5 secondary motor outcomes and with percent CST injury. The robotic version of the BBT correlated significantly with the clinical BBT but was less prone to floor effects. Robot-based assessments were comparable to the arm motor domain of the FMA score in relation to percent CST injury and superior in relation to extent of injury to the hand region of the primary motor cortex.ConclusionsThe present findings support using a battery of robot-based methods for assessing the upper extremity motor function in participants with chronic stroke

The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance.

Widespread Plasmodium falciparum resistance to first-line antimalarials underscores the vital need to develop compounds with novel modes of action and identify new druggable targets. Here, we profile five compounds that potently inhibit P. falciparum asexual blood stages. Resistance selection studies with three carboxamide-containing compounds, confirmed by gene editing and conditional knockdowns, identify point mutations in the parasite transporter ABCI3 as the primary mediator of resistance. Selection studies with imidazopyridine or quinoline-carboxamide compounds also yield changes in ABCI3, this time through gene amplification. Imidazopyridine mode of action is attributed to inhibition of heme detoxification, as evidenced by cellular accumulation and heme fractionation assays. For the copy-number variation-selecting imidazopyridine and quinoline-carboxamide compounds, we find that resistance, manifesting as a biphasic concentration-response curve, can independently be mediated by mutations in the chloroquine resistance transporter PfCRT. These studies reveal the interconnectedness of P. falciparum transporters in overcoming drug pressure in different parasite strains