Ufmylation reconciles salt stress-induced unfolded protein responses via ER-phagy in Arabidopsis.

In plants, the endomembrane system is tightly regulated in response to environmental stresses for maintaining cellular homeostasis. Autophagosomes, the double membrane organelles forming upon nutrient deprivation or stress induction, degrade bulky cytosolic materials for nutrient turnover. Though abiotic stresses have been reported to induce plant autophagy, few receptors or regulators for selective autophagy have been characterized for specific stresses. Here, we have applied immunoprecipitation followed by tandem mass spectrometry using the autophagosome marker protein ATG8 as bait and have identified the E3 ligase of the ufmylation system Ufl1 as a bona fide ATG8 interactor under salt stress. Notably, core components in the ufmylation cascade, Ufl1 and Ufm1, interact with the autophagy kinase complexes proteins ATG1 and ATG6. Cellular and genetic analysis showed that Ufl1 is important for endoplasmic reticulum (ER)-phagy under persisting salt stress. Loss-of-function mutants of Ufl1 display a salt stress hypersensitive phenotype and abnormal ER morphology. Prolonged ER stress responses are detected in ufl1 mutants that phenocopy the autophagy dysfunction atg5 mutants. Consistently, expression of ufmylation cascade components is up-regulated by salt stress. Taken together, our study demonstrates the role of ufmylation in regulating ER homeostasis under salt stress through ER-phagy.

Feasibility and Effects of Virtual Reality Motor-Cognitive Training in Community-Dwelling Older People With Cognitive Frailty: Pilot Randomized Controlled Trial.

BACKGROUND: Cognitive frailty refers to the coexistence of physical frailty and cognitive impairment, and is associated with many adverse health outcomes. Although cognitive frailty is prevalent in older people, motor-cognitive training is effective at enhancing cognitive and physical function. We proposed a virtual reality (VR) simultaneous motor-cognitive training program, which allowed older people to perform daily activities in a virtual space mimicking real environments. OBJECTIVE: We aimed to (1) explore the feasibility of offering VR simultaneous motor-cognitive training to older people with cognitive frailty and (2) compare its effects with an existing motor-cognitive training program in the community on the cognitive function and physical function of older people with cognitive frailty. METHODS: A two-arm (1:1), assessor-blinded, parallel design, randomized controlled trial was employed. The eligibility criteria for participants were: (1) aged ≥60 years, (2) community dwelling, and (3) with cognitive frailty. Those in the intervention group received cognitive training (ie, cognitive games) and motor training (ie, cycling on an ergometer) simultaneously on a VR platform, mimicking the daily living activities of older people. Those in the control group received cognitive training (ie, cognitive games) on tablet computers and motor training (ie, cycling on the ergometer) sequentially on a non-VR platform. Both groups received a 30-minute session twice a week for 8 weeks. Feasibility was measured by adherence, adverse outcomes, and successful learning. The outcomes were cognitive function, physical frailty level, and walking speed. RESULTS: Seventeen participants were recruited and randomized to either the control group (n=8) or intervention group (n=9). At baseline, the median age was 74.0 years (IQR 9.5) and the median Montreal Cognitive Assessment score was 20.0 (IQR 4.0). No significant between-group differences were found in baseline characteristics except in the number of chronic illnesses (P=.04). At postintervention, the intervention group (Z=-2.67, P=.01) showed a significantly larger improvement in cognitive function than the control group (Z=-1.19, P=.24). The reduction in physical frailty in the intervention group (Z=-1.73, P=.08) was similar to that in the control group (Z=-1.89, P=.06). Improvement in walking speed based on the Timed Up-and-Go test was moderate in the intervention group (Z=-0.16, P=.11) and greater in the control group (Z=-2.52, P=.01). The recruitment rate was acceptable (17/33, 52%). Both groups had a 100% attendance rate. The intervention group had a higher completion rate than the control group. Training was terminated for one participant (1/9, 11%) due to minimal VR sickness (Virtual Reality Sickness Questionnaire score=18.3/100). Two participants (2/8, 25%) in the control group withdrew due to moderate leg pain. No injuries were observed in either group. CONCLUSIONS: This study provides preliminary evidence that the VR simultaneous motor-cognitive training is effective at enhancing the cognitive function of older people with cognitive frailty. The effect size on frailty was close to reaching a level of significance and was similar to that observed in the control group. VR training is feasible and safe for older people with cognitive frailty. TRIAL REGISTRATION: ClinicalTrials.gov NCT04467216; https://clinicaltrials.gov/ct2/show/NCT04467216.

Robot-assisted therapy for upper-limb rehabilitation in subacute stroke patients: A systematic review and meta-analysis.

BACKGROUND: Stroke survivors often experience upper-limb motor deficits and achieve limited motor recovery within six months after the onset of stroke. We aimed to systematically review the effects of robot-assisted therapy (RT) in comparison to usual care on the functional and health outcomes of subacute stroke survivors. METHODS: Randomized controlled trials (RCTs) published between January 1, 2000 and December 31, 2019 were identified from six electronic databases. Pooled estimates of standardized mean differences for five outcomes, including motor control (primary outcome), functional independence, upper extremity performance, muscle tone, and quality of life were derived by random effects meta-analyses. Assessments of risk of bias in the included RCTs and the quality of evidence for every individual outcomes were conducted following the guidelines of the Cochrane Collaboration. RESULTS: Eleven RCTs involving 493 participants were included for review. At post-treatment, the effects of RT when compared to usual care on motor control, functional independence, upper extremity performance, muscle tone, and quality of life were nonsignificant (all ps ranged .16 to .86). The quality of this evidence was generally rated as low-to-moderate. Less than three RCTs assessed the treatment effects beyond post-treatment and the results remained nonsignificant. CONCLUSION: Robot-assisted therapy produced benefits similar, but not significantly superior, to those from usual care for improving functioning and disability in patients diagnosed with stroke within six months. Apart from using head-to-head comparison to determine the effects of RT in subacute stroke survivors, future studies may explore the possibility of conducting noninferiority or equivalence trials, given that the less labor-intensive RT may offer important advantages over currently available standard care, in terms of improved convenience, better adherence, and lower manpower cost.

Comparison of the Effects of Automated and Manual Record Keeping on Anesthetists' Monitoring Performance: Randomized Controlled Simulation Study.

BACKGROUND: Anesthesia information management systems (AIMSs) automatically import real-time vital signs from physiological monitors to anesthetic records, replacing part of anesthetists' traditional manual record keeping. However, only a handful of studies have examined the effects of AIMSs on anesthetists' monitoring performance. OBJECTIVE: This study aimed to compare the effects of AIMS use and manual record keeping on anesthetists' monitoring performance, using a full-scale high-fidelity simulation. METHODS: This simulation study was a randomized controlled trial with a parallel group design that compared the effects of two record-keeping methods (AIMS vs manual) on anesthetists' monitoring performance. Twenty anesthetists at a tertiary hospital in Hong Kong were randomly assigned to either the AIMS or manual condition, and they participated in a 45-minute scenario in a high-fidelity simulation environment. Participants took over a case involving general anesthesia for below-knee amputation surgery and performed record keeping. The three primary outcomes were participants' (1) vigilance detection accuracy (%), (2) situation awareness accuracy (%), and (3) subjective mental workload (0-100). RESULTS: With regard to the primary outcomes, there was no significant difference in participants' vigilance detection accuracy (AIMS, 56.7% vs manual, 56.7%; P=.50), and subjective mental workload was significantly lower in the AIMS condition than in the manual condition (AIMS, 34.2 vs manual, 46.7; P=.02). However, the result for situation awareness accuracy was inconclusive as the study did not have enough power to detect a difference between the two conditions. CONCLUSIONS: Our findings suggest that it is promising for AIMS use to become a mainstay of anesthesia record keeping. AIMSs are effective in reducing anesthetists' workload and improving the quality of their anesthetic record keeping, without compromising vigilance.

Spearcon Sequences for Monitoring Multiple Patients: Laboratory Investigation Comparing Two Auditory Display Designs.

OBJECTIVE: The aim was to compare the effectiveness of two auditory displays, implemented with spearcons (time-compressed speech), for monitoring multiple patients. BACKGROUND: Sequences of sounds can convey information about patients' vital signs, such as oxygen saturation (SpO2) and heart rate (HR). We tested whether participants could monitor five patients using spearcon-based sound sequences. METHOD: A 2 × 3 within-subjects design was used. The first factor was interface, with two levels: the ALL interface used spearcons to convey vital signs for all five patients, whereas the ABN (abnormal) interface represented patients who had normal vital signs with a low-pitched single-tone sound and patients who had at least one abnormal vital sign with spearcons. The second factor was the number of patients who had at least one abnormal vital sign: there were one, two, or three such patients in each monitoring sequence. Participants were 40 nonclinicians. RESULTS: Participants identified abnormal patients' SpO2 and HR levels and located abnormal patients in the sound sequence more accurately with the ABN interface than the ALL interface. Accuracy declined as the number of abnormal patients increased. Participants associated ABN with easier identification of vital signs, resulting in higher ratings of confidence and pleasantness compared with ALL. CONCLUSION: Sequences of spearcons may support effective eyes-free monitoring of multiple patients. APPLICATION: Sequences of spearcons may be useful in monitoring multiple patients and the underlying design principles may extend to monitoring in other domains such as industrial process control or control of multiple autonomous vehicles.