Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes.

A major hypothesis for the etiology of type 1 diabetes (T1D) postulates initiation by viral infection, leading to double-stranded RNA (dsRNA)-mediated interferon response and inflammation; however, a causal virus has not been identified. Here, we use a mouse model, corroborated with human islet data, to demonstrate that endogenous dsRNA in beta cells can lead to a diabetogenic immune response, thus identifying a virus-independent mechanism for T1D initiation. We found that disruption of the RNA editing enzyme adenosine deaminases acting on RNA (ADAR) in beta cells triggers a massive interferon response, islet inflammation, and beta cell failure and destruction, with features bearing striking similarity to early-stage human T1D. Glycolysis via calcium enhances the interferon response, suggesting an actionable vicious cycle of inflammation and increased beta cell workload.

Clinical significance and burden of carbapenem-resistant Enterobacterales (CRE) colonization acquisition in hospitalized patients.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) infections have a significant morbidity and mortality toll. The clinical significance and associated burden of CRE colonization rather than infection state are not frequently investigated. We aimed to assess the outcomes of CRE colonized patients compared to matched controls. METHODS: A secondary analysis of a 1:2 matched case-control study at a tertiary hospital in northern Israel (January-2014 to June-2017). Cases were adults who newly acquired CRE colonization during hospitalization. Controls were inpatients negatively screened for CRE, matched by age, hospitalization division and total days of hospitalization 90 days prior to screening. Our primary outcome was 1-year all-cause mortality. Secondary outcomes included 30-day mortality, diagnosis of any clinical infection, overall days of hospital stay and bloodstream infections all in 1-year follow-up. We estimated crude and propensity score weighted estimates for study outcomes. RESULTS: We included a total of 1019 patients: 340 CRE colonized and 679 non-colonized controls. After adjustment, CRE colonization was not associated with increased 1-year mortality (weighted OR 0.98, 95% CI 0.64-1.50, p = 0.936). CRE colonized patients had 1.7 times the odds of clinical infection of any cause (weighted odds ratio (OR) 1.65, 95% CI 1.06-2.56, p = 0.025). CRE colonized patients had increased length of hospital stay compared to controls (weighted OR 1.52, 95%CI 1.10-2.10, p < 0.001) among 1-year survivors. CONCLUSIONS: CRE colonization may not be independently associated with mortality but with higher risk of clinical infections and longer hospital stays. Infection prevention and antimicrobial stewardship are of utmost importance to prevent acquisition and infections in colonized patients.

Risk factors for acquisition of carbapenemase-producing versus non-carbapenemase-producing enterobacterales: a case-control study.

OBJECTIVES: We aimed to assess the association between carbapenem-resistant Enterobacterales (CRE) colonization pressure and carbapenem exposure and acquisition of carbapenemase-producing Enterobacterales (CPE) and non-carbapenemase-producing carbapenem-resistant Enterobacterales (non-CP-CRE). METHODS: We conducted a parallel 1:2 matched case-control study at Rambam Health Care Campus, Israel, from January 2014 to June 2017. The cases included all adults who acquired CPE or non-CP-CRE in hospital. The controls were hospitalized patients who were negative for CRE on screening and matched by age, hospitalization division and the number of hospitalization days 90 days prior to CRE screening. The exposures of interest were high CRE colonization pressure, defined as a higher-than-median proportion of CRE carriers in the concurrent patient's department before acquisition, and carbapenem exposure, assessed as days of treatment. Conditional logistic regression was used for analyses of CPE and non-CP-CRE. RESULTS: In total, 1058 patients were included: 278 CPE and 75 non-CP-CRE cases, matched to 556 and 149 controls, respectively. High CRE colonization pressure was associated with CPE acquisition (adjusted odds ratio [aOR], 2.6; 95% CI, 1.69-4.02); however, the duration of carbapenem treatment was not (aOR, 1.004; 95% CI, 0.98-1.03; 1-day increment). The duration of carbapenem treatment was significantly associated with non-CP-CRE acquisition (aOR per day, 1.07; 95% CI, 1.03-1.11). A source patient was identified significantly more frequently in epidemiological acquisition investigations of CPE than in those of non-CP-CRE (107/240, 44.6% vs. 18/64, 28.1%, respectively; p 0.017). CONCLUSIONS: CPE acquisition was associated with horizontal transmission, whereas non-CP-CRE was associated with carbapenem exposure. Differences in the drivers of acquisition mandate tailored infection prevention efforts.

A pilot study on the electrophysiological monitoring of patient's engagement in post-stroke physical rehabilitation.

Introduction: This study discusses the feasibility of an electrophysiological monitor for patient engagement during rehabilitation sessions. While patient engagement has a significant clinical role, it is not obvious how its real-time monitoring could be used.Objective: We designed this study to provide further support for the feasibility of such a tool based on the Brain Engagement Index (BEI), and to discuss clinical usefulness and its evaluation.Methods: The study involved 30 patients during post-stroke rehabilitation. Each patient underwent two sessions with BEI monitoring. In one session the therapist received real-time feedback from the monitor and in the other he did not. The BEI was compared to video-based evaluation of temporary functional change from the session start to its end and with a rater-based evaluation of the level of engagement evoked by the exercises in the session.Results: Irrespective of whether feedback is used, there is association between BEI and temporary functional change as well as with evaluated engagement. Furthermore, the contribution of the BEI monitor to rehabilitation may be demonstrated.Conclusions: It would be challenging to establish directly the monitor's contribution in large-scale studies. Nevertheless, it might be sufficient to demonstrate that the monitor provides important information regarding patient engagement.Implication for RehabilitationThis work presents an easy-to-use electrophysiological index for monitoring patient engagement in real-time.Enhanced engagement is of utmost importance for effective rehabilitation.The ability to identify in real-time barriers to engagement is expected to be of great contributive value.

Effect of telerehabilitation on mobility in people after hip surgery: a pilot feasibility study.

The goal of this study was to evaluate the effects of telerehabilitation on mobility in people following hip surgery. This feasibility pilot randomized controlled trial included a sample of 40 participants, with 22 male and 18 female patients and mean age (SD) of 67.5 (7.8) years following a surgical intervention. Participants were equally divided and randomly assigned to a telerehabilitation or control intervention group (6 weeks, 3 sessions/week). Telerehabilitation was based on video clips of common rehabilitation exercises focusing on the lower limbs. The control group received an exercise booklet. Both groups participated in physical therapy sessions, twice a week. Outcome measures included the Timed Up and Go test, 2-min walk test, 10-m walk test, sit to stand test, walking speed, and mean step length. Measurements were completed at baseline, at termination of the intervention, and at a 4-week follow-up examination. Improvements in both groups were demonstrated in all outcome measures in the postintervention evaluation. Improvements in the telerehabilitation group were greater in five of six tests compared with those achieved by the controls. The telerehabilitation group showed greater improvements in the 2-min walking test (86.1%) and walking speed (65.6%). During follow-up, the telerehabilitation group continued to improve in all outcome measures in contrast to the control group, who showed no changes in five of the six outcome measures. Telerehabilitation, a complementary treatment to standard physical therapy, generates a positive effect on mobility in people following hip surgery.

An EEG Tool for Monitoring Patient Engagement during Stroke Rehabilitation: A Feasibility Study.

OBJECTIVE: Patient engagement is of major significance in neural rehabilitation. We developed a real-time EEG marker for attention, the Brain Engagement Index (BEI). In this work we investigate the relation between the BEI and temporary functional change during a rehabilitation session. METHODS: First part: 13 unimpaired controls underwent BEI monitoring during motor exercise of varying levels of difficulty. Second part: 18 subacute stroke patients underwent standard motor rehabilitation with and without use of real-time BEI feedback regarding their level of engagement. Single-session temporary functional changes were evaluated based on videos taken before and after training on a given task. Two assessors, blinded to feedback use, assessed the change following single-session treatments. RESULTS: First part: a relation between difficulty of exercise and BEI was identified. Second part: temporary functional change was associated with BEI level regardless of the use of feedback. CONCLUSIONS: This study provides preliminary evidence that when BEI is higher, the temporary functional change induced by the treatment session is better. Further work is required to expand this preliminary study and to evaluate whether such temporary functional change can be harnessed to improve clinical outcome. CLINICAL TRIAL REGISTRATION: Registered with clinicaltrials.gov, unique identifier: NCT02603718 (retrospectively registered 10/14/2015).