The effects of glomerular and tubular renal progenitors and derived extracellular vesicles on recovery from acute kidney injury

BACKGROUND: Mesenchymal stromal cells (MSCs) and renal stem/progenitors improve the recovery of acute kidney injury (AKI) mainly through the release of paracrine mediators including the extracellular vesicles (EVs). Several studies have reported the existence of a resident population of MSCs within the glomeruli (Gl-MSCs). However, their contribution towards kidney repair still remains to be elucidated. The aim of the present study was to evaluate whether Gl-MSCs and Gl-MSC-EVs promote the recovery of AKI induced by ischemia-reperfusion injury (IRI) in SCID mice. Moreover, the effects of Gl-MSCs and Gl-MSC-EVs were compared with those of CD133(+) progenitor cells isolated from human tubules of the renal cortical tissue (T-CD133(+) cells) and their EVs (T-CD133(+)-EVs). METHODS: IRI was performed in mice by clamping the left renal pedicle for 35 minutes together with a right nephrectomy. Immediately after reperfusion, the animals were divided in different groups to be treated with: Gl-MSCs, T-CD133(+) cells, Gl-MSC-EVs, T-CD133(+)-EVs or vehicle. To assess the role of vesicular RNA, EVs were either isolated by floating to avoid contamination of non-vesicles-associated RNA or treated with a high dose of RNase. Mice were sacrificed 48 hours after surgery. RESULTS: Gl-MSCs, and Gl-MSC-EVs both ameliorate kidney function and reduce the ischemic damage post IRI by activating tubular epithelial cell proliferation. Furthermore, T-CD133(+) cells, but not their EVs, also significantly contributed to the renal recovery after IRI compared to the controls. Floating EVs were effective while RNase-inactivated EVs were ineffective. Analysis of the EV miRnome revealed that Gl-MSC-EVs selectively expressed a group of miRNAs, compared to EVs derived from fibroblasts, which were biologically ineffective in IRI. CONCLUSIONS: In this study, we demonstrate that Gl-MSCs may contribute in the recovery of mice with AKI induced by IRI primarily through the release of EVs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0478-5) contains supplementary material, which is available to authorized users

Prion-related peripheral neuropathy in sporadic Creutzfeldt-Jakob disease

OBJECTIVE: To assess whether the involvement of the peripheral nervous system (PNS) belongs to the phenotypic spectrum of sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: We examined medical records of 117 sCJDVV2 (ataxic type), 65 sCJDMV2K (kuru-plaque type) and 121 sCJDMM(V)1 (myoclonic type) subjects for clinical symptoms, objective signs and neurophysiological data. We reviewed two diagnostic nerve biopsies and looked for abnormal prion protein (PrP(Sc)) by western blotting and real-time quaking-induced conversion (RT-QuIC) in postmortem PNS samples from 14 subjects. RESULTS: Seventy-five (41.2%) VV2-MV2K patients, but only 11 (9.1%) MM(V)1, had symptoms or signs suggestive of PNS involvement occurring at onset in 18 cases (17 VV2-MV2K, 9.3%; and 1 MM(V)1, 0.8%) and isolated in 6. Nerve biopsy showed a mixed predominantly axonal and demyelinating neuropathy in two sCJDMV2K. Electromyography showed signs of neuropathy in half of the examined VV2-MV2K patients. Prion RT-QuIC was positive in all CJD PNS samples, whereas western blotting detected PrP(Sc) in the sciatic nerve in one VV2 and one MV2K. CONCLUSIONS: Peripheral neuropathy, likely related to PrP(Sc) deposition, belongs to the phenotypic spectrum of sCJDMV2K and VV2 and may mark the clinical onset. The significantly lower prevalence of PNS involvement in typical sCJDMM(V)1 suggests that the PNS tropism of sCJD prions is strain dependent

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

Endocavitary electrophysiological study by percutaneous antecubital vein and without X-ray for risk stratification of asymptomatic ventricular pre-excitation in young athletes

Background: Athletes with asymptomatic ventricular pre-excitation (VP) should undergo electrophysiological study for risk stratification. We aimed to evaluate the feasibility, efficacy, safety and tolerability of an electrophysiological study using a percutaneous antecubital vein access and without the use of X-ray (ESnoXr). Methods: We collected data from all young athletes < 18 year-old with AVP, who underwent ESnoXr from January 2000 to September 2020 for evaluation of accessory pathway refractoriness and arrhythmia inducibility using an antecubital percutaneous venous access. Endocavitary signals were used to advance the catheter in the right atrium and ventricle. Results: We included 63 consecutive young athletes (mean age 14.6 ± 1.9 years, 46% male). Feasibility of the ESnoXr technique was 87% while in 13% fluoroscopy and/or a femoral approach were needed. Specifically, fluoroscopy was used in 7 cases to position the catheter inside the heart cavities with an average exposure of 43 ± 38 s while in 2 femoral venous access was needed. The mean procedural time was 35 ± 11 min. The exam was diagnostic in all patients, there were no procedural complications and tolerability was excellent. 53% of the patients had an accessory pathway with high refractoriness and no inducible atrio-ventricular reentry tachycardia: this subgroup was considered eligible to competitive sports and no event was observed during long-term follow-up (13.6 ± 5.2 years) without drug use. The others underwent catheter ablation. Conclusion. ESnoXr has been shown to be a feasible, effective, safe and well-tolerated procedure for the assessment of arrhythmic risk in a population of young athletes with asymptomatic VP

Strategic reprogramming of implantable cardiac monitors reduces the false-positive remote alert burden in a nurse-led service

Aims Implantable cardiac monitors (ICMs) can generate false-positive (FP) alerts. Although these devices have an extended programmability, there are no recommendations on their optimization to reduce not-relevant activations. We tested a strategic programming optimization guide based on the type of FP and investigated the safety and feasibility of the nurse-led insertion of ICMs with a long-sensing vector. Methods and results Consecutive patients implanted by trained nurses with long-sensing vector ICM were enrolled in a 1-month observational stage (Phase A). Patients who had >= 10 FP episodes underwent ICM reprogramming based on the predefined guide and were followed for an additional month (Phase B). A total of 78 patients had successful ICM insertion by nurses with a mean R wave amplitude of 0.96 +/- 0.43 mV and an 86% P wave visibility. Only one patient reported a significant device-related issue, and nurse-delivered ICM was generally well accepted by the patients. During Phase A, 11 patients (14%) generated most of FP (3,627/3,849; 94%) and underwent ICM reprogramming. In the following month (Phase B), five patients (45%) were free from FP and six (55%) transmitted 57 FP alerts (98% reduction compared with Phase A). The median number of FP per patient was significantly reduced after reprogramming [195 (interquartile range, 50-311) vs. one (0-10), P = 0.0002]. Conclusion A strategic reprogramming of ICM in those patients with a high FP alert burden reduces the volume of erroneous activations with potential benefits for the remote monitoring service. No concerns were raised regarding nurse-led insertion of ICMs with a long-sensing vector

Effectiveness of High-Power Laser Therapy via Shear Wave Speed Analysis on Pain and Functioning in Patients with Lateral Epicondylitis: A Proof-of-Concept Study

Background: Lateral epicondylitis (LE) causes lateral elbow pain due to the overuse of the common extensor tendon. Several therapies have been proposed for pain relief and functional recovery, including physical therapy, minimally invasive injection approaches, and physical agent modalities such as laser therapy. Methods: Our study evaluates the impact of high-power laser therapy (HPLT) on pain and functioning. The HPLT protocol consists of 10 daily sessions using a LASERIX PRO device. The healthy elbow of each participant was also considered as a control group. The outcomes assessed were the Numerical Rating Scale (NRS) for pain, QuickDASH questionnaire for functionality, and shear wave velocity (SWS) through ultrasonography. Assessments were conducted at baseline (T0), post-treatment (T1), and 2-week follow-up (T2). Results: Sixteen participants (81.2% male, mean age 40.4 ± 5.53 years) completed the study. Post-treatment, pain significantly decreased (NRS: T0 6.13 ± 0.96; T1 2.75 ± 1.69; p p p Conclusions: At the 2-week follow-up, pain relief was maintained, and shear wave velocity showed no further significant change. Shear wave velocity assessments might be considered a useful diagnostic tool. However, further research is needed to support the role of HPLT and shear wave velocity in the rehabilitation management of LE

Additional file 1: Figure S1. of The effects of glomerular and tubular renal progenitors and derived extracellular vesicles on recovery from acute kidney injury

Renal cell proliferation in IRI-mice treated with Gl-MSCs-derived EVs. (A) Quantification of BrdU-positive cells/high power field (HPF) was performed in renal sections of IRI mice injected with vehicle alone (IRI-CTL), 400 × 106 EVs produced by Gl-MSCs (IRI-Gl-MSC-EV), 400 × 106 EVs produced by Gl-MSCs and obtained by floating process (IRI-Gl-MSC-EV-float), 400 × 106 EVs produced by Gl-MSCs and treated with RNase (IRI-RNase-Gl-MSC-EV), and in sham-operated SCID mice. ANOVA with Dunnett’s multiple comparison test was performed, (* p <0.05). (B) Representative micrographs of BrdU staining preformed on section of kidneys 2 days after IRI and treatments injection. Original magnification: ×40. (DOCX 135 kb