Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted Pancreatic Islets

Nonspecific inflammation in the transplant microenvironment results in β-cell dysfunction and death influencing negatively graft outcome. MicroRNA (miRNA) expression and gene target regulation in transplanted islets are not yet well characterized. We evaluated the impact of inflammation on miRNA expression in transplanted rat islets. Islets exposed in vitro to proinflammatory cytokines and explanted syngeneic islet grafts were evaluated by miRNA arrays. A subset of 26 islet miRNAs was affected by inflammation both in vivo and in vitro. Induction of miRNAs was dependent on NF-κB, a pathway linked with cytokine-mediated islet cell death. RT-PCR confirmed expression of 8 miRNAs. The association between these miRNAs and mRNA target-predicting algorithms in genome-wide RNA studies of β-cell inflammation identified 238 potential miRNA gene targets. Several genes were ontologically associated with regulation of insulin signaling and secretion, diabetes, and islet physiology. One of the most activated miRNAs was miR-21. Overexpression of miR-21 in insulin-secreting MIN6 cells downregulated endogenous expression of the tumor suppressor Pdcd4 and of Pclo, a Ca2+ sensor protein involved in insulin secretion. Bioinformatics identified both as potential targets. The integrated analysis of miRNA and mRNA expression profiles revealed potential targets that may identify molecular targets for therapeutic interventions

Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis

Background: Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM. Methods: A genome-wide association study for change in left ventricular ejection fraction was performed in 686 White subjects with recent-onset DCM who received standard pharmacotherapy. Genome-wide association study signals were subsequently functionally validated and studied in relevant cellular models to understand molecular mechanisms that may have contributed to the change in left ventricular ejection fraction. Results: The genome-wide association study identified a highly suggestive locus that mapped to the 5'-flanking region of the CDCP1 (CUB domain containing protein 1) gene (rs6773435; P=7.12×10-7). The variant allele was associated with improved cardiac function and decreased CDCP1 transcription. CDCP1 expression was significantly upregulated in human cardiac fibroblasts (HCFs) in response to the PDGF (platelet-derived growth factor) signaling, and knockdown of CDCP1 significantly repressed HCF proliferation and decreased AKT phosphorylation. Transcriptomic profiling after CDCP1 knockdown in HCFs supported the conclusion that CDCP1 regulates HCF proliferation and mitosis. In addition, CDCP1 knockdown in HCFs resulted in significantly decreased expression of soluble ST2, a prognostic biomarker for heart failure and inductor of cardiac fibrosis. Conclusions: CDCP1 may play an important role in myocardial recovery in recent-onset DCM and mediates its effect primarily by attenuating cardiac fibrosis

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

Mechanical Cavity Creation with Curettage and Vacuum Suction (Q-VAC) in Lytic Vertebral Body Lesions with Posterior Wall Dehiscence and Epidural Mass before Cement Augmentation.

Background and Objectives: We describe a novel technique for percutaneous tumor debulking and cavity creation in patients with extensive lytic lesions of the vertebral body including posterior wall dehiscence prior to vertebral augmentation (VA) procedures. The mechanical cavity is created with a combination of curettage and vacuum suction (Q-VAC). Balloon kyphoplasty and vertebral body stenting are used to treat neoplastic vertebral lesions and might reduce the rate of cement leakage, especially in presence of posterior wall dehiscence. However, these techniques could theoretically lead to increased intravertebral pressure during balloon inflation with possible mobilization of soft tissue tumor through the posterior wall, aggravation of spinal stenosis, and resultant complications. Creation of a void or cavity prior to balloon expansion and/or cement injection would potentially reduce these risks. Materials and Methods: A curette is coaxially inserted in the vertebral body via transpedicular access trocars. The intravertebral neoplastic soft tissue is fragmented by multiple rotational and translational movements. Subsequently, vacuum aspiration is applied via one of two 10 G cannulas that had been introduced directly into the fragmented lesion, while saline is passively flushed via the contralateral cannula, with lavage of the fragmented solid and fluid-necrotic tumor parts. Results: We applied the Q-VAC technique to 35 cases of thoracic and lumbar extreme osteolysis with epidural mass before vertebral body stenting (VBS) cement augmentation. We observed extravertebral cement leakage on postoperative CT in 34% of cases, but with no clinical consequences. No patients experienced periprocedural respiratory problems or new or worsening neurological deficit. Conclusion: The Q-VAC technique, combining mechanical curettage and vacuum suction, is a safe, inexpensive, and reliable method for percutaneous intravertebral tumor debulking and cavitation prior to VA. We propose the Q-VAC technique for cases with extensive neoplastic osteolysis, especially if cortical boundaries of the posterior wall are dehiscent and an epidural soft tissue mass is present

Ruptured lenticulostriate artery aneurysm: a report of a case treated with endovascular embolisation

A 65-year-old woman presented to the emergency department with sudden onset of left-sided weakness, headache and vomiting. A cerebral CT showed an acute intracerebral haemorrhage involving the right caudate nucleus and lentiform nucleus with mild midline shift and intraventricular extension. CT angiography did not reveal aneurysm or other vascular anomaly. Conventional cerebral angiography demonstrated a 3mm right medial lenticulostriate branch aneurysm, arising from the right anterior cerebral artery (ACA). Endovascular treatment was performed from the left internal carotid via the anterior communicating artery into the right ACA. Complete occlusion was achieved with injection of N-butyl-2-cyanoacrylate. The patient had neurological rehabilitation during hospitalisation followed by outpatient physical therapy. Two years later, clinical follow-up demonstrated excellent recovery

Machine Learning for Digital Twins to Predict Responsiveness of Cyber-Physical Energy Systems

Cyber-Physical Systems are becoming more autonomous, interconnected, complex and adaptive, and are expected to operate in highly dynamic environments. This is especially challenging for energy ecosystems that are increasingly difficult to control and maintain as the number of participating manufacturers and users grows. Digital Twins help analyze and predict these systems in the form of digital reflections that operate in parallel with the physical system. In this paper, we use Machine Learning to improve the predictive power of Digital Twins for Cyber-Physical Energy Systems. Specifically, we use a Temporal Convolutional Neural Network model to learn the temporal patterns in the system and predict its responsiveness to specific power setpoint instructions. Real-life data from ten batteries were used to predict the behavior over time. Compared to the baseline model that uses the prior probability of response and the average response rate within the configured time window, the model predicts the batteries' responsiveness more accurately. The more temporal information is used as input for prediction, the better the model performs in both precision and recall. The results show that this compensates for the lack of information when fewer metrics are used. The use of Machine Learning for Digital Twins can help maintain a heterogeneous energy ecosystem, while minimizing the need to acquire or disclose detailed information

A large scale ambient vibration survey in the area demaged by May-June 2012 seismic sequence in Emilia Romagna, Italy

Results of an extensive ambient vibration surveys carried out by different research teams in the area damaged by May–June 2012 seismic sequence in Emilia Romagna (Northern Italy) are summarized and analysed. In particular, ambient vibrations were acquired by both single station and seismic array configurations. Average horizontal to vertical spectral ratios (HVSR) at single station measurements were considered to evaluate local resonance phenomena. Despite the fact that general trends that can be detected are the effect of the subsoil configuration, H/V spectral ratios show a significant dependence on meteo-climatic conditions: in particular, HVSR amplitudes in the low frequency range (.5 Hz) correlate significantly with the sea wave activity in the Central Mediterranean. Anyway, resonance frequencies estimated from HVSR peaks appear persistent and have been used to estimate the local depth of impedance contrasts responsible for seismic resonance phenomena. To this purpose, average VS values up to any depth h(VSh) were assessed in the form of a standard power law constrained by Rayleigh dispersion curves deduced from the seismic arrays, and borehole data. In the whole area (except in the Mirandola area) two significant interfaces have been identified corresponding to two main resonance frequencies around 0.8–0.9 and 0.25–0.3 Hz respectively. The first one is attributed to a seismic impedance contrast located in the depth range 60–110 m. The second one corresponds to a deeper interface, possibly located at several hundreds of meters of depth. As concerns the Mirandola area, a single interface has been identified with depths varying in the range 50–115 m corresponding to resonant frequencies in the range 0.8–1.4 Hz. Finally a tentative geological interpretation of the above resonant interfaces is presented

Gantry-needle-target alignment technique for CT-guided needle approaches to the skull base and cranio-cervical junction.

PURPOSE CT-guided percutaneous procedures involving the skull base and atlanto-axial cervical spine pose particular challenges due to high density of vital vascular and nervous structures and because the ideal needle trajectory often has a cranio-caudal obliquity different from the axial scan plane. We describe how the variable CT gantry tilt, combined with gantry-needle-target alignment technique, is used to obtain precise and safe needle placement in conventional and non-conventional approaches to the skull base and the atlanto-axial spine. METHODS We retrospectively analyzed consecutive CT-guided needle accesses to the skull base and atlanto-axial spine performed for tissue sampling through fine-needle aspirates and core biopsies, cementoplasty of neoplastic lytic lesions of atlanto-axial spine, pain management injections, and dural puncture for cerebro-spinal fluid sampling. All the accesses were performed with the gantry-needle-target alignment technique. Procedural complications were recorded. RESULTS Thirty-nine CT-guided procedures were analyzed. Paramaxillary approach was used in 15 cases, postero-lateral in 11, subzygomatic in 3. Nine non-conventional approach were performed: submastoid in 3 cases, suprazygomatic in 2, trans-nasal in 2, trans-mastoid in 1, and trans-auricular in 1. Two peri-procedural complications occurred: one asymptomatic and one resolved within 24 h. All the procedures were successfully completed with successful needle access to the target. CONCLUSION The gantry tilt and gantry-needle-target alignment technique allows to obtain double-oblique needle accesses for CT-guided procedures involving the skull base and atlanto-axial cervical spine, minimizing uncertainty of needle trajectory and obtaining safe needle placement in conventional and non-conventional approaches

Rivestimenti ceramici di nuova generazione per termodeposizione plasma

Vengono riportati i risultati preliminari della realizzazione di barriere termiche ceramiche innovative (TBC) realizzate per termospruzzatura plasma. I materiali utilizzati fanno parte della classe degli zirconati di terre rare, in questo caso di lantanio e cerio, caratterizzati da struttura piroclorica e fluoritica. Il loro utilizzo consentirebbe di superare i limiti operativi imposti dai materiali di utilizzo corrente. Sono state messe a punto procedure di trattamento dei materiali di partenza (La2O3, ZrO2, CeO2), al fine di ottenere polveri idonee alla termodeposizione aventi le composizioni desiderate (La2Zr2O7, La2(Zr0.7Ce0.3)2O7). Le varie tipologie di polveri sono state quindi depositate utilizzando diversi set di parametri, permettendo di individuare il processo di deposizione più idoneo. Le analisi sui rivestimenti ottenuti hanno dimostrato in primo luogo la bontà della tecnica di trattamento delle polveri, e quindi del processo di deposizione, consentendo di ottenere rivestimenti contenenti la fase desiderata.We report the preliminary results of the implementation of innovative ceramic thermal barrier coatings (TBC) produced by plasma thermal spraying. The materials used are part of the class of rare earth zirconates, in this case, lanthanum and cerium, characterized by structure and piroclorica fluoritica. Their use would overcome the operational limits imposed by the materials of use corrente.Sono been developed procedures for treatment of the starting materials (La2O3, ZrO2, CeO2), in order to obtain powders suitable for termodeposizione having the desired compositions (La2Zr2O7 , La2 (Zr0.7Ce0.3) 2O7). The various types of powders were then deposited using different sets of parameters, allowing to identify the deposition process more idoneo.Le analysis on coatings obtained showed firstly the goodness of the treatment technique of the powders, and then the deposition process , allowing you to obtain coatings containing the desired phase