De novo fatty acid synthesis by Schwann cells is essential for peripheral nervous system myelination

Myelination calls for a remarkable surge in cell metabolism to facilitate lipid and membrane production. Endogenous fatty acid (FA) synthesis represents a potentially critical process in myelinating glia. Using genetically modified mice, we show that Schwann cell (SC) intrinsic activity of the enzyme essential for de novo FA synthesis, fatty acid synthase (FASN), is crucial for precise lipid composition of peripheral nerves and fundamental for the correct onset of myelination and proper myelin growth. Upon FASN depletion in SCs, epineurial adipocytes undergo lipolysis, suggestive of a compensatory role. Mechanistically, we found that a lack of FASN in SCs leads to an impairment of the peroxisome proliferator-activated receptor (PPAR) γ–regulated transcriptional program. In agreement, defects in myelination of FASN-deficient SCs could be ameliorated by treatment with the PPARγ agonist rosiglitazone ex vivo and in vivo. Our results reveal that FASN-driven de novo FA synthesis in SCs is mandatory for myelination and identify lipogenic activation of the PPARγ transcriptional network as a putative downstream functional mediator

Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women

Progression From Paroxysmal to Persistent Atrial Fibrillation. Clinical Correlates and Prognosis

Objectives: We investigated clinical correlates of atrial fibrillation (AF) progression and evaluated the prognosis of patients demonstrating AF progression in a large population. Background: Progression of paroxysmal AF to more sustained forms is frequently seen. However, not all patients will progress to persistent AF. Methods: We included 1,219 patients with paroxysmal AF who participated in the Euro Heart Survey on AF and had a known rhythm status at follow-up. Patients who experienced AF progression after 1 year of follow-up were identified. Results: Progression of AF occurred in 178 (15%) patients. Multivariate analysis showed that heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension were the only independent predictors of AF progression. Using the regression coefficient as a benchmark, we calculated the HATCH score. Nearly 50% of the patients with a HATCH score >5 progressed to persistent AF compared with only 6% of the patients with a HATCH score of 0. During follow-up, patients with AF progression were more often admitted to the hospital and had more major adverse cardiovascular events. Conclusions: A substantial number of patients progress to sustained AF within 1 year. The clinical outcome of these patients regarding hospital admissions and major adverse cardiovascular events was worse compared with patients demonstrating no AF progression. Factors known to cause atrial structural remodeling (age and underlying heart disease) were independent predictors of AF progression. The HATCH score may help to identify patients who are likely to progress to sustained forms of AF in the near future. \ua9 2010 American College of Cardiology Foundation

Interactive Design Studio: A spatial-computing framework fro non-IT specialists

In recent years, application domains outside information technology such as architecture have shown an increasing interest in the capabilities of networked systems such as localized computation, reduced power-consumption, and distributed interaction. These capabilities incline the design of interactive environments towards the IT-domain. In particular the employment of large scale distributed systems in interactive designs bring along new challenges for architects/designer such as distributed algorithm design, programming skills, embedded platform knowledge. As a consequence of this new trend, adequate software tools to bridge the gap between the IT-world and the field of interactive design are scarce. In order to fill that gap we propose a framework called Interactive Design Studio(IDS) which aims to provide the necessary tools to hide the technological aspects from the end-user when designing interactive environments. To tackle the problem of handling large scale networks of embedded platforms we are convinced that spatial computing is a promising paradigm. The main reasons are the scalability(network size does not influence node behavior) and resiliency to network dynamics(network is hidden by space abstraction). Therefore we present a spatial computing framework for non-IT specialists. We provide a way to specify agent-level behavior and to generate the corresponding code for a specific embedded platform. In our case, we use the eLua VM enhanced with the necessary spatial computing capabilities. We show that spatial computing is a good methodology for Industrial Design and Architecture. Moreover, we show that spatial computing is possible using off-the-shelf virtual machines for embedded platforms. In conclusion, we demonstrate that IDS succeeds within a certain extent in abstracting or hiding the underlying technological aspects(spatial computing) from end-users.Embedded SystemsEmbedded SoftwareElectrical Engineering, Mathematics and Computer Scienc

Role of radiosurgery/stereotactic radiotherapy in oligometastatic disease: Brain oligometastases

During the natural history of oncologic diseases, approximately 20-40% of patients affected by cancer will develop brain metastases. Non-small lung cancer, breast cancer, and melanoma are the primaries that are most likely to metastasize into the brain. To date, the role of Radiosurgery/Stereotactic Radiotherapy (SRS/SRT) without Whole brain irradiation (WBRT) is a well-recognized treatment option for patients with limited intracranial disease (1-4 BMs) and a life-expectancy of more than 3-6 months. In the current review, we focused on randomized studies that evaluate the potential benefit of radiosurgery/stereotactic radiotherapy for brain oligometastases. To date, no difference in overall survival has been observed between SRS/SRT alone compared to WBRT plus SRS. Notably, SRS alone achieved higher local control rates compared to WBRT. A possible strength of SRS adoption is the potential decreased neurocognitive impairment

Chemical weathering of volcanic rocks, Pantelleria Island: information from soil profile and soil solution investigations

Concentrations of major, minor and trace elements were determined in soil profiles and soil solutions from the island of Pantelleria, Sicily Channel, to evaluate the weathering extent of soils evolved on trachytic and pantelleritic rocks and the aqueous transport of elements by their soil solutions. The chemical index of alteration (CIA) indicates a low-to-moderate degree of weathering; consistently, the mineralogical and geochemical imprints of the parent rocks are generally preserved. The chemical weathering appears to be incongruent, owing to primary minerals and glass dissolving to a variable degree while secondary minerals have formed. Based on the calculated saturation state of primary and secondary minerals with respect to the soil solutions and on mineralogical observations, olivine and pyroxene are unstable and dissolving whereas magnetite and hematite are stable. The main weathering products are amorphous phases, such as ferrihydrite, amorphous aluminium hydroxide and silica. Clay mineral formation appears to be incipient and mainly limited to kaolinite and smectite, although for some soil profiles a hydrothermal origin is suggested for these minerals. Chemical characteristics of soil solutions and elemental mobility are controlled by the element source and water-rock interaction

Dual function of the PI3K-Akt-mTORC1 axis in myelination of the peripheral nervous system

Myelination is a biosynthetically demanding process in which mTORC1, the gatekeeper of anabolism, occupies a privileged regulatory position. We have shown previously that loss of mTORC1 function in Schwann cells (SCs) hampers myelination. Here, we genetically disrupted key inhibitory components upstream of mTORC1, TSC1 or PTEN, in mouse SC development, adult homeostasis, and nerve injury. Surprisingly, the resulting mTORC1 hyperactivity led to markedly delayed onset of both developmental myelination and remyelination after injury. However, if mTORC1 was hyperactivated after myelination onset, radial hypermyelination was observed. At early developmental stages, physiologically high PI3K-Akt-mTORC1 signaling suppresses expression of Krox20 (Egr2), the master regulator of PNS myelination. This effect is mediated by S6K and contributes to control mechanisms that keep SCs in a not-fully differentiated state to ensure proper timing of myelination initiation. An ensuing decline in mTORC1 activity is crucial to allow myelination to start, while remaining mTORC1 activity drives myelin growth.ISSN:2050-084