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

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

Tendenze evolutive per l'edilizia sostenibile: strumenti, tecniche e prodotti (paragrafi: Complessità del progetto sostenibile, Approcci integrati, Tecnologie sostenibili per la residenza)

La sfida della complessità ha rappresentato un concetto chiave nel recente dibattito scientifico, investendo numerosi campi del sapere e della ricerca tecnologica. Il superamento delle tecniche tradizionali e l'affermarsi di tecnologie evolute anche nell'edilizia diffusa delinea uno scenario in cui la compatibilità tecnologica diventa un concetto e una modalità chiave per l'assemblaggio di prodotti industrializzati. L'assemblaggio di prodotti e tecniche ibridate si correla nel panorama del progetto per l'edilizia eco compatibile con strategie energy saving, di building automation e di polivalenza prestazionale in campo ambientale ed energetico

1.5 T MR-guided and daily adapted SBRT for prostate cancer: Feasibility, preliminary clinical tolerability, quality of life and patient-reported outcomes during treatment

Background: Unity Elekta is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator.A prospective observational study for the clinical use of Elekta Unity is currently ongoing in our department. Herein, we present our preliminary report on the feasibility, quality of life, and patient-reported outcomes measures (PROMs) for localized prostate cancer (PC) treated with stereotactic body radiotherapy (SBRT). Methods: The SBRT protocol consisted of a 35 Gy schedule delivered in 5 fractions within 2 weeks. Toxicity and quality of life (QoL) were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v5.0, International Prostatic Symptoms Score (IPSS), ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires. Results: Between October 2019 and January 2020, 25 patients with localized PC were recruited. The median age was 68 years (range, 54-82); 4 were low risk, 11 favorable intermediate risk (IR) and 10 unfavorable IR. Median iPSA was 6.8 ng/ml (range, 1-19), and 9 of these patients (36%) received concurrent androgen deprivation therapy. Median prostate volume was 36 cc (range, 20-61); median baseline IPSS was 5 (range, 0-10). Median time for fraction was 53 min (range, 34-86); adaptive strategy with daily critical structure and target re-contouring and daily replanning (adapt to shape) was performed in all cases. No grade ≥ 3 adverse event was observed, three patients (12%) reported grade 2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention), while only one patient reported mild rectal pain. No relevant deteriorations were reported in PROMs. Conclusion: To the best of our knowledge, this is the first experience reporting feasibility, clinician-reported outcome measurements, and PROMs for 1.5 T MR-guided adaptive SBRT for localized prostate cancer. The preliminary data collected here report optimal safety and excellent tolerability, as also confirmed by PROMs questionnaires. Moreover, the data on technical feasibility and timing of online daily adapted planning and delivery are promising. More mature data are warranted. Trial registration: Date of approval April 2019 and numbered MRI/LINAC n°23,748

Feasibility and preliminary clinical results of linac-based Stereotactic Body Radiotherapy for spinal metastases using a dedicated contouring and planning system

Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) are well established local treatment approaches in several cancer settings. Although SBRT is still under investigation for spinal metastases, promising results in terms of a high effectiveness and optimal tolerability have been recently published on this topic. For spinal SBRT, one of the most relevant issues is represented by the inter-observer variability in target definition. Recently, several technological innovations, including specific tools such as multimodality-imaging (computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET-CT), automated volumes contouring and planning, could allow clinicians to minimize the uncertainties related to spinal SBRT workflow. Aim of this study is to report the feasibility of the clinical application of a dedicated software (Element®, Brainlab™ Germany) for spinal metastases SBRT

Scuola in piazza a levante

La Scuola e la Piazza a levante devono definire una nuova centralità: nel cuore della nuova città come motore per la valorizzazione della sua identità e per migliorare la qualità della vita dei suoi cittadini. Le attrezzature per lo sport e il parco pubblico devono essere un ecosistema integrato: devono ricreare, insieme alla dotazione sportiva, un microcosmo dell’ecosistema pugliese, con le sue tradizioni arboree ed agrarie, riletto e reinterpretato in base ai criteri di sostenibilità, di risparmio ed uso razionale delle risorse energetiche, della tutela dei valori ambientali, della permeabilità dei suoli, potenziando l’alberatura di specie, valorizzando il ruolo – non solo simbolico – e la presenza dell’acqua

Stereotactic body radiotherapy of central lung malignancies using a simultaneous integrated protection approach: A prospective observational study

It is recognized that stereotactic body radiotherapy (SBRT) for centrally located lung metastases is affected by higher rates of severe toxicity. In the present study, we report the clinical outcomes following a novel intensity-modulated radiotherapy prescription dose, termed simultaneous integrated protection (SIP), for nearby organs at risk (OARs)