18F-FDG-PET correlates of cognitive impairment in ALS

Objective: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET). Methods: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent brain 18F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n 5 94), full-blown frontotemporal dementia (ALS-FTD; n 5 20), executive or nonexecutive cognitive impairment not fulfilling FTD criteria (ALS-Ci; n 5 37), prevalent behavioral changes (n 5 9), or nonclassifiable impairment (n 5 10) according to neuropsychological testing. Group comparisons of 18F-FDG-PET pattern were carried out among the cognitive subgroups. Results: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex, being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the larger the size of the cluster and the statistical significance of 18F-FDG uptake differences. Conclusions: This study demonstrated in a large cohort of patients with ALS a continuum of frontal lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients with intermediate cognitive impairment display a characteristic metabolic pattern. Since 18F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases, it might be helpful to investigate in ALS its association with neuropsychological testing along the disease course to disclose the early metabolic signature of possible cognitive impairment

Endovascular treatment of carotid artery stenosis: evidences from randomized controlled trials and actual indications.

Atherosclerotic stenosis of common and internal carotid arteries is a well-recognized risk factor for ischemic stroke, and revascularization has been proven to be the main tool of prevention, particularly for patients with stenosis- related symptoms. While for many years surgical carotid endarterectomy (CEA) has been considered the gold-standard strategy to restore vascular patency, recently the endovascular treatment through percutaneous angioplasty and stent implantation (CAS) has become a valid alternative. In the last years, interesting data about the comparison of these strategies have emerged. CAS seems to cause more peri-procedural strokes, but may also avoid many adverse events related to surgery and general anaesthesia, including peri-procedural myocardial infarction. For these reasons, it was initially considered a second-choice strategy to be adopted in patients for whom surgery was contraindicated. However, more recent trials have shown that CAS might be considered an effective alternative to CEA. Moreover, the rapid evolution of CAS technique and materials suggests its potential to improve outcome and possible superiority compared to CEA in the next future. Purpose of this review is to discuss the most recent clinical evidences concerning the treatment of carotid artery stenosis, with a special focus on the endovascular treatment

3D echocardiographic reference ranges for normal left ventricular volumes and strain: Results fromthe EACVI NORRE study

Aim To obtain the normal ranges for 3D echocardiography (3DE) measurement of left ventricular (LV) volumes, function, and strain from a large group of healthy volunteers. Methods and results A total of 440 (mean age: 45613 years) out of the 734 healthy subjects enrolled at 22 collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study had good-quality 3DE data sets that have been analysed with a vendor-independent software package allowing homogeneous measurements regardless of the echocardiographic machine used to acquire the data sets. Upper limits of LV end-diastolic and end-systolic volumes were larger in men (97 and 42 mL/m2) than in women (82 and 35 mL/m2; P<0.0001). Conversely, lower limits of LV ejection fraction were higher in women than in men (51% vs. 50%; P<0.01). Similarly, all strain components were higher in women than in men. Lower range was -18.6% in men and -19.5% in women for 3D longitudinal strain, -27.0% and -27.6% for 3D circumferential strain, -33.2% and -34.4% for 3D tangential strain and 38.8% and 40.7% for 3D radial strain, respectively. LV volumes decreased with age in both genders (P<0.0001), whereas LV ejection fraction increased with age only in men. Among 3DE LV strain components, the only one, which did not change with age was longitudinal strain. Conclusion The NORRE study provides applicable 3D echocardiographic reference ranges for LV function assessment. Our data highlight the importance of age- and gender-specific reference values for both LV volumes and strain. All rights reserved

Survey on retinopathy of prematurity (ROP) in Italy

This study aims to investigate the incidence and the relative risk factors of retinopathy of prematurity (ROP) and posterior-ROP (P-ROP): ROP in Zone I and posterior Zone II, as well as to analyze the occurrence of surgical treatment of ROP and to evaluate the short term outcome of the disease in Italy

Genetic deletion of uncoupling protein 3 exaggerates apoptotic cell death in the ischemic heart leading to heart failure

BACKGROUND: Uncoupling protein 3 (ucp3) is a member of the mitochondrial anion carrier superfamily of proteins uncoupling mitochondrial respiration. In this study, we investigated the effects of ucp3 genetic deletion on mitochondrial function and cell survival under low oxygen conditions in vitro and in vivo. METHODS AND RESULTS: To test the effects of ucp3 deletion in vitro, murine embryonic fibroblasts and adult cardiomyocytes were isolated from wild-type (WT, n=67) and ucp3 knockout mice (ucp3(-/-), n=70). To test the effects of ucp3 genetic deletion in vivo, myocardial infarction (MI) was induced by permanent coronary artery ligation in WT and ucp3(-/-) mice. Compared with WT, ucp3(-/-) murine embryonic fibroblasts and cardiomyocytes exhibited mitochondrial dysfunction and increased mitochondrial reactive oxygen species generation and apoptotic cell death under hypoxic conditions in vitro (terminal deoxynucleotidyl transferase-dUTP nick end labeling-positive nuclei: WT hypoxia, 70.3 ± 1.2%; ucp3(-/-) hypoxia, 85.3 ± 0.9%; P<0.05). After MI, despite similar areas at risk in the 2 groups, ucp3(-/-) hearts demonstrated a significantly larger infarct size compared with WT (infarct area/area at risk: WT, 48.2 ± 3.7%; ucp3(-/-), 65.0 ± 2.9%; P<0.05). Eight weeks after MI, cardiac function was significantly decreased in ucp3(-/-) mice compared with WT (fractional shortening: WT MI, 42.7 ± 3.1%; ucp3(-/-) MI, 24.4 ± 2.9; P<0.05), and this was associated with heightened apoptotic cell death (terminal deoxynucleotidyl transferase-dUTP nick end labeling-positive nuclei: WT MI, 0.7 ± 0.04%; ucp3(-/-) MI, 1.1 ± 0.09%, P<0.05). CONCLUSIONS: Our data indicate that ucp3 levels regulate reactive oxygen species levels and cell survival during hypoxia, modulating infarct size in the ischemic heart

Combined cytogenetic and molecular methods for taxonomic verification and description of Brassica populations deriving from different origins

Agriculture faces great challenges to overcome global warming and improve system sustainability, requiring access to novel genetic diversity. So far, wild populations and local landraces remain poorly explored. This is notably the case for the two diploid species, Brassica oleracea L. (CC, 2n=2x=18) and B. rapa L. (AA, 2n=2x=20). In order to explore the genetic diversity in both species, we have collected populations in their centre of origin, the Mediterranean basin, on a large contrasting climatic and soil gradient from northern Europe to southern sub-Saharan regions. In these areas, we also collected 14 populations belonging to five B. oleracea closely related species. Our objective was to ensure the absence of species misidentification at the seedling stage among the populations collected and to describe thereafter their origins. We combined flow cytometry, sequencing of a species-specific chloroplast genomic region, as well as cytogenetic analyses in case of unexpected results for taxonomic verification. Out of the 112 B. oleracea and 154 B. rapa populations collected, 103 and 146, respectively, presented a good germination rate and eighteen populations were misidentified. The most frequent mistake was the confusion of these diploid species with B. napus. Additionally for B. rapa, two autotetraploid populations were observed. Habitats of the collected and confirmed wild populations and landraces are described in this study. The unique plant material described here will serve to investigate the genomic regions involved in adaptation to climate and microbiota within the framework of the H2020 Prima project ‘BrasExplor’

The plants, rituals and spells that 'cured' helminthiasis in Sicily

<p>Abstract</p> <p>Background</p> <p>The author reports on the plants, rituals and spells used against worms and the so-called <it>scantu </it>(fright) in some areas of Sicily. The work is based on ethnobotanical research carried out, prevalently, between 2002-2006, in some areas of Eastern, South-Eastern, North-Central and South-Central Sicily.</p> <p>Methods</p> <p>This research is based on dialogue. Senior 'healers' were contacted; furthermore, doctors, teachers, farmers and in general 'experts' with herbs and 'magic' rituals. Information was collected about the way the plants of folk medicine are prepared. The interviewees were also invited to recite prayers and spells against helminthiasis.</p> <p>Results</p> <p>The author has highlighted the importance of how, in some parts of Sicily, some ailments like helminthiasis and other correlated pathologies like <it>scantu </it>are 'treated' and, especially within the rural social classes, by folk medicine remedies, herbal practises, particular prayers, rituals and spells.</p> <p>Conclusion</p> <p>As regards health/illness, it should be noted that in the last ten years conventional medicine has provided very satisfactory results even resolving potentially mortal pathologies. However, in certain social classes, there is no real collaboration between conventional and folk medicine; so for some senior citizens, the 'healer' with his rituals and empirical and magical herbs is still the person to turn to for the 'cure' of particular ailments. Interest in these practises from ancestral heritage in an advanced country like Italy, is only relevant if the aim is to recoup a cultural identity which is already in decline.</p> <p>It is significant to report a piece: on 14 October 2007 the news on a well-known national Italian TV channel reported an interview with a 94 year-old man from Arbatax (Sardinia) referred to as a 'healer' because both his townspeople and others from all over the world go to him for his cures. He is not paid except in kind and has been known to cure St. Anthony's fire, burns, scalding and marine fungal infections, by smearing his saliva over the infected part and reciting 'special words'.</p

Synthesis of air‐stable, odorless thiophenol surrogates via Ni‐Catalyzed C−S cross‐coupling

Thiophenols are versatile synthetic intermediates whose practical appeal is marred by their air sensitivity, toxicity and extreme malodor. Herein we report an efficient catalytic method for the preparation of S-aryl isothiouronium salts, and demonstrate that these air-stable, odorless solids serve as user-friendly sources of thiophenols in synthesis. Diverse isothiouronium salts featuring synthetically useful functionality are readily accessible via nickelcatalyzed C-S cross-coupling of (hetero)aryl iodides and thiourea. Convenient, chromatography-free isolation of these salts is achieved via precipitation, allowing the methodology to be translated directly to large scales. Thiophenols are liberated from the corresponding isothiouronium salts upon treatment with a weak base, enabling an in situ release / S-functionalization strategy that entirely negates the need to isolate, purify or manipulate these noxious reagent

Outcomes of Patients with Asymptomatic Aortic Stenosis Followed Up in Heart Valve Clinics

Importance: The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era. Objective: To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database. Design, Setting, and Participants: This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2 or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018. Main Outcomes and Measures: Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations. Results: Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and Relevance: In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients