Ridefinizione biostratigrafica e geocronologica delle unità formazionali neogeniche della Sardegna centrale (Italia)

Recent, detailed geological and stratigraphic surveys of a large area of the Marmilla region (central Sardinia) have made it possible to reconsider the lithobiostratigraphic characteristics of the formal and informal units in the literature on the Cenozoic (Late Oligocene – Neogene) which have been in use up to now. Extension of the research to adjoining lands, including Alta Marmilla, Alto Oristanese, Sinis–Planargia, Barigadu, Baronie and Sarcidano, has also made it possible to perform an overall analysis of the entire Cenozoic basin of central Sardinia and, finally, to make significant comparisons with the coeval successions outcropping in southern and northern Sardinia. In this preliminary note we then report on new data concerning the biostratigraphic aspects of the successions considered, while eco-biostratigraphic data and the depositional and synthemic arrangement, now at an advanced stage of definition, will be discussed in a later, more complete work. Some units in the literature are once again proposed, albeit with amendments, as suggested by the new regulations governing the establishment of new formal depositional units and conservation of units in the literature, and with new geochronostratigraphic delimitations (e. g. the Gesturi Formation). Other units change their hierarchical rank (e. g. the Marmilla Group), while for others it was not deemed useful to keep them (e. g. Marne di Ales), since they might cause confusion. Most of the Formations, all of the Members and Groups are proposed in this work for the first time. The formation units outcropping in central Sardinia’s Cenozioc basin are represented for the most part by a sedimentary and volcano-sedimentary succession several hundreds of metres thick, the age of which is included within the Chattian-Aquitanian passage and the Plio-Quaternary. These are sediments from silicoclastics to mixed carbonatic-silicoclastics, in some cases richly fossiliferous, in which are inserted volcanic products from acid to intermediate-basic with a calcalkaline composition, the latter almost exclusively present starting from the Aquitanian up to the Late Burdigalian, with the strongest concentration in deposits of Burdigalian age. As is the case in northern and southern Sardinia, central Sardinia’s Miocene formations can be referred to three main sedimentary cycles recognized on the basis of heir litho-biostratigraphy and the analysis of associations of benthic macrofauna, which will be discussed in a specific article to be published shortly. The first Miocene sedimentary cycle evolved between the Chattian/Aquitanian limit and the Late Burdigalian (N6 Zone); the second cycle began in the Uppermost Burdigalian, in correspondence to the upper part of the Globigerinoides trilobus Zone (N7 Zone) and closes in the Late Serravallian (G. siakensis Zone, G. siakensis-G. obliqua obliqua Subzone); finally, after a clear regression phase, in the Tortonian (or perhaps already in the Uppermost Serravillian) the third cycle began and ended in the Early Messinian, in correspondence to the upper part of biostratigraphic N17a Zone. On the basis of a comparative analysis of autochthonous benthic associations, especially those with molluscs, and of the textural characteristics of the sediments, the prevalent depositional environment for the three cycles mentioned previously is that of a platform and secondly of a slope, but in some cases fluvio-lacustrine and deltaic. At the end of the third cycle there is a hiatus and/or erosion, or local continental sedimentation (Nuraghe Baboe Cabitza A n. Formation). A further marine sedimentary cycle locally (Sinis, Orosei) began and ends in the Lower Pliocene (Nuraghe Baboe Cabitza B n. Formation). In an overall biostratigraphic and geochronological frame, the comparison between the most important sedimentary, tectonic and volcanic occurrences in central Sardinia from the Oligocene to the Pliocene and those which occurred in the north and south of the island are pointed out. From the paleogeographic standpoint, the deposits of the first Miocene sedimentary cycle are part of the autochthonous cover of the southern European continental margin; those of the second and third cycles are instead connected with the aperture of the Balearic basin and the northern Tyrrhenian Sea; finally, the Early Pliocene marine succession is referred to the open of the southern Tyrrhenian basin, as well as the widespread volcanic activity of prevalently basaltic alkaline nature (the «Plio-Pleistocene volcanic cycle») towards the end of the Messinian and in the Pliocene

Abracadabra. Il potere curativo delle parole tra mito, tradizioni e neuroscienze

Sacred texts, myths and traditions worldwide attribute a healing power to words. Abracadabra, the magic word par excellence, is mentioned in the physician's book of Emperor Caracalla as a healing tool, and Gorgias in the 5th century BC compare drugs to words. What is the vision of science? What effect do words have on the brain? This volume addresses in a simple way the theme of the healing power of words both from the point of view of the history of religions, mythology and ethology and from a neuroscientific point of view. Speech produces changes in the activity of the brain that can be the basis of psychotherapy and contribute to the psychophysical wellness of the person in health and disease.PublishedTesti sacri, miti e tradizioni di tutto il mondo attribuiscono un potere curativo alle parole. Abracadabra, parola magica per eccellenza, è citata nel libro del medico dell’imperatore Caracalla come strumento di guarigione e Gorgia nel V secolo a.C. paragona i farmaci alle parole. Qual è la visione della scienza? Quali effetti hanno le parole sul cervello? Questo volume affronta in modo divulgativo il tema del potere curativo delle parole sia da un punto di vista della storia delle religioni, della mitologia e delle tradizioni popolari, che da un punto di vista neuroscientifico. La parola, produce modificazioni dell’attività del cervello che possono essere alla base della psicoterapia e contribuire al benessere psicofisico della persona

Peak functional ability and age at loss of ambulation in Duchenne muscular dystrophy

AIM: To correlate the North Star Ambulatory Assessment (NSAA) and timed rise from floor (TRF) recorded at age of expected peak with age at loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD). METHOD: Male children with DMD enrolled in the UK North Start Network database were included according to the following criteria: follow-up longer than 3 years, one NSAA record between 6 years and 7 years 6 months (baseline), at least one visit when older than 8 years. Data about corticosteroid treatment, LOA, genotype, NSAA, and TRF were analysed. Age at LOA among the different groups based on NSAA and TRF was determined by log-rank tests. Cox proportional hazard models were used for multivariable analysis. RESULTS: A total of 293 patients from 13 different centres were included. Mean (SD) age at first and last visit was 5 years 6 months (1 year 2 months) and 12 years 8 months (2 years 11 months) (median follow-up 7 years 4 months). Higher NSAA and lower TRF at baseline were associated with older age at LOA (p<0.001). Patients scoring NSAA 32 to 34 had a probability of 0.61 of being ambulant when older than 13 years compared with 0.34 for those scoring 26 to 31. In multivariable analysis, NSAA, TRF, and corticosteroid daily regimen (vs intermittent) were all independently associated with outcome (p=0.01). INTERPRETATION: Higher functional abilities at peak are associated with older age at LOA in DMD. This information is important for counselling families. These baseline measures should also be considered when designing clinical trials

Enhanced endocannabinoid-mediated modulation of rostromedial tegmental nucleus drive onto dopamine neurons in sardinian alcohol-preferring rats

The progressive predominance of rewarding effects of addictive drugs over their aversive properties likely contributes to the transition from drug use to drug dependence. By inhibiting the activity of DA neurons in the VTA, GABA projections from the rostromedial tegmental nucleus (RMTg) are well suited to shift the balance between drug-induced reward and aversion. Since cannabinoids suppress RMTg inputs to DA cells and CB1 receptors affect alcohol intake in rodents, we hypothesized that the endocannabinoid system, by modulating this pathway, might contribute to alcohol preference. Here we found that RMTg afferents onto VTA DA neurons express CB1 receptors and display a 2-arachidonoylglycerol (2-AG)-dependent form of short-term plasticity, that is, depolarization-induced suppression of inhibition (DSI). Next, we compared rodents with innate opposite alcohol preference, the Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats. We found that DA cells from alcohol-naive sP rats displayed a decreased probability of GABA release and a larger DSI. This difference was due to the rate of 2-AG degradation. In vivo, we found a reduced RMTg-induced inhibition of putative DA neurons in sP rats that negatively correlated with an increased firing. Finally, alcohol failed to enhance RMTg spontaneous activity and to prolong RMTg-induced silencing of putative DA neurons in sP rats. Our results indicate functional modifications of RMTg projections to DA neurons that might impact the reward/aversion balance of alcohol attributes, which may contribute to the innate preference observed in sP rats and to their elevated alcohol intak

Discordance between patient and physician global assessment of disease activity in Behçet's syndrome: a multicenter study cohort

Background: To compare the patients' and physician's global assessment of disease activity in Behçet's syndrome (BS) and investigate the frequency, magnitude, and determinants of potential discordance. Methods: A total of 226 adult BS patients with a median (IQR) age of 46.9 (35.6-55.2) years were enrolled across Italy, Greece, Portugal, and Spain. Demographic, clinical, and therapeutic variables, as well as the patient reported outcomes, were collected at the recruitment visit. The physical (PCS) and mental (MCS) component summary scores of the Short Form Questionnaire 36 (SF-36) and the Behçet's syndrome Overall Damage Index (BODI) were calculated. Disease activity was assessed by the patients' (PtGA) and physician's global assessment (PGA) in a 10-cm visual analog scale, as well as the Behçet Disease Current Activity Form (BDCAF). Discordance (∆) was calculated by subtracting the PGA from the PtGA and defined as positive (PtGA>PGA) and negative (PtGA 80%) of disagreements were due to patients rating higher their disease activity. Higher values of BDCAF were associated to increased rate of positive discordance. When BDCAF = 0, the median (IQR) values of PtGA and PGA were 0.2 (0-2) and 0 (0-1), respectively. PCS (adjusted odds ratio (adjOR) 0.96 per unit, 95% CI 0.93-0.98, p = 0.006) and MCS (adjOR 0.96 per unit, 95% CI 0.93-0.99, p = 0.003) were independently associated with positive discordance using both cutoffs. Active ocular involvement emerged as a potential determinant of negative discordance (adjOR 5.88, 95% CI 1.48-23.30, p = 0.012). Conclusions: PtGA and PGA should be considered as complementary measures in BS, as patients and physicians may be influenced by different factors when assessing active disease manifestations. Particularly, PtGA may be a useful tool in the assessment of BS disease activity, as it carries a low risk to misclassify an inactive disease, and may allow to capture aspects of the patient's health that negatively affect his well-being and the treatment

Disease Rescue and Increased Lifespan in a Model of Cardiomyopathy and Muscular Dystrophy by Combined AAV Treatments

The BIO14.6 hamster is an excellent animal model for inherited cardiomyopathy, because of its lethal and well-documented course, due to a spontaneous deletion of delta-sarcoglycan gene promoter and first exon. The muscle disease is progressive and average lifespan is 11 months, because heart slowly dilates towards heart failure.Based on the ability of adeno-associated viral (AAV) vectors to transduce heart together with skeletal muscle following systemic administration, we delivered human delta-sarcoglycan cDNA into male BIO14.6 hamsters by testing different ages of injection, routes of administration and AAV serotypes. Body-wide restoration of delta-SG expression was associated with functional reconstitution of the sarcoglycan complex and with significant lowering of centralized nuclei and fibrosis in skeletal muscle. Motor ability and cardiac functions were completely rescued. However, BIO14.6 hamsters having less than 70% of fibers recovering sarcoglycan developed cardiomyopathy, even if the total rescued protein was normal. When we used serotype 2/8 in combination with serotype 2/1, lifespan was extended up to 22 months with sustained heart function improvement.Our data support multiple systemic administrations of AAV as a general therapeutic strategy for clinical trials in cardiomyopathies and muscle disorders

Tumor Necrosis Factor Receptor SF10A (TNFRSF10A) SNPs Correlate With Corticosteroid Response in Duchenne Muscular Dystrophy

Background Duchenne muscular dystrophy (DMD) is a rare and severe X-linked muscular dystrophy in which the standard of care with variable outcome, also due to different drug response, is chronic off-label treatment with corticosteroids (CS). In order to search for SNP biomarkers for corticosteroid responsiveness, we genotyped variants across 205 DMD-related genes in patients with differential response to steroid treatment. Methods and Findings We enrolled a total of 228 DMD patients with identified dystrophin mutations, 78 of these patients have been under corticosteroid treatment for at least 5 years. DMD patients were defined as high responders (HR) if they had maintained the ability to walk after 15 years of age and low responders (LR) for those who had lost ambulation before the age of 10 despite corticosteroid therapy. Based on interactome mapping, we prioritized 205 genes and sequenced them in 21 DMD patients (discovery cohort or DiC = 21). We identified 43 SNPs that discriminate between HR and LR. Discriminant Analysis of Principal Components (DAPC) prioritized 2 response-associated SNPs in theTNFRSF10Agene. Validation of this genotype was done in two additional larger cohorts composed of 46 DMD patients on corticosteroid therapy (validation cohorts or VaC1), and 150 non ambulant DMD patients and never treated with corticosteroids (VaC2). SNP analysis in all validation cohorts (N= 207) showed that the CT haplotype is significantly associated with HR DMDs confirming the discovery results. Conclusion We have shown that TNFRSF10A CT haplotype correlates with corticosteroid response in DMD patients and propose it as an exploratory CS response biomarker

Organic waste biorefineries: looking towards implementation

The concept of biorefinery expands the possibilities to extract value from organic matter in form of either bespoke crops or organic waste. The viability of biorefinery schemes depends on the recovery of higher-value chemicals with potential for a wide distribution and an untapped marketability. The feasibility of biorefining organic waste is enhanced by the fact that the biorefinery will typically receive a waste management fee for accepting organic waste. The development and implementation of waste biorefinery concepts can open up a wide array of possibilities to shift waste management towards higher sustainability. However, barriers encompassing environmental, technical, economic, logistic, social and legislative aspects need to be overcome. For instance, waste biorefineries are likely to be complex systems due to the variability, heterogeneity and low purity of waste materials as opposed to dedicated biomasses. This article discusses the drivers that can make the biorefinery concept applicable to waste management and the possibilities for its development to full scale. Technological, strategic and market constraints affect the successful implementations of these systems. Fluctuations in waste characteristics, the level of contamination in the organic waste fraction, the proximity of the organic waste resource, the markets for the biorefinery products, the potential for integration with other industrial processes and disposal of final residues are all critical aspects requiring detailed analysis. Furthermore, interventions from policy makers are necessary to foster sustainable bio-based solutions for waste management

Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development.

Mutations in the thyroid hormone receptor α 1 gene (THRA) have recently been identified as a cause of intellectual deficit in humans. Patients present with structural abnormalities including microencephaly, reduced cerebellar volume and decreased axonal density. Here, we show that directed differentiation of THRA mutant patient-derived induced pluripotent stem cells to forebrain neural progenitors is markedly reduced, but mutant progenitor cells can generate deep and upper cortical layer neurons and form functional neuronal networks. Quantitative lineage tracing shows that THRA mutation-containing progenitor cells exit the cell cycle prematurely, resulting in reduced clonal output. Using a micropatterned chip assay, we find that spatial self-organization of mutation-containing progenitor cells in vitro is impaired, consistent with down-regulated expression of cell-cell adhesion genes. These results reveal that thyroid hormone receptor α1 is required for normal neural progenitor cell proliferation in human cerebral cortical development. They also exemplify quantitative approaches for studying neurodevelopmental disorders using patient-derived cells in vitro.NIHR Cambridge Biomedical Centr