Archaeobotanical analysis from the long-term rural settlement of Contrada Castro (Corleone, Palermo): preliminary data

The project ¿Harvesting Memories: Ecology and Archaeology of Monti Sicani landscapes¿ aims to analyse the long-term relationship of landscape dynamics and settlement patterns in a Mediterranean inland of Central-Western Sicily. The project combined different interdisciplinary approaches of vegetation science, landscape ecology, history and archaeology in order to diachronically understand and reconstruct the human- society-environment interactions. From 2017 to 2019 a new rural settlement has been investigated in Contrada Castro (Corleone, Palermo). The excavation in Contrada Castro showed a clear case of long-term occupation of an hill-top site during Late Archaic/Classical age (6 th -5 th c. BC) and the Byzantine and Islamic period (7 th -11 th c. AD). Soils from the archaeological excavation were sampled to obtain evidences about paleo-vegetation and vegetal paleo-diet. Archaeobotanical data (seeds and charcoal remains) represent an informative source in human-environmental dynamics to collect specific data on a small scale in terms of chronology and topography (Hastorf, Popper 1988; Pearsall 2009). Furthermore, presence of edible plants as cereals, pulses and fruit characterize their use as economical resources. Unfortunately, archaeobotanical analyses from archaeological sites in Sicily are still not very common (see http://brainplants.successoterra.net/sites.html). For the reconstruction of the paleo-environment and the use of arboreal resources from the three chronological phases of the site, a total of 239 liters of soils were analysed. Taxonomical identification was made by optical microscopy through the comparison with the reference collection and specific atlases (fig.). More than 400 wood charcoals were observed, about 80% of them was identified. Thanks to comparisons with the current vegetation, so far 8 species have been identified - Quercus cfr. ilex (fig.), Pistacia cfr. terebinthus, Rhamnus alathernus, Fraxinus ornus, Ulmus canescens, Acer cfr. campestris, Ostrya carpinifolia, Populus cf. nigra; identification reached the detail of genus or subfamily in 6 cases - Quercus cf. robur / pubescens, Phillyrea sp., Sorbus sp., Rosacea cfr. Pirus sp. and maybe Moracea. The arboreal vegetation is therefore represented by evergreen oaks, semi- and deciduous oaks, maples, ash trees, associated with riparian species such as elm, poplar and hornbeam, and shrub species such as backthorn, terebinth, sorb, plum. Cultivated species are mostly not represented. Despite the widespread presence of the evergreen oaks in the whole record, differences between the three chronological phases were identified, highlighting a selective use of the wild species present in the area and a specific collection of wood for the hearths. 1) Hastorf C.A., Popper V.F.1988, Current Paleoethnobotany. Analytical Methods and Cultural Interpretations of Archaeological Plant Remains, Chicago. ISBN: 978022631893 2) Pearsall D. M. 2009, Paleoethnobotany: A Handbook of Procedures, Second Edition, Walnut Creek. ISBN-10: 1598744720 3) BRAIN Network, http://brainplants.successoterra.net/sites.htmlFinanciación: beca "Juan de la Cierva-incorporación, IJCI-2017-31494, MINECO), IJCI-2017-31494" y proyecto "Harvesting Memories" de la Universidad de Palermo (financiado por Bona Furtuna LLC)

Oral contraceptives modify DNA methylation and monocyte-derived macrophage function

Background: Fertile women may be encouraged to use contraception during clinical trials to avoid potential drug effects on fetuses. However, hormonal contraception interferes with pharmacokinetics and pharmacodynamics and modifies internal milieus. Macrophages depend on the milieu to which they are exposed. Therefore, we assessed whether macrophage function would be affected by the use of combined oral contraceptives (OCs) and if this influence depended on the androgenic or nonandrogenic properties of progestin. Methods: Healthy adult women were enrolled and stratified into two groups: women who did not use OCs (Fs) and women treated with OCs (FOCs). FOCs were further stratified as a function of androgenic (FOCA+) and non-androgenic (FOCA-) properties of progestins. Routine hematological, biochemical, inflammatory and endothelial dysfunction parameters were measured. Monocyte-derived macrophages (MDMs) were evaluated for the expression and activity of estrogen receptors and androgen receptors, and release of tumor necrosis factor α (TNFα) was measured from unstimulated and lipopolysaccharide-stimulated cells. Results: As is already known, the use of OCs changed numerous parameters: the number of lymphocytes, iron levels, total iron-binding capacity of transferrin, triglycerides, high-density lipoprotein, total cholesterol, and C-reactive protein increased, while prothrombin time and alkaline phosphatase decreased. Hormonal levels also varied: cortisol was higher in FOCs, while luteinizing hormone, folliclestimulating hormone, and testosterone were lower in FOCs. Asymmetric dimethylarginine, an index of endothelial function, was lower in FOC than in Fs, as were cysteine and bilirubin. The androgenic properties of progestins affected the activity of OCs: in particular, white blood cell count, hemoglobin, high-density lipoprotein and calcium were higher in FOCA- than in FOCA+, whereas percentage oxygen saturation and γ-glutamyl transpeptidase were lower in FOCA- than in FOCA+. Importantly, FOCs had a lower global DNA methylation, indicating that OC may have epigenetic effects on gene expression. OC did not modify the expression of androgen receptor but increased estrogen receptor α expression, more considerably in FOCA+, and decreased estrogen receptor β, more considerably in FOCA-. Importantly, the activation state of estrogen receptor β in FOCs was decreased, while estrogen receptor α was not active in either Fs or FOCs. Unstimulated MDMs obtained from FOCs showed higher release of TNFα in comparison with Fs. After lipopolysaccharide stimulation, the release of TNFα was significantly higher in Fs than in FOCs. Conclusions: OC use induced many changes in hematological and plasmatic markers, modifying hormonal levels, endothelial function, inflammation index and some redox state parameters, producing a perturbation of the internal milieu that impacted macrophagic function. In fact, different levels of estrogen receptor expression and release of TNFα were observed in macrophages derived from OC users. Some of the above activities were linked to the androgenic properties of progestin. Even though it is not known whether these effects are reversible, the results indicate that to avoid potential skewing of results only a single type of OC should be used during a single clinical trial.</br

Constrained spherical deconvolution provides evidence of extensive subcortical direct cerebellumbasal ganglia connections in human brain

Traditionally, the basal ganglia (BG) are thought to play a major role in the selection and inhibition of motor commands, while the cerebellum plays a role in tuning and reshaping on-going movement. In the past, the connections between the cerebellum and the cerebral cortex have been considered to be anatomically and functionally distinct from those linking the BG with the cerebral cortex. Evidences from recent anatomical experiments, using retrograde transneuronal transport of rabies virus in macaques, have challenged this old perspective demonstrating disynaptic subcortical pathways that directly link the cerebellum with the BG. Since the application of these techniques to the human brain remains elusive, due to the invasive nature of such methods, whether and to what extent these specific connections between the BG and cerebellum exist in the human brain remains unclear. However, recent developments in Diffusion Magnetic Resonance Imaging (dMRI) and diffusion tractography may allow for non-invasive and in vivo studies of the anatomical substrate of basal ganglia systems. Indeed, in our previous paper we studied the basal ganglia connectome providing strong evidences of a direct connection from cortex to Globus Pallidum (GPe and GPi) [1]. Thirteen normal subjects with no history of any overt neurological and/or psychiatric disorders were examined to test the hypotheses that substantial interactions, at least on the level shown in animal studies, also exist in the human brain. We demonstrated that it is feasible to disclose these cerebellar-subcortical connections by using constrained spherical deconvolution (CSD), an innovative approach which allows a reliable reconstruction of small- and long-fiber pathways, with subvoxel resolution in brain regions with multiple fiber orientations [2]. In particular we found evidences of subthalamic-cerebellar, dentate-thalamo-striatal, dentate-rubral-thalamic, dentate-rubral-pallidal and dentate-nigral connections. In addition to these connections, we found a direct cerebellar-dentate-pallidal connection never reported in literature to our knowledge; we identified and isolated two well-distinct tracts presenting an ipsilateral and contralateral component, converging mainly on the antero-medial part of the globus pallidus

Targeting monocyte chemotactic protein-1 synthesis with bindarit induces tumor regression in prostate and breast cancer animal models

n/

The Metabolomic Profile in Amyotrophic Lateral Sclerosis Changes According to the Progression of the Disease: An Exploratory Study

Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative pathology of the upper or lower motor neuron. Evaluation of ALS progression is based on clinical outcomes considering the impairment of body sites. ALS has been extensively investigated in the pathogenetic mechanisms and the clinical profile; however, no molecular biomarkers are used as diagnostic criteria to establish the ALS pathological staging. Using the source-reconstructed magnetoencephalography (MEG) approach, we demonstrated that global brain hyperconnectivity is associated with early and advanced clinical ALS stages. Using nuclear magnetic resonance (1H-NMR) and high resolution mass spectrometry (HRMS) spectroscopy, here we studied the metabolomic profile of ALS patients’ sera characterized by different stages of disease progression—namely early and advanced. Multivariate statistical analysis of the data integrated with the network analysis indicates that metabolites related to energy deficit, abnormal concentrations of neurotoxic metabolites and metabolites related to neurotransmitter production are pathognomonic of ALS in the advanced stage. Furthermore, analysis of the lipidomic profile indicates that advanced ALS patients report significant alteration of phosphocholine (PCs), lysophosphatidylcholine (LPCs), and sphingomyelin (SMs) metabolism, consistent with the exigency of lipid remodeling to repair advanced neuronal degeneration and inflammatio

Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ

Hypertension affects nearly 20% of the population in Western countries and strongly increases the risk for cardiovascular diseases. In the pathogenesis of hypertension, the vasoactive peptide of the renin-angiotensin system, angiotensin II and its G protein–coupled receptors (GPCRs), play a crucial role by eliciting reactive oxygen species (ROS) and mediating vessel contractility. Here we show that mice lacking the GPCR-activated phosphoinositide 3-kinase (PI3K)γ are protected from hypertension that is induced by administration of angiotensin II in vivo. PI3Kγ was found to play a role in angiotensin II–evoked smooth muscle contraction in two crucial, distinct signaling pathways. In response to angiotensin II, PI3Kγ was required for the activation of Rac and the subsequent triggering of ROS production. Conversely, PI3Kγ was necessary to activate protein kinase B/Akt, which, in turn, enhanced L-type Ca2+ channel–mediated extracellular Ca2+ entry. These data indicate that PI3Kγ is a key transducer of the intracellular signals that are evoked by angiotensin II and suggest that blocking PI3Kγ function might be exploited to improve therapeutic intervention on hypertension

Assessing ChatGPT’s theoretical knowledge and prescriptive accuracy in bacterial infections: a comparative study with infectious diseases residents and specialists

Objectives: Advancements in Artificial Intelligence(AI) have made platforms like ChatGPT increasingly relevant in medicine. This study assesses ChatGPT's utility in addressing bacterial infection-related questions and antibiogram-based clinical cases. Methods: This study involved a collaborative effort involving infectious disease (ID) specialists and residents. A group of experts formulated six true/false, six open-ended questions, and six clinical cases with antibiograms for four types of infections (endocarditis, pneumonia, intra-abdominal infections, and bloodstream infection) for a total of 96 questions. The questions were submitted to four senior residents and four specialists in ID and inputted into ChatGPT-4 and a trained version of ChatGPT-4. A total of 720 responses were obtained and reviewed by a blinded panel of experts in antibiotic treatments. They evaluated the responses for accuracy and completeness, the ability to identify correct resistance mechanisms from antibiograms, and the appropriateness of antibiotics prescriptions. Results: No significant difference was noted among the four groups for true/false questions, with approximately 70% correct answers. The trained ChatGPT-4 and ChatGPT-4 offered more accurate and complete answers to the open-ended questions than both the residents and specialists. Regarding the clinical case, we observed a lower accuracy from ChatGPT-4 to recognize the correct resistance mechanism. ChatGPT-4 tended not to prescribe newer antibiotics like cefiderocol or imipenem/cilastatin/relebactam, favoring less recommended options like colistin. Both trained- ChatGPT-4 and ChatGPT-4 recommended longer than necessary treatment periods (p-value = 0.022). Conclusions: This study highlights ChatGPT's capabilities and limitations in medical decision-making, specifically regarding bacterial infections and antibiogram analysis. While ChatGPT demonstrated proficiency in answering theoretical questions, it did not consistently align with expert decisions in clinical case management. Despite these limitations, the potential of ChatGPT as a supportive tool in ID education and preliminary analysis is evident. However, it should not replace expert consultation, especially in complex clinical decision-making

MYC Rearranged Aggressive B-Cell Lymphomas: A Report on 100 Patients of the Fondazione Italiana Linfomi (FIL)

Supplemental Digital Content is available in the text