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Abstract Solanine (SOL) and chaconine (CHA) are glycoalkaloids (GAs) produced mainly by Solanum plants. These plant secondary metabolites affect insect metabolism; thus, they have the potential to be applied as natural plant protection products. However, it is not known which GA concentration induces physiological changes in animals. Therefore, the aim of this study was to perform a quantitative analysis of SOL and CHA in the larvae of Tenebrio molitor using LC‒MS to assess how quickly they are eliminated or metabolised. In this experiment, the beetles were injected with 2 μL of 10−5 M SOL or CHA solution, which corresponds to a dosage range of 0.12–0.14 ng/mg body mass. Then, 0.5, 1.5, 8, and 24 h after GA application, the haemolymph (H), gut (G), and the remainder of the larval body (FB) were isolated. GAs were detected in all samples tested for 24 h, with the highest percentage of the amount applied in the FB, while the highest concentration was measured in the H sample. The SOL and CHA concentrations decreased in the haemolymph over time, while they did not change in other tissues. CHA had the highest elimination rate immediately after injection, while SOL slightly later. None of the GA hydrolysis products were detected in the tested samples. One possible mechanism of the detoxification of GAs may be oxidation and/or sequestration. They may be excreted by Malpighian tubules, with faeces or with cuticles during moulting. The results presented are significant because they facilitate the interpretation of studies related to the effects of toxic substances on insect metabolism.

Abstract This study explores the seismotectonics of Kachchh in western India, a region with a low-to-moderate strain rate and a history of significant earthquakes, notably the 1819, Mw 7.8 Allah Bund, and the 2001, Mw 7.6 Bhuj. Despite its substantial seismic risk, comprehensive studies on Kachchh’s seismogenic sources are scarce. This is attributed to the concealed nature of active structures, hindering definitive age constraints in paleoseismological research. Our research comprises a detailed paleoseismic analysis of the north-verging, reverse Jhura Fault underlying the Jhura anticline, a segment of the Kachchh Mainland Fault. This fault segment shows evidence of surface-rupturing earthquakes in the area south of the Great Rann of Kachchh. The investigation reveals three paleoseismic events: Event I before 9.72 ka B.P., Event II between 8.63–8.20 ka B.P., and Event III between 6.20–6.09 ka B.P. The elapsed time since the last event on this fault is > 8000 years, suggesting that the area is exposed to a significant earthquake hazard. This highlights the need for more precise characterization of individual seismogenic sources for future earthquake preparedness.

Abstract Background Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of skin and several internal organs, including lungs. Macrophages are the main cells involved in the immune-inflammatory damage of skin and lungs, and alternatively activated (M2) macrophages seem to have a profibrotic role through the release of profibrotic cytokines (IL10) and growth factors (TGFβ1). Nintedanib is a tyrosine kinase inhibitor targeting several fibrotic mediators and it is approved for the treatment of SSc-related interstitial lung disease (ILD). The study aimed to evaluate the effect of nintedanib in downregulating the profibrotic M2 phenotype in cultured monocyte-derived macrophages (MDMs) obtained from SSc-ILD patients. Methods Fourteen SSc patients, fulfilling the 2013 ACR/EULAR criteria for SSc, 10 SSc patients affected by ILD (SSc-ILD pts), 4 SSc patients non affected by ILD (SSc pts no-ILD), and 5 voluntary healthy subjects (HSs), were recruited at the Division of Clinical Rheumatology-University of Genova, after obtaining Ethical Committee approval and patients’ informed consent. Monocytes were isolated from peripheral blood, differentiated into MDMs, and then maintained in growth medium without any treatment (untreated cells), or treated with nintedanib (0.1 and 1µM) for 3, 16, and 24 h. Gene expression of macrophage scavenger receptors (CD204, CD163), mannose receptor-1 (CD206), Mer tyrosine kinase (MerTK), identifying M2 macrophages, together with TGFβ1 and IL10, were evaluated by quantitative real-time polymerase chain reaction. Protein synthesis was investigated by Western blotting and the level of active TGFβ1 was evaluated by ELISA. Statistical analysis was carried out using non-parametric Wilcoxon test. Results Cultured untreated SSc-ILD MDMs showed a significant increased protein synthesis of CD206 (p

Background: Previous studies have shown that parents demand for information on vaccinations is universal. Nonetheless, parental knowledge demonstrated mixed results in vaccination intention, attitude, uptake, or confidence. In contrast, risk perception is a consistent predictor of vaccination-related outcomes. Objective: This study aimed to establish risk perception as a mediator between vaccination knowledge and intention. Method: Using a multistage random sampling technique, a cross-sectional survey was conducted with expectant mothers from maternity and child health clinics in the districts of Petaling, Klang, Gombak, and Hulu Langat. 416 respondents answered the self-administered questionnaire. Data was analysed using SPSS version 27 for descriptive statistics and Amos version 27 with bootstrapping procedure for mediation analysis. Results: Vaccination knowledge predicted risk perception [std β = 0.743, p = 0.036], risk perception predicted vaccination intention [std β = 0.934, p = 0.006], and risk perception fully mediate the relationship between vaccination knowledge and intention [std β = 0.694, p = 0.016]. The mediation model showed satisfactory fit indices: χ2/df (2.898), comparative fit index 0.946, Tucker-Lewis index 0.939, and root mean squared error of approximation 0.061. Conclusion: The goal of educational interventions is to increase vaccination intention by addressing vaccine information that influences both subjective and objective risk perception.

This article aims to discuss the criteria for choosing school principals in eleven municipalities in Tocantins, based on Law nº 14,113, of December 25, 2020, which regulates the Fund for the Maintenance and Development of Basic Education and the Valuation of Education Professionals (Fundeb) which establishes the distribution of the Complementary Value Student Year Result (VAAR) and its conditionalities to public education networks. The investigation was based on the historical-dialectical materialist perspective, with documentary and bibliographical research and revealed that the criteria of merit and performance adopted by the education systems weaken the effectiveness of the principles of democratic management.

Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: “vitamin D, muscle, rheumatic diseases.” Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020–2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold.

Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor, containing GBM stem cells (GSCs) that contribute to therapeutic resistance and relapse. Exposing potential GSC vulnerabilities may provide therapeutic strategies against GBM. Here, we interrogated the role of adenosine-to-inosine (A-to-I) RNA editing mediated by adenosine deaminase acting on RNA 1 (ADAR1) in GSCs and found that both ADAR1 and global RNA editomes were elevated in GSCs compared with normal neural stem cells. ADAR1 inactivation or blocking of the upstream JAK/STAT pathway through TYK2 inhibition impaired GSC self-renewal and stemness. Downstream of ADAR1, RNA editing of the 3'-UTR of GM2A, a key ganglioside catabolism activator, proved to be critical, as interference with ganglioside catabolism and disruption of ADAR1 showed a similar functional impact on GSCs. These findings reveal that RNA editing links ganglioside catabolism to GSC self-renewal and stemness, exposing a potential vulnerability of GBM for therapeutic intervention.

Este artigo tem como objetivo discutir a institucionalização do ICMS Educacional na região amazônica aprovado na Emenda Constitucional nº 108/2020 que regulamenta o Fundo de Manutenção e Desenvolvimento da Educação Básica e de Valorização dos Profissionais da Educação (Fundeb), a qual estabelece discricionariedade dos estados para elaborarem os critérios de redistribuição da cota parte do ICMS aos municípios. A investigação se assentou na perspectiva materialista histórico-dialética, com pesquisa documental e bibliográfica e revelou que os critérios adotados pelos estados estão relacionados ao desempenho dos estudantes nas avaliações de larga escala, com inovações por parte do estado do Tocantins que considerou a institucionalização do Sistema de Ensino/Educação como uma condicionante. Conclui-se que o ICMS Educacional pode contribuir para uma política de ranqueamento e de meritocracia e de ampliação das desigualdades educacionais.

ABSTRACTThis paper presents a novel geodiversity map of the Abruzzo, Lazio, and Molise National Park (Central Italy). The Park exhibits a wide range of geological-geomorphological environments of great scientific and touristic interest, offering unique landscapes and wild nature frequented by visitors year-around. All these features reflect a marked geodiversity and a valuable geoheritage, requiring protection and valorization activities. The geodiversity map that we present was realized following an integrated methodological approach, which includes and combines geological-geomorphological features, geoheritage elements, data from Park archives, and new field-based observations. In this framework, the map serves as a key outreach tool for the dissemination of the geological information of the area and for the promotion of its geodiversity through a modern, sustainable, and environmentally aware tourism in an highly frequented protected area.

ABSTRACTWe present the bathy-morphological map at a scale of 1: 50,000 of the area around the submerged Ferdinandea Island, the ‘Neverland’ of the Sicily Channel (central Mediterranean Sea). We investigate an area of 100 km2, between 10 and 350 m, which is part of a triangular morphological high, 360 km2 wide, representing the SE-wards prolongation of the Adventure Bank. The study is based on the morphometric analysis based on high resolution multibeam, and sub-bottom CHIRP profiles collected in 2015. The area around the remains of Ferdinandea Island is morphologically shaped by the interplay between volcanic, tectonic, fluid seepage, and oceanographic processes. Since the study area is considered a hot spot of biodiversity affected by maritime traffic (especially in Ferdinandea Channel) and hosting communication pipelines, this map provides insights both for habitat mapping purposes and preliminary marine geohazard assessment due to the occurrence of historically active submarine volcanoes, pockmarks, and mass transport deposits.

ABSTRACTWe present a new 1:25,000-scale geological map of the lower Belice River valley, the area struck by the M > 5.0 devastating 1968 seismic sequence, whose seismic source and seismotectonic framework are still controversial. The map, utilizing dating methods and traditional field survey approaches integrated by high-resolution topography, provides an unprecedented detail and precision on the spatial distribution and on the compressional growth geometries of the prominent sedimentary sequence. This map, supported by the first recognition of an on-shore Chibanian-Calabrian deposition and by identifying a flight of marine terraces, offers new insights on the long-lasting syn-depositional tectonic forces up to late-Pleistocene-Holocene times. Such tectonic forces may take part in the regional ongoing deformational phase, prompting detailed studies on the potential seismic sources affecting the area.

ABSTRACTThe coastal landscape of the Kachchh Upland (KU) region (NW-India) changed over the last few thousand years from a shallow marine gulf to a salty desert (1-4 meters asl). In this area, bordered to the south by the Northern Hill Range (NHR), the tectonic-climatic interaction triggered the sea level fall from +2/4 m circa (6000-2000 BP) to zero. An ancient river pattern deposited a tidally regulated delta area during the sea level fall that stopped 2000-3000 years ago due to tectonic activity and a dry climate.Deltaic-alluvial fans (DAF) in front of the NHR suggest that the KU's tectonic activity led to fast landscape evolution. We explored such drastic changes by integrating scientific information from a multidisciplinary literature review, identifying terraces and DAFs, and inferring faults through landform recognition, quantitative morphometry, and field surveys. Our interpretation, summarized in a map, provides new information on active processes along the NHR.

ABSTRACTWe present and discuss the results of a geomorphological and geological study aimed at reconstructing the Plio-Quaternary evolution of the NW Sicily coastal belt , a low strain rate region in the central Mediterranean Sea.We performed morphometric and field analysis of Quaternary marine terraces extracting more than 300 shoreline location points subdivided into six orders. The obtained dataset was validate by investigating the morphological changes along topographic profiles and comparing the extracted locations and elevations with the stratigraphic boundaries in the Plio-Quaternary units.We distinguished two contiguous coastal sectors characterized by different paleo-shoreline elevations and Plio-Quaternary evolution, whose estimated uplift rates fit well with the well-known, regional eastward uplift rate increase along the Northern Sicilian continental margin.Obtained results, summarized in a geomorphological map and a morpho-evolutionary model, provide new valuable data to characterize the active deformation processes and the seismotectonic setting in this critical sector of the Africa-Europe plate boundary.

Objectives Glucocorticosteroids (GCs) are the most used anti-inflammatory and immunosuppressive drugs due to their effectiveness in managing pain and disease modification in many immune-inflammatory rheumatic diseases (IRDs). However, their use is limited because of adverse effects (AEs). Material and methods The authors analyzed recent studies, including randomized controlled trials (RCTs), observational, translational studies and systematic reviews, providing an in-depth viewpoint on the benefits and drawbacks of GC use in rheumatology. Results Glucocorticosteroids are essential in managing life-threatening autoimmune diseases and a cornerstone in many IRDs given their swift onset of action, necessary in flares. Several RCTs and meta-analyses have demonstrated that when administered over a long time and on a low-dose basis, GC can slow the radiographic progression in early rheumatoid arthritis (RA) patients by at least 50%, satisfying the conventional definition of a disease-modifying anti-rheumatic drug (DMARD). In the context of RA treatment, the use of modified-release prednisone formulations at night may offer the option of respecting circadian rhythms of both inflammatory response and HPA activation, thereby enabling low-dose GC administration to mitigate nocturnal inflammation and prolonged morning fatigue and joint stiffness. Long-term GC use should be individualized based on patient characteristics and minimized due to their potential AEs. Their chronic use, especially at medium/high dosages, might cause irreversible organ damage due to the burden of metabolic systemic effects and increased risk of infections. Many international guidelines recommend tapering/withdrawal of GCs in sustained remission. Treat-to-target (T2T) strategies are critical in setting targets for disease activity and reducing/discontinuing GCs once control is achieved. Conclusions Glucocorticosteroids’ use in treating IRDs should be judicious, focused on minimizing use, tapering and discontinuing treatment, when possible, to improve long-term safety. Glucocorticosteroids remain part of many therapeutic regimens, particularly at low doses, and elderly RA patients, especially with associated chronic comorbidities, may benefit from long-term low-dose GC treatment. A personalized GC therapy is essential for optimal long-term outcomes.

Electrospinning is an advanced manufacturing strategy used to create innovative medical devices from continuous nanoscale fibers that is endowed with tunable biological, chemical, and physical properties. Innovative medical patches manufactured entirely by electrospinning are discussed in this paper, using a specific plant-derived formulation “1 Primary Wound Dressing©” (1-PWD) as an active pharmaceutical ingredient (API). 1-PWD is composed of neem oil (Azadirachta indica A. Juss.) and the oily extracts of Hypericum perforatum (L.) flowers, according to the formulation patented by the ENEA of proven therapeutic efficacy as wound dressings. The goal of this work is to encapsulate this API and demonstrate that its slow release from an engineered electrospun patch can increase the therapeutic efficacy for wound healing. The prototyped patch is a three-layer core–shell membrane, with a core made of fibers from a 1-PWD-PEO blend, enveloped within two external layers made of medical-grade polycaprolactone (PCL), ensuring mechanical strength and integrity during manipulation. The system was characterized via electron microscopy (SEM) and chemical and contact angle tests. The encapsulation, release, and efficacy of the API were confirmed by FTIR and LC-HRMS and were validated via in vitro toxicology and scratch assays.

Objective Nailfold videocapillaroscopy (NVC) allows the detection of microvascular damage in autoimmune connective tissue diseases (CTDs). The prevalence of the morphological capillary findings was retrospectively evaluated in a wide cohort of patients with Raynaud’s phenomenon secondary to a CTD at the time of the first single NVC, independently from their current treatment, autoantibody profile and comorbidities.Methods One-thousand-one-hundred-eighty-one patients affected by CTDs were included from 2001 to 2021. The considered CTDs were systemic sclerosis (SSc), undifferentiated connective tissue disease (UCTD), mixed connective tissue disease (MCTD), dermatomyositis (DM), systemic lupus erythematosus, Sjögren’s syndrome and primary antiphospholipid syndrome (aPS). The capillaroscopic parameters were distinguished between scleroderma patterns and non-scleroderma patterns.Results Giant capillaries were significantly more frequent in SSc, DM and MCTD than in other CTDs (respectively, in 73%, 73% and 61% of patients, p

ABSTRACTWe present maps of geohazard features identified across north-western Sicily and Pantelleria in the framework of the Magic project (MArine Geohazard along Italian Coasts), which involved Italian marine geological researchers in 2007-2013. These seafloor features were recognized using high-resolution bathymetry data and rely on the morphological expression of the seafloor and shallow sub-surface processes. The north-western Sicily is a complex continental margin, affected by morphodynamic, depositional, and tectonic processes. The Egadi offshore is controlled by fault escarpments and alternating retreating and progradational processes. Ustica and Pantelleria submerged edifices show the effect of volcanic activity. The Ustica seafloor is interested in volcanic, tectonic, and gravitational instability processes, while the Pantelleria offshore underwent erosive-depositional processes and the effect of bottom currents. Two levels of interpretation are represented: the physiographic domain at a scale of 1:250.000 and the morphological units and morpho-bathymetric elements at a 1:100.000 scale.

ABSTRACTA seismo-tectonic map depicting the principal structural elements of the northern Central American region has been meticulously crafted to characterize the tectonic setting and the individual seismo-tectonic structures of this area. This region is subject to heightened seismic activity, with a large number of medium-high Magnitude occurrences transpiring annually. This map is presented alongside an informative dataset wherein fault trace locations, geometry and kinematics descriptors and other available metadata have been stored. Therefore, the map offers a detailed and up-to-date depiction of the brittle deformation across the region, serving as a valuable resource for a comprehensive assessment of the seismo-tectonic framework. Moreover, the map and its accompanying database summarize fault characteristics for seismic hazard analysts and for civil protection workers, proving to be useful instruments in pinpointing areas where urgent fault research should be conducted from a seismic risk standpoint.

The SARS-CoV-2 infection causing the Coronavirus disease-19 (COVID-19) is characterized by a broad range of clinical manifestations, implicating microvascular damage with endothelial dysfunction and different organ involvement.