Clinical and molecular features and therapeutic perspectives of spinal muscular atrophy with respiratory distress type 1

Spinal muscular atrophy with respiratory distress (SMARD1) is an autosomal recessive neuromuscular disease caused by mutations in the IGHMBP2 gene, encoding the immunoglobulin μ-binding protein 2, leading to motor neuron degeneration. It is a rare and fatal disease with an early onset in infancy in the majority of the cases. The main clinical features are muscular atrophy and diaphragmatic palsy, which requires prompt and permanent supportive ventilation. The human disease is recapitulated in the neuromuscular degeneration (nmd) mouse. No effective treatment is available yet, but novel therapeutical approaches tested on the nmd mouse, such as the use of neurotrophic factors and stem cell therapy, have shown positive effects. Gene therapy demonstrated effectiveness in SMA, being now at the stage of clinical trial in patients and therefore representing a possible treatment for SMARD1 as well. The significant advancement in understanding of both SMARD1 clinical spectrum and molecular mechanisms makes ground for a rapid translation of pre-clinical therapeutic strategies in humans

Combined assessment of fluvial-marine sediment transport to determine the impact of coastal risks.

The study of morphological changes of a river channel, linked to erosion-deposition processes, taking place in the riverbed, is a topic of current interest in relation not only to the morphometric variations of the fluvial features (e.g., active channel width, area of sediment bars) and the sedimentary balance of the whole relative hydrographic basin but also in relation to the role of the sediment load transferred downstream up to the near shore area (Figure 1). These sediments constitute the solid transport that is pushed towards the coast and poured into the sea, representing a crucial sedimentary contribution to the beaches volumetric balance. The quantitative estimate of the volume of this fluvial load is currently achievable through robust approaches such as the morphological method grounded in the continuity principle applied to river sediments. To define the transport rates at selected locations (e.g., the river mouth) over a given time period, the method requires to measure the erosion and sedimentation volumes, which can be calculated using repeated Digital Elevation Models (DEM)and deriving a DEM of Difference (DoD) (Vericat et al., 2017; Capito et al., 2023). The coastal sedimentary balance is function of both the sediment load provided by rivers and the quantity of sediment transported by the longshore currents that move parallel to the coastline. For this reason, it is crucial to assess the impact of coastal erosion considering both the sediment input from the hydrographic basins and the longshore transport. Up to now there are no techniques capable of providing continuous and spatially distributed measurement of this sediment transfer, a fact of considerable interest if we think of the anthropic structures present along the shores, and the coast erosional problems. This study aims to evaluate, at the regional scale, the possibility of borrowing some techniques that are often used in fluvial contexts (e.g., geomorphological approach), to estimate the quantity of sediment that nourishes the coast. This information is essential as a preliminary step for further studies on the sediment transport process, considering, for instance, different climatic scenarios. A measured volume of sediments deposited over a specific time interval can be used to calibrate a physically-based sediment erosion and transport model, such as SMART-SED described by Gatti et al., 2023. Following calibration, the model can be employed to predict future scenarios by considering climate projections. An important aspect will be to assess the transferability of such methodologies taking into consideration the technical limitations (e.g., greater difficulty in acquiring bathymetric data in the submerged environment) and the morphodynamic differences of the two contexts (e.g., partial lack of lateral confinement of flows in the marine environment). Once it is established that meaningful estimates can be obtained, using the two solid transport estimates volumes (river and marine) it could be possible to obtain the budget of sediments that could benefit the near shore. This estimation certainly has a margin of error linked to all the uncertainties processes both in the river and coastal contexts, but it reveals an evaluation of sedimentary tendency of a coastal area: retreat, advancement or stationary. Today the studies of coastal balances certainly not considered the presence of submarine morphologies that favorthe sediments deposition (e.g., submerged bars and terraces) or the sediments removal (e.g., submarine canyons that arise very close to the coast) from near shore environment, significantly influencing the trend of longshore currents. In Italy there are many regions in which submarine canyons are very close to the coasts; these structures can act as collectors of sediments which are swallowed up towards greater depths (Lo Presti et al., 2022). Therefore, the quantitative study of sediment volume available on a near shore environment, linked to the presence of submarine morphologies favorable or not to the removal or stasis of sediments and to the intrinsic characteristic of the beach (e.g., long exposed beach, gulf, pocket beach), it constitutes a means of defining the sediment load that moves along a near shore area and which could influence and define possible scenarios of anthropic damage, as ports and fluvial bridges siltation but above coastal erosion risks

Assessment of Potential Nutrient Release from Phosphate Rock and Dolostone for Application in Acid Soils

This is the accepted manuscript of the following article: Rafael, R. B. A., Fernández-Marcos, M. L., Cocco, S., Ruello, M. L., Weindorf, D. C., Cardelli, V., and Corti, G. (2018). Assessment of Potential Nutrient Release from Phosphate Rock and Dolostone for Application in Acid Soils. Pedosphere 28, 44-58. doi: 10.1016/S1002- 0160(17)60437-5Finding alternative local sources of plant nutrients is a practical, low-cost, and long-term strategy. In this study, laboratory column experiments were conducted in a completely randomized design to evaluate the feasibility of using phosphate rock and dolostone as fertilizers or acid-neutralizing agents for application in tropical acid soils. The dissolution rates of different particle-size fractions (0.063–0.25, 0.25–0.5, and 0.5–2 mm) of both rocks were studied by citric acid solution at pH 4 and 2 and water, with extraction times of 1, 3, 5, 7, 12, 24, 72, 144, 240, and 360 h. The results showed that the dissolution of both rocks depended on the particle size, leaching solution, and extraction time. The dissolution rate of rock-forming minerals increased as the specific surface area increased, corresponding to a decrease in particle size. In all cases, the release kinetics was characterized by two phases: 1) a first stage of rapid release that lasted 24 h and would ensure short-term nutrient release, and 2) a second stage of slow release after 24 h, representing the long-term nutrient release efficiency. Both rocks were suitable as slow-release fertilizers in strongly acid soils and would ensure the replenishment of P, Ca, and Mg. A combination of fine and medium particle-size fractions should be used to ensure high nutrient-release efficiency. Much work could remain to determine the overall impact of considerable amounts of fresh rocks in soilsThis study was mainly supported by the “Applied Research and Multi-sectorial Program” (FIAM) (No. 5.2.1) granted by the Italian Cooperation and Development Agency (ICDA) to the Universidade Eduardo Mondlane. The authors also acknowledge the Polytechnic University of Marche, Italy for the PhD scholarship provided to the first author as well as research funding for this workS

Protein fingerprints of cultured CA3-CA1 hippocampal neurons: comparative analysis of the distribution of synaptosomal and cytosolic proteins

<p>Abstract</p> <p>Background</p> <p>All studies aimed at understanding complex molecular changes occurring at synapses face the problem of how a complete view of the synaptic proteome and of its changes can be efficiently met. This is highly desirable when synaptic plasticity processes are analyzed since the structure and the biochemistry of neurons and synapses get completely reshaped. Because most molecular studies of synapses are nowadays mainly or at least in part based on protein extracts from neuronal cultures, this is not a feasible option: these simplified versions of the brain tissue on one hand provide an homogeneous pure population of neurons but on the other yield only tiny amounts of proteins, many orders of magnitude smaller than conventional brain tissue. As a way to overcome this limitation and to find a simple way to screen for protein changes at cultured synapses, we have produced and characterized two dimensional electrophoresis (2DE) maps of the synaptic proteome of CA3-CA1 hippocampal neurons in culture.</p> <p>Results</p> <p>To obtain 2D maps, hippocampal cultures were mass produced and after synaptic maturation, proteins were extracted following subfractionation procedures and separated by 2D gel electrophoresis. Similar maps were obtained for the crude cytosol of cultured neurons and for synaptosomes purified from CA3-CA1 hippocampal tissue. To efficiently compare these different maps some clearly identifiable reference points were molecularly identified by mass spectrometry and immunolabeling methods. This information was used to run a differential analysis and establish homologies and dissimilarities in these 2D protein profiles.</p> <p>Conclusion</p> <p>Because reproducible fingerprints of cultured synapses were clearly obtained, we believe that our mapping effort could represent a simple tool to screen for protein expression and/or protein localization changes in CA3-CA1 hippocampal neurons following plasticity.</p

COVID-19-Associated Multisystem Inflammatory Syndrome in Children and Cardiovascular Autonomic Control: A Prospective Cohort Study Nine Months after SARS-CoV-2 Infection

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) has emerged as a severe pediatric complication during the SARS-CoV-2 pandemic, with potential long-term cardiovascular repercussions. We hypothesized that heart rate and blood pressure control at rest and during postural maneuvers in MIS-C patients, months after the remission of the inflammatory syndrome, may reveal long-term autonomic dysfunctions. Methods: We assessed 17 MIS-C patients (13 males; 11.9 +/- 2.6 years, m +/- SD) 9 months after acute infection and 18 age- (12.5 +/- 2.1 years) and sex- (13 males) matched controls. Heart rate and blood pressure variability, baroreflex function, and hemodynamic parameters were analyzed in supine and standing postures. Results: MIS-C patients exhibited reduced heart rate variability, particularly in parasympathetic parameters during standing (pNN50+: 6.1 +/- 6.4% in controls, 2.5 +/- 3.9% in MIS-C; RMSSD: 34 +/- 19 ms in controls, 21 +/- 14 ms in MIS-C, p &lt; 0.05), with no interaction between case and posture. Blood pressure variability and baroreflex sensitivity did not differ between groups except for the high-frequency power in systolic blood pressure (3.3 +/- 1.2 mmHg(2) in controls, 1.8 +/- 1.2 mmHg(2) in MIS-C, p &lt; 0.05). The MIS-C group also showed lower diastolic pressure-time indices (DPTI) and systolic pressure-time indices (SPTI), particularly in standing (DPTI: 36.2 +/- 9.4 mmHgs in controls, 29.4 +/- 6.2 mmHgs in MIS-C; SPTI: 26.5 +/- 4.3 mmHgs in controls, 23.9 +/- 2.4 mmHgs in MIS-C, p &lt; 0.05). Conclusions: Altered cardiovascular autonomic control may persist in MIS-C patients with, however, compensatory mechanisms that may help maintain cardiovascular homeostasis during light autonomic challenges, such as postural maneuvers. These results highlight the importance of assessing long-term cardiovascular autonomic control in children with MIS-C to possibly identify residual cardiovascular risks and inform targeted interventions and rehabilitation protocols

Impact of agricultural management on salts accumulation in dryland soils of central Tunisia

Drylands represent about one-third of the global land and mainly occur in Africa and Asia. Because of the arid conditions, dryland soils are characterized by salt accumulation. Although salt-affected soils are unsuitable for agriculture, some arid lands have been cultivated for a long time. However, especially in the last decades, because of the increasingly warmer climatic conditions and human migration toward favorable environments, a progressive abandonment and degradation of drylands has occurred. Therefore, it is necessary to assess the effects of cultivation on saline soils to develop appropriate soil management techniques to ensure their fertility. This work aims to evaluate the evolution of salinization from currently cultivated soils to soils that have been abandoned for different lengths of time in arid areas of central Tunisia. Morphological and physicochemical properties of the studied soils indicated that the cultivation, through irrigation and the presence of soil cover, reduced salt accumulation in the upper soil horizons. Salt leaching towards deeper horizons and depressed evaporation, which reduced capillary rising, maintained electrical conductivity within tolerable values for most crops. Conversely, the abandonment of previously cultivated fields compromised soil fertility, threatening soil conservation and stabilization of agricultural production in the medium to long term

Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives

In the last decade trans-arterial radioembolization has given promising results in the treatment of patients with intermediate or advanced stage hepatocellular carcinoma (HCC), both in terms of disease control and tolerability profile. This technique consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound (usually Yttrium90), and exerts its therapeutic effect through the radiation carried by these microspheres. A careful and meticulous selection of patients is crucial before performing the radioembolization to correctly perform the procedure and reduce the incidence of complications. Radioembolization is a technically complex and expensive technique, which has only recently entered clinical practice and is supported by scant results from phase III clinical trials. Nevertheless, it may represent a valid alternative to transarterial chemoembolization (TACE) in the treatment of intermediate-stage HCC patients, as shown by a comparative retrospective assessment that reported a longer time to progression, but not of overall survival, and a more favorable safety profile for radioembolization. In addition, this treatment has reported a higher percentage of tumor shrinkage, if compared to TACE, for pre-transplant downsizing and it represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume who are not immediately eligible for surgery. Radioembolization might also be a suitable companion to sorafenib in advanced HCC or it can be used as a potential alternative to this treatment in patients who are not responding or do not tolerate sorafenib

Species diversity and distribution of amphibians and reptiles in Sardinia, Italy

Although distribution databases are a dynamic tool, continuously updated, it is important to take "snapshots" of the species distribution over time to promptly identify potential conservation issues. With this work, we provide an update of the distribution of amphibians and reptiles in Sardinia and satellite islands. Data derive from both direct field observations (carried out since 2005 until July 2022) and literature, accounting for over 7000 records: 1416 records of 11 species of amphibians and 5600 records of 18 species of reptiles. Distribution maps (on 10 × 10 km UTM grid) of 29 species are provided in supplementary materials as well as the updated list of the amphibians and reptiles occurring in the circum-Sardinian islands. Most of the meshes were characterized by the presence of 1-3 amphibian species (73%) and 6-8 or 9-11 reptile species (32% with 6-8 species, 30% with 9-11 species). Species abundance was favoured by environmental heterogeneity, and mostly varied in relation to elevation range and edge density

Opening a window on the past: paleo-horizons across Pleistocene and Holocene. Madonna della Grotta, Praia a Mare, Southern Italy

The goal of this study was to identify and characterize three paleo-horizons along a stratigraphic succession embracing sediments from Paleolithic to historic that has been preserved inside a grotto close to the Tyrrhenian Sea in southern Italy. The studied paleo-horizons date back to the transition period between Pleistocene and Holocene, when swift alternations of cold and warm phases profoundly altered the range dynamics of many organisms, including salmonids like Salmo trutta and, consequently, the behavior of the humans that occupied the grotto. Morphological observations and preliminary analysis were run to assess if the paleo-horizons preserved information of the human modified behavior. Results confirmed that one of the three paleo-horizons (Bud horizon, dating back to 10,300 cal YBP) had a strongly affected anthropic origin as it contains the rests of terrestrial (mammals, birds, and snails) and sea food (Salmo trutta and Patella spp.), and showed a hard compaction acquired via hydroconsolidation