Background Several hemodynamic variables, such as blood pressure, vascular resistance, cardiac output, and heart rate, are regulated, among others, by sympathetic cardiovascular influences. This has ...led many years ago investigators to advance the hypothesis that alterations in the sympathetic modulation of the cardiovascular system may occur in hypertension and related disease. Methods The role of the sympathetic nervous system as promoter and amplifier of the hypertensive state has been examined in a consistent number of studies carried out by making use of sophisticated and sensitive approaches to evaluate adrenergic function, such as the norepinephrine spillover technique and the recording of efferent postganglionic muscle sympathetic-nerve traffic. Results The results of the above-mentioned investigations support the concept that adrenergic activation characterizes essential hypertension, correlating with the clinical severity of the disease. Furthermore, sympathetic cardiovascular influences may favor the hypertensive disease progression, by concurring with other hemodynamic and nonhemodynamic factors at the development of target organ damage. Finally, an adrenergic overdrive of pronounced degree also characterizes hypertension-related cardiovascular and metabolic disease. In several of these clinical conditions, the adrenergic overdrive plays a role in the disease's physiopathology and prognosis. Conclusions The data reviewed in this article provide evidence that sympathetic activation represents a hallmark of the essential hypertensive state. They further show that adrenergic neural factors may participate at the development and progression of the hypertensive state and its complications. This represents the rationale for the use of antihypertensive and, in more in general, cardiovascular drugs capable to exert sympatho-inhibitory effects.
The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin ...modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.
•Interaction of carboxylated polystyrene nanoparticles with copper and algae.•No adsorption of copper ions observed on PS-COOH NPs.•Alteration of PS-COOH NPs surface charge and hydrodynamic diameter ...support eco-corona formation.•PS-COOH food chain transfer plausible due to NPs ability to interact with algal exudates and adhere to algal cell wall.•Additional endpoints and longer exposure scenarios recommended for nanoplastics risk assessment.
Nanoplastics are recognized as able to interact with other pollutants including heavy metals, and with natural organic matter, with implications for the potential risks to biota. We investigated the interaction of carboxylated polystyrene nanoparticles (PS–COOH NPs) with copper (Cu) and algal exudates (EPS) and how such interaction could affect Cu toxicity towards the freshwater microalga Raphidocelis subcapitata. PS–COOH NPs behavior in the presence of Cu and EPS was determined by dynamic light scattering (DLS), while PS–COOH NPs surface interaction with Cu ions and EPS was investigated by fluorimetric analysis. ICP-MS was used to test Cu ion adsorption to PS–COOH NPs in the presence and absence of algae. The interaction between PS–COOH NPs and the algal cell wall was assessed by fluorescence microscopy. Short- and long-term toxicity tests were carried out in parallel to assess the impact of PS–COOH NPs on algal growth. Results showed altered nanoparticle surface charge and hydrodynamic diameter following algal EPS exposure, supporting the hypothesis of a protein corona formation. In contrast, no absorption of Cu ions was observed on PS–COOH NPs, either in the presence or absence of algae. No differences on algal growth inhibition were observed between exposure to Cu only, and to Cu in combination with PS–COOH NPs, in short-term as well as long-term tests. However, after 72 h of exposure, the adsorption of PS-COOH NPs to algal cell walls appeared to correspond to morphological alterations, revealing potential disturbances in the mitotic cycle. Our findings confirm the ability of PS–COOH NPs to interact with EPS as shown for other nanomaterials. Environmentally realistic exposure scenarios are thus needed for evaluating nanoplastic toxicity, as nanoparticles will not maintain their pristine nature once released into natural media. Prolonged exposure and use of different end-points such as cell morphological changes and EPS production seem more reliable for the investigation of nanoplastic/algal cell interactions which can drive food chain transfer of nanoplastics and ultimately toxicity.
The ultrafast motion of electrons and holes after light-matter interaction is fundamental to a broad range of chemical and biophysical processes. We advanced high-harmonic spectroscopy to resolve ...spatially and temporally the migration of an electron hole immediately after ionization of iodoacetylene while simultaneously demonstrating extensive control over the process. A multidimensional approach, based on the measurement and accurate theoretical description of both even and odd harmonic orders, enabled us to reconstruct both quantum amplitudes and phases of the electronic states with a resolution of ∼100 attoseconds. We separately reconstructed quasi–field-free and laser-controlled charge migration as a function of the spatial orientation of the molecule and determined the shape of the hole created by ionization. Our technique opens the prospect of laser control over electronic primary processes.
Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of bone fragility fractures compared to nondiabetic subjects. This increased fracture risk may occur despite normal or even ...increased values of bone mineral density (BMD), and poor bone quality is suggested to contribute to skeletal fragility in this population. These concepts explain why the only evaluation of BMD could not be considered an adequate tool for evaluating the risk of fracture in the individual T2DM patient. Unfortunately, nowadays, the bone quality could not be reliably evaluated in the routine clinical practice. On the other hand, getting further insight on the pathogenesis of T2DM-related bone fragility could consent to ameliorate both the detection of the patients at risk for fracture and their appropriate treatment. The pathophysiological mechanisms underlying the increased risk of fragility fractures in a T2DM population are complex. Indeed, in T2DM, bone health is negatively affected by several factors, such as inflammatory cytokines, muscle-derived hormones, incretins, hydrogen sulfide (H2S) production and cortisol secretion, peripheral activation, and sensitivity. All these factors may alter bone formation and resorption, collagen formation, and bone marrow adiposity, ultimately leading to reduced bone strength. Additional factors such as hypoglycemia and the consequent increased propensity for falls and the direct effects on bone and mineral metabolism of certain antidiabetic medications may contribute to the increased fracture risk in this population. The purpose of this review is to summarize the literature evidence that faces the pathophysiological mechanisms underlying bone fragility in T2DM patients.
The shear modulus G of the sputum obtained by expectoration from cystic fibrosis patients is fundamental to determine the mesh size of the polymeric network pervading the sputum, a parameter related ...to lung functionality. The Akaike criterion revealed that in 55.2% of the examined samples, the best approach (among those considered) to determine G relied on the mechanical spectrum fitting by the generalised Maxwell model with relaxation times scaled by a factor 10. Thus, this approach was adopted to evaluate the mesh size distribution combining G knowledge with the determination of the average magnetic relaxation time (T.sub.2m) of sputum. As G and T.sub.2m determination can be negatively affected by sputum contamination by saliva, whose presence increases T.sub.2m and depresses G, we developed a proper "decontamination" procedure to obtain more reliable T.sub.2m and G estimations (necessary in 21% of the samples). This procedure allowed to strengthen the T.sub.2m correlation with lung functionality evaluated by FEV.sub.1 (normalised air volume emitted in the first second during a spirometry test). Keywords: rheology, low field NMR, cystic fibrosis, shear modulus, mesh size, saliva contamination
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•Rheology and LF-NMR allowed describing the gelation kinetics of CS/β-GP.•T = 30 °C represents a threshold for the gelation process.•It was possible evaluating the time evolution of ...the gel mesh size upon gelation.
This work deals with the effect of temperature on the thermal-gelation process of water solutions containing chitosan β-glycerolphosphate disodium salt hydrate. In particular, the attention is focused on the role played by temperature on the gel final properties, a very important aspect in the frame of drug delivery systems. The study was performed by combining rheology and low field nuclear magnetic resonance, two approaches that revealed to be highly synergic as they can detect different aspects of the developing polymeric network. This study indicates that 30 °C represent a sort of threshold for both the gelation kinetics and the gel final properties. Indeed, above this temperature, gelation kinetics was rapid and yielded to a strong gel. On the contrary, a slow kinetics and a final weak gel occurred below 30 °C. Finally, rheology and low field NMR allowed, independently, evaluating the time evolution of the network mesh size upon gelation.
The impact of nanoplastics using model polystyrene nanoparticles (PS NPs), anionic (PS-COOH) and cationic (PS-NH2), has been investigated on the marine rotifer Brachionus plicatilis, a major ...component of marine zooplanktonic species. The role of different surface charges in affecting PS NP behaviour and toxicity has been considered in high ionic strength media. To this aim, the selected media were standardized reconstituted seawater (RSW) and natural sea water (NSW), the latter resembling more natural exposure scenarios. Hatched rotifer larvae were exposed for 24h and 48h to both PS NPs in the range of 0.5–50μg/ml using PS NP suspensions made in RSW and NSW. No effects on lethality upon exposure to anionic NPs were observed despite a clear gut retention was evident in all exposed rotifers. On the contrary, cationic NPs caused lethality to rotifer larvae but LC50 values resulted lower in rotifers exposed in RSW (LC50=2.75±0.67µg/ml) compared to those exposed in NSW (LC50=6.62±0.87µg/ml). PS NPs showed similar pattern of aggregation in both high ionic strength media (RSW and NSW) but while anionic NPs resulted in large microscale aggregates (Z-average 1109 ± 128nm and 998±67nm respectively), cationic NP aggregates were still in nano-size forms (93.99 ± 11.22nm and 108.3 ± 12.79nm). Both PDI and Z-potential of PS NPs slightly differed in the two media suggesting a role of their different surface charges in affecting their behaviour and stability. Our findings confirm the role of surface charges in nanoplastic behaviour in salt water media and provide a first evidence of a different toxicity in rotifers using artificial media (RSW) compared to natural one (NSW). Such evidence poses the question on how to select the best medium in standardized ecotoxicity assays in order to properly assess their hazard to marine life in natural environmental scenarios.
•PS NP behaviour in seawaters and ecotoxicity on marine zooplankton.•Surface charge and exposure medium as critical factors.•Suitability of natural seawater for resembling more natural exposure scenarios.•How to select the best medium in standardized ecotoxicity assays.
In response to the emerging crisis and growing calls from patients and clinicians for guidance 5, a working group of clinical experts from the International College of Obsessive Compulsive Spectrum ...Disorders (ICOCS) and the Obsessive-Compulsive and Related Disorders Research Network of the European College of Neuropsychopharmacology (OCRN) have produced this consensus statement with the aim of delivering pragmatic guidance at the earliest opportunity to clinicians for managing this complex challenge. Based on the risks associated with exposure and response prevention (ERP) in the pandemic (see below), and uncertainty as to which of the two evidence-based treatments, pharmacotherapy or cognitive behaviour therapy (CBT), represents the most efficacious first line treatment modality 11, pharmacotherapy should be the first option for adults and children with OCD with contamination, washing or cleaning symptoms during the COVID-19 pandemic. Consider A) type of medication; most patients should receive an SSRI, or if not responsive, another SSRI and as a third choice clomipramine (for which an ECG may be required in certain patient groups); Note US Food and Drug Administration "black box" warnings or advice from equivalent national regulatory authorities regarding increased risk in young people and other vulnerable patient groups. Check for adverse effects and be available for any concerns related to "activation" or newly emergent or increased suicidal ideation, which in the young can be mitigated by starting treatment at a low dose and titrating more gradually; B) dosage; if the patient is on a suboptimal dose, consider increasing it, paying attention to any contraindications; C) SSRI-resistance; consider a low dose of adjunctive antipsychotic (aripiprazole, risperidone, quetiapine, olanzapine), especially if a tic is present; D) adherence; ensure the patient is able to obtain an adequate supply and is taking the treatment regularly.
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