A Review on the Applications of Natural Biodegradable Nano Polymers in Cardiac Tissue Engineering.

As cardiac diseases, which mostly result in heart failure, are increasing rapidly worldwide, heart transplantation seems the only solution for saving lives. However, this practice is not always possible due to several reasons, such as scarcity of donors, rejection of organs from recipient bodies, or costly medical procedures. In the framework of nanotechnology, nanomaterials greatly contribute to the development of these cardiovascular scaffolds as they provide an easy regeneration of the tissues. Currently, functional nanofibers can be used in the production of stem cells and in the regeneration of cells and tissues. The small size of nanomaterials, however, leads to changes in their chemical and physical characteristics that could alter their interaction and exposure to stem cells with cells and tissues. This article aims to review the naturally occurring biodegradable nanomaterials that are used in cardiovascular tissue engineering for the development of cardiac patches, vessels, and tissues. Moreover, this article also provides an overview of cell sources used for cardiac tissue engineering, explains the anatomy and physiology of the human heart, and explores the regeneration of cardiac cells and the nanofabrication approaches used in cardiac tissue engineering as well as scaffolds.

In Search for an Ionic Liquid with the Best Performance during 210Pb/210Bi Cherenkov Counting in Waters on an LS Counter.

The research presented in this paper aims to investigate the performance of several newly synthesized ionic liquids during 210Pb/210Bi detection in water on a liquid scintillation spectrometer Quantulus 1220 via Cherenkov counting. These experiments have been triggered by the recent reports that certain ionic liquids can act as wavelength shifters, thus significantly increasing the detection efficiency of Cherenkov radiation. The benefit of ionic liquid's addition to the analysed samples is reflected in the detection limit's decrement during 210Pb quantification, which is pertinent considering naturally low levels of 210Pb in aqueous samples. Firstly, it was discovered that ionic liquid, 1-butyl-3-methylimidazolium salicylate, is more efficient than the previously explored 2-hydroxypropylammonium salicylate. Consequently, the impact of a few other ionic liquids on Cherenkov counting efficiency with the same cation group (1-butyl-3-methylimidazolium benzoate, 1-butyl-3-methylimidazolium 3-hydroxybenzoate and 1-butyl-3-methylimidazolium 4-hydroxybenzoate) was also explored to test their potential influence. Molecular simulations have been carried out to reveal which structures of ionic liquids assure wavelength-shifting behavior. The obtained results confirmed that, among the investigated ones, only ionic liquids with the salicylate anion exhibited a wavelength shifting effect.

Correction: Mancini et al. A Novel Strategy for the Assessment of Radon Risk Based on Indicators. Int. J. Environ. Res. Public Health 2021, 18, 8089.

In the original publication [...].

Experimental Studies to Test a Predictive Indoor Radon Model.

The accumulation of the radioactive gas radon in closed environments, such as dwellings, is the result of a quite complex set of processes related to the contribution of different sources. As it undergoes different physical mechanisms, all occurring at the same time, models describing the general dynamic turns out to be difficult to apply because of the dependence on many parameters not easy to measure or calculate. In this context, the authors developed, in a previous work, a simplified approach based on the combination of a physics-mathematical model and on-site experimental measurements. Three experimental studies were performed in order to preliminarily test the goodness of the model to simulate indoor radon concentrations in closed environments. In this paper, an application on a new experimental site was realized in order to evaluate the adaptability of the model to different house typologies and environmental contexts. Radon activity measurements were performed using a portable radon detector and results, showing again good performance of the model. Results are discussed and future efforts are outlined for the refining and implementation of the model into software.

Yesterday is history, tomorrow is a mystery: An eye-tracking investigation of the processing of past and future time reference during sentence reading.

The ability to think about nonpresent time is a crucial aspect of human cognition. Both the past and future imply a temporal displacement of an event outside the "now." They also intrinsically differ: The past refers to inalterable events; the future to alterable events, to possible worlds. Are the past and future processed similarly or differently? In this study, we addressed this question by investigating how Spanish speakers process past/future time reference violations during sentence processing, while recording eye movements. We also investigated the role of verbs (in isolation; within sentences) and adverbs (deictic; nondeictic) during time processing. Existing accounts propose that past processing, which requires a link to discourse, is more complex than future processing, which-like the present-is locally bound. Our findings show that past and future processing differs, especially at early stages of verb processing, but this difference is not limited to the presence/absence of discourse linking. We found earlier mismatch effects for past compared to future time reference in incongruous sentences, in line with previous studies. Interestingly, it took longer to categorize the past than the future tense when verbs were presented in isolation. However, it took longer to categorize the future than the past when verbs were presented in congruous sentences, arguably because the future implies alterable worlds. Finally, temporal adverbs were found to play an important role in reinspection and reanalysis triggered by the presence of undefined time frames (nondeictic adverbs) or incongruences (mismatching verbs). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Maintenance cost in the processing of subject-verb dependencies.

Although research in sentence comprehension has suggested that processing long-distance dependencies involves maintenance between the elements that form the dependency, studies on maintenance of long-distance subject-verb (SV) dependencies are scarce. The few relevant studies have delivered mixed results using self-paced reading or phoneme-monitoring tasks. In the current study, we used eye tracking during reading to test whether maintaining a long-distance SV dependency results in a processing cost on an intervening adverbial clause. In Experiment 1, we studied this question in Spanish and found that both go-past reading times and regressions out of an adverbial clause to the previous regions were significantly increased when the clause interrupts a SV dependency compared to when the same clause doesn't interrupt this dependency. We then replicated these findings in English (Experiment 2), observing significantly increased go-past reading times on a clause interrupting a SV dependency. The current study provides the first eye-tracking data showing a maintenance cost in the processing of SV dependencies cross-linguistically. Sentence comprehension models should account for the maintenance cost generated by SV dependency processing, and future research should focus on the nature of the maintained representation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Novel Strategy for the Assessment of Radon Risk Based on Indicators.

Among the physical pollutants affecting indoor air, the radioactive gas radon may turn out to be the most hazardous. Health effects related to radon exposure have been investigated for several decades, providing major scientific evidence to conclude that chronic exposures can cause lung cancer. Additionally, an association with other diseases, such as leukemia and cancers of the extra-thoracic airways, has been advanced. The implementation of a strategy to reduce the exposure of the population and minimize the health risk, according to the European Directive 59/2013/Euratom on ionizing radiations, is a new challenge in public health management. Starting from an understanding of the general state-of-the-art, a critical analysis of existing approaches has been conducted, identifying strengths and weaknesses. Then, a strategy for assessing the radon exposure of the general population, in a new comprehensive way, is proposed. It identifies three main areas of intervention and provides a list of hazard indicators and operative solutions to control human exposure. The strategy has been conceived to provide a supporting tool to authorities in the introduction of effective measures to assess population health risks due to radon exposure.

The Processing of Spanish Article-Noun Gender Agreement by Monolingual and Bilingual Toddlers.

We assessed monolingual Spanish and bilingual Spanish-Basque toddlers' sensitivity to gender agreement in correct vs. incorrect Spanish noun phrases (definite article + noun), using a spontaneous preference listening paradigm. Monolingual Spanish-learning toddlers exhibited a tendency to listen longer to the grammatically correct phrases (e.g., la casa; "the house"), as opposed to the incorrect ones (e.g., *el casa). This listening preference toward correct phrases is in line with earlier results obtained from French monolingual 18-month-olds (van Heugten & Christophe, 2015). Bilingual toddlers in the current study, however, tended to listen longer to the incorrect phrases. Basque was not a source of interference in the bilingual toddler's input as Basque does not instantiate grammatical gender agreement. Overall, our results suggest that both monolingual and bilingual toddlers can distinguish between the correct and incorrect phrases by 18 months of age; however, monolinguals and bilinguals allocate their attention differently when processing grammatically incorrect forms.

Alpha Spectrometry of Radon Short-Lived Progeny in Drinking Water and Assessment of the Public Effective Dose: Results from the Cilento Area, Province of Salerno, Southern Italy.

Radon is a naturally occurring radioactive gas present in the hydrosphere, lithosphere and atmosphere abundantly. Its ionizing radiation provides the largest human internal exposure by inhalation and ingestion to natural sources, constituting a serious health hazard. The contribution to total exposure is mainly due to inhalation, as ingestion by food or drinking water is typically very small. However, because of public health concerns, the contributions from all these sources are limited by regulations and remedial action should be taken in the event that the defined threshold values are overcome. In this paper, the first campaign of measurements to control the radon activity concentration in drinking water from public water supplies in the province of Salerno, south Italy, is described. The results represent a main reference for the area, as it was never investigated before. The purpose of this survey was to contribute to data compilation concerning the presence of radon-222 in groundwater in the Campania region and to determine the associated risk for different age groups. The maximum radon activity concentrations and the related total annual public effective dose turned out to be lower than the threshold values (100 Bq/l and 0.1 mSv/y, respectively) indicated by international guidelines and the national regulation, showing that the health risks for public consumption can be considered negligible.

Who are you talking to? The role of addressee identity in utterance comprehension.

Experimental evidence suggests that speaker and addressee quickly adapt to each other from the earliest moments of sentence processing, and that interlocutor-related information is rapidly integrated with other sources of nonpragmatic information (e.g., semantic, morphosyntactic, etc.). These findings have been taken as support for one-step models of sentence comprehension. The results from the present event-related potential study challenge this theoretical framework providing a case where discourse level information is integrated only at a late stage of processing, when morphosyntactic analysis has been already initiated. We considered the case of Basque allocutive agreement, where information about addressee gender is encoded in verbal inflection. Two different types of Basque grammatical violations were presented together with the corresponding control conditions: one could be detected based on a morphosyntactic mismatch (person agreement violation), while the other could be detected only if the addressee's gender was considered (allocutive violation). Morphosyntactic violations elicited greater N400 effects followed by P600 effects, while allocutive violations elicited only P600 effects. These results provide new constraints to one-step accounts as they represent a case where speakers do not immediately adjust to the addressee's perspective. We propose that the relevance of discourse-level information might be a crucial variable to reconcile the dichotomy between one- and two-step models.

Agreement and illusion of disagreement: An ERP study on Basque.

Agreement is a syntactic relation involving a controller (e.g., a noun) and a target with matching inflectional morphology (e.g., a verb). Across languages, electrophysiological studies consistently report that the presence of a mismatch yields late positive effects (P600), often preceded by early negativities. The current study focuses on person agreement in Basque to investigate whether online processing routines are modulated by the relative semantic prominence of nominal and verbal person features. In an event-related potentials experiment in Basque, we manipulated the semantic markedness of nominal and verbal person features, creating 1st (marked) and 3rd (unmarked) person correct and incorrect sentences [Japoniarrok1pleuskara ikasi dugu1pl/*dute3plgustora (We Japanese have1pl/*3pl learn Basque with pleasure); Japoniarrek3pleuskara ikasi dute3pl/*dugu1pl gustora (The Japanese have3pl/*1pl learnt Basque with pleasure)]. Both mismatches elicited an N400 effect, but only marked 1st person mismatches (Japoniarrok1pl … *dute3.pl) generated a P600, suggesting that (i) mismatches with unmarked 3rd person subjects (Japoniarrek3.pl… *dugu1.pl) are not treated as outright violations; (ii) the emergence of late positive effects is sensitive to fine-grained discourse information. Overall, these results call for a revision in the analysis of agreement relations from a theoretical and a processing perspective.

Functionalized liposomes and phytosomes loading Annona muricata L. aqueous extract: Potential nanoshuttles for brain-delivery of phenolic compounds.

BACKGROUND: Multi-target drugs have gained significant recognition for the treatment of multifactorial diseases such as depression. Under a screening study of multi-potent medicinal plants with claimed antidepressant-like activity, the phenolic-rich Annona muricata aqueous extract (AE) emerged as a moderate monoamine oxidase A (hMAO-A) inhibitor and a strong hydrogen peroxide (H2O2) scavenger. PURPOSE: In order to protect this extract from gastrointestinal biotransformation and to improve its permeability across the blood-brain barrier (BBB), four phospholipid nanoformulations of liposomes and phytosomes functionalized with a peptide ligand promoting BBB crossing were produced. METHODS: AE and nanoformulations were characterized by HPLC-DAD-ESI-MSn, HPLC-DAD, spectrophotometric, fluorescence and dynamic light scattering methods. Cytotoxicity and permeability studies were carried out using an in vitro transwell model of the BBB, composed of immortalized human microvascular endothelial cells (hCMEC/D3), and in vitro hMAO-A inhibition and H2O2 scavenging activities were performed with all samples. RESULTS: The encapsulation/binding of AE was more efficient with phytosomes, while liposomes were more stable, displaying a slower extract release over time. In general, phytosomes were less toxic than liposomes in hCMEC/D3 cells and, when present, cholesterol improved the permeability across the cell monolayer of all tested nanoformulations. All nanoformulations conserved the antioxidant potential of AE, while phosphatidylcholine interfered with MAO-A inhibition assay. CONCLUSIONS: Overall, phytosome formulations registered the best performance in terms of binding efficiency, enzyme inhibition and scavenging activity, thus representing a promising multipotent phenolic-rich nanoshuttle for future in vivo depression treatment.

Tracing the interplay between syntactic and lexical features: fMRI evidence from agreement comprehension.

The current fMRI study was designed to investigate whether the processing of different gender-related cues embedded in nouns affects the computation of agreement dependencies and, if so, where this possible interaction is mapped in the brain. We used the Spanish gender agreement system, which makes it possible to manipulate two different factors: the agreement between different sentence constituents (i.e., by contrasting congruent versus incongruent determiner-noun pairs) and the formal (i.e., orthographical/morphological) and/or lexical information embedded in the noun -i.e., by contrasting transparent (e.g., libromasc. [book]; lunafem. [moon]) and opaque nouns (e.g., lápizmasc. [pencil]; vejezfem. [old age]). Crucially, these data illustrated, for the first time, how the network underlying agreement is sensitive to different gender-to-ending cues: different sources of gender information associated with nouns affect the neural circuits involved in the computation of local agreement dependencies. When the gender marking is informative (as in the case of transparent nouns), both formal and lexical information is used to establish grammatical relations. In contrast, when no formal cues are available (as in the case of opaque nouns), gender information is retrieved from the lexicon. We demonstrated the involvement of the posterior MTG/STG, pars triangularis within the IFG, and parietal regions during gender agreement computation. Critically, in order to integrate the different available information sources, the dynamics of this fronto-temporal loop change and additional regions, such as the hippocampus, the angular and the supramarginal gyri are recruited. These results underpin previous neuroanatomical models proposed in the context of both gender processing and sentence comprehension. But, more importantly, they provide valuable information regarding how and where the brain's language system dynamically integrates all the available form-based and lexical cues during comprehension.

The ability of liposomes, tailored for blood-brain barrier targeting, to reach the brain is dramatically affected by the disease state.

AIM: To investigate if and how the ability of liposomes, previously designed for Alzheimer's therapy, to reach the brain changes in aging/pathological conditions with respect to the healthy state. METHODS: Biodistribution and pharmacokinetics of liposomes in young or aged healthy mice and in an Alzheimer's mouse model were measured by radiochemical techniques. The expression of brain receptors and structural proteins was evaluated by Western blot. RESULTS: At equal blood levels, the amount and integrity of liposomes in the brain were dramatically lower in Alzheimer's or aged mice, with respect to young animals. These differences are likely attributable to molecular alterations in the brain vasculature. CONCLUSION: Brain alterations in pathology or aging should be considered in the design of drug delivery systems for brain targeting.

Addressee Identity and Morphosyntactic Processing in Basque Allocutive Agreement.

Information about interlocutor identity is pragmatic in nature and has traditionally been distinguished from explicitly coded linguistic information, including mophosyntax. Study of speaker identity in language processing has questioned this distinction, but addressee identity has been less considered. We used Basque to explore how addressee identity is processed during morphosyntactic analysis. In the familiar register hika, Basque has obligatory allocutive agreement, where verbal morphology represents the gender of a non-argument addressee. We manipulated the gender of the allocutive verb and the congruence of addressee gender in conversations between two interlocutors. Items with person agreement manipulations were included as a control comparison. Basque speakers familiar with hika completed speeded acceptability judgments and unspeeded, offline naturalness ratings for each conversation. Results showed a main effect of addressee identity congruence for naturalness ratings, but there was no main effect for addressee identity congruence for reaction times or accuracy in the acceptability judgment. Interactions and correlations with biographical data showed that the effect of congruence was modulated by the gender of the allocutive verb and that hika proficiency was related to participants' performance for the acceptability judgment. These results show an interaction between morphosyntactic and pragmatic information and are the first experimental data of allocutive processing. In comparison, clear effects were seen for the person agreement condition, indicating that person disagreement is more disruptive to processing than addressee identity incongruence. This study has implications for investigation of the role of extralinguistic information in morphosyntactic processing, and suggests that not all such information plays an equal role.

Multifunctional liposomes delay phenotype progression and prevent memory impairment in a presymptomatic stage mouse model of Alzheimer disease.

The failure of clinical trials largely focused on mild to moderate stages of Alzheimer disease has suggested to the scientific community that the effectiveness of Amyloid-ß (Aß)-centered treatments should be evaluated starting as early as possible, well before irreversible brain damage has occurred. Accordingly, also the preclinical development of new therapies should be carried out taking into account this suggestion. In the present investigation we evaluated the efficacy of a treatment with liposomes multifunctionalized for crossing the blood-brain barrier and targeting Aß, carried out on young APP/PS1 Tg mice, taken as a model of pre-symptomatic disease stage. Liposomes were administered once a week to Tg mice for 7months, starting at the age of 5months and up to the age of 12 when they display AD-like cognitive and brain biochemical/anatomical features. The treatment prevented the onset of the long-term memory impairment and slowed down the deposition of brain Aß; at anatomical level, prevented both ventricle enlargement and entorhinal cortex thickness reduction, otherwise occurring in untreated mice. Strikingly, these effects were maintained 3months after treatment discontinuation. An increase of Aß levels in the liver was detected at the end of the treatment, then followed also by reduction of brain Amyloid Precursor Protein and increase of Aß-degrading enzymes. These results suggest that the treatment promotes brain Aß clearance by a peripheral 'sink' effect and ultimately affects Aß turnover in the brain. Worth of note, the treatment was apparently not toxic for all the organs analyzed, in particular for brain, as suggested by the lower brain TNF-α and MDA levels, and by higher level of SOD activity in treated mice. Together, these findings promote a very early treatment with multi-functional liposomes as a well-tolerated nanomedicine-based approach, potentially suitable for a disease-modifying therapy of AD, able to delay or prevent relevant features of the disease.

Disentangling meaning in the brain: Left temporal involvement in agreement processing.

Sentence comprehension is successfully accomplished by means of a form-to-meaning mapping procedure that relies on the extraction of morphosyntactic information from the input and its mapping to higher-level semantic-discourse representations. In this study, we sought to determine whether neuroanatomically distinct brain regions are involved in the processing of different types of information contained in the propositional meaning of a sentence, namely person and number. While person information indexes the role that an individual has in discourse (i.e., the speaker, the addressee or the entity being talked about by speaker and addressee), number indicates its cardinality (i.e., a single entity vs a multitude of entities). An event-related functional magnetic resonance imaging (fMRI) experiment was run using agreement-Correct and Person- and Number-violated sentences in Spanish, to disentangle the processing mechanisms and neural substrates associated with the building of discourse and cardinality representations. The contrast between Person and Number Violations showed qualitative and quantitative differences. A greater response for person compared to number was found in the left middle temporal gyrus (LMTG). However, critically, a posterior-to-anterior functional gradient emerged within this region. While the posterior portion of the LMTG was sensitive to both Person and Number Violations, the anterior portion of this region showed selective response for Person Violations. These results confirm that the comprehension of the propositional meaning of a sentence results from a composite, feature-sensitive mechanism of form-to-meaning mapping in which the nodes of the language network are differentially involved.

Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer's Aß peptide.

Aggregation of amyloid-ß peptide (Aß) is a key event in the pathogenesis of Alzheimer's disease (AD). We investigated the effects of nanoliposomes decorated with the retro-inverso peptide RI-OR2-TAT (Ac-rGffvlkGrrrrqrrkkrGy-NH2) on the aggregation and toxicity of Aß. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of Aß oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of ~1:2000 of liposome-bound RI-OR2-TAT to Aß. PINPs also bound to Aß with high affinity (Kd=13.2-50 nM), rescued SHSY-5Y cells from the toxic effect of pre-aggregated Aß, crossed an in vitro blood-brain barrier model (hCMEC/D3 cell monolayer), entered the brains of C57 BL/6 mice, and protected against memory loss in APPSWE transgenic mice in a novel object recognition test. As the most potent aggregation inhibitor that we have tested so far, we propose to develop PINPs as a potential disease-modifying treatment for AD.