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Background: The recently published New Italian version of the Wilkins Rate of Reading Test (standard Italian WRRT) was designed to measure reading speed in repeated-measures designs in research and/or clinical examinations. The test features 15 equivalent 10-line passages made up of unrelated words, adhering to the principles established by the Wilkins Rate of Reading Test in English (original WRRT). Aim: To develop a short Italian version of the WRRT (SI-WRRT), and to determine the equivalence across the new, shorter passages of text. The introduction of 5-line passages, instead of the original 10-line ones, aims to enhance the tool's suitability for the elderly or neuropsychological patients by reducing administration time. Method: The same 15 high-frequency Italian words from the standard Italian WRRT were used to generate 15 5-line passages for the SI-WRRT. Comprehensive eye examination and vision assessment, including the Radner Reading Charts, were performed before the administration of the SI-WRRT. Forty healthy Italian-speaking higher education students read the SI-WRRT passages aloud in random order. Reading speed and accuracy were measured offline from digital recordings of the readings. Equivalence across passages and the effects of practice and fatigue were assessed for reading speed and accuracy, along with test-retest reliability. Results: No significant difference in reading speed was found across 14 out of the 15 passages. In addition, no differences were observed in accuracy, and the error rate was very low. Practice and fatigue effects were minimal for reading speed, whereas they were absent for accuracy. Reading speed, the reference metric for the WRRT, showed moderate-to-good test-retest reliability. Conclusions: Equivalence was confirmed across 14 passages of the SI-WRRT. Therefore, the test may be suitable for examining the elderly or neuropsychological patients, as reading time of the 5-line passages is halved with respect to the standard Italian WRRT. However, the 5-line passages still allow the assessment of prolonged reading. Since one passage was not equivalent, we recommend avoiding the use of random rearrangements of words without formally checking their validity. [ABSTRACT FROM AUTHOR]

Background/Objectives: Horseradish (Armoracia rusticana L.) roots—largely used in traditional medicine for their multiple therapeutic effects—are a rich source of health-promoting phytochemicals. However, their efficacy can be compromised by low chemical stability and poor bioavailability. Incorporation into phospholipid vesicles is often proposed to tackle this problem. Methods: In this study, a hydroalcoholic extract was produced from horseradish roots. The extract was characterized by UPLC-MS and HPLC-PDA and formulated in conventional liposomes and Penetration Enhancer-containing Vesicles (PEVs) for skin application. Results: The obtained nanovesicles were small in size (<100 nm), negatively charged, uni/bilamellar, and with high values of entrapment efficiency (>85%) for the flavonoids identified in the extract. Both the free and the nanoformulated extract showed optimal biocompatibility, measured as the absence of hemolysis of erythrocytes and absence of cytotoxicity in skin cell lines. Furthermore, the nanoformulations displayed antioxidant activity in vitro. Conclusions: The proposed nananoformulations could be exploited to counteract oxidative stress involved in the pathogenesis and progression of numerous skin disorders. [ABSTRACT FROM AUTHOR]

Primary aluminum recycling has been demonstrated to play a pivotal role in sustainable manufacturing. Nevertheless, among all the Life Cycle Assessment (LCA) studies existing in the literature on aluminum products, very few focus on the rolling stage. In this work, LCA of two semi-finished products, plates and coated strips, made of AA8011 aluminum alloy have been carried out. Inventory data were collected by the Laminazione Sottile plant, except for coil coating data for pharmaceutical caps, which were collected in the Italcoat plant. For both semi-finished products, hot rolling and fusion mostly affect the environmental impact of the manufacturing. Moreover, results show that the substitution of virgin primary aluminum with secondary aluminum results in a remarkable minimization of the environmental impact. Indeed, a 50% reduction of primary aluminum results in about a 70% reduction of GWP to produce AA 8011 coated strips. [ABSTRACT FROM AUTHOR]

Background. Very low-calorie ketogenic diets (VLCKD) are an effective weight-loss strategy for obese individuals, reducing risks of liver conditions such as non-alcoholic steatohepatitis and fibrosis. Small extracellular vesicles (sEVs) are implicated in liver fibrosis by influencing hepatic cell phenotypes and contributing to liver damage. This study investigates sEVs derived from serum of 60 obese adults categorized into low fibrosis risk (LR) and intermediate/high fibrosis risk (IHR) groups based on FibroScan elastography (FIB E scores, limit value 8 kPa) and all participants underwent an 8-week VLCKD intervention. Methods. The study examines the impact of these sEVs on fibrosis markers, inflammation, and autophagy in a hepatocyte cell line (HEPA-RG) using bioinformatics, RNA sequencing, lipidomics, RT-PCR, and Western blotting before (T0) and after (T1) VLCKD. Results. sEVs from LR patients post-VLCKD reduced fibrosis related gene expression (e.g., ACTA2) and enhanced proteins associated with regeneration and inflammation (e.g., HDAC6). Conversely, sEVs from IHR patients increased fibrosis and inflammation related gene expression (PIK3CB, AKT1, ACTA2) in hepatocytes, raising concerns about VLCKD suitability for IHR patients. IHR sEVs also decreased expression of HDAC10, HDAC6, HDAC3, MMP19, and MMP2, while increasing modulation of p-AKT, α-SMA, and VIM. Conclusion. These findings underscore the critical role of sEVs in regulating inflammation, remodeling, and hepatic stress responses, particularly in IHR patients, and suggest sEVs could complement instrumental evaluations like FibroScan in fibrosis assessment. [ABSTRACT FROM AUTHOR]

In the original version of this Article, references in the Methods section incorrectly referred to references in the Supplementary References section. The relevant references (now numbered 20, 27, 42, 47, 69-80) have been removed from the Supplementary References section of the Supplementary Information file and added to the References section of the main manuscript, in both the PDF and HTML versions of the Article.

Antipsychotics are the most widely used medications for the treatment of schizophrenia spectrum disorders. While such drugs generally ameliorate positive symptoms, clinical responses are highly variable in terms of negative symptoms and cognitive impairments. However, predictors of individual responses have been elusive. Here, we report a pharmacogenetic interaction related to a core cognitive dysfunction in patients with schizophrenia. We show that genetic variations reducing dysbindin-1 expression can identify individuals whose executive functions respond better to antipsychotic drugs, both in humans and in mice. Multilevel ex vivo and in vivo analyses in postmortem human brains and genetically modified mice demonstrate that such interaction between antipsychotics and dysbindin-1 is mediated by an imbalance between the short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function within the prefrontal cortex. These findings reveal one of the pharmacodynamic mechanisms underlying individual cognitive response to treatment in patients with schizophrenia, suggesting a potential approach for improving the use of antipsychotic drugs.

Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) may increase metabolic rate by promoting thermogenesis, potentially through enhanced fat oxidation and improved insulin. More research is, however, needed to understand this intricate process. In this study, we used 22 lines from the Drosophila Genetic Reference Panel to assess the metabolic rate of virgin female and male flies that were either fed a standard medium or received lisinopril for one week or five weeks. We demonstrated that lisinopril affects the whole-body metabolic rate in Drosophila melanogaster in a genotype-dependent manner. However, the effects of genotypes are highly context-dependent, being influenced by sex and age. Our findings also suggest that lisinopril may increase the Drosophila metabolic rate via the accumulation of a bradykinin-like peptide, which, in turn, enhances cold tolerance by upregulating Ucp4b and Ucp4c genes. Finally, we showed that knocking down Ance, the ortholog of mammalian ACE in Malpighian/renal tubules and the nervous system, leads to opposite changes in metabolic rate, and that the effect of lisinopril depends on Ance in these systems, but in a sex- and age-specific manner. In conclusion, our results regarding D. melanogaster support existing evidence of a connection between ACEI drugs and metabolic rate while offering new insights into this relationship. [ABSTRACT FROM AUTHOR]

PPARγ is one of the three isoforms identified for the peroxisome proliferator-activated receptors (PPARs) and is the receptor for the thiazolidinedione class of anti-diabetic medications including pioglitazone. PPARγ has been long studied for its role in adipogenesis and glucose metabolism, but the discovery of the localization in ventral tegmental area (VTA) neurons opens new vistas for a potential role in the regulation of reward processing and motivated behavior in drug addiction. Here, we demonstrate that activation of PPARγ by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. These effects are associated with a marked reduction of heroin-induced increase in phosphorylation of DARPP-32 protein in the nucleus accumbens (NAc) and with a marked and selective reduction of acute heroin-induced elevation of extracellular dopamine (DA) levels in the NAc shell, as measured by in vivo microdialysis. Through ex vivo electrophysiology in acute midbrain slices, we also show that stimulation of PPARγ attenuates opioid-induced excitation of VTA DA neurons via reduction of presynaptic GABA release from the rostromedial tegmental nucleus (RMTg). Consistent with this finding, site-specific microinjection of pioglitazone into the RMTg but not into the VTA reduced heroin taking. Our data illustrate that activation of PPARγ may represent a new pharmacotherapeutic option for the treatment of opioid addiction.

Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) affecting the gastrointestinal tract that can also cause extra-intestinal complications. Following exposure to the mRNA vaccine BNT162b2 (Pfizer-BioNTech) encoding the SARS-CoV-2 Spike (S) protein, some patients experienced a lack of response to the biological drug Adalimumab and a recrudescence of the disease. In CD patients in progression, resistant to considered biological therapy, an abnormal increase in intestinal permeability was observed, more often with a modulated expression of different proteins such as Aquaporin 8 (AQP8) and in tight junctions (e.g., ZO-1, Claudin1, Claudin2, Occludin), especially during disease flares. The aim of this study is to investigate how the SARS-CoV-2 vaccine could interfere with IBD therapy and contribute to disease exacerbation. We investigated the role of the SARS-CoV-2 Spike protein, transported by extracellular vesicles (EVs), and the impact of various EVs components, namely, exosomes (EXOs) and microvesicles (MVs), in modulating the expression of molecules involved in the exacerbation of CD, which remains unknown. [ABSTRACT FROM AUTHOR]

The VLCKD is a diet recognized to promote rapid fat mobilization and reduce inflammation, hepatic steatosis, and liver fibrosis. Extracellular vesicles (EVs) mediate cell-to-cell communication. The aim of the study is to investigate the role of circulating EVs in cell proliferation, ketone bodies, and ROS production in patients on an 8-week VLCKD regimen. Participants were classified as responders (R) or non-responders (NR) to VLCKD treatment based on their fibroscan results. In vitro experiments with the hepatic cell lines HEPA-RG (normal hepatocytes) and LX-2 (stellate cells) were conducted to investigate the effects of circulating EVs on cell viability, ROS production, and ketone body presence. The findings reveal a notable reduction in cell viability in both cell lines when treated with exosomes (EXOs). In contrast, treatment with microvesicles (MVs) did not appear to affect cell viability, which remained unchanged. Additionally, the levels of ketone bodies measured in urine were not consistently correlated with the reduction of fibrosis in responders (R). Similarly, an increase in ketone bodies was observed in non-responders (NR), which was also not aligned with the expected reduction in fibrosis. This inconsistency stands in stark contrast to the levels of Reactive Oxygen Species (ROS), which exhibited a clear and consistent pattern in accordance with the dietary intervention. Finally, in this preliminary study, ROS has been identified as a potential diet adherence marker for VLCKD patients; the ROS levels reliably follow the progression of the fibrosis response, providing a more accurate reflection of the therapeutic effects. [ABSTRACT FROM AUTHOR]

In the last few years, many space surveillance initiatives have started to consider the problem represented by resident space object overpopulation. In particular, the European Space Surveillance and Tracking (EUSST) consortium is in charge of providing services like collision avoidance, fragmentation analysis, and re-entry, which rely on measurements obtained through ground-based sensors. BIRALES is an Italian survey radar belonging to the EUSST framework and is capable of providing measurements including Doppler shift, slant range, and angular profile. In recent years, the Music Approach for Track Estimate and Refinement (MATER) algorithm has been developed to retrieve angular tracks through an adaptive beamforming technique, guaranteeing the generation of more accurate and robust measurements with respect to the previous static beamforming approach. This work presents the design of a new data processing chain to be used by BIRALES to compute the angular track. The signal acquired by the BIRALES receiver array is down-converted and the receiver bandwidth is split into multiple channels, in order to maximize the signal-to-noise ratio of the measurements. Then, the signal passes through a detection block, where an isolation procedure creates, for each epoch, signal correlation matrices (CMs) related to the channels involved in the detection and then processes them to isolate the data stream related to a single detected source. Consequently, for each epoch and for each detected source, just the CM featuring the largest signal contribution is kept, allowing deriving the Doppler shift measurement from the channel illumination sequence. The MATER algorithm is applied to each CM stream, first estimating the signal directions of arrival, then grouping them in the observation time window, and eventually returning the target angular track. Ambiguous estimates may be present due to the configuration of the receiver array, which cause spatial aliasing phenomena. This problem can be addressed by either exploiting transit prediction (in the case of cataloged objects), or by applying tailored criteria (for uncatalogued objects). The performance of the new architecture was assessed in real operational scenarios, demonstrating the enhancement represented by the implementation of the channelization strategy, as well as the angular measurement accuracy returned by MATER, in both nominal and off-nominal scenarios. [ABSTRACT FROM AUTHOR]

The intestine is essential for the modulation of nutrient absorption and the removal of waste. Gut pathologies, such as cancer, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), and celiac disease, which extensively impact gut functions, are thus critical for human health. Targeted drug delivery is essential to tackle these diseases, improve therapy efficacy, and minimize side effects. Recent strategies have taken advantage of both active and passive nanocarriers, which are designed to protect the drug until it reaches the correct delivery site and to modulate drug release via the use of different physical–chemical strategies. In this systematic review, we present a literature overview of the different nanocarriers used for drug delivery in a set of chronic intestinal pathologies, highlighting the rationale behind the controlled release of intestinal therapies. The overall aim is to provide the reader with useful information on the current approaches for gut targeting in novel therapeutic strategies. [ABSTRACT FROM AUTHOR]