Validation of the italian version of the behavioral inhibition questionnaire (Biq) for preschool children

Behavioral Inhibition (BI) is a temperamental trait characterized by fear and wariness in reaction to new and unfamiliar stimuli, both social and non-social. BI has been recognized as possible forerunner of anxiety disorders, especially social anxiety and phobia; therefore, its assessment is clinically relevant. The present study aimed to examine the psychometric properties of the Italian adaptation of the Behavioral Inhibition Questionnaire (BIQ), which measures BI in preschool children. The BIQ was completed by 417 Italian parents (230 mothers, 187 fathers) of 270 preschoolers aged 3–5. Confirmatory factor analysis showed a good internal validity: the factorial structure was corresponding to the original six-factor version. Results showed excellent internal consistency, significant item-total correlations, good inter-rater reliability, convergent validity (by correlating the BIQ with the Italian Questionnaires of Temperament-QUIT, the Anxiety-Shy Conner’s Scale and the Laboratory Temperament Assessment Battery) and discriminant validity (i.e., no correlation with Conners’ ADHD scale). Significant correlations emerged between BI indexes and total BIQ scores of parents and maternal (but not paternal) versions of the questionnaire. Altogether, the results are promising and consistent with previous validation studies, suggesting the BIQ as a reliable and valid measure for evaluating parents’ perception of BI in Italian preschoolers

Virtual Flight Demonstration of the Stratospheric Dual-Aircraft Platform

A baseline configuration for the dual-aircraft platform (DAP) concept is described and evaluated in a physics-based flight dynamics simulations for two month-long missions as a communications relay in the lower stratosphere above central Florida, within 150-miles of downtown Orlando.The DAP configuration features two large glider-like (130 ft wing span) unmanned aerial vehicles connected via a long adjustable cable (total extendible length of 3000 ft) which effectively sail without propulsion using available wind shear. Use of onboard LiDAR wind profilers to forecast wind distributions are found to be necessary to enable the platform to efficiently adjust flight conditions to remain sailing by finding sufficient wind shear across the platform. The aircraft derive power from solar cells, like a conventional solar aircraft, but also extract wind power using the propeller as a turbine when there is an excess of wind shear available.Month-long atmospheric profiles (at 3-5 min intervals) in the vicinity of 60,000-ft are derived from archived data measured by the 50-Mhz Doppler Radar Wind Profiler at Cape Canaveral and used in the DAP flight simulations. A cursory evaluation of these datasets show that sufficient wind shear for DAP sailing is persistent, suggesting that DAP could potentially sail over 90% of the month-long durations even when limited by modest ascent/descent rates.DAP's novel guidance software uses a non-linear constrained optimization technique to define waypoints such that sailing mode of flight is maintained where possible, and minimal thrust is required where sailing is not practical. A set of constraints are identified which result in waypoints that enable efficient flight (i.e., minimal use of propulsion) over the two month-long flight simulations. Waypoint solutions may need to be tabulated for a wide range of potential atmospheric conditions and stored onboard for quick retrieval on a real DAP.DAP's flight control software uses an unconventional mixture of spacecraft and aircraft control techniques. Flight simulations confirms that this controls approach enables the platform to consistently reach successive waypoints over the month-long flight simulations.The ability of DAP to transition between the sailing mode (i.e., cable tension is high) and standard formation flight (i.e., cable tension is low) is a vital capability (e.g., to enable intermittent turns while stationkeeping). A new method to perform these transitions has been identified and characterized with flight simulation which requires special aircraft modifications.The energy-usage of the DAP configuration during two month-long stationkeeping missions over central Florida (i.e., stationkeeping over Orlando) is evaluated and compared to that of a pure solar aircraft of the same weight and aerodynamic performance. DAP is shown to consistently reduce net propulsion usage while simultaneously increasing solar energy capture.A baseline 700 GHz communications system is described and its performance evaluated for the proposed mission over central Florida. It is found that the variable roll orientation of the aircraft would increase the power required to maintain coverage over the stationkeeping radius of 150 miles (e.g., by as much as 100% when DAP is 150 miles from Orlando), compared to level flight. This effect can be mitigated via additional antenna design complexity or a more restricted stationkeeping radius

Myocardial extracellular volume fraction to differentiate healthy from cardiomyopathic myocardium using dual-source dual-energy CT

Objective: To evaluate the feasibility of dual-energy CT (DECT)-based iodine quantification to estimate myocardial extracellular volume (ECV) fraction in patients with and without cardiomyopathy (CM), as well as to assess its ability to distinguish healthy myocardial tissue from cardiomyopathic, with the goal of defining a threshold ECV value for disease detection. Methods: Ten subjects free of heart disease and 60 patients with CM (mean age 66.4 ± 9.4; 59 males and 11 females; 40 ischemic and 20 non-ischemic CM) underwent late iodine enhanced DECT imaging. Myocardial iodine maps were obtained using 3-material decomposition. ECV of the left ventricle was estimated from hematocrit levels and the iodine maps using the AHA 16-segment model. Receiver operating characteristic curve analysis was performed, with corresponding area under the curve, along with Youden's index assessment, to establish a threshold for CM detection. Results: The median ECV for healthy myocardium, non-ischemic CM, and ischemic CM were 25.4% (22.9–27.3), 38.3% (33.7–43.0), and 36.9% (32.4–41.1), respectively. Healthy myocardium showed significantly lower ECV values compared to ischemic and non-ischemic CM (p 29.5% would indicate the presence of CM in the myocardium (sensitivity = 90.3; specificity = 90.3); the AUC for this criterion was 0.950 (p < 0.001). Conclusion: The findings of this study resulted in a statistically significant distinction between healthy myocardium and CM ECVs. This led to the establishment of a promising threshold ECV value that could facilitate the differentiation between healthy and diseased myocardium, and highlights the potential of this DECT methodology to detect cardiomyopathic tissue

Early intrathecal infusion of everolimus restores cognitive function and mood in a murine model of Alzheimer's disease

The discovery that mammalian target of rapamycin (mTOR) inhibition increases lifespan in mice and restores/delays many aging phenotypes has led to the identification of a novel potential therapeutic target for the treatment of Alzheimer's disease (AD). Among mTOR inhibitors, everolimus, which has been developed to improve the pharmacokinetic characteristics of rapamycin, has been extensively profiled in preclinical and clinical studies as anticancer and immunosuppressive agent, but no information is available about its potential effects on neurodegenerative disorders. Using a reliable mouse model of AD (3 × Tg-AD mice), we explored whether short-term treatment with everolimus injected directly into the brain by osmotic pumps was able to modify AD-like pathology with low impact on peripheral organs. We first established in non-transgenic mice the stability of everolimus at 37 °C in comparison with rapamycin and, then, evaluated its pharmacokinetics and pharmacodynamics profiles through either a single peripheral (i.p.) or central (i.c.v.) route of administration. Finally, 6-month-old (symptomatic phase) 3 × Tg-AD mice were treated with continuous infusion of either vehicle or everolimus (0.167 μg/μl/day, i.c.v.) using the osmotic pumps. Four weeks after the beginning of infusion, we tested our hypothesis following an integrated approach, including behavioral (tests for cognitive and depressive-like alterations), biochemical and immunohistochemical analyses. Everolimus (i) showed higher stability than rapamycin at 37 °C, (ii) poorly crossed the blood-brain barrier after i.p. injection, (iii) was slowly metabolized in the brain due to a longer t 1/2 in the brain compared to blood, and (iv) was more effective in the CNS when administered centrally compared to a peripheral route. Moreover, the everolimus-induced mTOR inhibition reduced human APP/Aβ and human tau levels and improved cognitive function and depressive-like phenotype in the 3 × Tg-AD mice. The intrathecal infusion of everolimus may be effective to treat early stages of AD-pathology through a short and cyclic administration regimen, with short-term outcomes and a low impact on peripheral organs

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns

The evolution of the Galactic metallicity gradient from high-resolution spectroscopy of open clusters

Open clusters offer a unique possibility to study the time evolution of the radial metallicity gradients of several elements in our Galaxy, because they span large intervals in age and Galactocentric distance, and both quantities can be more accurately derived than for field stars. We re-address the issue of the Galactic metallicity gradient and its time evolution by comparing the empirical gradients traced by a sample of 45 open clusters with a chemical evolution model of the Galaxy. At variance with previous similar studies, we have collected from the literature only abundances derived from high--resolution spectra. The clusters have distances $7 < RGC<22$ kpc and ages from $\sim 30$ Myr to 11 Gyr. We also consider the $\alpha$-elements Si, Ca, Ti, and the iron-peak elements Cr and Ni. The data for iron-peak and $\alpha$-elements indicate a steep metallicity gradient for R_GC<12$kpc and a plateau at larger radii. The time evolution of the metallicity distribution is characterized by a uniform increase of the metallicity at all radii, preserving the shape of the gradient, with marginal evidence for a flattening of the gradient with time in the radial range 7-12 kpc. Our model is able to reproduce the main features of the metallicity gradient and its evolution with an infall law exponentially decreasing with radius and with a collapse time scale of the order of 8 Gyr at the solar radius. This results in a rapid collapse in the inner regions, i.e.$R_{\rm GC}\lesssim 12$ kpc (that we associate with an early phase of disk formation from the collapse of the halo) and in a slow inflow of material per unit area in the outer regions at a constant rate with time.Comment: 16 pages, 18 figures, A&A accepte

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Gene signature and immune cell profiling by high-dimensional, single-cell analysis in COVID-19 patients, presenting Low T3 syndrome and coexistent hematological malignancies

BACKGROUND: Low T3 syndrome is frequent in patients admitted to intensive care units for critical illness and pneumonia. It has been reported also in patients with COVID-19, Hodgkin disease and chronic lymphocytic leukemia. We analyzed the clinical relevance of Low T3 syndrome in COVID-19 patients and, in particular, in those with associated hematological malignancies.METHODS: Sixty-two consecutive patients, hospitalized during the first wave of SARS-CoV-2 outbreak in Sant'Andrea University Hospital in Rome, were subdivided in 38 patients (Group A), showing low levels of FT3, and in 24 patients (Group B), with normal FT3 serum values. During the acute phase of the disease, we measured serum, radiologic and clinical disease severity markers and scores, in search of possible correlations with FT3 serum values. In addition, in 6 COVID-19 patients, 4 with Low T3 syndrome, including 2 with a hematological malignancy, and 2 with normal FT3 values, we performed, high-dimensional single-cell analysis by mass cytometry, multiplex cytokine assay and gene expression profiling in peripheral blood mononuclear cells (PBMC).RESULTS: Low FT3 serum values were correlated with increased Absolute Neutrophil Count, NLR and dNLR ratios and with reduced total count of CD3+, CD4+ and CD8+ T cells. Low FT3 values correlated also with increased levels of inflammation, tissue damage and coagulation serum markers as well as with SOFA, LIPI and TSS scores. The CyTOF analysis demonstrated reduction of the effector memory and terminal effector subtypes of the CD4+ T lymphocytes. Multiplex cytokine assay indicates that mainly IL-6, IP-10 and MCAF changes are associated with FT3 serum levels, particularly in patients with coexistent hematological malignancies. Gene expression analysis using Nanostring identified four genes differently expressed involved in host immune response, namely CD38, CD79B, IFIT3 and NLRP3.CONCLUSIONS: Our study demonstrates that low FT3 serum levels are associated with severe COVID-19. Our multi-omics approach suggests that T3 is involved in the immune response in COVID-19 and coexistent hematological malignancy and new possible T3 target genes in these patients have been identified

3He in Planetary Nebulae: A Challenge to Stellar Evolution Models

The discrepancy between the observed abundances of 3He in the ISM and those predicted by stellar and galactic chemical evolution remains largely unexplained. In this paper, we attempt to shed some light on this unsolved problem by presenting a quantitative comparison of the 3He abundances recently measured in six planetary nebulae (PNe) with the corresponding predictions of stellar evolution theory. The determination of the mass of the PNe progenitors allows us to dismiss, to a good degree of confidence, the hypothesis that the abundance of 3He in the envelope of all low-mass stars is strongly reduced with respect to the standard theoretical values by some mixing mechanism acting in the latest phases of stellar evolution. The abundance versus mass correlation, allowance made for the limitation of the sample, is in fact found to be fully consistent with the classical prediction of stellar evolution. We examine the implications of this result on the galactic evolution of 3He with the help of a series of models with standard and non-standard nucleosynthesis prescriptions. The results are found to be consistent with the observed galactic abundances only if the vast majority of low-mass stars follows non-standard prescriptions. This implies that either the sample of PNe nebulae under exam is highly biased, or the solution to the 3He problem lies elsewhere.Comment: 13 pages, LaTeX, 4 Figures. To be published in The Astrophysical Journa

A microbially produced AhR ligand promotes a Tph1-driven tolerogenic program in multiple sclerosis

Multiple sclerosis is a debilitating autoimmune disease, characterized by chronic inflammation of the central nervous system. While the significance of the gut microbiome on multiple sclerosis pathogenesis is established, the underlining mechanisms are unknown. We found that serum levels of the microbial postbiotic tryptophan metabolite indole-3-carboxaldehyde (3-IAld) inversely correlated with disease duration in multiple sclerosis patients. Much like the host-derived tryptophan derivative l-Kynurenine, 3-IAld would bind and activate the Aryl hydrocarbon Receptor (AhR), which, in turn, controls endogenous tryptophan catabolic pathways. As a result, in peripheral lymph nodes, microbial 3-IAld, affected mast-cell tryptophan metabolism, forcing mast cells to produce serotonin via Tph1. We thus propose a protective role for AhR–mast-cell activation driven by the microbiome, whereby natural metabolites or postbiotics will have a physiological role in immune homeostasis and may act as therapeutic targets in autoimmune diseases