Chemical evolution models with a new stellar nucleosynthesis

Numerical models for the chemical evolution of the Galaxy have been computed with the new stellar yields published by Maeder (1992). These metallicity dependent yields represent an important improvement in the chemical evolution of galaxies but there are still uncertainties in the stellar evolution which prevent completely satisfactory results. {}From the comparison of the model predictions with the corresponding observational constraints we find that Maeder's nucleosynthesis reproduces the oxygen and carbon abundances and provides consistent $\Delta$Y/$\Delta$(O/H) ratios if a significant amount of gas is accreted by the galactic disc during its whole lifetime. The lower mass limit for the black hole formation (M$_{bh}$) must be larger than 22.5 M$_{\odot}$ to avoid oxygen underproduction.Comment: 6 pages, MNRAS LaTex style, figures available on request from [email protected]

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

Abnormal "low grade" transformation zone: current diagnostic gold standard

The aim of this work was to examine different methods of investigation in the diagnosis of the abnormal "low grade" transformation zone of the portio. Over a period of one year 41 patients subjected to colposcopic examination underwent exo-endocervical sampling for oncologic evaluation and for detection of viral and bacterial infections (HPV, HSV. adenovirus, mycoplasmas and chlamydia trachomatis), as well as portio biopsy. A 65.8% correlation was found between cytology and the HPV-DNA test results. while histology and the presence of the HPV virus agreed in 51.4% of cases. In those cases in which minimal histological alterations were found (koilocytosis) a high percentage of HPV negativity was found. In discordant negative cytologic tests that were however positive for HPV by PCR. the genotypes identified were always 6 and 11

XMM-Newton survey of the Local Group galaxy M 33

In an XMM-Newton raster observation of the bright Local Group spiral galaxy M 33 we study the population of X-ray sources (X-ray binaries, supernova remnants) down to a 0.2--4.5 keV luminosity of 10^35 erg/s -- more than a factor of 10 deeper than earlier ROSAT observations. EPIC hardness ratios and optical and radio information are used to distinguish between different source classes. The survey detects 408 sources in an area of 0.80 square degree. We correlate these newly detected sources with earlier M 33 X-ray catalogues and information from optical, infra-red and radio wavelengths. As M 33 sources we detect 21 supernova remnants (SNR) and 23 SNR candidates, 5 super-soft sources, and 2 X-ray binaries (XRBs). There are 267 sources classified as hard, which may either be XRBs or Crab-like SNRs in M 33 or background AGN. The 44 confirmed and candidate SNRs more than double the number of X-ray detected SNRs in M 33. 16 of these are proposed as SNR candidates from the X-ray data for the first time. On the other hand, there are several sources not connected to M 33: five foreground stars, 30 foreground star candidates, 12 active galactic nucleus candidates, one background galaxy and one background galaxy candidate. Extrapolating from deep field observations we would expect 175 to 210 background sources in this field. This indicates that about half of the sources detected are sources within M 33.Comment: 14 pages, 6 figures, accepted for publication in A&A, the images of Figs. 1,2,3,4,6 are available in jpg format, a full version of the paper is available at ftp://ftp.xray.mpe.mpg.de/people/fwh/docs/M33_AA0068.p

Non-invasive fractional flow reserve (FFRCT) in the evaluation of acute chest pain ? Concepts and first experiences

Objective: To evaluate 30 day rate of major adverse cardiac events (MACE) utilizing cCTA and FFRCT for evaluation of patients presenting to the Emergency Department (ED) with acute chest pain. Materials and methods: Patients between the ages of 18?95 years who underwent clinically indicated cCTA and FFRCT in the evaluation of acute chest pain in the emergency department were retrospectively evaluated for 30 day MACE, repeat presentation/admission for chest pain, revascularization, and additional testing. Results: A total of 59 patients underwent CCTA and subsequent FFRCT for the evaluation of acute chest pain in the ED over the enrollment period. 32 out of 59 patients (54 %) had negative FFRCT (>0.80) out of whom 18 patients (55 %) were discharged from the ED. Out of the 32 patients without functionally significant CAD by FFRCT, 32 patients (100 %) underwent no revascularization and 32 patients (100 %) had no MACE at the 30-day follow-up period. Conclusion: In this limited retrospective study, patients presenting to the ED with acute chest pain and with CCTA with subsequent FFRCT of >0.8 had no MACE at 30 days; however, for many of these patients results were not available at time of clinical decision making by the ED physician

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

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

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