Recent X-ray Observations and the Evolution of Hot Gas in Elliptical Galaxies: Evidence for Circumgalactic Gas

X-ray emitting gaseous halos, such as that in elliptical galaxies like NGC 4472, cannot have been produced solely from gas expelled from galactic stars. In traditional models for the evolution of hot interstellar gas (cooling flows) in ellipticals, the galaxies are assumed to have been cleared of gas by SNII-driven winds at some early time then gas is subsequently replenished by mass loss from an evolving population of old stars. To test this, we accurately determine the stellar and dark halo mass of NGC 4472 using hydrostatic equilibrium, then solve the standard time-dependent cooling flow equations to recover the observed hot gas temperature and density distributions when evolved to the present time. This procedure fails: the computed gas density gradient is too steep, the total gas mass is too low, and the gas temperatures are much too low. All variants on this basic procedure also fail: increasing the SNIa rate, using the mass dropout assumption, arbitrarily adjusting uncertain coefficients, etc. However, agreement is achieved if the galaxy is supplied with additional, spatially-extended hot gas early in its evolution. This old ``circumgalactic'' gas can be retained to the present time and may be related to cosmological ``secondary infall''.Comment: 15 pages in two-column AASTEX LaTeX including 1 table and 8 figures; abstract corrected in replacement; accepted by Astrophysical Journa

Amyloid/Melanin distinctive mark in invertebrate immunity

Protostomes and Deuterostomes show the same nexus between melanin production, and amyloid fibril production, i.e., the presence of melanin is indissolubly linked to amyloid scaffold that, in turn, is conditioned by the redox status/cytoplasmic pH modification, pro-protein cleavage presence, adrenocorticotropin hormone (ACTH), melanocyte-stimulating hormone (\u3b1-MSH), and neutral endopeptidase (NEP) overexpressions. These events represent the crucial component of immune response in invertebrates, while in vertebrates these series of occurrences could be interpreted as a modest and very restricted innate immune response. On the whole, it emerges that the mechanisms involving amyloid fibrils/pigment synthesis in phylogenetically distant metazoan (viz, cnidaria, molluscs, annelids, insects, ascidians and vertebrates) are evolutionary conserved. Furthermore, our data show the relationship between immune and neuroendocrine systems in amyloid/melanin synthesis. Indeed the process is closely associated to ACTH-\u3b1-MSH production, and their role in stress responses leading to pigment production reflects and confirms again their ancient phylogeny

Heated Cooling Flows

In conventional models of galactic and cluster cooling flows widespread cooling (mass dropout) is assumed to avoid accumulation of unacceptably large central masses. However, recent XMM observations have failed to find spectral evidence for locally cooling gas. This has revived the notion that cooling flows are heated by some process such as an intermittent, low-level AGN involving supermassive black holes in the central galaxy. To explore this hypothesis, we consider the gasdynamical consequences of galactic cooling flows heated by many different scenarios without specifying the detailed physics of the heating process. We are unable to find a single acceptable heated flow in reasonable agreement with well observed hot gas temperature and density profiles, even using finely tuned parameters. Idealized flows in which radiative cooling is perfectly balanced by global heating are grossly incompatible with observations. Flows heated by episodic central feedback generate quasi-cyclic changes in the hot gas density profile which are not supported by current observations. Paradoxically, centrally heated (or pressurized) cooling flows experience spontaneous non-linear compressions that result in spatially widespread cooling instabilities. Therefore, spectral evidence for cooling gas is difficult to avoid by central heating.Comment: 17 pages (emulateapj5) with 12 figures and Appendix; accepted by The Astrophysical Journa

When IL-17 inhibitors fail : real-life evidence to switch from secukinumab to adalimumab or ustekinumab

Psoriasis is a chronic, systemic inflammatory disease that in the moderate to severe forms may benefit of biologics, namely TNF and IL-12/23 and IL-17 inhibitors. Loss of response, lack of response or discontinuation due to adverse events represent a concrete therapeutic challenge for dermatologists that have to switch patients to other treatments. Although some evidences already exist toward the switch from IL-12/23 and TNF inhibitors to IL-17 inhibitors, conversely nothing is present toward the switch from IL-17 inhibitors to IL-12/23 and TNF inhibitors. We performed a real-life study enrolling 50 patients randomly switched to adalimuamb, a TNF inhibitor, or ustekinumab, an IL-12/23 inhibitor. Our observational study suggests that switching from IL-17i to TNFi and IL-12/23i is a safe and effective therapeutic strategy

Formation of Low Mass Stars in Elliptical Galaxy Cooling Flows

X-ray emission from hot (T = 10^7 K) interstellar gas in massive elliptical galaxies indicates that 10^{10} M_sun has cooled over a Hubble time, but optical and radio evidence for this cold gas is lacking. We provide detailed theoretical support for the hypothesis that this gas has formed into low luminosity stars. Within several kpc of the galactic center, interstellar gas first cools to T = 10^4 K where it is heated by stellar UV and emits the observed diffuse optical line emission. This cooling occurs at a large number (10^6) of isolated sites. After less than a solar mass of gas has accumulated (10^{-6} M_sun/yr) at a typical cooling site, a neutral (HI or H_2) core develops in the HII cloud where gas temperatures drop to T = 15 K and the ionization level (from thermal X-rays) is very low (x = 10^{-6}). We show that the maximum mass of cores that become gravitationally unstable is only about 2 M_sun. No star can exceed this mass. Fragmentation of collapsing cores produces a population of low mass stars with a bottom-heavy IMF and radial orbits. Gravitational collapse and ambipolar diffusion are rapid. The total mass of star-forming (dust-free) HI or H_2 cores in a typical bright elliptical is only 10^6 M_sun, below current observational thresholds.Comment: 23 pages in AASTEX LaTeX with 8 figures; accepted by Astrophysical Journa

Study of the MgB2 grain size role in ex-situ multifilamentary wires with thin filaments

The MgB2 superconductor has already demonstrated its applicative potential, in particular for DC applications such as MRI magnets, thanks to the low costs of the raw materials and to its simple production process. However further efforts have still to be made in order to broaden its employment also towards the AC applications such as SFCL, motors, transformers. The main issues are related to the reduction of the AC losses. Some of these can be faced by obtaining multifilamentary conductors with a large number of very fine filaments and, in this context, the powders granulometry can play a crucial role. We have prepared MgB2 starting powders with different granulometries and by the ex-situ P.I.T method we have realized multifilamentary wires with a number of filaments up to 361 and an average size of each filament lowered down to 30 microns. In particular we have studied the relationship between grain and filament size in terms of transport properties and show that the optimization of this ratio is possible in order to obtain suitable conductors for AC industrial applications

The Impact of Intermittent Fasting (Ramadan Fasting) on Psoriatic Arthritis Disease Activity, Enthesitis, and Dactylitis: A Multicentre Study

Intermittent circadian fasting, namely Ramadan, is a common worldwide practice. Such fasting has a positive impact on psoriasis, but no data exist on its role in psoriatic arthritis (PsA)—a disease that is clearly linked to body mass index. We enrolled 37 patients (23 females and 14 males) with a mean age 43.32 ± 7.81 and they fasted for 17 h for one month in 2016. The baseline PsA characteristics were collected and 12 (32.4%) patients had peripheral arthritis, 13 (35.1%) had axial involvement, 24 (64.9%) had enthesitis, and 13 (35.1%) had dactylitis. Three patients (8.1%) were treated with methotrexate, 28 (75.7%) with TNF-α blockers, and 6 (16.2%) with IL-17 blockers. After a month of intermittent fasting, C-reactive protein (CRP) levels decreased from 14.08 ± 4.65 to 12.16 ± 4.46 (p < 0.0001), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 2.83 ± 1.03 to 2.08 ± 0.67 (p = 0.0078), Psoriasis Area Severity Index (PASI) decreased from 7.46 ± 2.43 to 5.86 ± 2.37 (p < 0.0001), and Disease Activity index for PSoriatic Arthritis (DAPSA) decreased from 28.11 ± 4.51 to 25.76 ± 4.48 (p < 0.0001). Similarly, enthesitis improved after fasting, with Leeds Enthesitis Index (LEI) decreasing from 2.25 ± 1.11 to 1.71 ± 0.86 (p < 0.0001) and dactylitis severity score (DSS) decreasing from 9.92 ± 2.93 to 8.54 ± 2.79 (p = 0.0001). Fasting was found to be a predictor of a decrease in PsA disease activity scores (DAPSA, BASDAI, LEI, DSS) even after adjustment for weight loss. IL-17 therapy was found to be an independent predictor of decreases in LEI after fasting. These preliminary data may support the use of chronomedicine in the context of rheumatic diseases, namely PsA. Further studies are needed to support our findings

fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study

Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases

Age of HIV Acquisition Affects the Risk of Multi-Morbidity after 25 Years of Infection Exposure

Introduction: Understanding the intersection of HIV, aging and health is crucial due to the increasing number of people aging with HIV. Objective: The objective of the study was to assess the prevalence of, and risk factors for individual comorbidities and multi-morbidity in people living with HIV with similar duration of HIV infection, notwithstanding a 25-year difference at the time of HIV acquisition. Methods: In a cross-sectional multicentre retrospective study, we compared three match-control age groups. The "Young" were selected from Romania and included HIV-positive patients prenatally infected and assessed at the age of 25-30 years. The "Old" and the "Geriatric" were selected from Italy. These respectively included subjects infected with HIV at the age of 25 years and assessed at the age of 50-55 years, and those infected at the age of 50 years and assessed at the age of 75-80 years. Each group was sex and age matched in a 1: 5 ratio with controls selected from the CINECA ARNO database from Italy. We described non-infectious comorbidities (NICM), including cardiovascular disease, hypertension, dyslipidaemia, diabetes, chronic kidney disease, and multi-morbidity (MM >= 3 NICM). Results: MM prevalence in the "Young" group compared to controls was 6.2% vs 0%, while in the "Geriatric" was "68.2% vs 3.6%. Using "Young" as a reference, in multivariate analyses, predictors for MM were as follows: HIV serostatus (OR=47.75, IQR 14.78-154.25, p<0.01) and "Geriatric" vs "Young" (OR=30.32, IQR 5.89-155.98, p<0.01). Conclusion: These data suggest that age at acquisition of HIV should be considered as a risk factor for NICM and MM

Determinants of serum manganese levels in an Italian population.

Manganese (Mn) is both essential and toxic for humans, mainly depending on the total levels and its species. Main sources of exposure include food and air pollution, particularly motorized traffic. We sought to determine the potential influence of these sources on serum total levels of Mn and Mn species. We selected a random sample of municipality residents from an Italian urban municipality, from whom we collected detailed personal information, dietary habits and a blood sample for serum Mn determination. We also assessed outdoor air Mn exposure, by modeling levels of particulate matter 6410 \ub5m (PM10) from motorized traffic at the residence of geocoded subjects. Serum Mn species generally showed higher levels in males and positive correlation with age, while no such differences were found according to smoking habits or use of dietary supplements. Among nutrients, only iron intake showed a relation with Mn [an inverse correlation with Mn\u2011ferritin (Mn\u2011Fer) and a direct one with inorganic\u2011Mn (Inorg\u2011Mn)]. Meat consumption directly correlated and fish and seafood inversely correlated with total Mn, Mn\u2011transferrin (Mn\u2011Tf) and Mn-citrate (Mn-Cit). Fruits and vegetables, including legumes and nuts, generally showed a positive correlation with all Mn species, especially Mn\u2011Cit, and an inverse one with Inorg\u2011Mn. Odds ratios (ORs) of having serum Mn levels above median value increased with increasing PM10 tertiles, with an OR for highest\u2011to\u2011lowest tertile of 7.40 (1.36\u201140.25) in multivariate analysis. Analyses for Mn species did not highlight a clear comparable pattern. In conclusion, our results seem to demonstrate that PM10 exposure positively influences total Mn serum levels, while single Mn species show conflicting results