Long-term effects of chronic buspirone during adolescence reduce the adverse influences of neonatal inflammatory pain and stress on adaptive behavior in adult male rats

Neonatal pain and stress induce long-term changes in pain sensitivity and behavior. Previously we found alterations in pain sensitivity in adolescent rats exposed to early-life adverse events. We tested whether these alterations have long-lasting effects and if those effects can be improved by the 5-hydroxytryptamine 1A (5-HT1A) receptor agonist buspirone injected chronically during the adolescent period. This study investigates: (1) effects of inflammatory pain (the injection of formalin into the pad of a hind paw) or stress (short maternal deprivation-isolation, MI), or their combination in 1â\u80\u932-day-old rats on the adult basal pain, formalin-induced pain, anxiety and depression; (2) effects of adolescent buspirone in adult rats that experienced similar early-life insults. Changes in nociceptive thresholds were evaluated using the hot plate (HP) and formalin tests; levels of anxiety and depression were assessed with the elevated plus maze and forced swim tests respectively. Both neonatal painful and stressful treatments induced long-term alterations in the forced swim test. Other changes in adult behavioral responses were dependent on the type of neonatal treatment. There was a notable lack of long-term effects of the combination of early inflammatory pain and stress of MI on the pain responses, anxiety levels or on the effects of adolescent buspirone. This study provides the first evidence that chronic injection of buspirone in adolescent rats alters antinociceptive and anxiolytic effects limited to adult rats that showed behavioral alterations induced by early-life adverse treatments. These data highlight the role of 5-HT1A receptors in long-term effects of neonatal inflammatory pain and stress of short MI on adaptive behavior and possibility of correction of the pain and psychoemotional behavior that were altered by adverse pain/stress intervention using buspirone during critical adolescent period

An Exploratory Study of Field Failures

Field failures, that is, failures caused by faults that escape the testing phase leading to failures in the field, are unavoidable. Improving verification and validation activities before deployment can identify and timely remove many but not all faults, and users may still experience a number of annoying problems while using their software systems. This paper investigates the nature of field failures, to understand to what extent further improving in-house verification and validation activities can reduce the number of failures in the field, and frames the need of new approaches that operate in the field. We report the results of the analysis of the bug reports of five applications belonging to three different ecosystems, propose a taxonomy of field failures, and discuss the reasons why failures belonging to the identified classes cannot be detected at design time but shall be addressed at runtime. We observe that many faults (70%) are intrinsically hard to detect at design-time

Long-rising Type II Supernovae in the Zwicky Transient Facility Census of the Local Universe

SN 1987A was an unusual hydrogen-rich core-collapse supernova originating from a blue supergiant star. Similar blue supergiant explosions remain a small family of events, and are broadly characterized by their long rises to peak. The Zwicky Transient Facility (ZTF) Census of the Local Universe (CLU) experiment aims to construct a spectroscopically complete sample of transients occurring in galaxies from the CLU galaxy catalog. We identify 13 long-rising (>40 days) Type II supernovae from the volume-limited CLU experiment during a 3.5 year period from June 2018 to December 2021, approximately doubling the previously known number of these events. We present photometric and spectroscopic data of these 13 events, finding peak r-band absolute magnitudes ranging from -15.6 to -17.5 mag and the tentative detection of Ba II lines in 9 events. Using our CLU sample of events, we derive a long-rising Type II supernova rate of $1.37^{+0.26}_{-0.30}\times10^{-6}$ Mpc$^{-3}$ yr$^{-1}$, $\approx$1.4% of the total core-collapse supernova rate. This is the first volumetric rate of these events estimated from a large, systematic, volume-limited experiment.Comment: 32 pages, 17 figures, 5 tables. Submitted to Ap

CLASSY VIII: Exploring the Source of Ionization with UV ISM diagnostics in local High-zz Analogs

In the current JWST era, rest-frame UV spectra play a crucial role in enhancing our understanding of the interstellar medium (ISM) and stellar properties of the first galaxies in the epoch of reionization (EoR, $z>6$). Here, we compare well-known and reliable optical diagrams sensitive to the main ionization source (i.e., star formation, SF; active galactic nuclei, AGN; shocks) to UV counterparts proposed in the literature - the so-called ``UV-BPT diagrams'' - using the HST COS Legacy Archive Spectroscopic SurveY (CLASSY), the largest high-quality, high-resolution and broad-wavelength range atlas of far-UV spectra for 45 local star-forming galaxies. In particular, we explore where CLASSY UV line ratios are located in the different UV diagnostic plots, taking into account state-of-the-art photoionization and shock models and, for the first time, the measured ISM and stellar properties (e.g., gas-phase metallicity, ionization parameter, carbon abundance, stellar age). We find that the combination of C III] $\lambda\lambda$1907,9 He II $\lambda1640$ and O III] $\lambda$1666 can be a powerful tool to separate between SF, shocks and AGN at sub-solar metallicities. We also confirm that alternative diagrams without O III] $\lambda$1666 still allow us to define a SF-locus with some caveats. Diagrams including C IV $\lambda\lambda$1548,51 should be taken with caution given the complexity of this doublet profile. Finally, we present a discussion detailing the ISM conditions required to detect UV emission lines, visible only in low gas-phase metallicity (12+log(O/H) $\lesssim8.3$) and high ionization parameter (log($U$) $\gtrsim-2.5$) environments. Overall, CLASSY and our UV toolkit will be crucial in interpreting the spectra of the earliest galaxies that JWST is currently revealing.Comment: 31 pages, submitted to ApJ, comments welcom

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

T Cells Specifically Targeted to Amyloid Plaques Enhance Plaque Clearance in a Mouse Model of Alzheimer's Disease

Patients with Alzheimer's disease (AD) exhibit substantial accumulation of amyloid-β (Aβ) plaques in the brain. Here, we examine whether Aβ vaccination can facilitate the migration of T lymphocytes to specifically target Aβ plaques and consequently enhance their removal. Using a new mouse model of AD, we show that immunization with Aβ, but not with the encephalitogenic proteolipid protein (PLP), results in the accumulation of T cells at Aβ plaques in the brain. Although both Aβ-reactive and PLP-reactive T cells have a similar phenotype of Th1 cells secreting primarily IFN-γ, the encephalitogenic T cells penetrated the spinal cord and caused experimental autoimmune encephalomyelitis (EAE), whereas Aβ T cells accumulated primarily at Aβ plaques in the brain but not the spinal cord and induced almost complete clearance of Aβ. Furthermore, while a single vaccination with Aβ resulted in upregulation of the phagocytic markers triggering receptors expressed on myeloid cells-2 (TREM2) and signal regulatory protein-β1 (SIRPβ1) in the brain, it caused downregulation of the proinflammatory cytokines TNF-α and IL-6. We thus suggest that Aβ deposits in the hippocampus area prioritize the targeting of Aβ-reactive but not PLP-reactive T cells upon vaccination. The stimulation of Aβ-reactive T cells at sites of Aβ plaques resulted in IFN-γ-induced chemotaxis of leukocytes and therapeutic clearance of Aβ

The COS Legacy Archive Spectroscopy SurveY (CLASSY) Treasury Atlas

Far-ultraviolet (FUV; ~1200-2000 angstroms) spectra are fundamental to our understanding of star-forming galaxies, providing a unique window on massive stellar populations, chemical evolution, feedback processes, and reionization. The launch of JWST will soon usher in a new era, pushing the UV spectroscopic frontier to higher redshifts than ever before, however, its success hinges on a comprehensive understanding of the massive star populations and gas conditions that power the observed UV spectral features. This requires a level of detail that is only possible with a combination of ample wavelength coverage, signal-to-noise, spectral-resolution, and sample diversity that has not yet been achieved by any FUV spectral database. We present the COS Legacy Spectroscopic SurveY (CLASSY) treasury and its first high level science product, the CLASSY atlas. CLASSY builds on the HST archive to construct the first high-quality (S/N_1500 >~ 5/resel), high-resolution (R~15,000) FUV spectral database of 45 nearby (0.002 < z < 0.182) star-forming galaxies. The CLASSY atlas, available to the public via the CLASSY website, is the result of optimally extracting and coadding 170 archival+new spectra from 312 orbits of HST observations. The CLASSY sample covers a broad range of properties including stellar mass (6.2 < logM_star(M_sol) < 10.1), star formation rate (-2.0 < log SFR (M_sol/yr) < +1.6), direct gas-phase metallicity (7.0 < 12+log(O/H) < 8.8), ionization (0.5 < O_32 < 38.0), reddening (0.02 < E(B-V < 0.67), and nebular density (10 < n_e (cm^-3) < 1120). CLASSY is biased to UV-bright star-forming galaxies, resulting in a sample that is consistent with z~0 mass-metallicity relationship, but is offset to higher SFRs by roughly 2 dex, similar to z >~2 galaxies. This unique set of properties makes the CLASSY atlas the benchmark training set for star-forming galaxies across cosmic time.Comment: Accepted for publication in Ap

The Zwicky Transient Facility Census of the Local Universe. I. Systematic Search for Calcium-rich Gap Transients Reveals Three Related Spectroscopic Subclasses

Using the Zwicky Transient Facility alert stream, we are conducting a large spectroscopic campaign to construct a complete, volume-limited sample of transients brighter than 20 mag, and coincident within 100" of galaxies in the Census of the Local Universe catalog. We describe the experiment design and spectroscopic completeness from the first 16 months of operations, which have classified 754 supernovae. We present results from a systematic search for calcium-rich gap transients in the sample of 22 low-luminosity (peak absolute magnitude M > −17), hydrogen-poor events found in the experiment. We report the detection of eight new events, and constrain their volumetric rate to ≳ 15% ± 5% of the SN Ia rate. Combining this sample with 10 previously known events, we find a likely continuum of spectroscopic properties ranging from events with SN Ia–like features (Ca-Ia objects) to those with SN Ib/c–like features (Ca-Ib/c objects) at peak light. Within the Ca-Ib/c events, we find two populations distinguished by their red (g − r ≈ 1.5 mag) or green (g - r ≈ 0.5 mag) colors at the r-band peak, wherein redder events show strong line blanketing features and slower light curves (similar to Ca-Ia objects), weaker He lines, and lower [Ca ii]/[O i] in the nebular phase. We find that all together the spectroscopic continuum, volumetric rates, and striking old environments are consistent with the explosive burning of He shells on low-mass white dwarfs. We suggest that Ca-Ia and red Ca-Ib/c objects arise from the double detonation of He shells, while green Ca-Ib/c objects are consistent with low-efficiency burning scenarios like detonations in low-density shells or deflagrations

AIDS-related mycoses: the way forward.

The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries