Context . Observations of meteors in the Earth’s atmosphere offer a unique tool for determining the flux of meteoroids that are too small to be detected by direct telescopic observations. Although ...these objects are routinely observed from ground-based facilities, such as meteor and fireball networks, space-based instruments come with notable advantages and have the potential to achieve a broad and uniform exposure. Aims . In this paper, we describe the first observations of meteor events with Mini-EUSO, a very wide field-of-view telescope launched in August 2019 from the Baikonur cosmodrome and installed on board the Russian Zvezda module of the International Space Station. Mini-EUSO can map the night-time Earth in the near-UV range (290-130 nm) with a field of view equal to 44° × 44° and a spatial resolution of about 4.7 km at an altitude of 100 km from the ground. The detector saves triggered transient phenomena with a sampling frequency of 2.5 µs and 320 µs, as well as a continuous acquisition at 40.96 ms scale that is suitable for meteor observations. Methods . We designed two dedicated and complementary trigger methods, together with an analysis pipeline able to estimate the main physical parameters of the observed population of meteors, such as the duration, horizontal speed, azimuth, and absolute magnitude. To compute the absolute flux of meteors from Mini-EUSO observations, we implemented a simulation framework able to estimate the detection efficiency as a function of the meteor magnitude and the background illumination conditions. Results . The instrument detected 24 thousand meteors within the first 40 data-taking sessions from November 2019 to August 2021, for a total observation time of approximately 6 days with a limiting absolute magnitude of +6. Our estimation of the absolute flux density of meteoroids in the range of mass between 10 −5 kg to 10 −1 kg was found to be comparable to other results available in the literature. Conclusions . The results of this work prove the potential for space-based observations to increase the statistics of meteor observations achievable with instruments operating on the ground. The slope of the mass distribution of meteoroids sampled with Mini-EUSO suggests a mass index of either s = 2.09 ± 0.02 or s = 2.31 ± 0.03, according to two different methodologies for the computation of the pre-atmospheric mass starting from the luminosity of each event.
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Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to ...activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1β, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC.
Paclitaxel (PTX) is one of the most broadly used chemotherapeutic agents for the treatment of several tumor types including ovarian, breast, and non-small cell lung cancer. However, its use is ...limited by debilitating side effects, involving both gastrointestinal and behavioral dysfunctions. Due to growing evidence showing a link between impaired gut function and chemotherapy-associated behavioral changes, the aim of this study was to identify a novel therapeutic approach to manage PTX-induced gut and brain comorbidities.
Mice were pre-treated with sodium butyrate (BuNa) for 30 days before receiving PTX. After 14 days, mice underwent to behavioral analysis and biochemical investigations of gut barrier integrity and microbiota composition. Paired evaluations of gut functions revealed that the treatment with BuNa restored PTX-induced altered gut barrier integrity, microbiota composition and food intake suggesting a gut-to-brain communication. The treatment with BuNa also ameliorated depressive- and anxiety-like behaviors induced by PTX in mice, and these effects were associated with neuroprotective and anti-inflammatory outcomes. These results propose that diet supplementation with this safe postbiotic might be considered when managing PTX-induced central side effects during cancer therapy.
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•Paclitaxel induces gut dysbiosis, inflammation and influences behavior.•Sodium butyrate attenuates paclitaxel-induced intestinal dysfunction and inflammation.•Sodium butyrate improves both depressive- and anxiety- like behaviors.•Sodium butyrate enhances hippocampal BDNF signaling.
Purpose
The aims of this study are to evaluate the epidemiology of invasive fungal infections (IFIs) in patients admitted to an intensive care unit (ICU) in Southern Italy and the in vitro antifungal ...susceptibility of isolates.
Methods
A surveillance program was implemented in 18 ICUs. IFI cases were recorded using a standardized form.
Results
A total of 105 episodes of IFIs occurred in 5,561 patients during the 18-month study. The main infections were caused by yeasts, more than filamentous fungi (overall incidence of 16.5 cases per 1,000 admissions and 2.3 cases per 1,000 admissions, respectively). The overall crude mortality rate was high (42.8 %), particularly for mold infections (61.5 %). All yeast infections were
Candida
bloodstream infections. Over half (59.8 %) were caused by
Candida
non-
albicans
, with
C. parapsilosis
being the most common (61.8 %). In the multivariate model, trauma admission diagnosis, prolonged stay in the ICU, and parenteral nutrition were independently associated with candidemia due to
C. parapsilosis
odds ratio (OR) 3.5, (1.8–5.2); OR 3.5, (1.02–3.5); OR 3.6, (1.28–6.99), respectively. Among mold infections, 12 patients suffered from invasive pulmonary aspergillosis, with
Aspergillus fumigatus
as the predominant pathogen (41.7 %). One case of brain scedosporiosis was identified. Overall, azoles and echinocandins resistance was uncommon.
Conclusions
Candida
non-
albicans
species are the most frequent cause of candidemia in ICU patients. Mold infections are associated with a high mortality rate. This study confirms the importance of the epidemiological surveillance on IFIs in the ICU setting for documenting species distribution and antimicrobial susceptibility patterns to guide therapeutic choices.
The antibiotic-induced intestinal injury (AIJ) is associated with diarrhoea and gastrointestinal discomfort. However, the pathological intestinal mechanisms and related side effects associated with ...antibiotic use/misuse may be counteracted by probiotics. This study aims to evaluate the effect and the protective mechanisms of a probiotic formulation containing Alkalihalobacillus clausii (formerly Bacillus clausii; BC) spores in an experimental model of AIJ. C57/Bl6J mice were orally challenged with a high dose of ceftriaxone for five days along with BC treatment which lasted up to the 15th day. Our results showed the beneficial effect of the probiotic in preserving colonic integrity and limiting tissue inflammation and immune cell infiltration in AIJ mice. BC increased tight junction expression and regulated the unbalanced production of colonic pro- and anti-inflammatory cytokines, converging toward the full resolution of the intestinal damage. These findings were supported by the histological evaluation of the intestinal mucosa, suggesting a potential restoration of mucus production. Notably, BC treatment increased gene transcription of the secretory products responsible for epithelium repair and mucus synthesis and normalized the expression of antimicrobial peptides involved in immune activation. Reconstruction of complex and diverse gut microbiota in antibiotic-induced dysbiosis was recorded upon BC supplementation. Specifically, the expansion of A. clausii, Prevotella rara and Eubacterium ruminatium drove intestinal microbiota rebalance by primarily impacting Bacteroidota members. Taken together, our data indicate that BC administration alleviates AIJ by multiple converging mechanisms leading to restoring gut integrity and homeostasis and reshaping microbiota composition.
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•Antibiotic misuse is associated with intestinal damage and dysbiosis.•Probiotics can manage gut dysbiosis and related disorders induced by antibiotics.•BC administration restores intestinal architecture and integrity altered by CFX.•BC probiotic treatment reduces gut inflammation and immune response in AIJ mice.•BC spores induces a reshape of gut microbiota depleted by antibiotic treatment.
Diabetes mellitus (DM) and hypercholesterolemia (HC) have emerged as major risk factors for Alzheimer's disease, highlighting the importance of vascular health to normal brain functioning. Our ...previous study showed that DM and HC favor the development of advanced coronary atherosclerosis in a porcine model, and that treatment with darapladib, an inhibitor of lipoprotein-associated phospholipase A2, blocks atherosclerosis progression and improves animal alertness and activity levels. In the present study, we examined the effects of DM and HC on the permeability of the blood-brain barrier (BBB) using immunoglobulin G (IgG) as a biomarker. DMHC increased BBB permeability and the leak of microvascular IgG into the brain interstitium, which was bound preferentially to pyramidal neurons in the cerebral cortex. We also examined the effects of DMHC on the brain deposition of amyloid peptide (Aβ42), a well-known pathological feature of Alzheimer's disease. Nearly all detectable Aβ42 was contained within cortical pyramidal neurons and DMHC increased the density of Aβ42-loaded neurons. Treatment of DMHC animals with darapladib reduced the amount of IgG-immunopositive material that leaked into the brain as well as the density of Aβ42-containing neurons. Overall, these results suggest that a prolonged state of DMHC may have chronic deleterious effects on the functional integrity of the BBB and that, in this DMHC pig model, darapladib reduces BBB permeability. Also, the preferential binding of IgG and coincident accumulation of Aβ42 in the same neurons suggests a mechanistic link between the leak of IgG through the BBB and intraneuronal deposition of Aβ42 in the brain.
In several domains of physics, including
first principle
simulations and classical models for polarizable systems, the minimization of an energy function with respect to a set of auxiliary variables ...must be performed to define the dynamics of physical degrees of freedom. In this paper, we discuss a recent algorithm proposed to efficiently and rigorously simulate this type of systems: the Mass-Zero (MaZe) Constrained Dynamics. In MaZe, the minimum condition is imposed as a constraint on the auxiliary variables treated as degrees of freedom of zero inertia driven by the physical system. The method is formulated in the Lagrangian framework, enabling the properties of the approach to emerge naturally from a fully consistent dynamical and statistical viewpoint. We begin by presenting MaZe for typical minimization problems where the imposed constraints are holonomic and summarizing its key formal properties, notably the exact Born–Oppenheimer dynamics followed by the physical variables and the exact sampling of the corresponding physical probability density. We then generalize the approach to the case of conditions on the auxiliary variables that linearly involve their velocities. Such conditions occur, for example, when describing systems in external magnetic field and they require to adapt MaZe to integrate semiholonomic constraints. The new development is presented in the second part of this paper and illustrated via a proof-of-principle calculation of the charge transport properties of a simple classical polarizable model of NaCl.
ESPRESSO at VLT Pepe, F.; Cristiani, S.; Rebolo, R. ...
Astronomy and astrophysics (Berlin),
01/2021, Letnik:
645
Journal Article
Recenzirano
Context.
ESPRESSO is the new high-resolution spectrograph of ESO’s Very Large Telescope (VLT). It was designed for ultra-high radial-velocity (RV) precision and extreme spectral fidelity with the aim ...of performing exoplanet research and fundamental astrophysical experiments with unprecedented precision and accuracy. It is able to observe with any of the four Unit Telescopes (UTs) of the VLT at a spectral resolving power of 140 000 or 190 000 over the 378.2 to 788.7 nm wavelength range; it can also observe with all four UTs together, turning the VLT into a 16 m diameter equivalent telescope in terms of collecting area while still providing a resolving power of 70 000.
Aims.
We provide a general description of the ESPRESSO instrument, report on its on-sky performance, and present our Guaranteed Time Observation (GTO) program along with its first results.
Methods.
ESPRESSO was installed on the Paranal Observatory in fall 2017. Commissioning (on-sky testing) was conducted between December 2017 and September 2018. The instrument saw its official start of operations on October 1, 2018, but improvements to the instrument and recommissioning runs were conducted until July 2019.
Results.
The measured overall optical throughput of ESPRESSO at 550 nm and a seeing of 0.65″ exceeds the 10% mark under nominal astroclimatic conditions. We demonstrate an RV precision of better than 25 cm s
−1
during a single night and 50 cm s
−1
over several months. These values being limited by photon noise and stellar jitter shows that the performance is compatible with an instrumental precision of 10 cm s
−1
. No difference has been measured across the UTs, neither in throughput nor RV precision.
Conclusions.
The combination of the large collecting telescope area with the efficiency and the exquisite spectral fidelity of ESPRESSO opens a new parameter space in RV measurements, the study of planetary atmospheres, fundamental constants, stellar characterization, and many other fields.
Abstract
Background
Mechanisms of cardiotoxicity during chimeric antigen receptor (CAR)-T cell therapy remain unclear to this day, with the main hypotheses revolving around IL-6 mediated myocardial ...depression during cytokine release syndrome (CRS), stress-induced or takotsubo cardiomyopathy, and direct toxicity from CAR-T cells. Hereby we present the experience of a regional referral centre for CAR-T therapy and the program developed with a dedicated cardio-oncology centre.
Purpose
To provide preliminary data on cardiovascular-related toxicity of CAR-T therapy in terms of incidence and management.
Methods
All consecutive candidates for CAR-T therapy were prospectively enrolled since the inception of the CAR-T program in our institution (2021). All patients were refractory to at least two lines of immune chemotherapy and had already undergone anthracycline treatment. After conditioning, all patients were treated with autologous CAR-T cells (tisagenlecleucel, Kymriah). Prior to CAR-T cell therapy, all patients underwent baseline cardiac evaluation at our cardio-oncology facility, including a 12-lead ECG, a complete echocardiogram and cardiac biomarkers. The same routine was performed before discharge, after one month. Supplementary evaluations were performed by an on-call cardio-oncology team according to the attending physicians.
Results
Eleven patients (6 males, mean age 60±11 years) underwent CAR-T cell infusion. Over the course of follow-up, six patients (54%) experienced CRS after a median follow-up of 12 days (7-40). Two patients with mild symptoms (Grade I) were managed with non-cardiac-related therapy while three Grade 2 patients had to start cardioprotective drugs (ACE-Is and beta-blockers) for transient left ventricular systolic dysfunction (mean lowest LVEF 44.8±3.7%). One patient experienced a Grade IV CRS due to takotsubo syndrome complicated by cardiogenic shock on day 4 and required high-dose vasopressors and mechanical ventilation. Patients experiencing a CRS had similar demographical characteristics and medical history but standard echocardiogram before CAR-T showed a lower baseline LVEF (54.5±5.6% vs 64.6±6.7%; p=.02) and lower baseline right longitudinal systolic function markers (TAPSE: 19±3 vs. 24±4 mm; p=.02 S': .09±.01 vs .13±.02 m/s; p=.03). Cardiac biomarkers (high-sensitivity Troponin I and NT-proBNP) did not show any significant predictive power at baseline. All CRS patients showed a progressive recovery of ventricular function and survived up to one-year of follow-up.
Conclusions
CAR-T therapy is associated with an increased risk of cardiotoxicity, with up to 36% of all patients requiring unscheduled cardio-oncology evaluation and management both during admission and after discharge. Cardiac adverse events range in degree of severity and should be promptly managed by a dedicated team.
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