Reduced lysosomal acid lipase activity in blood and platelets is associated with nonalcoholic fatty liver disease

OBJECTIVES: To investigate whether blood total lysosomal acid lipase activity (BT-LAL) levels are uniquely associated with the noncirrhotic and cirrhotic stages of nonalcoholic fatty liver disease (NAFLD) and with protection from NAFLD in metabolically/genetically predisposed subjects and a normal liver. To clarify which enzyme-carrying circulating cells are involved in reduced BT-LAL of NAFLD.METHODS: In a cross-sectional study, BT-LAL was measured by a fluorigenic method in patients with NAFLD (n = 118), alcoholic (n = 116), and hepatitis C virus-related disease (n = 49), in 103 controls with normal liver and in 58 liver transplant recipients. Intracellular platelet and leukocyte LAL was measured in 14 controls and 28 patients with NAFLD.RESULTS: Compared with controls, (i) BT-LAL and LAL in platelets, but not in leukocytes, were progressively reduced in noncirrhotic NAFLD and in nonalcoholic steatohepatitis-related cirrhosis; (ii) platelet and leukocyte counts did not differ in patients with noncirrhotic NAFLD; and (iii) BT-LAL did not differ in alcoholic and hepatitis C virus noncirrhotic patients. BT-LAL progressively increased in controls with metabolic syndrome features according to their PNPLA3 rs738409 steatosis-associated variant status (II vs IM vs MM), and their BT-LAL was higher than that of noncirrhotic NAFLD, only when carriers of the PNPLA3 unfavorable alleles were considered. Liver transplant recipients with de novo NAFLD compared with those without de novo NAFLD had lower BT-LAL.DISCUSSION: LAL in blood and platelets is progressively and uniquely reduced in NAFLD according to disease severity. High BT-LAL is associated with protection from NAFLD occurrence in subjects with metabolic and genetic predisposition. Low LAL in platelets and blood could play a pathogenetic role in NAFLD

Gamma-Ray Burst observations by the high-energy charged particle detector on board the CSES-01 satellite between 2019 and 2021

In this paper we report the detection of five strong Gamma-Ray Bursts (GRBs) by the High-Energy Particle Detector (HEPD-01) mounted on board the China Seismo-Electromagnetic Satellite (CSES-01), operational since 2018 on a Sun-synchronous polar orbit at a $\sim$ 507 km altitude and 97$^\circ$ inclination. HEPD-01 was designed to detect high-energy electrons in the energy range 3 - 100 MeV, protons in the range 30 - 300 MeV, and light nuclei in the range 30 - 300 MeV/n. Nonetheless, Monte Carlo simulations have shown HEPD-01 is sensitive to gamma-ray photons in the energy range 300 keV - 50 MeV, even if with a moderate effective area above $\sim$ 5 MeV. A dedicated time correlation analysis between GRBs reported in literature and signals from a set of HEPD-01 trigger configuration masks has confirmed the anticipated detector sensitivity to high-energy photons. A comparison between the simultaneous time profiles of HEPD-01 electron fluxes and photons from GRB190114C, GRB190305A, GRB190928A, GRB200826B and GRB211211A has shown a remarkable similarity, in spite of the different energy ranges. The high-energy response, with peak sensitivity at about 2 MeV, and moderate effective area of the detector in the actual flight configuration explain why these five GRBs, characterised by a fluence above $\sim$ 3 $\times$ 10$^{-5}$ erg cm$^{-2}$ in the energy interval 300 keV - 50 MeV, have been detected.Comment: Accepted for publication in The Astrophysical Journal (ApJ

Antibiotic-Loaded Coatings to Reduce Fracture-Related Infections: Retrospective Case Series of Patients with Increased Infectious Risk

Local antibiotic delivery strategies have been increasingly employed for the prevention of fracture-related infections (FRIs). The aim of this study is to evaluate the efficacy and safety of antibiotic-coated implants in the prevention of FRIs after surgical treatment in patients with increased infectious risk. A retrospective observational study has been conducted on patients with upper and lower limb fractures treated with internal fixation or prosthetic replacements, using a gentamicin coated nail (CN) and/or antibiotic-loaded hydrogel applied to the implant of choice (ALH). The study included 37 patients (20 M, 17 F), with a mean age of 63 years. The mean estimated preoperative infectious risk score was 6.4%. ALH was used in 27 cases, tibial CNs were implanted in 4 cases, and both were employed in 6 cases. The antibiotics used locally were gentamicin in 72.97% of cases (27 patients) and a combination of gentamicin + vancomycin in 27.03% of cases (10 patients). Mean follow-up was 32 months. Only one case (2.94%) showed onset of FRI at 5 months after surgery. Local antibiotic prophylaxis by coating resulted in a reduction in the incidence FRI, as compared to the estimated preoperative risk. The use of ALH allows for the choice of antibiotic; however, the application of antibiotics seems more nonuniform when applied to a nail

Brief Report: Relationship Between Cotinine Levels and Peripheral Endogenous Concentrations of Oxytocin, β‐Endorphin, and Orexin in Individuals With Both Alcohol and Nicotine Use Disorders

Background and Objectives In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, β‐endorphin, melatonin, α‐melanocyte‐stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ‐glutamyl transferase [GGT]) as well as with self‐reported smoking and alcohol drinking. Methods Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune‐assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson\u27s correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two‐sided statistical tests. Results We found significant positive correlations for cotinine and oxytocin (P = .002), β‐endorphin (P = .008), and orexin (P \u3c .001), but not for either GGT or self‐reported smoking or alcohol drinking. Conclusion and Scientific Significance These preliminary results suggest a relationship between cotinine and oxytocin, β‐endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2020;00:00–00

Diagnosis of alcohol use disorder from a psychological point of view

Alcohol use disorder (AUD) is one of the most common psychiatric disease in the general population, characterized by having a pattern of excessive drinking despite the negative effects of alcohol on the individual's work, medical, legal, educational, and/or social life. Currently, the bio-psycho-social model describes properly AUD as a multidimensional phenomenon including biological, psychological, and socio-cultural variables affecting the nature, maintenance, and expression of the disorder. The AUD diagnostic process is crucial since the treatment success depends heavily on the accuracy and the adequacy of the diagnosis. The diagnosis is based on a comprehensive assessment of the patient's characteristics and uses interviews and psychometric instruments for collecting information. This paper will provide insights into the most important psychological dimensions of AUD and on the best psychometric instruments for proposing AUD diagnosis

Evidence of an upper ionospheric electric field perturbation correlated with a gamma ray burst

Abstract Earth’s atmosphere, whose ionization stability plays a fundamental role for the evolution and endurance of life, is exposed to the effect of cosmic explosions producing high energy Gamma-ray-bursts. Being able to abruptly increase the atmospheric ionization, they might deplete stratospheric ozone on a global scale. During the last decades, an average of more than one Gamma-ray-burst per day were recorded. Nevertheless, measurable effects on the ionosphere were rarely observed, in any case on its bottom-side (from about 60 km up to about 350 km of altitude). Here, we report evidence of an intense top-side (about 500 km) ionospheric perturbation induced by significant sudden ionospheric disturbance, and a large variation of the ionospheric electric field at 500 km, which are both correlated with the October 9, 2022 Gamma-ray-burst (GRB221009A)

Measurement of (anti)alpha production in central Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 5.02 TeV

International audienceIn this letter, measurements of (anti)alpha production in central (0$-$10%) Pb$-$Pb collisions at a center-of-mass energy per nucleon$-$nucleon pair of $\sqrt{s_{\rm NN}}$ = 5.02 TeV are presented, including the first measurement of an antialpha transverse-momentum spectrum. Owing to its large mass, (anti)alpha production yields and transverse-momentum spectra are of particular interest because they provide a stringent test of particle production models. The averaged antialpha and alpha spectrum is included into a common blast-wave fit with lighter particles, indicating that the (anti)alpha also participates in the collective expansion of the medium created in the collision. A blast-wave fit including only protons, (anti)alpha, and other light nuclei results in a similar flow velocity as the fit that includes all particles. A similar flow velocity, but a significantly larger kinetic freeze-out temperature is obtained when only protons and light nuclei are included in the fit. The coalescence parameter $B_4$ is well described by calculations from a statistical hadronization model but significantly underestimated by calculations assuming nucleus formation via coalescence of nucleons. Similarly, the (anti)alpha-to-proton ratio is well described by the statistical hadronization model. On the other hand, coalescence calculations including approaches with different implementations of the (anti)alpha substructure tend to underestimate the data

Measurements of jet quenching using semi-inclusive hadron+jet distributions in pp and central Pb−-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV

International audienceThe ALICE Collaboration reports measurements of the semi-inclusive distribution of charged-particle jets recoiling from a high transverse momentum (high $p_{\rm T}$) charged hadron, in pp and central Pb$-$Pb collisions at center of mass energy per nucleon$-$nucleon collision $\sqrt{s_{\rm NN}}=5.02$ TeV. The large uncorrelated background in central Pb$-$Pb collisions is corrected using a data-driven statistical approach, which enables precise measurement of recoil jet distributions over a broad range in $p_{\rm T,ch\,jet}$ and jet resolution parameter $R$. Recoil jet yields are reported for $R=0.2$, 0.4, and 0.5 in the range $7 < p_{\rm T,ch\, jet} < 140$ GeV$/c$ and $\pi/2<\Delta\varphi<\pi$, where $\Delta\varphi$ is the azimuthal angular separation between hadron trigger and recoil jet. The low $p_{\rm T,ch\,jet}$ reach of the measurement explores unique phase space for studying jet quenching, the interaction of jets with the quark-gluonnplasma generated in high-energy nuclear collisions. Comparison of $p_{\rm T,ch\,jet}$ distributions from pp and central Pb$-$Pb collisions probes medium-induced jet energy loss and intra-jet broadening, while comparison of their acoplanarity distributions explores in-medium jet scattering and medium response. The measurements are compared to theoretical calculations incorporating jet quenching

Multiplicity-dependent production of Σ(1385)±\Sigma(1385)^{\pm} and Ξ(1530)0\Xi(1530)^{0} in pp collisions at s=13\sqrt{s}=13 TeV

International audienceThe production yields of the $\Sigma(1385)^{\pm}$ and $\Xi(1530)^{0}$ resonances are measured in pp collisions at $\sqrt{s}=13$ TeV with ALICE. The measurements are performed as a function of the charged particle multiplicity $\langle \mathrm{d}N_\mathrm{ch}/\mathrm{d}\eta \rangle$, which is related to the energy density produced in the collision. The results include transverse momentum ($p_{\rm T}$) distributions, $p_{\rm T}$-integrated yields, mean transverse momenta of $\Sigma(1385)^{\pm}$ and $\Xi(1530)^{0}$, as well as ratios of the $p_{\rm T}$-integrated resonance yields relative to yields of other hadron species. The $\Sigma(1385)^{\pm}/\pi^{\pm}$ and $\Xi(1530)^{0}/\pi^{\pm}$ yield ratios are consistent with the trend of the enhancement of strangeness production from low to high multiplicity pp collisions, which was previously observed for strange and multi-strange baryons. The yield ratio between the measured resonances and the long-lived baryons with the same strangeness content exhibits a hint of a mild increasing trend at low multiplicity, despite too large uncertainties to exclude the flat behaviour. The results are compared to predictions from models such as EPOS-LHC and PYTHIA 8 with Rope shoving. The latter provides the best description of the multiplicity dependence of the $\Sigma(1385)^{\pm}$ and $\Xi(1530)^{0}$ production in pp collisions at $\sqrt{s}=13$ TeV