Crystal fields, disorder, and antiferromagnetic short-range order in Yb0.24Sn0.76Ru

We report extensive measurements on a new compound (Yb0.24Sn0.76)Ru that crystallizes in the cubic CsCl structure. Valence band photoemission and L3 x-ray absorption show no divalent component in the 4f configuration of Yb. Inelastic neutron scattering (INS) indicates that the eight-fold degenerate J-multiplet of Yb3+ is split by the crystalline electric field (CEF) into a {\Gamma}7 doublet ground state and a {\Gamma}8 quartet at an excitation energy 20 meV. The magnetic susceptibility can be fit very well by this CEF scheme under the assumption that a {\Gamma}6 excited state resides at 32 meV; however, the {\Gamma}8/{\Gamma}6 transition expected at 12 meV was not observed in the INS. The resistivity follows a Bloch- Gr\"uneisen law shunted by a parallel resistor, as is typical of systems subject to phonon scattering with no apparent magnetic scattering. All of these properties can be understood as representing simple local moment behavior of the trivalent Yb ion. At 1 K, there is a peak in specific heat that is too broad to represent a magnetic phase transition, consistent with absence of magnetic reflections in neutron diffraction. On the other hand, this peak also is too narrow to represent the Kondo effect in the {\Gamma}7 ground state doublet. On the basis of the field-dependence of the specific heat, we argue that antiferromagnetic shortrange order (possibly co-existing with Kondo physics) occurs at low temperatures. The long-range magnetic order is suppressed because the Yb site occupancy is below the percolation threshold for this disordered compound

Plant species of Sub-Family Valerianaceae—A review on its effect on the Central Nervous System

Valerianaceae, the sub-family of Caprifoliaceae, contains more than 300 species of annual and perennial herbs, worldwide distributed. Several species are used for their biological properties while some are used as food. Species from the genus Valeriana have been used for their antispasmodic, relaxing, and sedative properties, which have been mainly attributed to the presence of valepotriates, borneol derivatives, and isovalerenic acid. Among this genus, the most common and employed species is Valerianaofficinalis. Although valerian has been traditionally used as a mild sedative, research results are still controversial regarding the role of the different active compounds, the herbal preparations, and the dosage used. The present review is designed to summarize and critically describe the current knowledge on the different plant species belonging to Valerianaceae, their phytochemicals, their uses in the treatment of different diseases with particular emphasis on the effects on the central nervous system. The available information on this sub-family was collected from scientific databases up until year 2020. The following electronic databases were used: PubMed, Scopus, Sci Finder, Web of Science, Science Direct, NCBI, and Google Scholar. The search terms used for this review included Valerianaceae, Valeriana, Centranthus, Fedia, Patrinia, Nardostachys, Plectritis, and Valerianella, phytochemical composition, in vivo studies, Central Nervous System, neuroprotective, antidepressant, antinociceptive, anxiolytic, anxiety, preclinical and clinical studies.UIDB/05183/2020, DL 57/2016/CP1361/CT0022, UIDB/00313/2020info:eu-repo/semantics/publishedVersio

Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blinded, placebo controlled, multicenter study

IntroductionRight ventricular (RV) function is a major determinant of outcome in patients with precapillary pulmonary hypertension (PH). We studied the effect of ranolazine on RV function over 6 months using multi-modality imaging and biochemical markers in patients with precapillary PH (groups I, III, and IV) and RV dysfunction [CMR imaging ejection fraction (EF) < 45%] in a longitudinal, randomized, double-blinded, placebo-controlled, multicenter study of ranolazine treatment.MethodsEnrolled patients were assessed using cardiac magnetic resonance (CMR) imaging, 11C-acetate and 18-F-FDG positron emission tomography (PET), and plasma metabolomic profiling, at baseline and at the end of treatment.ResultsTwenty-two patients were enrolled, and 15 patients completed all follow-up studies with 9 in the ranolazine arm and 6 in the placebo arm. RVEF and RV/Left ventricle (LV) mean glucose uptake were significantly improved after 6 months of treatment in the ranolazine arm. Metabolomic changes in aromatic amino acid metabolism, redox homeostasis, and bile acid metabolism were observed after ranolazine treatment, and several changes significantly correlated with changes in PET and CMR-derived fluid dynamic measurements.DiscussionRanolazine may improve RV function by altering RV metabolism in patients with precapillary PH. Larger studies are needed to confirm the beneficial effects of ranolazine

Antiviral susceptibility of clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses isolated from birds and mammals in the United States, 2022

Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) A(H5N1) viruses that are responsible for devastating outbreaks in birds and mammals pose a potential threat to public health. Here, we evaluated their susceptibility to influenza antivirals. Of 1,015 sequences of HPAI A(H5N1) viruses collected in the United States during 2022, eight viruses (∼0.8%) had a molecular marker of drug resistance to an FDA-approved antiviral: three adamantane-resistant (M2-V27A), four oseltamivir-resistant (NA-H275Y), and one baloxavir-resistant (PA-I38T). Additionally, 31 viruses contained mutations that may reduce susceptibility to inhibitors of neuraminidase (NA) (n = 20) or cap-dependent endonuclease (CEN) (n = 11). A panel of 22 representative viruses was tested phenotypically. Overall, clade 2.3.4.4b A(H5N1) viruses lacking recognized resistance mutations were susceptible to FDA-approved antivirals. Oseltamivir was least potent at inhibiting NA activity, while the investigational NA inhibitor AV5080 was most potent, including against NA mutants. A novel NA substitution T438N conferred 12-fold reduced inhibition by zanamivir, and in combination with the known marker N295S, synergistically affected susceptibility to all five NA inhibitors. In cell culture-based assays HINT and IRINA, the PA-I38T virus displayed 75- to 108-fold and 37- to 78-fold reduced susceptibility to CEN inhibitors, baloxavir and the investigational AV5116, respectively. Viruses with PA-I38M or PA-A37T showed 5- to 10-fold reduced susceptibilities. As HPAI A(H5N1) viruses continue to circulate and evolve, close monitoring of drug susceptibility is needed for risk assessment and to inform decisions regarding antiviral stockpiling

Using Macro-Arrays to Study Routes of Infection of Helicobacter pylori in Three Families

allowed tracing the spread of infection through populations on different continents but transmission pathways between individual humans have not been clearly described.To investigate person-to-person transmission, we studied three families each including one child with persistence of symptoms after antibiotic treatment. Ten isolates from the antrum and corpus of stomach of each family member were analyzed both by sequencing of two housekeeping genes and macroarray tests. from outside the family appeared to be probable in the transmission pathways. infection may be acquired by more diverse routes than previously expected

Novel Small-Molecule Inhibitors of Hepatitis C Virus Entry Block Viral Spread and Promote Viral Clearance in Cell Culture

Combinations of direct-acting anti-virals offer the potential to improve the efficacy, tolerability and duration of the current treatment regimen for hepatitis C virus (HCV) infection. Viral entry represents a distinct therapeutic target that has been validated clinically for a number of pathogenic viruses. To discover novel inhibitors of HCV entry, we conducted a high throughput screen of a proprietary small-molecule compound library using HCV pseudoviral particle (HCVpp) technology. We independently discovered and optimized a series of 1,3,5-triazine compounds that are potent, selective and non-cytotoxic inhibitors of HCV entry. Representative compounds fully suppress both cell-free virus and cell-to-cell spread of HCV in vitro. We demonstrate, for the first time, that long term treatment of an HCV cell culture with a potent entry inhibitor promotes sustained viral clearance in vitro. We have confirmed that a single amino acid variant, V719G, in the transmembrane domain of E2 is sufficient to confer resistance to multiple compounds from the triazine series. Resistance studies were extended by evaluating both the fusogenic properties and growth kinetics of drug-induced and natural amino acid variants in the HCVpp and HCV cell culture assays. Our results indicate that amino acid variations at position 719 incur a significant fitness penalty. Introduction of I719 into a genotype 1b envelope sequence did not affect HCV entry; however, the overall level of HCV replication was reduced compared to the parental genotype 1b/2a HCV strain. Consistent with these findings, I719 represents a significant fraction of the naturally occurring genotype 1b sequences. Importantly, I719, the most relevant natural polymorphism, did not significantly alter the susceptibility of HCV to the triazine compounds. The preclinical properties of these triazine compounds support further investigation of entry inhibitors as a potential novel therapy for HCV infection