Physics of B_c mesons

In the framework of potential models for heavy quarkonium the mass spectrum for the system ($\bar b c$) is considered. Spin-dependent splittings, taking into account a change of a constant for effective coulomb interaction between the quarks, and widths of radiative transitions between the ($\bar b c$) levels are calculated. In the framework of QCD sum rules, masses of the lightest vector $B_c^*$ and pseudoscalar $B_c$ states are estimated, scaling relation for leptonic constants of heavy quarkonia is derived, and the leptonic constant $f_{B_c}$ is evaluated. The $B_c$ decays are considered in the framework of both the potential models and the QCD sum rules, where the significance of Coulomb-like corrections is shown. The relations, following from the approximate spin symmetry for the heavy quarks in the heavy quarkonium, are analysed for the form factors of the semileptonic weak exclusive decays of $B_c$. The $B_c$ lifetime is evaluated with the account of the corrections to the spectator mechanism of the decay, because of the quark binding into the meson. The total and differential cross sections of the $B_c$ production in different interactions are calculated. The analytic expressions for the fragmentational production cross sections of $B_c$ are derived. The possibility of the practical $B_c$ search in the current and future experiments at electron-positron and hadron colliders is analysed.Comment: 81 page, latex, ihep.sty is required and attached in the end of the file after \end{document}, figures are not availabl

Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections

Polyclonal infections occur when at least two unrelated strains of the same pathogen are detected in an individual. This has been linked to worse clinical outcomes in tuberculosis, as undetected strains with different antibiotic resistance profiles can lead to treatment failure. Here, we examine the amount of polyclonal infections in sputum and surgical resections from patients with tuberculosis in the country of Georgia. For this purpose, we sequence and analyse the genomes of Mycobacterium tuberculosis isolated from the samples, acquired through an observational clinical study (NCT02715271). Access to the lung enhanced the detection of multiple strains (40% of surgery cases) as opposed to just using a sputum sample (0-5% in the general population). We show that polyclonal infections often involve genetically distant strains and can be associated with reversion of the patient's drug susceptibility profile over time. In addition, we find different patterns of genetic diversity within lesions and across patients, including mutational signatures known to be associated with oxidative damage; this suggests that reactive oxygen species may be acting as a selective pressure in the granuloma environment. Our results support the idea that the magnitude of polyclonal infections in high-burden tuberculosis settings is underestimated when only testing sputum samples

Rifapentine access in Europe: growing concerns over key tuberculosis treatment component

[No abstract available]Support statement: C. Lange is supported by the German Center of Infection Research (DZIF). All other authors have no funding to declare for this study. Funding information for this article has been deposited with the Crossref Funder Registry

Genetic diversity within diagnostic sputum samples is mirrored in the culture of Mycobacterium tuberculosis across different settings

11 páginas, 6 figurasCulturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants' frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.This work has been supported by the following: European Research Council (ERC): H2020-ERC-COG/0800; Ministerio Español de Ciencia e Innovación: PID2022-137607OB-I00 and Fundació La Caixa: HR21-00415 received by I.C; Stop TB partnership (TB REACH): STBP/ TBREACH/GSA/W5-30 received by A.G.B; and International Science and Technology Center (ISTC): Project #G-2143; National Institute of Allergy and Infectious Diseases (NIH) received by N.S. We would like to thank Katharine Walter for reviewing the manuscript and providing her feedbackPeer reviewe

Clinical outcomes among patients with tuberculous meningitis receiving intensified treatment regimens

SETTING: National Center for Tuberculosis and Lung Diseases (NCTLD), Tbilisi, Georgia.OBJECTIVE: To determine clinical outcomes of patients with tuberculous meningitis (TBM) treated with an intensified regimen including a fluoroquinolone (FQ) and an injectable agent.DESIGN: Prospective cohort of patients aged ≥16 years initiating treatment for TBM at the NCTLD from January 2018 to December 2019. Treatment outcomes and neurologic disability at 1, 6 and 12 months after treatment initiation were assessed.RESULTS: Among 77 patients with median follow-up time of 363 days (IQR 269–374), 97% received a FQ, 62% an injectable agent, 44% linezolid and 39% a carbapenem. Fifty-seven patients (74%) successfully completed treatment, 2 (2.6%) had treatment failure, 6 (7.8%) died, and the remainder (12%) were lost to follow up. Among 11 patients treated for multidrug-resistant TBM, the median follow-up time was 467 days and one patient (8%) died. Regarding neurologic outcomes, 14/76 (18%) patients had Modified Rankin Scores of 0 at baseline, improving to 85% (56/66) and 94% (47/50) at 6 and 12 months, respectively.CONCLUSION: Intensified multidrug treatment regimens including a FQ and an injectable agent in all patients and newly implemented drugs in patients with multidrug-resistant TBM resulted in low mortality and favorable neurologic outcomes.</jats:p

DREADDs suppress seizure-like activity in a mouse model of pharmacoresistant epileptic brain tissue

Epilepsy is a neurological disorder with a prevalence of ≈1% of general population. Available antiepileptic drugs (AEDs) have multiple side effects and are ineffective in 30% of patients. Therefore, development of effective treatment strategies is highly needed, requiring drug-screening models that are relevant and reliable. We investigated novel chemogenetic approach, using DREADDs (designer receptors exclusively activated by designer drugs) as possible inhibitor of epileptiform activity in organotypic hippocampal slice cultures (OHSCs). The OHSCs are characterized by increased overall excitability and closely resemble features of human epileptic tissue. Studies suggest that chemically induced epileptiform activity in rat OHSCs is pharmacoresistant to most of AEDs. However, high-frequency electric stimulus train-induced bursting (STIB) in OHSCs is responsive to carbamazepine and phenytoin. We investigated whether inhibitory DREADD, hM4Di, would be effective in suppressing STIB in OHSC. hM4Di is a mutated muscarinic receptor selectively activated by otherwise inert clozapine-N-oxide, which leads to hyperpolarization in neurons. We demonstrated that this hyperpolarization effectively suppresses STIB in mouse OHSCs. As we also found that STIB in mouse OHSCs is resistant to common AED, valproic acid, collectively our findings suggest that DREADD-based strategy may be effective in suppressing epileptiform activity in a pharamcoresitant epileptic brain tissue