Individuals in close contact with multidrug-resistant tuberculosis (MDR-TB) patients are subject to an elevated risk of infection, and may develop latent MDR-TB infection. Numerous studies have described latent tuberculosis infection (LTBI) as a reservoir of new TB disease. The screening and treatment of latent MDR-TB infection are challenging. Hereby, we reviewed the epidemiology, current management and prevention approach of LTBI in MDR-TB close contacts, to provide additional information for future research direction and policy design formulation to reduce the LTBI reservoir.
Antimicrobial peptides (AMPs) are inherently occurring proteins that are produced by microorganisms as secondary metabolites. Members of genus Bacillus produce many types of AMPs by ribosomal (bacteriocins) and non-ribosomal (polymyxins and iturins) mechanisms. Bacteriocins are ribosomally synthesized peptides that inhibit the growth of closely related bacterial strains. Moreover, bacteriocins produced by Bacillus species have been widely used in pharmaceutical, food industry, fishery, livestock as well as in agriculture sector. The objective of this review is to assess the characterization of the Bacillus-derived bacteriocins, their potential use in different sectors and structure-activity relationships.
The purpose of this narrative review is to provide an overview of the real-world data on the use of tofacitinib in patients with active rheumatoid arthritis (RA) in Spain. Sixteen retrospective studies carried out in Spain between 2019 and 2021 have been analyzed, considering patients' characteristics, and treatment patterns, effectiveness, and safety. In those studies, approximately 511 patients received tofacitinib during the study period. They were predominantly women (mean age: 48-61 years). The percentage of patients receiving tofacitinib as monotherapy ranged between 20.0% and 67.9%. Only five studies reported the combined use of corticosteroids (42.0-84.5% of patients), with a mean dose varying from 1.8 to 7.2 mg. A wide range of patients (36.0-85.7%) had failed a previous biological disease-modifying anti-rheumatic drug. The most frequent reason for treatment discontinuation was the lack of efficacy, and the most common adverse event described was herpes zoster infection. Real-world studies complement clinical trials by adding efficacy and safety data in real-world settings to the benefit/risk profile of the drug. The profile of RA patients receiving tofacitinib in Spain has similarities with other real-world studies conducted in other countries.
The detergency of special electrolytic-reduction ion water (S-100) was evaluated in comparison with typical synthetic surfactants. Furthermore, to examine the cleaning mechanism of S-100, various physicochemical characteristics of S-100 were measured and a comprehensive evaluation of cleaning was performed. S-100 (10%) had a detergency comparable to that of various surfactants, such as sodium dodecyl sulfate and sodium dodecyl benzene sulfonate, which are generally blended or mixed in residential detergents. In addition, concentrated aqueous solutions of 10% or more of S-100 showed stronger detergency. The cleaning mechanism of S-100 is mainly attributed to the effect of surface tension reduction due to dissolved hydrogen or hydrogen nanobubbles in S-100, and the alkalinity generated by electrolysis charged the surface of the dirt or adherend, resulting in a peeling effect.
Smokers may have lower antibody titers after vaccination with a coronavirus disease 2019 (COVID-19) mRNA vaccine. However, to the best of our knowledge, no study has evaluated antibody titers after COVID-19 vaccination based on the level of smokers' cigarette dependence. In this study, we measured the level of serum anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) spike protein receptor-binding domain (S-RBD) immunoglobulin-G (IgG) by enzyme linked immunosorbent assay of 55 actively smoking Japanese social workers (firefighters, paramedics, and rescue workers) who had received two doses of the BNT162b2 vaccine. Further, we assessed their cigarette dependence using the Fagerstrom Test for Nicotine Dependence (FTND), measured their serum cotinine levels, and tested for their correlation with anti-RBD IgG levels. Serum anti-SARS-CoV-2 S-RBD protein IgG levels after BNT162b2 vaccination showed a significant negative correlation with FTND (ρ = -0.426, p = 0.001). In addition, serum cotinine level showed a significant positive correlation with FTND (ρ = 0.470, p = 0.000). However, no significant negative correlation was noted between serum cotinine and serum anti-SARS-CoV-2 S-RBD protein IgG levels (ρ = -0.156, p = 0.256). Our results suggest that smokers with strong cigarette dependence have inadequate anti-SARS-CoV-2 S-RBD protein IgG levels after COVID-19 mRNA vaccination.
Hepatitis B virus genotype C (HBV/C) is one of the most prevalent HBV strains worldwide, especially in the Western Pacific and the South-East Asia. However, the origin and evolutionary timescale of HBV/C remains largely unresolved. We analyzed the evolutionary rate and molecular clock phylogeny of 101 full-genome HBV/C sequences sampled globally using a Bayesian Markov Chain Monte Carlo (MCMC) approach. We inferred the spatiotemporal dynamics of the HBV/C worldwide by the Bayesian Stochastic Search Variable Selection (BSSVS). We found that the estimated mean evolution rate of the HBV/C genotype full-genome was 4.32 × 10-5 subs/site/year (95% highest posterior density 3.02 × 10-6 - 8.97 × 10-5). Phylogeographic reconstruction was able to identify a single location for the origin of the global HBV/C in Australia around A.D. 715. The subgenotype C4 diverged earliest and mainly circulated in Australia, C1 mainly in Southeast Asia, C2 mainly in East Asia and C3 in Remote Oceania. The effective number of HBV infection presented a rapid exponential increase between the 1760s and 1860s followed by a maintained high level until now. Our study, for the first time, provides an estimated timescale for the HBV/C epidemic, and brings new insight to the dispersal of HBV/C in humans globally. Based on the continuous presence of a highly effective viral population, this study provides further evidence of the challenge from a population-based molecular level to eliminate HBV by 2030, and calls for a concerted effort from policy makers, health providers, and society in the globalized world.
Recent studies revealed the involvement of "chronic inflammation" in the pathogenesis of schizophrenia. In schizophrenia and some neurodegenerative disorders that are caused by inflammation, T-lymphocytes and macrophages were hyperactivated or proliferated in the central nervous system, being accompanied by the overexpression of delayed rectifier K+-channels (Kv1.3) within the cells. In our previous basic studies, in addition to nonsteroidal anti-inflammatory drugs (NSAIDs) and statins, antibiotics (clarithromycin, chloroquine), anti-hypertensive drugs (nifedipine, benidipine, diltiazem, verapamil) and anti-allergic drugs (cetirizine, fexofenadine, azelastine, terfenadine) strongly suppressed the Kv1.3-channel activity and pro-inflammatory cytokine production from lymphocytes. Given such pharmacological properties of these commonly used drugs, they may be useful in the treatment of schizophrenia, in which the enhanced cellular immunity and the subsequent release of excessive cytokines are responsible for the pathogenesis.
Linezolid has been one of the key anti-tuberculosis agents for the treatment of multidrug-resistant tuberculosis (MDR-TB)/extensively drug-resistant tuberculosis (XDR-TB). It used to be very expensive and was not covered by social insurance from local governments. Nevertheless, a growing number of patients in China received linezolid in their anti- MDR/XDR TB regimens over the past decade. Many scholars in China have reported their experience using linezolid to treat patients with MDR/XDR-TB. In view of this, existing evidence of the efficacy and safety of linezolid and problems faced by Chinese patients with MDR/XDR-TB are summarized here.
Tuberculosis has become a great global public health threat. Compared with drug-susceptible tuberculosis (TB), the treatment regimens for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) involve more severe adverse events and poorer treatment outcomes. Linezolid (LZD) is the first oxazolidinones used for TB. Thanks to its potent activity against Mycobacterium tuberculosis, LZD has become one of the key agents in the regimens against MDR/XDR-TB. However, this drug may cause intolerability and other adverse events. Contezolid, another novel oxazolidinone, can also inhibit M. tuberculosis, still with fewer adverse effects compared with LZD. This paper is to prospect the potentials of contezolid in the treatment of MDR/XDR-TB, with focus on its efficacy and possible adverse effects.
Myelopathy in central nervous system tuberculosis is notorious for poor outcomes, determined by the severity of inflammation and cord level involved. Acute-onset quadriplegia or paraplegia in these cases represents a neuro-emergency. We report a young female with disseminated tuberculosis who presented with acute onset flaccid quadriparesis with loss of bladder and bowel function. Imaging helped identify the extensive involvement of the neuraxis. We propose that, in addition to anti-tubercular therapy, high-dose corticosteroids such as pulse methylprednisolone may result in a meaningful improvement and show greater rapidity of response in cases of severe central nervous system inflammation such as arachnoiditis or myelopathy.