Non-tuberculous mycobacterial disease associated with Mycobacterium montefiorense in salamanders.

Introduction: Mycobacterium montefiorense is one of the causes of non-tuberculous mycobacterial infections in moray eels and salamanders. Although M. montefiorense infection could be a threat to salamanders, little information is available regarding this pathogen and associated infection. This study aimed to provide fundamental information regarding M. montefiorense and its infection in salamanders. Methods: Nine M. montefiorense strains isolated from three species of salamanders, namely, Japanese black salamander (Hynobius nigrescens), Hakuba salamander (H. hidamontanus), and Tohoku hynobiid salamander (H. lichenatus), between 2010 and 2018, were characterized based on phenotypic and genetic examination. We also pathologically observed salamanders infected with the M. montefiorense strains, including Hakuba salamanders and Tohoku hynobiid salamanders. Results: The microbiological and chemical characteristics of the M. montefiorense salamander and an eel strain (reference strain) matched. Susceptibility testing for antimicrobials suggested that clarithromycin may be effective. Regarding disinfectants, phtharal, peracetic acid, glutaral, sodium hypochlorite, and benzalkonium chloride may be effective. Phylogenetic analyses revealed that the strains isolated from salamanders in 2014 and 2018 were genetically closely related, which could indicate an outbreak. The main gross findings in infected salamanders include skin ulcerative lesions or nodules in the enlarged liver. Microscopically, multifocal to coalescent granulomatous lesions composed of massive macrophages containing numerous acid-fast bacilli were prominently observed in the liver. Conclusion: This study contributes to our understanding of the genetic diversity and phenotypic characteristics of M. montefiorense, as well as the pathology of the infection.

Modulation of Double Zwitterionic Block Copolymer Aggregates by Zwitterion-Specific Interactions.

Transformable double hydrophilic block copolymer assemblies are valid as a biocompatible smart macromolecular system. The molecular mechanisms in the spontaneous assembly of double zwitterionic diblock copolymers composed of a poly(carboxybetaine methacrylate) (PCB2) and a poly(sulfobetaine methacrylate) (PSB4) chains (PCB2-b-PSB4) were investigated by the modulation of the aggregates in response to nondetergent zwitterions. The PCB2-b-PSB4 diblock copolymers with a high degree of polymerization PSB4 block produced aggregates in salt-free water through "zwitterion-specific" interactions. The PCB2-b-PSB4 aggregates were dissociated by the addition of nondetergent sulfobetaine (SB4) and carboxybetaine (CB2) molecules, while the aggregates showed different aggregation modulation processes for SB4 and CB2. Zwitterions with different charged groups from SB4 and CB2, glycine and taurine, hardly disrupted the PCB2-b-PSB4 aggregates. The PCB2-b-PSB4 aggregate modulation efficiency of SBs associated with the intercharge hydrocarbon spacer length (CSL) rather than the symmetry with the SB in the PSB chain. These zwitterion-specific modulation behaviors were rationalized based on the nature of zwitterions including partial charge density, dipole moment, and hydrophobic interactions depending on the charged groups and CSL.

Prognostic Value of BNP Reduction During Hospitalization in Patients With Acute Heart Failure.

BACKGROUND: Prognostication of patients discharged after acute heart failure (AHF) hospitalization remains challenging. Body weight (BW) reduction is often used as a surrogate marker of decongestion despite the paucity of evidence. We thought to test the hypothesis that B-type natriuretic peptide (BNP) reduction during hospitalization has independent prognostic value in AHF. METHODS AND RESULTS: We studied the prognostic predictability of percentage BNP reduction achieved during hospitalization in patients from the REALITY-AHF study. Percentage BNP reduction was defined as (BNP on admission - BNP at discharge) / BNP on admission × 100. The primary endpoint was 1-year all-cause death. In 1028 patients (age, 77 ± 13 years; 57% male; left ventricular ejection fraction, 47 ± 16%) with AHF, median BNP level at admission was 747 ng/L (interquartile range, 439-1367 ng/L) and median percentage BNP reduction was 62.5% (interquartile range, 36.5-78.5%). The smallest percentage BNP reduction quartile had more than 2-fold higher risk of all-cause death than the greatest quartile (23.0% vs 9.7%, P< .001). After adjusting for covariates including BNP at discharge, the percentage BNP reduction was significantly associated with all-cause death (hazard ratio 0.96, 95% confidence interval 0.93-0.99, P= .032), whereas percentage BW reduction was not. Percentage BNP reduction was more predictive in patients with heart failure with reduced ejection fraction than in those with preserved ejection fraction. CONCLUSIONS: The prognostic value of percentage BNP reduction during hospitalization was superior to that of percentage BW reduction and was independent of other risk markers, including BNP at discharge.

Draft Genome Sequence of Mycobacterium montefiorense Isolated from Japanese Black Salamander (Hynobius nigrescens).

Mycobacterium montefiorense is a member of the Mycobacterium simiae complex, the largest group of nontuberculous mycobacteria. Here, we report the genome sequence of M. montefiorense isolate BS, isolated from diseased Japanese black salamander (Hynobius nigrescens) reared in an aquarium in Japan. This is the first reported case of an M. montefiorense infection in an amphibian.

Metabonomic study on the biochemical response of spontaneously hypertensive rats to chronic taurine supplementation using (1)H NMR spectroscopic urinalysis.

There is a wealth of experimental information and some clinical evidence available in the literature suggesting that taurine exerts preventive effects on cardiovascular diseases. In particular, taurine has been shown to reduce blood pressure in not only hypertensive patients but also in a number of hypertensive rodent models such as spontaneously hypertensive rats (SHR). However, the molecular basis of the efficacy and toxicity of the compound has not been fully characterized. We have investigated the effects of taurine supplementation to urinary low-molecular-weight endogenous metabolites in SHR using a (1)H NMR-based urinary metabonomic approach. The SHR were chronically treated with 3% taurine in drinking water from four to 14 weeks of age, and 24-h urine samples were analyzed using (1)H NMR spectroscopy. Metabolic information was extracted from the NMR data by principal components analysis as well as visual inspection. Consequently, the metabolite profile started to change with considerable interindividual variation from six weeks of age. The extent of change became increasingly remarkable with the duration of treatment, with the concurrent observation of the hypotensive effect. The metabolic changes included a decreased urinary output of tricarboxylic acid cycle intermediates (citrate, α-ketoglutarate, and succinate) and an increased output of phenylacetylglycine and p-cresol sulfate. The results suggest that chronic taurine supplementation to the SHR resulted in an acceleration of metabolic acidosis with perturbation in the tricarboxylic acid cycle and the modulation of the intestinal microbial metabolism.

The plastid sigma factor SIG5 is involved in the diurnal regulation of the chloroplast gene psbD in the moss Physcomitrella patens.

We analyzed the function of a plastid sigma factor, SIG5, by targeted gene disruption in the moss Physcomitrella patens. High-intensity light induced the chloroplast gene psbD in the wild-type strain (WT), whereas this induction was nullified in the PpSig5-disrupted strains (DeltaSig5). Moreover, diurnally regulated changes of psbD transcription showed lowered amplitude in DeltaSig5 than in WT. We concluded that the moss SIG5 mediates multiple layers of signals to intricately regulate psbD transcription.

Estimation of benchmark doses for urinary cadmium based on beta2-microglobulin excretion in cadmium-polluted regions of the Kakehashi River basin, Japan.

A benchmark dose low (BMDL) is used as a replacement for the no observed adverse effect level. The threshold levels of urinary cadmium (Cd) as BMDL were estimated using data from the Kakehashi River basin. The target population (>or=50 years) comprised 3178 and 294 participants inhabiting Cd-polluted and non-polluted areas, respectively. Cut-off values for beta2-MG-uria were defined as the 84 and 95% upper limit values calculated from control subjects, and 1000 microg/l or microg/g cr of beta2-MG. Using these cut-off values, the BMDL at which the excess risk is 0.05 was determined to be 2.9 - 4.0 microg/g cr (males) and 1.5 - 3.6 microg/g cr (females). The present study demonstrated that a BMD approach is useful to estimate the threshold level of urinary Cd in Cd-exposed subjects and people living in general environment without any known Cd-pollution since a BMD approach does not need abnormality rates of urinary findings in the controls.