Modification of the immune response by bacteriophages alters methicillin-resistant Staphylococcus aureus infection.

There is an urgent need to develop phage therapies for multidrug-resistant bacterial infections. However, although bacteria have been shown to be susceptible to phage therapy, phage therapy is not sufficient in some cases. PhiMR003 is a methicillin-resistant Staphylococcus aureus phage previously isolated from sewage influent, and it has demonstrated high lytic activity and a broad host range to MRSA clinical isolates in vitro. To investigate the potential of phiMR003 for the treatment of MRSA infection, the effects of phiMR003 on immune responses in vivo were analysed using phiMR003-susceptible MRSA strains in a mouse wound infection model. Additionally, we assessed whether phiMR003 could affect the immune response to infection with a nonsusceptible MRSA strain. Interestingly, wounds infected with both susceptible and nonsusceptible MRSA strains treated with phiMR003 demonstrated decreased bacterial load, reduced inflammation and accelerated wound closure. Moreover, the infiltration of inflammatory cells in infected tissue was altered by phiMR003. While the effects of phiMR003 on inflammation and bacterial load disappeared with heat inactivation of phiMR003. Transcripts of proinflammatory cytokines induced by lipopolysaccharide were reduced in mouse peritoneal macrophages. These results show that the immune modulation occurring as a response to the phage itself improves the clinical outcomes of phage therapy.

Clinical impact of noncontrast percutaneous coronary intervention in patients with acute coronary syndrome.

PURPOSE: Contrast-induced acute kidney injury (CI-AKI) is one of the common serious complications of percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). This study aimed to assess the significance of noncontrast strategy in the setting of ACS. METHODS: CI-AKI was defined as an increase in serum creatinine of ?0.5 mg/dL or ?1.25 times from the baseline. One-year worsening renal function (WRF) was defined as an increase of ?0.3mg/dL in serum creatinine from the baseline after PCI. RESULTS: Of 250 ACS patients, 81 were treated with noncontrast PCI. The average doses of contrast medium in the noncontrast and conventional groups were 17 (9?22) ml and 150 (120?200) ml, respectively. CI-AKI was observed in 4 patients (5%) in the noncontrast group and 29 patients (17%) in the conventional group. Noncontrast PCI was associated with a lower incidence of CI-AKI (adjusted odds ratio, 0.26;95% confidence interval [CI], 0.08?0.82). The bootstrap method and inverse probability weighting led to similar results. CI-AKI was associated with a higher incidence of 1-year WRF (adjusted hazard ratio, 2.30;95% CI, 1.12?4.69), while noncontrast PCI was not. CONCLUSIONS: Noncontrast PCI was associated with the lower incidence of CI-AKI in ACS patients. J. Med. Invest. 69 : 57-64, February, 2022.

Pivotal Role of Heart for Orthostasis: Left Ventricular Untwisting Mechanics and Physical Fitness.

Augmentation of left ventricular (LV) untwisting due to central hypovolemia is likely to be a compensatory mechanism for maintaining stroke volume, which is reduced by a decrease in cardiac filling during orthostatic stress. Orthostatic intolerance observed in both high and low fitness levels may be explained by the impaired response of LV untwisting due to central hypovolemia.

Clinical impact of red blood cell transfusion on adverse clinical events in acute heart failure patients with anemia.

BACKGROUND: Anemia has been recognized as an important comorbidity in patients with acute heart failure (AHF) and is associated with adverse clinical events. However, the clinical impact of red blood cell (RBC) transfusion in such patients is unclear. METHOD: This study was a retrospective single-center registry including AHF patients admitted to Kyorin University Hospital between 2007 and 2014. Anemia was defined as a hemoglobin level < 130 g/L in males or < 120 g/L in females. Those with major bleeding with a fall in hemoglobin concentration of >20 g/L were excluded. AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were evaluated. RESULTS: Of 501 AHF patients, 38 were excluded owing to major bleeding; finally, 463 (age, 77 ± 11 years; males, 58%) were evaluated. RBC transfusion during hospitalization was performed in 112 patients (24%). Hemoglobin level on admission was 105 ± 16 g/L (transfusion, 89 ± 17 g/L; no transfusion, 110 ± 12 g/L; p < 0.001). AHF readmission at 3 months and in-hospital and 2-year all-cause mortality were observed in 46 (10%), 16 (3%), and 121 (26%) patients, respectively. Univariate Cox regression analysis demonstrated that RBC transfusion was not associated with AHF readmission at 3 months (hazard ratio: 0.80; 95% confidence interval: 0.39-1.66) The association did not differ at any hemoglobin concentration or left ventricular ejection fraction value. Multivariate Cox regression analysis revealed similar results. Furthermore, RBC transfusion was not correlated with in-hospital and 2-year all-cause mortality. CONCLUSIONS: RBC transfusion was not associated with AHF readmission or all-cause mortality.

Vertical distribution and temporal changes of 137Cs in soil profiles under various land uses after the Fukushima Dai-ichi Nuclear Power Plant accident.

We monitored the vertical distribution of (137)Cs in soil profiles under eight different land uses for the 2 y after the Fukushima Dai-ichi Nuclear Power Plant accident, and discussed the temporal changes in the early-stage of the migration and the determinants of the initial distribution. The soil samples were collected for four surveys using a scraper plate at each study site, which consisted of three forests (mixed forest, mature cedar, and young cedar), two grasslands (pasture and meadow) and three abandoned agricultural fields (farm land, tobacco field, and paddy field). The land use patterns have a large influence on some soil properties and the migration processes of (137)Cs above ground, resulting in different distribution of (137)Cs in those soil profiles. Specifically, the secondary deposition of (137)Cs from the coniferous canopy, retention of (137)Cs by litter layer, and the homogenization of (137)Cs concentrations in surface soil by natural soil mixing such as the disturbance by cattle grazing, roots growing and the formation of needle ice were important to cause redistribution of the deposited (137)Cs. Only in the paddy field, the (137)Cs inventory in subsurface soils (5-10 cm) gradually increased and comprised 26% of the total (137)Cs in 2 y, showing the downward migration of (137)Cs to subsurface soil. In the other sites, it was considered that (137)Cs were strongly adsorbed by soil particles and rarely migrated downward as soluble form. Vertical distributions during the first survey were able to be used as the initial distributions and were well fitted to the exponential equation. The distribution parameters α (relaxation depth) and ß (relaxation mass depth), calculated by the exponential equation were correlated with RIP (r = -0.806, p < 0.05), macro pore (r = 0.651, p = 0.11), and dispersible fine particle content (r = 0.856, p < 0.05). It indicated that the initial distribution would be influenced by the Cs fixation ability of soil, and the penetration process of water and particles in soils.