Reliable Ultra Trace Analysis of Cd, U and Zn Concentrations in Greenland Snow and Ice by Using Ultraclean Methods for Contamination Control.

This study presents ultraclean procedures used in the challenging task of determining trace elements at or below the pg/g concentration level encountered in Greenland snow and ice. In order to validate these ultraclean procedures, recent snowfall and Holocene ice from northwest Greenland were analyzed for Cd, U, and Zn concentrations. The total procedural blanks brought through the entire measurement procedure proved to be negligible, compared to trace element concentrations, measured in snow and ice samples. This validates the overall practicality of the proposed ultraclean procedures, thereby ensuring the reliable measurements of ultra-trace analysis. A comparison between our study and published data shows that improper procedures employed throughout all stages, from field sampling to analysis to elevate the concentrations by several orders of magnitude, relative to the reliable concentration ranges. The risk of contamination exposure for selected trace elements appears to increase in the order of U < As ≤ Pb < Cd < Zn. Reliable measurements of Cd, U, and Zn concentrations in snow and ice allowed us to interpret the data in terms of seasonal variations in the inputs of crustal and anthropogenic sources to Greenland ice sheet.

Del-1, an Endogenous Inhibitor of TGF-ß Activation, Attenuates Fibrosis.

Uncontrolled activation of transforming growth factor (TGF)-ß results in a wide range of pathologic conditions. Therapeutic interventions to regulate TGF-ß signaling during fibrosis have been developed but the effectiveness is still limited. Here, we show that developmental endothelial locus-1 (Del-1) ameliorates fibrosis in mice by inhibiting αv integrin-mediated activation of TGF-ß. Del-1 bound to αvß6 integrin, an important activator of TGF-ß, and inhibited the binding of αvß6 integrin to the latency-associated peptide (LAP), thereby suppressing αv integrin-mediated activation of TGF-ß. Lack of Del-1 increased colocalization of αv integrin and LAP in the lungs, which was reversed by Del-1 supplementation. The crucial role of Del-1 in regulating TGF-ß activity was recapitulated in a mouse model of fibrosis using an adenovirus expressing inactive TGF-ß1. Del-1 supplementation improved the pathological characteristics of the mice and reduced mortality. Thus, we propose that Del-1 is a negative regulator of TGF-ß activation and a potential anti-fibrotic factor.

Red Ginseng Attenuates Aß-Induced Mitochondrial Dysfunction and Aß-mediated Pathology in an Animal Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aß) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aß-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aß-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aß accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aß-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aß deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD.

In Vitro MIC Values of Rifampin and Ethambutol and Treatment Outcome in Mycobacterium avium Complex Lung Disease.

Although it is known that the in vitro MICs of rifampin and ethambutol are poorly correlated with the clinical response in Mycobacterium avium complex (MAC) lung disease (MAC-LD), evidence for this is limited. This study investigated the association between treatment outcome and the in vitro MICs of rifampin and ethambutol in patients with MAC-LD. Among patients diagnosed with macrolide-susceptible MAC-LD between January 2008 and December 2013, 274 patients who were treated with a standard regimen for ≥12 months until August 2017 and whose in vitro MIC results were available were enrolled at a tertiary referral center in South Korea. The MICs of antimicrobial agents were determined using the broth microdilution method. The mean age of the included patients was 60.4 years. The overall treatment success rate was 79.6% (218/274 patients) and tended to decrease with increasing MICs of rifampin and ethambutol, particularly at MICs of ≥8 µg/ml. Treatment success rate was significantly different between MAC isolates with MICs of ≥8 µg/ml for rifampin and ethambutol and those with MICs of <8 µg/ml for rifampin and/or ethambutol (64.9% versus 85.3%, P < 0.001). Multivariate analysis showed that an MIC of ≥8 µg/ml for both drugs and initial sputum acid-fast bacillus (AFB) smear positivity were independent risk factors for an unfavorable response (adjusted odds ratio [OR] = 3.154, 95% confidence interval [CI] = 1.641 to 6.063, and P = 0.001 for an MIC of ≥8 µg/ml; adjusted OR = 2.769, 95% CI = 1.420 to 5.399, and P = 0.003 for initial sputum AFB smear positivity). These findings suggest that the in vitro MICs of rifampin and ethambutol may be related to treatment outcome in MAC-LD.

Effect of the alveolar recruitment manoeuvre on haemodynamic parameters in patients with acute respiratory distress syndrome: relationship with oxygenation.

BACKGROUND AND OBJECTIVE: Although the alveolar recruitment manoeuvre (ARM) is considered to be an optimal method of recruiting collapsed alveoli in a short period, the haemodynamic effects of the ARM have not been investigated. The aim of this study was to assess whether the ARM causes haemodynamic instability in patients with ARDS, and any relationship this might have with arterial oxygenation. METHODS: Twenty-eight patients with ARDS (16 responders and 12 non-responders), who were admitted to the medical intensive care unit of a university-affiliated hospital, were enrolled in the study. ARM, using the extended sigh method, was performed within 48 h of the onset of ARDS. Haemodynamic parameters were measured at baseline, during the ARM, and at 2 min, 30 min and 1 h after the ARM. RESULTS: Responders and non-responders showed no significant changes in blood pressure or cardiac index during or after ARM. Mean pulmonary artery pressure (MPAP), pulmonary vascular resistance index (PVRI) and right ventricular stroke work index (RVSWI) were transiently increased compared with baseline, in responders and non-responders. During and after ARM, the systemic vascular resistance index was significantly higher in non-responders than in responders. CONCLUSIONS: Some haemodynamic parameters (MPAP, PVRI and RVSWI) changed significantly during ARM. However, these haemodynamic changes were minimal, transient and probably have no clinical significance.

Induced hypothermia as a new approach to lung rest for the acutely injured lung.

OBJECTIVE: To investigate whether low-frequency ventilation during hypothermia could attenuate lung injury associated with endotoxin and mechanical ventilation. DESIGN: : Experimental animal study. SETTING: University-affiliated animal laboratory. SUBJECTS: Forty-eight Sprague-Dawley rats. INTERVENTIONS: : Lipopolysaccharide was administered to rats intratracheally to induce acute lung injury. After 1 hr of this treatment, animals were assigned to normothermia-only (NO, rectal temperature 37 degrees C, ventilatory frequency 90/min), normothermia-lung rest (NR, 37 degrees C, 45/min), hypothermia-only (HO, 27 degrees C, 90/min), or hypothermia-lung rest (HR, 27 degrees C, 45/min). After 1 hr of injurious ventilation, the lungs of the rats were removed for bronchoalveolar lavage and histologic examination. MEASUREMENTS AND MAIN RESULTS: Compared with the normothermia groups (NO, NR), the neutrophil counts (per milliliter) (NO, 7708 +/- 5704; NR, 10,479 +/- 11,152; HO, 1638 +/- 955; HR, 805 +/- 591) and interleukin-1beta levels (pg/mL) (1180 +/- 439, 1081 +/- 652, 620 +/- 426, 420 +/- 182, respectively) in the bronchoalveolar lavage fluid, the wet-to-dry lung weight ratios (6.0 +/- 0.4, 5.7 +/- 0.4, 5.6 +/- 0.2, 5.2 +/- 0.2, respectively), and histologic acute lung injury scores (8.3 +/- 2.7, 10.4 +/- 3.1, 3.5 +/- 2.1, 3.1 +/- 2.2, respectively) of the hypothermia groups (HO, HR) were lower (all p < .001). Compared with the HO group, the neutrophil counts and protein content (HO, 1367 +/- 490 mug/mL vs. HR, 831 +/- 369 mug/mL) in the bronchoalveolar lavage fluid, the serum lactate dehydrogenase levels (units/mL) (9.1 +/- 3.6 vs. 5.3 +/- 1.5), and the wet-to-dry lung weight ratios of the HR group were lower (all p < .05). CONCLUSIONS: Reduction of ventilatory frequency in conjunction with hypothermia attenuated many variables of acute lung injury in rats. Use of hypothermia could be exploited as a new approach to lung rest for the ventilatory management of the acutely injured lung.