A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line ...treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile.
One of the most remarkable biochemical differences between the members of two domains Archaea and Bacteria is the stereochemistry of the glycerophosphate backbone of phospholipids, which are ...exclusively opposite. The enzyme responsible to the formation of Archaea-specific glycerophosphate was found to be NAD(P)-linked sn-glycerol-1-phosphate (G-1-P) dehydrogenase and it was first purified from Methanobacterium thermoautotrophicum cells and its gene was cloned. This structure gene named egsA (enantiomeric glycerophosphate synthase) consisted of 1,041 bp and coded the enzyme with 347 amino acid residues. The amino acid sequence deduced from the base sequence of the cloned gene (egsA) did not share any sequence similarity except for NAD-binding region with that of NAD(P)-linked sn-glycerol-3-phosphate (G-3-P) dehydrogenase of Escherichia coli which catalyzes the formation of G-3-P backbone of bacterial phospholipids, while the deduced protein sequence of the enzyme revealed some similarity with bacterial glycerol dehydrogenases. Because G-1-P dehydrogenase and G-3-P dehydrogenase would originate from different ancestor enzymes and it would be almost impossible to interchange stereospecificity of the enzymes, it seems likely that the stereostructure of membrane phospholipids of a cell must be maintained from the time of birth of the first cell. We propose here the hypothesis that Archaea and Bacteria were differentiated by the occurrence of cells enclosed by membranes of phospholipids with G-1-P and G-3-P as a backbone, respectively.
Abstract
Background
Trans-radial access (TRA) has been established as a safe and established approach for invasive coronary catheter procedures. However, protocols for post-procedural hemostasis ...varies depending on institutes and an evidence-based protocol is lacking.
Purpose
The objective of this study was to investigate the clinical implications of procedural hemostasis.
Methods
Consecutive patients who were referred to outpatient catheter examination before and after April 2018 were treated with an old and a new protocol, respectively. In both protocols, we used the same commercially available hemostasis band with injecting an air of 16 ml for hemostasis. In the old protocol, the amount and timing of deflation were fixed, whereas the air was removed as much as possible for every 30 minutes in the new protocol. Time to complete hemostasis, the rate of major bleeding, and the rate of radial artery occlusion (RAO) at 6 months after the catheter examination were compared between the protocols.
Results
Total of 1,843 (71±10 years old, 77% male) patients was included in the study. Between patients in the old and the new protocol group (n=1,000 and 843, respectively), there was no significant difference in age, gender, body size, or systolic blood pressure. The new group had significantly higher prevalence of diabetes (47% vs 39%, p=0.002), slightly larger sheath size (4.1±0.3 vs 4.0±0.2 Fr, p<0.001), and lower rate of dual antiplatelet therapy (DAPT: 24% vs. 35%, p<0.001). Time for complete hemostasis was about one-third with the new protocol compared with the old protocol (65±32 vs. 190±16 min, p<0.001) and there was no major bleeding in either group. The rate of radial artery occlusion was 0.7% and 9.8% in the old and the new group (p<0.001). Multivariate analysis showed that the significant predictor of prolonged hemostasis time were the old protocol (odds ratio: OR 80.5, p<0.001) and the prescription of DAPT (OR 2.9, p<0.001), while the factors associated with higher risk of radial occlusion were the old protocol (OR 13.9, p<0.001), the number of previous TRA (OR 1.1, p<0.001), and smaller body size (OR 0.127 per 1 m2 increase p=0.005).
Conclusions
Our new protocol for hemostasis after TRA was strongly associated with shorter hemostasis time and a lower rate of radial artery occlusion. This approach will decrease the post-procedural hospital time with even fewer complication rates.
Study outline
Funding Acknowledgement
Type of funding source: None
Few studies found that coronary microvascular dysfunction was highly prevalent in subjects with cardiac transthyretin amyloidosis (ATTR), even in the absence of epicardial coronary artery disease ...(CAD). The aim of this preliminary report is to confirm the coronary microvascular dysfunction using dynamic cardiac SPECT.
Adult patients with confirmed ATTR cardiomyopathy were included before Tafamidis treatment in a multicentric, prospective, observational cohort study (AMYTRE study, NCT05103943). Dynamic cardiac SPECT data were acquired on CZT-based pinhole cardiac cameras in listmode using a stress (249±13MBq)/rest (506±17MBq) one-day 99mTc-tetrofosmin protocol. Kinetic analysis was done with Corridor4DMTM software using a 1-tissue-compartment model and converted to myocardial blood flow using a previously determined extraction fraction correction. Myocardial flow reserve (MFR) was defined as the ratio between stress and rest myocardial blood flow.
Thirteen (9 male, 4 female) patients were prospectively included. Mean age was 77±18; mean BMI was 28±8.1. ATTR was diagnosed on 99mTc-HDP bone scintigraphy (8 grade 2 and 5 grade 3). LVEF was preserved, mean 57±7.5%. Twelve patients had normal perfusion imaging, without ischemia; 1 patient had moderate infero-basal ischemia (5–10% extent). MFR was significantly reduced both globally (1.5±0.35) and in all territories (1.5±0.34 for left anterior descending, 1.6±0.39 for left circumflex, and 1.6±0.45 for right coronary).
In this preliminary report, MFR is significantly reduced in all territories in patients with ATTR cardiomyopathy, undergoing cardiac dynamic SPECT. This confirms potential coronary microvascular dysfunction.
Short period AlN/GaN quantum cascade (QC) laser structures that utilize a polarization field for electron injection were fabricated by hot wall epitaxy. A (GaN)
n
/(AlN)
1 short period superlattice ...with several molecular layers of AlN was designed in order to realize a mid-infrared laser. The QC structures were analyzed by X-ray diffraction (XRD) measurements, atomic force microscopy and cross-sectional transmission electron microscopy observation. The XRD patterns and cross-sectional TEM images showed that a well-controlled quantum cascade structure could be prepared by hot wall epitaxy without inter-diffusion of the layers.
The membranes from Corynebacterium glutamicum cells contain a hydrophobic di-haem C protein as the cytochrome c subunit of the new type of cytochrome bc complex (complex III in the respiratory chain) ...encoded by the qcrCAB operon Sone, N., Nagata, K., Kojima, H., Tajima, J., Kodera, Y., Kanamaru, T., Noguchi, S. & Sakamoto, J. (2001). Biochim Biophys Acta 1503, 279-290. To characterize complex IV, cytochrome c oxidase and its structural genes were isolated. The oxidase is of the cytochrome aa(3) type, but mass spectrometry indicated that the haem is haem As, which contains a geranylgeranyl side-chain instead of a farnesyl group. The enzyme is a SoxM-type haem-copper oxidase composed of three subunits. Edman degradation and mass spectrometry suggested that the N-terminal signal sequence of subunit II is cleaved and that the new N-terminal cysteine residue is diacylglycerated, while neither subunit I nor subunit III is significantly modified. The genes for subunits II (ctaC) and III (ctaE) are located upstream of the qcrCAB operon, while that for subunit I (ctaD) is located separately. The oxidase showed low enzyme activity with extrinsic substrates such as cytochromes c from horse heart or yeast, and has the Cu(A)-binding motif in its subunit II. A prominent structural feature is the insertion of an extra charged amino acid cluster between the beta2 and beta4 strands in the substrate-binding domain of subunit II. The beta2-beta4 loop of this oxidase is about 30 residues longer than that of major cytochrome c oxidases from mitochondria and proteobacteria, and is rich in both acidic and basic residues. These findings suggest that the extra charged cluster may play a role in the interaction of the oxidase with the cytochrome c subunit of the new type of bc complex.
Considering water pollution as a potential threat to some endemic cichlids of Lake Barombi Mbo, Cameroon, an investigation was done in 2011 to determine trace metals in its water, linking their ...uptake in gills and liver of fish to water chemistry. ICP-MS and ICP-OES analyses of trace metals based on total concentration of unfiltered lake water samples showed the presence of trace metals. All fish species accumulated Al, Mn and Sr in the highest concentrations in their gills, with Cu, Cd, Co, Cr, Pb and U highest in the liver. Pungu maclareni accumulated Al, Cr, Co, Sr and Pb in the highest concentrations. The highest mean gill Al concentration of 140 µg g
−1
dry weight was measured in P. maclareni gills, this being one of the critically endangered cichlids of the lake. Stable isotope analyses of carbon δ
13
C and nitrogen δ
15
N showed that P. maclareni had the highest mean δ
13
C (−30.2‰) and highest concentrations of Cr, Co, Pb and U in liver, probably linking the carbon source to the accumulation of metals. Though trace metal levels in the lake water were low, their presence in fish tissues suggest they are bioavailable, bioaccumulate and may pose a threat to the aquatic biota, and therefore should be monitored.
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