Heterogeneous amplification of ERBB2 in primary lesions is responsible for the discordant ERBB2 status of primary and metastatic lesions in gastric carcinoma

Aims: To determine the extent of HER2 homogeneity/heterogeneity in primary versus metastatic gastric carcinoma ( GC). Materials and results: The human epidermal growth factor receptor 2 ( HER2) status in primary and metastatic lesions was evaluated by immunohistochemistry ( IHC) and fluorescence in-situ hybridization ( FISH). Four separate cohorts consisting of primary GC alone or primary GC paired with metastatic lesions were examined. In the FISH analysis of 325 primary GCs, eight cases ( 2.5%) showed amplification with a heterogeneous pattern, whereas 27 cases ( 8.3%) showed amplification with a homogeneous pattern, and in this cohort the discordant: concordant FISH ratio based on examination of three different areas in each primary lesion was 0.30: 1. FISH testing using 250 paired primary and metastatic lesions revealed seven cases (2.8%) with discordant amplification. In metastatic disease positive conversion occurred in six cases (2.4%), whereas negative conversion happened in one case (0.4%). The discordant: concordant ratio of primary versus secondary lesions was 0.23: 1. When the seven discordant cases were re-evaluated using whole sections of primary GCs, six showed a heterogeneous pattern of amplification. Conclusions: These findings suggest that the discordant HER2 amplification observed in metastatic lesions is explained substantially by heterogeneity within primary tumours

Morphological changes of the lateral meniscus in end-stage lateral compartment osteoarthritis of the knee.

OBJECTIVE: The aim of this study was to evaluate the morphological changes of the lateral meniscus in end-stage lateral compartment osteoarthritis (OA) of the knee. METHODS: One hundred fifty-eight knee joints from 133 patients that subsequently underwent total knee joint arthroplasty from January 2008 to December 2009 were enrolled. There were 26 men and 107 women. Their ages ranged from 56 to 81 (mean 67.4 + 6.5 years). All study participants had complete obliteration of the lateral joint space identified by weight-bearing radiography. Meniscal position was assessed by measuring meniscal subluxation and meniscal height. The meniscal morphology was assessed using a modification of the whole-organ magnetic resonance imaging score (WORMS). The frequency of different meniscal morphology and their respective positions was calculated. RESULTS: The predominant type (42.4%, 53.8% and 52.5% in the anterior horn, mid-body and posterior horn, respectively) of abnormal meniscal morphology was a complete maceration/destruction or complete resection. The anterior horn of non-macerated lateral meniscus was more subluxed than that of the non-macerated medial meniscus in patients with lateral OA. CONCLUSION: This study suggests that the lateral meniscus in persons with end-stage lateral OA are mostly macerated or destroyed. Also, unlike isolated end-staged medial compartment OA, the anterior horn of the lateral meniscus in isolated end-stage lateral OA is commonly affected. Copyright 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved

Incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer

Background: Subsyndromal delirium, a condition in which patients exhibit some, but not all, of the symptoms of delirium, can negatively affect the outcomes of patients with cancer. However, the incidence of subsyndromal delirium in patients with gastric cancer is unknown. Here, we investigated the incidence and risk factors of subsyndromal delirium after curative resection of gastric cancer. Methods: We recruited consecutive patients with gastric cancer who were scheduled for curative resection at a tertiary hospital. Patients' subsyndromal delirium symptoms were serially assessed preoperatively and 1, 2, 3, and 7 days postoperatively using the Delirium Rating Scale-Revised-98 (DRS-R-98). A DRS-R-98 score of 8-14 at any postoperative assessment was considered to indicate subsyndromal delirium. Sociodemographic and pre-/intraoperative clinical data were also assessed. Logistic regression analyses were used to determine the associated risk factors. Results: Data were analysed from 163 out of 217 eligible patients. Postoperative delirium occurred in one patient (0.6%) and subsyndromal delirium occurred in 19 patients (11.7%). Age >= 70 years (odds ratio, [OR] 3.85; 95% confidence interval [0], 136-10.92; p = 0.011) and education level <= 9 years (OR, 3.98; 95% CI, 139-11.41; p= 0.010) were independent risk factors of subsyndromal delirium after adjusting for preoperative cognitive function. Other pre-/intra-operative variables including anxiety/depression, poor sleep quality, and anaesthesia duration were not associated with subsyndromal delirium. Conclusions: In contrast to the low incidence of delirium among patients undergoing curative resection of gastric cancer, a substantial proportion of such patients experienced subsyndromal delirium. Considering the prognostic implications, more careful detection and management of subsyndromal delirium may be warranted in patients with gastric cance

The ancient phosphatidylinositol 3-kinase signaling system is a master regulator of energy and carbon metabolism in algae

Algae undergo a complete metabolic transformation under stress by arresting cell growth, inducing autophagy and hyperaccumulating biofuel precursors such as triacylglycerols and starch. However, the regulatory mechanisms behind this stress-induced transformation are still unclear. Here, we use biochemical, mutational, and “omics” approaches to demonstrate that PI3K signaling mediates the homeostasis of energy molecules and influences carbon metabolism in algae. In Chlamydomonas reinhardtii, the inhibition and knockdown (KD) of algal class III PI3K led to significantly decreased cell growth, altered cell morphology, and higher lipid and starch contents. Lipid profiling of wild-type and PI3K KD lines showed significantly reduced membrane lipid breakdown under nitrogen starvation (-N) in the KD. RNA-seq and network analyses showed that under -N conditions, the KD line carried out lipogenesis rather than lipid hydrolysis by initiating de novo fatty acid biosynthesis, which was supported by tricarboxylic acid cycle down-regulation and via acetyl-CoA synthesis from glycolysis. Remarkably, autophagic responses did not have primacy over inositide signaling in algae, unlike in mammals and vascular plants. The mutant displayed a fundamental shift in intracellular energy flux, analogous to that in tumor cells. The high free fatty acid levels and reduced mitochondrial ATP generation led to decreased cell viability. These results indicate that the PI3K signal transduction pathway is the metabolic gatekeeper restraining biofuel yields, thus maintaining fitness and viability under stress in algae. This study demonstrates the existence of homeostasis between starch and lipid synthesis controlled by lipid signaling in algae and expands our understanding of such processes, with biotechnological and evolutionary implications.Ministry of Science, ICT and Future Planning 2015M3A6A2065697Ministry of Oceans and Fisheries 2015018

Design of exceptionally strong and conductive Cu alloys beyond the conventional speculation via the interfacial energy-controlled dispersion of gamma-Al2O3 nanoparticles

The development of Cu-based alloys with high-mechanical properties (strength, ductility) and electrical conductivity plays a key role over a wide range of industrial applications. Successful design of the materials, however, has been rare due to the improvement of mutually exclusive properties as conventionally speculated. In this paper, we demonstrate that these contradictory material properties can be improved simultaneously if the interfacial energies of heterogeneous interfaces are carefully controlled. We uniformly disperse γ-Al2O3 nanoparticles over Cu matrix, and then we controlled atomic level morphology of the interface γ-Al2O3 //Cu by adding Ti solutes. It is shown that the Ti dramatically drives the interfacial phase transformation from very irregular to homogeneous spherical morphologies resulting in substantial enhancement of the mechanical property of Cu matrix. Furthermore, the Ti removes impurities (O and Al) in the Cu matrix by forming oxides leading to recovery of the electrical conductivity of pure Cu. We validate experimental results using TEM and EDX combined with first-principles density functional theory (DFT) calculations, which all consistently poise that our materials are suitable for industrial applications.1

Improved elimination of motion artifacts from a photoplethysmographic signal using a Kalman smoother with simultaneous accelerometry

A photoplethysmography (PPG) signal provides very useful information about a subject's hemodynamic status in a hospital or ubiquitous environment. However, PPG is very vulnerable to motion artifacts, which can significantly distort the information belonging to the PPG signal itself. Thus, the reduction of the effects of motion artifacts is an important issue when monitoring the cardiovascular system by PPG. There have been many adaptive techniques to reduce motion artifacts from PPG signals. In the present study, we compared a method based on the fixed-interval Kalman smoother with the usual adaptive filtering algorithms, e.g. the normalized least mean squares, recursive least squares and the conventional Kalman filter. We found that the fixed-interval Kalman smoother reduced motion artifacts from the PPG signal most effectively. Therefore, the use of the fixed-interval Kalman smoother can reduce motion artifacts in PPG, thus providing the most reliable information that can be deduced from the reconstructed PPG signals.This study was supported by the IT R&D program of MKE/KEIT (2009-S-014-01, On the development of Sensing-Based Emotive Service Mobile Handheld Devices) and also by a grant from the Institute of Medical System Engineering in the GIST, Korea

Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

<p>Abstract</p> <p>Background</p> <p>Phosphatidylcholine (PPC) formulation is used for lipolytic injection, even though its mechanism of action is not well understood.</p> <p>Methods</p> <p>The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways.</p> <p>Results</p> <p>PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC alone led to the phosphorylation of the stress signaling proteins, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD did not activate the apoptotic pathways. Instead, SD and PPC formulation induced cell membrane lysis, which may lead to necrosis of cells.</p> <p>Conclusions</p> <p>PPC results in apoptosis of 3T3-L1 cells.</p

Robot-assisted distal gastrectomy for gastric cancer in a situs inversus totalis patient

A 47-year-old man was referred to Seoul National University Bundang Hospital with an ulcerative lesion in the midbody of the stomach. Computed tomography revealed that he was a situs inversus totalis (SIT) patient. Robot-assisted distal gastrectomy with D1+β lymph node dissection and Billroth II anastomosis were performed. With the aid of robotic surgery, the surgeon didn't need to change his position and could perform the surgery without any confusion resulting from the patient's reversed anatomy. The operation took 300 minutes, with no intraoperative complications. The postoperative course was uneventful, and the patient was discharged on postoperative day 8. The final pathologic report was pT3N3a by American Joint Committee on Cancer 7th tumor-node-metastasis staging. We successfully performed robot-assisted distal gastrectomy for gastric cancer in a SIT patient. We believe that this is the first case of robotic surgery reported in a SIT patient with gastric cancer