A 680 nA ECG acquisition IC for leadless pacemaker applications.

A sub- µW ECG acquisition IC is presented for a single-chamber leadless pacemaker applications. It integrates a low-power, wide dynamic-range ECG readout front end together with an analog QRS-complex extractor. To save ASIC power, a current-multiplexed channel buffer is introduced to drive a 7 b-to-10 b self-synchronized SAR ADC which utilizes 4 fF/unit capacitors. The ASIC consumes only 680nA and achieves CMRR > 90 dB, PSRR > 80 dB, an input-referred noise of 4.9 µVrms in a 130 Hz bandwidth, and has rail-to-rail DC offset rejection. Low-power heartbeat detections are evaluated with the help of the ASIC acquiring nearly 20,000 beats across 10 different records from the MIT-BIH arrhythmia database. In the presence of muscle noise, both the average Sensitivity (Se) and Positive Predictivity (PP) show more than 90% when the input SNR > 6 dB.

A 13 µA analog signal processing IC for accurate recognition of multiple intra-cardiac signals.

A low-power analog signal processing IC is presented for the low-power heart rhythm analysis. The ASIC features 3 identical, but independent intra-ECG readout channels each equipping an analog QRS feature extractor for low-power consumption and fast diagnosis of the fatal case. A 16-level digitized sine-wave synthesizer together with a synchronous readout circuit can measure bio-impedance in the range of 0.1-4.4 kΩ with 33 mΩ(rms) resolution and higher than 97% accuracy. The proposed 25 mm² ASIC consumes only 13 µA from 2.2 V. It is a highly integrated solution offering all the functionality of acquiring multiple high quality intra-cardiac signals, requiring only a few limited numbers of external passives.

In vitro toxicity of silver nanoparticles at noncytotoxic doses to HepG2 human hepatoma cells.

Although it has been reported that silver nanoparticles (Ag-NPs) have strong acute toxic effects to various cultured cells, the toxic effects at noncytotoxic doses are still unknown. We, therefore, evaluated in vitro toxicity of Ag-NPs at noncytotoxic doses in human hepatoma cell line, HepG2, based on cell viability assay, micronucleus test, and DNA microarray analysis. We also used polystyrene nanoparticles (PS-NPs) and silver carbonate (Ag2CO3) as test materials to compare the toxic effects with respect to different raw chemical composition and form of silver. The cell viability assay demonstrated that Ag-NPs accelerated cell proliferation at low doses (< 0.5 mg/L), which was supported by the DNA microarray analysis showing significant induction of genes associated with cell cycle progression. However, only Ag-NPs exposure exhibited a significant cytotoxicity at higher doses (> 1.0 mg/L) and induced abnormal cellular morphology, displaying cellular shrinkage and acquisition of an irregular shape. In addition, only Ag-NPs exposure increased the frequency of micronucleus formation up to 47.9 +/- 3.2% of binucleated cells, suggesting that Ag-NPs appear to cause much stronger damages to chromosome than PS-NPs and ionic Ag+. Cysteine, a strong ionic Ag+ ligand, only partially abolished the formation of micronuclei mediated by Ag-NPs and changed the gene expression, indicating that ionic Ag+ derived from Ag-NPs could not fully explain these biological actions. Based on these discussions, it is concluded that both "nanosized particle of Ag" as well as "ionic Ag+" contribute to the toxic effects of Ag-NPs.

[A case of curatively resected biliary tract cancer with peritoneal dissemination through effective response to chemotherapy of S-1].

The patient is a 55-year-old woman who has biliary tract cancer with peritoneal dissemination (T3N1P2M0, Stage IV b). Since a curative operation was deemed impossible, we conducted chemotherapy using S-1. S-1 (120 mg/day) was administered for 2 weeks and then chemotherapy was discontinued for 1 week, which was regarded as one course. After 2 courses of the chemotherapy, CT scan showed that the metastatic lymph node and tumor of peritoneal dissemination were reduced in size, and that there was no ascites. Left lobectomy of the liver, cholecystectomy, and partial resection of omentum were carried out. The pathological diagnosis was also curative (pT1, pN0, pP0, Stage I). We think this case shows the possibility of S-1 for patients with unresectable biliary tract cancer.

[A successfully resected case of rectal cancer with liver metastases treated with mFOLFOX6 and bevacizumab].

A sixties-man had complained of melena. Colonoscopy revealed type 2 tumor at rectum. Computed tomography (CT)demonstrated lymph node metastasis in front of sacrum and two low density areas which were suspected metastases in the liver. The patient was diagnosed stageIV rectal cancer and resected primary focus and lymph node metastasis.[ Ra-RS, ant, type 2, moderately differentiated adenocarcinoma, ly1, v3, pSE, pN2, sH1(Grade C), sP0, pM1(No. 270)]without liver resection. It was due to high level of CEA and remote lymph node metastasis. The patient was treated with mFOLFOX6 and bevacizumab after the operation. The level of CEA decreased to normal level and CT revealed a partial response after 4 cycles of systemic chemotherapy. Liver resection was performed safely. Histological response was Grade 2 at liver metastases.

Differential regulation of cellular maturation in chondrocytes and osteoblasts by glycine.

Previous studies have demonstrated the functional expression, by osteoblasts, of N-methyl-D-aspartate (NMDA) receptors responsible for the promotion of cellular differentiation in bone. We have now evaluated the possible role of the endogenous co-agonist of NMDA receptors, glycine (Gly), in chondrogenesis. In ex vivo organotypic cultures of fetal mouse tibias, proximal and distal cartilaginous primordia were significantly increased in the presence of Gly, with the osteogenic center being unchanged. Exposure to Gly drastically increased mRNA expression of the calcified chondrocyte marker osteopontin, without markedly affecting that of a proliferating chondrocyte marker or a hypertrophic chondrocyte marker, as shown in organotypic cultures by in situ hybridization analysis. Gly significantly increased Ca2+ accumulation, osteopontin mRNA expression, and alkaline phosphatase activity in cultured rat costal chondrocytes, without significantly affecting those in cultured rat calvarial osteoblasts. The increase induced by Gly was significantly prevented by an NMDA receptor channel blocker and an antagonist at the Gly site on NMDA receptors, but not by an inhibitory Gly receptor antagonist or a Gly transporter inhibitor, in cultured chondrocytes. Constitutive mRNA expression was seen for NR1, NR2D, and NR3A subunits of NMDA receptors, but not for Gly receptors and transporters, in cultured chondrocytes. Corresponding immunoreactive proteins were detected for NR1 and NR2D subunits in cartilaginous zones of fetal mouse tibias. Thus, Gly might, at least in part, play a role as a trophic factor in the mechanisms associated with chondral calcification through the Gly site of NMDA receptors functionally expressed by chondrocytes in rodent cartilage.

Increased GABA transport activity in rat calvarial osteoblasts cultured under hyperglycemic conditions.

Several independent lines of evidence indicate the direct impairment by extracellular glucose at high concentrations of different osteoblastic functions with a marked decrease in bone mass toward osteoporosis, while the underlying mechanisms are not well clarified to date. We have previously demonstrated the functional expression of the neural amino acid gamma-aminobutyric acid (GABA) signaling system including betaine/GABA transporter-1 (BGT-1) with a temperature-, sodium- and chloride-dependent activity of [(3)H]GABA accumulation in cultured rat calvarial osteoblasts. In this study, therefore, we attempted to demonstrate the possible involvement of BGT-1 isoform in bone dysfunctions due to impaired mineralization in rat calvarial osteoblasts cultured under hyperglycemic conditions. No significant change was seen in [(3)H]GABA accumulation in osteoblasts cultured for 7 d in vitro (DIV) under hyperglycemic conditions (glucose=25.5-50.5 mM) compared to those cultured in normoglycemic (glucose=5.5 mM) and hyperosmotic (mannitol=25.5-50.5 mM) conditions. In osteoblasts cultured for 14 DIV under hyperglycemic conditions, however, [(3)H]GABA accumulation was significantly increased compared to those cultured under normoglycemic and hyperosmotic conditions. Kinetic analysis revealed that hyperglycemic cultivation resulted in a significant increase in V(max) values from 2.85 nmol/min/mg protein for normoglycemic conditions to 4.17 nmol/min/mg protein for hyperglycemic conditions without affecting K(m) values. However, experimental hyperglycemia did not significantly affect the expression of mRNA for BGT-1 isoform by osteoblasts. These results suggest that GABA transport system may at least in part play a role in pathological malfunctions and abnormalities through a mechanism not directly related to gene expression in osteoblasts under hyperglycemia.