Retention-aware zero-shifting technique for Tiki-Taka algorithm-based analog deep learning accelerator.

We present the fabrication of 4 K-scale electrochemical random-access memory (ECRAM) cross-point arrays for analog neural network training accelerator and an electrical characteristic of an 8 × 8 ECRAM array with a 100% yield, showing excellent switching characteristics, low cycle-to-cycle, and device-to-device variations. Leveraging the advances of the ECRAM array, we showcase its efficacy in neural network training using the Tiki-Taka version 2 algorithm (TTv2) tailored for non-ideal analog memory devices. Through an experimental study using ECRAM devices, we investigate the influence of retention characteristics on the training performance of TTv2, revealing that the relative location of the retention convergence point critically determines the available weight range and, consequently, affects the training accuracy. We propose a retention-aware zero-shifting technique designed to optimize neural network training performance, particularly in scenarios involving cross-point devices with limited retention times. This technique ensures robust and efficient analog neural network training despite the practical constraints posed by analog cross-point devices.

Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models.

Airway epithelium, the first defense barrier of the respiratory system, facilitates mucociliary clearance against inflammatory stimuli, such as pathogens and particulates inhaled into the airway and lung. Inhaled particulate matter 2.5 (PM2.5) can penetrate the alveolar region of the lung, and it can develop and exacerbate respiratory diseases. Although the pathophysiological effects of PM2.5 in the respiratory system are well known, its impact on mucociliary clearance of airway epithelium has yet to be clearly defined. In this study, we used two different 3D in vitro airway models, namely the EpiAirway-full-thickness (FT) model and a normal human bronchial epithelial cell (NHBE)-based air-liquid interface (ALI) system, to investigate the effect of diesel exhaust particles (DEPs) belonging to PM2.5 on mucociliary clearance. RNA-sequencing (RNA-Seq) analyses of EpiAirway-FT exposed to DEPs indicated that DEP-induced differentially expressed genes (DEGs) are related to ciliary and microtubule function and inflammatory-related pathways. The exposure to DEPs significantly decreased the number of ciliated cells and shortened ciliary length. It reduced the expression of cilium-related genes such as acetylated α-tubulin, ARL13B, DNAH5, and DNAL1 in the NHBEs cultured in the ALI system. Furthermore, DEPs significantly increased the expression of MUC5AC, whereas they decreased the expression of epithelial junction proteins, namely, ZO1, Occludin, and E-cadherin. Impairment of mucociliary clearance by DEPs significantly improved the release of epithelial-derived inflammatory and fibrotic mediators such as IL-1ß, IL-6, IL-8, GM-CSF, MMP-1, VEGF, and S100A9. Taken together, it can be speculated that DEPs can cause ciliary dysfunction, hyperplasia of goblet cells, and the disruption of the epithelial barrier, resulting in the hyperproduction of lung injury mediators. Our data strongly suggest that PM2.5 exposure is directly associated with ciliary and epithelial barrier dysfunction and may exacerbate lung injury.

Electrochemical random-access memory: recent advances in materials, devices, and systems towards neuromorphic computing.

Artificial neural networks (ANNs), inspired by the human brain's network of neurons and synapses, enable computing machines and systems to execute cognitive tasks, thus embodying artificial intelligence (AI). Since the performance of ANNs generally improves with the expansion of the network size, and also most of the computation time is spent for matrix operations, AI computation have been performed not only using the general-purpose central processing unit (CPU) but also architectures that facilitate parallel computation, such as graphic processing units (GPUs) and custom-designed application-specific integrated circuits (ASICs). Nevertheless, the substantial energy consumption stemming from frequent data transfers between processing units and memory has remained a persistent challenge. In response, a novel approach has emerged: an in-memory computing architecture harnessing analog memory elements. This innovation promises a notable advancement in energy efficiency. The core of this analog AI hardware accelerator lies in expansive arrays of non-volatile memory devices, known as resistive processing units (RPUs). These RPUs facilitate massively parallel matrix operations, leading to significant enhancements in both performance and energy efficiency. Electrochemical random-access memory (ECRAM), leveraging ion dynamics in secondary-ion battery materials, has emerged as a promising candidate for RPUs. ECRAM achieves over 1000 memory states through precise ion movement control, prompting early-stage research into material stacks such as mobile ion species and electrolyte materials. Crucially, the analog states in ECRAMs update symmetrically with pulse number (or voltage polarity), contributing to high network performance. Recent strides in device engineering in planar and three-dimensional structures and the understanding of ECRAM operation physics have marked significant progress in a short research period. This paper aims to review ECRAM material advancements through literature surveys, offering a systematic discussion on engineering assessments for ion control and a physical understanding of array-level demonstrations. Finally, the review outlines future directions for improvements, co-optimization, and multidisciplinary collaboration in circuits, algorithms, and applications to develop energy-efficient, next-generation AI hardware systems.

WOx channel engineering of Cu-ion-driven synaptic transistor array for low-power neuromorphic computing.

The multilevel current states of synaptic devices in artificial neural networks enable next-generation computing to perform cognitive functions in an energy-efficient manner. Moreover, considering large-scale synaptic arrays, multiple states programmed in a low-current regime may be required to achieve low energy consumption, as demonstrated by simple numerical calculations. Thus, we propose a three-terminal Cu-ion-actuated CuOx/HfOx/WO3 synaptic transistor array that exhibits analogously modulated channel current states in the range of tens of nanoamperes, enabled by WO3 channel engineering. The introduction of an amorphous stoichiometric WO3 channel formed by reactive sputtering with O gas significantly lowered the channel current but left it almost unchanged with respect to consecutive gate voltage pulses. An additional annealing process at 450 °C crystallized the WO3, allowing analog switching in the range of tens of nanoamperes. The incorporation of N gas during annealing induced a highly conductive channel, making the channel current modulation negligible as a function of the gate pulse. Using this optimized gate stack, Poole-Frenkel conduction was identified as a major transport characteristic in a temperature-dependent study. In addition, we found that the channel current modulation is a function of the gate current response, which is related to the degree of progressive movement of the Cu ions. Finally, the synaptic characteristics were updated using fully parallel programming and demonstrated in a 7 × 7 array. Using the CuOx/HfOx/WO3 synaptic transistors as weight elements in multilayer neural networks, we achieved a 90% recognition accuracy on the Fashion-MNIST dataset.

Exogenous 8-Hydroxydeoxyguanosine Attenuates PM2.5-Induced Inflammation in Human Bronchial Epithelial Cells by Decreasing NLRP3 Inflammasome Activation.

Particulate matter 2.5 (PM2.5) induces lung injury by increasing the generation of reactive oxygen species (ROS) and inflammation. ROS aggravates NLRP3 inflammasome activation, which activates caspase-1, IL-1ß, and IL-18 and induces pyroptosis; these factors propagate inflammation. In contrast, treatment with exogenous 8-hydroxydeoxyguanosine (8-OHdG) decreases RAC1 activity and eventually decreases dinucleotide phosphate oxidase (NOX) and ROS generation. To establish modalities that would mitigate PM2.5-induced lung injury, we evaluated whether 8-OHdG decreased PM2.5-induced ROS generation and NLRP3 inflammasome activation in BEAS-2B cells. CCK-8 and lactate dehydrogenase assays were used to determine the treatment concentration. Fluorescence intensity, Western blotting, enzyme-linked immunosorbent assay, and immunoblotting assays were also performed. Treatment with 80 µg/mL PM2.5 increased ROS generation, RAC1 activity, NOX1 expression, NLRP3 inflammasome (NLRP3, ASC, and caspase-1) activity, and IL-1ß and IL-18 levels in cells; treatment with 10 µg/mL 8-OHdG significantly attenuated these effects. Furthermore, similar results, such as reduced expression of NOX1, NLRP3, ASC, and caspase-1, were observed in PM2.5-treated BEAS-2B cells when treated with an RAC1 inhibitor. These results show that 8-OHdG mitigates ROS generation and NLRP3 inflammation by inhibiting RAC1 activity and NOX1 expression in respiratory cells exposed to PM2.5.

Effect of Low or High Pressure Alveolar Recruitment Maneuver on Postoperative Pain and Quality of Recovery in Patients with Obesity Undergoing Laparoscopic Sleeve Gastrectomy.

Background: This study aimed to evaluate whether a low- or high-pressure alveolar recruitment maneuver (ARM) might reduce postoperative pain and improve the quality of recovery after laparoscopic bariatric surgery. Methods: 90 patients with a body mass index > 30 kg/m2 scheduled for laparoscopic sleeve gastrectomy were randomly assigned to control (n = 30), low ARM (n = 30), or high ARM groups (n = 30). For the low and high ARM groups, ARM was repeated five times to hold the peak airway pressure at 30 cmH2O and 60 cmH2O for 5 s, respectively, before removal of the trocar. Conventional methods to reduce post-laparoscopic pain, such as intraperitoneal saline irrigation, hemovac drainage, and gentle abdominal compression were performed in all patients, regardless of the assigned group. Results: Shoulder and surgical site pain scores 24 h postoperatively and rescue meperidine requirement were similar between the groups (p = 0.141, 0.101, and 0.82, respectively). The quality of recovery 40 (QoR40) score 24 h postoperatively was similar between the groups (p = 0.755). Postoperative pulmonary complications were similar between the groups (p = 0.124). Conclusion: Application of a low- or high-pressure ARM in addition to conventional methods to remove remnant peritoneal CO2 gas did not reduce postoperative shoulder or surgical site pain or improve the quality of recovery after laparoscopic sleeve gastrectomy.

Effects of Anesthetic Techniques on the Risk of Postoperative Complications Following Lower Extremity Amputation in Diabetes Patients with Coagulation Abnormalities: A Retrospective Cohort Study Using Propensity Score Analysis.

Diabetic foot amputation is associated with high morbidity and mortality rates. To prevent cardiovascular complications along with vasculopathy in the course of diabetes mellitus, a high number of patients receive anticoagulant therapy. However, anticoagulants are contraindicated in neuraxial anesthesia limiting available anesthetic modalities. Therefore, in this retrospective study, we aimed to compare between general anesthesia and peripheral nerve block (PNB) with respect to postoperative complications following lower extremity amputation (LEA) in patients with coagulation abnormalities. In total, 320 adult patients who underwent LEA for diabetic foot were divided into two groups according to the anesthetic type (general anesthesia vs. PNB). The inverse probability of treatment weighting was performed to balance the baseline patient characteristics and surgical risk between the two groups. The adjusted analysis showed that compared with the general anesthesia group, the PNB group had lower risks of pneumonia (odds ratio: 0.091, 95% confidence interval [CI]: 0.010-0.850, p = 0.0355), acute kidney injury (odds ratio: 0.078, 95% CI: 0.007-0.871, p = 0.0382), and total major complications (odds ratio: 0.603, 95% CI: 0.400-0.910, p = 0.0161). Additionally, general anesthesia was associated with a higher amount of intraoperative crystalloid administration and a requirement for more frequent vasopressors. In conclusion, PNB appears to be protective against complications following LEA in diabetes patients with coagulopathy.

Comparison of the Effects of Normocapnia and Mild Hypercapnia on the Optic Nerve Sheath Diameter and Regional Cerebral Oxygen Saturation in Patients Undergoing Gynecological Laparoscopy with Total Intravenous Anesthesia.

Cerebral hemodynamics may be altered by hypercapnia during a lung-protective ventilation (LPV), CO2 pneumoperitoneum, and Trendelenburg position during general anesthesia. The purpose of this study was to compare the effects of normocapnia and mild hypercapnia on the optic nerve sheath diameter (ONSD), regional cerebral oxygen saturation (rSO2), and intraoperative respiratory mechanics in patients undergoing gynecological laparoscopy under total intravenous anesthesia (TIVA). Sixty patients (aged between 19 and 65 years) scheduled for laparoscopic gynecological surgery in the Trendelenburg position. Patients under propofol/remifentanil total intravenous anesthesia were randomly assigned to either the normocapnia group (target PaCO2 = 35 mmHg, n = 30) or the hypercapnia group (target PaCO2 = 50 mmHg, n = 30). The ONSD, rSO2, and respiratory and hemodynamic parameters were measured at 5 min after anesthetic induction (Tind) in the supine position, and at 10 min and 40 min after pneumoperitoneum (Tpp10 and Tpp40, respectively) in the Trendelenburg position. There was no significant intergroup difference in change over time in the ONSD (p = 0.318). The ONSD increased significantly at Tpp40 when compared to Tind in both normocapnia and hypercapnia groups (p = 0.02 and 0.002, respectively). There was a significant intergroup difference in changes over time in the rSO2 (p < 0.001). The rSO2 decreased significantly in the normocapnia group (p = 0.01), whereas it increased significantly in the hypercapnia group at Tpp40 compared with Tind (p = 0.002). Alveolar dead space was significantly higher in the normocapnia group than in the hypercapnia group at Tpp40 (p = 0.001). In conclusion, mild hypercapnia during the LPV might not aggravate the increase in the ONSD during CO2 pneumoperitoneum in the Trendelenburg position and could improve rSO2 compared to normocapnia in patients undergoing gynecological laparoscopy with TIVA.

A phytoestrogen secoisolariciresinol diglucoside induces browning of white adipose tissue and activates non-shivering thermogenesis through AMPK pathway.

Secoisolariciresinol diglucoside (SDG) is the main phytoestrogen component of flaxseed known as an antioxidant. Current study focused on the effect of SDG in white adipose tissue (WAT) browning. Browning of WAT is considered as a promising treatment strategy for metabolic diseases. To demonstrate the effect of SDG as an inducer of browning, brown adipocyte markers were investigated in inguinal WAT (iWAT) of high fat diet-fed obese mice and genetically obese db/db mice after SDG administration. SDG increased thermogenic factors such as uncoupling protein 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha and PR domain containing 16 in iWAT and brown adipose tissue (BAT) of mice. Similar results were shown in beige-induced 3T3-L1 adipocytes and primary cultured brown adipocytes. Furthermore, SDG increased factors of mitochondrial biogenesis and activation. We also observed SDG-induced alteration of AMP-activated protein kinase α (AMPKα). As AMPKα is closely related in the regulation of adipogenesis and thermogenesis, we then evaluated the effect of SDG in AMPKα-inhibited conditions. Genetic or chemical inhibition of AMPKα demonstrated that the role of SDG on browning and thermogenesis was dependent on AMPKα signaling. In conclusion, our data suggest SDG as a potential candidate for improvement of obesity and other metabolic disorders.

Zileuton, a 5-Lipoxygenase Inhibitor, Exerts Anti-Angiogenic Effect by Inducing Apoptosis of HUVEC via BK Channel Activation.

The arachidonic acid metabolism through 5-lipoxygenase (5-LO) pathways is involved in modulating both tumorigenesis and angiogenesis. Although anti-carcinogenic activities of certain 5-LO inhibitors have been reported, the role of zileuton, a well known 5-LO inhibitor, on the endothelial cell proliferation and angiogenesis has not been fully elucidated. Here, we report that zileuton has an anti-angiogenic effect, and the underlying mechanisms involved activation of the large-conductance Ca2+-activated K+ (BK) channel. Our results show that zileuton significantly prevented vascular endothelial growth factor (VEGF)-induced proliferation of human umbilical vein endothelial cells (HUVECs) in vitro, as well as in vivo. However, such anti-angiogenic effect of zileuton was abolished by iberiotoxin (IBTX), a BK channel blocker, suggesting zileuton-induced activation of BK channel was critical for the observed anti-angiogenic effect of zileuton. Furthermore, the anti-angiogenic effect of zileuton was, at least, due to the activation of pro-apoptotic signaling cascades which was also abolished by IBTX. Additionally, zileuton suppressed the expression of VCAM-1, ICAM-1, ETS related gene (Erg) and the production of nitric oxide (NO). Taken together, our results show that zileuton prevents angiogenesis by activating the BK channel dependent-apoptotic pathway, thus highlighting its therapeutic capacity in angiogenesis-related diseases, such as cancer.

What is the proper ventilation strategy during laparoscopic surgery?

The main stream of intraabdominal surgery has changed from laparotomy to laparoscopy, but anesthetic care for laparoscopic surgery is challenging for clinicians, because pneumoperitoneum might aggravate respiratory mechanics and arterial oxygenation. The authors reviewed the literature regarding ventilation strategies that reduce deleterious pulmonary physiologic changes during pneumoperitoneum for laparoscopic surgery under general anesthesia and make appropriate recommendations.

Reactive Oxygen Species-Producing Myeloid Cells Act as a Bone Marrow Niche for Sterile Inflammation-Induced Reactive Granulopoiesis.

Both microbial infection and sterile inflammation augment bone marrow (BM) neutrophil production, but whether the induced accelerated granulopoiesis is mediated by a common pathway and the nature of such a pathway are poorly defined. We recently established that BM myeloid cell-derived reactive oxygen species (ROS) externally regulate myeloid progenitor proliferation and differentiation in bacteria-elicited emergency granulopoiesis. In this article, we show that BM ROS levels are also elevated during sterile inflammation. Similar to in microbial infection, ROS were mainly generated by the phagocytic NADPH oxidase in Gr1+ myeloid cells. The myeloid cells and their ROS were uniformly distributed in the BM when visualized by multiphoton intravital microscopy, and ROS production was both required and sufficient for sterile inflammation-elicited reactive granulopoiesis. Elevated granulopoiesis was mediated by ROS-induced phosphatase and tensin homolog oxidation and deactivation, leading to upregulated PtdIns(3,4,5)P3 signaling and increased progenitor cell proliferation. Collectively, these results demonstrate that, although infection-induced emergency granulopoiesis and sterile inflammation-elicited reactive granulopoiesis are triggered by different stimuli and are mediated by distinct upstream signals, the pathways converge to NADPH oxidase-dependent ROS production by BM myeloid cells. Thus, BM Gr1+ myeloid cells represent a key hematopoietic niche that supports accelerated granulopoiesis in infective and sterile inflammation. This niche may be an excellent target in various immune-mediated pathologies or immune reconstitution after BM transplantation.

G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling.

Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation.

McGrath Video Laryngoscopy Facilitates Routine Nasotracheal Intubation in Patients Undergoing Oral and Maxillofacial Surgery: A Comparison With Macintosh Laryngoscopy.

PURPOSE: The McGrath video laryngoscope (VL) offers excellent laryngoscopic views and increases the success rate of orotracheal intubation in patients with normal and difficult airways. The purpose of this randomized controlled trial was to compare the McGrath VL with the Macintosh laryngoscope to investigate the efficacy of the McGrath VL for routine nasotracheal intubation in patients with an expected normal airway. MATERIALS AND METHODS: To address the research purpose, the efficacy of the McGrath VL for routine nasotracheal intubation was compared with that of the Macintosh laryngoscope. The predictor variable was the laryngoscopic technique (McGrath VL vs Macintosh laryngoscope). The outcome variables were the time to successful intubation, laryngoscopic views before and after optimal external laryngeal manipulation (OELM), use of Magill forceps, ease of intubation, and severity of oropharyngeal bleeding. RESULTS: Data from 35 patients undergoing oral and maxillofacial surgery were assessed. The time to intubation was 10.5 seconds shorter in the McGrath group than in the Macintosh group (34.4 ± 13.7 vs 44.9 ± 15.6 seconds; P = .004). The incidence of grade 1 glottic view before OELM was higher in the McGrath group than in the Macintosh group (83 vs 57%; P = .019). The frequency of Magill forceps use was lower in the McGrath group than in the Macintosh group (6 vs 34%; P = .003). CONCLUSION: McGrath VL facilitates routine nasotracheal intubation in expected normal airways by providing a shorter intubation time and better laryngoscopic views compared with the Macintosh laryngoscope.

Myeloid cell-derived reactive oxygen species externally regulate the proliferation of myeloid progenitors in emergency granulopoiesis.

The cellular mechanisms controlling infection-induced emergency granulopoiesis are poorly defined. Here we found that reactive oxygen species (ROS) concentrations in the bone marrow (BM) were elevated during acute infection in a phagocytic NADPH oxidase-dependent manner in myeloid cells. Gr1(+) myeloid cells were uniformly distributed in the BM, and all c-kit(+) progenitor cells were adjacent to Gr1(+) myeloid cells. Inflammation-induced ROS production in the BM played a critical role in myeloid progenitor expansion during emergency granulopoiesis. ROS elicited oxidation and deactivation of phosphatase and tensin homolog (PTEN), resulting in upregulation of PtdIns(3,4,5)P3 signaling in BM myeloid progenitors. We further revealed that BM myeloid cell-produced ROS stimulated proliferation of myeloid progenitors via a paracrine mechanism. Taken together, our results establish that phagocytic NADPH oxidase-mediated ROS production by BM myeloid cells plays a critical role in mediating emergency granulopoiesis during acute infection.

Cigarette smoke (CS) and nicotine delay neutrophil spontaneous death via suppressing production of diphosphoinositol pentakisphosphate.

Diphosphoinositol pentakisphosphate (InsP7), a higher inositol phosphate containing energetic pyrophosphate bonds, is beginning to emerge as a key cellular signaling molecule. However, the various physiological and pathological processes that involve InsP7 are not completely understood. Here we report that cigarette smoke (CS) extract and nicotine reduce InsP7 levels in aging neutrophils. This subsequently leads to suppression of Akt deactivation, a causal mediator of neutrophil spontaneous death, and delayed neutrophil death. The effect of CS extract and nicotine on neutrophil death can be suppressed by either directly inhibiting the PtdIns(3,4,5)P3/Akt pathway, or increasing InsP7 levels via overexpression of InsP6K1, an inositol hexakisphosphate (InsP6) kinase responsible for InsP7 production in neutrophils. Delayed neutrophil death contributes to the pathogenesis of CS-induced chronic obstructive pulmonary disease. Therefore, disruption of InsP6K1 augments CS-induced neutrophil accumulation and lung damage. Taken together, these results suggest that CS and nicotine delay neutrophil spontaneous death by suppressing InsP7 production and consequently blocking Akt deactivation in aging neutrophils. Modifying neutrophil death via this pathway provides a strategy and therapeutic target for the treatment of tobacco-induced chronic obstructive pulmonary disease.

The PPARδ ligand L-165041 inhibits VEGF-induced angiogenesis, but the antiangiogenic effect is not related to PPARδ.

Peroxisome proliferator-activated receptor (PPAR)δ is known to be expressed ubiquitously and involved in lipid and glucose metabolism. Recent studies have demonstrated that PPARδ is expressed in endothelial cells (ECs) and plays a potential role in endothelial survival and proliferation. Although PPARα and PPARγ are well recognized to play anti-inflammatory, antiproliferative, and antiangiogenic roles in ECs, the general effect of PPARδ on angiogenesis in ECs remains unclear. Thus, we investigated the effect of the PPARδ ligand L-165041 on vascular EC proliferation and angiogenesis in vitro as well as in vivo. Our data show that L-165041 inhibited VEGF-induced cell proliferation and migration in human umbilical vein ECs (HUVECs). L-165041 also inhibited angiogenesis in the Matrigel plug assay and aortic ring assay. Flow cytometric analysis indicated that L-165041 reduced the number of ECs in the S phase and the expression levels of cell cycle regulatory proteins such as cyclin A, cyclin E, CDK2, and CDK4; phosphorylation of the retinoblastoma protein was suppressed by pretreatment with L-165041. We confirmed whether these antiangiogenic effects of L-165041 were PPARδ-dependent using GW501516 and PPARδ siRNA. GW501516 treatment did not inhibit VEGF-induced angiogenesis, and transfection of PPARδ siRNA did not reverse this antiangiogenic effect of L-165041, suggesting that the antiangiogenic effect of L-165041 on ECs is PPARδ-independent. Together, these data indicate that the PPARδ ligand L-165041 inhibits VEGF-stimulated angiogenesis by suppressing the cell cycle progression independently of PPARδ. This study highlights the therapeutic potential of L-165041 in the treatment of many disorders related to pathological angiogenesis.

The effect of heating insufflation gas on acid-base alterations and core temperature during laparoscopic major abdominal surgery.

BACKGROUND: Carbon dioxide (CO(2)) has different biophysical properties under different thermal conditions, which may affect its rate of absorption in the blood and the related adverse events. The present study was aimed to investigate the effects of heating of CO(2) on acid-base balance using Stewart's physiochemical approach, and body temperature during laparoscopy. METHODS: Thirty adult patients undergoing laparoscopic major abdominal surgery were randomized to receive either room temperature CO(2) (control group, n = 15) or heated CO(2) (heated group, n = 15). The acid-base parameters were measured 10 min after the induction of anesthesia (T1), 40 min after pneumoperitoneum (T2), at the end of surgery (T3) and 1 h after surgery (T4). Body temperature was measured at 15-min intervals until the end of the surgery. RESULTS: There were no significant differences in pH, PaCO(2), the apparent strong ion difference, the strong ion gap, bicarbonate ion, or lactate between two groups throughout the whole investigation period. At T2, pH was decreased whereas PaCO(2) was increased in both groups compared with T1 but these changes were not significantly different. Body temperatures in the heated group were significantly higher than those in the control group from 30 to 90 min after pneumoperitoneum. CONCLUSIONS: The heating of insufflating CO(2) did not affect changes in the acid-base status and PaCO(2) in patients undergoing laparoscopic abdominal surgery when the ventilator was set to maintain constant end-tidal CO(2). However, the heated CO(2) reduced the decrease in the core body temperature 30 min after the pneumoperitoneum.

Comparison of the effects of sevoflurane and propofol on core body temperature during laparoscopic abdominal surgery.

BACKGROUND: A decrease in core body temperature caused by heat distribution depends on the anesthetic agent used. The purpose of this study is to investigate the effects of sevoflurane and propofol on core temperature during laparoscopic major abdominal surgery requiring pneumoperitoneum of more than 90 min. METHODS: Fifty adult patients undergoing laparoscopic major abdominal surgery were randomly assigned to either a sevoflurane group (n = 25) or a propofol group (n = 25). In the sevoflurane group, anesthesia was induced with propofol 2 mg/kg, remifentanil 1.0 µg/kg, and maintained with 0.8-2.0 vol% sevoflurane and 0.1-0.2 µg/kg/min remifentanil. In the propofol group, anesthesia was induced with the effect-site concentration of propofol of 5.0 µg/ml and remifentanil 4 ng/ml, and maintained with the effect-site concentration of propofol of 2-3.5 µg/ml and remifentanil 3-5 ng/ml. Core body temperature was measured with an esophageal stethoscope with a temperature sensor after the start of the pneumoperitoneum (baseline) and at 15-min intervals until completion of surgery. RESULTS: During the study period, core temperature was comparable between the two groups. When compared with baseline values, core temperatures in both groups were significantly decreased 45 min after pneumoperitoneum. CONCLUSIONS: This study demonstrated that in patients undergoing prolonged laparoscopic surgery, a decrease in core body temperature during sevoflurane-remifentanil anesthesia was not different than propofol-remifentanil anesthesia, and the incidence of hypothermia of the two groups did not differ.