Sepsis will induce stroke, new-onset atrial fibrillation (AF) increase ischemic stroke (IS) in in-hospitalization and long-term period after sepsis. Physicians must alert this condition and given ...suitable treatment.
The associated of IS and new-onset AF in septicemia survivors after discharge have to be evaluated.
The inpatient data was used of the Taiwan National Health Insurance Database (NHIRD) in 2010. We identified patients suffered their first occurrence of septicemia (International Classification of Disease, Ninth Revision, Clinical Modification ICD-9-CM is 038, 003.1, 036.1) and excluded less than 18 years old. Patients had AF (ICD-9-CM to 427.3×) during the same admission or after septicemia hospitalization discharged were defined as new-onset AF. The outcome was IS happened after septicemia discharge (ICD-9-CM as 433-437).
The factors related to IS after septicemia survival were established using multivariate logistic regression with forward stepwise selection.
There were 1286 new-onset AF and 1026 IS happened after septicemia discharge. The crude odds ratio (OR) were 3.88 (95% confidence interval C.I.: 1.69-8.89) and 1.62 (95% C.I.: 1.14-2.3) in middle-aged and elderly septicemia survivors with new-onset AF induced IS. The risk of IS after septicemia survivors was noticed adjusted OR 1.74 (95% C.I.: 1.26-2.41) for new-onset AF.
The middle-aged and elderly septicemia survivors suffered from new-onset AF had increased incidence of IS within three months. New-onset AF was a mediator factor of IS in septicemia survivors of Asian population.
At the end of a rush lasting over half a century, in which CMOS technology has been experiencing a constant and breathtaking increase of device speed and density, Moore's law is approaching the ...insurmountable barrier given by the ultimate atomic nature of matter. A major challenge for 21st century scientists is finding novel strategies, concepts and materials for replacing silicon-based CMOS semiconductor technologies and guaranteeing a continued and steady technological progress in next decades. Among the materials classes candidate to contribute to this momentous challenge, oxide films and heterostructures are a particularly appealing hunting ground. The vastity, intended in pure chemical terms, of this class of compounds, the complexity of their correlated behaviour, and the wealth of functional properties they display, has already made these systems the subject of choice, worldwide, of a strongly networked, dynamic and interdisciplinary research community.
Oxide science and technology has been the target of a wide four-year project, named Towards Oxide-Based Electronics (TO-BE), that has been recently running in Europe and has involved as participants several hundred scientists from 29 EU countries. In this review and perspective paper, published as a final deliverable of the TO-BE Action, the opportunities of oxides as future electronic materials for Information and Communication Technologies ICT and Energy are discussed. The paper is organized as a set of contributions, all selected and ordered as individual building blocks of a wider general scheme. After a brief preface by the editors and an introductory contribution, two sections follow. The first is mainly devoted to providing a perspective on the latest theoretical and experimental methods that are employed to investigate oxides and to produce oxide-based films, heterostructures and devices. In the second, all contributions are dedicated to different specific fields of applications of oxide thin films and heterostructures, in sectors as data storage and computing, optics and plasmonics, magnonics, energy conversion and harvesting, and power electronics.
We have previously demonstrated that peroxisome proliferator-activated receptor (PPARγ) activation inhibits hepatocarcinogenesis. We aim to investigate the effect of PPARγ on hepatocellular carcinoma ...(HCC) metastatic potential and explore its underlying mechanisms.
Human HCC cells (MHCC97L, BEL-7404) were infected with adenovirus-expressing PPARγ (Ad-PPARγ) or Ad-lacZ and treated with or without PPARγ agonist (rosiglitazone). The effects of PPARγ on cell migration and invasive activity were determined by wound healing assay and Matrigel invasive model in vitro, and in an orthotopic liver tumour metastatic model in mice.
Pronounced expression of PPARγ was demonstrated in HCC cells (MHCC97L, BEL-7404) treated with Ad-PPARγ, rosiglitazone or Ad-PPARγ plus rosiglitazone, compared with control (Ad-LacZ). Such induction markedly suppressed HCC cell migration. Moreover, the invasiveness of MHCC97L and BEL-7404 cells infected with Ad-PPARγ, or treated with rosiglitazone was significantly diminished up to 60%. Combination of Ad-PPARγ and rosiglitazone showed an additive effect. Activation of PPARγ by rosiglitazone significantly reduced the incidence and severity of lung metastasis in an orthotopic HCC mouse model. Key mechanisms underlying the effect of PPARγ in HCC include upregulation of cell adhesion genes, E-cadherin and SYK (spleen tyrosine kinase), extracellular matrix regulator tissue inhibitors of metalloproteinase (TIMP) 3, tumour suppressor gene retinoblastoma 1, and downregulation of pro-metastatic genes MMP9 (matrix metallopeptidase 9), MMP13, HPSE (heparanase), and Hepatocyte growth factor (HGF). Direct transcriptional regulation of TIMP3, MMP9, MMP13, and HPSE by PPARγ was shown by ChIP-PCR.
Peroxisome proliferator-activated receptor-gamma exerts an inhibitory effect on the invasive and metastatic potential of HCC in vitro and in vivo, and is thus, a target for the prevention and treatment of HCC metastases.
The evolution of ocean temperature measurement systems is presented with a focus on the development and accuracy of two critical devices in use today (expendable bathythermographs and ...conductivity‐temperature‐depth instruments used on Argo floats). A detailed discussion of the accuracy of these devices and a projection of the future of ocean temperature measurements are provided. The accuracy of ocean temperature measurements is discussed in detail in the context of ocean heat content, Earth's energy imbalance, and thermosteric sea level rise. Up‐to‐date estimates are provided for these three important quantities. The total energy imbalance at the top of atmosphere is best assessed by taking an inventory of changes in energy storage. The main storage is in the ocean, the latest values of which are presented. Furthermore, despite differences in measurement methods and analysis techniques, multiple studies show that there has been a multidecadal increase in the heat content of both the upper and deep ocean regions, which reflects the impact of anthropogenic warming. With respect to sea level rise, mutually reinforcing information from tide gauges and radar altimetry shows that presently, sea level is rising at approximately 3 mm yr−1 with contributions from both thermal expansion and mass accumulation from ice melt. The latest data for thermal expansion sea level rise are included here and analyzed.
Key Points
Oceanographic techniques and analysis have improved over many decades
These improvements allow more accurate Earth‐energy balance estimates
Understanding of ocean heat content and sea‐level rise has also increased
The ribosomal incorporation of nonnative amino acids into polypeptides in living cells provides the opportunity to endow therapeutic proteins with unique pharmacological properties. We report here ...the first clinical study of a biosynthetic protein produced using an expanded genetic code. Incorporation of p-acetylphenylalanine (pAcF) at distinct locations in human growth hormone (hGH) allowed site-specific conjugation with polyethylene glycol (PEG) to produce homogeneous hGH variants. A mono-PEGylated mutant hGH modified at residue 35 demonstrated favorable pharmacodynamic properties in GH-deficient rats. Clinical studies in GH-deficient adults demonstrated efficacy and safety comparable to native human growth hormone therapy but with increased potency and reduced injection frequency. This example illustrates the utility of nonnative amino acids to optimize protein therapeutics in an analogous fashion to the use of medicinal chemistry to optimize conventional natural products, low molecular weight drugs, and peptides.
Multi-protein complexes called inflammasomes have recently been identified and shown to contribute to cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic ...modality used for various inflammatory diseases. The objective of this study is to investigate dynamic responses of the NLRP1 and NLRP3 inflammasomes in stroke and to determine whether the NLRP1 and NLRP3 inflammasomes can be targeted with IVIg for therapeutic intervention. Primary cortical neurons were subjected to glucose deprivation (GD), oxygen-glucose deprivation (OGD) or simulated ischemia-reperfusion (I/R). Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion. Neurological assessment was performed, brain tissue damage was quantified, and NLRP1 and NLRP3 inflammasome protein levels were evaluated. NLRP1 and NLRP3 inflammasome components were also analyzed in postmortem brain tissue samples from stroke patients. Ischemia-like conditions increased the levels of NLRP1 and NLRP3 inflammasome proteins, and IL-1β and IL-18, in primary cortical neurons. Similarly, levels of NLRP1 and NLRP3 inflammasome proteins, IL-1β and IL-18 were elevated in ipsilateral brain tissues of cerebral I/R mice and stroke patients. Caspase-1 inhibitor treatment protected cultured cortical neurons and brain cells in vivo in experimental stroke models. IVIg treatment protected neurons in experimental stroke models by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Our findings provide evidence that the NLRP1 and NLRP3 inflammasomes have a major role in neuronal cell death and behavioral deficits in stroke. We also identified NLRP1 and NLRP3 inflammasome inhibition as a novel mechanism by which IVIg can protect brain cells against ischemic damage, suggesting a potential clinical benefit of therapeutic interventions that target inflammasome assembly and activity.
Remission induction therapy for acute lymphoblastic leukemia (ALL) includes medications that may cause hepatotoxicity, including asparaginase. We used a genome‐wide association study to identify loci ...associated with elevated alanine transaminase (ALT) levels after induction therapy in children with ALL enrolled on St. Jude Children's Research Hospital (SJCRH) protocols. Germline DNA was genotyped using arrays and exome sequencing. Adjusting for age, body mass index, ancestry, asparaginase preparation, and dosage, the PNPLA3 rs738409 (C>G) I148M variant, previously associated with fatty liver disease risk, had the strongest genetic association with ALT (P = 2.5 × 10‐8). The PNPLA3 rs738409 variant explained 3.8% of the variability in ALT, and partly explained race‐related differences in ALT. The PNPLA3 rs738409 association was replicated in an independent cohort of 2,285 patients treated on Children's Oncology Group protocol AALL0232 (P = 0.024). This is an example of a pharmacogenetic variant overlapping with a disease risk variant.
Simultaneous measurements of atmospheric organic and elemental carbon (OC and EC) were taken during winter and summer seasons at 2003 in 14 cities in China. Daily PM2.5 samples were analyzed for OC ...and EC by the Interagency Monitoring of Protected Visual Environments (IMPROVE) thermal/optical reflectance protocol. Average PM2.5 OC concentrations in the 14 cities were 38.1 μg m−3 and 13.8 μg m−3 for winter and summer periods, and the corresponding EC were 9.9 μg m−3 and 3.6 μg m−3, respectively. OC and EC concentrations had summer minima and winter maxima in all the cities. Carbonaceous matter (CM), the sum of organic matter (OM = 1.6 × OC) and EC, contributed 44.2% to PM2.5 in winter and 38.8% in summer. OC was correlated with EC (R2: 0.56–0.99) in winter, but correlation coefficients were lower in summer (R2: 0.003–0.90). Using OC/EC enrichment factors, the primary OC, secondary OC and EC accounted for 47.5%, 31.7% and 20.8%, respectively, of total carbon in Chinese urban environments. More than two thirds of China's urban carbon is derived from directly emitted particles. Average OC/EC ratios ranged from 2.0 to 4.7 among 14 cities during winter and from 2.1 to 5.9 during summer. OC/EC ratios in this study were consistent with a possible cooling effect of carbonaceous aerosols over China.
Photochemical upconversion is performed, whereby emitter triplet states are produced through triplet energy transfer from sensitizer molecules excited with low energy photons. The triplet emitter ...molecules undergo triplet-triplet annihilation to yield excited singlet states which emit upconverted fluorescence. Experiments comparing the 560 nm prompt fluorescence when rubrene emitter molecules are excited directly, using 525 nm laser pulses, to the delayed, upconverted fluorescence when the porphyrin sensitizer molecules are excited with 670 nm laser pulses reveal annihilation efficiencies to produce excited singlet emitters in excess of 20%. Conservative measurements reveal a 25% annihilation efficiency, while a direct comparison between the prompt and delayed fluorescence yield suggests a value as high as 33%. Due to fluorescence quenching, the photon upconversion efficiencies are lower, at 16%.