Background
Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up‐regulation of T helper (Th) 17 cells, and ...down‐regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease.
Methods
Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17‐ and Treg‐related cytokines including IL‐6, IL‐17A, IL‐10, TGF‐β, and mRNA expression levels of RORγt and Foxp3 were tested.
Results
Patients with Kawasaki disease had higher levels of plasma IL‐17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL‐6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL‐6 and IL‐17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL‐10 and IL‐17A.
Conclusion
Kawasaki disease was associated with higher IL‐17A and IL‐6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg‐related FoxP3. IVIG resistance was associated with higher levels of IL‐10 and IL‐17A. Our findings provide further evidence that Kawasaki disease is an autoimmune‐like disease.
Despite diversity in genetic events in oncogenesis, cancer cells exhibit a common set of functional characteristics. Otto Warburg discovered that cancer cells have consistently higher rates of ...glycolysis than normal cells. The underlying mechanisms leading to the Warburg phenomenon include mitochondrial changes, upregulation of rate-limiting enzymes/proteins in glycolysis and intracellular pH regulation, hypoxia-induced switch to anaerobic metabolism, and metabolic reprogramming after loss of p53 function. The regulation of energy metabolism can be traced to a “triad” of transcription factors: c-MYC, HIF-1 and p53. Oncogenetic changes involve a nonrandom set of gene deletions, amplifications and mutations, and many oncogenes and tumor suppressor genes cluster along the signaling pathways that regulate c-MYC, HIF-1 and p53. Glycolysis in cancer cells has clinical implications in cancer diagnosis, treatment and interaction with diabetes mellitus. Many drugs targeting energy metabolism are in development. Future advances in technology may bring about transcriptome and metabolome-guided chemotherapy.
Summary
Background
Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. The Chronic Liver Failure–Sequential Organ Failure Assessment (CLIF‐SOFA) score, a modified ...Sequential Organ Failure Assessment (SOFA) score, is a newly developed scoring system exclusively for patients with end‐stage liver disease.
Aim
To externally validate the efficacy of the CLIF‐SOFA score and evaluate other scoring systems for 6‐month mortality in critically ill cirrhotic patients.
Methods
This study prospectively recorded and analysed the data for 30 demographical parameters and some clinical characteristic variables on day 1 of 250 cirrhotic patients admitted to a 10‐bed specialised hepatogastroenterology ICU in a 2000‐bed tertiary care referral hospital during the period from September 2010 to August 2013.
Results
The overall in‐hospital and 6‐month mortality rate were 58.8% (147/250) and 78.0% (195/250), respectively. Liver diseases were mostly attributed to hepatitis B virus infection (32%). Multiple Cox logistic regression hazard analysis revealed that Glasgow coma scale, both the CLIF‐SOFA and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of ICU admission were independent predictors of 6‐month mortality. Analysis of the area under the receiver operating characteristic curve revealed that the CLIF‐SOFA score had the best discriminatory power (0.900 ± 0.020). Moreover, the cumulative 6‐month survival rates differed significantly for patients with a CLIF‐SOFA score ≤11 and those with a CLIF‐SOFA score >11 on the ICU admission day.
Conclusion
Both CLIF‐SOFA and APACHE III scores are excellent prognosis evaluation tools for critically ill cirrhotic patients.
Epithelial-mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, ...emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis. Overexpression of miR-218 inhibited cell migration and invasion as well as the EMT process. Of particular importance, miR-218 was involved in the metastatic process of lung cancer cells in vivo by suppressing local invasion and distant colonization. We identified Slug and ZEB2 as direct functional targets of miR-218. Inverse correlations were observed between miR-218 levels and Slug/ZEB2 levels in cancer tissue samples. In addition, overexpression of miR-218 in H1299 increased chemosensitivity of cells to cisplatin treatment through suppression of Slug and ZEB2. These findings highlight an important role of miR-218 in the regulation of EMT-related traits and metastasis of lung cancer in part by modulation of Slug/ZEB2 signaling, and provide a potential therapeutic strategy by targeting miR-218 in NSCLC.
Summary
Background
Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection.
Aim
To determine the ...safety and effectiveness of ETV in ‘real‐world’ HBV patients in the United States (US).
Methods
Treatment‐naïve HBV patients ≥18 years old who received ETV for ≥12 months between 2005 and 2013 were included in a retrospective, cohort study. Rates of ALT normalisation, undetectable HBV DNA, HBeAg and HBsAg loss/seroconversion, adverse events (AE) and clinical outcomes were evaluated.
Results
Of 841 patients, 658 65% male, 83% Asian; median age 47 years met the inclusion criteria. 36% were HBeAg+ and 9.3% cirrhotic. 89% had abnormal ALT. Baseline median HBV DNA was 5.8 log 10 IU/mL. Median duration of ETV treatment was 4 years. Rates of ALT normalisation at 1, 3 and 5 years were 37.2%, 48.7% and 56.2% in HBeAg+ and 39.6%, 46.8% and 55.6% in HBeAg‐ patients. HBV DNA was undetectable at 1, 3 and 5 years in 34.6%, 64.7% and 84.6% in HBeAg+ patients, and 81.9%, 90.3% and 96.2% in HBeAg patients. Five‐year cumulative probability of HBeAg loss and seroconversion was 46% and 33.7% and HBsAg loss was 4.6%. ETV was discontinued due to adverse events in 1.2% of patients. Hepatic decompensation occurred in 0.8%, liver cancer in 2.7% and death in 0.6%.
Conclusion
Entecavir treatment was safe in a large cohort of US patients, but ALT normalisation and hepatitis B virus DNA suppression rates were lower than previously reported in clinical trials.
Two-dimensional (2D) materials have been studied extensively as monolayers, vertical or lateral heterostructures. To achieve functionalization, monolayers are often patterned using soft lithography ...and selectively decorated with molecules. Here we demonstrate the growth of a family of 2D materials that are intrinsically patterned. We demonstrate that a monolayer of PtSe
can be grown on a Pt substrate in the form of a triangular pattern of alternating 1T and 1H phases. Moreover, we show that, in a monolayer of CuSe grown on a Cu substrate, strain relaxation leads to periodic patterns of triangular nanopores with uniform size. Adsorption of different species at preferred pattern sites is also achieved, demonstrating that these materials can serve as templates for selective self-assembly of molecules or nanoclusters, as well as for the functionalization of the same substrate with two different species.
Abstract Chronic neuropathic pain remains an unmet clinical problem because it is often resistant to conventional analgesics. Metabotropic glutamate receptors (mGluRs) are involved in nociceptive ...processing at the spinal level, but their functions in neuropathic pain are not fully known. In this study, we investigated the role of group III mGluRs in the control of spinal excitatory and inhibitory synaptic transmission in a rat model of neuropathic pain induced by L5/L6 spinal nerve ligation. Whole-cell recording of lamina II neurons was performed in spinal cord slices from control and nerve-ligated rats. The baseline amplitude of glutamatergic EPSCs evoked from primary afferents was significantly larger in nerve-injured rats than in control rats. However, the baseline frequency of GABAergic and glycinergic inhibitory postsynaptic currents (IPSCs) was much lower in nerve-injured rats than in control rats. The group III mGluR agonist l (+)-2-amino-4-phosphonbutyric acid ( l -AP4) produced a greater inhibition of the amplitude of monosynaptic and polysynaptic evoked EPSCs in nerve-injured rats than in control rats. l -AP4 inhibited the frequency of miniature EPSCs in 66.7% of neurons in control rats but its inhibitory effect was observed in all neurons tested in nerve-injured rats. Furthermore, l -AP4 similarly inhibited the frequency of GABAergic and glycinergic IPSCs in control and nerve-injured rats. Our study suggests that spinal nerve injury augments glutamatergic input from primary afferents but decreases GABAergic and glycinergic input to spinal dorsal horn neurons. Activation of group III mGluRs attenuates glutamatergic input from primary afferents in nerve-injured rats, which could explain the antinociceptive effect of group III mGluR agonists on neuropathic pain.
The NCEP Climate Forecast System Saha, S.; Nadiga, S.; Thiaw, C. ...
Journal of climate,
08/2006, Letnik:
19, Številka:
15
Journal Article
Recenzirano
Odprti dostop
The Climate Forecast System (CFS), the fully coupled ocean–land–atmosphere dynamical seasonal prediction system, which became operational at NCEP in August 2004, is described and evaluated in this ...paper. The CFS provides important advances in operational seasonal prediction on a number of fronts. For the first time in the history of U.S. operational seasonal prediction, a dynamical modeling system has demonstrated a level of skill in forecasting U.S. surface temperature and precipitation that is comparable to the skill of the statistical methods used by the NCEP Climate Prediction Center (CPC). This represents a significant improvement over the previous dynamical modeling system used at NCEP. Furthermore, the skill provided by the CFS spatially and temporally complements the skill provided by the statistical tools. The availability of a dynamical modeling tool with demonstrated skill should result in overall improvement in the operational seasonal forecasts produced by CPC.
The atmospheric component of the CFS is a lower-resolution version of the Global Forecast System (GFS) that was the operational global weather prediction model at NCEP during 2003. The ocean component is the GFDL Modular Ocean Model version 3 (MOM3). There are several important improvements inherent in the new CFS relative to the previous dynamical forecast system. These include (i) the atmosphere–ocean coupling spans almost all of the globe (as opposed to the tropical Pacific only); (ii) the CFS is a fully coupled modeling system with no flux correction (as opposed to the previous uncoupled “tier-2” system, which employed multiple bias and flux corrections); and (iii) a set of fully coupled retrospective forecasts covering a 24-yr period (1981–2004), with 15 forecasts per calendar month out to nine months into the future, have been produced with the CFS.
These 24 years of fully coupled retrospective forecasts are of paramount importance to the proper calibration (bias correction) of subsequent operational seasonal forecasts. They provide a meaningful a priori estimate of model skill that is critical in determining the utility of the real-time dynamical forecast in the operational framework. The retrospective dataset also provides a wealth of information for researchers to study interactive atmosphere–land–ocean processes.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a ...candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding TACI, in 13 individuals with common variable immunodeficiency. Homozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF. Family members heterozygous with respect to the C104R mutation and individuals with sporadic common variable immunodeficiency who were heterozygous with respect to the amino acid substitutions A181E, S194X and R202H had humoral immunodeficiency. Although signs of autoimmunity and lymphoproliferation are evident, the human phenotype differs from that of the Tnfrsf13b-/- mouse model.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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