The combination of soluble tumor necrosis factor receptor type 1 and fibroblast growth factor 21 exhibits better prediction of renal outcomes in patients with type 2 diabetes mellitus.

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

Binocular rivalry from luminance and contrast.

Binocular rivalry is the phenomenon that when two incompatible images are simultaneously presented, one to each eye, the two images compete with each other to be the dominant percept. Studying the underlying neural mechanisms of binocular rivalry is useful for understanding the mechanisms of interocular inhibition. Levelt's Propositions, a set of four propositions that were originally published over fifty years ago, are not only useful for characterizing the perceptual dynamics of binocular rivalry, but can also provide a metric for assessing the common or differential neural mechanisms of binocular rivalry when diverse stimulus types are used. In the present study, we conducted a series of psychophysics experiments, where we compared the rivalry dynamics of two quite different types of stimuli. Orthogonal gratings, a classic type of rivalry stimulus, were contrasted with luminance patches, a type of rivalry stimulus that is relatively less studied. Our results showed that, similar to the orthogonal gratings, the alternate percepts in luminance-only rivalry were described by the modified Levelt's Propositions, despite the clearly slower alternation rates for luminance patches. However, unlike the mixed percepts observed during transitions between oriented gratings, fusion percepts during luminance rivalry were common, could be lustrous, and obeyed the same Propositions, suggesting a regime of tri-stability. Overall, both types of rivalry are consistent with recent models that posit separate binocular and monocular channels embedded within neural circuits that also accomplish contrast normalization. Finally, luminance rivalry is discussed in the contexts of binocular summation and suppression, as well as Fechner's paradox.

Helix B surface peptide protects against acute lung injury through reducing oxidative stress and endoplasmic reticulum stress via activation of Nrf2/HO-1 signaling pathway.

OBJECTIVE: Acute lung injury (ALI) is a clinical problem with poor prognosis and high mortality. The purpose of this study was to explore the effects of helix B position peptide (HBSP) on ALI and its mechanism. MATERIALS AND METHODS: C57/BL6 male mice were used to construct ALI models by LPS tracheal injection and detect the effect of HBSP on mouse ALI by subcutaneously injecting HBSP. In addition, normal human lung epithelial cell line (BEAS-2B) were cultured and stimulated with HBSP. Then, the effects of HBSP on oxidative stress and endoplasmic reticulum stress (ERS) in BEAS-2B cells were examined. Finally, the effect of HBSP on the Nrf2/HO-1 signaling pathway was examined, and the mechanism of action of HBSP was verified using the Nrf2/HO-1 signaling pathway inhibitor ML385. RESULTS: In vitro, HBSP increased the expression of SOD1/2 and decreased the expression of ERS-related molecules such as CHOP, GRP-78, and caspase-12, indicating that HBSP effectively reduces the level of oxidative stress and ERS in BEAS-2B cells. In addition, HBSP also increased the activity of the Nrf2/HO-1 signaling pathway and ML385 reduced the protective effect of HBSP on BEAS-2B cells. In vivo, HBSP significantly reduced LPS-induced mouse ALI. W/D and inflammatory factors in the BALF of the mouse lung were significantly reduced and the level of oxidative stress was also reduced. CONCLUSIONS: HBSP plays an important role in relieving ALI by activating Nrf2/HO-1 signaling pathway, which reduces the level of inflammation in lung tissue and oxidative stress and ERS in lung epithelial cells.

[Feasibility of echocardiography-guided repeated intraventricular blood sampling in mice].

Objective: To investigate the feasibility of echocardiography-guided closed-chest repeated intraventricular blood sampling in mice, and to clarify the maximum blood volume that can be collected by this method, and whether the method can be used for long-term repeated blood collection in mice. Methods: Twenty-four male C57BL/6J mice (10-14 weeks old) were divided into the terminal experiment group (n=4, for investigating the maximum blood amount that could be sampled at one time), the repeated 0.5 ml blood collection group (n=10, sampling 0.5 ml whole blood each time, once every two days for consecutive 4 weeks), and the repeated 0.75 ml blood collection group (n=10, sampling 0.75 ml whole blood each time, once every two days for consecutive 4 weeks). High-frequency echocardiography was used to display the largest section of the left ventricle, guiding the insulin syringe needle through the thorax into the left ventricle for blood collection. In the repeated 0.5 ml blood collection group, echocardiography was used to detect the cardiac structure and function before blood collection, three minutes after blood collection, and one week after the last (the 14th) blood collection. Results: We successfully performed echocardiography-guided closed-chest intraventricular blood sampling, with an average operating time (88±19)s per mouse, and a maximum blood volume (1.43±0.11)ml per mouse. In the repeated 0.5 ml blood collection group, heart rate, left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic dimension and left ventricular posterior wall end-diastolic thickness remained uncganged before the first blood collection and after 4 weeks of repeated blood collection (all P>0.05). No death in the repeated 0.5 ml blood collection group. However, in the 0.75 ml blood collection group, two mice died before the end point. Conclusions: The echocardiography-guided closed-chest intraventricular blood sampling is a safe, minimally invasive, convenient and efficient method, and can be used repeatedly for long-term blood collection in mice.

Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia.

Epithelial-mesenchymal transition (EMT) is a critical process for inducing stem-like properties of epithelial cancer cells. However, the role of EMT inducers in hematological malignancies is unknown. Twist1, an EMT inducer necessary for cell migration, has recently been found to have transcriptionally regulatory activity on the expression of Bmi1, and these two are capable of promoting tumorigenesis in a synergized manner. Knowing that Bmi1 expression is essential for maintenance of leukemic stem cells, we speculate that Twist1 might govern the pathogenesis of acute myeloid leukemia (AML) development as well. We found that upregulated Twist1 increased Bmi1 expression in AML and endued leukemic cells a higher proliferative potential and increased resistance to apoptosis. In primary AML samples, there was strong positive correlation between the expression levels of Twist1 and Bmi1. AML patients whose leukemic blasts harbored overexpressed Twist1 had a more aggressive clinical phenotype, but they were more likely to have a better clinical outcome after standard therapy. In vitro studies confirmed that Twist1-overexpressing leukemic cells were more susceptible to cytarabine, but not daunorubicin, cytotoxicity. Our findings suggest that, in a subset of AML patients, Twist1 has a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes.

Renal replacement therapy: available information versus demands of patients.

OBJECTIVE: This study examined the current state of information on renal replacement therapy and the educational demands of kidney transplant recipients. METHODS: The study was conducted through a survey. The questionnaire of this study was developed by researchers and was completed by 72 kidney recipients. RESULTS: The recipients were most frequently informed of hemodialysis (87.5%), followed by kidney transplantation (69.4%) or peritoneal dialysis (48.6%) as a modality of renal replacement therapy at the time of diagnosis of chronic renal failure. Information about kidney transplantation was provided when they were diagnosed with end-stage renal disease (ESRD; 33.3%) or right after initiation of dialysis (15.3%) or a few years thereafter (9.7%). They were informed about kidney transplantation mostly by transplantation surgeons (mean degree score = 3.1 ± 1.3; range, 1-4), followed in order by transplant coordinators, nephrologists, family members, other patients, artificial kidney unit nurses, and mass media or internet. Regarding the influence of the information on their decision to receive a transplant, the mean score was 3.2 ± 1.2 (range, 1-5). Also, kidney transplantation was evaluated as the best renal replacement therapy for work, pregnancy/delivery, traveling, and diet. CONCLUSION: Patients diagnosed with ESRD are not fully informed of transplantation as a primary optimal renal replacement therapy for their quality of life.

Cost-effectiveness of postremission intensive therapy in patients with acute leukemia.

BACKGROUND: We assessed the cost-effectiveness of high-dose arabinoside (HiDAC)-based and allogeneic stem-cell transplantation (alloSCT)-based therapy in patients with acute leukemia. PATIENTS AND METHODS: We analyzed the outcome, cost and cost-effectiveness of 106 patients treated from January 1994 to January 2002 [94 acute myelogenous leukemia (AML)/12 acute lymphoblastic leukemia (ALL)]. Forty-two young patients at either intermediate or unknown cytogenetic risk received postremission intensive therapy (24 HiDAC-based/18 alloSCT-based therapy). RESULTS: After a median follow-up of 50 months, the estimated 7-year overall survival for the HiDAC-based group showed a tendency to be higher than the alloSCT-based group (48% versus 28%, P = 0.1452). The HiDAC-based group spent a significantly lower total cost ($US51,857 versus 75,474, P = 0.004) than the alloSCT-based group. Cost-effectiveness analysis showed that the mean cost per year of life saved for the HiDAC-based group is considerably less expensive than the alloSCT-based group ($US11,224 versus 21,564). The reduced total cost for the HiDAC-based group originated from lower cost in room fees, medication, laboratory and procedure, but not in blood transfusion and professional manpower fees. CONCLUSION: For the postremission therapy in young AML patients at either intermediate or unknown cytogenetic risk, cost-effectiveness of HiDAC-based therapy compares favorably with that of alloSCT-based therapy, which deserves further clinical trials.

Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) generally have an unfavorable clinical course and are under-represented in clinical trials. The aim of this study was to analyze the prognosis and treatment outcome of elderly AML patients. PATIENTS AND METHODS: We studied 205 AML patients aged 65 years or older at our hospital. Prior to study initiation, we designated 13 variables to be analyzed for their impact on complete remission (CR) rate and overall survival (OS). RESULTS: Induction regimen (standard chemotherapy) and good performance status (PS) (Eastern Cooperative Oncology Group PS 0-1) independently influenced the achievement of CR. Multivariate analysis also determined five poor prognostic factors for OS: poor PS (score 2-4), presence of comorbidities, elevated serum lactate dehydrogenase level (> or =2x upper normal limit), extreme leukocytosis (> or =100 x 10(9)/l) and marked thrombocytopenia (< or =20 x 10(9)/l). Age was not an independent contributing factor in terms of either CR attainment or OS duration. Low-risk patients, who possessed one or less non-leukocytosis poor prognostic factor, had significantly longer disease-free survival and OS than their high-risk counterparts. CONCLUSIONS: Elderly AML patients should be risk-stratified at diagnosis. Anthracycline-based induction chemotherapy would be the best therapeutic option for such patients.

Radiation therapy versus chemotherapy as initial treatment for localized nasal natural killer (NK)/T-cell lymphoma: a single institute survey in Taiwan.

BACKGROUND: To clarify the role of intention to treat for patients with localized nasal natural killer (NK)/T-cell lymphoma, and to determine the prognostic factors for these patients. PATIENTS AND METHODS: We conducted a retrospective review of 46 patients with localized nasal NK/T-cell lymphomas treated at a single institute between January 1988 and July 2002. RESULTS: The type of intended treatment was a significant factor for overall survival (OS) (5-year OS: RT versus CT = 83.3% versus 28.6%, P = 0.0269) or failure-free survival (FFS) (5-year FFS: RT versus CT = 83.3% versus 27.1%, P = 0.0247). In the intended chemotherapy group, salvage with radiotherapy was superior to chemotherapy alone for OS (5-year OS: 42.2% versus 20.0%, P = 0.0252) or FFS (5-year FFS: 41.0% versus 20.0%, P = 0.0352). On multivariate analysis, both N stage and serum lactate dehydrogenase level were independent factors for OS and FFS. No radiotherapy was an independent adverse factor for OS; advanced T stage and more than one extranodal involvement were independent adverse factors for FFS. CONCLUSIONS: Patients with localized nasal NK/T-cell lymphomas were better managed with radiotherapy as front-line therapy. The advantage of radiotherapy persisted even as palliative therapy after chemotherapy.

Diagnostic value of serum transferrin receptor and glycosylated hemoglobin on hemolytic anemia.

Soluble serum transferritin receptor (sTfR) is a new diagnostic tool for iron depletion and erythropoiesis. Glycosylated hemoglobin (GHb) can be used to detect hemolysis. The present study was thus conducted to compare the diagnostic value of sTfR and GHb (measured as Hb A(1)c) in patients with hemolytic anemia. Four groups of subjects entered into our study. Group A included 13 patients with hemolytic anemia with effective erythropoiesis (EE). Group B included 13 patients with hemolytic anemia with ineffective erythropoiesis (IE). Group C included 15 healthy controls and group D summated groups A and B. sTfR, serum ferritin, plasma hemoglobin, complete blood count, reticulocyte, haptoglobin, lactic dehydrogenase (LDH), Hb A(1)c, liver and renal function, direct and indirect bilirubin, and fasting blood sugar were measured. Plasma Hb, hematocrit, mean corpuscular volume (MCV), platelet, haptoglobin, LDH, indirect bilirubin, Hb A(1)c, and sTfR were found to be significantly different between the controls and the hemolytics, either with effective or ineffective erythropoiesis. Reticulocyte count was significantly different only between the two hemolytic groups. Hb A(1)c and sTfR were both good for the diagnosis of hemolysis. Reticulocyte count was a good tool for distinguishing EE from IE.

Helicobacter pylori in dental plaque and saliva.

BACKGROUND: About half of the world population is infected with H. pylori, but the transmission and the source of this infection are still unclear. Recently, dental plaque (DP) and saliva have been implicated as possible sources of H. pylori infection. This study was done to investigate the detection rates of H. pylori in the DP and saliva by use of PCR depending on H. pylori infection state of gastric mucosa. METHODS: In 46 subjects, gastric H. pylori colonization was evaluated with CLO test, microscopy of Gram stained mucosal smear, culture and histology after modified Giemsa staining in the antrum and body, respectively. A patient was regarded as H. pylori positive if one or more of the four aforementioned test methods demonstrated H. pylori colonization of the gastric mucosa. For detection of H. pylori in the DP and saliva, PCR assay was done with ET4-U and ET4-L primers. To estimate the sensitivity and specificity of this PCR, H. pylori positivity was evaluated in the antrum and body, separately. RESULTS: The sensitivity of mucosal PCR was 50.0% (27/54) and the specificity 86.8% (33/38). When a subject was regarded as H. pyloi positive, if either antrum or body mucosal H. pylori was is positive, the positive rate of mucosal PCR was 62.1% (18 subjects) in the 29 H. pylori-positive and 17.6% (3 subjects) in the 17 H. pylori-negative subjects. DP PCR was positive in 2 of 29 H. pylori-positive subjects (6.9%) and none in the 17 H. pylori-negative (0%). Saliva PCR was positive in 4 of 14 H. pylori-positive subjects (28.6%) and none of 6 H. pylori-negative (0%). CONCLUSION: The detection rates of H. pylori in DP and saliva by PCR were rather low, 6.9% and 28.6%, respectively, and these rates might have been underestimated by low sensitivity of the PCR method used in this study. However, the results that H. pylori was found in the DP and saliva suggest that the oral cavity can perform a role as a reservoir of H. pylori in Korea.