Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0% (n = 17) and 9.0% (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3% vs. 25.0%). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0% vs. 12.0%, and hyperbilirubinemia, 20.0% vs. 1.6%, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory

Ample Pairs

We show that the ample degree of a stable theory with trivial forking is preserved when we consider the corresponding theory of belles paires, if it exists. This result also applies to the theory of $H$-structures of a trivial theory of rank $1$.Comment: Research partially supported by the program MTM2014-59178-P. The second author conducted research with support of the programme ANR-13-BS01-0006 Valcomo. The third author would like to thank the European Research Council grant 33882

Retinal Vessel Density in Optical Coherence Tomography Angiography in Optic Atrophy after Nonarteritic Anterior Ischemic Optic Neuropathy

Aims. To compare optical coherence tomography angiography (OCT-A) retinal vasculature measurements between normal and optic atrophy after nonarteritic anterior ischemic optic neuropathy (NAION) subjects. Design. This prospective observational study was conducted between July 2015 and August 2016 at the ophthalmology outpatient department of a referral center in Taiwan. Peripapillary (4.5 × 4.5 mm) and parafoveal (6 × 6 mm) OCT-A scans were acquired. Measurements of the peripapillary region were obtained in two areas: (1) circumpapillary vessel density (cpVD) and (2) whole enface image vessel density (wiVD). Results. 13 participants with optic atrophy after NAION had lower peripapillary vessel density than the 18 age-matched participants in the healthy control (HC) group (p<0.001 for both cpVD and wiVD). However, the parafoveal vessel density was not significantly different between the two groups (p=0.49). The areas under the receiver operating characteristic curve for the HC and NAION eyes were 0.992 for cpVD and 0.970 for wiVD. cpVD and wiVD were significantly correlated with the average retinal nerve fiber layer thickness (p<0.001 for both). Conclusion. Peripapillary retinal perfusion is significantly decreased in optic atrophy after NAION. OCT-A may aid in the understanding of structure-function-perfusion relationships in NAION

Antcin-H Isolated from Antrodia cinnamomea

Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, Antrodia cinnamomea, in Taiwan. This study showed that antcin-H inhibited the growth of human renal carcinoma 786-0 cells; the IC50 value (for 48 h) was 170 μM. Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (<100 μM); these events were accompanied by inhibition of FAK and Src kinase activities, decrease of paxillin phosphorylation, impairment of lamellipodium formation, and upregulation of TIMPs and downregulation of MMPs, especially MMP-7 expression. Luciferase reporter assay showed that antcin-H repressed the MMP-7 promoter activity, in parallel to inhibiting c-Fos/AP-1 and C/EBP-β transactivation abilities. Moreover, antcin-H suppressed the activity of ERK1/2 and decreased the binding ability of C/EBP-β and c-Fos on the upstream/enhancer region of MMP-7 promoter. Overall, this study demonstrated that the anti-invasive effect of antcin-H in human renal carcinoma 786-0 cells might be at least in part by abrogating focal adhesion complex and lamellipodium formation through inhibiting the Src/FAK-paxillin signaling pathways and decreasing MMP-7 expression through suppressing the ERK1/2-AP-1/c-Fos and C/EBP-β signaling axis. Our findings provide the evidence that antcin-H may be an active component existing in A. cinnamomea with anticancer effect

Plasma Low-Density Lipoprotein Cholesterol Correlates With Heart Function in Individuals With Type 2 Diabetes Mellitus: A Cross-Sectional Study

Background: Heart failure is a frequent complication of type 2 diabetes mellitus (T2DM). Plasma cholesterol, particularly the proatherogenic low-density lipoprotein (LDL) cholesterol, impairs heart function by promoting atheroma formation and ventricular dysfunction. Considering the established effect of cholesterol on the cardiovascular system, we hypothesized that plasma LDL cholesterol may influence left ventricular function in individuals with T2DM.Methods: This cross-sectional study was conducted at a tertiary care hospital in Taiwan. Enrollment criteria were patients exceeding 21 years of age with T2DM who received antidiabetic and cholesterol-lowering medications. Candidates were excluded if they had heart failure, acute cardiovascular events, or familial hypercholesterolemia. Participants received blood sampling for plasma lipids after a 12-h fast, followed by transthoracic echocardiography in the cardiology clinic.Results: The study enrolled 118 participants who were divided into two groups according to their plasma LDL cholesterol levels. Demographic characteristics including age (69.7 vs. 66.9 years, P = 0.159), body mass index (26.2 vs. 25.9 kg/m2, P = 0.66), diabetes duration (5.4 vs. 5.1 years, P = 0.48), hemoglobin A1c (7.2 vs. 7.5%, P = 0.225), and systolic blood pressure (129 vs. 130 mm Hg, P = 0.735) were similar between these groups. Moreover, all participants received similar antihypertensive medications. Participants with lower plasma LDL cholesterol levels had better heart function, as measured by the left ventricular ejection fraction (LVEF), than patients with higher LDL cholesterol levels (58.0 vs. 50.5%, P = 0.022). Multivariate regression analysis also showed an inverse correlation between plasma LDL cholesterol and left ventricular function (β coefficient: −0.110, P = 0.024).Conclusion: This study observed an inverse correlation between plasma LDL cholesterol and heart function in individuals with T2DM. Patients with higher levels of plasma LDL cholesterol had worse left ventricular function. Therefore, plasma LDL cholesterol may be a modifiable risk factor of heart failure in diabetes, but prospective studies are necessary to confirm this finding

Sox2, a stemness gene, regulates tumor-initiating and drug-resistant properties in CD133-positive glioblastoma stem cells

AbstractBackgroundGlioblastoma multiforme (GBM) is the most lethal type of adult brain cancer and performs outrageous growth and resistance regardless of adjuvant chemotherapies, eventually contributing to tumor recurrence and poor outcomes. Considering the common heterogeneity of cancer cells, the imbalanced regulatory mechanism could be switched on/off and contribute to drug resistance. Moreover, the subpopulation of GBM cells was recently discovered to share similar phenotypes with neural stem cells. These cancer stem cells (CSCs) promote the potency of tumor initiation. As a result, targeting of glioma stem cells has become the dominant way of improving the therapeutic outcome against GBM and extending the life span of patients. Among the biomarkers of CSCs, CD-133 (prominin-1) has been known to effectively isolate CSCs from cancer population, including GBM; however, the underlying mechanism of how stemness genes manipulate CSC-associated phenotypes, such as tumor initiation and relapse, is still unclear.MethodsTumorigenicity, drug resistance and embryonic stem cell markers were examined in primary CD133-positive (CD133+) GBM cells and CD133+ subpopulation. Stemness signature of CD133+ GBM cells was identified using microarray analysis. Stem cell potency, tumorigenicity and drug resistance were also tested in differential expression of SOX2 in GBM cells.ResultsIn this study, high tumorigenic and drug resistance was noticed in primary CD-133+ GBM cells; meanwhile, plenty of embryonic stem cell markers were also elevated in the CD-133+ subpopulation. Using microarray analysis, we identified SOX2 as the most enriched gene among the stemness signature in CD133+ GBM cells. Overexpression of SOX2 consistently enhanced the stem cell potency in the GBM cell lines, whereas knockdown of SOX2 dramatically withdrew CD133 expression in CD133+ GBM cells. Additionally, we silenced SOX2 expression using RNAi system, which abrogated the ability of tumor initiation as well as drug resistance of CD133+ GBM cells, suggesting that SOX2 plays a crucial role in regulating tumorigenicity in CD133+ GBM cells.ConclusionSOX2 plays a crucial role in regulating tumorigenicity in CD133+ GBM cells. Our results not only revealed the genetic plasticity contributing to drug resistance and stemness but also demonstrated the dominant role of SOX2 in maintenance of GBM CSCs, which may provide a novel therapeutic target to overcome the conundrum of poor survival of brain cancers

Fluoride Doping in Crystalline and Amorphous Indium Oxide Semiconductors

In this contribution, the structural and electronic effects of fluoride doping in both crystalline and amorphous indium oxides are investigated by both experimental and theoretical techniques. Pristine crystalline and amorphous fluoride-doped indium oxide (F:In-O) phases were prepared by solution-based combustion synthesis and sol-gel techniques, respectively. The chemical composition, environment, and solid-state microstructure of these materials were extensively studied with a wide array of state-of-the-art techniques such as UV-vis, X-ray photoelectron spectroscopy, grazing incidence X-ray diffraction, 19F and 115In solid-state NMR, high-resolution transmission electron microscopy (HR-TEM), and extended X-ray absorption fine structure (EXAFS) as well as by density functional theory (DFT) computation combined with MD simulations. Interestingly, the UV-vis data reveal that while the band gap increases upon F-doping in the crystalline phase, it decreases in the amorphous phase. The 19F solid-state NMR data indicate that upon fluorination, the InO3F3 environment predominates in the crystalline oxide phase, whereas the InO4F2 environment is predominant in the amorphous oxide phase. The HR-TEM data indicate that fluoride doping inhibits crystallization in both crystalline and amorphous In-O phases, a result supported by the 115In solid-state NMR, EXAFS, and DFT-MD simulation data. Thus, this study establishes fluoride as a versatile anionic agent to induce disorder in both crystalline and amorphous indium oxide matrices, while modifying the electronic properties of both, but in dissimilar ways

The Effect of Co-Exposure to Glyphosate, Cadmium, and Arsenic on Chronic Kidney Disease

The usage of glyphosate is increasing worldwide. Glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA), are of potential toxicological concern in unknown chronic kidney disease (CKDu). As with Cd and other elements, glyphosate exposure has been reported as risk factor for CKDu in farmers. This study aimed to evaluate the influence of co-exposure to glyphosate and metals or metalloids in chronic kidney disease (CKD). In this study, the urine samples from 55 patients with CKD and 100 participants without CKD were analyzed for glyphosate, arsenic (As), cadmium (Cd), and lead (Pb) concentrations, and estimated glomerular filtration rate (eGFR). Negative associations between glyphosate, AMPA, As, and Cd concentrations in the urine and eGFR were found for study subjects (p  1 μg/g creatinine; OR = 7.57, 95% CI = 1.91–29.95). With regard to the effect of co-exposure, the OR for subjects with an of eGFR  1 μg/g creatinine; OR = 1.57, 95% CI = 1.13–2.16) and As concentration (> 1 μg/g creatinine; OR = 1.01, 95% CI = 1.00–1.02). These results showed that glyphosate, AMPA, As, and Cd have an effect on CKD; notably, Cd, As, and glyphosate exposure can be important risk factors after stage 3a of CKD, and that there was a co-exposure effect of As and glyphosate in CKD after stage 3b. The potential health impacts of glyphosate should be considered, especial for patients with CKD and eGFR below 45 mL/min/1.73 m2