Head and Neck Diseases by Alexandros G.Sfakianakis: 02/27/18

Τρίτη 27 Φεβρουαρίου 2018

Geographical origin traceability of tea based on multi-element spatial distribution and the relationship with soil in district scale

Publication date: August 2018
Source:Food Control, Volume 90
Author(s): Lei Li, Bo Wen, Xiaolei Zhang, Yue Zhao, Yu Duan, Xiangfei Song, Shuang Ren, Yuhua Wang, Wanping Fang, Xujun Zhu
In this study, a discriminant model was established by determining mineral element contents in tea leaves and the soil, collected from Lishui, Jiangsu Province, China. The contents of 12 elements (Se, Zn, Ni, Mn, Cr, Pb, Mg, Ca, Cu, Al, Na, and K) were determined in both tea leaves and soil samples. Cluster analysis and principal component analysis (PCA) were employed for regional classification of tea samples. After data conversion and correlation analysis, spatial and quantitative prediction models were established by ordinary Kriging interpolation and multiple linear regressions. The results indicated a corresponding relationship of elements between tea and soil, and the cluster analysis and PCA showed a clear distinction between tea from the north to that from the middle and south of Lishui. Kriging interpolation predicted the levels of 12 elements, and among them, Se, Ca, and Cr showed a related spatial distribution. Three linear regression equations were established using Mn, Al, Ni, and K contents and soil pH, and these equations fitted well between predicted and actual values. The established linear equations can be used to identify the predominant mineral elements in tea plants and soil from Lishui and to identify the geographical origin of the tea product.

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Review of reduction factors by buildings for gamma radiation from radiocaesium deposited on the ground due to fallout

Publication date: July 2018
Source:Journal of Environmental Radioactivity, Volume 187
Author(s): Hiroko Yoshida-Ohuchi, Norihiro Matsuda, Kimiaki Saito
In order to estimate residents' external dose due to radionuclide exposure resulting from fallout deposit on the ground, the shielding and dose reduction effects provided by structures such as houses and workplaces are taken into account as most individuals spend a large portion of their time indoors. Many works on both calculation and measurement for European and American settlements have been reported and factors such as, shielding factors, protection factors, reduction factors, and location factors have been determined. However, measurement data for Japanese settlements are lacking. Thus, the Japanese government used reduction factors given in the International Atomic Energy Agency documents from American and European settlements when Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident occurred. The United Nations Scientific Committee on the Effects of Atomic Radiation used location factors from European settlements for the same reason. Soon after the FDNPP accident, several measurements and calculations were performed to obtain specific reduction factors for Japanese settlements due to this lack of data. This research reviews previous studies that determined factors such as, shielding factors, protection factors, reduction factors, and location factors and summarizes specific results for Japan. We discuss the issues in determining these factors and in applying them to estimate indoor dose. The contribution of surface contamination to the indoor ambient dose equivalent rate is also discussed.

http://ift.tt/2EZnLSc

7Be concentration in the near-surface layer of the air in Bialystok (north-eastern Poland) in the years 1992–2010

Publication date: July 2018
Source:Journal of Environmental Radioactivity, Volume 187
Author(s): Jacek Kapała, Maria Karpińska, Stanisław Mnich, Anna Gromotowicz-Popławska, Grzegorz Kulesza
Weekly measurements of air ⁷Be concentrations (n = 769) were performed in the years 1992–2010 in Bialystok (north-eastern Poland) using gamma spectrometry. The arithmetic mean (AM) concentration of ⁷Be was 2.51 mBq m⁻³, and the median (M) was 2.24 mBq m⁻³ (range 0.47–7.81 mBq m⁻³). The observed ⁷Be concentrations were within the range of levels recorded in Europe. Typical seasonal variability was observed. Concentrations of ⁷Be in the warm season (May, June, July) were almost twice as high as those in the cold season (November, December, January).A correlation was found between weekly ⁷Be concentrations and mean weekly values of relative humidity, temperature, and wind speed throughout the observation period. Pearson's correlation coefficients were −0.63, p < 0.001; 0.477, p < 0.001; −0.288, p < 0.001, respectively.The correlation coefficient between sunspot number and mean annual ⁷Be concentrations in the air in the years 1992–2010 was −0.609.

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Identification of a unique insertion in Plant Organellar DNA polymerases responsible for 5'-dRP lyase and strand-displacement activities: Implications for Base Excision Repair

Publication date: Available online 27 February 2018
Source:DNA Repair
Author(s): Carlos H. Trasviña-Arenas, Noe Baruch-Torres, Francisco J. Cordoba-Andrade, Víctor M. Ayala-García, Paola L. García-Medel, Corina Díaz-Quezada, Antolín Peralta-Castro, José Juan Ordaz-Ortiz, Luis G. Brieba
Plant mitochondrial and chloroplast genomes encode essential proteins for oxidative phosphorylation and photosynthesis. For proper cellular function, plant organelles must ensure genome integrity. Although plant organelles repair damaged DNA using the multi-enzyme Base Excision Repair (BER) pathway, the details of this pathway in plant organelles are largely unknown. The initial enzymatic steps in BER produce a 5'-deoxyribose phosphate (5'-dRP) moiety that must be removed to allow DNA ligation and in plant organelles, the enzymes responsible for the removal of a 5'-dRP group are unknown. In metazoans, DNA polymerases (DNAPs) remove the 5'-dRP moiety using their intrinsic lyase and/or strand-displacement activities during short or long-patch BER sub-pathways, respectively. The plant model Arabidopsis thaliana encodes two family-A DNAPs paralogs, AtPolIA and AtPolIB, which are the sole DNAPs in plant organelles identified to date. Herein we demonstrate that both AtPolIs present 5'-dRP lyase activities. AtPolIB performs efficient strand-displacement on a BER-associated 1-nt gap DNA substrate, whereas AtPolIA exhibits only moderate strand-displacement activity. Both lyase and strand-displacement activities are dependent on an amino acid insertion that is exclusively present in plant organellar DNAPs. Within this insertion, we identified that residue AtPollB-Lys593 acts as nucleophile for lyase activity. Our results demonstrate that AtPolIs are functionally equipped to play a role in short-patch BER and suggest a major role of AtPolIB in a predicted long-patch BER sub-pathway. We propose that the acquisition of insertion 1 in the polymerization domain of AtPolIs was a key component in their evolution as BER associated and replicative DNAPs.

Graphical abstract

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Erratum to “DNA Replication and associated repair pathways are involved in the mutagenesis of methylated cytosine”[DNA Repair, 62 (2018) 1–7]

Publication date: Available online 27 February 2018
Source:DNA Repair
Author(s): Marketa Tomkova, Michael McClellan, Skirmantas Kriaucionis, Benjamin Schuster-Boockler

http://ift.tt/2GRf0tI

Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice

Publication date: Available online 27 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Zixia Wang, Dan Xu, Linlin She, Yirui Zhang, Qingli Wei, Jiye Aa, Guangji Wang, Baolin Liu, Yuan Xie
ObjectiveThis study is designed to investigate whether curcumin reduces excessive hepatic glucose production (HGP) via regulation of second messenger cAMP.MethodsHigh-fat diet (HFD)-fed mice were orally administrated of metformin (200 mg/kg) or curcumin (50 mg/kg) daily for 10 weeks. Meanwhile, we stimulated mouse primary hepatocytes with palmitate (PA).ResultsCurcumin reduced hepatic cAMP accumulation by preserving PDE4B induction, thereby suppressing gluconeogenesis via blocking cAMP/PKA activation. Curcumin reduced lipid deposition by reducing free fatty acid uptake and prevented acetyl CoA accumulation by combating mitochondrial oxidation. As a result from inhibiting acetyl CoA accumulation, curcumin protected pyruvate dehydrogenase (PDH) activity and inhibited pyruvate carboxylase (PC), limiting the shift of mitochondrial pyruvate from oxidation to gluconeogenesis via the carboxylation.ConclusionCurcumin reduced cAMP accumulation by preserving PDE4B activity and inhibited acetyl CoA production by reducing mitochondrial fatty acid oxidation, thereby restraining pyruvate-driven hepatic glucose production.

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Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Molecular and thyroid hormone binding properties of lamprey transthyretins: The role of an N-terminal histidine-rich segment in hormone binding with high affinity

Publication date: Available online 27 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Kentaro Kasai, Norihito Nishiyama, Kiyoshi Yamauchi
Transthyretin (TTR) is a plasma thyroid hormone (TH) binder that emerged from an ancient hydroxyisourate hydrolase by gene duplication. To know how an ancient TTR had high affinity for THs, molecular and TH binding properties of lamprey TTRs were investigated. In adult serum, the lipoprotein LAL was a major T3 binder with low affinity. Lamprey TTRs had an N-terminal histidine-rich segment, and had two classes of binding sites for 3,3′,5-triiodo-L-thyronine (T3): a high-affinity and a low-affinity site. Mutant TTRΔ3-11, lacking the N-terminal histidine-rich segment, lost the high-affinity T3 binding site. [¹²⁵I]T3 binding to wild type TTR and mutant TTRΔ3-11, was differentially modulated by Zn²⁺. Zn²⁺ contents of wild type TTR were 7–10/TTR (mol/mol). Our results demonstrate that lamprey TTR is a Zn²⁺-dependent T3 binder. The N-terminal histidine-rich segment may be essential for neo-functionalization (i.e., high-affinity T3 binding activity) of an ancient TTR after gene duplication.

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Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27

http://ift.tt/2F32VS4

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Neighborhood Resolved Fiber Orientation Distributions (NRFOD) in Automatic Labeling of White Matter Fiber Pathways

Publication date: Available online 27 February 2018
Source:Medical Image Analysis
Author(s): Devran Ugurlu, Zeynep Firat, Ugur Ture, Gozde Unal
Accurate digital representation of major white matter bundles in the brain is an important goal in neuroscience image computing since the representations can be used for surgical planning, intra-patient longitudinal analysis and inter-subject population connectivity studies. Reconstructing desired fiber bundles generally involves manual selection of regions of interest by an expert, which is subject to user bias and fatigue, hence an automation is desirable. To that end, we first present a novel anatomical representation based on Neighborhood Resolved Fiber Orientation Distributions (NRFOD) along the fibers. The resolved fiber orientations are obtained by generalized q-sampling imaging (GQI) and a subsequent diffusion decomposition method. A fiber-to-fiber distance measure between the proposed fiber representations is then used in a density-based clustering framework to select the clusters corresponding to the major pathways of interest. In addition, neuroanatomical priors are utilized to constrain the set of candidate fibers before density-based clustering. The proposed fiber clustering approach is exemplified on automation of the reconstruction of the major fiber pathways in the brainstem: corticospinal tract (CST); medial lemniscus (ML); middle cerebellar peduncle (MCP); inferior cerebellar peduncle (ICP); superior cerebellar peduncle (SCP). Experimental results on Human Connectome Project (HCP)'s publicly available "WU-Minn 500 Subjects + MEG2 dataset" and expert evaluations demonstrate the potential of the proposed fiber clustering method in brainstem white matter structure analysis.

Graphical abstract

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Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27

http://ift.tt/2F32VS4

Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27

http://ift.tt/2F32VS4

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Editorial Board

Publication date: January 2018
Source:Gene Expression Patterns, Volume 27

http://ift.tt/2F32VS4

Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid Carcinoma

Thyroid , Vol. 0, No. 0.

http://ift.tt/2ozzX50

Polymorphisms in Pediatric Idiopathic Nephrotic Syndrome.

Polymorphisms in Pediatric Idiopathic Nephrotic Syndrome.

Clin Lab. 2018 Jan 01;64(1):221-0

Authors: Wiwanitkit BJAV

PMID: 29479899 [PubMed - in process]

http://ift.tt/2HRbCR3

Glycoprofiling of Early Gastric Cancer Using Lectin Microarray Technology.

Glycoprofiling of Early Gastric Cancer Using Lectin Microarray Technology.

Clin Lab. 2018 Jan 01;64(1):153-161

Authors: Li T, Mo C, Qin X, Li S, Liu Y, Liu Z

Abstract
BACKGROUND: Recently, studies have reported that protein glycosylation plays an important role in the occurrence and development of cancer. Gastric cancer is a common cancer with high morbidity and mortality owing to most gastric cancers are discovered only at an advanced stage. Here, we aim to discover novel specific serum glycanbased biomarkers for gastric cancer.
METHODS: A lectin microarray with 50 kinds of tumor-associated lectin was used to detect the glycan profiles of serum samples between early gastric cancer and healthy controls. Then lectin blot was performed to validate the differences.
RESULTS: The result of the lectin microarray showed that the signal intensities of 13 lectins showed significant differences between the healthy controls and early gastric cancer. Compared to the healthy, the normalized fluorescent intensities of the lectins PWA, LEL, and STL were significantly increased, and it implied that their specifically recognized GlcNAc showed an especially elevated expression in early gastric cancer. Moreover, the binding affinity of the lectins EEL, RCA-II, RCA-I, VAL, DSA, PHA-L, UEA, and CAL were higher in the early gastric cancer than in healthy controls. These glycan structures containing GalNAc, terminal Galβ 1-4 GlcNAc, Tri/tetraantennary N-glycan, β-1, 6GlcNAc branching structure, α-linked fucose residues, and Tn antigen were elevated in gastric cancer. While the two lectins CFL GNL reduced their binding ability. In addition, their specifically recognized N-acetyl-D-galactosamine structure and (α-1,3) mannose residues were decreased in early gastric cancer. Furthermore, lectin blot results of LEL, STL, PHA-L, RCA-I were consistent with the results of the lectin microarray.
CONCLUSIONS: The findings of our study clarify the specific alterations for glycosylation during the pathogenesis of gastric cancer. The specific high expression of GlcNAc structure may act as a potential early diagnostic marker for gastric cancer.

PMID: 29479898 [PubMed - in process]

http://ift.tt/2GRXEND

The rs2839698 Single Nucleotide Polymorphism of lncRNA H19 is Associated with Post-Operative Prognosis in T3 Gastric Adenocarcinoma.

The rs2839698 Single Nucleotide Polymorphism of lncRNA H19 is Associated with Post-Operative Prognosis in T3 Gastric Adenocarcinoma.

Clin Lab. 2018 Jan 01;64(1):105-112

Authors: Wang W, Yang Q, Huang Q, Zhang H, Zhang Z, Gao J, Ren W, Hu Y, Lin Y, Dang Y, Zhang F, Wang W, Wang L

Abstract
BACKGROUND: It has been widely demonstrated that long non-coding RNA H19 (lncRNA H19) plays an important role in the progression of various human cancers. However, the associations of common genetic variations with recurrence and survival in gastric adenocarcinoma in this lncRNA remain largely unknown.
METHODS: The rs2839698 single nucleotide polymorphism (SNP) of H19 was genotyped in tissue samples from 441 patients with T3 gastric adenocarcinoma who had surgical operations between 2004 to 2009, and the relationships between the different genotypes and recurrence and survival after surgery alone (n = 156) or surgery plus chemotherapy (n = 285) were assessed using 3 different statistical-methods.
RESULTS: Based on the final day of investigation (November 2014), the GA genotype was significantly associated with recurrence and survival in patients treated with surgery alone, but not in patients treated with surgery plus chemotherapy. In patients treated with surgery alone, individuals with the GA genotype had significantly lower risks of recurrence and death [adjusted hazard ratio (HR) 0.57, 95% CI 0.37 - 0.88; adjusted HR: 0.58, 95% CI 0.38 - 0.88] than the GG genotype (p = 0.010 and p = 0.010), respectively. More importantly, patients treated with surgery alone who carried the GA genotype achieved significantly longer median disease-free survival time and overall survival than carriers of the GG genotype (45 vs. 26 months, p = 0.010; 44 vs. 23 months, p = 0.013).
CONCLUSIONS: The rs2839698 SNP of H19 may have potential as a novel prognostic factor for survival in T3 gastric adenocarcinoma after surgery alone; these finding have special relevance to patients who are not suitable for postoperative chemotherapy.

PMID: 29479897 [PubMed - in process]

http://ift.tt/2HP1cBj

Evaluation of Serum α-Fetoprotein Levels During Different Infection Phases of CHB Patients.

Evaluation of Serum α-Fetoprotein Levels During Different Infection Phases of CHB Patients.

Clin Lab. 2018 Jan 01;64(1):43-49

Authors: Yang N, Feng J, Li ZR, Ming KH, Lei XX, Xu BL

Abstract
BACKGROUND: Chronic hepatitis B patients carry a high risk of developing hepatocellular carcinoma (HCC). α-Fetoprotein (AFP) is one of the most commonly used and reliable biomarkers for HCC. However, the AFP level during different phases of CHB is not well understood. We aimed to identify the AFP levels during the different infection phases of CHB patient and explore which phase is at high risk of developing HCC.
METHODS: Three hundred and fifty-five CHB patients were divided into four groups: a. immune tolerant HBeAgpositive phase (IT); b. immune reactive HBeAg-positive phase (IR), c. inactive carrier state (IC), d. HBeAg-negative activation phase (ENA). The risk of development of HCC in different group is assessed by the serum AFP levels. An electrochemiluminescence assay was used to analyze serum AFP levels.
RESULTS: Mean AFP levels were different in each phase of CHB (p < 0.001): IT (9.6 ng/mL), IR (33.7 ng/mL), IC (3.2 ng/mL), and ENA (71.6 ng/mL). The ENA phase had the highest AFP level and IC phase has the lowest. There was no correlation between serum AFP level and HBV viral load. A significant correlation between serum ALT levels and HBV viral load was observed (r = 0.272, p < 0.01).
CONCLUSIONS: These findings suggest that high levels of AFP during HBeAg-negative activation phase (ENA) may be associated with a high risk of developing of HCC. Furthermore, higher burden of HBV viral load is associated with more severe liver damage.

PMID: 29479896 [PubMed - in process]

http://ift.tt/2HNxPzz

Diagnostic Value of MicroRNA-18a for Gastric Cancer: a Meta-Analysis.

Diagnostic Value of MicroRNA-18a for Gastric Cancer: a Meta-Analysis.

Clin Lab. 2018 Jan 01;64(1):177-184

Authors: Liang Q, Zhang G, Wang J, Sheng S

Abstract
BACKGROUND: Emerging data demonstrated that circulating microRNA-18a (miR-18a) expression level was significantly different between gastric carcinoma individuals and healthy groups, implying that miR-18a may be a potential biomarker for gastric cancer. Nevertheless, the reports remain inconsistent. This meta-analysis was performed to evaluate the diagnostic value of miR-18a in gastric tumor detection.
METHODS: All the relevant papers were searched and collected until July 2017 in PubMed, Cochrane Library, Wiley Online Library, Chinese National Knowledge Infrastructure (CNKI), Technology of Chongqing (VIP), and Wanfang Database. Data was extracted from eligible studies. Diagnostic performance of miR-18a for gastric cancer were evaluated using STATA (version 12.0) and MetaDisc (version 1.4) statistical software.
RESULTS: Three studies were included in this meta-analysis with a total of 235 gastric cancer patients and 136 controls enrolled. The pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of circulating miR-18a to discriminate GC patients were 0.76 (95% confidence interval CI: 0.70, 0.81), 0.73 (95% CI: 0.65, 0.80), 2.76 (95% CI: 2.08, 3.65), 0.32 (95% CI: 0.19, 0.55), and 9.12 (95% CI: 4.36, 19.09), respectively. The area under the summary receiver operator characteristic (SROC) curve was 0.82.
CONCLUSIONS: miR-18a could be a promising noninvasive biomarker in gastric carcinoma diagnosis. Further prospective studies should be conducted to highlight the theoretical strengths before its use in clinic.

PMID: 29479894 [PubMed - in process]

http://ift.tt/2HQFxc9

Analysis of miRNA-221 Expression Level in Tumors and Marginal Biopsies from Patients with Breast Cancer (Cross-Sectional Observational Study).

Analysis of miRNA-221 Expression Level in Tumors and Marginal Biopsies from Patients with Breast Cancer (Cross-Sectional Observational Study).

Clin Lab. 2018 Jan 01;64(1):169-175

Authors: Abak A, Amini S, Estiar MA, Montazeri V, Sakhinia E, Abhari A

Abstract
BACKGROUND: miRNA-221 and miRNA-222 are two homologous microRNAs, the high-expression levels of which have been commonly demonstrated in the most current human cancer types as well as breast cancer. The purpose of this research was to determine the clinical value of measuring the expression level of hsa-miR-221-3p in breast cancer tissues and evaluate its biological and prognostic importance in breast cancer (BC).
METHODS: A total of 40 tumor samples and matched tumor-free margin specimens were obtained during surgery from patients with BC. After total RNA extraction and cDNA synthesis, the relative expression level of hsa-miR221-3p in tumor and marginal tissues was examined by quantitative real-time PCR. Moreover, the association between hsa-miR-221-3p expression and clinicopathological features of patients was detected.
RESULTS: The relative expression level of hsa-miR-221-3p in BC tissues was significantly higher than that in adjacent noncancerous breast biopsies (p ≤ 0.0001). Also, there was no significant association between hsa-miR-221-3p expression with clinicopathological characteristics (p > 0.05). The receiver operating characteristic (ROC) curve analyses also represented an optimum cutoff point of < 4.34 to show that hsa-miR-221-3p is an effective molecular biomarker for BC diagnosis.
CONCLUSIONS: This study illustrated that analysis of hsa-miR-221-3p relative gene expression may be applied as a biomarker for screening BC patients and could be a substantial tool in diagnosis and prognosis. Also, that could be advantageous in decreasing surgical mistakes in tumor elimination through the surgery and enhancing all over the progression of surgery with reformed tumor clearance.

PMID: 29479893 [PubMed - in process]

http://ift.tt/2GNoF4Q

The Clinical Implications of Thrombelastography in the Diagnosis of Acute Cerebral Infarction.

The Clinical Implications of Thrombelastography in the Diagnosis of Acute Cerebral Infarction.

Clin Lab. 2018 Jan 01;64(1):147-152

Authors: Liang Y, Wu J, Liu J, Liu H, Chen J

Abstract
BACKGROUND: Thrombelastography (TEG) is an analyzer reflecting the dynamic changes of blood coagulation. It has been used as a diagnosis index in many diseases. The aim of this study was to evaluate the relationship between TEG and acute cerebral infarction.
METHODS: Eighty patients with acute cerebral infarction and 80 healthy controls were enrolled. Each patient's TEG results and routine coagulation indices were recorded. All analyses were conducted with SPSS16.0 software.
RESULTS: Patients with acute cerebral infarction showed lower TEG R and K levels but higher TEG MA levels. There was a significantly negative correlation between TEG R and fibrinogen in the patient group. In addition, receiver operator characteristic curve analysis showed that TEG MA (cutoff value 63.9 mm) was a predictor of acute cerebral infarction (AUC value = 0.741, sensitivity 61%, specificity 81%).
CONCLUSIONS: TEG results have important clinical implications in the early diagnosis of acute cerebral infarction.

PMID: 29479891 [PubMed - in process]

http://ift.tt/2GQWEt3

CircRNAs as Potential Biomarkers in Gastrointestinal Tract Tumors: Opportunities and Challenges.

CircRNAs as Potential Biomarkers in Gastrointestinal Tract Tumors: Opportunities and Challenges.

Clin Lab. 2018 Jan 01;64(1):141-145

Authors: Liu C, Liu N, Cao B, Zhou Z, Yang G, Zhou P

Abstract
Most digestive system tumors have poor prognoses due to the lack of specific biomarkers. Circular RNAs (circRNAs) regulate the expression of genes and play essential roles in digestive system tumorigenesis. Here we review circRNA functions in gastrointestinal tract tumors. CircRNAs are promising biomarkers for clinical applications for gastrointestinal tract tumors.

PMID: 29479890 [PubMed - in process]

http://ift.tt/2HQaFIP

Reference Intervals of Cytokeratin-19 Fragment (CYFRA 21-1) in Healthy Adults in China.

Reference Intervals of Cytokeratin-19 Fragment (CYFRA 21-1) in Healthy Adults in China.

Clin Lab. 2018 Jan 01;64(1):123-133

Authors: Dai Y, Qu W, Sang S, Tao S, Li Y, Wang Y, Li Q, Wu T, Zhu A, Chen Q, Song J, Li Q, Ji Y, Zheng Y, Wang F

Abstract
BACKGROUND: The reference intervals for serum cytokeratin-19 fragment (CYFRA 21-1) have not been established in Chinese population. This study aimed to measure serum CYFRA 21-1 levels in healthy Chinese subjects.
METHODS: This cross-sectional, four-center study in two Chinese provinces enrolled participants (aged 18 - 85 years) with normal liver/kidney function and normal results for routine blood tests/urinalysis. Serum CYFRA 211 level was measured by ARCHITECT immunoassay (Abbott Diagnostics).
RESULTS: The study included 3,366 participants. The median (interquartile range) value for serum CYFRA 21-1 level was 1.38 (1.00 - 1.89) ng/mL and tended to increase with age. The upper limit of the 97.5th percentile was 3.55 ng/mL and tended to increase with age. Serum CYFRA 21-1 median level varied between the four centers from 1.22 (0.89, 1.71) to 1.55 (1.12, 2.18) ng/mL, while the 97.5th percentile varied from 3.24 to 4.09 ng/mL. CYFRA 21-1 level correlated weakly with age and creatinine level.
CONCLUSIONS: These new data can help to establish the 'normal range' of serum CYFRA 21-1 in people in China.

PMID: 29479889 [PubMed - in process]

http://ift.tt/2GM5msk

Decreased Serum Level of miR-155 is Associated with Obesity and its Related Metabolic Traits.

Decreased Serum Level of miR-155 is Associated with Obesity and its Related Metabolic Traits.

Clin Lab. 2018 Jan 01;64(1):77-84

Authors: Mahdavi R, Ghorbani S, Alipoor B, Panahi G, Khodabandehloo H, Esfahani EN, Razi F, Meshkani R

Abstract
BACKGROUND: Type 2 diabetes is the most common metabolic disease, affecting many of the adult population all around the world. In recent years much attention has been paid to the role of circulating miRNAs as novel biomarkers for various diseases. The aim of this study was to investigate the expression level of miR-155 in serum samples of diabetic and healthy subjects.
METHODS: 42 healthy and 45 type 2 diabetic subjects participated in the study. Serum miR-155 level of the subjects was measured using real-time PCR. The levels of IL-6 and TNF-α were quantified using ELISA.
RESULTS: There was no significant difference in the level of miR-155 between the diabetic and non-diabetic groups. The level of miR-155 in non-diabetic obese group was significantly lower than the non-diabetic lean subjects. Correlation analyses in non-diabetic group revealed a significant negative correlation between the amount of miR155 and body mass index and cholesterol levels after the elimination of the confounding factors. In diabetic group, a negative correlation was found between miR-155 and insulin, HOMA-IR, and waist circumference levels. Furthermore, no significant relationship between miR-155 and inflammatory cytokines (TNF-α and IL-6) was observed in both diabetic and healthy groups.
CONCLUSIONS: A reduced level of miR-155 might associate with obesity and its related metabolic traits such as hyperinsulinemia and dyslipidemia.

PMID: 29479888 [PubMed - in process]

http://ift.tt/2HTzR1a

Niemann-Pick Disease, Type C1 Gene Expression in PBMCs is Associated with Interleukin 10 Serum Concentration: a Case-Control Study.

Niemann-Pick Disease, Type C1 Gene Expression in PBMCs is Associated with Interleukin 10 Serum Concentration: a Case-Control Study.

Clin Lab. 2018 Jan 01;64(1):17-24

Authors: Zali F, Teimouri M, Shabani P, Vatannejad A, Najafi M, Shateri H, Asadnia M, Doosti M

Abstract
BACKGROUND: Recent studies showed that atherosclerosis is a lysosomal storage disease (LSD) and Niemann-Pick disease type C1 (NPC1) is the most important protein of the lysosomal membrane that is involved in the removal of FC from lysosomes. Whereas several in vitro and in vivo studies have described the crosstalk between lysosomal cholesterol accumulation and increased inflammation, there is no study addressing the correlation between NPC1 gene expression and an anti-inflammatory cytokine, interleukin 10 (IL-10) serum concentration in atherosclerotic patients.
METHODS: IL-10 and 25-hydroxyvitamin D serum concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) in atherosclerotic patients (n = 40) and a control group (n = 40). NPC1 gene expression analysis was performed by quantitative real-time PCR, and correlation between the two parameters was assessed.
RESULTS: Mean IL-10 serum concentration and peripheral blood mononuclear cells' (PBMCs) gene expression of NPC1, adjusted for drug consumption, age, and BMI, was not significantly different between the patient and control groups (p = 0.6 and 0.67 respectively). However, NPC1 gene expression showed positive significant correlation with IL-10 serum concentration (p = 0.04, r = 0.29). We also observed lower serum concentration of IL-10 in the subjects with lower 25-hydroxyvitamin D serum concentration (p = 0.034).
CONCLUSIONS: Our findings supported the previous observations showing the contribution of lysosomal lipid homeostasis of PBMCs to inflammation and pathogenesis of atherosclerosis.

PMID: 29479887 [PubMed - in process]

http://ift.tt/2GOxkUq

Application of Bone Turnover Markers PICP and β-CTx in the Diagnosis and Treatment of Breast Cancer with Bone Metastases.

Application of Bone Turnover Markers PICP and β-CTx in the Diagnosis and Treatment of Breast Cancer with Bone Metastases.

Clin Lab. 2018 Jan 01;64(1):11-16

Authors: Song B, Li X, Zhou Q, Yang X, Jiang Y, Wang A

Abstract
BACKGROUND: This study is to investigate the application of the bone turnover markers type I procollagen carboxyterminal propeptide (PICP) and β-isomerized forms of type I collagen breakdown products (β-CTx) in the diagnosis and treatment of breast cancer with bone metastases.
METHODS: A total of 162 breast cancer patients were included in this study. There were 70 cases with bone metastasis (BM group) and 92 cases without bone metastasis (non-bone metastasis, NBM group). The levels of the bone turnover markers PICP and β-CTx were measured using Electro-Chemiluminescence Immunoassay to compare the difference between BM and NBM group, before and after treatments in the NBM group, and to analyse the relationship with therapeutic effects.
RESULTS: The BM group had higher PICP and β-CTx levels than the NBM group and also higher in the non-luminal type group than the luminal type group, the differences were all statistically significant. However, no statistically significant differences were found among the pN0, pN1, pN2, and pN3 subgroups of the NBM group. Among the 70 cases of BM patient after 3 months of treatment, there were 48 cases that showed clinical benefits, with significantly reduced PICP and β-CTx levels (p = 0.02, p = 0.00, respectively), but 22 cases showed disease progression with elevated PICP and β-CTx levels (p = 0.01, p = 0.04, respectively).
CONCLUSIONS: The bone turnover markers PICP and β-CTx have crucial value in the diagnosis and treatment efficacy evaluation for women of breast cancer with bone metastases.

PMID: 29479886 [PubMed - in process]

http://ift.tt/2HQfyl5

Comparison of Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry Methods in the Measurement of Serum Androstenedione Levels.

Comparison of Immunoassay and Liquid Chromatography-Tandem Mass Spectrometry Methods in the Measurement of Serum Androstenedione Levels.

Clin Lab. 2018 Jan 01;64(1):69-75

Authors: Yucel K, Abusoglu S, Unlu A

Abstract
BACKGROUND: Recent reports have described inherent problems with androgen immunoassays compared with mass spectrometry analyses. In this study, a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed according to CLSI rules. The developed method was compared with two immunoassay methods, the enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA).
METHODS: After liquid-liquid extraction, a Shimadzu Prominence LC unit coupled to an ABSCIEX API 3200 mass spectrometer with atmospheric pressure chemical ionization was used to quantify serum androstenedione levels. Serum androstenedione results taken from tandem mass spectrometry were compared with the immunoassays.
RESULTS: The androstenedione assay was linear up to 50 ng/mL. Lower limit of quantitation and lower limit of detection were 0.195 ng/mL and 0.097 ng/mL, respectively. This method was not affected by matrix effect and other steroid hormone interferences. In this study, the obtained recovery was 69 - 99%, carryover value was determined as 0.026 ng/mL. According to the results of an interference study, androstenedione bias % did not exceed the limit of allowable bias % and 88.7% recovery was acquired for androstenedione. In the LC-MS/MS and ELISA comparison study, the slope value was found as 18.412, intercept -22.87, and r2 value as 0.1033. In the LC-MS/MS and RIA comparison study, slope value was found as 1.085, intercept 0.4541, and r2 value as 0.3712. In the RIA and ELISA comparison study, slope value was found as 9.57, intercept -15.5, and r2 value as 0.19.
CONCLUSIONS: The LC-MS/MS provides agreement with the results of radioimmunoassay but not with ELISA. This method offers better selectivity compared to immunoassay systems.

PMID: 29479885 [PubMed - in process]

http://ift.tt/2GPZw9o

Extramedullary Blast Crisis in a Patient with T315I BCR-ABL Mutated Chronic Myeloid Leukemia.

Extramedullary Blast Crisis in a Patient with T315I BCR-ABL Mutated Chronic Myeloid Leukemia.

Clin Lab. 2018 Jan 01;64(1):193-196

Authors: Zhang J, Zhang X, Lu Y, Jiao J, Chen Y, Lin D

Abstract
BACKGROUND: Extramedullary blast crisis (EBC) of T315I BCR-ABL mutated chronic myelogenous leukemia (CML) is extremely rare.
METHODS: We report an unusual case characterized by fever, right shoulder swelling, pleural effusion, and multiple bone destruction as the first signs of EBC of T315I BCR-ABL mutated CML.
RESULTS: The patient did not respond to chemotherapy consisting of anthracyclines, cytarabine and etoposide. His condition improved after the treatment with ponatinib combined with allogenic stem cell transplantation (alloHCT), but soon worsened after ponatinib withdrawal. He got slight relief after he continued ponatinib.
CONCLUSIONS: Ponatinib is an important treatment to control EBC even after allo-HCT.

PMID: 29479884 [PubMed - in process]

http://ift.tt/2HNxvAR

Use of the Polymerase Chain Reaction as a Complementary Method for the Detection of Central Nervous System Involvement in Children and Adolescents with Acute Lymphoblastic Leukemia.

Use of the Polymerase Chain Reaction as a Complementary Method for the Detection of Central Nervous System Involvement in Children and Adolescents with Acute Lymphoblastic Leukemia.

Clin Lab. 2018 Jan 01;64(1):205-209

Authors: Cancela CSP, Assumpcao JG, Paula FDF, Murao M, Viana MB, Oliveira BM

Abstract
BACKGROUND: Cytological analysis of the cerebrospinal fluid (CSF) remains the most widely used method for diagnosing central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL). This study aimed at evaluating the use of polymerase chain reaction (PCR), in comparison to other methods, for the assessment of the presence of blast cells in the CSF at the time of diagnosis of ALL.
METHODS: This was a prospective, single-centre, study enrolling all patients up to the age of 18 years who were admitted to a university hospital between November 2011 and November 2014 with a diagnosis of ALL and from whom it was possible to draw a sufficient amount of CSF for analysis by conventional cytology (CT), immunophenotyping (IMP), and PCR.
RESULTS: A total of 46 CSF samples from 44 ALL pediatric patients were included. CT was performed in all samples, IMP in 44, and PCR in 34. Thirteen (28.2%) samples showed positive results: two by CT, four by IMP, four by PCR, and three by both IMP and PCR.
CONCLUSIONS: The results of this study showed that PCR should be considered a complementary method for the evaluation of the CSF in ALL patients at diagnosis.

PMID: 29479883 [PubMed - in process]

http://ift.tt/2GRTMfh

Cadmium and Lead in Women Who Miscarried.

Cadmium and Lead in Women Who Miscarried.

Clin Lab. 2018 Jan 01;64(1):59-67

Authors: Omeljaniuk WJ, Socha K, Soroczynska J, Charkiewicz AE, Laudanski T, Kulikowski M, Kobylec E, Borawska MH

Abstract
BACKGROUND: Cadmium (Cd) and lead (Pb) are toxic elements which, when ingested excessively in food and drinking water, accumulate in selected organs and pass through the placenta barrier to the foetus, showing teratogenic effects. The aim of the study was to determine the concentration of Cd and Pb in blood and placental tissue in women who miscarried.
METHODS: The study group consisted of 83 women who miscarried. The control group included 35 women in the first trimester of pregnancy and after childbirth. The experimental materials consisted of whole blood and fragments of placental tissue. The concentrations of Cd and Pb were determined using atomic absorption spectrometry (AAS) with electrothermal atomization in a graphite furnace and by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in standard mode.
RESULTS: The average concentration of Cd (2.730 ± 2.07 µg/L) and Pb (35.54 ± 11.0 µg/L) in the blood of women with miscarriage was higher in comparison to the level of these toxic metals in the blood of women from the control group (Cd 1.035 ± 0.59 µg/L; Pb 27.11 ± 4.6 µg/L). The average Cd (214.4 ± 514 µg/L) and Pb (199.6 ± 348 µg/L) content in the placenta of women with miscarriage was higher in comparison to the amount of these elements in the placenta of women from the control group (Cd 127.4 ± 85 ng/L; Pb 26.35 ± 7.9 ng/L). Tobacco smoking significantly affected cadmium blood levels and the placental tissue content in women who miscarried.
CONCLUSIONS: Elevated Cd and Pb concentrations in the blood and placenta of pregnant women may be connected with the occurrence of miscarriage; therefore, the levels of these heavy metals should be monitored in women who plan pregnancy. It seems that determining the level of molar ratio between toxic metal and antioxidant elements can be analyzed as a marker for selection for control examinations as a valuable complement to existing diagnostic procedures in prevention, especially in early pregnancy. Additional diagnostic methods should be established as new tools in perinatal care in order to enable early diagnosis of pregnancy pathology and, especially, to prevent miscarriage.

PMID: 29479882 [PubMed - in process]

http://ift.tt/2t5xd58

The Relationship Between Serum Thiol Levels and Thiol/Disulfide Homeostasis with Head Trauma in Children.

The Relationship Between Serum Thiol Levels and Thiol/Disulfide Homeostasis with Head Trauma in Children.

Clin Lab. 2018 Jan 01;64(1):163-168

Authors: Giden R, Gokdemir MT, Erel O, Buyukaslan H, Karabag H

Abstract
BACKGROUND: Oxidative stress may induce brain injury. Thiols are one of the most important antioxidant agents, and thiol/disulphide (SH/SS) homeo stasis is a novel oxidative stress marker. The goal of the study was to investigate the relationship of thiol levels and SH/SS homeostasis with head trauma in pediatric patients.
METHODS: This prospective study was conducted in 85 consecutive pediatric patients aged < 18 years with isolated head trauma and 58 age- and gender-matched healthy controls in the Emergency Department (ED).
RESULTS: The mean age was 4.40 ± 3.03 years for the patient group and 4.75 ± 1.81 years for the controls (p > 0.05). There were no significant differences in biochemical parameters including serum albumin, urea, alanine aminotransferase, total bilirubin, uric acid, high-sensitivity C-reactive protein (hs-CRP), and white blood cells (WBC) in the patient and control groups (for each, p > 0.05). The thiol (SH) level was significantly higher in the patient group than in the controls (388.83 ± 51.949 vs. 369.04 ± 37.62 μmol/L; p = 0.009). The total thiol (TT) level was somewhat higher in the patient group, but the difference was not significant (416.11 ± 47.29 vs. 405.08 ± 35.27 μmol/L; p = 0.113). The disulphide (SS) level was lower in the patient group (p < 0.001). The SS/SH and SS/TT ratios were significantly lower in the patient group, while the SH/ TT ratio was significantly higher (p < 0.001).
CONCLUSIONS: Analysis of serum thiol levels and SH/SS homeostasis might be useful in order to determine the head trauma in pediatric patients.

PMID: 29479881 [PubMed - in process]

http://ift.tt/2Cq5Mqe

Lesch-Nyhan Syndrome in a Chinese Family with Mutation in the Hypoxanthine-Guanine Phosphoribosyltransferase Gene.

Lesch-Nyhan Syndrome in a Chinese Family with Mutation in the Hypoxanthine-Guanine Phosphoribosyltransferase Gene.

Clin Lab. 2018 Jan 01;64(1):197-200

Authors: Huang J, Zhang C, Guo Q, Zhang X, Ma L, Zhan Y, Chen Y

Abstract
BACKGROUND: Lesch-Nyhan syndrome (LNS) is a congenital X-linked recessive neurogenetic disorder caused by mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene. The main clinical manifestation includes hyperuricemia, juvenile-onset gouty arthritis, and neurological developmental disorders. Studies have reported more than 400 HPRT gene mutation sites, but the incidence of LNS in the Chinese population is extremely low.
METHODS: Here we report a 16-year-old male patient who suffered neurological dysfunction at an early age and gouty arthritis in his youth.
RESULTS: No activity of the HPRT enzyme was detected in the erythrocytes. Furthermore, we found a mutation on exon 3 of the HPRT gene in the patient and his mother (exon 3: c.143G>A), which resulted in arginine to histidine (p.R48H) substitution in the encoded protein. The same mutation was reported in several European families, but was found for the first time in a Chinese family.
CONCLUSIONS: Clinicians in China have poor experience in diagnosing LNS cases due to the low incidence in China. Therefore, LNS screening for infants or adolescents with hyperuricemia, gouty arthritis, and neurological dysfunction should be performed.

PMID: 29479880 [PubMed - in process]

http://ift.tt/2t5xaGu

Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice

In Vivo Imaging of Microvasculature during Anesthesia with High-Resolution Photoacoustic Microscopy

Publication date: Available online 28 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): Xiang Zhang, Xiaoqin Qian, Chao Tao, Xiaojun Liu
Anesthesia monitoring is extremely important in improving the quality of anesthesia and ensuring the safety of patients in operation. Photoacoustic microscopy (PAM) is proposed to in vivo image the skin microvasculature of 10 nude mice undergoing general anesthesia by using the isoflurane gas with a concentration of 3%. Benefiting from strong optical absorption of hemoglobin, PAM has good contrast and high resolution in mapping of microvasculature. A series of high quality images can clearly reveal the subtle changes of capillaries in morphology over time. Two indices, vessel intensity and vessel density, are extracted from these images to measure the microvasculature quantitatively. The imaging results show that the vessel intensity and density are increased over time. After 65 min, the vessel intensity increased 42.7 ± 8.6% and the density increased 28.6 ± 12.2%. These indices extracted from photoacoustic images accurately reflect the greater blood perfusion undergoing general anesthesia. Additionally, abnormal reductions of vessel intensity and density are also observed as overtime anesthesia. This preclinical study suggests that PAM holds potential to monitor anesthesia by imaging the skin microvasculature.

http://ift.tt/2BWlw3t

Generation of Reactive Oxygen Species in Heterogeneously Sonoporated Cells by Microbubbles with Single-Pulse Ultrasound

Publication date: Available online 27 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): Caixia Jia, Lin Xu, Tao Han, Ping Cai, Alfred C.H. Yu, Peng Qin
To develop and realize sonoporation-based macromolecule delivery, it is important to understand the underlying cellular bioeffects involved. It is known that an appropriate level of reactive oxygen species (ROS) is necessary to maintain normal physiologic function, but excessive ROS triggers adverse downstream bioeffects. However, it is still unclear whether a relationship exists between intracellular ROS levels and sonoporation. Using a customized platform for 1.5-MHz ultrasound exposure (13.33 µs duration and 0.70 MPa peak negative pressure) and imaging the dynamics of sonoporation and intracellular ROS at the single-cell level, we quantified the exogenous molecular uptake and the concentration of intracellular ROS indicator to evaluate the extent of sonoporation and ROS change, respectively. Our results revealed that the intracellular ROS level was correlated with the degree of the sonoporation. (i) Within ~120 s of the onset of ultrasound, during which membrane perforation and complete membrane resealing occurred, intracellular ROS rapidly decreased because of extracellular diffusion of dichlorofluorescein through the perforated membrane and positively correlated with the degree of the sonoporation. (ii) In the following 270 s (120–390 s post-exposure), ROS generation in reversibly sonoporated cells gradually increased and was positively correlated with the degree of the sonoporation. (iii) The ROS level in irreversibly sonoporated cells reduced to depletion during this time interval. It is possible that ROS generation in reversibly sonoporated cells can impact their long-term fate. These results thus provide new insight into the biological response to sonoporation.

http://ift.tt/2EYlwm9

Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice

Silymarin ameliorates expression of urotensin II (U-II) and its receptor (UTR) and attenuates toxic oxidative stress in the heart of rats with type 2 diabetes

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Rahimeh Rahimi, Jamshid Karimi, Iraj Khodadadi, Heidar Tayebinia, Nejat Kheiripour, Mohammad Hashemnia, Fatemeh Goli
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD). Urotensin II ((U-II)) and its receptor (UTR) are involved in the progression of CVD through enhancement in the production of reactive oxygen species (ROS). Since silymarin (SMN) is a natural agent with anti-diabetic effects, this study aimed to investigate the antioxidant potency of SMN on the expression of (U-II)/UTR system and oxidative stress status in the heart of type 2 diabetic rats. Thirty-six male Wistar rats were randomly divided into six groups (n = 6). Control and diabetic groups treated with or without SMN (60 and 120 mg/kg/day) for 2 months. Fasting blood sugar (FBS), insulin, lipid profile, creatine kinase-MB ((CK-MB)), lactate dehydrogenase (LDH) and markers of oxidative stress were measured by spectrophotometric methods while (U-II) and UTR gene expression was determined by qPCR method. SMN significantly reduced the FBS level, increased the concentration of insulin and improved HOMA-IR. SMN prevented diabetes-induced weight loss, and attenuated the increased levels of total oxidative status (TOS), malondialdehyde (MDA), and nitric oxide (NO). Diabetes-induced reduction of total thiol molecules content (TTM) was normalized to the normal level in SMN treated rats. SMN significantly modulated serum lipid profile, reduced the expression of (U-II) and UTR in the heart, and improved histopathological changes in the heart tissues. Therefore, the current study indicated that SMN ameliorated unpleasant diabetic characteristics via down-regulation of (U-II) and UTR gene expression and modulation of oxidative stress in the heart tissue of type 2 diabetic rats.

http://ift.tt/2EWOAdM

Serine peptidase inhibitor Kunitz type 2 (SPINT2) in cancer development and progression

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Fernanda Marconi Roversi, Sara Teresinha Olalla Saad, João Agostinho Machado-Neto
Understanding the molecular basis and mechanisms involved in neoplastic transformation and progression is important for the development of novel selective target therapeutic strategies. Hepatocyte growth factor (HGF)/c-MET signaling plays an important role in cell proliferation, survival, migration and motility of cancer cells. Serine peptidase inhibitor Kunitz type 2 (SPINT2) binds to and inactivates the HGF activator (HGFA), behaving as an HGFA inhibitor (HAI) and impairing the conversion of pro-HGF into bioactive HGF. The scope of the present review is to recapitulate and review the evidence of SPINT2 participation in cancer development and progression, exploring the clinical, biological and functional descriptions of the involvement of this protein in diverse neoplasias. Most studies are in agreement as to the belief that, in a large range of human cancers, the SPINT2 gene promoter is frequently methylated, resulting in the epigenetic silence of this gene. Functional assays indicate that SPINT2 reactivation ameliorates the malignant phenotype, specifically reducing cell viability, migration and invasion in diverse cancer cell lines. In sum, the SPINT2 gene is epigenetically silenced or downregulated in human cancers, altering the balance of HGF activation/inhibition ratio, which contributes to cancer development and progression.

http://ift.tt/2EWv4hs

The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Adel Abdel-Moneim, Heba H. Bakery, Gamal Allam
Diabetes mellitus (DM) is a serious medical problem affecting millions of peoples worldwide, and has a great socio-economic impacts. Cytokines possess a pivotal role in modulation of immune reactions and disease pathogenesis. T-helper type 17 (Th17) cells, an important proinflammatory CD4⁺ T cell subset secreting interleukin 17 (IL-17), has been embroiled in development of DM. There are recent evidences supporting a definitive role of Th17 cells in the etiology of type 1 diabetes (T1D). In addition, IL-17 has been shown to play a crucial role in inflammation, insulin resistance, and type 2 diabetes (T2D). Recently, small molecules which have been specified to block Th17 cells differentiation are considered as potential therapeutics for the disease. Anti-IL-17 neutralizing antibodies and/or antibodies targeting Th17 cells have been investigated to protect individuals at risk from disease development. In this review we aimed to shed light on the potential role of IL-17 and Th17 cells in both T1D and T2D pathogenesis and future therapeutic strategies.

http://ift.tt/2BUVaig

miR-24 inhibited the killing effect of natural killer cells to colorectal cancer cells by downregulating Paxillin

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Ling-li Zhang, Lian-feng Zhang, Yun-bo Shi
ObjectiveTo identify the molecular mechanism that modulates the killing effect of natural killer (NK) cells to colorectal cancer cells.Materials and methods: Expressions of miR-24 and Paxillin were detected by qRT-PCR and Western blot. Secretions of IFN-γ and TNF-α were measured by ELISA. The killing effect of NK cells was detected by CytoTox 96 non-radioactive cytotoxicity assay. Luciferase reporter assay was conducted to confirm the regulation of miR-24 on Paxillin.ResultsmiR-24 was overexpressed in NK cells from patients with colorectal cancer than healthy volunteers. Secretions of IFN-γ and TNF-α in activated NK cells were significantly increased, indicating the enhancement of the killing effect of NK cells. Paxillin expression was overexpressed in activated NK cells. Interference of Paxillin significantly decreased Paxillin expression, secretions of IFN-γ and TNF-α, and the killing effect of NK cells to colorectal cancer cells. In addition, we confirmed that Paxillin was a direct target of miR-24, and miR-24 was negatively correlated with Paxillin. Moreover, overexpression of miR-24 inhibited secretions of IFN-γ and TNF-α, and decreased cytotoxicity by downregulating Paxillin expression. Finally, we observed that overexpression of Paxillin significantly decreased tumor volume of colorectal cancer.ConclusionOverexpression of miR-24 supressed the killing effect of NK cells to colorectal cancer cells by downregulating Paxillin expression.

http://ift.tt/2EXffqQ

Association between apolipoprotein E genotype and warfarin response during initial anticoagulation

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Shuai He, Huangmengjie Zhang, Yide Cao, Fulai Nian, Hongwei Chen, Wen Chen, Merveesh L. Auchoybur, Li Yin, Zhonghao Tao, Shaowen Tang, Xin Chen
Apolipoprotein E (APOE) genotypes are associated with warfarin dose requirements in various populations. Whether APOE genotypes mediate the warfarin response is unknown. The aim of this study was to evaluate the genetic contributions of different APOE genotypes to the early phase of anticoagulation in Han Chinese patients. We conducted a retrospective cohort study and assessed APOE genotypes, clinical characteristics, international normalized ratio (INR) responses, warfarin dose requirements and bleeding events in 429 Han Chinese patients. The study outcomes were the time to the first INR within the therapeutic range, the time to the first INR of more than 4, the INR response over time, and the warfarin dose requirement. Compared with patients with the ε3/ε3 genotype, patients with at least one ε4 allele had significantly longer times to the first INR of more than 4 during both the initial 20 days (P = 0.001, HR 2.9; 95%CI, 1.54–5.45) and the entire follow-up period (P < 0.001, HR 3.26; 95%CI,1.94–5.47), but this allele was not a significant predictor of the time to the first INR within the therapeutic range. No association was observed between the ε2 allele and INR response, and both the ε4 allele and the ε2 allele did not significantly affect the required warfarin dose during the follow-up. These observations suggest that genetic variants of APOE are associated with an increased risk of overanticoagulation among the Han Chinese population. However, these variants may not be useful in predicting warfarin maintenance dose requirements.

http://ift.tt/2BUVa1K

The possible role of stress induced hormonal disbalance in the patophysiology of insulin resistane in lean individuals

Publication date: Available online 27 February 2018
Source:Medical Hypotheses
Author(s): K. Blaslov, I. Kruljac, G. Mirošević, Lora S. Kirigin Biloš, M. Vrkljan
Insulin resistance (IR) is a common denominator of metabolic and hemodynamic disorders simultaneously present in one person and responsible for elevated risk of developing type 2 diabetes (T2DM) and cardiovascular incidents. According to the latest research, IR is present in 25-45% of the general population. Therefore, the mechanism of its development is in the center of scientific and professional interest. Established or acquired factors, or combinations thereof, which disturb any step of the physiological insulin action mechanism: its binding to the cellular receptor, through the complex cascade of intracellular signaling pathways might cause IR. Although the adiposity and its underlying risk factors are considered to be the primary cause of IR, it is present in a great porportion in lean individuals as well.There are insights of the possible role of psychological factors: exposure to stress and deprssion to IR development, although the mechanism of this relationship has not been comperhensively studied. Data driven from cell cultures and experimental animal models suggest that there is an elevated level of counter-regulatory insulin hormones: growth hormone, prolactin and cortisol due to acute stress exposure. However, the relationship between these psychological disorders with the hyperreactivity of the axis of the hypothalamic-pituitary-adrenal axis as the underlying mechanism in the patophysiology of IR in lean individuals has not been systematically investigated. Based on the aforementioned, we hypothesise that this mechanism would be responsible for the formation of IR, and consequently, T2DM in lean individuals.The possible effect of the amount of stress in conjunction with the serum concentration of growth hormone, cortisol, prolactin and dehydroepiandrostendone to the abnormal 5-hour oral glucose tollerance test results could contribute to the primary prevention of diabetes and its complications.

http://ift.tt/2CoYIdD

Individual Differences in Semantic Processing: Insights From the Calgary Semantic Decision Project.

Author: Pexman, Penny M.; Yap, Melvin J.

DOI: 10.1037/xlm0000499

Publication Date: POST AUTHOR CORRECTIONS, 26 February 2018

http://ift.tt/2EWKUZl

Acquired perforating collagenosis in a non-diabetic patient with advanced prostate carcinoma: A review of perforating dermatosis associated with malignancy

http://ift.tt/2Fdur2e

Unusual association between digital mucous cyst and acquired ungual fibrokeratoma: A case report

http://ift.tt/2ovoJPP

Case of pyoderma gangrenosum-like sporotrichosis caused by Sporothrix globosa in a patient with ulcerative colitis

http://ift.tt/2COanON

Perspective From Sweden on the Global Impact of the 2017 American College of Cardiology/American Heart Association Hypertension Guidelines: A "Sprint" Beyond Evidence in the United States.

Author: Brunstrom, Mattias MD; Carlberg, Bo MD, PhD; Lindholm, Lars H. MD, PhD

Page: 886-888

http://ift.tt/2t0D3V4

Global Impact of the 2017 American College of Cardiology/American Heart Association Hypertension Guidelines: A Perspective From Italy.

Author: Mancia, Giuseppe MD; Corrao, Giovanni PhD

Page: 889-890

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Derivation and Validation of a Novel Right-Sided Heart Failure Model After Implantation of Continuous Flow Left Ventricular Assist Devices: The EUROMACS (European Registry for Patients with Mechanical Circulatory Support) Right-Sided Heart Failure Risk Score.

Author: Soliman, Osama I.I. MD, PhD; Akin, Sakir MD; Muslem, Rahatullah BSc; Boersma, Eric PhD; Manintveld, Olivier C. MD, PhD; Krabatsch, Thomas MD, PhD; Gummert, Jan F. MD, PhD; de By, Theo M.M.H. MBA; Bogers, Ad J.J.C. MD, PhD; Zijlstra, Felix MD, PhD; Mohacsi, Paul MD, eMBA; Caliskan, Kadir MD, PhD; On behalf of the EUROMACS Investigators

Page: 891-906

http://ift.tt/2sXy9bs

When VAD Things Happen to Good People.

Author: Samsky, Marc D. MD; Rogers, Joseph G. MD

Page: 907-909

http://ift.tt/2CoC9FN

Autonomic Nervous System in Pulmonary Arterial Hypertension: Time to Rest and Digest.

Author: Hemnes, Anna R. MD; Brittain, Evan L. MD, MSCI

Page: 925-927

http://ift.tt/2Cq26Vz

Atrial Fibrillation Burden in Young Patients With Congenital Heart Disease.

Author: Mandalenakis, Zacharias MD, PhD; Rosengren, Annika MD, PhD; Lappas, Georg MSc; Eriksson, Peter MD, PhD; Gilljam, Thomas MD, PhD; Hansson, Per-Olof MD, PhD; Skoglund, Kristofer MD, PhD; Fedchenko, Maria MD; Dellborg, Mikael MD, PhD

Page: 928-937

http://ift.tt/2t0CRoO

Pericardial Adipose Tissue Regulates Granulopoiesis, Fibrosis, and Cardiac Function After Myocardial Infarction.

Author: Horckmans, Michael PhD; Bianchini, Mariaelvy MSc; Santovito, Donato MD; Megens, Remco T.A. PhD; Springael, Jean-Yves PhD; Negri, Irene MSc; Vacca, Michele MD; Di Eusanio, Marco MD; Moschetta, Antonio MD; Weber, Christian MD; Duchene, Johan PhD; Steffens, Sabine PhD

Page: 948-960

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2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

Author: Hicks, Karen A. MD ,*; Mahaffey, Kenneth W. MD ,*; Mehran, Roxana MD ,*; Nissen, Steven E. MD ,*; Wiviott, Stephen D. MD; Dunn, Billy MD; Solomon, Scott D. MD; Marler, John R. MD; Teerlink, John R. MD; Farb, Andrew MD; Morrow, David A. MD, MPH; Targum, Shari L. MD, MPH; Sila, Cathy A. MD; Hai, Mary T. Thanh MD; Jaff, Michael R. DO; Joffe, Hylton V. MD, MMSC; Cutlip, Donald E. MD; Desai, Akshay S. MD; Lewis, Eldrin F. MD, MPH; Gibson, C. Michael MD, MS; Landray, Martin J. PHD; Lincoff, A. Michael MD; White, Christopher J. MD; Brooks, Steven S. MD, MBA; Rosenfield, Kenneth MD; Domanski, Michael J. MD; Lansky, Alexandra J. MD; McMurray, John J.V. MD; Tcheng, James E. MD; Steinhubl, Steven R. MD; Burton, Paul MD, PHD; Mauri, Laura MD, MSC; O'Connor, Christopher M. MD; Pfeffer, Marc A. MD, PHD; Hung, H.M. James PHD; Stockbridge, Norman L. MD, PHD; Chaitman, Bernard R. MD; Temple, Robert J. MD; on behalf of the Standardized Data Collection for Cardiovascular Trials Initiative (SCTI)

Page: 961-972

http://ift.tt/2FaUUNS

Outcomes of Patients With Hypoplastic Left Heart Syndrome Reaching Adulthood After Fontan Palliation: Multicenter Study.

Author: Wilson, William M. MBBS; Valente, Anne M. MD; Hickey, Edward J. MD; Clift, Paul MBBS, MD; Burchill, Luke MBBS, PhD; Emmanuel, Yaso MBChB, DPhil; Gibson, Patrick BMBCH, MD; Greutmann, Matthias MD; Grewal, Jasmine MD; Grigg, Leeanne E. MBBS; Gurvitz, Michelle MD; Hickey, Kelsey BA; Khairy, Paul MD, PhD; Mayer, John E. Jr MD; Teo, Eliza MBBS; Vonder Muhll, Isabelle MD; Roche, S. Lucy MBChB; Silversides, Candice K. MD; Wald, Rachel M. MD

Page: 978-981

http://ift.tt/2t15Wkb

Letter by Tampaki et al Regarding Article, "Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)".

Author: Tampaki, Ekaterini Christina MD, PhD, PharmD; Tampakis, Athanasios MD; Pantos, Costas MD, PhD

Page: 982-983

http://ift.tt/2F86Y2C

Letter by Koh Regarding Article, "Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)".

Author: Koh, Kwang Kon MD, PhD

Page: 984-985

http://ift.tt/2sYJc4h

Letter by Taegtmeyer and Karlstaedt Regarding Article, "Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)".

Author: Taegtmeyer, Heinrich MD, DPhil; Karlstaedt, Anja MD, PhD

Page: 986-987

http://ift.tt/2CqKwks

Letter by Jin-shan and Xue-bin Regarding Article, "Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)".

Author: Jin-shan, He MD; Xue-bin, Li MD

Page: 988

http://ift.tt/2t48j5P

Response by Kosiborod et al to Letters Regarding Article, "Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)".

Author: Kosiborod, Mikhail MD; Cavender, Matthew A. MD, MPH; Fu, Alex Z. PhD; Wilding, John P. MD, PhD; Khunti, Kamlesh MD, PhD; Holl, Reinhard W. MD, PhD; Norhammar, Anna MD; Birkeland, Kare I. MD, PhD; Jorgensen, Marit Eika MD, PhD; Thuresson, Marcus PhD; Arya, Niki MSc; Bodegard, Johan MD, PhD; Hammar, Niklas PhD; Fenici, Peter MD, PhD; On Behalf of the CVD-REAL Investigators and Study Group

Page: 989-991

http://ift.tt/2F7Y4SD

A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy‐Naïve Advanced or Metastatic Nonsquamous Non‐Small Cell Lung Cancer

AbstractBackground.In the absence of a targeted oncogenic driver mutation or high programmed death‐ligand 1 expression, systemic therapy with platinum‐based doublet chemotherapy with or without bevacizumab has been the standard treatment in advanced or metastatic non‐small cell lung cancer (NSCLC). Metformin has been shown to have antitumor effects via a variety of insulin‐dependent and insulin‐independent mechanisms and to be potentially synergistic with chemotherapy.Materials and Methods.This open‐label single‐center phase II study (NCT01578551) enrolled patients with chemotherapy‐naïve advanced or metastatic nonsquamous NSCLC and randomized them (3:1) to receive carboplatin, paclitaxel, and bevacizumab with (Arm A) or without (Arm B) concurrent metformin for four to six cycles followed by maintenance therapy with bevacizumab ± metformin continued until disease progression, intolerable toxicity, or study withdrawal. The primary outcome was 1‐year progression free survival (PFS). Secondary outcomes included overall survival, response to therapy, and toxicity.Results.A total of 25 patients were enrolled from August 2012 to April 2015, of whom 24 received at least one cycle of therapy administration. The study was stopped early due to slow accrual and changes in standard first‐line therapy of advanced NSCLC. The 1‐year PFS on Arm A (n = 18) was 47% (95% confidence interval [CI]: 25%–88%), which exceeded the historical control 1‐year PFS of 15%. Median overall survival of patients treated on Arm A was 15.9 months (95% CI: 8.4–not available [NA]) and 13.9 months (95% CI: 12.7–NA) on Arm B. There were no significant differences in toxicity between the study arms.Conclusion.To the authors' knowledge, this is the first study to show a significant benefit in PFS with the use of metformin in this patient population and is a signal of efficacy for metformin in advanced NSCLC.Implications for Practice.The anticancer effects of metformin continue to be elucidated. To the authors' knowledge, this is the first trial in nondiabetic advanced non‐small cell lung cancer patients to show a significant change in outcome with the addition of metformin to standard first‐line chemotherapy. Well tolerated and widely available, metformin is a drug that should be considered for further study in the lung cancer treatment landscape.

http://ift.tt/2ouynSQ

A Phase II Study of Tumor Ablation in Patients with Metastatic Sarcoma Stable on Chemotherapy

AbstractLessons Learned. Ablation therapy appears to be a reasonably safe and effective approach to obtain a significant treatment‐free interval for a subset of patients with limited sites of metastatic disease for which systemic control can be obtained with six cycles of chemotherapy.Background.Metastatic sarcoma often becomes resistant to treatment by chemotherapy. There is sometimes prolonged stable disease from active chemotherapy that provides a window of opportunity for an intervention to prolong disease‐free survival.Materials and Methods.We performed a phase II study in patients with metastatic sarcoma who had been stable on six cycles of chemotherapy who then received ablation therapy to their residual disease. Histologies captured in this study included leiomyosarcoma, malignant peripheral nerve sheath tumor, pleiomorphic rhabdomyosarcoma, and myxoid liposarcoma. Sites ablated included lung metastases and retroperitoneal metastatic deposits. In this study, up to three lesions were ablated in any given interventional radiology session. After ablation, patients were not treated with any further therapy but were followed by surveillance imaging to determine progression‐free rate (PFR).Results.Although terminated early because of slow accrual, this study demonstrated a 3‐month PFR of 75% for this cohort of eight patients treated with ablation performed after completion of six cycles of chemotherapy with stable disease. Median progression‐free survival (PFS) was 19.74 months, and the median overall survival (OS) was not reached.Conclusion.Our data are the first prospective study to suggest that ablation therapy in selected patients who are stable on chemotherapy can provide a significant progression‐free interval off therapy and warrants further study in a randomized trial.

http://ift.tt/2CPVA6s

Next‐Generation Sequencing of Circulating Tumor DNA Reveals Frequent Alterations in Advanced Hepatocellular Carcinoma

AbstractBackground.Because imaging has a high sensitivity to diagnose hepatocellular carcinoma (HCC) and tissue biopsies carry risks such as bleeding, the latter are often not performed in HCC. Blood‐derived circulating tumor DNA (ctDNA) analysis can identify somatic alterations, but its utility has not been characterized in HCC.Materials and Methods.We evaluated 14 patients with advanced HCC (digital ctDNA sequencing [68 genes]). Mutant relative to wild‐type allele fraction was calculated.Results.All patients (100%) had somatic alterations (median = 3 alterations/patient [range, 1–8]); median mutant allele fraction, 0.29% (range, 0.1%–37.77%). Mutations were identified in several genes: TP53 (57% of patients), CTNNB1 (29%), PTEN (7%), CDKN2A (7%), ARID1A (7%), and MET (7%); amplifications, in CDK6 (14%), EGFR (14%), MYC (14%), BRAF (7%), RAF1 (7%), FGFR1 (7%), CCNE1 (7%), PIK3CA (7%), and ERBB2/HER2 (7%). Eleven patients (79%) had ≥1 theoretically actionable alteration. No two patients had identical genomic portfolios, suggesting the need for customized treatment. A patient with a CDKN2A‐inactivating and a CTNNB1‐activating mutation received matched treatment: palbociclib (CDK4/6 inhibitor) and celecoxib (COX‐2/Wnt inhibitor); des‐gamma‐carboxy prothrombin level decreased by 84% at 2 months (1,410 to 242 ng/mL [normal: ≤7.4 ng/mL]; alpha fetoprotein [AFP] low at baseline). A patient with a PTEN‐inactivating and a MET‐activating mutation (an effect suggested by in silico molecular dynamic simulations) received sirolimus (mechanistic target of rapamycin inhibitor) and cabozantinib (MET inhibitor); AFP declined by 63% (8,320 to 3,045 ng/mL [normal: 0–15 ng/mL]).Conclusion.ctDNA derived from noninvasive blood tests can provide exploitable genomic profiles in patients with HCC.Implications for Practice.This study reports that blood‐derived circulating tumor DNA can provide therapeutically exploitable genomic profiles in hepatocellular cancer, a malignancy that is known to be difficult to biopsy.

http://ift.tt/2ouLhAq

Effect of Concomitant pH‐Elevating Medications with Pazopanib on Progression‐Free Survival and Overall Survival in Patients with Metastatic Renal Cell Carcinoma

AbstractBackground.Pazopanib is an oral tyrosine‐kinase inhibitor that is approved by the U.S. Food and Drug Administration for treatment of metastatic renal cell carcinoma (mRCC). Pharmacokinetic data have shown that concomitant administration of pazopanib and esomeprazole, a proton pump inhibitor (PPI), leads to decreased area under the curve and thus decreased exposure of pazopanib by 40%. Despite the pharmacokinetic data published to date, the clinical significance and impact on patient outcomes resulting from decreased pazopanib exposure remains unknown.Materials and Methods.In this retrospective, observational, cohort study, 90 patients with mRCC who either received pazopanib in combination with a PPI or histamine 2 receptor antagonist (H2RA; concurrent PPI/H2RA group) or who did not take concurrent pH‐elevating medications (no PPI/H2RA group) were compared to determine if there was an impact on progression‐free survival (PFS), the primary endpoint, and secondary endpoints, overall survival (OS) and safety.Results.The differences between the PFS of 9.0 months and OS of 28.0 months for the concomitant PPI/H2RA group versus 11.0 months and 30.1 months, respectively, for the no PPI/H2RA group were not statistically significant. Rates of adverse events were similar between the concomitant PPI/H2RA and no PPI/H2RA groups.Conclusion.Concomitant PPI or H2RA usage was not shown to be associated with a reduction in PFS or OS for patients receiving pazopanib for mRCC, with a similar toxicity profile in each group. Based on the results of this retrospective cohort study and the palliative nature of the treatment of patients with mRCC, clinicians should consider allowing patients to remain on concomitant pazopanib and acid‐reducing therapy.Implications for Practice.Pazopanib is a preferred category‐one first‐line treatment for predominant clear cell metastatic renal cell carcinoma (mRCC). However, because of an aging demographic, coupled with patients with mRCC presenting with multiple comorbidities, including symptomatic dyspepsia or gastroesophageal reflux disease, patients are commonly required to take pazopanib concomitantly with a proton pump inhibitor (PPI) or a histamine 2 receptor antagonist (H2RA). Despite earlier pharmacokinetic reports suggesting that an alkaline pH may result in poorer absorption, this institutional retrospective study found no effect on clinical outcomes. These data suggest that concurrent treatment of mRCC with pazopanib and a PPI or H2RA may be safe in everyday practice.

http://ift.tt/2CPVhsk

A Phase II Trial of Selinexor, an Oral Selective Inhibitor of Nuclear Export Compound, in Abiraterone‐ and/or Enzalutamide‐Refractory Metastatic Castration‐Resistant Prostate Cancer

AbstractLessons Learned. In abiraterone‐ and/or enzalutamide‐refractory metastatic castration‐resistant prostate cancer (mCRPC) patients, selinexor led to prostate‐specific antigen and/or radiographic responses in a subset of patients, indicating clinical activity in this indication.Despite twice‐a‐week dosing and maximal symptomatic management, selinexor was associated with significant anorexia, nausea, and fatigue in mCRPC patients refractory to second‐generation anti‐androgen therapies, limiting further clinical development in this patient population.This study highlights the challenge of primary endpoint selection for phase II studies in the post‐abiraterone and/or post‐enzalutamide mCRPC space.Background.Selinexor is a first‐in‐class selective inhibitor of nuclear export compound that specifically inhibits the nuclear export protein Exportin‐1 (XPO‐1), leading to nuclear accumulation of tumor suppressor proteins.Methods.This phase II study evaluated the efficacy and tolerability of selinexor in patients with metastatic castration‐resistant prostate cancer (mCRPC) refractory to abiraterone and/or enzalutamide.Results.Fourteen patients were enrolled. Selinexor was initially administered at 65 mg/m2 twice a week (days 1 and 3) and was subsequently reduced to 60 mg flat dose twice a week (days 1 and 3), 3 weeks on, 1 week off, to improve tolerability. The median treatment duration was 13 weeks. At a median follow‐up of 4 months, two patients (14%) had ≥50% prostate‐specific antigen (PSA) decline, and seven patients (50%) had any PSA decline. Of eight patients with measurable disease at baseline, two (25%) had a partial response and four (50%) had stable disease as their best radiographic response. Five patients (36%) experienced serious adverse events (SAEs; all unrelated to selinexor), and five patients (36%) experienced treatment‐related grade 3–4 AEs. The most common drug‐related adverse events (AEs) of any severity were anorexia, nausea, weight loss, fatigue, and thrombocytopenia. Three patients (21%) came off study for unacceptable tolerability.Conclusion.Selinexor demonstrated clinical activity and poor tolerability in mCRPC patients refractory to second‐line anti‐androgenic agents.

http://ift.tt/2CPUZle

Second‐Line Treatment Landscape for Renal Cell Carcinoma: A Comprehensive Review

AbstractThe management of advanced clear‐cell renal cell carcinoma has steadily improved over the past decade with the introduction of antiangiogenic and targeted therapies. Recently, three new therapies have been approved for use as second‐line options that further advance the treatment armamentarium: nivolumab, a monoclonal antibody targeting the programmed cell death receptor; cabozantinib, a small‐molecule tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR), MET, and AXL; and lenvatinib, a small‐molecule TKI of VEGF and fibroblast growth factor receptors that is used in combination with everolimus, an inhibitor of the mechanistic target of rapamycin. Together, these and previously approved second‐line treatments offer clinicians the ability to better individualize treatment for patients after progression on first‐line VEGFR‐targeted therapies. In this comprehensive review, we discuss the efficacy and safety results from the pivotal trials of these newly approved therapies, including the quality of study design, the level of evidence, subgroup analyses, and how these data can help to guide clinicians to select the most appropriate second‐line therapy for their patients.Implications for Practice.This review article provides the reader with a comprehensive overview of current treatment options for patients with advanced clear‐cell renal cell carcinoma (RCC) whose disease has progressed after their first therapy. As many patients with RCC experience disease progression with initial treatments, effective second‐line therapies are critical. Nivolumab, cabozantinib, and lenvatinib plus everolimus have recently been approved as second‐line treatments. The new agents discussed in this review increase the therapeutic options available and provide physicians with opportunities to individualize treatments for their patients, with a view to improving disease control and survival outcomes.

http://ift.tt/2F9v7pr

Meeting Kristoff

http://ift.tt/2CMv2CW

[Prognostic factors in high grade gliomas].

[Prognostic factors in high grade gliomas].

Neurocirugia (Astur). 2018 Feb 22;:

Authors: Gelabert-González M, González-Gómez L, Arán-Echabe E

PMID: 29478626 [PubMed - as supplied by publisher]

http://ift.tt/2GPdl81

Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice

Graphene/Semiconductor Hybrid Heterostructures for Optoelectronic Device Applications

Publication date: Available online 28 February 2018
Source:Nano Today
Author(s): Chao Xie, Yi Wang, Zhi-Xiang Zhang, Di Wang, Lin-Bao Luo
As one of the most appealing two-dimensional materials, graphene (Gr) has attracted tremendous research interest in optoelectronic device applications for its plenty of exceptional electrical and optical properties. The emergence of Gr/semiconductor hybrid heterostructures provides a promising platform for assembling high-performance optoelectronic devices that can overcome intrinsic limitations of Gr. However, although significant achievements have been made, many challenges still exist. Here, we comprehensively review the progress in the development of various optoelectronic devices based on Gr/semiconductor hybrid heterostructures, including /group II-VI nanostructures, /group III-V semiconductors, /group IV semiconductors, /metal oxides and /other semiconductors, in terms of the device design, device performance and physics, processing techniques for performance optimization, etc. In the final section, conclusions of the existing techniques are presented and future challenges in optoelectronic applications of Gr/semiconductor hybrid heterostructures are addressed.

Graphical abstract

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Volitional and Automatic Control of the Hand When Reaching to Grasp Objects.

Author: Chen, Zhongting; Saunders, Jeffrey Allen

DOI: 10.1037/xhp0000492

Publication Date: POST AUTHOR CORRECTIONS, 26 February 2018

http://ift.tt/2FDfPHo

Curcumin restrains hepatic glucose production by blocking cAMP/PKA signaling and reducing acetyl CoA accumulation in high-fat diet (HFD)-fed mice

Landiolol hydrochloride to successfully treat refractory ventricular arrhythmia during weaning from cardiopulmonary bypass

We effectively treated refractory ventricular arrhythmia (RVA) at the time of weaning from the cardiopulmonary bypass (CPB) during aortic valve replacement with landiolol for three patients who failed to respond to electrical defibrillation. Demographic data, comorbid factors, and preoperative finding were noted [Table 1].

http://ift.tt/2oss0iX

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Τρίτη 27 Φεβρουαρίου 2018

Graphical abstract

Graphical abstract

Graphical abstract

Αρχειοθήκη ιστολογίου