Label-free upconversion nanoparticles-based fluorescent probes for sequential sensing of Cu2+, pyrophosphate and alkaline phosphatase activity

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Fangfang Wang, Cuiling Zhang, Qin Xue, Huaping Li, Yuezhong Xian
An efficient near-infrared fluorescence probe has been developed for the sequential detection of Cu²⁺, pyrophosphate (P2O7⁴⁻, PPi), and alkaline phosphatase (ALP), which is based on the "off−on−off" fluorescence switch of branched polyethyleneimine (PEI)-capped NaGdF4:Yb/Tm upconversion nanoparticles (UCNPs). The fluorescence is quenched via energy transfer from UCNPs to Cu²⁺ for the coordination of PEI with Cu²⁺. The strong affinity between Cu²⁺ and PPi leads to the formation of Cu²⁺-PPi complex and results in the detachment of Cu²⁺ from the surface of UCNPs, thus the fluorescence is triggered on. ALP-directed hydrolysis of PPi causes the disassembly of Cu²⁺-PPi complex and re-conjugation between Cu²⁺ with PEI, which leads to the switch-off fluorescence of UCNPs. The system allows sequential analysis of Cu²⁺, PPi, and ALP by modulating the switch of the fluorescence of UCNPs with detection limits of 57.8nM, 184nM, and 0.019U/mL for Cu²⁺, PPi, and ALP, respectively. By virtue of the NIR feature and excellent biocompatibility, the UCNPs-based probes are suitable for bioimaging. Taking Cu²⁺ visualization as a model, the nanoprobes have been successfully applied for intracellular imaging of Cu²⁺ in living cells.



http://ift.tt/2nLCcVe

Potential-resolved “in-electrode” type electrochemiluminescence immunoassay based on functionalized g-C3N4 nanosheet and Ru-NH2 for simultaneous determination of dual targets

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Zhiyong Guo, Lin Wu, Yufang Hu, Sui Wang, Xing Li
Here, a novel potential-resolved "in-electrode" type electrochemiluminescence (ECL) immunosensor was fabricated based on two different types of luminant Ru-NH2 and AuNPs/g-C3N4 to realize simultaneous detection of dual targets. In this strategy, anti-CA1251 and anti-SCCA1 were immobilized on bare gold electrode as capture probes, which could catch the two corresponding target CA125 and SCCA, and the immobilization of the signal tags was allowed via the interaction between antigen and antibody. In this process, (Ru&anti-CA1252)@GO and anti-SCCA2-AuNPs/g-C3N4 could exhibit two strong and stable ECL emissions at 1.25V and −1.3V respectively, which could be used as effective signal tags. Taking advantage of "in-electrode" type ECL immunosensor, all the electrochemiluminophores near the outer Helmholtz plane are "effective" in participating in the electrochemical reactions and emitting ECL signals. Therefore, the dual targets CA125 and SCCA could be detected within the linear ranges of 0.001–100U/mL and 0.001–100ng/mL, with detection limits of 0.4mU/mL and 0.33pg/mL, respectively. All these results demonstrated that the present potential-resolved "in-electrode" type electrochemiluminescence approach provided a promising analytical method for dual targets analysis with the advantages of simple analytical procedure, small sample volume and lower cost, which made the proposed method potential for clinical detection.

Graphical abstract

http://ift.tt/2pfKe68

CdS:Mn quantum dot-functionalized g-C3N4 nanohybrids as signal-generation tags for photoelectrochemical immunoassay of prostate specific antigen coupling DNAzyme concatamer with enzymatic biocatalytic precipitation

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Kangyao Zhang, Shuzhen Lv, Zhenzhen Lin, Dianping Tang
A new photoelectrochemical (PEC) immunosensor based on Mn-doped CdS quantum dots (CdS:Mn QDs) on g-C3N4 nanosheets was developed for the sensitive detection of prostate specific antibody (PSA) in biological fluids. The signal derived from the as-synthesized Cd:Mn QDs-functionalized g-C3N4 nanohybrids via a hydrothermal method and was amplified through DNAzyme concatamers on gold nanoparticles accompanying enzymatic biocatalytic precipitation. Experimental results by UV–vis absorption spectra and photoluminescence revealed that CdS:Mn QDs/g-C3N4 nanohybrids exhibited higher photocurrent than those of CdS:Mn QDs and g-C3N4 alone. Upon addition of target PSA, a sandwich-type immunoreaction was carried out between capture antibodies and the labeled detection antibodies. Accompanying introduction of gold nanoparticles, the labeled initiator strands on the AuNPs triggered hybridization chain reaction and the formation of DNAzyme concatamers in the presence of hemin. The formed DNAzyme catalyzed 4-chloro-1-naphthol (4-CN) to produce an insoluble/insulating precipitate on the Mn:CdS QDs/g-C3N4, and blocked the light harvesting of Mn:CdS QDs/g-C3N4, thus resulting in the decreasing photocurrent. Under optimal conditions, the immunosensor exhibited good photocurrent responses for determination of target PSA, and allowed detection of PSA at a concentration as low as 3.8pgmL⁻¹. The specificity, reproducibility and precision of this system were acceptable. Significantly, this methodology was further evaluated for analyzing human serum samples, giving well-matched results with referenced PSA enzyme-linked immunosorbent assay (ELISA) method.



http://ift.tt/2pfOX7K

Development of near-infrared ratiometric fluorescent probe based on cationic conjugated polymer and CdTe/CdS QDs for label-free determination of glucose in human body fluids

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Mengze Yu, Kunli Zhao, Xiaohua Zhu, Shiyun Tang, Zhou Nie, Yan Huang, Peng Zhao, Shouzhuo Yao
Quantum dots (QDs) have attracted extensive attention in biomedical applications， because of their broad excitation spectra, narrow and symmetric emission peaks etc. Furthermore, near-infrared (NIR) QDs have further advantages including low autofluorescence, good tissue penetration and low phototoxicity. In this work, the electrostatic interaction and fluorescence resonance energy transfer (FRET) between NIR CdTe/CdS QDs and cationic conjugated polymer (CCP) was studied for the first time. Based on the newly discovered phenomena and the result that hydrogen peroxide (H2O2) can efficiently quench the fluorescence of NIR CdTe/CdS QDs, a novel NIR ratiometric fluorescent probe for determination of H2O2 and glucose was developed. Under the optimized conditions, the detection limit of H2O2 and glucose assay were 0.1mM and 0.05mM (S/N=3), with a linear range of 0.2–4mM and 0.1–5mM, respectively. Because of the NIR spectrum, this ratiometric probe can be also applied for the determination of glucose in whole blood samples directly, providing a valuable platform for glucose sensing in clinic diagnostic and drug screening.



http://ift.tt/2pfEb1p

Gold nanoparticle-based low limit of detection Love wave biosensor for carcinoembryonic antigens

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Shuangming Li, Ying Wan, Yan Su, Chunhai Fan, Venkat R. Bhethanabotla
In this work, a Love wave biosensing platform is described for detecting cancer-related biomarker carcinoembryonic antigen (CEA). An ST 90°-X quartz Love wave device with a layer of SiO2 waveguide was combined with gold nanoparticles (Au NPs) to amplify the mass loading effect of the acoustic wave sensor to achieve a limit of detection of 37pg/mL. The strategy involves modifying the Au NPs with anti-CEA antibody conjugates to form nanoprobes in a sandwich immunoassay. The unamplified detection limit of the Love wave biosensor is 9.4ng/mL. This 2–3 order of magnitude reduction in the limit of detection brings the SAW platform into the range useful for clinical diagnosis. Measurement electronics and microfluidics are easily constructed for acoustic wave biosensors, such as the Love wave device described here, allowing for robust platforms for point of care applications for cancer biomarkers in general.



http://ift.tt/2nLth6x

A wireless point-of-care testing system for the detection of neuron-specific enolase with microfluidic paper-based analytical devices

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Yan Fan, Juntao Liu, Yang Wang, Jinping Luo, Huiren Xu, Shengwei Xu, Xinxia Cai
Neuron-specific enolase (NSE) had clinical significance on diagnosis, staging, monitoring effect and judging prognosis of small cell lung cancer. Thus, there had a growing demand for the on-site testing of NSE. Here, a wireless point-of-care testing (POCT) system with electrochemical measurement for NSE detection was developed and verified. The wireless POCT system consisted of microfluidic paper-based analytical devices (μPADs), electrochemical detector and Android's smartphone. Differential pulse voltammetry (DPV) measurement was adopted by means of electrochemical detector which including a potentiostat and current-to-voltage converter. μPADs were modified with nanocomposites synthesized by Amino functional graphene, thionine and gold nanoparticles (NH2-G/Thi/AuNPs) as immunosensors for NSE detection. Combined with μPADs, the performance of the wireless POCT system was evaluated. The peak currents showed good linear relationship of the logarithm of NSE concentration ranging from 1 to 500ngmL⁻¹ with the limit of detection (LOD) of 10pgmL⁻¹. The detection results were automatically stored in EEPROM memory and could be displayed on Android's smartphone through Bluetooth in real time. The detection results were comparable to those measured by a commercial electrochemical workstation. The wireless POCT system had the potential for on-site testing of other tumor markers.



http://ift.tt/2pfRlLV

Reliable clinical serum analysis with reusable electrochemical sensor: Toward point-of-care measurement of the antipsychotic medication clozapine

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Mijeong Kang, Eunkyoung Kim, Thomas E. Winkler, George Banis, Yi Liu, Christopher A. Kitchen, Deanna L. Kelly, Reza Ghodssi, Gregory F. Payne
Clozapine is one of the most promising medications for managing schizophrenia but it is under-utilized because of the challenges of maintaining serum levels in a safe therapeutic range (1–3μM). Timely measurement of serum clozapine levels has been identified as a barrier to the broader use of clozapine, which is however challenging due to the complexity of serum samples. We demonstrate a robust and reusable electrochemical sensor with graphene-chitosan composite for rapidly measuring serum levels of clozapine. Our electrochemical measurements in clinical serum from clozapine-treated and clozapine-untreated schizophrenia groups are well correlated to centralized laboratory analysis for the readily detected uric acid and for the clozapine which is present at 100-fold lower concentration. The benefits of our electrochemical measurement approach for serum clozapine monitoring are: (i) rapid measurement (≈20min) without serum pretreatment; (ii) appropriate selectivity and sensitivity (limit of detection 0.7μM); (iii) reusability of an electrode over several weeks; and (iv) rapid reliability testing to detect common error-causing problems. This simple and rapid electrochemical approach for serum clozapine measurements should provide clinicians with the timely point-of-care information required to adjust dosages and personalize the management of schizophrenia.

Graphical abstract

http://ift.tt/2nLpLIZ

Additional value of venous phase added to aortic CT angiography in patients with aortic aneurysm

Publication date: Available online 13 April 2017
Source:Clinical Imaging
Author(s): Yukichi Tanahashi, Satoshi Goshima, Hiroshi Kondo, Yoshifumi Noda, Kota Sakurai, Hiroshi Kawada, Nobuyuki Kawai, Shigeru Furui, Masayuki Matsuo
PurposeTo compare diagnostic performance of unenhanced and CTA images (Image set 1) to that of combined unenhanced, CTA, and venous-phase images (Image set 2) for incidentalomas in patients with aortic aneurysm.MethodsPreoperative CT Images of consecutive 240 patients were reviewed by two observers for incidentalomas. Diagnostic performance was assessed.ResultsSensitivity was higher in Image set 2 than Image set 1 in observer 1 and overall (P=0.03 and 0.00). AUCs for both observers were higher in Image set 2 than Image set 1 (P=0.03 and 0.01).ConclusionAddition of venous-phase to CTA significantly improved diagnostic performance of incidentalomas.



http://ift.tt/2pdcmtf

Liver enzyme elevations in a cohort of HIV/AIDS patients on first-line antiretroviral therapy in Namibia: Findings and implications

Publication date: Available online 13 April 2017
Source:Alexandria Journal of Medicine
Author(s): P.A. Mataranyika, D. Kibuule, F. Kalemeera, H. Kaura, B. Godman, W.T. Rennie
IntroductionAll antiretroviral therapies (ARTs) are potentially toxic to the liver. In sub-Saharan Africa, the rising incidence of ART induced adverse events has complicated treatment leading to recent revisions of Namibian ART guidelines. Unfortunately there have been limited studies to date evaluating ART induced liver injury in Namibia to guide further revisions if needed.ObjectiveDetermine the current patterns and grades of ALT elevation in Namibia's HIV/AIDS.MethodsRetrospective cohort analysis. Patterns of alanine amino transferase (ALT) liver enzyme elevation were determined in a cohort of ART naïve HIV patients on firstline ART regimen in a referral hospital in Namibia over a 1year treatment period. Patterns of ALT changes at baseline, 3months and 6months were analyzed using ANOVA and Bonferroni test for pairwise comparisons.ResultsOf 79 eligible patients, 72 developed significant ALT elevation within 3months of ART initiation (F (3, 76)=6.4, p=0.002, η²=0.193). Four 4 (5.6%) and 1 (1.38%) patient respectively developed grade 2 and grade 3 ALT elevation by month 3. There was no significant difference between mean ALT levels at baseline and month 6. A CD4 count of <350cells/mm³; female gender and age over 40years were the main factors associated with moderate or severe ALT elevation.ConclusionsFirst line ART commonly induces mild self-limiting liver enzyme elevation in Namibian HIV patients especially in the first 3months. Consequently, there is a need to monitor ALT levels for at least 3months after initiation mainly in high risk patients to reduce side-effect concerns. This is already happening.



http://ift.tt/2nLwqmA

Place over traits? Purchasing edibles from medical marijuana dispensaries in Los Angeles, CA

Publication date: October 2017
Source:Addictive Behaviors, Volume 73
Author(s): Nancy Jo Kepple, Bridget Freisthler
ObjectivesTo examine discrete purchasing behaviors of marijuana-infused edibles from medical marijuana dispensaries with the aim to identify potential venue- and individual-level targets for prevention.MethodsTwo-stage, venue-based sampling approach was used to randomly select patrons exiting 16 medical marijuana dispensaries in Los Angeles, California during Spring 2013. Hierarchical generalized linear modeling was used to examine the likelihood of purchasing edibles among 524 patrons reporting a discrete purchase regressed on characteristics of the sampled dispensaries and their patrons.ResultsAt a venue level, patrons were more likely to purchase edibles from dispensaries located within Census tracts with higher median incomes or in close proximity to a higher number of dispensaries. At an individual level, patrons who identified as Black or Hispanic were associated with a lower likelihood of purchasing edibles when compared to patrons who identified as other non-White, non-Hispanic race/ethnicity.ConclusionsPlace-based policies focused on regulating edible sales through dispensaries may be fruitful in influencing access to edibles. Additionally, social marketing campaigns may benefit from targeting both locations where edible purchases are more likely and populations who are more likely to purchase edibles.



http://ift.tt/2oFoQJo

Facilitating Microneedling Over the Cheeks.

No abstract available

http://ift.tt/2osdLt7

Successful Treatment of a Residual, Thick, Infantile Hemangioma in a Darker Phototype Pediatric Patient Using the 755 nm Long-Pulsed Alexandrite Laser.

No abstract available

http://ift.tt/2p28Dit

Multistep Approach for Improved Aesthetic and Functional Outcomes for Lower Extremity Wound Closure After Mohs Micrographic Surgery.

BACKGROUND: Lower extremity wounds present a major clinical challenge. OBJECTIVE: This paper introduces a new multistep approach for improved aesthetic and functional outcome for lower extremity wound closure after Mohs micrographic surgery. PATIENTS AND METHODS: In this prospective case series, 12 consecutive patients undergoing Mohs micrographic surgery for cutaneous malignancies of the lower extremities underwent closure assisted by elastic bandages, proper positioning with 45[degrees] flexion of the knee, buried vertical mattress sutures, and careful eversion, using a premium angled stapler. Assessment of cosmetic outcome was performed by 2 blinded observers, using the Hollander Wound Evaluation Scale. RESULTS: The mean age was 73 +/- 9 years with most patients having at least one comorbidity. Six patients (50%) underwent resection of a basal cell carcinoma and 5 patients (42%) underwent resection of a squamous cell carcinoma and 1 patient (8%) underwent resection of a keratoacanthomatous carcinoma. There were no wound complications, and at the 3- to 6-month follow-up, 11 of the 12 wounds (92%) had an optimal Hollander Wound Evaluation Scale score of 6. CONCLUSION: This new approach to lower extremity wounds provides excellent cosmetic outcome with no reported complications. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2oswBAj

Editorial board

Publication date: 15 May 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 10





http://ift.tt/2pfeRbT

Synthesis of new 3-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-benzenesulfonamides with strong inhibition properties against the tumor associated carbonic anhydrases IX and XII

Publication date: 15 May 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 10
Author(s): Murat Bozdag, Ahmed Mahmoud Alafeefy, Abdul Malik Altamimi, Fabrizio Carta, Claudiu T. Supuran, Daniela Vullo
We report a series of novel metanilamide-based derivatives 3a–q bearing the 2-mercapto-4-oxo-4H-quinazolin-3-yl moiety as tail. All compounds were synthesized by means of straightforward condensation procedures and were investigated in vitro for their inhibition potency against the human (h) carbonic anhydrase (CA; EC 4.2.1.1.1) isoforms I, II, IX and XII. Among all compounds tested the 6-iodo 3g and the 7-fluoro 3i derivatives were the most potent inhibitors against the tumor associated CA IX and XII isoform (KIs 1.5 and 2.7nM respectively for the hCA IX and KIs 0.57 and 1.9nM respectively for the hCA XII).The kinetic data reported here strongly support compounds of this type for their future development as radiotracers in tumor pathologies which are strictly dependent on the enzymatic activity of the hCA IX and XII isoforms.

Graphical abstract

http://ift.tt/2nLbuMJ

Novel 5-HT7R antagonists, arylsulfonamide derivatives of (aryloxy)propyl piperidines: Add-on effect to the antidepressant activity of SSRI and DRI, and pro-cognitive profile

Publication date: 15 May 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 10
Author(s): Vittorio Canale, Anna Partyka, Rafał Kurczab, Martyna Krawczyk, Tomasz Kos, Grzegorz Satała, Bartłomiej Kubica, Magdalena Jastrzębska-Więsek, Anna Wesołowska, Andrzej J. Bojarski, Piotr Popik, Paweł Zajdel
A novel series of arylsulfonamide derivatives of (aryloxy)propyl piperidines was designed to obtain potent 5-HT7R antagonists. Among the compounds evaluated herein, 3-chloro-N-{1-[3-(1,1-biphenyl-2-yloxy)2-hydroxypropyl]piperidin-4-yl}benzenesulfonamide (25) exhibited antagonistic properties at 5-HT7R and showed selectivity over selected serotoninergic and dopaminergic receptors, as well as over serotonin, noradrenaline and dopamine transporters. Compound 25 demonstrated significant antidepressant-like activity in the forced swim test (0.625–2.5mg/kg, i.p.) and in the tail suspension test (1.25mg/kg, i.p.), augmented the antidepressant effect of inactive doses of escitalopram (selective serotonin reuptake inhibitor) and bupropion (dopamine reuptake inhibitor) in the FST in mice, and similarly to SB-269970, exerted pro-cognitive properties in the novel object recognition task in cognitively unimpaired conditions in rats (0.3mg/kg, i.p.). Such an extended pharmacological profile, especially the augmentation effect of the identified 5-HT7R antagonist on SSRI activity, seems promising regarding the complexity of affective disorders and potentially improved outcomes, including mnemonic performance.

Graphical abstract

http://ift.tt/2nL67Ny

Design, synthesis, and biological activity of novel tetrahydropyrazolopyridone derivatives as FXa inhibitors with potent anticoagulant activity

Publication date: 15 May 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 10
Author(s): Xiaoqing Sun, Zexin Hong, Moyi Liu, Su Guo, Di Yang, Yong Wang, Tian Lan, Linyu Gao, Hongxia Qi, Ping Gong, Yajing Liu
A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant potency, and compounds 15b, 15c, 20b, 20c, and 22b were further examined for their inhibitory activity against human FXa in vitro. While compounds 15c and 22b were tested for rat venous thrombosis in vivo. The most promising compound 15c, with an IC50 (FXa) value of 0.14μM and 98% inhibition rate, warranted further investigation as an FXa inhibitor.

Graphical abstract

http://ift.tt/2nL1Fy9

Corrigendum to “Synthesis and evaluation of novel 1H-pyrrolo[2,3-b]pyridine-5-carboxamide derivatives as potent and orally efficacious immunomodulators targeting JAK3” [Bioorg. Med. Chem. 23 (2015) 4871–4883]

Publication date: 15 May 2017
Source:Bioorganic & Medicinal Chemistry, Volume 25, Issue 10
Author(s): Yutaka Nakajima, Takayuki Inoue, Kazuo Nakai, Koichiro Mukoyoshi, Hisao Hamaguchi, Keiko Hatanaka, Hiroshi Sasaki, Akira Tanaka, Fumie Takahashi, Shigeki Kunikawa, Hiroyuki Usuda, Ayako Moritomo, Yasuyuki Higashi, Masamichi Inami, Shohei Shirakami




http://ift.tt/2nL9FPL

Research of material removal and deformation mechanism for single crystal GGG (Gd3Ga5O12) based on varied-depth nanoscratch testing

Publication date: 5 July 2017
Source:Materials & Design, Volume 125
Author(s): Chen Li, Feihu Zhang, Binbin Meng, Xiaoshuang Rao, Yue Zhou
The varied-depth nanoscratch test is carried out on the (111) plane of single crystal GGG along 〈110〉 direction. Two indenters with different tip radii are used in this work. During the nanoscratch process, continuous chips and the bottom of the groove with micro cracks and slip lines are obtained by using a sharp indenter. Segmental chips and the bottom of the smooth groove are obtained by using a blunt indenter. Compared with using a blunt indenter, using a sharp indenter can obtain deeper scratch depth, deeper residual depth and lower elastic recovery under the identical normal force. The subsurface deformation in the ductile removal regime is composed of plastic flow zone, micro crack zone and median cracks. The ductile deformation mechanism of single crystal GGG during the nanoscratch process is a combination of "material poly-crystallization of nanocrystalline" and "amorphous transformation" with no other forms of crystalline structure found. The generation of median cracks is caused by the severe slip of crystal planes which are subjected to the concentrated stress.

Graphical abstract

http://ift.tt/2pzCHhA

Effects of three-dimensional coating interfaces on thermo-mechanical stresses within plasma spray thermal barrier coatings

Publication date: 5 July 2017
Source:Materials & Design, Volume 125
Author(s): Si Kyaw, Arthur Jones, Mark A.E. Jepson, Tom Hyde, Rachel C. Thomson
It has been acknowledged that stresses within a thermal barrier coating (TBC) and its durability are significantly affected by the coating interfaces. This paper presents a finite element approach for stress analysis of the plasma sprayed TBC system, using three-dimensional (3D) coating interfaces. 3D co-ordinates of the coating surfaces were measured through 3D reconstruction of scanning electron microscope (SEM) images. These co-ordinates were post processed to reconstruct finite element models for use in stress analyses. A surface profile unit cell approach with appropriate boundary conditions was applied to reduce the problem size and hence computation time. It has been shown that for an identical aspect ratio of the coating interface, interfacial out-of-plane stresses for 3D models are around twice the values predicted using 2D models. Based on predicted stress development within the systems, possible crack development and failure mechanisms of the TBC systems can be predicted.

Graphical abstract

http://ift.tt/2pzAJOf

Catalytic activities of Ni-decorated boron particles

Publication date: 5 July 2017
Source:Materials & Design, Volume 125
Author(s): Hye Jin Jung, Kyusuk Nam, Jisuk Lee, Doo-Hee Han, Hong-Gye Sung, Hyung Soo Hyun, Youngku Sohn, Weon Gyu Shin
Ni-decorated boron (Ni/B) particles were prepared by a ball-milling method, and their physicochemical properties were fully characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDX) elemental mapping, and X-ray photoelectron spectroscopy (XPS). Upon decoration by Ni, the previously inactive boron particles showed enhanced activity in CO oxidation and photoelectrochemical hydrogen/oxygen evolution reactions (HERs/OERs). The CO oxidation onset and T10% were observed around 320 and 350°C, respectively. In preliminary tests, the Ni/B (1:3 w/w) sample showed UV and visible light current responses, and current densities of 600 and 240μA/cm² were observed at a potential of 500mV for HER and OER, respectively. The present study emphasizes the potential application of boron as a catalyst support material for air quality control and photoelectrochemical hydrogen/oxygen evolution.

Graphical abstract

http://ift.tt/2pzAHpB

Modulating the electric and magnetic properties of BiFeO3 ceramics

Publication date: 5 July 2017
Source:Materials & Design, Volume 125
Author(s): Jing Lv, Hui Zhao, Ming Wu, Xiaojie Lou, Jiagang Wu
In this work, the electric and magnetic properties of BiFeO3 (BFO) ceramics are modulated by changing the defect-dipoles using different Bi2O3 contents, where excessive Bi2O3 gives rise to the formation of iron (VFe) and oxygen (VO) vacancies and Bi2O3 deficiency mainly leads to the formation of bismuth (VBi) and oxygen vacancies (VO). It is of great interest to note that a rather low leakage current density can be achieved in both Bi2O3 deficient and excessive ceramics. We also find that a moderate level of Bi2O3 deficiency (<9%) has little influence on d33. Surprisingly, Bi2O3 excess, widely used for fabricating BFO ceramics with better properties in the past, cannot improve d33. An enhanced piezoelectricity (d33=49–51 pC/N) can be obtained in the BFO ceramics with a wide Bi2O3 content range (i.e., x=−0.09–0.09). A large remanent polarization (2Pr~90–119μC/cm²) and a tunable magnetization (Mr=0.022–0.038emu/g and Hc=0.87–4.04kOe) are achieved in BFO ceramics with x=−0.15–0.15. These defect-dipoles induced by Bi2O3 deficiency or excess can well modulate the electric and magnetic properties of BiFeO3 ceramics.

Graphical abstract

http://ift.tt/2pzCYRM

Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-104531

Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2oxpuIt

Effects of A One-week Fasting Therapy in Patients with Type-2 Diabetes Mellitus and Metabolic Syndrome – A Randomized Controlled Explorative Study

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-101700

There is increasing experimental evidence for beneficial effects of calorie restriction and intermittent fasting in type 2 diabetes mellitus (T2DM). In humans, prolonged fasting is established as a health-promoting complementary treatment in Europe and claimed to improve metabolism by a complex hormetic response. We aimed to investigate effects of a one-week fasting period compared to usual care in T2DM by means of a pilot trial. Patients with manifest T2DM medically treated with oral hypoglycemic agents and/or insulin were randomly assigned to a 7-day fasting program followed by dietary advice or to usual care and dietary advice only. Fasting was performed according to the method of Buchinger with a nutritional energy intake of 300kcal/day by liquids only and stepwise re-introduction of solid food thereafter. Outcomes were assessed baseline and after 4 months. Of 46 enrolled participants, 32 (n=16 each group) completed the trial and were included for final analyses. Fasting was well accepted, there were no serious adverse events. After 4 months mean weight decreased by 3.5 kg and 2.0 kg in the fasting vs. control group (p=0.03) paralleled by greater reduction of abdominal circumference (p=0.001). Fasting led to a significant decrease of systolic/diastolic blood pressure (p=0.01; p=0.003) and increased quality-of-life (p=0.04), while for HbA1c, insulin and HOMA-index only non-significant improvements were observed. Results of this study suggest that prolonged fasting is feasible and might have beneficial clinical effects. The effectiveness of fasting should be proved in larger confirmatory trials that include intermittent fasting in follow-ups to enable more pronounced and long-term effects.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2odTu8T

The Effects of Calcium, Vitamins D and K co-Supplementation on Markers of Insulin Metabolism and Lipid Profiles in Vitamin D-Deficient Women with Polycystic Ovary Syndrome

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-104530

Data on the effects of calcium, vitamins D and K co-supplementation on markers of insulin metabolism and lipid profiles among vitamin D-deficient women with polycystic ovary syndrome (PCOS) are scarce. This study was done to determine the effects of calcium, vitamins D and K co-supplementation on markers of insulin metabolism and lipid profiles in vitamin D-deficient women with PCOS. This randomized double-blind, placebo-controlled trial was conducted among 55 vitamin D-deficient women diagnosed with PCOS aged 18–40 years old. Subjects were randomly assigned into 2 groups to intake either 500 mg calcium, 200 IU vitamin D and 90 µg vitamin K supplements (n=28) or placebo (n=27) twice a day for 8 weeks. After the 8-week intervention, compared with the placebo, joint calcium, vitamins D and K supplementation resulted in significant decreases in serum insulin concentrations (−1.9±3.5 vs. +1.8±6.6 µIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (−0.4±0.7 vs. +0.4±1.4, P=0.01), homeostasis model of assessment-estimated b cell function (−7.9±14.7 vs. +7.0±30.3, P=0.02) and a significant increase in quantitative insulin sensitivity check index (+0.01±0.01 vs. −0.008±0.03, P=0.01). In addition, significant decreases in serum triglycerides (−23.4±71.3 vs. +9.9±39.5 mg/dL, P=0.03) and VLDL-cholesterol levels (−4.7±14.3 vs. +2.0±7.9 mg/dL, P=0.03) was observed following supplementation with combined calcium, vitamins D and K compared with the placebo. Overall, calcium, vitamins D and K co-supplementation for 8 weeks among vitamin D-deficient women with PCOS had beneficial effects on markers of insulin metabolism, serum triglycerides and VLDL-cholesterol levels.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2oxbD59

The Effects of Omega-3 Fatty Acids and Vitamin E Co-Supplementation on Indices of Insulin Resistance and Hormonal Parameters in Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-117773

This study was conducted to determine the effects of omega-3 fatty acids and vitamin E co-supplementation on indices of insulin resistance and hormonal parameters in women with polycystic ovary syndrome (PCOS). This randomized double-blind, placebo-controlled trial was done on 68 women diagnosed with PCOS according to the Rotterdam criteria aged 18–40 years old. Participants were randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-Linolenic acid plus 400 IU vitamin E supplements (n=34) or placebo (n=34) for 12 weeks. Hormonal parameters were quantified at the beginning of the study and after 12-week intervention. After 12 weeks of intervention, compared to the placebo, omega-3 fatty acids and vitamin E co-supplementation resulted in a significant decrease in insulin (−1.0±3.5 vs. +2.7±6.6 µIU/mL, P=0.004), homeostasis model of assessment-estimated insulin resistance (−0.2±0.8 vs. +0.6±1.5, P=0.005), homeostasis model of assessment-estimated B cell function (−4.3±14.3 vs. +10.5±24.5, P=0.004) and a significant increase in quantitative insulin sensitivity check index (+0.006±0.02 vs. −0.01±0.04, P=0.008). Supplementation with omega-3 fatty acids plus vitamin E led to significant reductions in serum total testosterone (−0.5±0.7 vs. −0.1±0.5 ng/mL, P=0.008) and free testosterone (−1.2±2.1 vs. −0.2±1.7, P=0.04) compared to the placebo group. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on fasting plasma glucose and other hormonal profiles. Omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PCOS women significantly improved indices of insulin resistance, total and free testosterone.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2odRkWK

Fenugreek, A Potent Hypoglycaemic Herb Can Cause Central Hypothyroidism Via Leptin – A Threat To Diabetes Phytotherapy

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-103458

Fenugreek (Trigonella foenum graecum), a medicinal herb with potent antihyperglycaemic and hypoglycaemic effects, is used to treat diabetes. This study is aimed to explore the interaction of fenugreek seed extract (FSE) and HPT (hypothalamic-pituitary-thyroid) axis in context of leptin secretion which have important role in normal and type-1 diabetic subjects. FSE (confirmed to contain trigonelline, diosgenin, 4 hydroxyisoleucine) was gavaged (0.25 gm/kg body weight/day) to normal and alloxan-induced type-1 diabetic rats for 4 weeks. Expression of hypothalamic prepro-TRH (Thyrotropin releasing hormone) mRNA, serum levels of TRH, TSH (Thyroid stimulating hormone), fT3, fT4, insulin, leptin, glucose; thyroperoxidase activity and growth of thyroid gland, food intake, adiposity index were also studied FSE significantly down regulated prepro-TRH mRNA expression; decreased serum TRH, TSH, fT3, fT4 levels, and regressed thyroid gland in FSE-fed normal and diabetic rats than those observed in normal diet-fed control and diabetic rats. FSE decreased (p<0.005–0.001) adiposity index and leptin secretion, increased food intake and body weight in all FSE-fed rats. FSE improved insulin secretion, decreased glucose level but impaired HPT axis in diabetic rats, indicating insulin-independent central hypothyroidism. Results suggested that the dominant signal to hypothalamus suppressing HPT axis is the fall in leptin level which i resulted from decreased adiposity index following FSE feeding. Fenugreek simultaneously having hypoglycaemic and hypothyroidal actions raises questions whether it can be safely used to treat diabetes and/or hyperthyroidism as was suggested by many workers.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2oxbC15

Effect of Carnosine on Renal Function, Oxidation and Glycation Products in the Kidneys of High-Fat Diet/Streptozotocin-Induced Diabetic Rats

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-100117

High fat diet (HFD) and low dose of streptozotocin (STZ)-treated rats provide an animal model for type 2 Diabetes Mellitus (T2DM). Oxidative stress plays a role in the development of diabetic complications. Carnosine (CAR) has antioxidant and antiglycating properties. We investigated effects of CAR on renal function, oxidation and glycation products in HFD+STZ-rats. Rats were fed with HFD (60% of total calories from fat) for 4 weeks and then a single dose STZ (40 mg/kg; i.p.) was applied. Rats with blood glucose levels above 200 mg/dL were fed with HFD until the end of the 12th week. CAR (250 mg/kg body weight; i.p.; 5 times a week) was administered to rats for the last 4 weeks. Glycated hemoglobin (HbA1c), glucose, lipids, and andrenal function tests in serum as well as reactive oxygen species, malondialdehyde, protein carbonyl, advanced oxidation protein products, advanced glycation end products (AGEs), antioxidant power, and antioxidant enzyme activities and their mRNA expressions in kidneys were determined. CAR treatment did not alter glucose and HbA1c, but it decreased serum lipids, creatinine, and urea levels in HFD+STZ rats. Oxidation products of lipids and proteins and AGEs levels decreased, but antioxidant enzyme activities and their mRNA expressions remained unchanged due to CAR treatment. Our results indicate that CAR treatment alleviated renal function and decreased accumulation of oxidation and glycation products in kidneys in HFD+STZ-rats.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2odPFkc

Effect of Saxagliptin on Circulating Endothelial Progenitor Cells and Endothelial Function in Newly Diagnosed Type 2 Diabetic Patients

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-124421

Endothelial dysfunction is associated with the risk of cardiovascular complications in diabetic patients. Endothelial progenitor cells (EPCs) and flow-mediated dilation (FMD) are common markers of endothelial function. In this study, we aim to investigate whether the DPP-4 inhibitor saxagliptin modulate EPCs number and FMD in newly diagnosed, treatment-naive type 2 diabetic patients. This was a controlled, randomized, open-label clinical trial. Saxagliptin group and metformin group consumed either saxagliptin 5 mg per day or metformin 1 500 mg per day respectively for 12 weeks. Changes of FMD and EPCs number after 12-week intervention were the primary endpoints. 31 patients were initially enrolled and randomized to saxagliptin group (n=16) and metformin group (n=15). 27 patients completed the trial (saxagliptin group n=14 and metformin group n=13), and 4 patients dropped out during the study. FMD and EPCs number increased significantly in both saxagliptin group and metformin group, and there was no significant difference between groups. 2-h postprandial plasma glucose, HbA1c and diastolic blood pressure improved significantly in both groups, and there was no significant difference between groups. Saxagliptin and metformin had comparable beneficial effects on endothelial function.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2oxgDXh

Peripheral Immunological Cells in Pregnant Women and their Change during Diabetes

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-104935

During the last decades the incidence of diabetes has dramatically increased as well as the number of pregnant diabetic women. There is still missing data regarding patterns and shifts of immune cell populations due to pregnancy with or without diabetes. The study aimed to investigate the impact of pregnancy, type 1 diabetes (T1D) and gestational diabetes mellitus (GDM) on different immune cells in female. The number and proportion of CD3-, CD4-, CD8- and γδ T-cells as well as B-, NK-, NKT- and dendritic cells (DC) incl. rate of apoptosis was analyzed in peripheral blood samples from 24 non-pregnant women, 24 pregnant controls, 25 non-pregnant T1D, 18 women with GDM and 15 pregnant T1D (PT1D) women. Compared to healthy controls, healthy pregnant women had reduced numbers of lymphoid DC and γδ T-cells, while women with gestational diabetes presented with increased numbers of γδ T-cells. Pregnant women with T1D showed increased NKT cells and a decrease of NK cells compared to healthy pregnant or non-pregnant T1D women. Apoptosis of γδ T-cells in healthy pregnant women was found to be decreased in comparison to their non-pregnant controls while apoptosis of myeloid and lymphoid DC was increased in pregnant T1D in comparison to non-pregnant T1D. Those results may indicate that increased complication rates during diabetic pregnancies might be due to an impaired adaptation of the immune system.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2odKLDK

The Diagnostic Value of Whole Blood lncRNA ENST00000550337.1 for Pre-Diabetes and Type 2 Diabetes Mellitus

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-100018

This study aims to investigate long noncoding RNA (lncRNA) as biomarker for pre-diabetes and T2DM. LncRNAs in the peripheral blood of 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. Then 5 candidate biomarkers from the differentially expressed lncRNAs were chosen and verified in a larger independent cohort (control group=20; pre-diabetes group=20; and T2DM group=20). The diagnostic capacity of ENST00000550337.1 was further tested in the third cohort (control group, n=60; pre-diabetes group, n=63; and T2DM group, n=64). A total of 17 lncRNAs were found to be differentially expressed between the 2 groups. 14 lncRNAs of these were upregulated in T2DM patients and 3 were downregulated. 5 upregulated lncRNAs were selected as potential biomarkers and verified in the second cohort, and the expression levels of 3 lncRNAs increased gradually from the control group to the pre-diabetes group to the T2DM group. The diagnostic value of ENST00000550337.1 was then tested in the third cohort, and its high diagnostic value for pre-diabetes and T2DM was confirmed. LncRNA ENST00000550337.1 is a potential diagnostic biomarker for pre-diabetes and T2DM.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2ox0KQO

Influence of Erythropoiesis-Stimulating Agents on HbA1c and Fructosamine in Patients with Haemodialysis

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0042-124577

HbA1c is the most accepted laboratory parameter for the long term observation of glucose control. There is still much of a debate about the use of HbA1c as a metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte turn over in patients with chronic kidney disease and haemodialysis (CKD5D). In 102 CKD5 patients with and without diabetes mellitus, we examined the dose dependent variability in HbA1c and fructosamine levels under haemodialysis and treated with epoetin α (n=48) and a new generation agent with continuous stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n=54). HbA1c levels were affected by therapy with ESA treatments. ESA dose was inversely correlated with HbA1c and an escalation of 10.000 IU per week induced an estimated decrease of HbA1c of 0.6 percent. In addition, the increase of reticulocyte number as a marker for erythropoiesis was significantly inversely correlated with the increase of ΔHbA1c. ESA treatments had no such effect on the alternative metabolic parameter fructosamine. When compared, both therapeutic agents had comparable success in attaining haemoglobin (Hb) target values. C.E.R.A. showed better correlation and was more effective over a longer dose interval. Our results show that HbA1c levels in patients should be carefully interpreted based on interfering factors. Nevertheless, HbA1c is currently the most consistent parameter for use ascertaining metabolic status of patients suffering from diabetes mellitus.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2odKvon

Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes – What We Know so Far and the Missing Links

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-106443

Hyperglycemia explains the development of late diabetic complications in patients with diabetes type 1 and type 2 only partially. Most therapeutic efforts relying on intensive glucose control failed to decrease the absolute risk for complications by more than 10%, especially in patients with diabetes type 2. Therefore, alternative pathophysiological pathways have to be examined, in order to develop more individualized treatment options for patients with diabetes in the future. One such pathway might be the metabolism of dicarbonyls, among them methylglyoxal and the accumulation of advanced glycation end products. Here we review currently available epidemiological data on dicarbonyls and AGEs in association with human diabetes type 1 and type 2.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2odPPYO

Metformin Inhibits N-Methyl-N-Nitrosourea Induced Gastric Tumorigenesis in db/db Mice

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-100118

Type 2 diabetes can elevate risk of gastric cancer and metformin, an anti-diabetic agent, has an inhibitory effect against gastric cancer cell in vitro. However, the effect of metformin on type 2 diabetes-related gastric tumorigenesis in vivo is still not clear. In the present study, we aim to detect whether metformin can inhibit increased risk of gastric cancer in diabetic db/db mice and which the potential anti-cancer mechanisms of metformin are. 4-week-old mice were divided into 3 groups (2 db/db mice groups and one wild type mice group). All diabetic and non-diabetic mice were treated with N-Methyl-N-Nitrosourea (MNU) for 20 weeks to induce gastric tumorigenesis. At week 21, one db/db mice group were treated with metformin (5 mg/ml) for 10 weeks and the other 2 groups were treated with saline. Blood samples were collected for testing insulin and insulin-like growth factor (IGF)-1. Stomach tissues were collected for histopathological evaluation and mRNAs analysis. Metformin significantly decreased incidence of MNU-induced gastric dysplasia and cancer in diabetic db/db mice. Furthermore, metformin reduced serum insulin as well as IGF-1, and also suppressed expression of insulin receptor, IGF-1, IGF-1 receptor and several pro-inflammatory cytokines mRNAs in stomach of db/db mice, but did not significantly influence IGF-2 and IGF-2 receptor expressions. The results show that metformin can prevent the risk of gastric cancer in type 2 diabetes and the protective mechanisms may involve in an inhibitory effect of metformin on insulin as well as IGF-1 signals and cancer related pro-inflammatory cytokines.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2oxf2kx

Monitoring Thyroid Function in Patients on Levothyroxine. Assessment of Conformity to National Guidance and Variability in Practice

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-103018

With demand for endocrine tests steadily increasing year-on-year, we examined thyroid function test (TFT) frequencies in patients on levothyroxine replacement therapy to assess the effect of initial TFT results and request source on TFT re-testing interval. All TFTs performed by the Clinical Biochemistry Departments at the Salford Royal Hospital (2009–2012; 288 263 requests from 139 793 patients) and University Hospital of North Midlands (2011–2014; 579 156 requests from 193 035 patients) were extracted from the laboratory computer systems. Of these, 54 894 tests were on 13 297 patients confirmed to be on levothyroxine therapy in the test cohort (Salford) and 67 298 requests on 11 971 patients in the confirmatory cohort (North Midlands). In the test cohort, median TFT re-testing interval in the total group was 19.1 weeks (IQR 9.1–37.7 weeks), with clearly defined peaks in TFT re-testing evident at 6 and 12 months and a prominent broad peak at 1–3 months. Median re-test interval was much lower than recommended (52 weeks) for those with normal TFTs at 31.3 weeks (30.6 weeks for the confirmatory cohort). Where thyroid-stimulating hormone (TSH) was elevated and free thyroxine (fT4) was below the reference range, re-test interval was much longer than is recommended (8 weeks) at 13.4–17.6 weeks (7.1–23.4 weeks in the confirmatory cohort), as was the interval when TSH was below and fT4 was above the normal range, at 16.7–25.6 weeks (27.5–31.9 weeks in the confirmatory cohort). Our findings show that the majority of TFT requests are requested outside recommended intervals and within-practice variability is high. A new approach to ensuring optimum monitoring frequency is required. Direct requesting from the clinical laboratory may provide one such solution.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2odRflU

Type 2 Diabetes is Associated with Lower Cardiorespiratory Fitness Independent of Pulmonary Function in Severe Obesity

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-100102

Both severe obesity and type 2 diabetes (T2DM) are associated with reduced pulmonary function and reduced cardiorespiratory fitness. We investigated whether T2DM further aggravates the impaired pulmonary function and cardiorespiratory fitness in subjects with severe obesity. In this cross-sectional study pulmonary function (forced expiratory volume within 1 s, FEV1; vital capacity, VC) was assessed in 65 severely obese subjects with T2DM (T2DM group) and 65 severely obese subjects without T2DM (non-T2DM group), pairwise matched for sex, age, weight, and height. In 30 of the matched pairs, cardiorespiratory fitness was assessed by an incremental bicycle test (peak workload, Wpeak, oxygen uptake, V̇O2,peak). FEV1 and VC did not differ between the T2DM and non-T2DM group (all p≥0.110), whereas Wpeak and V̇O2,peak - absolute values as well as relative to body mass - were significantly lower in subjects with T2DM compared to those without T2DM (all p≤0.030). Objective markers of maximal exertion, i. e., maximal heart rate and respiratory exchange ratio, did not differ between the 2 groups (both p≥0.245). The presence of T2DM in subjects with severe obesity is associated with lower cardiorespiratory fitness but with no further reduction in pulmonary function compared to subjects with severe obesity but without T2DM. While the cause-effect relationship of this association is not yet clear, these findings highlight the interplay between cardiorespiratory fitness and metabolic health, even in subjects with severe obesity.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2ox9u9F

Granulomatous Reaction After Complete Resolution of Primary Varicella.

No abstract available

http://ift.tt/2pzwbro

Plaque-Like Myofibroblastic Tumor: Report of 4 Cases.

Plaque-like myofibroblastic tumor of infancy was first characterized in 2007 by Clarke et al. In the first 2 cases described, large plaque-like tumors presented in the first 3 months of life exhibited microscopic features consistent with dermatofibroma but with immunohistochemical features of myofibroblastic lineage. In 2013, Marqueling et al reported 3 additional cases, 2 of which presented in early childhood, prompting the authors to recommend that the name of this condition be shortened to plaque-like myofibroblastic tumor. We present here 4 additional cases to better characterize clinical and histopathological features of this newly recognized entity. This benign lesion is of myofibroblastic lineage and demonstrates features consistent with multiple clustered dermatofibroma. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2ox6xFT

Nail Matrix Pathology in Cronkhite-Canada Syndrome: The First Case Report.

Cronkhite-Canada Syndrome (CCS) presents with gastrointestinal polyposis and the triad of cutaneous abnormalities including nail dystrophy, alopecia, and hyperpigmentation of the skin. The etiology is not well understood. The histology of skin lesion in CCS has not been routinely described. Especially, the nail matrix pathology has not been reported. In this study, the authors report the nail matrix pathology in a patient with CCS. Interestingly, the histologic evaluation revealed matrix hypergranulosis. Because matrix hypergranulosis is commonly found in several inflammatory nail diseases, this discovery points out that an inflammatory process is probably one of the important pathogeneses in CCS. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2pzFpnz

CD4 and CD30 Coexpression in a Cutaneous Manifestation of Systemic Mastocytosis-A Pitfall.

No abstract available

http://ift.tt/2owW1P8

A 75-Year-Old Man With Progressive Generalized Erythroderma and History of Anaplastic Large Cell Lymphoma.

No abstract available

http://ift.tt/2pzOkoR

A lamprey view on the origins of neuroendocrine regulation of the thyroid axis

Publication date: Available online 13 April 2017
Source:Molecular and Cellular Endocrinology
Author(s): Stacia A. Sower, Krist N. Hausken
This mini review summarizes the current knowledge of the hypothalamic-pituitary-thyroid (HPT) endocrine system in lampreys, jawless vertebrates. Lampreys and hagfish are the only two extant members of the class of agnathans, the oldest lineage of vertebrates. The high conservation of the hypothalamic-pituitary-gonadal (HPG) axis in lampreys makes the lamprey model highly appropriate for comparative and evolutionary analyses. However, there are still many unknown questions concerning the hypothalamic-pituitary (HP) axis in its regulation of thyroid activities in lampreys. As an example, the hypothalamic and pituitary hormone(s) that regulate the HPT axis have not been confirmed and/or characterized. Similar to gnathostomes (jawed vertebrates), lampreys produce thyroxine (T4) and triiodothyronine (T3) from thyroid follicles that are suggested to be involved in larval development, metamorphosis, and reproduction. The existing data provide evidence of a primitive, overlapping yet functional HPG and HPT endocrine system in lamprey. We hypothesize that lampreys are in an evolutionary intermediate stage of hypothalamic-pituitary development, leading to the emergence of the highly specialized HPG and HPT endocrine axes in jawed vertebrates. Study of the ancient lineage of jawless vertebrates, the agnathans, is key to understanding the origins of the neuroendocrine system in vertebrates.

Graphical abstract

http://ift.tt/2oaR1wT

Effects of rhamnolipids on microorganism characteristics and applications in composting: A review

Publication date: Available online 13 April 2017
Source:Microbiological Research
Author(s): Binbin Shao, Zhifeng Liu, Hua Zhong, Guangming Zeng, Guansheng Liu, Mingda Yu, Yang Liu, Xin Yang, Zhigang Li, Zhendong Fang, Juntao Zhang, Chenghao Zhao
Biosurfactant rhmnolipids have been applied in many fields, especially in environmental bioremediation. According to previous researches, many research groups have studied the influence of rhamnolipids on microorganism characteristics and/or its application in composting. In this review, the effects of rhamnolipids on the cell surface properties of microorganisms was discussed firstly, such as cell surface hydrophobicity (CSH), electrical, surface compounds, etc. Moreover, the deeper mechanisms were also discussed, such as the effects of rhamnolipids on the structural characteristics and functional characteristics of the cell membrane, and the effects of rhamnolipids on the related enzymes and genes. Additionally, the application of rhamnolipids in composting was discussed, which is an important way for pollutant biodegradation and resource reutilization. It is believed that rhamnolipids will play more and more important role in composting.

Graphical abstract

http://ift.tt/2peYI61

Effect of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of amorphous solid dispersions

Publication date: Available online 13 April 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Weiwei Sun, Baoliang Pan
This study investigates the effects of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of micro-environment pH modifying solid dispersions (pHM-SD) for the poorly water-soluble model drug Toltrazuril (TOL). Various pHM-SDs were prepared using Ca(OH)2 as a pH-modifier in hydrophilic polymers, including polyethylene glycol 6000 (PEG6000), polyvinylpyrrolidone k30 (PVPk30) and hydroxypropyl methylcellulose (HPMC). Based on the results of physicochemical characterizations and in-vitro dissolution testing, the representative ternary (Ca(OH)2:TOL:PEG6000/HPMC/PVPk30=1:8:24, w/w/w) and binary (TOL:PVPk30=1:3, w/w) solid dispersions were selected and optimized to perform in-vivo pharmacokinetic study. The micro-environment pH modification improved the in-vitro water-solubility and in-vivo bioavailability of parent drug TOL. Furthermore, the addition of alkalizers not only enhanced the release and absorption of prototype drug, but also promoted the generation of active metabolites, including toltrazuril sulfoxide (TOLSO) and toltrazuril sulfone (TOLSO2). The in-vitro dissolution profiles and in-vivo absorption, distribution and metabolism behaviors of the pHM-SDs varied with polymer type. Moreover, in-vivo bioavailability of three active pharmaceutical ingredients increased with an increase in in-vitro dissolution rates of the drug from the pHM-SDs prepared with various polymers. Therefore, a non-sink in-vitro dissolution method can be used to predict the in-vivo performance of pHM-SDs formulated with various polymers with trend consistency. In-vitro and in-vivo screening procedures revealed that the pHM-SD composed of Ca(OH)2, TOL and PVPk30 at a weight ratio of 1:8:24, of which the safety was adequately proved via histopathological examination, may be a promising candidate for providing better clinical outcomes.

Graphical abstract

http://ift.tt/2ox0NMo

Impact of demographics and disease progression on the relationship between glucose and HbA1c

Publication date: Available online 13 April 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Anetta Claussen, Jonas B. Møller, Niels R. Kristensen, Søren Klim, Maria C. Kjellsson, Steen H. Ingwersen, Mats O. Karlsson
ContextSeveral studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012).ObjectiveTo assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model.DataLongitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c.The analysed covariates included age group, BMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component.ParticipantsParticipants included 47% females and 20% above 65years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races.AnalysisEstimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model.ResultsThe analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG.However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship.ConclusionOur analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials.

Graphical abstract

http://ift.tt/2ox0LEg

Dapagliflozin-citric acid cocrystal showing better solid state properties than dapagliflozin

Publication date: Available online 13 April 2017
Source:European Journal of Pharmaceutical Sciences
Author(s): Jun-Hui Deng, Tong-Bu Lu, Changquan Calvin Sun, Jia-Mei Chen
Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2 inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO-H2O, 1:1:1) is the solid form used in the current tablet product to address the severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the problem of instability when exposed to high temperature, which renders it amorphous. In this work, we report on the preparation and evaluation of a new 1:1 cocrystal between DAP and citric acid (DAP-CA). The DAP-CA cocrystal exhibits superior stability against high temperature and high relative humidity without compromising dissolution and tableting performance. Thus, DAP-CA is a promising solid form for developing the next generation DAP tablet products with improved performance.

Graphical abstract

http://ift.tt/2owPx2K

Nothing to Spit At.

No abstract available

http://ift.tt/2pz5EdB

CONTENTS 1

Publication date: March 2017
Source:Materials Today, Volume 20, Issue 2





http://ift.tt/2odmi1p

CONTENTS 2

Publication date: March 2017
Source:Materials Today, Volume 20, Issue 2





http://ift.tt/2ox2wkU

Self-injury and aggression in adults with tuberous sclerosis complex: Frequency, associated person characteristics, and implications for assessment

Publication date: May 2017
Source:Research in Developmental Disabilities, Volume 64
Author(s): Lucy Wilde, Kate Eden, Petrus de Vries, Jo Moss, Alice Welham, Chris Oliver
Even though self-injury and aggression are common in tuberous sclerosis complex (TSC), understanding of these behaviours in adults with TSC and intellectual disability (ID) is limited. Little is known about their frequency in comparison to other ID-related genetic disorders or their association with other TSC-Associated Neuropsychiatric Disorders (TAND). This study determined the caregiver-reported frequency of self-injury and aggression in adults with TSC plus ID in comparison to Down syndrome (DS) and Angelman syndrome (AS), and assessed demographic and behavioural characteristics associated with the occurrence of each behaviour in TSC. Rates of self-injury and aggression in adults with TSC plus ID were 31% and 37.9% respectively. The odds of self-injury for adults with TSC were nearly twice as high as the odds for adults with DS, and the odds of aggression were over 2.5 times higher for adults with TSC than for adults with DS. When compared to adults with AS, odds of self-injury in TSC were around half those of the AS group, and odds of aggression were less than a third of those for adults with AS. These differences were not statistically significant. In adults with TSC, poorer communication and socialisation skills, gastric health problems and impulsivity were associated with self-injury; compulsive behaviour and impulsivity were associated with aggression. Caregivers and professionals should be alert to the likelihood of these behaviours in adults with TSC plus ID, and to characteristics associated with increased risk for their occurrence. We suggest assessment strategies to identify those at elevated risk.What this paper addsThis paper adds specific examination of behavioural difficulties in adults with tuberous sclerosis complex who also have intellectual disability, a population at heightened risk of adverse behavioural outcomes which has received limited focussed examination to date. Findings support existing suggestions that there is relatively high risk for both self-injury and aggression, and provide novel insight into characteristics that may be associated with the presence of these behaviours.



http://ift.tt/2owT016

Multivariate statistical assessment of a polluted river under nitrification inhibition in the tropics

Abstract

A large complex water quality data set of a polluted river, the Tay Ninh River, was evaluated to identify its water quality problems, to assess spatial variation, to determine the main pollution sources, and to detect relationships between parameters. This river is highly polluted with organic substances, nutrients, and total iron. An important problem of the river is the inhibition of the nitrification. For the evaluation, different statistical techniques including cluster analysis (CA), discriminant analysis (DA), and principal component analysis (PCA) were applied. CA clustered 10 water quality stations into three groups corresponding to extreme, high, and moderate pollution. DA used only seven parameters to differentiate the defined clusters. The PCA resulted in four principal components. The first PC is related to conductivity, NH₄-N, PO₄-P, and TP and determines nutrient pollution. The second PC represents the organic pollution. The iron pollution is illustrated in the third PC having strong positive loadings for TSS and total Fe. The fourth PC explains the dependence of DO on the nitrate production. The nitrification inhibition was further investigated by PCA. The results showed a clear negative correlation between DO and NH₄-N and a positive correlation between DO and NO₃-N. The influence of pH on the NH₄-N oxidation could not be detected by PCA because of the very low nitrification rate due to the constantly low pH of the river and because of the effect of wastewater discharge with very high NH₄-N concentrations. The results are deepening the understanding of the governing water quality processes and hence to manage the river basins sustainably.

http://ift.tt/2od7dNb

Evaluation of zeolite-supported microscale zero-valent iron as a potential adsorbent for Cd 2+ and Pb 2+ removal in permeable reactive barriers

Abstract

A new composite adsorbent, zeolite-supported microscale zero-valent iron (Z-mZVI) was evaluated as a potential adsorbent for the removal of Cd²⁺ and Pb²⁺ from aqueous solution using batch and column experiments. Adsorption isotherms were well fitted by Langmuir model, and the maximum adsorption capacity was 63.14 mg/g for Cd²⁺ and 154.61 mg/g for Pb²⁺, respectively. Both adsorption processes followed the pseudo-second-order model which indicated that the rate-limiting step for different initial concentration was dominated by chemical adsorption process. The coexistence of Cd²⁺ and Pb²⁺ caused the reduction of Cd²⁺ removal efficiency, but not for Pb²⁺. Z-mZVI has a high removal capacity for Cd²⁺ and Pb²⁺ over a wide pH range (3.0–6.8) as well as in the presence of competitive Ca²⁺ or Mg²⁺ ions (<2 mmol/L). Moreover, Z-mZVI shows a high immobilization capacity for the adsorbed Cd²⁺ and Pb²⁺ products, even at the acid solution (pH = 3.95). Column experiment confirmed that Z-mZVI could simultaneously remove Cd²⁺ and Pb²⁺ from solution efficiently. Thomas model can simulate the equilibrium adsorption capacity of Cd²⁺ and Pb²⁺ of the Z-mZVI column well. This study demonstrates that Z-mZVI is an efficient and promising reactive material in permeable reactive barriers for Cd²⁺ and Pb²⁺ removal from aqueous solution.

http://ift.tt/2pc3YdF

Spatio-temporal distribution of metals in household dust from rural, semi-urban and urban environments in the Niger Delta, Nigeria

Abstract

Concentrations of metals in household dust samples from rural, semi-urban and urban zones of the Niger Delta in Nigeria were measured during both 2009 and 2014 with the aim of providing information on changes in the concentrations, distribution patterns, sources and risks of metals in these zones. The concentrations of metals in the dust samples were quantified by using inductively coupled plasma atomic emission spectrophotometry (ICP-AES) after digestion with aqua regia. The measured concentrations (mg kg⁻¹) of metals in the three zones within the study periods were as follows: <LOQ–21.2; <LOQ–182; 7.90–265; <LOQ–117; <LOQ–471; 3.37–2310; 0.35–7.9; 4.25–365; 6.78–61,600; 219–37,700; and 1180–18,000 for Cd, Pb, Ba, Cr, Ni, Cu, Co, Mn, Zn, Fe and Al, respectively. The results from the two periods indicate significant changes in the concentrations, distribution patterns and risk factors which reflects a deterioration of the quality of the household environment over this time span. The hazard index (HI) values calculated for children were greater than 1 indicating significant non-cancer risks for these subjects in these areas. The HI values for adults were less than 1 and consequently do not pose a significant risk. The carcinogenic risk levels for exposure to metals for both adults and children in these zones were below the range specified as safe by the US EPA (×10⁻⁶ and ×10⁻⁴) thereby indicating a low cancer risk. The sources of metals in household dust from these zones include emissions from industries, traffic, artisanal workshops and releases from household furniture, metal-based fittings, metal roofing and pesticides.

http://ift.tt/2od1jMj

Environment polluting conventional chemical control compared to an environmentally friendly IPM approach for control of diamondback moth, Plutella xylostella (L.), in China: a review

Abstract

The diamondback moth, Plutella xylostella, is recognized as a widely distributed destructive insect pest of Brassica worldwide. The management of this pest is a serious issue, and an estimated annual cost of its management has reached approximately US$4 billion. Despite the fact that chemicals are a serious threat to the environment, lots of chemicals are applied for controlling various insect pests especially P. xylostella. An overreliance on chemical control has not only led to the evolution of resistance to insecticides and to a reduction of natural enemies but also has polluted various components of water, air, and soil ecosystem. In the present scenario, there is a need to implement an environmentally friendly integrated pest management (IPM) approach with new management tactics (microbial control, biological control, cultural control, mating disruption, insecticide rotation strategies, and plant resistance) for an alternative to chemical control. The IPM approach is not only economically beneficial but also reduces the environmental and health risks. The present review synthesizes published information on the insecticide resistance against P. xylostella and emphasizes on adopting an alternative environmentally friendly IPM approach for controlling P. xylostella in China.

http://ift.tt/2pdJ5Mh

A Host-Dependent Prognostic Model for Elderly Patients with Diffuse Large B-Cell Lymphoma

Background.

Decision-making models for elderly patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) are in great demand.

Patients and Methods.

The Society of Lymphoma Treatment in Japan (SoLT-J), in collaboration with the West-Japan Hematology and Oncology Group (West-JHOG), collected and retrospectively analyzed the clinical records of ≥65-year-old patients with DLBCL treated with R-CHOP from 19 sites across Japan to build an algorithm that can stratify adherence to R-CHOP.

Results.

A total of 836 patients with a median age of 74 years (range, 65–96 years) were analyzed. In the SoLT-J cohort (n = 555), age >75 years, serum albumin level <3.7 g/dL, and Charlson Comorbidity Index score ≥3 were independent adverse risk factors and were defined as the Age, Comorbidities, and Albumin (ACA) index. Based on their ACA index score, patients were categorized into "excellent" (0 points), "good" (1 point), "moderate" (2 points), and "poor" (3 points) groups. This grouping effectively discriminated the 3-year overall survival rates, mean relative total doses (or relative dose intensity) of anthracycline and cyclophosphamide, unanticipated R-CHOP discontinuance rates, febrile neutropenia rates, and treatment-related death rates. Additionally, the ACA index showed comparable results for these clinical parameters when it was applied to the West-JHOG cohort (n = 281).

Conclusion.

The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP. The Oncologist 2017;22:1–7

Implications for Practice: Currently, little is known regarding how to identify elderly patients with diffuse large B-cell lymphoma who may tolerate a full dose of chemotherapy or to what extent cytotoxic drugs should be reduced in some specific conditions. The Society of Lymphoma Treatment in Japan developed a host-dependent prognostic model consisting of higher age (>75 years), hypoalbuminemia (<3.7 g/dL), and higher Charlson Comorbidity Index score (≥3) for such elderly patients. This model can stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of these patients and thus help clinicians in formulating personalized treatment strategies for this growing patient population.

http://ift.tt/2oaolE9

Treatment Paradigms for Advanced Non-Small Cell Lung Cancer at Academic Medical Centers: Involvement in Clinical Trial Endpoint Design

Based on the positive results of various clinical trials, treatment options for non-small cell lung cancer (NSCLC) have expanded greatly over the last 25 years. While regulatory approvals of chemotherapeutic agents for NSCLC have largely been based on improvements in overall survival, recent approvals of many targeted agents for NSCLC (afatinib, crizotinib, ceritinib, osimertinib) have been based on surrogate endpoints such as progression-free survival and objective response. As such, selection of appropriate clinical endpoints for examining the efficacy of investigational agents for NSCLC is of vital importance in clinical trial design. This review provides an overview of clinical trial endpoints previously utilized for approved agents for NSCLC and highlights the key efficacy results for these trials. Trends for more recent approvals in NSCLC, including those for the immunotherapeutic agents nivolumab and pembrolizumab, are also discussed. The results of a correlative analysis of endpoints from 18 clinical trials that supported approvals of investigational agents in clinical trials for NSCLC are also presented. The Oncologist 2017;22:1–9

Implications for Practice While improving survival remains the ultimate goal of oncology clinical trials, overall survival may not always be the most feasible or appropriate endpoint to assess patient response. Recently, several investigational agents, both targeted agents and immunotherapies, have gained U.S. Food and Drug Administration approval in non-small cell lung cancer based on alternate endpoints such as progression-free survival or response rate. An understanding of the assessment of response and trial endpoint choice is important for future oncology clinical trial design.

http://ift.tt/2owwyoK

Endocrine Therapy Initiation and Medical Oncologist Utilization Among Women Diagnosed with Ductal Carcinoma in Situ

Background.

Though randomized clinical trials have demonstrated a reduction in second breast events with endocrine therapy among women with ductal carcinoma in situ (DCIS), use of these therapies remains highly variable. The purpose of this study was to evaluate patient and treatment-related factors associated with endocrine therapy initiation and medical oncology specialty utilization after DCIS.

Materials and Methods.

We identified women with a DCIS diagnosis during 2006–2010 in the North Carolina Central Cancer Registry with linked public and private insurance claims in the University of North Carolina Integrated Cancer Information Surveillance System data resource. Multivariable generalized linear regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) for endocrine therapy initiation in the year following DCIS diagnosis.

Results.

Among 2,090 women with a DCIS diagnosis, 37% initiated endocrine therapy. Initiation was less common among women aged 75+ at diagnosis (RR = 0.79; 95% CI: 0.64–0.97 vs. age 45–54) and women treated with breast-conserving surgery (BCS) who did not receive radiation (RR = 0.63; 95% CI: 0.50–0.78 vs. BCS plus radiation). Consultation with a medical oncologist was strongly associated with endocrine therapy initiation (RR = 1.40; 95% CI: 1.23–1.61). Women who saw a medical oncologist more often had private insurance, higher census tract-level income, hormone receptor positive disease, and treatment with BCS and radiation.

Conclusion.

Treatment strategies for DCIS remain controversial. Our data suggest that endocrine therapy is more often used in addition to standard therapies such as BCS plus radiation, rather than as an alternative to radiation. The Oncologist 2017;22:1–7

Implications for Practice: Randomized trials have demonstrated a reduction in second breast cancer events with use of endocrine therapy for ductal carcinoma in situ (DCIS). However, notable variation exists in the uptake of these therapies among DCIS patients. In this study, factors associated with endocrine therapy initiation in the year following a DCIS diagnosis included consultation with a medical oncologist and treatment with breast-conserving surgery with radiation. Our findings help to explain the wide variation in endocrine therapy initiation and suggest the need for clear guidelines in the treatment of DCIS.

http://ift.tt/2oasCHR

Phase II Study of Bortezomib in Combination with Cyclophosphamide and Rituximab for Relapsed or Refractory Mantle Cell Lymphoma

Background.

Relapsed or refractory mantle cell lymphoma (MCL) has a poor prognosis. The best outcome is achieved in patients who have a partial or complete response to salvage treatment and proceed to allogeneic stem cell transplant.

Patients and Methods.

Twenty-one patients were given a combination regimen of bortezomib, cyclophosphamide, and rituximab at MD Anderson Cancer Center as part of a single-arm, prospective, open-label phase II clinical trial. The median age was 66 years, with a median number of prior treatments of three. Sixty-seven percent had failed intensive chemoimmunotherapy and 43% were intermediate/high risk according to the MCL international prognostic index score, with a median Ki-67 proliferation index of 45% in those who were tested.

Results.

The rates of overall and complete response achieved were 74% and 42%, respectively, with median progression-free and overall survivals of 9 months and 36.4 months, respectively. The regimen's toxicity profile was acceptable; only 25% of the cycles resulted in grade 3 or 4 neutropenia or thrombocytopenia, and only 3% of cycles produced grade 3–4 fatigue. There were no episodes of grade 3–4 neuropathy.

Conclusion.

The combination of bortezomib with cyclophosphamide and rituximab is an effective and well-tolerated regimen in patients with relapsed/refractory MCL. Because of its low toxicity, future combinations of this regimen with other promising drugs that have different mechanisms of action offer a realistic possibility that may improve outcomes for patients who have MCL. The Oncologist 2017;22:1–5

Implications for Practice: The combination of bortezomib with cyclophosphamide and rituximab represents an additional effective novel salvage regimen for mantle cell lymphoma. This combination adds to the growing list of treatment options available for patients with mantle cell lymphoma.

http://ift.tt/2owyuxz

Oncofertility: Fertile Ground for Conflict Between Patient Autonomy and Medical Values

Oncofertility is a unique, multidisciplinary field that serves to bridge the gap between available fertility resources and the special reproductive needs of cancer patients. Oncofertility is a growing field due to the increasing number of survivors, development of new oncologic therapies, extension of duration of therapies, and development and refinement of reproductive therapies. While the technologies and demand for services expand, clinicians need to be appropriately prepared for dealing with various clinical scenarios that may require ethical deliberation. Three real cases are presented in which the patient wishes to pursue reproductive assistance, but her decision is met with hesitance or uncertainty by her care team. Discussion of these clinical scenarios highlights ethical implications of oncofertility practice and serves to highlight the need for the establishment of multidisciplinary care teams and guidelines to support both clinicians and patients. The Oncologist 2017;22:1–4

Implications for Practice: The growing field of oncofertility is ripe for conflict between patient autonomy and medical values due to the nature of cancer and associated threat on an individual's health and survival, as well as the personal significance of childbearing. Cases are presented and ethical implications are discussed to further explore the inherent difficulties in oncofertility practice and guide clinicians in similar situations. Developing guidelines and establishing multidisciplinary teams to facilitate oncofertility discussions and care, as well as training of clinical team members, may improve patient safety, well-being, and satisfaction within the context of fertility decision making, care, and outcomes.

http://ift.tt/2oaqGPx

Data Linkage to Improve Geriatric Oncology Research: A Feasibility Study

Older adults (aged 65 years and older) diagnosed with cancer account for most cancer-related morbidity and mortality in the United States but are often underrepresented on clinical trials. Recent attention from a variety of professional, research, regulatory, and patient advocacy groups has centered on data linkage and data sharing as a means to capture patient information and outcomes outside of clinical trials to accelerate progress in the fight against cancer. The development of a more robust observational research data infrastructure would help to address gaps in the evidence base regarding optimal approaches to treating cancer among the growing and complex population of older adults. To demonstrate the feasibility of building such a resource, we linked information from a sample of older adults with cancer in North Carolina using three distinct, but complementary, data sources: (a) the Carolina Senior Registry, (b) the North Carolina Central Cancer Registry, and (c) North Carolina fee-for-service Medicare claims data. A description of the linkage process, metrics, and characteristics of the final cohort is reported. This study highlights the potential for data linkage to improve the characterization of health status among older adults with cancer and the possibility to conduct passive follow-up for outcomes of interest over time. Extensions of these linkage efforts in partnership with other institutions will enhance our ability to generate evidence that can inform the management of older adults with cancer. The Oncologist 2017;22:1–4

http://ift.tt/2owziTa

Association Study Confirmed Three Breast Cancer-Specific Molecular Subtype-Associated Susceptibility Loci in Chinese Han Women

Background.

Breast cancer is a heterogeneous and polygenic disease that can be divided into different molecular subtypes based on histological and genomic features. To date, numerous susceptibility loci of breast cancer have been discovered by genome-wide association studies and may expand the genetic features. However, few loci have been further studied according to molecular subtypes.

Materials and Methods.

We genotyped 23 recently discovered single nucleotide polymorphisms using the Sequenom iPLEX platform in a female Chinese cohort of 3,036 breast cancer patients (2,935 samples matched molecular subtypes) and 3,036 healthy controls.

Results.

Through a stratification analysis, 5q11.2/MAP3K1 (rs16886034, rs16886364, rs16886397, rs1017226, rs16886448) and 7q32.3/LINC-PINT (rs4593472) were associated with Luminal A, and 10q26.1/FGFR2 (rs35054928) was associated with Luminal B.

Conclusion.

In our study, breast cancer-specific molecular subtype-associated susceptibility loci were confirmed in Chinese Han women, which contributes to a better genetic understanding of breast cancer in different molecular subtypes. The Oncologist 2017;22:1–5

Implications for Practice: To date, genome-wide association studies have identified more than 90 susceptibility loci associated with breast cancer. However, few loci have been further studied according to molecular subtype. The results of this study are that breast cancer-specific molecular subtype-associated susceptibility loci were confirmed in Chinese Han women, which contributes to a better genetic understanding of breast cancer in different molecular subtypes.

http://ift.tt/2oag2rY

National Policies Fostering Hospice Care Increased Hospice Utilization and Reduced the Invasiveness of End-of-Life Care for Cancer Patients

Background.

In 2011, two national policies aiming to foster hospice services for terminal cancer patients took effect in Taiwan. The single-payer National Health Insurance of Taiwan started to reimburse full hospice services. The national hospital accreditation program, which graded all hospitals, incorporated hospice utilization in its evaluation. We assessed the impact of these national policies.

Methods.

A cohort of 249,394 patients aged ≥18 years who died of cancer between 2008 and 2013 were identified from the National Death Registry. We retrieved utilization data of medical services and compared the health care utilization in the final month of life before and after the implementation of the new policies.

Results.

After the policy changes, hospice utilization increased from 20.8% to 36.2%. In a multivariate analysis adjusting for patient demographics, cancer features, and hospital characteristics, hospice utilization significantly increased after 2011 (adjusted odds ratio [AOR] 2.35, p < .001), accompanied by a decrease in intensive care unit (ICU) admissions, invasive mechanical ventilation (IMV), and cardiopulmonary resuscitation (CPR; AORs 0.87, 0.75, and 0.80, respectively; all p < .001). The patients who received hospice services were significantly less likely to receive ICU admissions, IMV, and CPR (AORs 0.20, 0.12, and 0.10, respectively; all p < .001). Hospice utilization was associated with an adjusted net savings of U.S. $696.90 (25.2%, p < .001) per patient in the final month of life.

Conclusion.

The national policy changes fostering hospice care significantly increased hospice utilization, decreased invasive end-of-life care, and reduced the medical costs of terminal cancer patients. The Oncologist 2017;22:1–7

Implications for Practice: National policies fostering hospice care significantly increased hospice utilization, decreased invasive end-of-life care, and reduced the medical costs of terminal cancer patients.

http://ift.tt/2owyttG

Clinical Variant Classification: A Comparison of Public Databases and a Commercial Testing Laboratory

Background.

There is a growing move to consult public databases following receipt of a genetic test result from a clinical laboratory; however, the well-documented limitations of these databases call into question how often clinicians will encounter discordant variant classifications that may introduce uncertainty into patient management. Here, we evaluate discordance in BRCA1 and BRCA2 variant classifications between a single commercial testing laboratory and a public database commonly consulted in clinical practice.

Materials and Methods.

BRCA1 and BRCA2 variant classifications were obtained from ClinVar and compared with the classifications from a reference laboratory. Full concordance and discordance were determined for variants whose ClinVar entries were of the same pathogenicity (pathogenic, benign, or uncertain). Variants with conflicting ClinVar classifications were considered partially concordant if ≥1 of the listed classifications agreed with the reference laboratory classification.

Results.

Four thousand two hundred and fifty unique BRCA1 and BRCA2 variants were available for analysis. Overall, 73.2% of classifications were fully concordant and 12.3% were partially concordant. The remaining 14.5% of variants had discordant classifications, most of which had a definitive classification (pathogenic or benign) from the reference laboratory compared with an uncertain classification in ClinVar (14.0%).

Conclusion.

Here, we show that discrepant classifications between a public database and single reference laboratory potentially account for 26.7% of variants in BRCA1 and BRCA2. The time and expertise required of clinicians to research these discordant classifications call into question the practicality of checking all test results against a database and suggest that discordant classifications should be interpreted with these limitations in mind. The Oncologist 2017;22:1–7

Implications for Practice: With the increasing use of clinical genetic testing for hereditary cancer risk, accurate variant classification is vital to ensuring appropriate medical management. There is a growing move to consult public databases following receipt of a genetic test result from a clinical laboratory; however, we show that up to 26.7% of variants in BRCA1 and BRCA2 have discordant classifications between ClinVar and a reference laboratory. The findings presented in this paper serve as a note of caution regarding the utility of database consultation.

http://ift.tt/2oaBrkM

Infection control practices in Mohs micrographic surgery: a U.K. national survey

Abstract

Mohs micrographic surgery (MMS) is generally considered a safe and effective method of treating certain types of skin cancers, with low reported rates of surgical site infections.^1,2 Practices relating to infection control vary considerably amongst surgeons. Furthermore, emerging evidence suggests clean surgical techniques do not increase infection rates compared to sterile surgical techniques. We sought to establish the current infection control practices amongst surgeons practising MMS in the U.K.

This article is protected by copyright. All rights reserved.

http://ift.tt/2nKo3HZ

A novel link between keratoderma and cardiomyopathy: Contiguous gene deletion involving the desmoglein gene cluster

Abstract

Desmocollin and desmoglein proteins are important in intercellular adhesion in both the skin and the heart.¹ Heterozygous mutations in desmocollin 2 (DSC2)² and desmoglein 2 (DSG2)³ can both result in desmosomal dysfunction in cardiomyocytes, leading to development of fibro-fatty tissue, termed arrythmogenic right ventricular cardiomyopathy (ARVC). Heterozygous truncating mutations in desmoglein 1 (DSG1), an intervening gene, can present as a striate palmoplantar keratoderma, whilst homozygous DSG1 mutations can cause severe dermatitis, allergies and metabolic wasting.⁴ Unlike mutations in plakoglobins and desmoplakins that affect both tissues, the desmogleins, desmocollins and plakophillins typically affect either skin or heart.¹ Here we present a patient with a novel heterozygous deletion resulting in loss of a 2.6Mb region including DSC2, DSG2 and DSG1, associated with ARVC and keratoderma (Fig. 1).

This article is protected by copyright. All rights reserved.

http://ift.tt/2pes6JL

Evolution of the skin manifestations of X-linked Pigmentary Reticulate Disorder

Abstract

X-linked reticulate pigmentary disorder (XLPDR, MIM 301220) is a rare syndrome first recognized by Partington¹. The cardinal manifestations of the disorder are diffuse reticulate hyperpigmentation, hypohidrosis, and unique facial features, as well as recurrent pneumonias and sterile inflammation in various organs^1-9. The syndrome is exceedingly rare and only 20 patients have been reported worldwide. Recently, we identified that the disorder is associated with a recurrent intronic mutation in POLA1, the gene encoding the catalytic subunit of DNA Polymerase-α⁹. Here, we report a new case of XLPDR and include the first detailed description of the evolution of its dermatologic features, as well as confirmation of the same intronic POLA1 mutation.

This article is protected by copyright. All rights reserved.

http://ift.tt/2nKgJw1

Targeted next-generation sequencing identifies 9 novel FLG variants in Chinese Han patients with ichthyosis vulgaris

Abstract

Ichthyosis vulgaris (IV, OMIM #146700) is a common semidominant disorder of keratinization, which is characterized by the xerosis, scaling, keratosis pilaris, palmar and plantar hyperlinearity, and a strong association with atopic disorders.¹

This article is protected by copyright. All rights reserved.

http://ift.tt/2peq3Wc

Intracellular DNA sensing pathway of cGAS-cGAMP is decreased in human newborns and young children

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Zhan-sheng Wang, Yu-lu Liu, Nan Mi, Dao-yun Duan
Newborns are highly susceptible to DNA virus infections, which may result from the characteristics of neonatal innate immune systems. Here we analyzed for the first time the development of innate immune sensing and signaling of intracellular DNA virus infection in human newborns and young children. Both mRNA and protein expression of cGAS, an intracellular DNA sensor, were shown to be significantly reduced in neonatal peripheral blood mononuclear cells (PBMCs). In addition, cGAS expression in neonatal PBMCs could be induced upon herpes simplex virus type 1 (HSV-1) or interferon-α (IFNα) stimulation. Furthermore, production of the second messenger cGAMP and activation of the transcriptional factor IRF3 was severely decreased in neonatal cord blood mononuclear cells (CBMCs) or PBMCs compared with adults. In contrast, the downstream signaling STING-TBK1-IRF3 appeared to be functional in neonatal PBMCs, as demonstrated by the fact that IRF3 phosphorylation and IFNβ production in these cells could be activated by cGAMP. Intriguingly, decreased expression of cGAS in neonatal cells can be rescued by DNA demethylation, with concomitant enhancement in IFNβ induction by HSV-1. Thus, cGAS restoration or STING stimulation by small molecules during infancy might improve the age-dependent susceptibility to DNA virus infection.



http://ift.tt/2p1zGur