Application of electrochemical processes to membrane bioreactors for improving nutrient removal and fouling control

Abstract

Membrane bioreactor (MBR) technology is becoming increasingly popular as wastewater treatment due to the unique advantages it offers. However, membrane fouling is being given a great deal of attention so as to improve the performance of this type of technology. Recent studies have proven that the application of electrochemical processes to MBR represents a promising technological approach for membrane fouling control. In this work, two intermittent voltage gradients of 1 and 3 V/cm were applied between two cylindrical perforated electrodes, immersed around a membrane module, at laboratory scale with the aim of investigating the treatment performance and membrane fouling formation. For comparison purposes, the reactor also operated as a conventional MBR. Mechanisms of nutrient removal were studied and membrane fouling formation evaluated in terms of transmembrane pressure variation over time and sludge relative hydrophobicity. Furthermore, the impact of electrochemical processes on transparent exopolymeric particles (TEP), proposed as a new membrane fouling precursor, was investigated in addition to conventional fouling precursors such as bound extracellular polymeric substances (bEPS) and soluble microbial products (SMP). All the results indicate that the integration of electrochemical processes into a MBR has the advantage of improving the treatment performance especially in terms of nutrient removal, with an enhancement of orthophosphate (PO₄-P) and ammonia nitrogen (NH₄-N) removal efficiencies up to 96.06 and 69.34 %, respectively. A reduction of membrane fouling was also observed with an increase of floc hydrophobicity to 71.72 %, a decrease of membrane fouling precursor concentrations, and, thus, of membrane fouling rates up to 54.33 %. The relationship found between TEP concentration and membrane fouling rate after the application of electrochemical processes confirms the applicability of this parameter as a new membrane fouling indicator.

http://ift.tt/2dACU03

Lifetime cancer risk assessment for inhalation exposure to di(2-ethylhexyl) phthalate (DEHP)

Abstract

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is ubiquitous in the environment and considered as carcinogen; however, the carcinogenic risk of human exposure to DEHP in the air via inhalation is lacking. A probabilistic incremental lifetime cancer risk (ILCR) model was implemented to quantitatively estimate the potential cancer risk of DEHP via human inhalation by using Monte Carlo simulation. We assessed the cancer risk in different age groups (children, adolescents, and adults) exposed to different DEHP concentrations (background low, indoor moderate, and occupational high) for different durations (2, 8, and 20 years). Results showed that the cancer risk of exposure to DEHP was below the acceptable limit (10⁻⁶) in the ambient air but was serious in indoor and occupational environments even at short exposure duration (2 years). The cancer risk of DEHP via inhalation in children was lower than that in adolescents and adults, but the risk in children via dermal and oral exposure to indoor dust and soft PVC toys should be considered. Sensitivity analysis indicated that the exposure concentration of DEHP was the strongest factor that influenced ILCR. Our work provides the evidence of cancer risk of DEHP via inhalation and highlights the risk in indoor and occupational environments.

http://ift.tt/2dSUm3y

Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D 3

Abstract

The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D ₃—not previously investigated—will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D₃. The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D₃ did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D₃ provide equal efficacy and safety profiles.

http://ift.tt/2dFV8Nx

Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D 3

Abstract

The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D ₃—not previously investigated—will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D₃. The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D₃ did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D₃ provide equal efficacy and safety profiles.

http://ift.tt/2dFV8Nx

Quantitative method for determination of oleocanthal and oleacein in virgin olive oils by liquid chromatography–tandem mass spectrometry

Publication date: 1 January 2017
Source:Talanta, Volume 162
Author(s): Verónica Sánchez de Medina, Hristofor Miho, Eleni Melliou, Prokopios Magiatis, Feliciano Priego-Capote, María Dolores Luque de Castro
Oleocanthal and oleacein, two key secoiridoid derivatives present in virgin olive oil (VOO), are gaining clinical and nutritional interest thanks to their proved bioactivity; therefore, the determination of both phenols is a growing demanded application to increase the value of VOO. The main problem of previously reported liquid chromatography-based methods for oleocanthal and oleacein measurement is their interaction with water or other polar solvents such as methanol to promote the formation of hemiacetal or acetal derivatives. This interaction can occur during either sample extraction, basically liquid–liquid extraction, and/or chromatographic separation. The aim of this research was to evaluate the suitability of LC–MS/MS for absolute quantitation of oleocanthal and oleacein in VOO. For this purpose, both liquid–liquid extraction and chromatographic separation were studied as potential promoters of acetals and hemiacetals formation from oleocanthal and/or oleacein. The results showed that the use of methanol–water solutions for phenols extraction was not influential on the formation of these artifacts. Acetals and hemiacetals from oleocanthal and/or oleacein were only detected at very low concentrations when methanol gradients under acidic conditions were used for chromatographic separation. With this premise, a protocol based on extraction with acetonitrile and a reverse chromatographic gradient with methanol was established to quantify in absolute terms oleocanthal and oleacein in VOO samples. The resulting protocol was applied to three VOO samples characterized by high, medium, and low levels of these two phenols.



http://ift.tt/2dQAZDC

The Rising Zebrafish Research in China: Meeting Report of the 3rd Chinese Zebrafish Principal Investigator Meeting & the Inaugural Meeting of China Zebrafish Society

Publication date: Available online 6 October 2016
Source:Journal of Genetics and Genomics
Author(s): Dongyuan Ma, Yuanyuan Xue, Yifan Zhang, Yonghua Sun, Anming Meng, Feng Liu




http://ift.tt/2dQpXy7

Priming Hand Motor Training with Repetitive Stimulation of the Fingertips; Performance Gain and Functional Imaging of Training Effects

Publication date: Available online 6 October 2016
Source:Brain Stimulation
Author(s): Martin Lotze, Aija Marie Ladda, Sybille Roschka, Thomas Platz, Hubert R. Dinse
BackgroundApplication of repetitive electrical stimulation (rES) of the fingers has been shown to improve tactile perception and sensorimotor performance in healthy individuals.ObjectiveTo increase motor performance by priming the effects of active motor training (arm ability training; AAT) using rES.MethodsWe compared the performance gain for the training increase of the averaged AAT- tasks of both hands in two groups of strongly right-handed healthy volunteers. Functional Magnetic Resonance Imaging (fMRI) before and after AAT was assessed using three tasks for each hand separately: finger sequence tapping, visually guided grip force modulation, and writing. Performance during fMRI was controlled for preciseness and frequency. A total of 30 participants underwent a two-week unilateral left hand AAT, 15 participants with 20 minutes rES priming of all fingertips of the trained hand, and 15 participants without rES priming.ResultsrES-primed AAT improved the trained left-hand performance across all training tasks on average by 32.9%, non-primed AAT improved by 29.5%. This gain in AAT performance with rES priming was predominantly driven by an increased finger tapping velocity. Functional imaging showed comparable changes for both training groups over time. Across all participants, improved AAT performance was associated with a higher contralateral primary somatosensory cortex (S1) fMRI activation magnitude during the grip force modulation task.ConclusionsThis study highlights the importance of S1 for hand motor training gain. In addition, it suggests the usage of rES of the fingertips for priming active hand motor training.



http://ift.tt/2d93bmE

Prognostic and predictive value of tumor infiltrating lymphocytes in early breast cancer

Publication date: Available online 6 October 2016
Source:Cancer Treatment Reviews
Author(s): Carmen Criscitiello, Angela Esposito, Dario Trapani, Giuseppe Curigliano
It is well recognized that the immune system plays an essential role in tumor defense. The presence of tumor-infiltrating lymphocytes reflects an individual immunological response. In early breast cancer, the presence of TILs is associated with a more favorable outcome and response to therapy. In this review, we describe how TILs are assessed. Also, we discuss their role as prognostic and predictive biomarker in the neoadjuvant and adjuvant settings as well as in residual disease. Moreover, we discuss the possible implementation of TILs in daily clinical practice as well as in future clinical trials in order to fine tune prognosis and improve treatments.



http://ift.tt/2d03ltp

Current perspectives of sentinel lymph node dissection at the time of radical surgery for prostate cancer

Publication date: Available online 6 October 2016
Source:Cancer Treatment Reviews
Author(s): Gavish Munbauhal, Thomas Seisen, Florie Gomez, Benoit Peyronnet, Olivier Cussenot, Shahrokh F. Shariat, Morgan Rouprêt
The sentinel lymph node dissection (SLND) concept relies on the accurate detection of primary nodal landing sites and could represent a major advancement towards accurate, non-invasive pelvic staging in prostate cancer (PCa). Different iterations of the technique have now been validated and reproduced mostly in large-volume centres. The existing evidence denotes the feasibility and sensitivity of SLND, with encouraging pre- and intraoperative detection rates of 98% and 96%. Yet, current surgical practice mandates a backup template dissection due to a false negative rate, up to 7.1%, of tracer-guided surgery. In practice, SLND failed to achieve nodal detection in up to 20% of pelvic sidewalls. Despite scarce validated evidence, current consensus mainly attributes these false negative cases to altered prostatic drainage secondary to malignant obliteration of lymphovascular structures. In parallel, multiple SLND studies have highlighted the complex and variable drainage pathways from the prostate, furthering the established anatomical atlases. The most promising approach may therefore rely in magnetic nanoparticles and PCa-targeting ligands. However, in the absence of a clear sentinel node or region for the prostate, formal SLND is difficult to integrate in routine surgical practice for now. As such, tracer-guided dissection is only used as a complementary intervention to highlight first- echelon nodes and aberrant lymphatic pathways found beyond the commonly adopted pelvic lymphadenectomy templates.



http://ift.tt/2dSB8ee

Matrin 3 variants are frequent in Italian ALS patients

Publication date: Available online 6 October 2016
Source:Neurobiology of Aging
Author(s): Giuseppe Marangi, Serena Lattante, Paolo Niccolò Doronzio, Amelia Conte, Giorgio Tasca, Mauro Monforte, Agata Katia Patanella, Giulia Bisogni, Emiliana Meleo, Salvatore La Spada, Marcella Zollino, Mario Sabatelli
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of motor neurons in the primary motor cortex, brainstem, and spinal cord. Recently, missense variants in MATR3 were identified in familial and sporadic ALS patients, but very few additional ALS patients have been reported so far. The p.S85C MATR3 variant was previously associated to a different phenotype, namely a distal myopathy associated with dysphagia and dysphonia. Here, we assessed the contribution of MATR3 variants in a cohort of 322 Italian ALS patients. We identified 5 different missense MATR3 variants (p.Q66K, p.G153C, p.E664A, p.S707L, p.N787S) in 6 patients (1.9%). None of our patients showed signs of myopathy at electrophysiological examination. Muscle biopsy, performed in two patients, showed neurogenic changes and normal nuclear staining with anti-matrin 3 antibody. Our results confirm that MATR3 variants are associated with ALS and suggest that they are more frequent in Italian ALS patients. Further studies are needed to elucidate the pathogenic significance of identified variants in sporadic and familial ALS.



http://ift.tt/2d8UgBL

Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson’s disease: analysis of a large multi-center study

Publication date: Available online 6 October 2016
Source:Neurobiology of Aging
Author(s): L. Wang, M.G. Heckman, J.O. Aasly, G. Annesi, M. Bozi, S.J. Chung, C. Clarke, D. Crosiers, G. Eckstein, G. Garraux, G.M. Hadjigeorgiou, N. Hattori, B. Jeon, Y.J. Kim, M. Kubo, S. Lesage, J.J. Lin, T. Lynch, P. Lichtner, G.D. Mellick, V. Mok, K.E. Morrison, A. Quattrone, W. Satake, P.A. Silburn, L. Stefanis, J.D. Stockton, E.K. Tan, T. Toda, A. Brice, C. Van Broeckhoven, R.J. Uitti, K. Wirdefeldt, Z. Wszolek, G. Xiromerisiou, D.M. Maraganore, T. Gasser, R. Krüger, M.J. Farrer, O.A. Ross, M. Sharma
A recent study has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of PD (MacLeod D. et al, 2013). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multi-center series of PD patients (5769) and controls (4988) from sites participating in the Genetic Epidemiology of Parkinson's Disease (GEoPD) consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however given the role of retromer and lysosomal pathways in PD, further studies are warranted.



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Signet ring cell lymphoma: Clinicopathologic, immunohistochemical and FISH studies of seven cases

Publication date: Available online 7 October 2016
Source:Annals of Diagnostic Pathology
Author(s): Shanxiang Zhang, Jihong Sun, Yanan Fang, Mehdi Nassiri, Lanting Liu, Jiehao Zhou, Ryan Stohler, Haki Choi, Gail H Vance




http://ift.tt/2dSu2Xh

The Potential Impact of Essential Nutrients Vitamins C and D upon Periodontal Disease Pathogenesis and Therapeutic Outcomes

Abstract

Diet has powerful effects upon inflammatory status, arguably as strong or stronger than microbial plaque. Despite a relationship between diet and periodontal inflammatory markers being established over 30 years ago, it is only recently that the mechanisms underpinning these effects have begun to be examined in detail. Following an analysis of the evidence base in 2011, this review focuses upon the most contemporaneous evidence relating specifically to the micronutrient vitamins C and D and their potential impact upon periodontal disease pathogenesis and/or therapeutic outcomes. The authors bring together both epidemiological and laboratory data and aim to outline avenues for potential studies given the limited number of larger well-conducted clinical interventional trials completed to date.

http://ift.tt/2e9VXRt

Equivalent cross-relaxation rate imaging and diffusion weighted imaging for early prediction of response to bevacizumab-containing treatment in colorectal liver metastases—preliminary study

Publication date: January–February 2017
Source:Clinical Imaging, Volume 41
Author(s): Shigeru Matsushima, Takeshi Sato, Hideyuki Nishiofuku, Yozo Sato, Shinichi Murata, Yasutomi Kinosada, Seiichi Era, Yoshitaka Inaba
PurposeTo evaluate and compare the usefulness of equivalent cross-relaxation rate (ECR) imaging (ECRI) and diffusion-weighted imaging (DWI) in the early prediction of the response of bevacizumab-containing treatments of colorectal liver metastases.Methods and materialSeven patients received bevacizumab-containing treatments for colorectal liver metastases. Serial magnetic resonance imaging was performed to evaluate responses before and 2 weeks after starting chemotherapy. In the ECRI, we adopted the off-resonance technique for preferential saturation of immobile protons to evaluate the ECR values. A single saturation transfer pulse frequency was used at a frequency of 3.5 ppm downfield from the water resonance. In the DWI, the apparent diffusion coefficient (ADC) value commonly used with two b-values was acquired by using diffusion weightings of 0 and 800 s/mm². The region of interest of the metastatic lesions in the liver was separately measured by ECRI and DWI. Tumor response was assessed by response evaluation criteria in solid tumors criteria 8 weeks after starting chemotherapy.ResultsIn this study, we had four responders and three nonresponders. There was a significant difference in the pretreatment ECR values between the responders and nonresponders (P=.01); there was no significant difference in the ADC values between the two groups. Analysis of the percentage difference between the pretreatment and post-treatment values, termed as percentage change, showed that there were no significant differences in the percentage change of the ADC values between both groups; however, the percentage change in the ECR value was significantly greater for the responders than for the nonresponders (−41.6%±17.1% vs. –12.9%±6.9%, respectively; P=.04).ConclusionThe pretreatment ECR value and percentage change of the ECR value 2 weeks after starting chemotherapy were useful parameters in the early prediction of response to bevacizumab-containing treatment in colorectal liver metastases.



http://ift.tt/2e9WMJL

Imaging of Pancreatic Cancer: What the Surgeon Wants to Know

Publication date: Available online 7 October 2016
Source:Clinical Imaging
Author(s): Randy Yeh, Jonathan Steinman, Lyndon Luk, Michael Kluger, Elizabeth Hecht
Pancreatic cancer is the fourth leading cause of cancer-related death. Early detection is challenging because symptoms are relatively non-specific. Imaging is vital in detecting and staging pancreatic tumors and management depends on imaging findings. Radiologists should be aware of current surgical treatments for pancreatic neoplasms as surgeons rely on interpretation of cross-sectional imaging for pre-surgical planning. Understanding post-surgical anatomy is critical to assess for complications and recurrence. This review will emphasize the role of the radiologist in planning for surgery and will review post-operative changes based on surgical intervention and common complications.



http://ift.tt/2dFhIFY

Differentiation of subtypes of renal cell carcinoma: Dynamic contrast-enhanced MR imaging versus diffusion-weighted MR imaging

Publication date: Available online 7 October 2016
Source:Clinical Imaging
Author(s): Akira Yamamoto, Tsutomu Tamada, Katsuyoshi Ito, Teruki Sone, Akihiko Kanki, Daigo Tanimoto, Yasufumi Noda
ObjectiveTo compare the performance of DCE and DW MR imaging in the differentiation of subtypes of RCC.Materials/MethodsThis study included 45 renal tumors of clear (n=36) and non-clear cell (n=9) RCC. The contrast enhancement ratios (CERs) and the ADC values on MRI were compared between the clear and non-clear cell RCC groups.ResultsDiagnostic performance of DCE and DW MR imaging, AUCs were 0.968 and 0.797 for the CERs of the corticomedullary and the ADC value.ConclusionThe CER of the corticomedullary phase was more reliable in distinguishing between clear and non-clear cell RCCs.



http://ift.tt/2e9VI8H

Adhesion of multimode adhesives to enamel and dentin after one year of water storage

Abstract

Objectives

This study aimed to evaluate the ultramorphological characteristics of tooth–resin interfaces and the bond strength (BS) of multimode adhesive systems to enamel and dentin.

Methods

Multimode adhesives (Scotchbond Universal (SBU) and All-Bond Universal) were tested in both self-etch and etch-and-rinse modes and compared to control groups (Optibond FL and Clearfil SE Bond (CSB)). Adhesives were applied to human molars and composite blocks were incrementally built up. Teeth were sectioned to obtain specimens for microtensile BS and TEM analysis. Specimens were tested after storage for either 24 h or 1 year. SEM analyses were performed to classify the failure pattern of beam specimens after BS testing.

Results

Etching increased the enamel BS of multimode adhesives; however, BS decreased after storage for 1 year. No significant differences in dentin BS were noted between multimode and control in either evaluation period. Storage for 1 year only reduced the dentin BS for SBU in self-etch mode. TEM analysis identified hybridization and interaction zones in dentin and enamel for all adhesives. Silver impregnation was detected on dentin–resin interfaces after storage of specimens for 1 year only with the SBU and CSB.

Conclusions

Storage for 1 year reduced enamel BS when adhesives are applied on etched surface; however, BS of multimode adhesives did not differ from those of the control group. In dentin, no significant difference was noted between the multimode and control group adhesives, regardless of etching mode.

Clinical relevance

In general, multimode adhesives showed similar behavior when compared to traditional adhesive techniques. Multimode adhesives are one-step self-etching adhesives that can also be used after enamel/dentin phosphoric acid etching, but each product may work better in specific conditions.

http://ift.tt/2dF6UYi

Optimizing matrix and fiber/matrix interface to achieve combination of strength, ductility and toughness in carbon nanotube-reinforced carbon/carbon composites

Publication date: 5 January 2017
Source:Materials & Design, Volume 113
Author(s): Lei Feng, Kezhi Li, Bei Xue, Qiangang Fu, Leilei Zhang
The direct attachment of carbon nanotubes (CNTs) on carbon fibers (CFs) always leads to a decrease of fiber-dominated properties (e.g., flexural strength) and a brittle fracture behavior of C/Cs, although the matrix-dominated properties (e.g., compressive strength and interlaminar shear strength (ILSS)) exhibit an obvious enhancement. To achieve the combination of mechanical strength, ductility and toughness in C/Cs, in this work, efforts were spent on simultaneously optimizing the matrix and fiber/matrix (F/M) interface. CNTs with radial orientation were grown onto the CFs by double-injection chemical vapor deposition to modify the microstructure of matrix. Pyrocarbon was deposited on the surface of CFs before CNT growth to protect CFs and to weaken interfacial strength between CFs and CNT/matrix. These optimal designs create strengthening and toughness mechanisms such as crack deflection and long pullout of CFs in the failure process of composites, which endow C/Cs with improved flexural strength of 31.5%, flexural ductility of 118%, compressive strength of 81.5% and ILSS of 82%, accompanied by a clear change from brittle fracture to pseudo-plastic fracture during flexural test. This work may provide a meaningful way to not only enhance both the fiber- and matrix-dominated strength but to substantially improve the ductility and toughness of C/Cs.

Graphical abstract

http://ift.tt/2e9OUbm

p16 immunostaining in keratinocytic neoplasia in organ transplant recipients: Bowen's disease shows a characteristic pattern. “R1”

Abstract

Background

For selecting therapy it is important to distinguish different types of keratinocytic neoplasia. It is sometimes difficult to make histopathologic diagnosis, especially in organ transplant recipients (OTR) who develop numerous lesions.

Methods

To investigate p16 immunostaining in different types of keratinocytic neoplasia in OTR, we studied 59 actinic keratoses(AK), 51 Bowen' s disease(BD), 63 squamous cell carcinomas(SCC) , 16 benign keratotic lesions(BKL) from 31 OTR patients and 25 controls (eczema and psoriasis). Tissue sections were stained for H&E and p16. We scored intensity, proportion and distribution of p16 positive lesional cells.

Results

In 19% of AK, 92% of BD, 35% of SCC and 12% of BKL more than fifty percent of lesional cells were p16-positive. In 16% of AK, 80% of BD, 18% of SCC and 13% of BKL strong p16 staining was observed. BKL, AK and SCC showed focal and patchy staining, BD showed diffuse pattern with strong staining of all atypical cells. Sparing of the basal layer was predominantly seen in BD. No control specimen showed p16-overexpression.

Conclusions

P16 immunostaining shows a characteristic pattern in BD, but not in AK, SCC and BKL. It appears useful in recognising BD, but not in differentiating between other keratinocytic neoplasia.

http://ift.tt/2dB0QAV

“HINTS” IN THE HORN: DIAGNOSTIC CLUES IN THE STRATUM CORNEUM

ABSTRACT

The stratum corneum or horny layer is the uppermost layer of the epidermis, and is mainly responsible for the skin's barrier function. In spite of its complexity at the ultrastructural and molecular level, the features accessible to visualization on conventional histology are relatively limited. Nevertheless, knowledge of subtle clues that one may observe in the stratum corneum can prove useful in a wide range of situations in dermatopathology.

We herein review a selection of common and rare entities in which the horny layer may reveal significantly important hints for the diagnosis. These clues include parakeratosis and its different patterns (focal, confluent, alternating, associated with spongiosis, epidermal hyperplasia or lichenoid changes), subcorneal acantholysis, infectious organisms in the stratum corneum (including fungal, bacterial and parasitic), thickening or thinning of the stratum corneum and the presence of different kinds of pigment. Even when normal, the horny layer may prove to be useful when seen in association with severe epidermal damage, a combination of features testifying to the acute nature of the underlying pathological process.

http://ift.tt/2dZesZi

Detection of IgE autoantibodies to BP180 and BP230 and their relationship to clinical features in bullous pemphigoid

Abstract

Background

IgE autoantibodies are considered to be involved in pathogenesis of bullous pemphigoid (BP), particularly inflammatory and erythematous phenotypes.

Objective

To develop reliable ELISAs for detection of IgE autoantibodies to both BP180 and BP230 in BP sera, and to compare the ELISA results with clinical features.

Methods

We used commercially available IgG ELISAs to develop IgE ELISAs for both BP180 and BP230. To determine the influence of excess amount of IgG autoantibodies, all normal and BP sera were tested before and after IgG adsorption. The results of IgE ELISAs were statistically compared among various ELISAs, and with various clinical parameters, including our own severity scores and BP phenotypes.

Results

IgG adsorption generally showed no changes in sensitivity and specificity of IgE ELISAs, although slight cross-reactivity of anti-IgE secondary antibody to IgG and interference of excess amount of IgG autoantibodies to IgE reactivity were suggested. IgE autoantibodies to BP180 and BP230 were found in 21 and 18 of 36 BP sera, respectively. The results of IgG and IgE ELISAs for both BP180 and BP230 well correlated. IgG and IgE anti-BP180 antibodies, but not IgG and IgE anti-BP230 autoantibodies, correlated with disease activity. IgE anti-BP30 autoantibodies correlated with nodular phenotype but not erythematous phenotype.

Conclusion

The results in this study indicated that IgE autoantibodies to both BP180 and BP230 are frequently detected in BP sera. IgE anti-BP180 autoantibodies seemed to be pathogenic, while association between IgE autoantibodies and inflammatory BP phenotype was not indicated.

This article is protected by copyright. All rights reserved.

http://ift.tt/2d8HP9e

Decreased level of IL-10-producing B cells in patients with pemphigus but not with pemphigoid

Abstract

Background

hile the frequency of IL-10-producing B cells (B10 cells) is reported to have an inverse correlation with disease activity in some human autoimmune diseases, the association between B10 cells and autoimmune blistering diseases (AIBD) has not been well-evaluated. Although several phenotypes of human regulatory B cells have been proposed, the most appropriate one was not established.

Objective

This study aimed to evaluate B10 cells in AIBD including their phenotypes.

Methods

Peripheral blood mononuclear cells were isolated from 39 patients with AIBD, including 14 pemphigus and 25 pemphigoid patients, and 10 healthy controls. We investigated the frequencies of B10 cells and CD19⁺CD24^hiCD38^hi B cells using flow cytometry.

Results

The frequencies of B10 cells and CD19⁺CD24^hiCD38^hi B cells were significantly lower and higher, respectively, in patients with pemphigus compared with healthy controls. Comparing patients with pemphigoid and healthy controls, no significant difference in the frequencies of B10 cells and CD19⁺CD24^hiCD38^hi B cells was observed. B10 cell level in pemphigus was not associated with disease severity but inversely correlated with the required dosage of steroid for treatment. While no significant difference in the frequency of IL-10-producing cells among CD19⁺CD24^hiCD38^hi B cells was observed, in CD9⁺ and CD27^- B cell subsets, it was significantly decreased in patients with pemphigus compared with healthy controls.

Conclusion

Our results suggest the association of B10 cells with pemphigus but not with pemphigoid. The decrease in B10 cell level in pemphigus is partly caused by the lower production of IL-10 in CD9⁺ and CD27^- B cell subsets.

This article is protected by copyright. All rights reserved.

http://ift.tt/2dRuFe3

Chemoprevention of basal cell carcinoma: reply from authors

http://ift.tt/2d8HhzX

Transition metal (Fe, Co, Ni, and Mn) oxides for oxygen reduction and evolution bifunctional catalysts in alkaline media

Publication date: Available online 6 October 2016
Source:Nano Today
Author(s): Hannah Osgood, Surya V. Devaguptapu, Hui Xu, Jaephil Cho, Gang Wu
In recent years, a large amount of focus has been given to the development of alternative energy sources that are clean and efficient; among these, electrochemical energy holds potential for its compatibility with solar and wind energy, as well as their applications in fuel cells, and metal-air batteries, and water electrolyzers. However, these technologies require the use of highly active and stable catalysts to make these applications feasible. Current catalysts consist of precious metals such as platinum and iridium, which are expensive and block common access to electrochemical energy. Transition metals, and their oxides, serve as a promising alternative to these precious metals. due to their intrinsic activity and sufficient stability in oxidative electrochemical environments. Among wide range of these metals, cobalt, manganese, nickel, and iron, have been extensively explored as bifunctional catalysts, capable of simultaneously catalyzing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) for energy storage and conversion. Not only do they show innate electrochemical capabilities, but their structural diversity, as well as their ability to be mixed, doped, and combined with other materials such as graphene, make transition metal oxides a highly attractive subject in electrochemical and materials research. This review serves to summarize the research currently available concerning transition metal oxides, and their applications as a bifunctional catalyst for the utilized fuel cells and rechargeable metal-air batteris in alkaline media. Particularly, oxide synthesis and their structural properties are related to their electrochemical abilities, along with their behavior when introduced to other catalytic materials and dopants.

Graphical abstract

http://ift.tt/2dRskjn

Synapse engineering: A new level of brain modulation

Publication date: Available online 6 October 2016
Source:Brain Research Bulletin
Author(s): Yelin Chen, Yang Geng
Brain modulation is a powerful approach to study brain function in vivo. Tremendous progress had been made by controlling brain activity with different brain modulation tools. Synapse is the more fundamental functional unit of brain. In theory, synapse engineering could modulate brain function more precisely. However this had not been possible until recently. Our review provides a brief introduction of various brain modulation methods, and elaborates on a recently developed synapse-engineering tool. This technique allows modulation of specific synapses in vivo for the first time and has been used to clarify the causal role of synaptic plasticity in learning and memory. We also discuss its potentials for further development.



http://ift.tt/2e9sdUH

The Purkinje cell as a model of synaptogenesis and synaptic specificity

Publication date: Available online 6 October 2016
Source:Brain Research Bulletin
Author(s): Marco Sassoè-Pognetto, Annarita Patrizi
Since the groundbreaking work of Ramon y Cajal, the cerebellar Purkinje cell has always represented an ideal model for studying the organization, development and function of synaptic circuits. Purkinje cells receive distinct types of glutamatergic and GABAergic synapses, each characterized by exquisite sub-cellular and molecular specificity. The formation and refinement of these connections results from a temporally-regulated sequence of events that involves molecular interactions between distinct sets of secreted and surface proteins, as well as activity-dependent competition between converging inputs. Insights into the mechanisms controlling synaptic specificity in Purkinje cells may help understand synapse development also in other brain regions and disclose circuit abnormalities that underlie neurodevelopmental disorders.



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Treats for your team

British Dental Journal 221, 430 (2016). doi:10.1038/sj.bdj.2016.738

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New version of 'perio bible' published

British Dental Journal 221, 374 (2016). doi:10.1038/sj.bdj.2016.717

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An incredibly versatile adhesive on display

British Dental Journal 221, 432 (2016). doi:10.1038/sj.bdj.2016.741

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New radiation safety guidance launched

British Dental Journal 221, 375 (2016). doi:10.1038/sj.bdj.2016.718

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Coaching patients into better habits

British Dental Journal 221, 433 (2016). doi:10.1038/sj.bdj.2016.745

http://ift.tt/2dj16SW

Elections to the Principal Executive Committee of the British Dental Association

British Dental Journal 221, 375 (2016). doi:10.1038/sj.bdj.2016.719

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Full range optical and electrical properties of Zn-doped SnO2 and oxide/metal/oxide multilayer thin films deposited on flexible PET substrate

Publication date: 15 February 2017
Source:Journal of Alloys and Compounds, Volume 694
Author(s): Yoonho Cho, Narendra S. Parmar, Sahn Nahm, Ji-Won Choi
As a potential replacement of indium-tin oxide (ITO), Zn-doped SnO2/Ag/Zn-doped SnO2 multilayer transparent conducting electrodes were prepared on the flexible poly ethylene terephthalate (PET) substrates by RF sputtering at room temperature. To find the optimized composition of Zn-doped SnO2 thin film, which will have higher conductivity and transmittance as compared to the undoped SnO2 thin film, an off-axis Continuous Composition Spread (CCS) sputtering method was used. Zn-doped SnO2 thin films have lower resistivity than undoped SnO2 thin films due to excess oxygen vacancies (Vo) and/or zin interstitials (Zni) in thin films. The minimum resistivity of thin film was 0.13 Ω cm at optimized 2.43 wt% Zn-doping. Zn-doped SnO2/Ag/Zn-doped SnO2 multilayer thin films were prepared using the optimized composition deposited by an on-axis RF sputter. The multilayer TCO film has the resistivity ∼5.33 × 10⁻⁵ Ω cm and the average transmittance >85% in the 550 nm wavelength region.



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Highly efficient Pd-doped aluminate spinel catalysts with different divalent cations for the selective catalytic reduction of NO with H2 at low temperature

Publication date: 15 January 2017
Source:Chemical Engineering Journal, Volume 308
Author(s): Chaochao Xu, Wei Sun, Limei Cao, Tingting Li, Xuanxuan Cai, Ji Yang
The performance of pure and Pd-doped aluminate spinel catalysts (i.e., MAl2O4 and MAl1.95Pd0.05O4, where M=Cu, Co, Zn) for the selective catalytic reduction of NO by H2 (H2-SCR) were investigated in this paper. The catalytic performance over MAl2O4 is poor but can be improved significantly by incorporating Pd into the lattice, resulting in NO conversion over Co-AlPd, Zn-AlPd and Cu-AlPd catalysts of approximately 95%, 90.5% and 84%, respectively, in the presence of 2% O2 at a low temperature range of 100–350°C. Both the pure and Pd-doped aluminate spinel catalysts showed the same sequences with respect to activity: Co-Al>Zn-Al>Cu-Al and Co-AlPd>Zn-AlPd>Cu-AlPd, indicating that the selection of divalent metal M is of essential importance in designing spinel catalysts and in modifying their SCR performance. Co-AlPd catalyst showed stable activity in the presence of 3% and 5% H2O at 250°C, whereas the SCR reaction was promoted and a slight positive influence of the NO conversion was observed with a further increase of the H2O concentration to 5%. The presence of 100ppm SO2 in the feed resulted in almost a 23% NO reduction at 250°C for the Co-AlPd catalyst, whereas only a 1.2% decrease of NO conversion was observed with further increase in the SO2 concentration to 150ppm, and the NO conversion recovered rapidly to approximately 82% after removing the SO2 from the feed stream.

Graphical abstract

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Optogenetic Control of Protein Function: From Intracellular Processes to Tissue Morphogenesis

Publication date: Available online 7 October 2016
Source:Trends in Cell Biology
Author(s): Giorgia Guglielmi, Henning Johannes Falk, Stefano De Renzis
Optogenetics is an emerging and powerful technique that allows the control of protein activity with light. The possibility of inhibiting or stimulating protein activity with the spatial and temporal precision of a pulse of laser light is opening new frontiers for the investigation of developmental pathways and cell biological bases underlying organismal development. With this powerful technique in hand, it will be possible to address old and novel questions about how cells, tissues, and organisms form. In this review, we focus on the applications of existing optogenetic tools for addressing issues in animal morphogenesis.



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Electroconductive natural polymer-based hydrogels

Publication date: December 2016
Source:Biomaterials, Volume 111
Author(s): Zhijun Shi, Xing Gao, Muhammad Wajid Ullah, Sixiang Li, Qun Wang, Guang Yang
Hydrogels prepared from natural polymers have received immense considerations over the past decade due to their safe nature, biocompatibility, hydrophilic properties, and biodegradable nature. More recently, when treated with electroactive materials, these hydrogels were endowed with high electrical conductivity, electrochemical redox properties, and electromechanical properties; consequently, forming a smart hydrogel. The biological properties of these smart hydrogels, classified as electroconductive hydrogels, can be combined with electronics. Thus, they are considered as good candidates for some potential uses, which include bioconductors, biosensors, electro-stimulated drug delivery systems, as well as neuron-, muscle-, and skin-tissue engineering. However, there is lacking comprehensive information on the current state of these electroconductive hydrogels which complicates our understanding of this new type of biomaterials as well as their potential applications. Hence, this review provides a summary on the current development of electroconductive natural polymer-based hydrogels (ENPHs). We have introduced various types of ENPHs, with a brief description of their advantages and shortcomings. In addition, emerging technologies regarding their synthesis developed during the past decade are discussed. Finally, two attractive potential applications of ENPHs, cell culture and biomedical devices, are reviewed, along with their current challenges.



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Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes Dysregulation of Autophagy and the Ubiquitin-Proteasome System

Publication date: Available online 6 October 2016
Source:Cell Reports
Author(s): John D. Murdoch, Christine M. Rostosky, Sindhuja Gowrisankaran, Amandeep S. Arora, Sandra-Fausia Soukup, Ramon Vidal, Vincenzo Capece, Siona Freytag, Andre Fischer, Patrik Verstreken, Stefan Bonn, Nuno Raimundo, Ira Milosevic
Endophilin-A, a well-characterized endocytic adaptor essential for synaptic vesicle recycling, has recently been linked to neurodegeneration. We report here that endophilin-A deficiency results in impaired movement, age-dependent ataxia, and neurodegeneration in mice. Transcriptional analysis of endophilin-A mutant mice, complemented by proteomics, highlighted ataxia- and protein-homeostasis-related genes and revealed upregulation of the E3-ubiquitin ligase FBXO32/atrogin-1 and its transcription factor FOXO3A. FBXO32 overexpression triggers apoptosis in cultured cells and neurons but, remarkably, coexpression of endophilin-A rescues it. FBXO32 interacts with all three endophilin-A proteins. Similarly to endophilin-A, FBXO32 tubulates membranes and localizes on clathrin-coated structures. Additionally, FBXO32 and endophilin-A are necessary for autophagosome formation, and both colocalize transiently with autophagosomes. Our results point to a role for endophilin-A proteins in autophagy and protein degradation, processes that are impaired in their absence, potentially contributing to neurodegeneration and ataxia.

Graphical abstract

Teaser

Regulation of protein homeostasis and autophagy has become a promising line of research in the neurodegeneration field. Murdoch et al. now find that endophilin-A, a key factor in clathrin-mediated endocytosis, regulates protein homeostasis through the Foxo3a-Fbxo32 network.


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Multifaceted properties of 1,4-dimethylcarbazoles: Focus on trimethoxybenzamide and trimethoxyphenylurea derivatives as novel human topoisomerase II inhibitors

Publication date: 1 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 96
Author(s): Domenico Iacopetta, Camillo Rosano, Francesco Puoci, Ortensia Ilaria Parisi, Carmela Saturnino, Anna Caruso, Pasquale Longo, Jessica Ceramella, Aurélie Malzert-Fréon, Patrick Dallemagne, Sylvain Rault, Maria Stefania Sinicropi
Natural or synthetic carbazole derivatives have recently attracted the attention of the scientific world because of their multiple biological activity, leading to an increase of designed, synthesized and studied analogues. In this paper, four 1,4-dimethylcarbazole derivatives, analogues of Ellipticine, have been investigated for their ability to block cancer cells growth, with low effects on the proliferation of normal cells. DNA topoisomerases inhibition assays, docking simulations, stability studies and effects on a membrane model are reported. Particularly, compounds 2 and 3 have been found thermally stable and able to inhibit, strongly and selectively, the human DNA topoisomerase II. These properties confer a good and broad antitumoral activity in vitro, with very low cytotoxic effect on the proliferation of normal cell lines and without damaging, in contrast with Ellipticine, the cell membrane model. The presented outcomes set the most active compounds as good candidates for pre-clinical studies useful in cancer treatment.

Graphical abstract

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Risk management and statistical multivariate analysis approach for design and optimization of satranidazole nanoparticles

Publication date: 1 January 2017
Source:European Journal of Pharmaceutical Sciences, Volume 96
Author(s): Shalaka Dhat, Swati Pund, Chandrakant Kokare, Pankaj Sharma, Birendra Shrivastava
Rapidly evolving technical and regulatory landscapes of the pharmaceutical product development necessitates risk management with application of multivariate analysis using Process Analytical Technology (PAT) and Quality by Design (QbD). Poorly soluble, high dose drug, Satranidazole was optimally nanoprecipitated (SAT-NP) employing principles of Formulation by Design (FbD). The potential risk factors influencing the critical quality attributes (CQA) of SAT-NP were identified using Ishikawa diagram. Plackett-Burman screening design was adopted to screen the eight critical formulation and process parameters influencing the mean particle size, zeta potential and dissolution efficiency at 30min in pH7.4 dissolution medium. Pareto charts (individual and cumulative) revealed three most critical factors influencing CQA of SAT-NP viz. aqueous stabilizer (Polyvinyl alcohol), release modifier (Eudragit® S 100) and volume of aqueous phase. The levels of these three critical formulation attributes were optimized by FbD within established design space to minimize mean particle size, poly dispersity index, and maximize encapsulation efficiency of SAT-NP. Lenth's and Bayesian analysis along with mathematical modeling of results allowed identification and quantification of critical formulation attributes significantly active on the selected CQAs. The optimized SAT-NP exhibited mean particle size; 216nm, polydispersity index; 0.250, zeta potential; −3.75mV and encapsulation efficiency; 78.3%. The product was lyophilized using mannitol to form readily redispersible powder. X-ray diffraction analysis confirmed the conversion of crystalline SAT to amorphous form. In vitro release of SAT-NP in gradually pH changing media showed <20% release in pH1.2 and pH6.8 in 5h, while, complete release (>95%) in pH7.4 in next 3h, indicative of burst release after a lag time. This investigation demonstrated effective application of risk management and QbD tools in developing site-specific release SAT-NP by nanoprecipitation.

Graphical abstract

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Editorial Board

Publication date: October 2016
Source:Clinical Immunology, Volume 171





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Psychiatric Comorbidity

Condition:   Otorhinolaryngologic Diseases
Intervention:   Other: Questionnaires
Sponsor:   Duke University
Not yet recruiting - verified September 2016

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Design, synthesis and biological evaluation of novel non-covalent piperidine-containing peptidyl proteasome inhibitors

Publication date: Available online 6 October 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Jiankang Zhang, Lixin Gao, Jianjun Xi, Li Sheng, Yanmei Zhao, Lei Xu, Yidan Shao, Shourong Liu, Rangxiao Zhuang, Yubo Zhou, Jia Li
A series of novel non-covalent piperidine-containing dipeptidyl derivatives were designed, synthesized and evaluated as proteasome inhibitors. All target compounds were tested for their proteasome chymotrypsin-like inhibitory activities, and selected derivatives were evaluated for the anti-proliferation activities against two multiple myeloma (MM) cell lines RPMI 8226 and MM-1S. Among all of these compounds, eight exhibited significant proteasome inhibitory activities with IC50 less than 20 nM, and four are more potent than the positive control Carfilzomib. Compound 28 displayed the most potent proteasome inhibitory activity (IC50: 1.4±0.1 nM) and cytotoxicities with IC50 values at 13.9±1.8 nM and 9.5±0.5 nM against RPMI 8226 and MM-1S, respectively. Additionally, the ex vivo blood cell proteasome inhibitory activities of compounds 24 and 27-29 demonstrated that the enzymatic metabolism in the whole blood could be well tolerated. All these experiments confirmed that the piperidine-containing non-covalent proteasome inhibitors are potential leads for exploring new anti-cancer drugs.

Graphical abstract

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Discovery and preliminary structure-activity relationship of 1H-indazoles with promising indolamine-2,3-dioxygenase 1(IDO1) inhibition properties

Publication date: Available online 6 October 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Shan Qian, Tao He, Wei Wang, Yanying He, Man Zhang, Lingling Yang, Guobo Li, Zhouyu Wang
Indoleamine 2, 3-dioxygenase 1 (IDO1)-mediated kynurenine pathway of tryptophan degradation is identified as an important immune effector pathway in the tumor cells to escape a potentially effective immune response. IDO1 is an attractive target for anticancer therapy and the discovery of IDO1 inhibitors has been intensely ongoing in both academic research laboratories and pharmaceutical organizations. Our study discovered that 1H-indazole was a novel key pharmacophore with potent IDO1 inhibitory activity. A series of new 1H-indazole derivatives were synthesized and determined the enzyme inhibitory activities, and the compound 2g exhibited the highest activity with an IC50 value of 5.3 μM. The structure-activity relationships (SARs) analysis of the 1H-indazole derivatives as novel IDO1 inhibitors indicated that the 1H-indazole scaffold is necessary for IDO1 inhibition, and the substituent groups at the both 4-position and 6-position largely affect inhibitory activity. The docking model exhibited that the effective interactions of 1H-indazoles with ferrous ion of heme and key residues of hydrophobic Pocket A and B ensured the IDO1 inhibitory activities. The study suggested that the 1H-indazole was a novel interesting scaffold for IDO inhibition for further development.

Graphical abstract

http://ift.tt/2dxLRZm

Melanogenesis inhibitory activity of a 7-O-9’-linked neolignan from Alpinia galanga fruit

Publication date: Available online 6 October 2016
Source:Bioorganic & Medicinal Chemistry
Author(s): Yoshiaki Manse, Kiyofumi Ninomiya, Ryosuke Nishi, Iyori Kamei, Yushi Katsuyama, Takahito Imagawa, Saowanee Chaipech, Osamu Muraoka, Toshio Morikawa
An aqueous acetone extract from the fruit of Alpinia galanga (Zingiberaceae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC50 = 7.3 μg/mL). Through bioassay-guided separation of the extract, a new 7-O-9'-linked neolignan, named galanganol D diacetate (1), was isolated along with 16 known compounds including 14 phenylpropanoids (2–15). The structure of 1, including its absolute stereochemistry in the C-7 position, was elucidated by means of extensive NMR analysis and total synthesis. Among the isolates, 1 (IC50 = 2.5 μM), 1'S-1'-acetoxychavicol acetate (2, 5.0 μM), and 1'S-1'-acetoxyeugenol acetate (3, 5.6 μM) exhibited a relatively potent inhibitory effect without notable cytotoxicity at effective concentrations. The following structural requirements were suggested to enhance the inhibitory activity of phenylpropanoids on melanogenesis: (i) compounds with 4-acetoxy group exhibit higher activity than those with 4-hydroxy group; (ii) 3-methoxy group dose not affect the activity; (iii) acetylation of the 1'-hydroxy moiety enhances the activity; and (iv) phenylpropanoid dimers with the 7-O-9'-linked neolignan skeleton exhibited higher activity than those with the corresponding monomer. Their respective enantiomers [1' (IC50 = 1.9 μM) and 2' (4.5 μM)] and racemic mixtures [(±)-1 (2.2 μM) and (±)-2 (4.4 μM)] were found to exhibit melanogenesis inhibitory activities equivalent to those of the naturally occurring optical active compounds (1 and 2). Furthermore, the active compounds 1–3 inhibited tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA expressions, which could be the mechanism of melanogenesis inhibitory activity.

Graphical abstract

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Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events

Publication date: Available online 6 October 2016
Source:Journal of Anxiety Disorders
Author(s): Amy E. Lansing, Wendy Y. Plante, Audrey N. Beck
Despite growing recognition that cumulative adversity (total stressor exposure), including complex trauma, increases the risk for psychopathology and impacts development, assessment strategies lag behind: Trauma-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (parental separations) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities.



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Is Disgust Proneness Sensitive to Treatment for OCD Among Youth? Examination of Diagnostic Specificity and Symptom Correlates

Publication date: Available online 6 October 2016
Source:Journal of Anxiety Disorders
Author(s): Kelly A. Knowles, Megan A. Viar-Paxton, Bradley C. Riemann, David M. Jacobi, Bunmi O. Olatunji
Although disgust proneness has been implicated in obsessive-compulsive disorder (OCD), there is a paucity of research examining change in disgust proneness during treatment as well as the correlates of such change, especially in children. This study examined the relationship between changes in disgust proneness and disorder-specific symptoms during residential treatment among youth with OCD, anxiety, and mood disorders. Youth ages 12-18 (n=472) completed pre- and post-outcome measures of OCD, anxiety, and mood symptoms and disgust proneness. Results indicate that although disgust proneness decreases during treatment for youth with OCD, anxiety, and mood disorders, youth with primary OCD experienced the greatest decrease in disgust proneness over the course of treatment. Reductions in disgust proneness during treatment were significantly correlated with reductions in multiple symptom measures, with the strongest correlations between reductions in disgust proneness and OCD symptoms. Implications and directions for future research are discussed.



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4-Hydroxynonenal dependent alteration of TRPV1-mediated coronary microvascular signaling

Publication date: December 2016
Source:Free Radical Biology and Medicine, Volume 101
Author(s): Daniel J. DelloStritto, Pritam Sinharoy, Patrick J. Connell, Joseph N. Fahmy, Holly C. Cappelli, Charles K. Thodeti, Werner J. Geldenhuys, Derek S. Damron, Ian N. Bratz
We demonstrated previously that TRPV1-dependent regulation of coronary blood flow (CBF) is disrupted in diabetes. Further, we have shown that endothelial TRPV1 is differentially regulated, ultimately leading to the inactivation of TRPV1, when exposed to a prolonged pathophysiological oxidative environment. This environment has been shown to increase lipid peroxidation byproducts including 4-Hydroxynonenal (4-HNE). 4-HNE is notorious for producing protein post-translation modification (PTM) via reactions with the amino acids: cysteine, histidine and lysine. Thus, we sought to determine if 4-HNE mediated post-translational modification of TRPV1 could account for dysfunctional TRPV1-mediated signaling observed in diabetes. Our initial studies demonstrate 4-HNE infusion decreases TRPV1-dependent coronary blood flow in C57BKS/J (WT) mice. Further, we found that TRPV1-dependent vasorelaxation was suppressed after 4-HNE treatment in isolated mouse coronary arterioles. Moreover, we demonstrate 4-HNE significantly inhibited TRPV1 currents and Ca²⁺ entry utilizing patch-clamp electrophysiology and calcium imaging respectively. Using molecular modeling, we identified potential pore cysteines residues that, when mutated, could restore TRPV1 function in the presence of 4-HNE. Specifically, complete rescue of capsaicin-mediated activation of TRPV1 was obtained following mutation of pore Cysteine 621. Finally, His tag pull-down of TRPV1 in HEK cells treated with 4-HNE demonstrated a significant increase in 4-HNE binding to TRPV1, which was reduced in the TRPV1 C621G mutant. Taken together these data suggest that 4-HNE decreases TRPV1-mediated responses, at both the in vivo and in vitro levels and this dysfunction can be rescued via mutation of the pore Cysteine 621. Our results show the first evidence of an amino acid specific modification of TRPV1 by 4-HNE suggesting this 4-HNE-dependent modification of TRPV1 may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes.



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Scholar : These new articles for Atmospheric and Oceanic Science Letters are available online

The online platform for Taylor & Francis Online content New for Atmospheric and Oceanic Science Letters and online now on Taylor & Francis Online: Original Articles Simulation of the evolution of the latent heat processes in a mesoscale convective system accompanied by heavy rainfall over the Guangzhou region of South China | Jiang-Nan LI, Kai-Lu WU, Chen-Hui DING, Chao-Feng YANG, Fang-Zhou LI, Dong-Hai WANG & Ye-Rong FENG Pages: 1-15 | DOI: 10.1080/16742834.2017.1243441This is the author accepted version which has not been proofed or edited Is the interdecadal circumglobal teleconnection pattern excited by the Atlantic multidecadal Oscillation? | Jian-She LIN, Bo WU & Tian-Jun ZHOU Pages: 1-7 | DOI: 10.1080/16742834.2016.1233800 Passionate about Social Media? Read our Social Media Research collection. This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Corrections are available online

The online platform for Taylor & Francis Online content New for Corrections and online now on Taylor & Francis Online: Original Articles Capital and Punishment: A Novel Model of Reoffending Amanda P. Cook Pages: 1-19 | DOI: 10.1080/23774657.2016.1234952 Time and tide wait for no man (or woman). Explore the multidisciplinary TIME Collection now. This message is personalised to your status as a society member. Please do not forward this email. To recommend content, please use the social sharing tools on the website. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Filler characteristics of modern dental resin composites and their influence on physico-mechanical properties

Publication date: Available online 6 October 2016
Source:Dental Materials
Author(s): Luc D. Randolph, William M. Palin, Gaëtane Leloup, Julian G. Leprince
ObjectiveThe mechanical properties of dental resin-based composites (RBCs) are highly dependent on filler characteristics (size, content, geometry, composition). Most current commercial materials are marketed as "nanohybrids" (i.e. filler size <1μm). In the present study, filler characteristics of a selection of RBCs were described, aiming at identifying correlations with physico-mechanical properties and testing the relevance of the current classification.MethodsMicron/sub-micron particles (> or <500nm) were isolated from 17 commercial RBCs and analyzed by laser diffractrometry and/or electron microscopy. Filler and silane content were evaluated by thermogravimetric analysis and a sedimentation technique. The flexural modulus (Eflex) and strength (σflex) and micro-hardness were determined by three-point bending or with a Vickers indenter, respectively. Sorption was also determined. All experiments were carried out after one week of incubation in water or 75/25 ethanol/water.ResultsAverage size for micron-sized fillers was almost always higher than 1μm. Ranges for mechanical properties were: 3.7<Eflex^water<16.3GPa, 86<σflex^water<161MPa and 23.7<hardness^water<108.3HV0.2/30. Values generally decreased after storage in ethanol/water (Δmax=86%). High inorganic filler contents (>75wt%) were associated with the highest mechanical properties (Eflex and σflex>12GPa and 130MPa, respectively) and lowest solvent sorption (∼0.3%).SignificanceMechanical properties and filler characteristics significantly vary among modern RBCs and the current classification does not accurately illustrate either. Further, the chemical stability of RBCs differed, highlighting differences in resin and silane composition. Since Eflex and sorption were well correlated to the filler content, a simple and unambiguous classification based on such characteristic is suggested, with three levels (ultra-low fill, low-fill and compact resin composites).



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Assessing head and neck cancer patient preferences and expectations: A systematic review

Publication date: November 2016
Source:Oral Oncology, Volume 62
Author(s): Pierre Blanchard, Robert J. Volk, Jolie Ringash, Susan K. Peterson, Katherine A. Hutcheson, Steven J. Frank
IntroductionTo enhance the value of care, interventions should aim at improving endpoints that matter to patients. The preferences of head and neck cancer patients regarding treatment outcomes are therefore a major topic for patient-centered research.MethodsA systematic review (PROSPERO number CRD42016035692) was conducted by searching electronic databases (Medline, Embase, Cochrane, CINAHL) for articles evaluating patient or surrogate preferences in head and neck cancer. A qualitative review was performed but no quantitative synthesis.ResultsOf 817 references retrieved, 20full-text articles were eventually included in the qualitative analysis Disease sites included mixed head and neck tumor sites, n=9; larynx, n=6; oropharynx/oral cavity, n=5. Overall, patients prioritized survival over functional endpoints. However, preferences and utility scores varied greatly between patients and healthy subjects, and differences were less pronounced with spouses or healthcare providers. Findings from studies of laryngeal preservation are consistent and conclude that a subset of patients would be willing to compromise a certain amount of survival to avoid laryngectomy. On the other hand, studies of patients with oropharyngeal cancer are too heterogeneous to draw conclusions about acceptable functional trade-offs or priorities, and should be the focus of future research.ConclusionFuture research surrounding head and neck cancer patients will most likely be clinically applicable if the questions are focused on well-defined patient groups and treatment options. Gathering reliable and valid quality-of-life data, designing patient preference studies that use reliable and generalizable methods, and using the results to develop decision aids for shared decision-making strategies are recommended going forward.



http://ift.tt/2dVeUYC

Identification of a gene expression signature in peripheral blood of multiple sclerosis patients treated with disease-modifying therapies

Publication date: Available online 5 October 2016
Source:Clinical Immunology
Author(s): Chiara Cordiglieri, Fulvio Baggi, Pia Bernasconi, Dimos Kapetis, Elisa Faggiani, Alessandra Consonni, Francesca Andreetta, Rita Frangiamore, Paolo Confalonieri, Carlo Antozzi, Renato Mantegazza
Multiple Sclerosis (MS) is an inflammatory disease with neurodegenerative alterations, ultimately progressing to neurological handicap. Therapies are effective in counteracting inflammation but not neurodegeneration. Biomarkers predicting disease course or treatment response are lacking. We investigated whether altered gene and protein expression profiles were detectable in the peripheral blood of 78 relapsing remitting MS (RR-MS) patients treated by disease-modifying therapies. A discovery/validation study on RR-MS responsive to glatiramer acetate identified 8 differentially expressed genes: ITGA2B, ITGB3, CD177, IGJ, IL5RA, MMP8, P2RY12, and S100β. A longitudinal study on glatiramer acetate, Interferon-β, or Fingolimod treated RR-MS patients confirmed that 7 out of 8 genes were downregulated with reference to the different therapies, whereas S100β was always upregulated. Thus, we identified a peripheral gene signature associated with positive response in RR-MS which may also explain drug immunomodulatory effects. The usefulness of this signature as a biomarker needs confirmation on larger series of patients.



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Successful treatment of palmoplantar pustulosis with rheumatoid arthritis, with tofacitinib: Impact of this JAK inhibitor on T-cell differentiation

Publication date: Available online 5 October 2016
Source:Clinical Immunology
Author(s): Tomohiro Koga, Tomohito Sato, Masataka Umeda, Shoichi Fukui, Yoshiro Horai, Shin-ya Kawashiri, Naoki Iwamoto, Kunihiro Ichinose, Hideki Nakamura, Atsushi Kawakami




http://ift.tt/2dNMg6O

HIC1 epigenetically represses CIITA transcription in B lymphocytes

Publication date: Available online 6 October 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Sheng Zeng, Yuyu Yang, Xian Cheng, Bisheng Zhou, Ping Li, Yuhao Zhao, Xiaocen Kong, Yong Xu
Differentiation of B lymphocytes into isotope-specific plasma cells represents a hallmark event in adaptive immunity. During B cell maturation, expression of class II transactivator (CIITA) gene is down-regulated although the underlying epigenetic mechanism is not completely defined. Here we report that hypermethylated in cancer 1 (HIC1) was up-regulated in differentiating B lymphocytes paralleling CIITA repression. Over-expression of HIC1 directly repressed endogenous CIITA transcription in B cells. Reporter assay and chromatin immunoprecipitation (ChIP) assay confirmed that HIC1 bound to the proximal CIITA type III promoter (−545/−113); mutation of a conserved HIC1 site within this region abrogated CIITA trans-repression. More important, depletion of HIC1 with small interfering RNA (siRNA) restored CIITA expression in differentiating B cells. Mechanistically, HIC1 preferentially interacted with and recruited DNMT1 and DNMT3b to the CIITA promoter to synergistically repress CIITA transcription. On the contrary, silencing of DNMT1/DNMT3b or inhibition of DNMT activity with 5-aza-dC attenuated CIITA trans-repression. Therefore, our data identify HIC1 as a novel factor involved in B cell differentiation acting as an epigenetic repressor of CIITA transcription.



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New properties with old materials: Layered black phosphorous

Publication date: Available online 5 October 2016
Source:Nano Today
Author(s): Tianchao Niu
Layered black phosphorous (BP), its tunable direct bandgap, higher carrier mobility and unique in-plane anisotropy, enables it to a promising candidate in design and optimization of electronics and optoelectronic devices with excellent performance. Although recent studies and perspectives aim at bringing this material to a level of maturity, the lack of wafer scale production and the surface reactivity of BP hindered a fully industrial processes. Here, we addressed the probable solutions to overcome these challenges black phosphorous was facing.

Graphical abstract

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Interaction of O2 with monolayer MoS2: Effect of doping and hydrogenation

Publication date: 5 January 2017
Source:Materials & Design, Volume 113
Author(s): B. Zhao, L.L. Liu, G.D. Cheng, T. Li, N. Qi, Z.Q. Chen, Z. Tang
The interaction of O2 with doped monolayer MoS2 and the effect of hydrogenation are studied by first-principles calculations coupled with the CI-NEB method. Surface chemically inertness of the MoS2 (001) plane can be broken by doping with Co, Ni and Cu atoms. Impurity levels are induced around the Fermi level and lead to the decrease of band gap, which is beneficial to the adsorption of O2 molecule. The activated oxygen atoms are produced through a dissociation reaction. The introduction of hydrogen atoms into the surface of doped MoS2 system presents favorable effect for O2 adsorption and dissociation. More impurity levels appear in the hydrogenated MoS2-Co/Ni system, and more electrons are localized at 3d orbital of Co/Ni atom, these systems all present excellent adsorption capacity. Hydrogenation reaction occurs by a hydrogen adatom smoothly migrating to the adsorbed O2 with the formation of OOH radical. The elongated OO bond of OOH radical can be dissociated with a lower activation energy barrier, producing an OH radical and activated oxygen atom. Our theoretical studies suggest that the doped monolayer MoS2 system is effective for capturing O2 molecule, and the hydrogenation is found to facilitate adsorption and dissociation of O2 molecule.

Graphical abstract

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Histopathologic Validation of Grayscale Carotid Plaque Characteristics Related to Plaque Vulnerability

Publication date: Available online 5 October 2016
Source:Ultrasound in Medicine & Biology
Author(s): Carol C. Mitchell, James H. Stein, Thomas D. Cook, Shahriar Salamat, Xiao Wang, Tomy Varghese, Daren C. Jackson, Carolina Sandoval Garcia, Stephanie M. Wilbrand, Robert J. Dempsey
Inflammation and angiogenesis play major roles in carotid plaque vulnerability. The purpose of this study was to determine whether gray-scale features of carotid plaques are associated with histologic markers for inflammation. Thirty-eight individuals completed a dedicated research carotid ultrasound exam before carotid endarterectomy. Gray-scale analysis was performed on plaque images to measure plaque echogenicity (gray-scale median [GSM] pixel brightness), plaque area, presence of discrete white areas (DWAs) and the percent of black area near the lumen on any one component of the plaque. Plaques with higher ultrasound GSM had greater percent calcification (p = 0.013) on histopathology. Presence of an ultrasound DWA was associated with more plaque hemosiderin (p = 0.0005) and inflammation (p = 0.019) on histopathology examination. The percent of plaque black area in any one component was associated with a higher score for macroscopic ulceration (p = 0.028). Ultrasound plaque characteristics (GSM, DWAs and black areas) represent histopathologic markers associated with plaque vulnerability. ClinicalTrials.gov identifier: NCT02476396.



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Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI

Objective

To determine if functional imaging using ¹¹C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment.

Design/methods

Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied.

Results

Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS.

Conclusions

In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).

http://ift.tt/2dB5GNR

Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome

Objective

McCune–Albright syndrome (MAS) is a rare disorder with a broad spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP.

Design

Retrospective cohort analysis.

Methods

Clinical data, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height and adult height.

Results

Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 ± 2.6 years (mean ± 1 s.d.) (range: 0.5–10.9) and mean follow-up was 6.0 ± 3.3 years (range: 0.5–15.0), for a total of 135.9 person-years of follow-up. Letrozole treatment was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (BA/CA) from 1.7 (IQR: 2.3) to 0.5 (IQR: 0.4) (P < 0.0001), and growth velocity Z-scores, which declined from 2.2 ± 2.3 to –0.6 ± 1.6 (P = 0.0004). Predicted adult height Z-scores increased significantly from –2.9 ± 3.2 to –0.8 ± 1.5 for subjects on treatment (P = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from –1.5 to 1.7 (median: –0.6), which were increased in comparison with untreated historical controls (P = 0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period.

Conclusions

In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height.

http://ift.tt/2e5B0qM

ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves disease

Thyroid hormones are essential developmental factors, and Graves' disease (GD) may severely complicate a pregnancy. This review describes how pregnancy changes the risk of developing GD, how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD. Standard therapy of GD in pregnancy is anti-thyroid drugs. However, new studies have shown considerable risk of birth defects if these drugs are used in specific weeks of early pregnancy, and this should be taken into consideration when planning therapy and control of women who may in the future become pregnant. Early pregnancy is a period of major focus in GD, where pregnancy should be diagnosed as soon as possible, and where important and instant change in therapy may be warranted. Such change may be an immediate stop of anti-thyroid drug therapy in patients with a low risk of rapid relapse of hyperthyroidism, or it may be an immediate shift from methimazole/carbimazole (with risk of severe birth defects) to propylthiouracil (with less risk), or maybe to other types of therapy where no risk of birth defects have been observed. In the second half of pregnancy, an important concern is that not only the mother with GD but also her foetus should have normal thyroid function.

http://ift.tt/2dB5zlh

MECHANISMS IN ENDOCRINOLOGY: Parity and risk of type 2 diabetes: a systematic review and dose-response meta-analysis

Objective

Epidemiologic studies regarding the association between parity and risk of type 2 diabetes have yielded inconsistent results. Therefore, we performed a systematic review and dose-response meta-analysis to determine the relation between parity and type 2 diabetes risk.

Methods

We searched PubMed and Embase for published epidemiologic studies that assessed the relation between parity and risk of type 2 diabetes up to 31 March 2016. A dose-response random-effects model was used to combine study-specific relative risks (RRs) and 95% confidence intervals (CIs). Potential sources of heterogeneity were explored by meta-regression and subgroup analyses.

Results

Seven cohort studies, 1 case-control study and 9 cross-sectional studies including 296 923 participants were eligible for inclusion. The combined RR for the highest versus lowest category of parity indicated a 54% increment in type 2 diabetes risk (95% CI: 29–83%). In the cubic spline model, a nonlinear association was found between parity and risk of type 2 diabetes (P = 0.02 for nonlinearity). Compared with nulliparous women, the estimated RR (95% CI) of type 2 diabetes for women with one to seven children was 1.01 (0.96–1.07), 1.08 (1.00–1.16), 1.20 (1.12–1.30), 1.32 (1.22–1.42), 1.37 (1.27–1.48), 1.39 (1.26–1.52) and 1.39 (1.23–1.57) respectively.

Conclusions

Higher parity is significantly associated with an increased risk of type 2 diabetes. Further studies are warranted to fully adjust for the potential confounders and explore the causality between parity and type 2 diabetes risk.

http://ift.tt/2e5z3um

The link between metabolic features and TSH levels in polycystic ovary syndrome is modulated by the body weight: an euglycaemic-hyperinsulinaemic clamp study

Objective

To evaluate the link among thyroid function, glucose/insulin metabolism and steroid hormones in women with polycystic ovary syndrome (PCOS), and to verify if the body mass index (BMI) might influence the interplay between PCOS features and subclinical hypothyroidism (SCH).

Study design

Case–control study conducted from January to December 2014.

Methods

One-hundred fifty-four young women with PCOS, according to Rotterdam criteria, and 88 controls were enrolled in an academic research environment. Anthropometric evaluation, hormonal and lipid assays, oral glucose tolerance test (OGTT) and euglycaemic–hyperinsulinaemic clamp were performed. Hirsutism was assessed with the Ferriman–Gallwey (FG) score.

Main results

SCH was found in 14% of PCOS subjects and in 1% of controls (P < 0.01). In PCOS women, TSH levels were directly correlated with fasting glycaemia, but not with other hormonal and metabolic parameters. When PCOS patients were classified on the basis of BMI, TSH levels significantly correlated with insulin secretion, insulin resistance, DHEAS and cortisol levels in obese PCOS women. Inverse correlations were found between TSH and both oestradiol and SHBG in the same group. In nonobese PCOS patients, only waist-to-hip ratio values were correlated with TSH. The prevalence of SCH was not different between nonobese and obese PCOS groups (14 and 15% respectively). However, SCH was associated with higher levels of insulin, DHEAS, cortisol and FG score only in the obese subgroup.

Conclusions

Our data confirm that the prevalence of SCH is increased in PCOS women. The presence of SCH is associated with endocrine and metabolic imbalances of PCOS, and the excessive body weight seems to promote this interplay.

http://ift.tt/2dB5iip

Epidemiological characteristics and methodological quality of meta-analyses on diabetes mellitus treatment: a systematic review

Objective

Well-conducted meta-analyses (MAs) are considered as one of the best sources of clinical evidence for treatment decision. MA with methodological flaws may introduce bias and mislead evidence users. The aim of this study is to investigate the characteristics and methodological quality of MAs on diabetes mellitus (DM) treatments.

Design

Systematic review.

Methods

Cochrane Database of Systematic Review and Database of Abstract of Reviews of Effects were searched for relevant MAs. Assessing methodological quality of systematic reviews (AMSTAR) tool was used to evaluate the methodological quality of included MAs. Logistic regression analysis was used to identify association between characteristics of MA and AMSTAR results.

Results

A total of 252 MAs including 4999 primary studies and 13,577,025 patients were included. Over half of the MAs (65.1%) only included type 2 DM patients and 160 MAs (63.5%) focused on pharmacological treatments. About 89.7% MAs performed comprehensive literature search and 89.3% provided characteristics of included studies. Included MAs generally had poor performance on the remaining AMSTAR items, especially in assessing publication bias (39.3%), providing lists of studies (19.0%) and declaring source of support comprehensively (7.5%). Only 62.7% MAs mentioned about harm of interventions. MAs with corresponding author from Asia performed less well in providing MA protocol than those from Europe.

Conclusions

Methodological quality of MA on DM treatments was unsatisfactory. There is considerable room for improvement, especially in assessing publication bias, providing lists of studies and declaring source of support comprehensively. Also, there is an urgent need for MA authors to report treatment harm comprehensively.

http://ift.tt/2e5z7dD

Impact of sleep behavior on glycemic control in type 1 diabetes: the role of social jetlag

Background

Sleep behavior is changing toward shorter sleep duration and a later chronotype. It results in a sleep debt that is acquitted on work-free days, inducing a small but recurrent sleep misalignment each week, referred to as "social jetlag". These sleep habits could affect health through misalignment with circadian rhythms.

Objectives

The primary objective is to address the impact of sleep behavior on glycemic control, assessed by HbA1c, in patients with type 1 diabetes, independently of other lifestyle or sleep-related factors. The secondary objective is to address whether circadian phase affects glycemic control.

Design

In total, 80 adult patients with type 1 diabetes (46% female) were included in a clinical cohort study.

Methods

Sleep behavior was addressed objectively by a 7-day actimetry, lifestyle by questionnaires, sleep breathing disorders by nocturnal oximetry and circadian phase by dim light melatonin onset (DLMO).

Results

Univariate analyses showed that chronotype (r = 0.23, P = 0.042) and social jetlag (r = 0.30, P = 0.008) were significantly associated with HbA1c. In multivariable analysis, social jetlag was the only sleep habit independently associated with HbA1c (β = 0.012 (0.006; 0.017), P < 0.001). HbA1c was lower in patients with a social jetlag below versus above the median (7.7% (7.1–8.7) and 8.7% (7.6–9.8), P = 0.011). DLMO was not associated with HbA1c. However, the later the DLMO, the worse the sleep efficiency (r = –0.41, P < 0.001) and fragmentation index (r = 0.35, P = 0.005).

Conclusions

Social jetlag, a small but recurrent circadian misalignment, is associated with worse glycemic control in type 1 diabetes, whereas circadian phase is not. Further intervention studies should address the potential improvement of glycemic control by correcting social jetlag.

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Limited value for urinary 5-HIAA excretion as prognostic marker in gastrointestinal neuroendocrine tumours

Objective

To determine if urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion is of prognostic value for overall survival (OS) in patients with a gastrointestinal neuroendocrine tumour (NET) and to compare the prognostic value with patient characteristics, ENETS/WHO grading, ENETS TNM staging and biomarkers.

Design and methods

Data was collected from patients with a gastrointestinal NET or a NET with gastrointestinal metastases and available 5-HIAA excretion in 24-h urine samples. Laboratory results were stratified for urinary 5-HIAA and chromogranin A (CgA): <2x upper limit of normal (ULN), 2–10x ULN, or >10x ULN. For neuron-specific enolase (NSE), this was the reference range or >1x ULN. OS was compared using Kaplan–Meier and log-rank tests, and hazard ratios were calculated using Cox regression for univariate and multivariate analyses.

Results

A total of 371 patients were included, 46.6% female with a mean age of 59.9 years. OS was shortest in patients with urinary 5-HIAA excretion >10x ULN vs reference range (median 83 months vs 141 months, P = 0.002). In univariate analysis, urinary 5-HIAA excretion >10x ULN was a negative predictor (HR 1.62, 95% CI: 1.09–2.39). However, in multivariate analysis, only age (HR 1.04, 95% CI: 1.01–1.08), grade 3 disease (HR 5.09, 95% CI: 2.20–11.79), NSE >1x ULN (HR 2.36, 95% CI: 1.34–4.14) and CgA >10x ULN (HR 3.61, 95% CI: 1.56–8.34) remained as the predictors.

Conclusion

Urinary 5-HIAA excretion >10x ULN is a negative predictor for OS. However, when added to other biomarkers and grading, it is no longer a predictor for OS. Therefore, it should only be determined to assess carcinoid syndrome and not for prognostic value.

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Stress hormone release is a key component of the metabolic response to lipopolysaccharide: studies in hypopituitary and healthy subjects

Objective

Acute and chronic inflammatory and metabolic responses are generated by lipopolysaccharide (LPS) during acute illness and in the pathogenesis of the metabolic syndrome, type 2 diabetes and cardiovascular disease, but whether these responses depend on intact pituitary release of hormones are not clearly identified. We compared the metabolic effects of LPS in hypopituitary patients (HPs) (in the absence of growth hormone (GH) and ACTH responses) and healthy control subjects (CTR) (with normal pituitary hormone responses).

Design

Single-blind randomized.

Methods

We compared the effects of LPS on glucose, protein and lipid metabolism in eight HP and eight matched CTR twice during 4-h basal and 2-h hyperinsulinemic–euglycemic clamp conditions with muscle and fat biopsies in each period during infusion with saline or LPS.

Results

LPS increased cortisol and GH levels in CTR but not in HP. Also, it increased whole-body palmitate fluxes (3-fold) and decreased palmitate-specific activity (SA) 40–50% in CTR, but not in HP. G(0)/G(1) Switch Gene 2 (G0S2 – an inhibitor of lipolysis) adipose tissue (AT) mRNA was decreased in CTR. Although LPS increased phenylalanine fluxes significantly more in CTR, there was no difference in glucose metabolism between groups and intramyocellular insulin signaling was unaltered in both groups.

Conclusions

LPS increased indices of lipolysis and amino acid/protein fluxes significantly more in CTR compared with HP and decreased adipocyte G0S2 mRNA only in CTR. Thus, in humans intact pituitary function and appropriate cortisol and GH release are crucial components of the metabolic response to LPS.

http://ift.tt/2dB66Uo

Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

Objective

Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional.

Design and methods

We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers.

Results

Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin.

Conclusions

Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function.

http://ift.tt/2e5yKQ2