Cutaneous malignancies identified on an inpatient Dermatology consult service

Abstract

The role of inpatient Dermatology consultation and biopsy in evaluating suspicious cutaneous lesions is unknown.^1-3 Previous studies analyzed the diagnostic accuracy and utility of consultations for common rashes and infectious diseases, without considering suspicious lesions.^4-6 We sought to describe the frequency, clinicopathologic characteristics, and outcomes of suspicious lesions biopsied on an inpatient Dermatology consult service

This article is protected by copyright. All rights reserved.

http://ift.tt/2mpyxaK

Better compliance with hypofractionation vs. conventional fractionation in adjuvant breast cancer radiotherapy

Abstract

Background

The aim of the study was to identify factors significantly associated with the occurrence of unintended treatment interruptions in adjuvant breast cancer radiotherapy.

Patients and methods

Patients treated with postoperative radiotherapy of the breast or chest wall between March 2014 and August 2016 were evaluated. The radiotherapy regimens and techniques applied were either conventional fractionation (CF; 28 daily fractions of 1.8 Gy or 25 fractions of 2.0 Gy) or hypofractionation (HF; 15 daily fractions of 2.67 Gy) with inverse planned intensity-modulated radiotherapy (IMRT) or three-dimensional planned conformal radiotherapy (3DCRT). Logistic regression analysis was used to identify factors associated with noncompliance. Noncompliance was defined as the missing of at least one scheduled radiotherapy fraction.

Results

In all, 19 of 140 (13.6%) patients treated with HF and 39 of 146 (26.7%) treated with CF experienced treatment interruptions. Of 23 factors tested, the fractionation regimen emerged as the only independent significant prognostic factor for noncompliance on multivariate analysis (CF; p = 0.007; odds ratio, 2.3; 95% confidence interval, 1.3–4.2). No statistically significant differences concerning the reasons for treatment interruptions could be detected between patients treated with CF or HF.

Conclusion

HF is significantly associated with a better patient compliance with the prescribed radiotherapy schedule compared with CF. The data suggest that this finding is basically related to the shorter overall treatment time of HF.

http://ift.tt/2mh9tn3

Complexity in cancer stem cells and tumor evolution: towards precision medicine

Publication date: Available online 23 February 2017
Source:Seminars in Cancer Biology
Author(s): Caterina A.M. La Porta, Stefano Zapperi
In this review, we discuss recent advances on the plasticity of cancer stem cells and highlight their relevance to understand the metastatic process and to guide therapeutic interventions. Recent results suggest that the strict hierarchical structure of cancer cell populations advocated by the cancer stem cell model must be reconsidered since the depletion of cancer stem cells leads the other tumor cells to switch back into the cancer stem cell phenotype. This plasticity has important implications for metastasis since migrating cells do not need to be cancer stem cells in order to seed a metastasis. We also discuss the important role of the immune system and the microenvironment in modulating phenotypic switching and suggest possible avenues to exploit our understanding of this process to develop an effective strategy for precision medicine.



http://ift.tt/2l4dxVO

Editorial Board

Publication date: 1 March 2017
Source:Acta Biomaterialia, Volume 50





http://ift.tt/2l4iMVn

Biomimetic collagen/elastin meshes for ventral hernia repair in a rat model

Publication date: 1 March 2017
Source:Acta Biomaterialia, Volume 50
Author(s): Silvia Minardi, Francesca Taraballi, Xin Wang, Fernando J. Cabrera, Jeffrey L. Van Eps, Andrew B. Robbins, Monica Sandri, Michael R. Moreno, Bradley K. Weiner, Ennio Tasciotti
Ventral hernia repair remains a major clinical need. Herein, we formulated a type I collagen/elastin crosslinked blend (CollE) for the fabrication of biomimetic meshes for ventral hernia repair. To evaluate the effect of architecture on the performance of the implants, CollE was formulated both as flat sheets (CollE Sheets) and porous scaffolds (CollE Scaffolds). The morphology, hydrophylicity and in vitro degradation were assessed by SEM, water contact angle and differential scanning calorimetry, respectively. The stiffness of the meshes was determined using a constant stretch rate uniaxial tensile test, and compared to that of native tissue. CollE Sheets and Scaffolds were tested in vitro with human bone marrow-derived mesenchymal stem cells (h-BM-MSC), and finally implanted in a rat ventral hernia model. Neovascularization and tissue regeneration within the implants was evaluated at 6weeks, by histology, immunofluorescence, and q-PCR. It was found that CollE Sheets and Scaffolds were not only biomechanically sturdy enough to provide immediate repair of the hernia defect, but also promoted tissue restoration in only 6weeks. In fact, the presence of elastin enhanced the neovascularization in both sheets and scaffolds. Overall, CollE Scaffolds displayed mechanical properties more closely resembling those of native tissue, and induced higher gene expression of the entire marker genes tested, associated with de novo matrix deposition, angiogenesis, adipogenesis and skeletal muscles, compared to CollE Sheets. Altogether, this data suggests that the improved mechanical properties and bioactivity of CollE Sheets and Scaffolds make them valuable candidates for applications of ventral hernia repair.Statement of SignificanceDue to the elevated annual number of ventral hernia repair in the US, the lack of successful grafts, the design of innovative biomimetic meshes has become a prime focus in tissue engineering, to promote the repair of the abdominal wall, avoid recurrence. Our meshes (CollE Sheets and Scaffolds) not only showed promising mechanical performance, but also allowed for an efficient neovascularization, resulting in new adipose and muscle tissue formation within the implant, in only 6weeks. In addition, our meshes allowed for the use of the same surgical procedure utilized in clinical practice, with the commercially available grafts. This study represents a significant step in the design of bioactive acellular off-the-shelf biomimetic meshes for ventral hernia repair.

Graphical abstract

http://ift.tt/2lvmhrp

The Placebo and Nocebo Phenomena: Their Clinical Management and Impact on Treatment Outcomes

Publication date: Available online 23 February 2017
Source:Clinical Therapeutics
Author(s): Victor Chavarria, João Vian, Círia Pereira, João Data-Franco, Brisa S. Fernandes, Michael Berk, Seetal Dodd
PurposeThis overview focuses on placebo and nocebo effects in clinical trials and routine care. Our goal was to propose strategies to improve outcomes in clinical practice, maximizing placebo effects and reducing nocebo effects, as well as managing these phenomena in clinical trials.MethodsA narrative literature search of PubMed was conducted (January 1980–September 2016). Systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on placebo or nocebo effects in clinical practice were included in the qualitative synthesis. Search terms included: placebo, nocebo, clinical, clinical trial, clinical setting, placebo effect, nocebo effect, adverse effects, and treatment outcomes. This search was augmented by a manual search of the references of the key articles and the related literature.FindingsPlacebo and nocebo effects are psychobiological events imputable to the therapeutic context. Placebo is defined as an inert substance that provokes perceived benefits, whereas the term nocebo is used when an inert substance causes perceived harm. Their major mechanisms are expectancy and classical conditioning. Placebo is used in several fields of medicine, as a diagnostic tool or to reduce drug dosage. Placebo/nocebo effects are difficult to disentangle from the natural course of illness or the actual effects of a new drug in a clinical trial. There are known strategies to enhance clinical results by manipulating expectations and conditioning.ImplicationsPlacebo and nocebo effects occur frequently and are clinically significant but are underrecognized in clinical practice. Physicians should be able to recognize these phenomena and master tactics on how to manage these effects to enhance the quality of clinical practice.



http://ift.tt/2lds1mZ

Erratum to “Pitavastatin vs Pravastatin in Reduction of Remnant Lipoprotein Cholesterol in Patients with Dyslipidemias” Clin Ther. 2016;39:1250--1251

Publication date: Available online 22 February 2017
Source:Clinical Therapeutics
Author(s): Leonardo Roever




http://ift.tt/2lK13H3

Interleukin-10: A Compelling Therapeutic Target in Patients With Irritable Bowel Syndrome

Publication date: Available online 23 February 2017
Source:Clinical Therapeutics
Author(s): Sunil Kumar, Ratnakar Shukla, Prabhat Ranjan, Awanish Kumar
PurposePro- and antiinflammatory cytokines are important modulators of the immune response and play a major role in conditions of intestinal inflammation, such as irritable bowel syndrome (IBS). Cytokine production is regulated genetically, and imbalances in cytokine secretion may affect disease susceptibility and clinical outcomes of various conditions. There is a rapidly growing body of evidence to support an etiologic role for gastrointestinal infection and the associated immune activation in the development of postinfectious IBS. Other factors such as psychological stress, anxiety, and depression may likely be involved in the altered profiles of pro- and antiinflammatory cytokines that lead to chronic IBS.MethodsWe searched the literature using PubMed, MEDLINE, and Google Scholar with related key terms and prepared this review article on that basis.FindingsInterleukin (IL)-10 is a regulatory cytokine that inhibits both antigen presentation and the release of proinflammatory cytokines. Therefore, it is proposed as a potent antiinflammatory biological therapy for IBS.ImplicationsRecently, a strong interest in the therapeutic potential of IL-10 for IBS has developed. The diverse roles of IL-10 in IBS are reviewed here. We conducted an in-depth review on IL-10 and IBS to address this question. Future studies of IL-10 may provide new insights into IBS therapy.



http://ift.tt/2ldjNLM

Study on strengthening mechanism of Ti/Cu electron beam welding

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Shun Guo, Qi Zhou, Yong Peng, Xiangfang Xu, Chenglei Diao, Jian Kong, TianYuan Luo, KeHong Wang, Jun Zhu
Welding-brazing method is widely used for dissimilar metals welding. However, it is becoming increasingly difficult to further improve the connection strength by controlling the formation of the transition layer. In this study, an innovative welding method referred to as adjacent welding was addressed, which greatly improved the tensile strength of Ti/Cu dissimilar joint. The strength of new joint could reach up to 89% that of copper base metal, compared to the use of a traditional welding-brazing method which strength coefficient is within the limit of 70%. In order to determine the strengthening mechanism of adjacent welding, optical microscopy, SEM, EDS and XRD were applied for the analysis of microstructure and phase structure. Furthermore, tensile strength was also tested. The results show that due to the process of remelting and reverse solidification of intermetallic compounds (IMCs) layer, a less complex and thinner IMCs layer was formed and TiCu (553HV) with high embrittlement existing in the front of titanium substrate was changed into Ti2Cu (442HV). Performances of joints were optimized by these changes. An interpretation module was presented for the mechanism.

Graphical abstract

http://ift.tt/2lvhXbE

Phase transformations of the L12-Ti3Al phase in γ-TiAl alloy

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Shouzhen Cao, Shulong Xiao, Yuyong Chen, Lijuan Xu, Xiaopeng Wang, Jianchao Han, Yi Jia
A new phase L12-Ti3Al was found in the Ti-46Al-6Nb alloy after rapid-cooling and then annealing at 850°C for 5h. The transformation kinetics involving the L12 phase were observed by transmission electron microscopy (TEM): The plate-like L12 phase precipitates in the massive γ (γm) phase and then partially transforms into α2 or B2 phase; the transformations of bulk α2 (αb)→L12/L12→γ were also observed to form a fine lamellar structure with an average interlamellar spacing <20nm. The orientation relationships between γ, α2 and L12 phases were confirmed by TEM observation and crystallographic calculation, which are (001)γ//(001)L12, [010]γ//[010]L12, [100]γ//[100]L12 and (0001)α2//{111}L12, 〈112¯0〉α2//〈11¯0〉L12. The L12 phase was also observed in Ti-the 47Al alloy after the quenching-annealing process. Thermodynamic analysis of the transformations indicates that the γ→L12 transformation is extremely susceptible to temperature changes while transformations between the α2 and L12 phases are not.

Graphical abstract

http://ift.tt/2lva9qy

Highly sensitive and selective ethanol and acetone gas sensors based on modified ZnO nanomaterials

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Jinxiao Wang, Jun Yang, Ning Han, Xinyuan Zhou, Shuyan Gong, Jianfeng Yang, Peng Hu, Yunfa Chen
Nowadays, highly sensitive metal oxide semiconductor gas sensors are exerting a growing important influence on the detection of target gases. It is still challenging to get both high sensitivity and selectivity to effectively distinguish gas mixtures. In this study, Mn doped ZnO (MZO) is prepared by a facile co-precipitation method and then further modified by CdO addition. The results show that 2.2mol% MZO has high responses to both acetone and ethanol, while 10 mol% CdO activated 1mol% MZO exhibits excellent sensitivity to ethanol and neglectable response to acetone. This is explained by the enhanced alkalinity of ZnO by the CdO addition expelling acetone from adsorption onto the sensor surface, which is verified by temperature–programmed CO2 desorption. Moreover, the CdO-MZO gas sensor has an optimized working temperature of 240°C, far lower than 340°C of MZO, due to the higher oxidativity as proved by the temperature-programmed H2 reduction. The MZO and CdO-MZO gas sensors are then used as a sensor array to distinguish the ethanol and acetone concentrations in mixtures with varied ratios, showing the promise of the gas sensor property tailoring approach for future high performance gas sensors.

Graphical abstract

http://ift.tt/2lvgrGB

Defects engineering induced room temperature ferromagnetism in transition metal doped MoS2

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Yiren Wang, Li-Ting Tseng, Peter P. Murmu, Nina Bao, John Kennedy, Mihail Ionesc, Jun Ding, Kiyonori Suzuki, Sean Li, Jiabao Yi
First principle calculations are employed to calculate the electronic structure and magnetic properties of transition-metal doped MoS2 considering the effects of defect/defect complex. It shows that pure MoS2 with both Mo and S vacancy are nonmagnetic. Mn, Fe, Co and Ni substitution in Mo site all lead to spin polarized state. Considering defect complex, the results show that (TMMo+TMMo) defect complex has the lowest formation energy at high S pressure and prefers close to each other except for (CoMo+CoMo). Experimentally, we doped Mn, Co, Ni and Fe into MoS2 single crystals. The doping leads to room temperature ferromagnetic ordering and clustering, agreeing well with the first principle calculations.

Graphical abstract

http://ift.tt/2lvkBy7

Influence of WO3 addition on the material transfer behavior of the AgTiB2 contact material

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Hangyu Li, Xianhui Wang, Yong Xi, Yanfeng Liu, Xiuhua Guo
To clarify the effect of WO3 addition on the electrical performance of Ag-4wt.%TiB2 contact material, each contact pair was made 20,000 operations at 12 V, 29 A for the Ag-4wt.%TiB2 contact materials without and with WO3 addition. The morphology and chemical composition of arc eroded contact surface were characterized by scanning electron microscope and energy dispersive spectrometer, and the mass change before and after electrical contact test was determined as well. The results show that WO3 addition not only decreases the arc duration and arc energy, but also changes the arc erosion characteristics and material transfer mode. For the Ag-4wt.%TiB2 contact material without WO3 addition, the material transfer occurs from cathode to anode. However, it has an opposite change for the Ag-4wt.%TiB2 contact material with WO3 addition. Furthermore, WO3 addition can prevent the formation of cracks on the eroded surface.

Graphical abstract

http://ift.tt/2lvn23N

Shear dependent electrical property of conductive shear thickening fluid

Publication date: 5 May 2017
Source:Materials & Design, Volume 121
Author(s): Qian Chen, Mei Liu, Shouhu Xuan, Wanquan Jiang, Saisai Cao, Xinglong Gong
Conductive shear thickening fluid (C-STF) consisting of SiO2 particles, carbon nanotube (CNT) and ethyl glycol (EG) was developed. The shear thickening effect of C-STF was strengthened with the increasing CNT mass fraction. Different from the traditional shear thickening fluid (STF), the as-prepared C-STF showed unique electrical property due to presence of the conductive doping CNT. The initial resistance of C-STF varied from 94 kΩ to 18 kΩ at different CNT mass fractions (0.1wt%, 0.2wt%, 0.3wt% and 0.4wt%). Moreover, the resistance could be critically decreased once accounting the unexpected shear and the decrements reached to as high as 90%. Meanwhile, the shear dependent impedance spectroscopies at different shear rates were analyzed and an equivalent circuit model was proposed to investigate the microstructure dependent electrical property. This phenomenon not only gave much valuable information for understanding the detail shear thickening mechanism but also broadened their application in anti-impact sensor.

Graphical abstract

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Bone age in unilateral spastic cerebral palsy: is there a correlation with hand function and limb length?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Individualized early death and long-term survival prediction after stereotactic radiosurgery for brain metastases of non-small cell lung cancer: Two externally validated nomograms

Publication date: Available online 23 February 2017
Source:Radiotherapy and Oncology
Author(s): Jaap D. Zindler, Arthur Jochems, Frank J. Lagerwaard, Rosemarijne Beumer, Esther G.C. Troost, Daniëlle B.P. Eekers, Inge Compter, Peter-Paul van der Toorn, Marion Essers, Bing Oei, Coen W. Hurkmans, Anna M.E. Bruynzeel, Geert Bosmans, Ans Swinnen, Ralph T.H. Leijenaar, Philippe Lambin
IntroductionCommonly used clinical models for survival prediction after stereotactic radiosurgery (SRS) for brain metastases (BMs) are limited by the lack of individual risk scores and disproportionate prognostic groups. In this study, two nomograms were developed to overcome these limitations.Methods495 patients with BMs of NSCLC treated with SRS for a limited number of BMs in four Dutch radiation oncology centers were identified and divided in a training cohort (n=214, patients treated in one hospital) and an external validation cohort n=281, patients treated in three other hospitals). Using the training cohort, nomograms were developed for prediction of early death (<3months) and long-term survival (>12months) with prognostic factors for survival. Accuracy of prediction was defined as the area under the curve (AUC) by receiver operating characteristics analysis for prediction of early death and long term survival. The accuracy of the nomograms was also tested in the external validation cohort.ResultsPrognostic factors for survival were: WHO performance status, presence of extracranial metastases, age, GTV largest BM, and gender. Number of brain metastases and primary tumor control were not prognostic factors for survival. In the external validation cohort, the nomogram predicted early death statistically significantly better (p<0.05) than the unfavorable groups of the RPA, DS-GPA, GGS, SIR, and Rades 2015 (AUC=0.70 versus range AUCs=0.51–0.60 respectively). With an AUC of 0.67, the other nomogram predicted 1year survival statistically significantly better (p<0.05) than the favorable groups of four models (range AUCs=0.57–0.61), except for the SIR (AUC=0.64, p=0.34). The models are available on http://ift.tt/2mp6oAm nomograms predicted early death and long-term survival more accurately than commonly used prognostic scores after SRS for a limited number of BMs of NSCLC. Moreover these nomograms enable individualized probability assessment and are easy into use in routine clinical practice.



http://ift.tt/2lv3T1Q

Mismatch Repair Deficiency, Microsatellite Instability, and Survival in the MAGIC Trial

This study examines the association among mismatch repair deficiency, microsatellite instability, and survival in patients with resectable gastroesophageal cancer randomized to surgery alone or perioperative chemotherapy.

http://ift.tt/2mbCkMz

Telomere Length and Risk of Cancer and Non-Neoplastic Diseases

This Mendelian randomization study evaluates the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.

http://ift.tt/2mp2fwn

Using the National Cancer Database for Outcomes Research

This review describes the use of the National Cancer Database to study cancer care, with a focus on the advantages of using the database and important considerations that affect the interpretation of National Cancer Database studies.

http://ift.tt/2mbMJrC

A Large Skin Cancer Screening Quality Initiative

This study evaluates a skin cancer screening initiative for risk level of screened population and incidence and thickness of detected melanomas in screened vs unscreened patients of primary care clinics of a large health care system.

http://ift.tt/2mp60lI

PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle

Publication date: Available online 22 February 2017
Source:Journal of Dermatological Science
Author(s): Teruki Yanagi, Hiroo Hata, Eri Mizuno, Shinya Kitamura, Keisuke Imafuku, Shinichi Nakazato, Lei Wang, Hiroshi Nishihara, Shinya Tanaka, Hiroshi Shimizu
BackgroundPCTAIRE1 (also known as cyclin-dependent kinase 16 (Cdk16) and PCTK1) is a Cdk family protein that has been implicated in spermatogenesis. We recently revealed the function of PCTAIRE1 in the tumorigenesis of malignancies, including breast and prostate cancers; however, the tumorigenic function of PCTAIRE1 in cutaneous squamous cell carcinoma (SCC) remains unclear.ObjectiveIn this study, we investigated the role of PCTAIRE1 in the tumorigenesis of cutaneous SCCs.Methods and ResultsIn cutaneous/oral SCC A431, DJM-1, HSC-3 cells, PCTAIRE1 gene-knockdown was found to diminish cell proliferation as assessed by cell counting and clonogenic assays. FACS analyses of annexin V-PI staining and DNA content showed PCTAIRE1 knockdown to cause G2/M arrest followed by apoptosis. The depletion of PCTAIRE1 was found to lead to the accumulation of tumor suppressor p27 and down-regulation of c-Myc. In tumor xenografts of A431 cells, the conditional knockdown of PCTAIRE1 restores p27 protein expression and suppresses tumor growth. Clinically, in primary tumors from patients with SCC, PCTAIRE1 is more highly expressed in malignant lesions than in adjacent normal epidermis. Conversely, expression levels of p27 are significantly lower in SCC than in normal epidermis.ConclusionsOur findings reveal a crucial function for PCTAIRE1 in regulating p27, c-Myc levels and tumor growth in cutaneous SCC cells, suggesting that PCTAIRE1 could be a novel target for skin tumor treatment.



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Radionuclide therapy of malignant bone lesions

http://ift.tt/2mgFmvS

18F-FDG PET/CT in gastric MALT lymphoma: a bicentric experience

Abstract

Purpose

The role of 18F-FDG-PET/CT in evaluating gastric MALT lymphoma is still controversial. In the literature the detection rate of 18F-FDG-PET/CT in patients with gastric MALT lymphoma is variable, and the reason for this heterogeneity is not still clear. Our aim was to investigate the particular metabolic behavior of these lymphoma.

Materials and methods

Sixty-nine patients (26 female, 43 male) with histologically confirmed gastric MALT lymphoma who underwent a 18F-FDG-PET/CT for initial staging from two centers were included. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax), lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio and compared with Ann Arbor stage, epidemiological (age, sex), histological (presence of gastritis, ulcer, H. pylori infection, plasmacytic differentiation, Ki-67 index), and morphological (tumor size, superficial lesions or mass-forming) characteristics.

Results

Thirty-six patients (52 %) had positive PET/CT (average SUVmax was 9±6.7; lesion-to-liver SUVmax ratio 3.7±2.6, lesion-to-blood pool SUVmax ratio 4.8±3.3) at the corresponding gastric lesion; the remaining 33 were not 18F-FDG-avid. In the univariate analysis, 18F-FDG avidity was significantly associated with morphological features (mass forming p<0.001 and high maximum diameter p<0.001), Ann Arbor stage (p=0.010), and Ki67 index (p<0.001) and not correlated with age, sex, presence of gastritis, ulcer, Helicobacter pylori infection, and plasmacytic differentiation. In the multivariate analysis, the correlations with gross morphological appearance, Ann Arbor stage, and Ki-67 score were confirmed. SUVmax, lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio correlated significantly only with Ki67 index (p=0.047; p=0.012; p=0.042).

Conclusions

18F-FDG avidity was noted in 52 % of gastric MALT lymphoma and this avidity is correlated with gross morphological characteristics, tumor stage, and Ki-67 index. SUVmax, lesion-to-liver SUVmax ratio, and lesion-to-blood pool SUVmax ratio are correlated only with Ki-67 index, and only lesion-to-liver SUVmax ratio was independently associated with Ki-67 score.

http://ift.tt/2luVQ58

Diffuse 18 F-FDG accumulation in the subarachnoid space detected by PET/CT in a patient with subarachnoid hemorrhage and hyperglycemia

http://ift.tt/2mgngtQ

Targets and probes for non-invasive imaging of β-cells

Abstract

β-cells, located in the islets of the pancreas, are responsible for production and secretion of insulin and play a crucial role in blood sugar regulation. Pathologic β-cells often cause serious medical conditions affecting blood glucose level, which severely impact life quality and are life-threatening if untreated. With 347 million patients, diabetes is one of the most prevalent diseases, and will continue to be one of the largest socioeconomic challenges in the future. The diagnosis still relies mainly on indirect methods like blood sugar measurements. A non-invasive diagnostic imaging modality would allow direct evaluation of β-cell mass and would be a huge step towards personalized medicine. Hyperinsulinism is another serious condition caused by β-cells that excessively secrete insulin, like for instance β-cell hyperplasia and insulinomas. Treatment options with drugs are normally not curative, whereas curative procedures usually consist of the resection of affected regions for which, however, an exact localization of the foci is necessary. In this review, we describe potential tracers under development for targeting β-cells with focus on radiotracers for PET and SPECT imaging, which allow the non-invasive visualization of β-cells. We discuss either the advantages or limitations for the various tracers and modalities. This article concludes with an outlook on future developments and discuss the potential of new imaging probes including dual probes that utilize functionalities for both a radioactive and optical moiety as well as for theranostic applications.

http://ift.tt/2luXYd7

Erratum to: A rare case of rectal carcinoma and prostate carcinoma with coexistent Paget’s disease mimicking bone metastases in both 18F-FDG and 68Ga PSMA PET/CT

http://ift.tt/2mgF2xk

The intensity of 18FDG uptake does not predict tumor growth in patients with metastatic differentiated thyroid cancer

Abstract

Purpose

In patients with metastatic differentiated thyroid carcinoma (DTC), fluorodeoxyglucose (FDG) uptake as well as age, tumor size and radioactive iodine (RAI) uptake are prognostic factors for survival. High FDG uptake is a poor prognostic factor and lesions with high FDG uptake are often considered aggressive, but the predictive value of FDG uptake for morphological progression is unknown. The principal aim of this retrospective single center study was to determine whether the intensity of FDG uptake was correlated on a per lesion analysis with tumor growth rate (TGR) expressed as the percentage of increase in tumor size during 1 year (1-year TGR).

Methods

Fifty five patients with DTC were included between July 2012 and May 2014 with the following criteria: (i) at least one distant metastasis measuring ≥ 1 cm in diameter on CT scan (ii) evaluation by FDG-positron emission tomography/computed tomography (PET/CT) performed at our center (iii) at least one CT or another FDG-PET/CT performed 3 to 12 months after the reference FDG-PET/CT in the absence of systemic or local treatment between the two imaging procedures.

Results

One hundred and fifty-six metastatic lesions located in lungs (63), neck lymph nodes (28), chest lymph nodes (42), bone (11), liver (2) and other sites (12) were studied. The median size was 16 mm, median SUVmax/lesion: 8.7; median metabolic tumor volume/lesion (Metab.TV/lesion): 3.7 cm³. The median 1-year TGR was 40.68 %. SUVmax and Metab.TV/lesion were not correlated to their 1-year TGR (p = 0.38 and p = 0.74 respectively). Among single patients with multiple lesions, the lesions with the highest SUVmax/lesion or the highest Metab.TV/lesion did not disclose the higher 1-year TGR.

Conclusion

The intensity of FDG uptake on a per lesion analysis is not correlated to its 1-year TGR and cannot be used as a surrogate marker of tumour progression.

http://ift.tt/2lv3aOl

THIEME Atlas of Anatomy – Internal Organs , 2nd Edition. Michael Schuenke, Erik Schulte, Udo Schumacher (Editors), Wayne A. Cass (Consulting Editor), Markus Voll, Karl Wesker (Illustrations)

http://ift.tt/2mgzFhl

Phase I/II trials of 186 Re-HEDP in metastatic castration-resistant prostate cancer: post-hoc analysis of the impact of administered activity and dosimetry on survival

Abstract

Purpose

To investigate the role of patient-specific dosimetry as a predictive marker of survival and as a potential tool for individualised molecular radiotherapy treatment planning of bone metastases from castration-resistant prostate cancer, and to assess whether higher administered levels of activity are associated with a survival benefit.

Methods

Clinical data from 57 patients who received 2.5–5.1 GBq of ¹⁸⁶Re-HEDP as part of NIH-funded phase I/II clinical trials were analysed. Whole-body and SPECT-based absorbed doses to the whole body and bone lesions were calculated for 22 patients receiving 5 GBq. The patient mean absorbed dose was defined as the mean of all bone lesion-absorbed doses in any given patient. Kaplan–Meier curves, log-rank tests, Cox's proportional hazards model and Pearson's correlation coefficients were used for overall survival (OS) and correlation analyses.

Results

A statistically significantly longer OS was associated with administered activities above 3.5 GBq in the 57 patients (20.1 vs 7.1 months, hazard ratio: 0.39, 95 % CI: 0.10–0.58, P = 0.002). A total of 379 bone lesions were identified in 22 patients. The mean of the patient mean absorbed dose was 19 (±6) Gy and the mean of the whole-body absorbed dose was 0.33 (±0.11) Gy for the 22 patients. The patient mean absorbed dose (r = 0.65, P = 0.001) and the whole-body absorbed dose (r = 0.63, P = 0.002) showed a positive correlation with disease volume. Significant differences in OS were observed for the univariate group analyses according to disease volume as measured from SPECT imaging of ¹⁸⁶Re-HEDP (P = 0.03) and patient mean absorbed dose (P = 0.01), whilst only the disease volume remained significant in a multivariable analysis (P = 0.004).

Conclusion

This study demonstrated that higher administered activities led to prolonged survival and that for a fixed administered activity, the whole-body and patient mean absorbed doses correlated with the extent of disease, which, in turn, correlated with survival. This study shows the importance of patient stratification to establish absorbed dose–response correlations and indicates the potential to individualise treatment of bone metastases with radiopharmaceuticals according to patient-specific imaging and dosimetry.

http://ift.tt/2ldaviW

Stefano Fanti and Egesta Lopci (Editors): Diagnostic nuclear medicine and radionuclide therapy

http://ift.tt/2kQGut8

Michael Schuenke, Erik Schulte, Udo Schumacher (Editors): Atlas of anatomy: head, neck, and neuroanatomy

http://ift.tt/2lcZyhr

Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [ 68 Ga]PSMA I&T and comparison with published data of [ 68 Ga]PSMA HBED-CC

Abstract

Purpose

To determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [⁶⁸Ga]PSMA I&T and to compare it with published detection rates of [⁶⁸Ga]PSMA HBED-CC.

Methods

We performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [⁶⁸Ga]PSMA I&T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [⁶⁸Ga]PSMA I&T were statistically compared with published detection rates of [⁶⁸Ga]PSMA HBED-CC using exact Fisher's test.

Results

Median PSA was 0.81 (range: 0.01 – 128) ng/mL. In 58/83 patients (70 %) at least one [⁶⁸Ga]PSMA I&T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [⁶⁸Ga]PSMA I&T and published detection rates of [⁶⁸Ga]PSMA HBED-CC (all p>0.05).

Conclusions

[⁶⁸Ga]PSMA I&T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [⁶⁸Ga]PSMA HBED-CC.

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Contribution of SPECT/CT for sentinel node localization in patients with ipsilateral breast cancer relapse

Abstract

Background

In recent years repeat sentinel node (SN) biopsy has been proven to be feasible in local breast cancer recurrence (LBCR). However, in these patients SNs outside the ipsilateral axilla are frequently observed. This study evaluates the contribution of SPECT/CT for SN localization and surgical adjustment in LBCR patients.

Methods

SN biopsy was performed in 122 LBCR patients (median age 60.5 years, range 24–87), enrolled from August 2006 to July 2015. Median disease-free time lapse was 109.5 months (range 9–365). Axillary lymph node dissection (ALND) had previously been performed in 55 patients, SN biopsy in 44, both techniques in 13 and fine-needle aspiration in 10. Primary breast cancer treatment included radiotherapy in 104 patients (85.3 %) and chemotherapy in 40 (32.8 %). Preoperative lymphatic mapping, using planar scintigraphy (PS) and SPECT/CT included report of SN location according to lymph node territory. In case of a territorial PS-SPECT/CT mismatch, surgery was adjusted according to SPECT/CT findings.

Results

SPECT/CT SN visualization rate was higher than PS (53.3 % vs. 43.4 %, p n.s.) with, in total, 19 additional SN (118 vs. 99, p n.s.). PS-SPECT/CT territory mismatch, found in 60 % (39/65) of patients with SN visualization, led to surgical adjustment in 21.3 % (26/122) of patients. The SN procedure was finally performed in 104 patients resulting in a 65.7 % surgical retrieval rate with a total of 132 removed SNs (1.86/patient). SN metastases were found in 17/71 patients (23.9 %), in 16 of them (94 %) in ipsilateral basins outside the axilla or in the contralateral axilla.

Conclusion

Using SPECT/CT there is a trend to visualize more SNs in LBCR, providing at the same time important anatomical information to adjust intraoperative SN procedures. The addition of SPECT/CT to the standard imaging protocol may lead to better staging mainly in patients presenting drainage outside the ipsilateral axilla.

http://ift.tt/2ldciEu

Efficacy of qualitative response assessment interpretation criteria at 18F-FDG PET-CT for predicting outcome in locally advanced cervical carcinoma treated with chemoradiotherapy

Abstract

Objectives

To evaluate the utility of a standardized qualitative scoring system for treatment response assessment at 18F-FDG PET-CT in patients undergoing chemoradiotherapy for locally advanced cervical carcinoma and correlate this with subsequent patient outcome.

Methods

Ninety-six consecutive patients with locally advanced cervical carcinoma treated with radical chemoradiotherapy (CRT) in a single centre between 2011 and 2014 underwent 18F-FDG PET-CT approximately 3 months post-treatment. Tumour metabolic response was assessed qualitatively using a 5-point scale ranging from background level activity only through to progressive metabolic disease. Clinical and radiological (MRI pelvis) follow-up was performed in all patients. Progression-free (PFS) and overall survival (OS) was calculated using the Kaplan-Meier method (Mantel-Cox log-rank) and correlated with qualitative score using Chi-squared test.

Results

Forty patients (41.7 %) demonstrated complete metabolic response (CMR) on post-treatment PET-CT (Score 1/2) with 38 patients (95.0 %) remaining disease free after a minimum follow-up period of 18 months. Twenty-four patients (25.0 %) had indeterminate residual uptake (ID, Score 3) at primary or nodal sites after treatment, of these eight patients (33.3 %) relapsed on follow-up, including all patients with residual nodal uptake (n = 4Eleven11 of 17 patients (64.7 %) with significant residual uptake (partial metabolic response, PMR, Score 4) subsequently relapsed. In 15 patients (15.6 %) PET-CT demonstrated progressive disease (PD, Score 5) following treatment. Kaplan-Meier analysis showed a highly statistically significant difference in PFS and OS between patients with CMR, indeterminate uptake, PMR and PD (Log-rank, P < 0.0001). Chi-squared test demonstrated a highly statistically significant association between increasing qualitative score and risk of recurrence or death (P < 0.001).

Conclusion

Use of a 5-point qualitative scoring system to assess metabolic response to CRT in locally advanced cervical carcinoma predicts survival outcome and this prognostic information may help guide further patient management.

http://ift.tt/2kQPvST

The reconstruction algorithm used for [ 68 Ga]PSMA-HBED-CC PET/CT reconstruction significantly influences the number of detected lymph node metastases and coeliac ganglia

Abstract

Purpose

To investigate whether the numbers of lymph node metastases and coeliac ganglia delineated on [⁶⁸Ga]PSMA-HBED-CC PET/CT scans differ among datasets generated using different reconstruction algorithms.

Methods

Data were constructed using the BLOB-OS-TF, BLOB-OS and 3D-RAMLA algorithms. All reconstructions were assessed by two nuclear medicine physicians for the number of pelvic/paraaortal lymph node metastases as well the number of coeliac ganglia. Standardized uptake values (SUV) were also calculated in different regions.

Results

At least one [⁶⁸Ga]PSMA-HBED-CC PET/CT-positive pelvic or paraaortal lymph node metastasis was found in 49 and 35 patients using the BLOB-OS-TF algorithm, in 42 and 33 patients using the BLOB-OS algorithm, and in 41 and 31 patients using the 3D-RAMLA algorithm, respectively, and a positive ganglion was found in 92, 59 and 24 of 100 patients using the three algorithms, respectively. Quantitatively, the SUVmean and SUVmax were significantly higher with the BLOB-OS algorithm than with either the BLOB-OS-TF or the 3D-RAMLA algorithm in all measured regions (p < 0.001 for all comparisons). The differences between the SUVs with the BLOB-OS-TF- and 3D-RAMLA algorithms were not significant in the aorta (SUVmean, p = 0.93; SUVmax, p = 0.97) but were significant in all other regions (p < 0.001 in all cases). The SUVmean ganglion/gluteus ratio was significantly higher with the BLOB-OS-TF algorithm than with either the BLOB-OS or the 3D-RAMLA algorithm and was significantly higher with the BLOB-OS than with the 3D-RAMLA algorithm (p < 0.001 in all cases).

Conclusion

The results of [⁶⁸Ga]PSMA-HBED-CC PET/CT are affected by the reconstruction algorithm used. The highest number of lesions and physiological structures will be visualized using a modern algorithm employing time-of-flight information.

http://ift.tt/2ldj7pF

68 Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients

Abstract

Background

To report on imaging findings using ⁶⁸Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients.

Methods

⁶⁸Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status.

Results

Out of 81 tumor lesions identified, 84% were identified on ⁶⁸Ga-PSMA-HBED-CC PET. ⁶⁸Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p = 0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p = 0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and ⁶⁸Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r = 0.407, p = 0.015).

Conclusions

⁶⁸Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry.

http://ift.tt/2kQKidY

Synthesis and pre-clinical evaluation of a new class of high-affinity 18 F-labeled PSMA ligands for detection of prostate cancer by PET imaging

Abstract

Purpose

Current clinical imaging of PSMA-positive prostate cancer by positron emission tomography (PET) mainly features ⁶⁸Ga-labeled tracers, notably [⁶⁸Ga]Ga-PSMA-HBED-CC. The longer half-life of fluorine-18 offers significant advantages over Ga-68, clinically and logistically. We aimed to develop high-affinity PSMA inhibitors labeled with fluorine-18 as alternative tracers for prostate cancer.

Methods

Six triazolylphenyl ureas and their alkyne precursors were synthesized from the Glu-urea-Lys PSMA binding moiety. PSMA affinity was determined in a competitive binding assay using LNCaP cells. The [¹⁸F]triazoles were isolated following a Cu(I)-catalyzed click reaction between the alkynes and [¹⁸F]fluoroethylazide. The ¹⁸F-labeled compounds were evaluated in nude mice bearing LNCaP tumors and compared to [⁶⁸Ga]Ga-PSMA-HBED-CC and [¹⁸F]DCFPyL. Biodistribution studies of the two tracers with the highest imaged-derived tumor uptake and highest PSMA affinity were undertaken at 1 h, 2 h and 4 h post-injection (p.i.), and co-administration of PMPA was used to determine whether uptake was PSMA-specific.

Results

F-18-labeled triazolylphenyl ureas were prepared with a decay-corrected RCY of 20–40 %, >98 % radiochemical and chemical purity, and specific activity of up to 391 GBq/μmol. PSMA binding (IC₅₀) ranged from 3–36 nM. The position of the triazole influenced tumor uptake (3 > 4 > 2), and direct conjugation of the triazole with the phenylurea moiety was preferred to insertion of a spacer group. Image-derived tumor uptake ranged from 6–14 %ID/g at 2 h p.i., the time of maximum tumor uptake; uptake of [⁶⁸Ga]Ga-PSMA-HBED-CC and [¹⁸F]DCFPyL was 5–6 %ID/g at 1–3 h p.i., the time of maximum tumor uptake. Biodistribution studies of the two most promising compounds gave maximum tumor uptakes of 10.9 ± 1.0 % and 14.3 ± 2.5 %ID/g, respectively, as compared to 6.27 ± 1.44 %ID/g for [⁶⁸Ga]Ga-PSMA-HBED-CC.

Conclusions

Six [¹⁸F]triazolylphenyl ureas were prepared in good radiochemical yield. Compounds showed PSMA-specific uptake in LNCaP tumors as high as 14 % ID/g, more than a 2-fold increase over [⁶⁸Ga]Ga-PSMA-HBED-CC. The facile and high-yielding radiosynthesis of these ¹⁸F-labeled triazoles as well as their promising in vitro and in vivo characteristics make them worthy of clinical development for PET imaging of prostate cancer.

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Reply by L. Maffioli

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F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients

Abstract

Purpose

The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer ⁶⁸Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, ⁶⁸Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of ¹⁸F-labelled analogs. ¹⁸F-PSMA-1007 was selected among several ¹⁸F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of ¹⁸F-PSMA-1007 in human volunteers and patients.

Methods

Radiation dosimetry of ¹⁸F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent ¹⁸F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining.

Results

With an effective dose of approximately 4.4–5.5 mSv per 200–250 MBq examination, ¹⁸F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other ¹⁸F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, ¹⁸F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to ¹⁸F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2–3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. ¹⁸F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter.

Conclusion

¹⁸F-PSMA-1007 performs at least comparably to ⁶⁸Ga-PSMA-11, but its longer half-life combined with its superior energy characteristics and non-urinary excretion overcomes some practical limitations of ⁶⁸Ga-labelled PSMA-targeted tracers.

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Personalized medicine: a new option for nuclear medicine and molecular imaging in the third millennium

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Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor

Abstract

Purpose

Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients.

Experimental Design

Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis.

Results

All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis.

Conclusions

We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

http://ift.tt/2ld8T8Y

Modeling tics in rodents: Conceptual challenges and paths forward

Publication date: Available online 22 February 2017
Source:Journal of Neuroscience Methods
Author(s): Marco Bortolato, Christopher Pittenger
BackgroundRecent advances in our understanding of the neurobiology of tics have led to the development of novel rodent models capturing different pathophysiological and phenotypic aspects of Tourette syndrome. The proliferation of these models, however, raises vexing questions on what standards should be adopted to assess their theoretical validity and empirical utility. Assessing the homology of a rodent motoric burst with a tic remains problematic, due to our incomplete knowledge of the underpinnings of tics, their high phenotypic complexity and variability, limitations in our ability test key aspects of tic phenomenology (such as premonitory sensory phenomena) in animals, and between-species differences in neuroanatomy and behavioral repertoire. These limitations underscore that any interpretation of behavioral output in an animal model cannot exclusively rely on the recognition of features that bear superficial resemblance with tics, but must be supported by other etiological and convergent phenomenological criteria.New methodHere, we discuss two complementary approaches for the study and validation of tic-like manifestations in rodents, based respectively on the use of contextual modulators and accompanying features of repetitive motor manifestations and on the reproduction of pathogenic factors.ResultsNeither strategy can by itself provide convincing evidence that a model informatively recapitulates tic pathophysiology. Their combination holds promise to enhance the rigorous evaluation and translational relevance of rodent models of tic disorders.ConclusionsThis systematic consideration of different approaches to the validation and study of animal models of tic pathophysiology provides a framework for future work in this area.



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Nuevos tiempos para la neuroimagen de Medicina Nuclear en España: ¿de dónde partimos?

Publication date: Available online 22 February 2017
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): M.A. Balsa, V. Camacho, P. Garrastachu, D. García-Solís, M. Gómez-Río, S. Rubí, X. Setoain, J. Arbizu
Objetivoconocer la situación de los estudios de neuroimagen de Medicina Nuclear que se realizaron en España en el año 2013 y primer trimestre del 2014, con el fin de definir las actividades del grupo de trabajo de Neuroimagen de la Sociedad Española de Medicina Nuclear e Imagen Molecular (SEMNIM).Material y métodosSe diseñó un cuestionario de 14 preguntas dividido en 3 partes: características de los servicios (equipamiento y profesionales involucrados), tipo de exploraciones e indicaciones clínicas y métodos de evaluación. El cuestionario se remitió a los 166 servicios de Medicina Nuclear que figuraban en la secretaría de la Sociedad Española de Medicina Nuclear e Imagen Molecular.ResultadosRespondieron a la encuesta un total de 54 centros distribuidos entre todas las comunidades autónomas. La mayoría de los centros realizaron entre 300 y 800 exploraciones de neuroimagen al año, representando más de 25 exploraciones al mes. La media de equipos por servicio era de 3, teniendo la mitad de ellos equipos PET/TC y SPECT/TC. Las exploraciones realizadas con más frecuencia son la SPECT cerebral con ¹²³I-FP-CIT, seguida de la SPECT cerebral de perfusión y de la PET con ¹⁸F-FDG, siendo las indicaciones clínicas más frecuentes los estudios de deterioro cognitivo seguidos por los de trastornos del movimiento. Para la evaluación de las pruebas la mayoría de los centros utilizaron únicamente la valoración visual, en la valoración cuantitativa la cuantificación por regiones de interés fue la más utilizada.ConclusionesLos resultados reflejan cuál fue la actividad clínica del año 2013 y primer trimestre del 2014, siendo las indicaciones principales los estudios de deterioro cognitivo y trastorno del movimiento. La variabilidad en la evaluación de los estudios PET y la colaboración con los especialistas clínicos que demandan las exploraciones de neuroimagen de Medicina Nuclear son algunos de los retos que debemos afrontar en los próximos años.ObjectiveTo determine the status of neuroimaging studies of Nuclear Medicine in Spain during 2013 and first quarter of 2014, in order to define the activities of the neuroimaging group of the Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM).Material and methodsA questionnaire of 14 questions was designed, divided into 3 parts: characteristics of the departments (equipment and professionals involved); type of scans and clinical indications; and evaluation methods. The questionnaire was sent to 166 Nuclear Medicine departments.ResultsA total of 54 departments distributed among all regions completed the questionnaire. Most departments performed between 300 and 800 neuroimaging examinations per year, representing more than 25 scans per month. The average pieces of equipment were three; half of the departments had a PET/CT scanner and SPECT/CT equipment. Scans performed more frequently were brain SPECT with ¹²³I-FP-CIT, followed by brain perfusion SPECT and PET with ¹⁸F-FDG. The most frequent clinical indications were cognitive impairment followed by movement disorders. For evaluation of the images most sites used only visual assessment, and for the quantitative assessment the most used was quantification by region of interest.ConclusionsThese results reflect the clinical activity of 2013 and first quarter of 2014. The main indications of the studies were cognitive impairment and movement disorders. Variability in the evaluation of the studies is among the challenges that will be faced in the coming years.



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Evaluation of the Congressionally Directed Medical Research Programs Review Process.

The medical research landscape in the United States is supported by a variety of organizations that spend billions of dollars in government and private funds each year to seek answers to complex medical and public health problems. The largest government funder is the National Institutes of Health (NIH), followed by the Department of Defense (DoD). Almost half of DoD's medical research funding is administered by the Congressionally Directed Medical Research Programs (CDMRP).

http://ift.tt/2lcQPMh

Life Expectancy Calculators [Internet].

Estimation of life expectancy serves an important role in clinical decisions about screening for disease and treatment in primary care practices. Increasingly, clinical guidelines recommend a course of action in context of the patient's life expectancy. While many tools have been developed to estimate life expectancy or the likelihood of surviving for a period of time, there are no well-established decision support tools that are broadly applicable to primary care.

http://ift.tt/2lJsArV

Modifiable Risk Factors in the Progression of Multiple Sclerosis: A Systematic Review of the Epidemiology and Treatment [Internet].

Multiple sclerosis (MS) is the most common progressive disease of the central nervous system in young adults and the cause of serious physical disability in adults of working age. Epidemiologic data suggest that rates of MS vary with demographic and environmental factors. The disease presentation is very heterogeneous with diverse clinical manifestations. Progression of MS may vary with modifiable risk factors.

http://ift.tt/2ld1ztI

Genetically Engineered Crops: Experiences and Prospects.

Genetically engineered (GE) crops were first introduced commercially in the 1990s. After two decades of production, some groups and individuals remain critical of the technology based on their concerns about possible adverse effects on human health, the environment, and ethical considerations. At the same time, others are concerned that the technology is not reaching its potential to improve human health and the environment because of stringent regulations and reduced public funding to develop products offering more benefits to society. While the debate about these and other questions related to the genetic engineering techniques of the first 20 years goes on, emerging genetic-engineering technologies are adding new complexities to the conversation.

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Metrics That Matter for Population Health Action: Workshop Summary.

In times of rapid change and constrained resources, measures that are important, focused, and reliable are vital. However there is an overabundance of measures available for evaluating various aspects of population health and previous efforts to simplify existing sets to meet the needs of all decision makers have been unsuccessful. The National Academies of Sciences, Engineering, and Medicine convened a workshop to explore the status and uses of measures and measurement in the work of improving population health. Participants explored existing and emerging population health metric sets and characteristics of metrics necessary for stakeholder action across multiple sectors. This report summarizes the presentations and discussions from the workshop.

http://ift.tt/2lJC8TH

Countering Violent Extremism Through Public Health Practice: Proceedings of a Workshop [Prepublication Draft].

Countering violent extremism consists of various prevention and intervention approaches to increase the resilience of communities and individuals to radicalization toward violent extremism, to provide nonviolent avenues for expressing grievances, and to educate communities about the threat of recruitment and radicalization to violence. To explore the application of health approaches in community-level strategies to countering violent extremism and radicalization, the National Academies of Sciences, Engineering, and Medicine held a public workshop in September 2016. Participants explored the evolving threat of violent extremism and radicalization within communities across America, traditional versus health-centered approaches to countering violent extremism and radicalization, and opportunities for cross-sector and interdisciplinary collaboration and learning among domestic and international stakeholders and organizations. This publication summarizes the presentations and discussions from the workshop.

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Clinical Thyroidology High-Impact Articles

FREE ACCESS through March 9, 2017.
Read Now:

Sequential TSH Determinations May Help in Assessing the Adequacy of Treatment for Overt Hypothyroidism in Older Patients
Stephen W. Spaulding

Age Cutoff of 45 Years May Not Be Appropriate for Papillary Thyroid Cancer Staging
Masha J. Livhits, Michael W. Yeh

Recurrence Rates in Patients with Intermediate-Risk Differentiated Thyroid Cancer Are Similar after Low-Dose and High-Dose Radioiodine Ablation in a Korean Series
Martin Biermann

 

The post Clinical Thyroidology High-Impact Articles appeared first on American Thyroid Association.

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Luminex LiquiChip System for the Evaluation of Cytokine Levels in Patients with Contact Dermatitis to Potassium Dichromate

Background: Allergic contact dermatitis (ACD) is associated with increased production of cytokines. The patch test is the "gold-standard" diagnostic method, but it poses a risk of false results. Objective: To evaluate a novel laboratory technique, the Luminex LiquiChip, which simultaneously measures blood levels of multiple cytokines, as a diagnostic tool in patients with chrome-induced ACD. Methods: The study group included 20 patients with ACD and relevant patch test results for potassium dichromate and 19 patients with ACD for nickel or fragrance as control. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence and absence of potassium dichromate. The Luminex LiquiChip was used to measure levels of the following cytokines: granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-#x03B3;, and tumor necrosis factor (TNF)-α. Results: Potassium dichromate-stimulated PBMCs secreted significantly higher amounts of all cytokines except TNF-α than nonstimulated PBMCs. PBMCs from patients with ACD to chromium secreted significantly higher amounts of all cytokines tested, except IL-4, compared to PBMCs from patients with ACD to nickel or fragrance. Conclusions: Potassium dichromate stimulates the production of both Th1- and Th2-type cytokines in patients with chrome allergy. The Luminex LiquiChip is a promising in vitro method and may serve as a diagnostic tool for ACD.
Dermatology

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Stromal Vascular Fraction for Treatment of Xerostomia

Condition:   Xerostomia Due to Radiotherapy (Disorder)
Interventions:   Biological: Stromal Vascular Fraction;   Other: Usual Care
Sponsor:   Midwestern Regional Medical Center
Not yet recruiting - verified February 2017

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Validation of a Multi-Genetic Test for the Diagnosis of Indeterminate Thyroid Nodules

Condition:   Indeterminate Thyroid Cytology
Intervention:  
Sponsor:   Hernán González
Recruiting - verified February 2017

http://ift.tt/2lJx7ul

Concurrent Chemotherapy for Elderly Patients With Locoregionally Advanced Nasopharyngeal Carcinoma

Condition:   Nasopharyngeal Carcinoma
Interventions:   Radiation: Radiotherapy alone;   Radiation: Concurrent chemoradiotherapy
Sponsor:   Zhejiang Cancer Hospital
Recruiting - verified February 2017

http://ift.tt/2l3DKng

Turmeric Supplementation on Polyp Number and Size in Patients With Familial Adenomatous Polyposis.

Conditions:   Familial Adenomatous Polyposis;   FAP;   FAP Gene Mutation
Interventions:   Dietary Supplement: Wholistic Turmeric capsules;   Other: Placebo
Sponsor:   Tel-Aviv Sourasky Medical Center
Not yet recruiting - verified February 2017

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The Microenvironment in Barrett's Esophagus

Conditions:   Barrett Esophagus;   Esophageal Adenocarcinoma
Interventions:   Device: Tethered capsule sponge;   Device: Electronic nose device
Sponsors:   Columbia University;   Mayo Clinic;   University of Pennsylvania
Not yet recruiting - verified February 2017

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Inflammation and the Metabolic Syndrome: The Tissue-Specific Functions of NF-κB

Publication date: Available online 23 February 2017
Source:Trends in Cell Biology
Author(s): Leen Catrysse, Geert van Loo
Obesity is becoming a major health concern in Western society, and medical conditions associated with obesity are grouped in the metabolic syndrome. Overnutrition activates several proinflammatory signaling pathways, leading to a condition of chronic low-grade inflammation in several metabolic tissues affecting their proper function. Nuclear factor kappa B (NF-κB) signaling is a crucial pathway in this process and has been studied extensively in the context of obesity and the metabolic syndrome. Here we give an overview of the molecular mechanisms behind the inflammatory function of NF-κB in response to overnutrition and the effect this has on several metabolic tissues.



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A mathematical coffee filter

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): David Bradley




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Ultra-long nanofibers could build better lithium-ion batteries

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Laurie Winkless




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3D printed magnets with little waste

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Laurie Donaldson




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Mussel-inspired scaffolds help treat bone cancer

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Modelling the crashworthiness of graphene composites

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Laurie Winkless




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Events Diary

Publication date: Available online 23 February 2017
Source:Materials Today





http://ift.tt/2lOyb0K

Solution-based method for processing solar cells

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2lz9D9g

Metallica's nano color

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): David Bradley




http://ift.tt/2lOEwcn

Superconductors induced at critical temperatures

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2lzmqss

Polymer layer boosts perovskite solar cells

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Cordelia Sealy




http://ift.tt/2lOD1uM

Hybrid film ideal candidate as rewritable material

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Laurie Donaldson




http://ift.tt/2lz7UAH

Nanoparticles give organic dyes a clean break

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Cordelia Sealy




http://ift.tt/2lOEtgH

Stiff water down the nanotubes

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): David Bradley




http://ift.tt/2lzge3n

Recycling scattered light for energy conversion

Publication date: Available online 22 February 2017
Source:Materials Today
Author(s): Mario Pagliaro




http://ift.tt/2lOLRbR

A preferential delivery method to investigate direct neuromuscular blockade effect of inhaled anesthetics on skeletal muscle

Publication date: Available online 22 February 2017
Source:Medical Hypotheses
Author(s): Ling Ye, Pingliang Yang
Inhaled anesthetics can enhance the effect of neuromuscular blocker, but whether inhaled anesthetics such as sevoflurane have a direct effect on skeletal muscle contractility is unknown. Selectively blocking skeletal muscle may prevent the interference effect of central nervous system. So we decided to evaluate a local application of neuromuscular blocker (NMB) atracurium to prevent the general effect on skeletal muscle. In part 1, sevoflurane (a inhaled anesthetic)minimum alveolar concentrations (MAC) of 1.0, 1.5 and 2.0 would be apllied in succession. Neuromuscular function was assessed at each MAC. In part 2, patients are randomized into four groups: group1 (propofol + NMB, sevoflurane 0 MAC), and groups 2 to 4 (NMB+ sevoflurane 1.0, 1.5 and 2.0 MAC respectively). In group 1, patients were anesthetized by propofol, then 0.01 mg/kg atracurium was injected into the tested arm intravenously after the arterial blood flow was blocked using a tourniquet. For the other 3 groups, patients inhaled 1.0 MAC, 1.5 MAC, or 2.0 MAC of sevoflurane. Then 0.01 mg/kg atracurium was injected. Neuromuscular function was recorded for the 4 groups. Neuromuscular function was assessed by acceleromyography measurement of evoked responses to train-of four (TOF) stimuli (2 Hz for 2s applied every 12 s) at the adductor pollicis using a TOF-Guard^TM neuromuscular transmission monitor. If proven, our hypothesis would demonstrate the inhaled anesthetics have no direct effect on contractility but only by increasing the skeletal muscle sensitivity to NMB.



http://ift.tt/2lcxOth

Title page/Editorial Board

Publication date: March 2017
Source:Medical Hypotheses, Volume 100





http://ift.tt/2lckepT

Genetic variants of the dna repair genes from exome aggregation consortium (exac) database: Significance in cancer

Publication date: Available online 22 February 2017
Source:DNA Repair
Author(s): Raima Das, Sankar Kumar Ghosh
DNA repair pathway is a primary defense system that eliminates wide varieties of DNA damage. Any deficiencies in them are likely to cause the chromosomal instability that leads to cell malfunctioning and tumorigenesis. Genetic polymorphisms in DNA repair genes have demonstrated a significant association with cancer risk.Our study attempts to give a glimpse of the overall scenario of the germline polymorphisms in the DNA repair genes by taking into account of the Exome Aggregation Consortium (ExAC) database as well as the Human Gene Mutation Database (HGMD) for evaluating the disease link, particularly in cancer.It has been found that ExAC DNA repair dataset (which consists of 228 DNA repair genes) comprises 30.4% missense, 12.5% dbSNP reported and 3.2% ClinVar significant variants. 27% of all the missense variants has the deleterious SIFT score of 0.00 and 6% variants carrying the most damaging Polyphen-2 score of 1.00, thus affecting the protein structure and function. However, as per HGMD, only a fraction (1.2%) of ExAC DNA repair variants was found to be cancer-related, indicating remaining variants reported in both the databases to be further analyzed. This, in turn, may provide an increased spectrum of the reported cancer linked variants in the DNA repair genes present in ExAC database.Moreover, further in silico functional assay of the identified vital cancer-associated variants, which is essential to get their actual biological significance, may shed some lights in the field of targeted drug development in near future.



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Editorial board

Publication date: March 2017
Source:Biological Psychology, Volume 124





http://ift.tt/2motjvI

Inside front cover continued (editorial board members)

Publication date: March 2017
Source:Biological Psychology, Volume 124





http://ift.tt/2mb33cq

PERCEIVED SOCIAL SUPPORT PREDICTS LOWER CARDIOVASCULAR REACTIVITY TO STRESS IN OLDER ADULTS

Publication date: Available online 22 February 2017
Source:Biological Psychology
Author(s): Siobhán Howard, Ann-Marie Creaven, Brian M. Hughes, Éanna D. O'Leary, Jack E. James
The benefits of perceived social support for physical and psychological health are well-established. However, little research has explored associations between perceived social support and cardiovascular reactivity in older adults. This exploratory study recruited a sample of older adults (Mage=69years, SD=5.62) and examined quality and quantity of perceived social support as predictors of cardiovascular reactivity to laboratory-based stress (N=39 participants) and ambulatory cardiovascular activity in everyday life (n=28). The results suggest that quality, but not quantity, of perceived social support predicts reduced blood pressure reactivity to stress in the laboratory. Although quality of support was not associated with ambulatory blood pressure, results suggest that quantity of daily social support may be associated with higher ambulatory heart rate, but not with social contact during measurement. This preliminary study extends prior work on social support and cardiovascular function to a group of older adults in both laboratory and field settings. Challenges for much-needed future research in this area are discussed.



http://ift.tt/2mb8Z51

The combined effects of menstrual cycle phase and acute stress on reward-related processing

Publication date: Available online 22 February 2017
Source:Biological Psychology
Author(s): Stella Banis, Monicque M. Lorist
We investigated the combined effects of menstrual cycle phase and acute stress on reward-related processing, employing a monetary incentive delay task in combination with EEG. Females participated during late follicular and late luteal phases, performing in both control and stress conditions. We found evidence for both independent and interaction effects of phase and stress on reward-related brain activity. Phase modulated the sensitivity to feedback valence, with a stronger signaling of negative performance outcomes in the late follicular versus late luteal phase. In contrast, in the control condition, the late luteal versus late follicular phase was associated with a heightened sensitivity to reward condition, with enhanced performance monitoring in potential-reward versus no-reward trials. Stress decreased attentional preparation during reward anticipation, but increased the influence of reward condition on the processing of positive performance outcomes. We found no evidence for an increased sensitivity to stress during the late luteal versus late follicular phase.



http://ift.tt/2moCBYB

The Complex Roles of Mechanistic Target of Rapamycin in Adipocytes and Beyond

Publication date: Available online 22 February 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Peter L. Lee, Su Myung Jung, David A. Guertin
Having healthy adipose tissue is essential for metabolic fitness. This is clear from the obesity epidemic, which is unveiling a myriad of comorbidities associated with excess adipose tissue including type 2 diabetes, cardiovascular disease, and cancer. Lipodystrophy also causes insulin resistance, emphasizing the importance of having a balanced amount of fat. In cells, the mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1 and mTORC2, respectively) link nutrient and hormonal signaling with metabolism, and recent studies are shedding new light on their in vivo roles in adipocytes. In this review, we discuss how recent advances in adipose tissue and mTOR biology are converging to reveal new mechanisms that maintain healthy adipose tissue, and discuss ongoing mysteries of mTOR signaling, particularly for the less understood complex mTORC2.



http://ift.tt/2kPJgyY

The common, autoimmunity-predisposing 620Arg > Trp variant of PTPN22 modulates macrophage function and morphology

Publication date: Available online 22 February 2017
Source:Journal of Autoimmunity
Author(s): Meihang Li, Hugues Beauchemin, Natalija Popovic, Alan Peterson, Eva d'Hennezel, Ciriaco A. Piccirillo, Chao Sun, Constantin Polychronakos
The C1858T single nucleotide polymorphism (SNP) in PTPN22 (protein tyrosine phosphatase nonreceptor 22) leads to the 620 Arg to Trp polymorphism in its encoded human protein LYP. This allelic variant is associated with multiple autoimmune diseases, including type 1 diabetes (T1D), Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus. However, the underlying mechanisms are poorly understood. To study how this polymorphism influences the immune system, we generated a mouse strain with a knock-in of the Trp allele, imitating the human disease-associated variant. We did not find significant difference between the polymorphic and the wild type mice on the proportion of total CD4 T cell, CD8 T cell, NK cell, memory T lymphocyte, macrophage, dendritic cells in both peripheral lymph nodes and spleen. However, macrophages from Trp/Trp mice showed altered morphology and enhanced function, including higher expression of MHCII and B7 molecules and increased phagocytic ability, which further leads to a higher T-cell activation by specific antigen. Our model shows no alteration in immune cell profile by the Trp allele, but brings up macrophages as an important player to consider in explaining the PTPN22 Trp allele effect on autoimmune disease risk.



http://ift.tt/2lIOQCj

Long term changes in the concentration of radium in discharge waters of coal mines and Upper Silesian rivers

Publication date: May 2017
Source:Journal of Environmental Radioactivity, Volume 171
Author(s): Stanisław Chałupnik, Małgorzata Wysocka, Ewa Janson, Izabela Chmielewska, Marta Wiesner
According to the latest guidelines of the International Atomic Energy Agency (IAEA, 2016), coal mining is one of the most important contributors to occupational exposure. Coal mining contributes about 45% of the total annual collective dose obtained by workers due to the exposure at places of working. One of the sources of exposure in mining are formation brines with elevated concentrations of natural radionuclides, the most common are radium ²²⁶Ra and ²²⁸Ra. Radium isotopes often occur in formation waters in underground collieries in the Upper Silesian region (USCB) in Poland. Significant amounts of radium remain underground in the form of radioactive deposits created as a result of spontaneous deposition or water treatment. This phenomenon leads to the increase of radiation hazard for miners. The remaining activities of ²²⁶Ra and ²²⁸Ra are released into the rivers with mine effluents, causing the contamination of bottom sediments and river banks.The results of radioactivity monitoring of effluents and river waters are presented here to illustrate a trend of long-term changes in environmental contamination, caused by mining industry in the Upper Silesian Region.



http://ift.tt/2lc7BuT

Relationship of meteorological factors and acute stroke events in Kaunas (Lithuania) in 2000–2010

Abstract

Some researchers have hypothesised that meteorological factors may have an impact on acute cerebrovascular diseases. The aim of this study was to determine an impact of some meteorological factors on occurrence of acute cerebrovascular events in the middle-aged Kaunas population. Kaunas stroke register data were used. Data on meteorological factors for the time period from 2000 to 2010 were obtained from the Lithuanian Hydrometeorological Service Kaunas Meteorological Station. We analysed 4038 cases with stroke. Ischemic strokes composed 80.4% and haemorrhagic strokes—19.6%. According to Poisson regression analysis, significant negative correlation between ischemic, haemorrhagic and all types of stroke and ambient air temperature was found (β coefficient − 0.007, −0.016, −0.009, p < 0.001, respectively). Results of ARIMA showed that ambient temperature of the day of stroke onset was associated with the occurrence of ischemic, haemorrhagic and all types of stroke: when temperature was lower, the risk of stroke was higher (−0.006, −0.003, −0.009, p < 0.001, respectively). Low temperature on the event day and 1 and 2 days before the event was associated with higher incidence of haemorrhagic stroke in women. Low ambient temperature on the event day increased incidence of haemorrhagic stroke in subjects 55–64 years. High wind speed on the event day was associated with higher incidence of ischemic stroke in older subjects. Meteorological factors may have some impact on the risk of acute cerebrovascular events. Health care providers should focus on preventive measures, which can reduce these risks.

http://ift.tt/2kPL2zQ

miRNA-based heavy metal homeostasis and plant growth

Abstract

Plants have been naturally gifted with mechanisms to adjust under very high or low nutrient concentrations. Heavy metal toxicity is considered as a major growth and yield-limiting factor for plants. This stress includes essential as well as non-essential metals. MicroRNAs (miRNAs) are known for mediating post-transcriptional regulation by cleaving transcripts or translational inhibition. It is commonly agreed that an extensive understanding of plant miRNAs will significantly help in the induction of tolerance against environmental stresses. With the introduction of the latest technology like next generation sequencing (NGS), a growing figure of miRNAs has been productively recognized in several plants for their diverse roles. These miRNAs are well-known modulators of plant responses to heavy metal (HM) stress. Data regarding metal-responsive miRNAs point out the vital role of plant miRNAs in supplementing metal detoxification by means of transcription factors (TF) or gene regulation. Acting as systemic signals, miRNAs also synchronize different physiological processes for plant responses to metal toxicities. In contrast to practicing techniques, using miRNA is a greatly helpful, pragmatic, and feasible approach. The earlier findings point towards miRNAs as a prospective target to engineer heavy metal tolerance in plants. Therefore, there is a need to augment our knowledge about the orchestrated functions of miRNAs during HM stress. We reviewed the deterministic significance of plant miRNAs in heavy metal tolerance and their role in mediating plant responses to HM toxicities. This review also summarized the topical developments by identification and validation of different metal stress-responsive miRNAs.

http://ift.tt/2l2XuaC

Enhanced degradation of spiro-insecticides and their leacher enol derivatives in soil by solarization and biosolarization techniques

Abstract

The leaching potential of three insecticides (spirodiclofen, spiromesifen, and spirotetramat) was assessed using disturbed soil columns. Small quantities of spirodiclofen and spiromesifen were detected in leachate fraction, while spirotetramat residues were not found in the leachates. In addition, the transformation products (enol derivatives) are relatively more mobile than the parent compounds and may leach into groundwater. Moreover, the use of disinfection soil techniques (solarization and biosolarization) to enhance their degradation rates in soil was investigated. The results show that both practices achieved a reduction in the number of juvenile nematodes, enhancing in a parallel way degradation rates of the insecticides and their enol derivatives as compared with the non-disinfected soil. This behavior can be mainly attributed to the increase in soil temperature and changes in microbial activity. All insecticides showed similar behavior under solarization and biosolarization conditions. As a consequence, both agronomic techniques could be considered as suitable strategies for detoxification of soils polluted with the studied pesticides.

http://ift.tt/2kPQjr9

A phase 1 trial of intravenous liposomal irinotecan in patients with recurrent high-grade glioma

Abstract

Purpose

Preclinical activity of irinotecan has been seen in glioma models, but only modest efficacy has been noted in clinical studies, perhaps related to drug distribution and/or pharmacokinetic limitations. In preclinical testing, irinotecan liposome injection (nal-IRI) results in prolongation of drug exposure and higher tissue levels of drug due to slower metabolism and the effect of enhanced permeability and retention. The objective of the current study was to assess the safety and pharmacokinetics (PK) of nal-IRI and to determine the maximum tolerated dose (MTD) in patients with recurrent high-grade glioma stratified based on UGT1A1 genotyping.

Methods

This phase I study stratified patients with recurrent high-grade glioma into 2 groups by UGT1A1 status: homozygous WT ("WT") vs heterozygous WT/*28 ("HT"). Patients who were homozygous *28 were ineligible. The design was a standard 3 + 3 phase I design. WT patients were started at 120 mg/m² intravenously every 3 weeks with dose increases in 60 mg/m² increments. HT patients were started at 60 mg/m², with dose increases in 30 mg/m² increments. The assessment period for dose-limiting toxicity was 1 cycle (21 days).

Results

In the WT cohort (n = 16), the MTD was 120 mg/m². In the HT cohort (n = 18), the MTD was 150 mg/m². Dose-limiting toxicity in both cohorts included diarrhea, some with associated dehydration and/or fatigue. PK results were comparable to those seen in other PK studies of nal-IRI; UGT1A1*28 genotype (WT vs. HT) did not affect PK parameters.

Conclusions

Nal-IRI had no unexpected toxicities when given intravenously. Of note, UGT1A1 genotype did not correlate with toxicity or affect PK profile.

http://ift.tt/2lbO1Pr

The important functionality of 14-3-3 isoforms in rice roots revealed by affinity chromatography

Publication date: Available online 22 February 2017
Source:Journal of Proteomics
Author(s): Zhixing Zhang, Yiping Zhang, Hong Zhao, Fenglian Huang, Zefeng Zhang, Wenxiong Lin
Plant 14-3-3 proteins belong to a large family of proteins involved in numerous physiological processes, and function by binding to phosphorylated client proteins to regulate their function. However, little is known about their regulatory mechanisms in rice root growth. In this study, four 14-3-3 isoforms (GF14b, GF14c, GF14e, GF14f) exhibiting prominent expression profiles in rice roots, were selected for further investigation. Through a pull-down assay using four 14-3-3 isoforms in rice roots, 87 client proteins were identified that are involved in metabolism, protein synthesis and trafficking, energy metabolism, cell structure and growth, and other cellular processes. Importantly, we found that 14-3-3 proteins may play an important role in the root stress response through interactions with proteins functioning in oxidative stress, pathogenesis and secondary metabolism. By using real-time RT–PCR, it was found that 14-3-3 proteins exhibited diverse patterns of gene expression in response to salinity and drought stresses in rice root. The results revealed the isoform-specific functions of root 14-3-3 proteins. Our current study provides insight into understanding the functional roles of 14-3-3 proteins during rice root growth.SignificanceRice (Oryza sativa L.) is one of the most important food crops in the world, as it is consumed by more than 3 billion people. Regulation of root growth plays an important role in rice adaption to biotic and abiotic, stress such as rhizosphere microbes and nutrient stress, and this process is directly related to the final yield. 14-3-3 proteins form a multi-gene family regulating developmental processes in plants. However, the correlation between the 14-3-3 protein family and its role in rice root growth has very little study. We applied an affinity chromatographic approach, in combination with LC-MS/MS, to explore the client proteins of four 14-3-3 isoforms that exhibit much more prominent gene expression than other members of the 14-3-3 family in rice roots. Assessments of the identified client proteins are able to obtain novel information toward understanding the functional mechanism of 14-3-3 proteins in rice root growth as expected.

Graphical abstract

http://ift.tt/2kP39Gk

Editorial Board

Publication date: 30 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 100





http://ift.tt/2lbBQ4V

TH1 and TH2 cytokine data in insulin secretagogues users newly diagnosed with breast cancer

Publication date: Available online 22 February 2017
Source:Data in Brief
Author(s): Zachary A.P. Wintrob, Jeffrey P. Hammel, George K. Nimako, Dan P. Gaile, Alan Forrest, Alice C. Ceacareanu
Stimulation of insulin production by insulin secretagogue use may impact T helper cells' cytokine production. This dataset presents the relationship between baseline insulin secretagogues use in women diagnosed with breast cancer and type 2 diabetes mellitus, the T-helper 1 and 2 produced cytokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis evaluating the relationship between T-helper cytokines stratified by of insulin secretagogues use and controls is also provided.



http://ift.tt/2maAueV

Dataset of tensile strength development of concrete with manufactured sand

Publication date: Available online 22 February 2017
Source:Data in Brief
Author(s): Shunbo Zhao, Xinxin Ding, Mingshuang Zhao, Changyong Li, Songwei Pei
This article presents 755 groups splitting tensile strength tests data of concrete with manufactured sand (MSC) in different curing age ranged from 1day to 388 days related to the research article "Experimental study on tensile strength development of concrete with manufactured sand" (Zhao et al., 2017) [1]. These data were used to evaluate the precision of the prediction formulas of tensile strength of MSC, and can be applied as dataset for further studies.



http://ift.tt/2modlBE

Data report on inflammatory C-C chemokines among insulin-using women with diabetes mellitus and breast cancer

Publication date: Available online 22 February 2017
Source:Data in Brief
Author(s): Zachary A.P. Wintrob, Jeffrey P. Hammel, George K. Nimako, Zahra S. Fayazi, Dan P. Gaile, Erin E. Davis, Alan Forrest, Alice C. Ceacareanu
Injectable insulin use may interfere with pro-inflammatory cytokines' production and, thus, play a role in the activation of tumor-associated macrophages - a process mainly influenced by inflammatory C-C chemokines. The data presented shows the relationship between pre-existing use of injectable insulin in women diagnosed with breast cancer and type 2 diabetes mellitus, the inflammatory C-C chemokine profiles at the time of breast cancer diagnosis, and subsequent cancer outcomes. A Pearson correlation analysis stratified by insulin use and controls is also provided. We present the observed relationship between the investigated C-C chemokines and between each of these biomarkers and previously reported adipokines levels in this study population [1].



http://ift.tt/2maBn7v

Data supporting the role of Fyn in embryonic sciatic nerve fasciculation

Publication date: Available online 22 February 2017
Source:Data in Brief
Author(s): Tomohiro Torii, Yuki Miyamoto, Kazuko Kawahara, Akito Tanoue, Yoichi Seki, Takako Morimoto, Masahiro Yamamoto, Junji Yamauchi
Fyn is the cytoplasmic tyrosine kinase that has critical roles in many aspects of biological functions. In the central [1] and peripheral nervous systems [2,3], Fyn plays the key role in initiating myelination by myelin-forming glial cells (Schwann cells and oligodendrocytes). Herein we provide the data regarding the role of Fyn in fasciculation and branching of embryonic peripheral nerves.



http://ift.tt/2mnZYSf

Electrode positions, transformation coordinates for ECG reconstruction from S-ICD vectors

Publication date: Available online 22 February 2017
Source:Data in Brief
Author(s): G. Wilson David, L. Cronbach Peter, D. Panfilo, E. Greenhut Saul, P. Stegemann Berthold, M. Morgan John
The article contains data pertaining to the reconstruction of an 8-lead ECG from 2 subcutaneous implantable cardioverter defibrillator vectors. The location of electrodes on the precordium required for the data collection are detailed; the flow chart for patient selection and exclusion is shown; the summary data of the root mean square error (RMSE) (in microvolts) and Pearson r for the ECG transformation all cases and the pearson correlation for all the leads measured and reconstructed leads are also shown. Detailed background, methodology and discussion can be found in the linked research article.



http://ift.tt/2matG0T

Thyroid volume and serum calcitonin changes during pregnancy

Abstract

Background

Pregnancy has a profound impact on thyroid homeostasis which results in change of thyroid function and thyroid volume (TV). Moreover, calcitonin (CT), and its gene-related peptide have been demonstrated to play an important role in the implantation process.

Purpose

To evaluate changes in TV and serum CT levels during pregnancy.

Methods

One hundred and fifty-five pregnant women were consecutively enrolled at the first trimester of gestation and underwent clinical, biochemical and sonographic assessment at enrollment, at the second and third trimesters and at 6 months after delivery.

Results

Throughout gestation serum TSH exceeded the upper specific first trimester cut-off in 5% of patients. TV significantly increased at the third trimester of gestation and returned to baseline levels at 6 months after delivery, while serum CT levels did not show significant changes. TV directly correlated with BMI or gestational weight gain at each trimester of pregnancy, while no significant association between serum CT levels and either weight or TV were found. Finally, in none of the patients with nodular goiter an increase in the volume of the nodules was noted. The appearance of a nodule was recorded during the second trimester in one patient.

Conclusion

This study confirms a prevalence of thyroid autoimmunity/hypertropinemia in 3–5% of pregnant women and shows that serum CT does not change in relation to the transient increase in TV occurring during gestation. An adequate daily iodine supplementation might be particularly useful during pregnancy to limit the TSH increase and the resulting thyroid gland and nodule enlargement.

http://ift.tt/2l1MOJF

EMERGENCY Computed Tomography Angiogram (CTA) Of The CHEST, ABDOMEN AND PELVIS

Publication date: Available online 22 February 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Kimberly Weatherspoon, Wayne Gilbertie, Tara Catanzano
In the setting of blunt trauma, the rapid assessment of internal injuries is essential in order to prevent potentially fatal outcomes. CT is a useful diagnostic tool for both screening and diagnosis. In addition to trauma, acute chest syndromes often warrant emergent CTA, looking for etiologies such as aortic aneurysms and/or complications of aortic aneurysms, pulmonary emboli, as well as other acute vascular process like aortic dissection and Takayasu′s aortitis. With continued improvements in diagnostic imaging, CTA of the chest, abdominal and pelvis proves to be an effective modality to image the aorta and other major vascular structures.



http://ift.tt/2kPjTwX

IFC (editorial board)

Publication date: March 2017
Source:Peptides, Volume 89





http://ift.tt/2mnNdXT

The International Neuropeptide society pages

Publication date: March 2017
Source:Peptides, Volume 89





http://ift.tt/2ma9QTw

Gayle & Richard Olson prize pages

Publication date: March 2017
Source:Peptides, Volume 89





http://ift.tt/2mnJFoC

Glucagon-like peptide-1 (GLP-1) increases in plasma and colon tissue prior to estrus and circulating levels change with increasing age in reproductively competent Wistar rats

Publication date: Available online 22 February 2017
Source:Peptides
Author(s): Michelle L. Johnson, M. Jill Saffrey, Victoria J. Taylor
There is a well-documented association between cyclic changes to food intake and the changing ovarian hormone levels of the reproductive cycle in female mammals. Limited research on appetite-controlling gastrointestinal peptides has taken place in females, simply because regular reproductive changes in steroid hormones present additional experimental factors to account for. This study focussed directly on the roles that gastrointestinal-secreted peptides may have in these reported, naturally occurring, changes to food intake during the rodent estrous cycle and aimed to determine whether peripheral changes occurred in the anorexigenic (appetite-reducing) hormones peptide-YY (PYY) and glucagon-like peptide-1 (GLP-1) in female Wistar rats (32-44 weeks of age). Total forms of each peptide were measured in matched fed and fasted plasma and descending colon tissue samples for each animal during the dark (feeding) phase. PYY concentrations did not significantly change between defined cycle stages, in either plasma or tissue samples. GLP-1 concentrations in fed plasma and descending colon tissue were significantly increased during proestrus, just prior to a significant reduction in fasted stomach contents at estrus, suggesting increased satiety and reduced food intake at this stage of the cycle. Increased proestrus GLP-1 concentrations could contribute to the reported reduction in food intake during estrus and may also have biological importance in providing the optimal nutritional and metabolic environment for gametes at the potential point of conception. Additional analysis of the findings demonstrated significant interactions of ovarian cycle stage and fed/fasted status with age on GLP-1, but not PYY plasma concentrations. Slightly older females had reduced fed plasma GLP-1 suggesting that a relaxation of regulatory control of this incretin hormone may also take place with increasing age in reproductively competent females.



http://ift.tt/2kOVrfi

Long Time No See: Enduring Behavioral and Neuronal Changes in Perceptual Learning of Motion Trajectories 3 Years After Training

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Here, we report on the long-term stability of changes in behavior and brain activity following perceptual learning of conjunctions of simple motion features. Participants were trained for 3 weeks on a visual search task involving the detection of a dot moving in a "v"-shaped target trajectory among inverted "v"-shaped distractor trajectories. The first and last training sessions were carried out during functional magnetic resonance imaging (fMRI). Learning stability was again examined behaviorally and using fMRI 3 years after the end of training. Results show that acquired behavioral improvements were remarkably stable over time and that these changes were specific to trained target and distractor trajectories. A similar pattern was observed on the neuronal level, when the representation of target and distractor stimuli was examined in early retinotopic visual cortex (V1–V3): training enhanced activity for the target relative to the surrounding distractors in the search array and this enhancement persisted after 3 years. However, exchanging target and distractor trajectories abolished both neuronal and behavioral effects, suggesting that training-induced changes in stimulus representation are specific to trained stimulus identities.</span>

http://ift.tt/2kP4Sez