Nurses' Perception of Challenges in the Use of an Electronic Nursing Documentation System.

This qualitative study was based on the Technology Acceptance Model and conducted through directed content analysis to explore perceptions of nurses in Iran of the challenges of using an electronic documentation system. Participants were selected through purposive sampling via interview from a teaching hospital in western Iran. Data were analyzed using MAXQDA 10. Data consistency was ensured through validation methods and by the researcher's prolonged engagement in the subject. Twelve codes, four subcategories, and two main categories ("perceived usefulness" and "perceived difficulty") emerged from the analysis of the data based on the Technology Acceptance Model. "Perceived usefulness" consisted of the subcategories "subjective norms" and "experienced benefits"; and "perceived difficulty" contained the subcategories "rationalization" as well as "challenges in accepting change." According to the Technology Acceptance Model, to promote acceptance of this system, the benefits of usage should be highlighted. The biggest hurdle to acceptance is familiarity and comfort with previous methods. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Development of a Smartphone Application to Monitor Pediatric Patient-Reported Outcomes.

Patient-reported outcomes are increasingly emphasized in clinical trials and population health studies. Our research team developed a smartphone app to track patient-reported outcomes of children with chronic diseases. The purpose of this study is to develop a patient-reported outcome reporting app and evaluate its usability. A multidisciplinary research team including health services researchers, pediatric nurses, and software engineers worked collaboratively in developing the patient-reported outcome app and administration portal. Group discussions and several rounds of feedback and modification were used. Ten pediatric patients with cancer, five parents, and two nurses participated in the usability study. We conducted content analyses in app development and usability evaluation. The app collected demographic information and patient-reported outcomes. Patient-reported outcomes were collected by Chinese versions of pediatric Patient-Reported Outcomes Measurement Information System Short Forms and Patient-Reported Outcomes Measurement Information System Parent Proxy Report Scales for Children. Pediatric patients aged 8 to 17 years and parents with a 5- to 7-year-old pediatric child used different age-appropriate questionnaires. The Web-based administration portal helped to manage demographic information, questionnaires, administrators, and survey-conducting organizations. The users liked the app. All participants felt that this app was easy to use and the interfaces were friendly to children. Nurses thought the administration portal interfaces were simple and the data were convenient to download for further analysis. We conclude that the app and its administration portal meet researchers and clinical nurses' demand and have potential to promote patient-reported outcomes in assessing quality of life and symptoms of pediatric patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Fine-needle aspiration cytology in primary cutaneous tumors

Background

Fine-needle aspiration biopsy (FNAB) is occasionally used in the evaluation of primary skin tumors. However, in routine evaluation of any soft tissue swelling we encounter the cases of skin lesions. It is essential to know FNAB features of skin lesions.

Materials and methods

We present detailed cytomorphologic features with histologic correlation of 28 primary skin tumors, evaluated over a period of 4 years.

Result

An accurate diagnosis was provided in 42.8% cases, while benign or malignant nature was correctly established in 82.1% cases.

Conclusions

The most common cause of incorrect diagnosis was sampling error and a definitive diagnosis was not provided in adnexal tumors due to overlap of cytologic features and lack of availability of architectural features. The knowledge of cytological features of the skin adnexal tumor is helpful to avoid any mistaken diagnosis.

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Unusual presentation of disseminated histoplasmosis in an immunocompetent patient

Abstract

Disseminated histoplasmosis (DH) is a systemic granulomatous disease caused by the fungus Histoplasma capsulatum. This disease occurs mainly in immunocompromised individuals with CD 4 counts less than 200 cell/µL and is rarely noted in immunocompetent person. In India, this disease has been reported from several parts of the country of which most cases are from eastern India which is considered to be endemic for this disease. Inhalation of the spores can lead to a self-limiting flulike illness in immunocompetent hosts. The most common organs involved are liver, spleen, bone marrow, lymphoreticular system, and gastrointestinal tract. Cutaneous manifestations of histoplasmosis are rare and are seen predominantly in persons with advanced human immunodeficiency virus (HIV) infections. We present a case of DH with generalized cutaneous lesions in a non-HIV infected adult which posed a diagnostic challenge to our clinical colleagues.

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The role of angled-tip microcatheter and microsphere injection velocity in liver radioembolization: a computational particle–hemodynamics study

Summary

Liver radioembolization is a promising treatment option for combating liver tumors. It is performed by placing a microcatheter in the hepatic artery and administering radiation-emitting microspheres through the arterial bloodstream so that they get lodged in the tumoral bed. In avoiding nontarget radiation, the standard practice is to conduct a pretreatment, in which the microcatheter location and injection velocity are decided. However, between pretreatment and actual treatment some of the parameters that influence the particle distribution in the liver can vary, resulting in radiation-induced complications. The present study aims to analyze the influence of a commercially available microcatheter with an angled tip and particle injection velocity in terms of segment-to-segment particle distribution. Specifically, four tip orientations and two injection velocities are combined to yield a set of eight numerical simulations of the particle–hemodynamics in a patient-specific truncated hepatic artery. For each simulation, four cardiac pulses are simulated. Particles are injected during the first cycle, and the remaining pulses enable the majority of the injected particles to exit the computational domain. Results indicate that, in terms of injection velocity, particles are more spread out in the cross-sectional lumen areas as the injection velocity increases. The tip's orientation also plays a role because it influences the near-tip hemodynamics, therefore altering the particle travel through the hepatic artery. However, results suggest that particle distribution tries to match the blood flow split, therefore particle injection velocity and microcatheter tip orientation playing a minor role in segment-to-segment particle distribution.

http://ift.tt/2pc2GeC

Deguelin induced differentiation of mutated NPM1 acute myeloid leukemia in vivo and in vitro.

Nucleophosmin (NPM1), a restricted nucleolar localization protein, shuttles between the nucleus and the cytoplasm. Mutated (Mt)-NPM1 protein, which has aberrant cytoplasmic dislocation of nucleophosmin, occurs in approximately one-third of acute myeloid leukemia cases. Deguelin, a rotenoid isolated from several plant species, is a strong antitumor agent. NOD/SCID mice xenografted with human Mt-NPM1 OCI/AML3 cell lines served as in-vivo models. Wright-Giemsa staining and flow cytometry analysis were used for differentiation assays. Associated molecular events were assessed by western blot and histological analyses. Kaplan-Meier estimates were used to calculate survival. Deguelin toxicity in mice was assessed by immunohistochemistry staining and serum markers. Clinical samples were differentiated by flow cytometry analysis. Deguelin induced differentiation by downregulating the Mt-NPM1 protein levels, which was accompanied by a decrease in SIRT1, p21, and HDAC1 and an increase in CEBP[beta] and granulocyte colony-stimulating factor receptor protein expression levels. A low-deguelin dose prolonged survival compared with the control group, and there were no apparent lesions to the brain, liver, heart, and kidney in vivo. In clinical samples, deguelin induced the differentiation of fresh blasts with Mt-NPM1 protein, but not with the wild-type NPM1 protein. Taken together, these findings further provide new evidence that the Mt-NPM1 protein plays an important role in inducing differentiation in vivo and in vitro. Mutated NPM1 protein may be a therapeutic target of deguelin in acute myeloid leukemia with the NPM1 mutation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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3-Bromopyruvate enhances TRAIL-induced apoptosis in human nasopharyngeal carcinoma cells through CHOP-dependent upregulation of TRAIL-R2.

Past reports have shown that the sensitivity of cancer cells to TRAIL-induced apoptosis is related to their expression of TRAIL-death receptors on the cell surface. However, the level of TRAIL-death receptors expression on cancer cells is always low. Our previous research showed that nasopharyngeal carcinoma (NPC) cells have a poor sensitivity to low doses of TRAIL. Here, we evaluated combined treatment with the energy inhibitor 3-bromopyruvate (3BP) and TRAIL as a method to produce an increased apoptotic response in NPC cells. The results showed that 3BP and TRAIL together produced higher cytotoxicity and increased TRAIL-R2 expression in NPC cells compared with the effects of either 3BP or TRAIL alone. These findings led us to hypothesize that 3BP may sensitize NPC cells to TRAIL. 3BP is a metabolic blocker that inhibits hexokinase II activity, suppresses ATP production, and induces endoplasmic reticulum (ER) stress. Our results showed that 3BP also activated AMP-activated protein kinase, which we found to play an important role in the induction of ER stress by 3BP. Furthermore, the induction of TRAIL-R2 expression and the sensitization of the NPC cells to TRAIL by 3BP were reduced when we inhibited the expression of CHOP. Taken together, our results showed that a low dose of 3BP sensitized NPC cells to TRAIL-induced apoptosis by the upregulation of CHOP, which was mediated by the activation of AMP-activated protein kinase and ER stress. The results showed that 3BP is a promising candidate agent for enhancing the therapeutic response to TRAIL in NPC. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Antitumor activities of the synthetic retinoid ST1926 in two-dimensional and three-dimensional human breast cancer models.

Despite recent advances in chemotherapy, aggressive and metastatic breast cancers remain refractory to targeted therapy and the development of novel drugs is urgently needed. Retinoids are crucial regulators of cellular proliferation, differentiation, and cell death, and have shown potent chemotherapeutic and chemopreventive properties. The major drawback of the use of all-trans retinoic acid (ATRA) in cancer therapy is disease relapse. Therefore, synthetic retinoids, specifically ST1926, have emerged as potent anticancer agents. Given the importance of the microenvironment in modulating the response of cancer cells to chemotherapeutic drugs, we investigated the antitumor activities of ST1926 in two-dimensional (2D) and different three-dimensional (3D) human breast cancer models and compared them with ATRA. We have shown that in 2D cell culture models, ATRA-resistant MCF-7 and MDA-MB-231 cells were sensitive to ST1926 at submicromolar concentrations that spared the 'normal-like' breast epithelial cells. ST1926 induced apoptosis and S-phase arrest, caused DNA damage, and downregulated the Wnt/[beta]-catenin pathway in breast cancer cells in 2D and 3D cell culture models. ST1926-mediated growth inhibition was independent of the retinoid receptor-signaling pathway. Long-term treatments with low submicromolar ST1926 concentrations reduced the anchorage-independent growth and decreased the sphere-forming ability of breast cancer progenitor cells in the sphere formation assay. Furthermore, ST1926 potently induced cell death of breast cancer cells under 3D conditions and spared the lumen-forming ability of normal-like breast epithelial cells. In tested 3D models, ATRA had minimal effects on the growth of breast cancer cells compared with ST1926. In summary, our results highlight the therapeutic potential of ST1926 in breast cancer and warrant its further clinical development. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Clusterin inhibition mediates sensitivity to chemotherapy and radiotherapy in human cancer.

Since its discovery in 1983, the protein clusterin (CLU) has been isolated from almost all human tissues and fluids and linked to the development of different physiopathological processes, including carcinogenesis and tumor progression. During the last few years, several studies have shown the cytoprotective role of secretory CLU in tumor cells, inhibiting their apoptosis and enhancing their resistance to conventional treatments including hormone depletion, chemotherapy, and radiotherapy. In an effort to determine the therapeutic potential that the inhibition of this protein could have on the development of new strategies for cancer treatment, numerous studies have been carried out in this field, with results, in most cases, satisfactory but sometimes contradictory. In this document, we summarize for the first time the current knowledge of the effects that CLU inhibition has on sensitizing tumor cells to conventional cancer treatments and discuss its importance in the development of new strategies against cancer. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Enhanced Neuronal Synchrony During Skilled Reaching at High Altitude

High Altitude Medicine & Biology , Vol. 0, No. 0.


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Primary Ewing’s sarcoma/primitive neuroectodermal tumor of the ileum: case report of a 16-year-old Chinese female and literature review

Ewing's sarcoma (ES) and primitive neuroectodermal tumors (PNET) are closely related tumors. Although soft tissue ES/PNET are common in clinical practice, they are rare in the small intestine. Because of the a...

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Androgen receptor variant AR-V9 is co-expressed with AR-V7 in prostate cancer metastases and predicts abiraterone resistance

Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies.  Accordingly, efforts are underway to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC).  The purpose of this study was to understand whether other AR variants may be co-expressed with AR-V7 and promote resistance to AR-targeted therapies.<br /><br /> Experimental Design:  We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models.  Co-expression of AR-V7 and AR-V9 mRNA in CRPC metastases and circulating tumor cells was assessed by RNA-seq and RT-PCR, respectively.  Expression of AR-V9 protein in CRPC models was evaluated with polyclonal antisera.  Multivariate analysis was performed to test whether AR variant mRNA expression in metastatic tissues was associated with a 12-week progression-free survival endpoint in a prospective clinical trial of 78 CRPC-stage patients initiating therapy with the androgen synthesis inhibitor, abiraterone acetate.   <br /><br />Results: AR-V9 was frequently co-expressed with AR-V7.  Both AR variant species were found to share a common 3' terminal cryptic exon, which rendered AR-V9 susceptible to experimental manipulations that were previously-thought to target AR-V7 uniquely.  AR-V9 promoted ligand-independent growth of prostate cancer cells.  High AR-V9 mRNA expression in CRPC metastases was predictive of primary resistance to abiraterone acetate (HR = 4.0, 95% CI = 1.31-12.2, P = 0.02).  <br /><br />Conclusions: AR-V9 may be an important component of therapeutic resistance in CRPC.

http://ift.tt/2pFKnls

Elacestrant (RAD1901), a selective estrogen receptor degrader (SERD), has anti-tumor activity in multiple ER+ breast cancer patient-derived xenograft models

PURPOSE: Estrogen receptor-positive (ER+) breast cancers are typically treated with endocrine agents, and dependence on the ER pathway is often retained even after multiple rounds of anti-estrogen therapy. Selective estrogen receptor degraders (SERDs) are being developed as a strategy to more effectively target ER and exploit ER dependence in these cancers, which includes inhibiting both wild-type and mutant forms of ER. The purpose of this study was to evaluate the efficacy of a novel orally bioavailable SERD, elacestrant (RAD1901), in preclinical models of ER+ breast cancer. <p>EXPERIMENTAL DESIGN: Elacestrant was evaluated as a single agent and in combination with palbociclib or everolimus in multiple ER+ breast cancer models, including several patient-derived xenograft models.</p> <p>RESULTS: Elacestrant induces the degradation of ER, inhibits ER-mediated signaling and growth of ER+ breast cancer cell lines in vitro and in vivo and significantly inhibits tumor growth of multiple PDX models. Furthermore, we demonstrate that elacestrant in combination with palbociclib or everolimus can lead to greater efficacy in certain contexts. Finally, elacestrant exhibits significant anti-tumor activity both as a single agent and in combination with palbociclib in two patient-derived breast cancer xenograft models harboring ESR1 mutations.</p> <p> </p> <p>CONCLUSIONS: These data underscore the potential clinical utility of elacestrant as a single agent and as a combination therapy, for both early and late stage ER+ disease.

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Aluminum Trichloride Inhibited Osteoblastic Proliferation and Downregulated the Wnt/β-Catenin Pathway

Abstract

Aluminum (Al) exposure inhibits bone formation. Osteoblastic proliferation promotes bone formation. Therefore, we inferred that Al may inhibit bone formation by the inhibition of osteoblastic proliferation. However, the effects and molecular mechanisms of Al on osteoblastic proliferation are still under investigation. Osteoblastic proliferation can be regulated by Wnt/β-catenin signaling pathway. To investigate the effects of Al on osteoblastic proliferation and whether Wnt/β-catenin signaling pathway is involved in it, osteoblasts from neonatal rats were cultured and exposed to 0, 0.4 mM (1/20 IC₅₀), 0.8 mM (1/10 IC₅₀), and 1.6 mM (1/5 IC₅₀) of aluminum trichloride (AlCl₃) for 24 h, respectively. The osteoblastic proliferation rates; Wnt3a, lipoprotein receptor-related protein 5 (LRP-5), T cell factor 1 (TCF-1), cyclin D1, and c-Myc messenger RNA (mRNA) expressions; and p-glycogen synthase kinase 3β (GSK3β), GSK3β, and β-catenin protein expressions indicated that AlCl₃ inhibited osteoblastic proliferation and downregulated Wnt/β-catenin signaling pathway. In addition, the AlCl₃ concentration was negatively correlated with osteoblastic proliferation rates and the mRNA expressions of Wnt3a, c-Myc, and cyclin D1, while the osteoblastic proliferation rates were positively correlated with mRNA expressions of Wnt3a, c-Myc, and cyclin D1. Taken together, these findings indicated that AlCl₃ inhibits osteoblastic proliferation may be associated with the inactivation of Wnt/β-catenin signaling pathway.

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Cardioprotective Effect of Aloe vera Biomacromolecules Conjugated with Selenium Trace Element on Myocardial Ischemia-Reperfusion Injury in Rats

Abstract

The present study was undertaken to evaluate the cardioprotection potential and underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se-AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo. Myocardial I/R injury was induced by occluding the left anterior descending coronary artery (LAD) for 30 min followed by 2-h continuous reperfusion. Pretreatment with Se-AVP (100, 200, and 400 mg/kg) attenuated myocardial damage, as evidenced by reduction of the infarct sizes, increase in serum and myocardial endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP is further supported by the decreased levels of cardiac marker enzymes creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities in I/R rats. Additionally, cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining and the result showed that the percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a protective effect against myocardial I/R injury in rats by augmenting endogenous antioxidants and protecting rat hearts from oxidative stress-induced myocardial apoptosis.

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Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner

Abstract

The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2′,7′-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 μM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.

http://ift.tt/2pLXG2c

Fluoride Exposure Aggravates the Testicular Damage and Sperm Quality in Diabetic Mice: Protective Role of Ginseng and Banaba

Abstract

Fluoride toxicity is known to pose infertility in fluoride-intoxicated animals as well as in people residing in fluoride endemic zones. The present study addresses the degree of impairments caused due to co-exposure of high fluoride toxicity in diabetic mice. Swiss mice, Mus musculus, were subjected to fluoride toxicity by providing fluoride-supplemented drinking water (600 ppm NaF) for a period of 30 days after the confirmation of streptozotocin-induced diabetes(STZ, 50 mg/kgbw). Consequently, aggravated hyperglycemia and tissue fluoride accumulation were witnessed in fluoride-intoxicated diabetic mice; later, these toxicated mice were treated with ginseng extract (GE) and banaba leaf extract, (BLE) at dose of 150 mg/kgbw/day alone and in combination for 15 and 30-day duration to check the efficacy of phytoextracts in reversing the toxicity. The spermatological indices studied, such as sperm density, motility, viability and morphology as well as the testicular biochemical parameters showed enhanced impairment in reproductive status of fluoride-intoxicated diabetic mice. Further, 15-days administration of GE and BLE in combination at a dose of 150 mg/kgbw/day was found to be beneficial in normalizing the alterations observed upon fluoride intoxication to diabetic mice. However, the correlates showed moderate association between blood glucose levels and the spermatological as well as biochemical indices wherein the tissue fluoride levels correlate least.

http://ift.tt/2pMvjD9

Levels of Metals in Kidney, Liver, and Muscle Tissue and their Influence on the Fitness for the Consumption of Wild Boar from Western Slovakia

Abstract

Due to environmental pollution, wild animals are exposed to various pollutants. Some game animals, such as wild boars are used by people for food, but their meat is not evaluated regarding pollution transfer, since they are unavailable on the official market. The aim of this paper is to present the concentrations of chosen metals (Cd, Co, Cu, Hg, Pb, and Zn) in the kidneys, liver, and muscles of wild boars (n = 40) hunted in eastern Slovakia, as derivatives of physiological distribution and anthropogenic pollution. We found that sex was not a statistically significant factor for metal concentrations. Tissue differences were observed for all the metals studied except for Co. Cd, Cu, and Hg showed the highest median concentrations in kidney tissue with the lowest in muscle tissue (2.73, 3.78, and 0.061 μg/g w.w., respectively). The highest Zn median concentration was noted in the liver tissue with the lowest in muscle tissue. Co and Cu concentrations varied according to the age groups. Correlations between metal concentrations in muscle and kidney tissue were not especially strong; such relationships were not found in liver tissue. Among all the potential relationships of the given metal concentrations between tissues, the only significant relationship, albeit weak, was noted for Pb in muscle and liver tissue. The concentrations found seem not to be extremely high, but according to EU maximum permitted residue levels for Cd and Pb concentrations in meat, none of the samples studied was fully fit for human consumption. TWI and risk was also excessive for both metals.

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Individual and Combined Effects of Arsenic and Lead on Behavioral and Biochemical Changes in Mice

Abstract

Arsenic (As) toxicity has caused an environmental tragedy affecting millions of people in the world. Little is known about the toxic effects of As on neurobehavioral and biochemical changes in vivo. Along this line of metal toxicity, co-exposure of lead (Pb) could aggravate the situation in the host. The present study was designed to explore the combined effects of As and Pb on behavioral changes like anxiety, spatial memory and learning impairment, and blood indices related to organ dysfunction. Exposure of mice to As (10 mg/kg body weight), Pb (10 mg/kg body weight), and As + Pb via drinking water significantly decreased the time spent exploring the open arms while it increased the time spent in the closed arms compared to control mice in the elevated plus maze. The mean latency time of the control group to find the platform decreased significantly during the learning for 7 days compared to all three treated groups in the Morris water maze test, and the As-exposed group spent significantly less time in the desired quadrant as compared to the control group in the probe trial. Both metals posed an anxiety-like behavior and deficits in spatial memory and learning, and also altered blood indices related to liver and kidney dysfunction, and a combined exposure of these metals inhibited the individual accumulation of As and Pb. Taken together, these data suggest that As has more toxic effects on neurobehavioral and biochemical changes than Pb, and there may be antagonism in the effects and accumulation between these two toxicants.

http://ift.tt/2pLRZ45

Combined Effects of Phytoestrogen Genistein and Silicon on Ovariectomy-Induced Bone Loss in Rat

Abstract

This study was performed to evaluate the effect of concomitant supplementation of genistein and silicon on bone mineral density and bone metabolism-related markers in ovariectomized rat. Three-month-old Sprague Dawley female rats were subjected to bilateral ovariectomy (OVX) or sham surgery, and then the OVX rats were randomly divided into four groups: OVX-GEN, OVX-Si, OVX-GEN-Si, and OVX. Genistein and silicon supplementation was started immediately after OVX and continued for 10 weeks. In the OVX-GEN group, 5 mg genistein per gram body weight was injected subcutaneously. The OVX-Si group was given soluble silicon daily in demineralized water (Si 20 mg/kg body weight/day). The OVX-GEN-Si group was given subcutaneous injections of 5 mg genistein per gram body weight, at the same time, given soluble silicon daily (Si 20 mg/kg body weight/day). The results showed that the genistein supplementation in the OVX rats significantly prevented the loss of uterus weight; however, the silicon supplementation showed no effect on the uterus weight loss. The lumbar spine and femur bone mineral density was significantly decreased after OVX surgery; however, this decrease was inhibited by the genistein and/or silicon, and the BMD of the lumbar spine and femur was the highest in the OVX-GEN-Si-treated group. Histomorphometric analyses showed that the supplementation of genistein and/or silicon restored bone volume and trabecular thickness of femoral trabecular bone in the OVX group. Besides, the treatment with genistein and silicon for 10 weeks increased the serum levels of calcium and phosphorus in the OVX rats; serum calcium and serum phosphorus in the OVX-GEN-Si group were higher than those in the OVX-GEN and OVX-Si group (P < 0.05). At the same time, the treatment with genistein and/or silicon decreased serum alkaline phosphatase (ALP) and osteocalcin, which were increased by ovariectomy; serum ALP and osteocalcin in the OVX-GEN-Si group were lower than those in the OVX-GEN and OVX-Si groups (P < 0.05). The results above indicate that genistein and silicon have synergistic effects on bone formation in ovariectomized rats.

http://ift.tt/2pMTyAV

Analysis of Hair Trace Elements in Children with Autism Spectrum Disorders and Communication Disorders

Abstract

The primary objective of the present study is analysis of hair trace elements content in children with communication disorder (CD) and autism spectrum disorder (ASD). A total of 99 children from control, CD, and ASD groups (n = 33) were examined. All children were additionally divided into two subgroups according to age. Hair levels of trace elements were assessed using inductively coupled plasma mass spectrometry. The difference was considered significant at p < 0.01. The obtained data demonstrate that children with CD are characterized by significantly increased hair lithium (Li) (96 %; p = 0.008), selenium (Se) (66 %; p < 0.001), arsenic (As) (96 %; p = 0.005), beryllium (Be) (150 %; p < 0.001), and cadmium (Cd) (72 %; p = 0.007) content, being higher than the respective control values. In the ASD group, hair copper (Cu), iodine (I), and Be levels tended to be lower than the control values. In turn, the scalp hair content of Se significantly exceeded the control values (33 %; p = 0.004), whereas the level of iron (Fe) and aluminum (Al) tended to increase. After gradation for age, the most prominent differences in children with CD were detected in the elder group (5–8 years), whereas in the case of ASD—in the younger group (3–4 years old). Taking into account the role of hair as excretory mechanism for certain elements including the toxic ones, it can be proposed that children suffering from ASD are characterized by more profound alteration of metal handling and excretion in comparison to CD.

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Anemia and Dental Caries in Pregnant Women: a Prospective Cohort Study

Abstract

The objective was to evaluate the effect of anemia during pregnancy on the risk of dental caries development in pregnant women. A prospective cohort including a sample of pregnant women in a prenatal care unit of São Luís, Brazil, was done. The incidence of dental caries during pregnancy, according to Nyvad's criteria, was the outcome. The main independent variables were serum iron, ferritin, hemoglobin, erythrocyte, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW). Pregnant women (n = 121) were evaluated at two moments: up to 16th week of gestational age (T1) and in the last trimester of pregnancy (T2). Crude and adjusted associations were estimated by the incidence ratio risk (IRR) and respective 95% confidence intervals (95%CI). After adjustment, higher serum concentrations of ferritin (IRR = 0.97, 95%CI 0.95–0.99) in T1, and Fe (IRR = 0.99, 95%CI 0.98–0.99), ferritin (IRR = 0.99, 95%CI 0.98–0.99), erythrocyte (IRR = 0.71, 95%CI 0.50–0.99), hemoglobin (IRR = 0.84, 95%CI 0.73–0.96), hematocrit (IRR = 0.93, 95%CI 0.88–0.98), MCV (IRR = 0.91, 95%CI 0.86–0.96), and MCH (IRR = 0.83, 95%CI 0.74–0.93) in T2, were associated with fewer incidence of dental caries in pregnant women. Iron deficiency anemia during pregnancy is a risk factor for the incidence of dental caries in these women.

http://ift.tt/2pMulXg

Pre-Clinical Study for the Antidiabetic Potential of Selenium Nanoparticles

Abstract

This research was delineated to explore the efficacy of selenium nanoparticles delivered in liposomes (L-Se) in the mitigation of type-2 diabetes mellitus. Adult female Wistar rats were assigned into four groups: group I, the normal control group in which the rats received normal saline solution orally; group II, the diabetic control group in which the rats were injected intraperitoneally with a single dose of streptozotocin (STZ) for induction of diabetes; group III, the metformin (Met)-treated group in which the diabetic rats were treated orally with Met; and group IV, the L-Se-treated group in which the diabetic rats were treated orally with L-Se. All treatments were delivered for 21 days. Blood and pancreas tissue samples were obtained for biochemical analysis, immunohistochemical examinations, and histopathological investigation. The L-Se-treated group showed significant drop in serum glucose and pancreatic malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-α (TNF-α), and prostaglandin F2α (PGF2α) levels associated with significant rise in serum insulin and pancreatic glutathione, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) values, in addition to significant improvement in the immunohistochemical indices (insulin and glucagon). Aforementioned results are appreciated by the histopathological findings of pancreatic tissue. In conclusion, our data have brought about compelling evidence favoring the antidiabetic potency of elemental selenium nanoparticles delivered in liposomes through preservation of pancreatic β cell integrity with consequent increment of insulin secretion and in turn glucose depletion, repression of oxidative stress, potentiation of the antioxidant defense system, and inhibition of pancreatic inflammation.

http://ift.tt/2pMGwng

Metabolomics and Trace Element Analysis of Camel Tear by GC-MS and ICP-MS

Abstract

Camel tear metabolomics and elemental analysis are useful in getting the information regarding the components responsible for maintaining the protective system that allows living in the desert and dry regions. The aim of this study was to correlate that the camel tears can be used as artificial tears for the evaluation of dryness in the eye. Eye biomarkers of camel tears were analyzed by gas chromatography-mass spectroscopy (GC-MS) and inductively coupled plasma mass spectroscopy (ICP-MS). The major compounds detected in camel tears by GC-MS were alanine, valine, leucine, norvaline, glycine, cadaverine, urea, ribitol, sugars, and higher fatty acids like octadecanoic acid and hexadecanoic acid. GC-MS analysis of camel tears also finds several products of metabolites and its associated metabolic participants. ICP-MS analysis showed the presence of different concentration of elemental composition in the camel tears.

http://ift.tt/2pM4dKi

Beer as a Rich Source of Fluoride Delivered into the Body

Abstract

Fluoride is an element which in the minimum amount is necessary for the proper construction of the teeth and bones. But on the other hand, it increases the synthesis of reactive oxygen species, inflammatory mediators, and impairs the action of enzymes. Beer is the most popular alcoholic beverage in the world. Due to its prevalence and volume of consumption, it should be considered as a potential source of F- and taken into account in designing a balanced diet. Therefore, the aim of this study was to analyze beer samples in terms of F- levels. The concentrations of fluoride were examined using ion-selective electrode Thermo Scientific Orion and statistical analysis was based on two-way ANOVA and t test. When compared to imported beers, Polish beers were characterized by the lowest mean F- concentration (0.089 ppm). The highest mean F- concentrations were recorded in beers from Thailand (0.260 ppm), Italy (0.238 ppm), Mexico (0.210 ppm), and China (0.203 ppm). Our study shows that beer is a significant source of fluoride for humans, which is mainly associated with the quality of the water used in beer production.

http://ift.tt/2pMD2RH

Tissue-Specific Regulation of the Contents and Correlations of Mineral Elements in Hens by Zinc Oxide Nanoparticles

Abstract

Due to their small size, zinc oxide (ZnO) nanoparticles (NPs) are readily absorbed and easily cross biological barriers, which make them promising candidates as diet additives. However, some studies have reported that ZnO NPs cause toxicity; therefore, their safety and potency as diet additives for farm animals should be established. This study was the first to fully evaluate the effects of ZnO NPs on the homeostasis of eight elements in seven organs/tissues. The regulation of element homeostasis was found to be organ specific with no influence on oxidation status, anti-oxidation capability, or organ damage. ZnO NPs may specifically regulate the homeostasis of mineral elements and affect the following correlations: (1) between the element content in each organ and the concentration of Zn used in ZnSO₄ or ZnO NP treatments; (2) between ZnO NP and ZnSO₄ treatments for the same element in each organ; and (3) between elements (in each organ in ZnSO₄ or ZnO NP treatments) in layers' organs/tissues. The use of ZnO NPs as diet additives for animals should be implemented cautiously because, among other uncertainties, they may affect mineral element content.

http://ift.tt/2pMQzbF

An Optimal Dietary Zinc Level of Brown-Egg Laying Hens Fed a Corn–Soybean Meal Diet

Abstract

An experiment was conducted to estimate the optimal dietary zinc (Zn) level of brown-egg laying hens fed a corn–soybean meal diet from 20 to 40 weeks of age. A total of 120 20-week-old Beijing Red commercial laying hens were randomly allotted by bodyweight to one of five treatments with six replicates of four birds each in a completely randomized design, and fed a Zn-unsupplemented corn–soybean meal basal diet containing 27.95 mg Zn/kg by analysis and the basal diets supplemented with 30, 60, 90, or 120 mg Zn/kg as Zn sulfate (reagent grade ZnSO₄·7H₂O) for a duration of 20 weeks. Laying performance, egg quality, tissue Zn concentrations, and activities of serum alkaline phosphatase (AKP), and liver copper-Zn superoxide dismutase (CuZnSOD) were measured. Regression analyses were performed to estimate an optimal dietary Zn level whenever a significant quadratic response (P < 0.05) was observed. Tibia Zn concentration (P = 0.002) and serum AKP activity (P = 0.010) showed significant quadratic responses to dietary supplemental Zn levels. The estimates of dietary Zn requirements for brown-egg laying hens from 20 to 40 weeks of age were 71.95 and 64.63 mg/kg for tibia Zn concentration and serum AKP activity, respectively. The results from this study indicate that the tibia Zn might be a more suitable and reliable parameter for Zn requirement estimation, and the optimal dietary Zn level would be about 72 mg/kg for brown-egg laying hens fed a corn–soybean meal diet from 20 to 40 weeks of age.

http://ift.tt/2pLRXct

Fitness Evaluation of Ruditapes philippinarum Exposed to Ni

Abstract

In this study, long-term effects of Ni, a widespread heavy metal in the aquatic ecosystems, have been determined on growth and lethality of the clam Ruditapes philippinarum, a known bioindicator of the marine environment. Three/four-month-old bivalves have been exposed to different concentrations of Ni dissolved in synthetic seawater. Growth and lethality as endpoints after 28 days of treatment have been observed. Obtained results are the following: EC₂₅ = 3.97 ± 0.94 and 9.45 ± 1.59 mg/L and NOEC = 1.56 and 6.25 mg/L for growth and mortality, respectively. Moreover, this study can be considered a new tool for the evaluation of fitness of bivalve clam, together with other biological responses following to the biological impacts of metal pollution.

http://ift.tt/2pMGAU2

Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats

Abstract

The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30–40 days of age, pre-pubertal period) of 40–50 g body weight were divided into the following: the ZC (zinc control) group—fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group—fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group—received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P < 0.05) decrease in diet consumption, body weight and pituitary weight and decrease in gradation of intensity of zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.

http://ift.tt/2q56DGN

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

Abstract

Fluorides occur naturally in the environment, the daily exposure of human organism to fluorine mainly depends on the intake of this element with drinking water and it is connected with the geographical region. In some countries, we can observe the endemic fluorosis—the damage of hard and soft tissues caused by the excessive intake of fluorine. Recent studies showed that fluorine is toxic to the central nervous system (CNS). There are several known mechanisms which lead to structural brain damage caused by the excessive intake of fluorine. This element is able to cross the blood-brain barrier, and it accumulates in neurons affecting cytological changes, cell activity and ion transport (e.g. chlorine transport). Additionally, fluorine changes the concentration of non-enzymatic advanced glycation end products (AGEs), the metabolism of neurotransmitters (influencing mainly glutamatergic neurotransmission) and the energy metabolism of neurons by the impaired glucose transporter—GLUT1. It can also change activity and lead to dysfunction of important proteins which are part of the respiratory chain. Fluorine also affects oxidative stress, glial activation and inflammation in the CNS which leads to neurodegeneration. All of those changes lead to abnormal cell differentiation and the activation of apoptosis through the changes in the expression of neural cell adhesion molecules (NCAM), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and MAP kinases. Excessive exposure to this element can cause harmful effects such as permanent damage of all brain structures, impaired learning ability, memory dysfunction and behavioural problems. This paper provides an overview of the fluoride neurotoxicity in juveniles and adults.

http://ift.tt/2pLRWVX

Effect of Feeding and Withdrawal of Vanadium and Vitamin C on Egg Quality and Vanadium Residual Over Time in Laying Hens

Abstract

This experiment examined the egg quality of hens fed vanadium (V) and vitamin C (VC) during storage, as well as the V and VC withdrawal on egg quality and V residual in egg. A total of 360 laying hens (31 weeks old) were randomly allotted into a 3 × 2 factorial arrangement treatments (6 replicates and 10 chicks per replicate) with three levels of dietary V (0, 5, and 10 mg/kg) and two levels of VC (0 and 100 mg/kg) for 19 weeks (feeding V and VC 12 weeks, recovery 7 weeks). The V residual in eggs at 4, 8, and 12th weeks were increased (linear effect, P ≤ 0.01) as V levels increased and was not detected in albumen at 7th week after V withdrawal. Followed by 12-week feeding period, albumen height and Haugh unit of eggs during 2-week storage were decreased (linear and quadratic effect, P < 0.01) by dietary V supplementation. Lightness value was increased (linear effect, P < 0.01), whereas redness and yellowness value of the eggshell were lowered (linear effect, P < 0.01) in V-containing diet. During 7-week withdrawal period, eggs from groups pre-feeding 5 and 10 mg/kg V had lower (linear effect, P < 0.01) overall albumen height and Haugh unit. The reducing effect on albumen height and HU continued to be observed until the seventh week, whereas the bleaching effect on eggshell color disappeared after 1-week withdrawal. The results indicated that feeding 5 or 10 mg/kg V increases egg V residual and reduces egg albumen quality and bleached the shell color, and the impaired albumen quality induced by 10 mg/kg of V lasted at least 6 weeks after changing to no V supplementation diet. The addition of VC did not show to affect egg quality during storage or recovery phase.

http://ift.tt/2q5gPiz

Effect of Gestational Intake of Fisetin (3,3′,4′,7-Tetrahydroxyflavone) on Developmental Methyl Mercury Neurotoxicity in F 1 Generation Rats

Abstract

Methyl mercury (MeHg) is a developmental neurotoxin that causes irreversible cognitive damage in offspring of gestationally exposed mothers. Currently, no preventive drugs are established against MeHg developmental neurotoxicity. The neuroprotective effect of gestational administration of a flavanoid against in utero toxicity of MeHg is not explored much. Hence, the present study validated the effect of a bioactive flavanoid, fisetin, on MeHg developmental neurotoxicity outcomes in rat offspring at postnatal weaning age. Pregnant Wistar rats were simultaneously given MeHg (1.5 mg/kg b.w.) and two doses of fisetin (10 and 50 mg/kg b.w. in two separate groups) orally from gestational day (GD) 5 till parturition. Accordingly, after parturition, on postnatal day (PND) 24, weaning F₁ generation rats were studied for motor and cognitive behavioural changes. Biochemical and histopathological changes were also studied in the cerebral cortex, cerebellum and hippocampus on PND 25. Administration of fisetin during pregnancy prevented behavioural impairment due to transplacental MeHg exposure in weaning rats. Fisetin decreased the levels of oxidative stress markers, increased enzymatic and non-enzymatic antioxidant levels and increased the activity of membrane-bound ATPases and cholinergic function in F₁ generation rats. In light microscopic studies, fisetin treatment protected the specific offspring brain regions from significant morphological aberrations. Between the two doses of fisetin studied, 10 mg/kg b.w. was found to be more satisfactory and effective than 50 mg/kg b.w. The present study shows that intake of fisetin during pregnancy in rats ameliorated in utero MeHg exposure-induced neurotoxicity outcomes in postnatal weaning F₁ generation rats.

http://ift.tt/2pLYXWY

Evaluation of Serum Trace Element Levels and Superoxide Dismutase Activity in Patients with Inflammatory Bowel Disease: Translating Basic Research into Clinical Application

Abstract

The relationship of minerals and trace elements with inflammatory bowel disease (IBD) is complex. Alterations in their metabolism can be induced by the diseases and their complications. To study the role of trace elements in IBD patients' serum zinc and copper and their related enzymes, including superoxide dismutase (SOD), activity were measured in patients with IBD patients as well as in healthy subjects. In addition, the correlation between serum trace element levels, albumin, total protein, urea level, copper/zinc ratio, and disease activity (DA) was determined in these subjects. Serum samples were obtained from 35 patients (19 ulcerative colitis (UC) and 16 Crohn's disease (CD)) in the active phase of the disease and 30 healthy control subjects. Serum levels of zinc, copper, SOD activity, albumin, total protein, and urea were measured. The results were compared between the two groups using independent Student's t test in statistical analysis. Serum levels of zinc, SOD activity, albumin, and total protein were significantly lower (P < 0.05) in patients than controls, while serum urea level was significantly higher in patients compared to controls. Copper concentrations did not differ between patients with IBD (mean ± SD, 58.8 ± 20.7 μg/d) and controls (55.57 ± 12.6 μg/d). Decreased levels of zinc and SOD activity are associated with increased inflammatory processes indicating inappropriate antioxidant system in patients with IBD. Additionally, lower levels of albumin and total protein with higher level of urea reflect metabolic problems in liver system.

http://ift.tt/2q5cuvA

Modeling Renal Cell Carcinoma in mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade [Research Articles]

Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutation, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with Pax8, a developmental lineage-specific transcription factor, led to ccRCC of different grade. Bap1-deficient tumors were high grade and showed greater mTORC1 activation than Pbrm1-deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1, in Pbrm1-deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histological grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCC may arise from Bowman capsule cells.

http://ift.tt/2pbCcK7

Uncertainty quantification of two models of cardiac electromechanics

Summary

Computational models of the heart have reached a maturity level that render them useful for in-silico studies of arrhythmia and other cardiac diseases. However, the translation to the clinic of cardiac simulations critically depends on demonstrating the accuracy, robustness and reliability of the underlying computational models under the presence of uncertainties. In this work, we study for the first time the effect of parameter uncertainty on two state-of-the-art coupled models of excitation-contraction of cardiac tissue. To this end, we perform forward uncertainty propagation and sensitivity analyses to understand how variability in key maximal conductances affect selected quantities of interest, such as the action potential duration (APD₉₀), maximum intracellular calcium concentration, cardiac stretch and stress. redOur results suggest a strong linear relationship between selected maximal conductances and quantities of interest for a variability in parameters up to 25%, which justifies the construction of linear response surfaces that are used to compute the empirical probability density functions of all the QOIs under study. For both electromechanical models analyzed, uncertainty in the material parameters associated to the passive mechanical response of cardiac tissue does not affect the duration of action potentials, neither the amplitude of intracellular calcium concentrations. Our results confirm the poor mechanoelectric feedback that classical models of cardiac electromechanics have, even under the presence of parameter uncertainty. This article is protected by copyright. All rights reserved.

http://ift.tt/2pbL4zn

Bilateral versus unilateral placement of metal stents for inoperable high-grade malignant hilar biliary strictures: a multicenter, prospective, randomized study (with video)

The efficacy of palliative biliary drainage using bilateral or unilateral self-expandable metal stents (SEMSs) for a malignant hilar biliary stricture (MHS) remains controversial. This prospective, randomized, multicenter study investigated whether bilateral drainage using SEMSs is superior to unilateral drainage in patients with inoperable MHS.

http://ift.tt/2qxipcG

Gastric Mucosal Devitalization Reduces Adiposity and Improves Lipid and Glucose Metabolism in Obese Rats

The gastric mucosa is an endocrine organ that regulates satiation pathways by expression of orexigenic and anorexigenic hormones. Vertical sleeve gastrectomy (VSG), excludes gastric mucosa and reduces gastric volume. Our study aims to investigate the independent effects of altering gastric mucosa on obesity and its related comorbidities.

http://ift.tt/2pLOrPj

Su1624 Efficacy of Endoscopic Submucosal Dissection for Early Rectal Cancer

The operative method for early stage low rectal cancer must be selected carefully from the perspective of functional preservation. Compared with other operative techniques, endoscopic resection, especially endoscopic submucosal dissection (ESD), is a minimally invasive treatment that has a high en bloc resection rate and using which, surgical resection may be avoided. Furthermore, ESD is considered an effective treatment for lesions extending to the dentate line, residual recurrent lesions, scar tissue lesions, and large lesions (≥ 5 cm), which were considered difficult to resect using conventional endoscopic treatments (Endoscopic mucosal resection :EMR and Endoscopic piecemeal mucosal resection :EPMR).

http://ift.tt/2qxnaTH

Novel androgen receptor co-regulator GRHL2 exerts both oncogenic and anti-metastatic functions in prostate cancer

Alterations to the expression and activity of androgen receptor (AR) co-regulators in prostate cancer is an important mechanism driving disease progression and therapy resistance. Using a novel proteomic technique, we identified a new AR co-regulator, the transcription factor Grainyhead-like 2 (GRHL2), and demonstrated its essential role in the oncogenic AR signaling axis. GRHL2 colocalized with AR in prostate tumors and was frequently amplified and upregulated in prostate cancer. Importantly, GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR's transcriptional activity, and co-located with AR at specific sites on chromatin to regulate genes relevant to disease progression. GRHL2 is itself an AR-regulated gene, creating a positive feedback loop between the two factors. The link between GRHL2 and AR also applied to constitutively active truncated AR variants (ARVs), as GRHL2 interacted with and regulated ARVs and vice versa. These oncogenic functions of GRHL2 were counterbalanced by its ability to suppress epithelial-mesenchymal transition and cell invasion. Mechanistic evidence suggested that AR assisted GRHL2 in maintaining the epithelial phenotype. In summary, this study has identified a new AR co-regulator with a multifaceted role in prostate cancer, functioning as an enhancer of the oncogenic AR signaling pathway but also a suppressor of metastasis-related phenotypes.

http://ift.tt/2pemPBG

Oncogenic RAS regulates long non-coding RNA Orilnc1 in human cancer

RAS and its downstream cascades transmit cellular signals resulting in increased transcription of genes involved in cell growth and division. Protein-coding gene targets of RAS signaling have been characterized extensively, but long non-coding RNAs (lncRNA) regulated by these processes have not. Using a custom-designed lncRNA microarray, we identified the lncRNA Orilnc1 as a genetic target of RAS that is critical for RAS oncogenicity. Orilnc1 expression was regulated by RAS-RAF-MEK-ERK signaling via the transcription factor AP1. Orilnc1 was highly expressed in BRAF-mutant cancers such as melanoma. Silencing of Orilnc1 blocked tumor cell proliferation and growth in vitro and in vivo. Additionally, Orilnc1 blockade reduced expression of Cyclin E1 and induced G1/S cell cycle arrest in tumor cells. Taken together, our results identify Orilnc1 as a novel, non-protein mediator of RAS/RAF activation which may serve as a therapeutic target in RAS/RAF-driven cancers.

http://ift.tt/2p3eFQn

Beta-blocker drug use and survival among patients with pancreatic adenocarcinoma

Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register (n=2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register. Cancer-specific mortality was assessed using the Swedish Cause of Death Register. We used multivariable Cox regression adjusted for sociodemographic factors, tumor characteristics, comorbidity score and other medications to estimate hazard ratios (HR) and 95% confidence intervals (CI) for cancer-specific mortality associated with beta-blocker use during the 90 day period before cancer diagnosis. A total of 2,054 (86%) died with pancreatic cancer recorded as the underlying cause of death during a maximum of 5 years follow-up (median 5 months). Patients who used beta-blockers (n=522) had a lower cancer-specific mortality rate than non-users (adjusted HR 0·79; 95% CI 0·70-0·90, p<0·001). This observed rate reduction was more pronounced among patients with localized disease at diagnosis (n=517; adjusted HR 0·60; 95% CI 0·43-0·83, p=0·002), especially for users with higher daily doses (HR 0·54; 95% CI 0·35-0·83, p=0·005). No clear rate differences were observed by beta-blocker receptor selectivity. Our results support the concept that beta-blocker drugs may improve the survival of PDAC patients, particularly among those with localized disease.

http://ift.tt/2peYD1T

Analysis of electroencephalogram characteristics of anti-NMDA receptor encephalitis patients in China

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis was first reported by Dalmau et al in 2007 (Dalmau et al., 2007). This autoimmune encephalitis is serious and can be fatal; however, the disease condition can be significantly improved or even cured after early diagnosis and active treatment. Due to the limitations of detection techniques, the identification of anti-NMDAR encephalitis or the rapid obtainment of detection of anti-NMDAR encephalitis-specific antibodies cannot be achieved in many regions.

http://ift.tt/2q521AC

A Novel Scheme for the Validation of an Automated Classification Method for Epileptic Spikes by Comparison with Multiple Observers

As part of standard practice for assessing patients with epilepsy, clinical neurophysiologists are able to detect interictal epileptiform discharges (IED or 'epileptic spikes') during interictal EEG recordings. Although there is no gold standard as to what constitutes an epileptic spike, they tend to comprise a high amplitude deflection event lasting approximately 40-100ms (De Curtis and Avanzani 2001). Some patients evaluated for resective surgical treatment for epilepsy are investigated with intracranial EEG (icEEG) usually when there is strong evidence of an epileptogenic focus but not sufficient information to define a surgically resectable area using non-invasive methods.

http://ift.tt/2pLTPSN

(P111) Long Term Visual Outcomes for Ocular Melanoma Patients Treated With I-125 Brachytherapy Eye Plaques

To report our experience with respect to toxicity with long-term follow-up of ocular melanoma patients treated with COMS design custom I-125 low dose rate brachytherapy eye plaques.

http://ift.tt/2pLNRBj

(P113) Impact of Radiotherapy Technique on Normal Tissue Dose in Treatment of Spinal Vertebral Metastases

Optimal management of uncomplicated spinal vertebral metastases has yet to be determined. Single fraction therapy has been associated with fewer gastrointestinal side effects but the associated radiotherapy (RT) technique has not been reported. Traditional single field PA technique has been largely replaced by CT treatment planning to achieve dose homogeneity in the target vertebrae. CT treatment planning may pose acute toxicity risk as the normal tissue single fraction dose increases and needs further study.

http://ift.tt/2q54vPe

(P095) Assessing Changes in the Activity Levels of Breast Cancer Patients During Radiation Therapy

Radiation therapy (RT) is often implemented in the treatment of breast cancer (BC). While a common side effect of RT is fatigue, the exact effect on energy levels and sleep is unknown. This study analyzed the change in activity levels and sleep before, during, and after RT for women with early stage BC and ductal carcinoma in situ (DCIS) undergoing adjuvant RT.

http://ift.tt/2q4Sh9o

(P103) Preoperative Versus Postoperative Radiotherapy in Localized Soft Tissue Sarcoma: Nationwide Patterns of Care and Trends in Utilization

The optimal timing of perioperative radiotherapy (RT) in the treatment of localized soft tissue sarcoma (STS) remains a matter of debate. In this study, we aimed to characterize patterns of care, trends in utilization, and survival outcomes with preoperative (preop) versus postoperative (postop) RT in the management of primary STS.

http://ift.tt/2q5227I

(P035) Stereotactic Body Radiation Therapy for Organ-Confined Prostate Cancer

To investigate the long term effectiveness and toxicity of stereotactic body radiation therapy (SBRT) for localized prostate cancer.

http://ift.tt/2pLXcZY

(P107) Anomalous Variations in Nuclear Decay: Potential Radiation Oncology Implications

In violation of the presumed immutable nuclear decay law, recent observations in the measured decays of some radioisotopes have demonstrated anomalous variations in decay rate. These observations raise the possibility that such variations could have clinical relevance for temporary brachytherapy (both LDR and HDR), teletherapy and Gamma Knife radiosurgery.

http://ift.tt/2q5lvoH

(P099) Low-Dose Radiotherapy Is an Effective Treatment for Refractory Post-Operative Chylous Ascites: A Case Report

We report the first clinical case in the United States on the successful use of low-dose radiation (LD-RT) in the management of refractory chylous ascites.

http://ift.tt/2pLXcJs

(P063) Brachytherapy for Previously Irradiated Head and Neck Cancer

To evaluate our institutional experience using brachytherapy for re-irradiation of the head and neck.

http://ift.tt/2pLOPNN

(P109) Factors Associated With Increase in Fatigue in Prostate Cancer (PC) Patients Undergoing External Beam Radiation Therapy (EBRT)

Fatigue is a commonly-reported symptom among cancer patients undergoing EBRT. Despite high penetrance of fatigue and its adverse impact on quality-of-life in this population, the biology of radiation-related fatigue is unclear. The underlying disease- and treatment-related factors influencing fatigue are also poorly understood. This study aims to characterize fatigue development and potential drivers of increased fatigue in PC patients during EBRT.

http://ift.tt/2pLScEq

(P105) Characterization and Predictive Value of Volume Changes of Extremity and Pelvis Soft-Tissue Sarcomas During Radiotherapy Prior to Surgical Resection

In treating extremity soft tissue sarcomas with radiotherapy (RT) preceding surgical resection, pre-treatment tumor volume predicts survival and recurrence. However, changes in tumor volume during RT are not well-characterized, and their relationship to outcomes is unknown.

http://ift.tt/2q4Vq95

(P101) Burnout Evaluation of Radiation Residents Nationwide (BERRN): Results of a Survey of United States Residents

Burnout is an increasing problem among U.S. physicians. Up to half experience professional burnout which is associated with many negative consequences, including decreased job satisfaction, increased medical errors, divorce, and even self-harm. Burnout varies widely among residents in different specialties and has been associated with a drop in medical knowledge equivalent to one full year of training. However, burnout has never been formally assessed among U.S. radiation oncology residents.

http://ift.tt/2pLQEdO

(P097) Two-and-a-Half Year Clinical Experience With Magnetic Resonance Image Guided Radiation Therapy

Magnetic resonance image-guided radiation therapy (MR-IGRT) has been implemented at our institution since 2014. We report on the two-and-a-half year clinical experience in treating patients utilizing the world's first commercially available MR-IGRT system.

http://ift.tt/2q520wC

Erratum to: clinical predictors of seizure recurrence after the first post-ischemic stroke seizure

http://ift.tt/2pMMLHr

End of life place of care, health care settings and health care transitions among cancer patients: impact of an integrated Cancer Palliative Care plan

Frequent end-of-life health care setting transitions can lead to an increased risk of fragmented care and exposure to unnecessary treatments.

http://ift.tt/2q4Vohy

“I Just Felt Like I Was Stuck in the Middle”: Physician Assistants’ Experiences Communicating with Terminally Ill Patients and their Families in the Acute Care Setting

Terminally ill hospitalized patients and their families consistently rank effective communication and shared decision-making among their top priorities. Advance Practice Providers such as Physician Assistants (PAs) are increasingly providing care in the hospital setting and are often called to communicate with patients and families. A first step to improving PA communication is to better understand PAs' current experiences in their daily practices.

http://ift.tt/2qFWFbT

Self-Reported Bothersome Symptoms Across Different Socioepidemiological Groups of People Living with HIV Attending French Hospitals: Results from the ANRS-VESPA2 Survey

Twenty years after the advent of combined antiretroviral therapies (cART), there is a growing need for up-to-date information about the daily experience of people living with HIV (PLWH).

http://ift.tt/2qFQODw

Is higher acceptance associated with less anticipatory grief among patients in palliative care?

Patients in palliative care can experience substantial psychological suffering. Acceptance based interventions from approaches like Acceptance and Commitment Therapy (ACT) have demonstrated effectiveness in helping people cope with a range of life challenges. However, there is a dearth of research examining mechanisms of therapeutic change for patients in palliative care.

http://ift.tt/2qFPOiB

Impact of Undertreatment of Cancer Pain with Analgesic Drugs on Patient Outcomes: A Nationwide Survey of Outpatient Cancer Patient Care in Taiwan

Undertreatment of cancer pain among outpatient cancer patients needs to be addressed to enhance care and improve patients' quality of life.

http://ift.tt/2q54BXm

Gait Speed and Survival in Patients with Brain Metastases

Accurate estimation of life expectancy in patients with brain metastases is critical for counselling and choosing appropriate therapy. Performance status is the single greatest determinant of overall survival in this population. However, current measures of performance status are subjective and often based on brief clinical encounters. Gait speed is an objective, reliable predictor of overall health and survival.

http://ift.tt/2qFITpT

Off-label Medication Use in the Inpatient Palliative Care Unit

Although off-label medications are frequently prescribed in palliative care, there are no published studies examining their use in the United States.

http://ift.tt/2q5gkFp

Validation of the Persian version of the Brief Pain Inventory (BPI-P) in chronic pain patients

Chronic pain needs to be evaluated with a standard instrument. The Brief Pain Inventory (BPI) is a pain assessment tool which has been validated in many languages.

http://ift.tt/2q4Ub9T

Perceived Family Functioning Predicts Baseline Psychosocial Characteristics in U.S. Participants of a Family Focused Grief Therapy Trial

Screening and baseline data on 170 American families (620 individuals), selected by screening from a palliative care population for inclusion in a RCT of Family Focused Grief Therapy (FFGT), were examined to determine whether family dysfunction conferred higher levels of psychosocial morbidity. We hypothesized that greater family dysfunction would indeed be associated with poorer psychosocial outcomes among palliative care patients and their family members.

http://ift.tt/2qFHzDa

Magnitude and Kinetics of Decrease in Liver Stiffness After Anti-viral Therapy in Patients With Chronic Hepatitis C: A Systematic Review and Meta-analysis

We performed a systematic review and meta-analysis to estimate the decrease in liver stiffness, measured by vibration-controlled transient elastrography (VCTE), in patients with hepatitis C virus (HCV) infection who achieved a sustained virologic response (SVR).

http://ift.tt/2pLCTM6

Statin Use and Risk of Cirrhosis and Related Complications in Patients with Chronic Liver Diseases: a Systematic Review and Meta-analysis

Statins have been variably shown to decrease risk and complications of chronic liver diseases (CLDs). We performed a systematic review and meta-analysis to evaluate the association between statins and risk of cirrhosis and related complications in patients with CLDs.

http://ift.tt/2q4Mj8y

Reply to Dr. Gregersen

http://ift.tt/2pLJGFC

Infliximab vs. Adalimumab for UC: Is There A Difference?

http://ift.tt/2q4VwgY

IBS in IBD: A label to stick with caution - authors' reply

http://ift.tt/2pLBk0T

Porphyria Cutanea Tarda as the Initial Manifestation of Subclinical Hereditary Hemochromatosis

http://ift.tt/2q4MsbV

Histologic Scores for Fat and Fibrosis Associate With Development of Type 2 Diabetes in Patients With Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a strong risk factor for development of type 2 diabetes, but little is known about how long-term NAFLD or its histologic features affect risk. We aimed to investigate the cumulative incidence of type 2 diabetes in patients with NAFLD, and to identify histologic factors that affect risk of diabetes.

http://ift.tt/2pLD0au

Sex differences in the association between area deprivation and generalised anxiety disorder: British population study

Objective

Studies have shown that area-level deprivation measured by factors, such as non-home ownership, non-car ownership and household overcrowding, can increase the risk for mental disorders over and above individual-level circumstances, such as education and social class. Whether area-level deprivation is associated with generalised anxiety disorder (GAD) independent of personal circumstances, and whether this association is different between British women and men is unknown.

Design

Large, population study.

Setting

UK population-based cohort.

Participants

30 445 people from the general population aged 40 years and older and living in England consented to participate at study baseline, and of these, 21 921 participants completed a structured health and lifestyle questionnaire used to capture GAD. Area deprivation was measured in 1991 using Census data, and GAD was assessed in 1996–2000. 10 275 women and 8219 men had complete data on all covariates.

Main outcome measure

Past-year GAD defined according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV).

Results

In this study, 2.5% (261/10 275) of women and 1.8% (145/8219) of men had GAD. Women living in the most deprived areas were over 60% more likely to develop anxiety than those living in areas that were not deprived (OR=1.63, 95% CI 1.21 to 2.21; p=0.001), but this association between deprivation and GAD was not apparent in men (OR=1.13, 95% CI 0.72 to 1.77; p=0.598).

Conclusions

The absolute numbers of people living in deprived conditions are large worldwide. This, combined with a growing mental health burden, means that the findings obtained in this study remain highly relevant. The WHO has emphasised the need to reduce social and health inequalities. Our findings provide a strong evidence base to this call, showing that the environment needs to be taken into account when developing mental health policy; gender is important when it comes to assessing the influence of the environment on our mental health.

http://ift.tt/2pboWVS

Antigen processing and presentation in the thymus: implications for T cell repertoire selection

Kenta Kondo | Kensuke Takada | Yousuke Takahama

http://ift.tt/2qJZXdi

3D Volumetric Measurements of GH Secreting Adenomas Correlate with Baseline Pituitary Function, Initial Surgery Success Rate, and Disease Control

Horm Metab Res
DOI: 10.1055/s-0043-107245

There is scarce data on the clinical utility of volume measurement for growth hormone (GH)-secreting pituitary adenomas. The current study objective was to assess the association between pituitary adenoma volumes and baseline endocrine evaluation, initial surgical success rate, and disease control among patients with acromegaly. A retrospective cohort study was conducted at a clinical research center including patients with acromegaly due to GH-secreting pituitary adenomas. Baseline hormonal evaluation and adenoma characteristics according to MRI were collected. Volumetric measurements of pituitary adenomas were performed using a semi-automated lesion segmentation and tumor-volume assessment tools. Rates of post-operative medical treatment, radiation therapy, and re-operation were gathered from the patients' medical records. Twenty seven patients (11 females) were included, median age 21.0 years (interquartile range 29 years, range 3–61 years). Patients harboring adenomas with a volume <2 000 mm3 had higher chance to achieve disease remission [94.1% (n=16) vs. 50.0% (n=4), p<0.05]. Adenoma volumes positively correlated with baseline plasma GH levels before and after oral glucose administration, and with plasma IGF-I and PRL levels. Adenoma volume had negative correlation with morning plasma cortisol levels. Finally, patients harboring larger adenomas required 2nd surgery and/or medical treatment more often compared with subjects with smaller adenomas. Accurate 3D volume measurement of GH-secreting pituitary adenomas may be used for the prediction of initial surgery success and for disease control rates among patients with a GH-secreting pituitary adenomas and performs better than standard size assessments.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

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T372R Mutation Status in Yin Yang 1 Gene in Insulinoma Patients

Horm Metab Res
DOI: 10.1055/s-0043-107244

Insulinomas are rare pancreatic neuroendocrine tumors. The genetic causes underlying insulinoma are still being investigated. Recently, 3 independent studies reported a recurrent somatic mutation in YY1 gene (C>G; Thr372Arg) among insulinoma patients belonging to Chinese and Western Caucasian populations, which was found to increase insulin secretion by β-cells. However, the status of this key gene variation remains unknown in patients of other ethnicities. We, therefore, screened Indian sporadic insulinoma patients for YY1 T372R mutation in the present study. Seventeen patients diagnosed with insulinoma were recruited retrospectively and their records of family history and clinical parameters were collected. Formalin-fixed paraffin-embedded tumor tissues were used to extract genomic DNA, which was subjected to PCR amplification of YY1 exon 5, followed by Sanger sequencing. Nucleotide sequences thus obtained were aligned against the documented sequence of YY1 exon 5. We found absence of C to G mutation at YY1 codon 372 in all 17 (100%) insulinoma tissues analyzed. On comparison with the mutation frequency observed in the Chinese patients, our results point to genetic heterogeneity in the pathogenesis of insulinoma. This is the first report on the status of YY1 T372R in insulinoma cases of Indian origin. This also warrants analysis of other documented as well as novel mutations in genes in insulinoma tumorigenesis.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

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Prevalence of Cardiac Arrhythmias in Hypothyroid and Euthyroid Patients

Horm Metab Res
DOI: 10.1055/s-0043-105275

The thyroid functions as a regulator of cardiac function and rhythm through genomic and nongenomic actions of triiodothyronine (T3) in cardiac myocytes. Atrial fibrillation is a common complication of thyrotoxicosis. Hypothyroidism is not considered a risk factor for arrhythmias despite well-known EKG changes in this condition. This case control study was conducted to analyze the differences, if any, in the prevalence of cardiac arrhythmias between hypothyroid patients and euthyroid controls. Three hundred and four consecutive patients admitted at our medical center for a period of one year were included in the study. The study population was divided into 2 groups (age, gender and race matched): patients with hypothyroidism and euthyroid subjects as a control group. Major arrhythmia data were obtained from telemetry recordings and from known past medical history. There were 152 subjects in each arm of the study. The mean age was 61.9 years. Mean TSH in hypothyroid group was 40.4 mIU/l (95% CI 33.3–47.5) (range 10.09–304, SE 3.62) and in euthyroid group was 0.89 mIU/l (95% CI 0.82–0.96). Chi-square analysis revealed a higher prevalence of ventricular tachycardia (p=0.04) and any ventricular arrhythmia in the hypothyroid group (p=0.007). This relatively large case control study revealed a statistically higher prevalence of ventricular arrhythmias in hypothyroidism. Our study has thrown light on the prevalence of arrhythmias in hypothyroidism and the observation of increased ventricular arrhythmias necessitates future large scale prospective studies to better define the risk of such ventricular arrhythmias and the effects of thyroid supplementation on this risk.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

http://ift.tt/2pFqb39

MicroRNA-524-5p Functions as a Tumor Suppressor in a Human Pituitary Tumor-Derived Cell Line

Horm Metab Res
DOI: 10.1055/s-0043-106437

Clinical nonfunctional pituitary adenomas (NFAs) account for about 40% of pituitary adenomas with almost no clinically relevant hormonal symptoms. Increasing evidence shows that many microRNAs are involved in the development and progression of pituitary adenomas. MicroRNA-524-5p (miR-524-5p) has been reported to cause characteristic alterations in various tumors. However, the functional importance of miR-524-5p in NFAs remains unknown. The aim of this study was to explore the effects of overexpressing miR-524-5p on the proliferation, migration, invasion, and tumorigenicity of pituitary-derived folliculostellate (PDFS) cells using lentiviral transfection. Interestingly, the results showed that overexpressing miR-524-5p downregulated pituitary tumor-transforming gene 1 (PTTG1) binding factor (PBF) expression at both mRNA and protein levels and significantly attenuated cell proliferation, clonogenicity, migration, and invasion in vitro. Moreover, enhancing miR-524-5p blocked tumor growth in a nude mouse xenograft model in vivo. These findings suggest that miR-524-5p appears to play a critical role in the regulation of biological properties of PDFS cells, and may represent a potential therapeutic target for NFAs.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

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Letter on “Natural history of pure autonomic failure: A United States prospective cohort.”

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Pure autonomic failure vs. manifest CNS synucleinopathy: Relevance of stridor and autonomic biomarkers

http://ift.tt/2qK0IDg

Cancer Immunotherapy with Cytokine-Induced Killer Cells

Abstract

Cytokine-induced killer (CIK) cells form under certain stimulation conditions in cultures of peripheral blood mononuclear cells (PBMCs). They are a heterogeneous immune cell population and contain a high percentage of cells with a mixed T-NK phenotype (CD3+CD56+). The ready availability of a lymphocyte source, together with the high proliferative rate and potent anti-tumor activity of CIK cells, has allowed their use as immunotherapy in a wide variety of neoplasms. Cytotoxicity mediated by CD3+CD56+ T cells depends on the major histocompatibility antigen (MHC)-independent recognition of tumor cells and the activation of signaling pathways through the natural killer group 2 member D (NKG2D) cell-surface receptor. Clinical trials have demonstrated the feasibility and efficacy of CIK cell immunotherapy even in advanced stage cancer patients or those that have not responded to first-line treatment. This review summarizes biological and technical aspects of CIK cells, as well as past and current clinical trials and future trends in this form of immunotherapy.

http://ift.tt/2pMgDUn

The Frequency and Severity of Magnetic Resonance Imaging Abnormalities in Infants with Mild Neonatal Encephalopathy

To assess and contrast the incidence and severity of abnormalities on cerebral magnetic resonance imaging (MRI) between infants with mild, moderate, and severe neonatal encephalopathy who received therapeutic hypothermia.

http://ift.tt/2p2JmFx

Corrigan Pulse and Fullness of the Neck Vessels in a Neonate

A 3-day-old girl was admitted to the neonatal intensive care unit with symptoms of congestive heart failure. On examination, she was noted to have bounding carotid pulses (Corrigan pulse) (Videos 1 and 2; available at www.jpeds.com), intercostal, subcostal retractions, and bilateral rales over the lungs. A strong continuous bruit was auscultated on the whole skull. The chest radiograph showed an enlarged heart and echocardiography revealed coarctation of the aorta. An urgent balloon dilatation was performed, and cranial arteriovenous malformation was also detected during angiography.

http://ift.tt/2pLlKlG

The 150 most important questions in cancer research and clinical oncology series: Questions 25–30

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 6 more questi...

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Clinical value of R-spondins in triple-negative and metaplastic breast cancers

http://ift.tt/2p2vpY1

One-carbon metabolism in cancer

http://ift.tt/2qKcuh3

Efficacy and safety of gemcitabine plus S-1 in pancreatic cancer: a pooled analysis of individual patient data

http://ift.tt/2p2Rplx

Human papillomavirus association is the most important predictor for surgically treated patients with oropharyngeal cancer

http://ift.tt/2qK1i3T

Acute kidney injury in the ICU: from injury to recovery: reports from the 5th Paris International Conference

The French Intensive Care Society organized its yearly Paris International Conference in intensive care on June 18–19, 2015. The main purpose of this meeting is to gather the best experts in the field in order...

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Randomized Trial of Thymectomy in Myasthenia Gravis

New England Journal of Medicine, Ahead of Print.


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Evaluation of Healthcare Interventions and Big Data: Review of Associated Data Issues

Abstract

Although the analysis of 'big data' holds tremendous potential to improve patient care, there remain significant challenges before it can be realized. Accuracy and completeness of data, linkage of disparate data sources, and access to data are areas that require particular focus. This article discusses these areas and shares strategies to promote progress. Improvement in clinical coding, innovative matching methodologies, and investment in data standardization are potential solutions to data validation and linkage problems. Challenges to data access still require significant attention with data ownership, security needs, and costs representing significant barriers to access.

http://ift.tt/2pe8Xaj

Ventricular Assist Device Controllers and DC Adapter by Medtronic Mechanical Circulatory Support (formerly HeartWare Inc.): Class I Recall - Updated Controller, Power Management Software

Audience: Cardiology, Risk Manager, Transplantation, Nursing, Patient [Posted 05/04/2017] ISSUE: Medtronic Mechanical Circulatory Support is expanding this recall to include an additional product code and instructions to exchange recalled...

http://ift.tt/2qJB41r

Retraction Note: MicroRNA-203 suppresses gastric cancer growth by targeting PIBF1/Akt signaling

http://ift.tt/2pdXTKz

Ventricular Assist Device Controllers and DC Adapter by Medtronic Mechanical Circulatory Support (formerly HeartWare Inc.): Class I Recall - Updated Controller, Power Management Software

Audience: Cardiology, Risk Manager, Transplantation, Nursing, Patient [Posted 05/04/2017] ISSUE: Medtronic Mechanical Circulatory Support is expanding this recall to include an additional product code and instructions to exchange recalled...

http://ift.tt/2qJB41r

Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor Treating Fields (TTFields)

Tumor Treating Fields (TTFields) are an effective anti-tumor treatment modality delivered via the continuous, noninvasive application of low-intensity, intermediate-frequency, alternating electric fields. TTFields application to cell lines using a TTFields in vitro application system allows for the determination of the optimal frequency that leads to the highest reduction in cell counts.

http://ift.tt/2paJttL

Evaluation for inherited and acquired prothrombotic defects predisposing to symptomatic thromboembolism in children with acute lymphoblastic leukemia: a protocol for a prospective, observational, cohort study

Abstract

Background

Thromboembolism (TE) is a serious complication in children with acute lymphoblastic leukemia (ALL). The incidence of symptomatic thromboembolism is as high as 14% and case fatality rate of ~15%. Further, development of thromboembolism interferes with the scheduled chemotherapy with potential impact on cure rates. The exact pathogenesis of ALL-associated thromboembolism is unknown. Concomitant administration of asparaginase and steroids, two important anti-leukemic agents, is shown to increase the risk of ALL-associated TE. Dana-Farber Cancer Institute (DFCI) ALL studies reported ~10% incidence of thrombosis with significantly increased risk in older children (≥10 yrs.) and those with high-risk ALL. The majority (90%) of thromboembolic events occurred in the Consolidation phase of therapy with concomitant asparaginase and steroids when high-risk patients (including all older patients) receive higher dose steroids. Certain inherited and acquired prothrombotic defects are known to contribute to the development of TE. German investigators documented ~50% incidence of TE during therapy with concomitant asparaginase and steroids, in children with at least one prothrombotic defect. However, current evidence regarding the role of prothrombotic defects in the development of ALL-associated TE is contradictory. Although thromboprophylaxis can prevent thromboembolism, ALL and it's therapy can increase the risk of bleeding. For judicious use of thromboprophylaxis, identifying a population at high risk for TE is important. The risk factors, including prothrombotic defects, predisposing to thrombosis in children with ALL have not been defined.

Methods

This prospective, observational cohort study aims to evaluate the prevalence of inherited prothrombotic defects in children with ALL treated on DFCI 05–01 protocol and the causal relationship of prothrombotic defects in combination with patient and disease-related factors to the development of TE. We hypothesize that the combination of prothrombotic defects and the intensive therapy with concomitant high dose steroids and asparaginase increases the risk of TE in older patients and patients with high-risk ALL.

Discussion

The results of the proposed study will help design studies of prophylactic anticoagulant therapy. Thromboprophylaxis given to a targeted population will likely reduce the incidence of TE in children with ALL and ultimately improve their quality of life and prospects for cure.

http://ift.tt/2paHiqa

Quality of Life Measurements: Any Value for Clinical Practice?

Opinion statement

Quality of life measurements are well established in cancer clinical trials. In daily clinical practice, where cancer patients often suffer from disease-specific symptoms and report unmet needs regarding their treatment, these measurements are not systematically implemented. The systematic (often computer-based) assessment of quality of life in daily cancer care has shown to be beneficial for patient-physician communication, symptom management, shared decision-making, and in creating a learning health system. Unfortunately, to date, routine electronic quality of life assessments are usually limited to large cancer facilities. Patient and physician barriers as well as barriers from the administrative side in particular are currently hindering the implementation of these systems into the broad spectrum of clinical cancer care. Cost-effectiveness analyses of existing systems, the inclusion of all relevant stakeholders, and clear implementation guidelines are required to introduce quality of life measurements in clinical cancer practice to improve the treatment of cancer survivors and to create a health care system that addresses all their disease-related needs.

http://ift.tt/2qIFXYI

The Latest Advancements in Selective Neck Dissection for Early Stage Oral Squamous Cell Carcinoma

Opinion Statement

The management of cervical lymph node metastasis remains a crucial component of the treatment of head and neck cancers. However, the proper management of clinical N ₀ cases with early-stage oral squamous cell carcinoma (OSCC) remains undefined. In the advent of minimally invasive techniques in the 1980s, these techniques have gained popularity among numerous surgeons in all fields of surgery. Although there are no randomized controlled trial data comparing the outcomes of minimally invasive techniques (endoscopically assisted selective neck dissection (SND), robot-assisted SND) with conventional techniques, encouraging evidence from several studies suggests that both endoscopically assisted SND and robot-assisted SND are safe, minimally invasive techniques with achieved short-term oncologic outcomes and can reach a better cosmetic outcome than conventional SND. In this review, we also compare the indications, surgical approaches, and relative advantages and disadvantages of conventional SND, endoscopically assisted SND, and robot-assisted SND to provide surgeons with a means to better consider these techniques for the treatment of early-stage OSCC.

http://ift.tt/2qvscjJ

Gene Expression Signatures for Head and Neck Cancer Patient Stratification: Are Results Ready for Clinical Application?

Opinion statement

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide and considering the recent EUROCARE-5 population-based study the 5-year survival rate of HNSCC patients in Europe ranges between 69% in localized cases and 34% in patients with regional involvement. The development of high-throughput gene expression assays in the last two decades has provided the invaluable opportunity to improve our knowledge on cancer biology and to identify predictive signatures in the most deeply analyzed malignancies, such as hematological and breast cancers. At variance, till 2010, the number of reliable reports referring gene expression data related to HSNCC biology and prediction was quite limited. A critical revision of the literature reporting gene expression data in HNSCC indicated that in the last 6 years, there were new important studies with a relevant increase in the sample size and a more accurate selection of cases, the publication of a growing number of studies applying a computational integration (meta-analysis) of different microarray datasets addressing similar clinical/biological questions, the increased use of molecular sub-classification of tumors according to their gene expression, and the release of the publicly available largest dataset in HNSCC by The Cancer Genome Atlas (TCGA) consortium. Overall, also for this disease, it become evident that the expression analysis of the entire transcriptome has been enabling to achieve the identification of promising molecular signatures for (i) disclosure of the biology behind carcinogenesis with special focus on the HPV-related one, (ii) prediction of tumor recurrence or metastasis development, (iii) identification of subgroups of tumors with different biology and associated prognosis, and (iv) prediction of outcome and/or response to therapy. The increasing awareness of the relevance of strict collaboration among clinicians and translational researchers would in a near future enable the application of a personalized HNSCCs patients' treatment in the clinical practice based also on gene expression signatures.

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Meningiomas induced by low-dose radiation carry structural variants of NF2 and a distinct mutational signature

http://ift.tt/2pE4aBP

Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats

Oxidative stress through chronic stress destroys the brain function. There are many documents have shown that carnosol may have a therapeutic effect versus free radical induced diseases. The current research f...

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Effect of solvents extraction on phytochemical components and biological activities of Tunisian date seeds (var. Korkobbi and Arechti)

The interest in natural antioxidants, especially polyphenols, is growing more and more thanks to their positive contribution to human health. Thus, the prevention from the harmful action of oxidative stress wh...

http://ift.tt/2pdGQrX

Use of complementary and alternative medicine by patients with end-stage renal disease on haemodialysis in Trinidad: A descriptive study

Despite the paucity of scientific evidence, complementary and alternative medicine (CAM) is widely used for the prevention and treatment of illness, holistic care, and counteracting the adverse effects of conv...

http://ift.tt/2q3P4XN

Isolation of the Side Population in Myc-induced T-cell Acute Lymphoblastic Leukemia in Zebrafish

Here, we describe a technique to isolate the side population cells from a zebrafish model of myc-induced T-cell acute lymphoblastic leukemia (T-ALL). This side population assay is highly sensitive and is described for zebrafish T-ALL, but it may be applicable to other malignant and non-malignant zebrafish cell types.

http://ift.tt/2pdnOSB

Time course of upper limb function and return-to-work post-radiotherapy in young adults with breast cancer: a pilot randomized control trial on effects of targeted exercise program

Abstract

Purpose

Breast cancer (BC) diagnosis in young adults (YA) is rising, and both disease and treatments are aggressive in this population. Evidence supports the use of physical activity in reducing shoulder dysfunction, which is common among BC survivors. A pilot randomized clinical trial was performed to determine the effectiveness of a 12-week post-radiation exercise program in minimizing upper extremity dysfunction in YA with BC.

Methods

Participants were randomized to either an exercise arm or a control arm receiving standard care. Data was collected over six time points using: the Disability of Arm, Shoulder, and Hand (DASH); the Metabolic Equivalent of Task-hours per week (MET-hours/week), and a post hoc questionnaire on return to work.

Results

In total, 59 young women participated in the study (n = 29 exercise; n = 30 control). No statistically significant differences were found in overall DASH results between groups; however, those who underwent total mastectomy had residual upper limb dysfunction (p < 0.05). Both groups returned to pre-diagnosis activity levels by 18 months. Final evaluation showed that 86% of the women returned to work, and 89% resumed prior work activities with a decrease of 8.5 h/week.

Conclusion

Although the short-term targeted exercise program had no effect on long-term upper limb function post-radiation, timing and program specificity may require consideration of tissue healing post-radiation and surgery type. The majority of participants returned to work, however not returning to pre-diagnosis work hours.

Implications for Cancer Survivors

Exercise interventions alone may not reverse the long-term sequelae of breast cancer treatment and allow young adult patients to return to work.

http://ift.tt/2q3RPYV

Programmed cell death ligand 1 as a biomarker in head and neck cancer

The evaluation of programmed cell death ligand 1 has a potential role in the application of immune checkpoint inhibitors for select cancers of the head and neck. See related commentary on pages 000-000.

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Programmed death-ligand 1 immunohistochemistry testing for non-small cell lung cancer in practice

Given the recent approval by the US Food and Drug Administration of an anti-programmed cell death protein 1 agent as a first-line therapy for patients with advanced non-small cell lung cancer, programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) testing has become routine in pathology laboratories in the United States. Each pathology laboratory needs to select a PD-L1 IHC assay among the multiple assays available, conduct appropriate optimization and validation processes, and pay close attention to appropriate preanalytical tissue handling and the selection of optimal tissue samples. See also pages 000-000.

http://ift.tt/2pDG4ap

In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis

This protocol describes the in vitro comparison of two key functional characteristics of rituximab: target binding and complement-dependent cytotoxicity (CDC) induction. The methods were employed for a side-to-side comparison between reference rituximab and a rituximab biosimilar. These assays can be employed during biosimilar development or as a quality control in their production.

http://ift.tt/2q3tRwO

Inside EMS Podcast: Is EMS an entry-level job?

<!--cke_bookmark_136S--><!--cke_bookmark_136E--> Download this podcast on iTunes, SoundCloud or via RSS feed ​​In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss EMS1 columnist Mike Rubin's article breaking down the 10 worst reasons for joining EMS. They talk about each reason and provide their unique spin. Learn more about the EMS1 ...

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Emergency physicians urge Congress to vote 'no' on AHCA

American College of Emergency Physicians WASHINGTON — The American College of Emergency Physicians today issued a brief statement in advance of the House of Representatives' expected vote on the American Health Care Act, urging members to vote against the bill. "Members of Congress should vote 'no' on the AHCA," Dr. Rebecca Parker, ACEP's president, said. "We are ...

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Cancer as a stressful life event: Perceptions of children with cancer and their peers

BACKGROUND

The medical traumatic stress model is commonly applied to childhood cancer, assuming that the diagnosis of cancer is a traumatic event. However, to the authors' knowledge, little is known regarding what specifically children perceive as stressful about cancer or how it compares with other stressful events more often experienced by children.

METHODS

Children with cancer (254 children) and demographically similar peers without a history of serious illness (202 children) identified their most stressful life event as part of a diagnostic interview assessing for symptoms of posttraumatic stress disorder (PTSD). The events identified as most stressful were categorized thematically, with categories established separately for cancer-related and non-cancer-related events. Events also were examined to assess whether they met Diagnostic and Statistical Manual of Mental Disorders (DSM) A criteria for PTSD.

RESULTS

In the group of children with cancer, 54% described a cancer-related event as the most stressful event they had experienced. Six distinct categories of cancer-related events and 10 categories of non-cancer-related events were identified. The same noncancer events were identified by children in both groups, and occurred at similar frequencies. The percentage of cancer-related events that met DSM A criteria for PTSD differed dramatically depending on which version of the DSM was applied.

CONCLUSIONS

Children do not necessarily view their cancer experience as their most stressful life event. The findings of the current study suggest that the diagnosis of cancer might be better viewed as a manageable stressor rather than a major trauma, and are consistent with the change in the fifth edition of the DSM to eliminate the diagnosis of a life-threatening illness as a qualifying trauma for PTSD. Cancer 2017. © 2017 American Cancer Society.

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Cost-effectiveness of human papillomavirus vaccination for adolescent girls in Punjab state: Implications for India's universal immunization program

BACKGROUND

Introduction of human papillomavirus (HPV) vaccination for adolescent girls is being considered in the Punjab state of India. However, evidence regarding cost-effectiveness is sought by policy makers when making this decision. The current study was undertaken to evaluate the incremental cost per quality-adjusted life-years (QALYs) gained with introduction of the HPV vaccine compared with a no-vaccination scenario.

METHODS

A static progression model, using a combination of decision tree and Markov models, was populated using epidemiological, cost, coverage, and effectiveness data to determine the cost-effectiveness of HPV vaccination. Using a societal perspective, lifetime costs and consequences (in terms of QALYs) among a cohort of 11-year-old adolescent girls in Punjab state were modeled in 2 alternate scenarios with and without vaccination. All costs and consequences were discounted at a rate of 3%.

RESULTS

Although immunizing 1 year's cohort of 11-year-old girls in Punjab state costs Indian National Rupees (INR) 135 million (US dollars [USD] 2.08 million and International dollars [Int$] 6.25 million) on an absolute basis, its net cost after accounting for treatment savings is INR 38 million (USD 0.58 million and Int$ 1.76 million). Incremental cost per QALY gained for HPV vaccination was found to be INR 73 (USD 1.12 and Int$ 3.38). Given all the data uncertainties, there is a 90% probability for the vaccination strategy to be cost-effective in Punjab state at a willingness-to-pay threshold of INR 10,000, which is less than one-tenth of the per capita gross domestic product.

CONCLUSIONS

HPV vaccination appears to be a very cost-effective strategy for Punjab state, and is likely to be cost-effective for other Indian states. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2pKjECD