Optical, Thermal, and Mechanical Characterization of Ga2Se3-Added GLS Glass

Gallium lanthanum sulfide glass (GLS) has been widely studied in the last 40 years for middle-infrared applications. In this work, the results of the substitution of selenium for sulphur in GLS glass are described. The samples are prepared via melt-quench method in an argon-purged atmosphere. A wide range of compositional substitutions are studied to define the glass-forming region of the modified material. The complete substitution of Ga₂S₃ by Ga₂Se₃ is achieved by involving new higher quenching rate techniques compared to those containing only sulfides. The samples exhibiting glassy characteristics are further characterized. In particular, the optical and thermal properties of the sample are investigated in order to understand the role of selenium in the formation of the glass. The addition of selenium to GLS glass generally results in a lower glass transition temperature and an extended transmission window. Particularly, the IR edge is found to be extended from about 9 µm for GLS glass to about 15 µm for Se-added GLS glass defined by the 50% transmission point. Furthermore, the addition of selenium does not affect the UV edge dramatically. The role of selenium is hypothesized in the glass formation to explain these changes.

Theresults of the addition of Se to gallium lanthanum sulfide(GLS) glass through the substitution of Ga₂S₃ by Ga₂Se₃ are described. An innovative open melting apparatus is used. The addition of selenium to GLS glass generally results in a lower glass transition temperature and an extended transmission window up to 15 µm with minor effect on the visible transmission.

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Vertically Aligned Niobium Nanowire Arrays for Fast-Charging Micro-Supercapacitors

Planar micro-supercapacitors are attractive for system on chip technologies and surface mount devices due to their large areal capacitance and energy/power density compared to the traditional oxide-based capacitors. In the present work, a novel material, niobium nanowires, in form of vertically aligned electrodes for application in high performance planar micro-supercapacitors is introduced. Specific capacitance of up to 1 kF m⁻² (100 mF cm⁻²) with peak energy and power density of 2 kJ m⁻² (6.2 MJ m⁻³ or 1.7 mWh cm⁻³) and 150 kW m⁻² (480 MW m⁻³ or 480 W cm⁻³), respectively, is achieved. This remarkable power density, originating from the extremely low equivalent series resistance value of 0.27 Ω (2.49 µΩ m² or 24.9 mΩ cm²) and large specific capacitance, is among the highest for planar micro-supercapacitors electrodes made of nanomaterials.

Fast-charging micro-supercapacitors are made from vertically aligned niobium nanowire arrays. Thanks to the high electrical conductivity of the nanowires, the micro-supercapacitor exhibits a very small characteristic relaxation time constant of 8.4 ms. With 1 m sulfuric acid, cycling rates of up to 300 V s⁻¹ are achieved while with 1-ethyl-3-methylimidazolium tetrafluoroborate an operating voltage of up to 4 V is obtained.

http://ift.tt/2q5s49k

Magnetic Resonance Elastography Measured Shear Stiffness as a Biomarker of Fibrosis in Pediatric Nonalcoholic Fatty Liver Disease

Abstract

Magnetic Resonance Elastography (MRE) is promising for non-invasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. Study aims were to determine accuracy of MRE for detection of fibrosis and advanced fibrosis in children with NAFLD, and to assess agreement between manual and novel automated reading methods. We performed a prospective, multi-center study of 2D-MRE in children with NAFLD. MR-elastograms were analyzed manually at 2 reading centers and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross-validated. In 90 children with mean age of 13.1 ± 2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r=0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ρ=0.53; center 2, ρ=0.55; and automated analysis, ρ=0.52; p<0.001). Overall cross-validated accuracy for detecting any fibrosis was the same for all methods: 72.2% (61.8 – 81.1). Overall cross-validated accuracy for assessing advanced fibrosis varied by method: 88.9% (80.5% - 94.5%) for center 1, 90.0% (81.9% – 95.3%) for center 2, and 86.7% (77.9 – 92.9) for automated analysis. Conclusions: 2D-MRE can estimate hepatic stiffness in children with NAFLD. Further refinement and validation of automated analysis techniques will be an important step in standardizing MRE. How to best integrate MRE into clinical protocols for the assessment of NAFLD in children will need prospective evaluation. This article is protected by copyright. All rights reserved.

http://ift.tt/2pzL0Kb

Dificultades y factores favorables para la atención al final de la vida en residencias de ancianos: un estudio con grupos focales

María Remedios Sánchez-García, Marina Moreno-Rodríguez, César Hueso-Montoro, Concepción Campos-Calderón, Ana Varella-Safont, Rafael Montoya-Juárez
Aten Primaria 2017;49:278-85

Resumen - Texto completo - PDF

http://ift.tt/2qVFFBA

Hacia un modelo de atención a la multimorbilidad en atención primaria

Daniel Prados-Torres, Isabel del Cura-González, Alexandra Prados-Torres
Aten Primaria 2017;49:261-2

Resumen - Texto completo - PDF

http://ift.tt/2qVSagi

Variabilidad e idoneidad del tratamiento antiasmático en pediatría de atención primaria

Cristina Suárez-Castañón, Gracia Modroño-Riaño, Gonzalo Solís-Sánchez
Aten Primaria 2017;49:263-70

Resumen - Texto completo - PDF

http://ift.tt/2qVS5tb

Los servicios de cafeterías y la promoción de la salud en el entorno escolar

Francisca M. García-Padilla, Angustias González-Rodríguez
Aten Primaria 2017;49:271-7

Resumen - Texto completo - PDF

http://ift.tt/2qVsNv6

Estudio transversal de comorbilidades y medicaciones concomitantes en una cohorte de pacientes infectados por el virus de la inmunodeficiencia humana

Maria Asunción García Gonzalo, María Isabel Santamaría Mas, Lidia Pascual Tomé, Maialen Ibarguren Pinilla, Francisco Rodríguez-Arrondo
Aten Primaria 2017;49:286-93

Resumen - Texto completo - PDF

http://ift.tt/2qVtsww

Lixisenatida en pacientes con diabetes tipo 2 y obesidad: más allá del control glucémico

M. Mar Roca-Rodríguez, María Teresa Muros de Fuentes, Gonzalo Piédrola-Maroto, Miguel Quesada-Charneco, Silvia Maraver-Selfa, Francisco J. Tinahones, Isabel Mancha-Doblas
Aten Primaria 2017;49:294-9

Resumen - Texto completo - PDF

http://ift.tt/2qVMTp1

Multimorbilidad en medicina de familia y los principios Ariadne. Un enfoque centrado en la persona

Alexandra Prados-Torres, Isabel del Cura-González, Juan Daniel Prados-Torres, Francisca Leiva-Fernández, Juan Antonio López-Rodríguez, Amaia Calderón-Larrañaga, Christiane Muth
Aten Primaria 2017;49:300-7

Resumen - Texto completo - PDF

http://ift.tt/2qVBjKP

Factores determinantes de la sobrecarga del cuidador. Estudio de las diferencias de género

Enrique Ramón-Arbués, Blanca Martínez-Abadía, Susana Martín-Gómez
Aten Primaria 2017;49:308-9

Resumen - Texto completo - PDF

http://ift.tt/2qVxVQ3

Incremento en el número de casos diagnosticados de tosferina; ¿pensamos más en ella?

Raquel Martínez Lorenzo, Yolanda González Piñeiro, Ana María López Vázquez, Matilde Trigo Daporta
Aten Primaria 2017;49:309-11

Resumen - Texto completo - PDF

http://ift.tt/2qVFDJY

¿Son los grupos de morbilidad ajustados concordantes con el criterio clínico de intervención en una estrategia de crónicos?

Jose M. Inoriza, Inma Sánchez-Pérez, Marc Carreras, Jordi Coderch
Aten Primaria 2017;49:311-2

Resumen - Texto completo - PDF

http://ift.tt/2qVzNbn

Prescripción de nuevos anticoagulantes orales en un área de salud

Sara Suárez-Varela Pineda, Leoncio Rodríguez Pérez, Rogelio Gallego Fuentes, Francisco Buitrago
Aten Primaria 2017;49:312-3

Resumen - Texto completo - PDF

http://ift.tt/2qVOnjk

Bowel cancer screening in England

Before the UK national bowel cancer screening programmes were implemented, a pilot was set-up in England to see if results from randomised controlled trials could be replicated in the general population. Gut has recently published findings from the third round of this.

Co-author David Weller, Centre for Population Health Sciences–General Practice, University of Edinburgh, UK, talks to Gut's associate editor William Grady about effectiveness of screening, uptake and its link to ethnicity, and the potential of different methods.

See also:

Performance measures in three rounds of the English bowel cancer screening pilot (http://ift.tt/2qVS7kC)

http://ift.tt/2qVOn2O

PUFAS and neoplasms

Mairi McLean, Gut education editor, talks to Professor Mark Hull, Leeds Institute of Molecular Medicine, about his research into the action of polyunsaturated fatty acids on the formation of neoplams.

See also:

Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer (http://ift.tt/2pzCrz0)

http://ift.tt/2pzB2IL

Cancer treatment induced gastrointestinal symptoms

In the UK chronic gastrointestinal symptoms after cancer therapies have a similar impact as IBD. However, in contrast to patients with IBD, most of these patients won't see a gastroenterologist. In this month's Gut Editor's Choice the causes of these side effects of cancer treatment are discussed, as well as the benefits of investigation and treatment.

In this podcast Mairi McLean, senior clinical lecturer and consultant in gastroenterology at the University of Aberdeen talks to some key stakeholders in this issue:

Professor Sir Mike Richards, national clinical director for cancer and end of life care, Department of Health

Jane Maher, chief medical officer for McMillian Cancer Support

Jon Rhodes, professor of gastroenterology and president of the British Society of Gastroenterology

Jervoise Andeyev, consultant gastroenterologist in pelvic radiation disease at the Royal Marsden NHS Trust, London

See also:

Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer (http://ift.tt/2qVS4VY)

http://ift.tt/2qVLwH1

Bifidobacterium and gastrointestinal inflammation

Liam O'Mahony (Swiss Institute of Allergy and Asthma Research) talks to Mairi McLean (senior clinical lecturer and consultant in gastroenterology at the University of Aberdeen) about his paper looking at Bifidobacterium infantis's interaction with T cells, and the bacterium's potential to protect against gastrointestinal inflammation.

See also:

Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells (http://ift.tt/2pzCpHo)

http://ift.tt/2pzJkju

High-fat diet and gut microbiota

Mairi Mclean, Gut's education editor, talks to Matteo Serino from the Institut National de la Santé et de la Recherche Médicale (INSERM), about his article Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota (http://ift.tt/2qVCmdw), which is this month's editor's choice.

http://ift.tt/2qVS602

The Failure of Solanezumab — How the FDA Saved Taxpayers Billions

The November 2016 announcement that Eli Lilly's investigational drug solanezumab failed in a phase 3 clinical trial dashed hopes that it would be a long-anticipated disease-modifying treatment for Alzheimer's disease. For people living with Alzheimer's — along with their relatives and caregivers,…

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Overexpression of the X-Linked Inhibitor of Apoptosis Protects Against Retinal Degeneration in a Feline Model of Retinal Detachment

Human Gene Therapy , Vol. 0, No. 0.


http://ift.tt/2qVFyWG

Rhadinoviral interferon regulatory factor homologues

Authors: Koch, Sandra / Schulz, Thomas F.


http://ift.tt/2q7FUqf

Chronic viral hepatitis and its association with liver cancer

Authors: Tu, Thomas / Bühler, Sandra / Bartenschlager, Ralf


http://ift.tt/2q4VrJF

Erratum to: Effects of aging on the relationship between cognitive demand and step variability during dual-task walking

http://ift.tt/2qu6GvR

Risk factors for single crowns supported by short (6-mm) implants in the posterior region: A prospective clinical and radiographic study

Abstract

Background

The use of short implants is still not a consensus for challenging clinical situations, such as unfavorable crown-to-implant (C/I) ratio.

Purpose

This prospective study evaluated the rates of prosthetic complications and implant failure, the mean marginal bone loss of 6-mm dental implants with single crowns in posterior regions and the potential risk factors.

Materials and Methods

Forty-six dental implants, 6-mm long and 4.1-mm wide, were placed in the posterior region in 20 patients. Patients were clinically and radiographically examined after the restoration with single crowns and on a yearly basis. Potential risk factors (arch, bruxism, maximum bite force, anatomical and clinical C/I ratios, and occlusal table area) were analyzed according to the following outcomes: implant survival, bone loss, and prosthetic complications.

Results

The mean follow-up time was 45 ± 9 (16-57) months. There was no early loss of implants. After prosthetic loading, 4 implants were lost (2 in the mandible and 2 in the maxilla; 91.3% survival), and there were 13 prosthetic complications (28.3%), yielding a 65.2% success rate. The frailty term showed a 95% greater chance of loss in the mandible than the maxilla. Mean peri-implant bone loss was of 0.2 ± 0.4 mm, 0.1 ± 0.2 mm, 0.1 ± 0.3 mm, and 0.2 ± 0.4 mm in the first, second, third, and fourth years, respectively, with a mean cumulative loss of 0.3 ± 0.5 mm at 48 months. In the multilevel model, the effects of the clinical C/I ratio and time were significant for bone loss (P < .001). It was estimated that a mean bone loss of 0.1 mm is associated with both a one-unit increase in time (12 months) and a 0.1 increase in the clinical C/I ratio. The other potential risk factors showed no significant relationship with the outcomes.

Conclusions

The 6-mm implants supporting single crowns performed well, but the mandible shows a higher risk of failure. The time and clinical C/I ratio are predictors for bone loss.

http://ift.tt/2r27LaB

Effects of different loading protocols on the secondary stability and peri-implant bone density of the single implants in the posterior maxilla

Abstract

Background

Immediate or early loading of dental implants becomes a clinically feasible concept.

Purpose

The aim was to evaluate the effects of different loading protocols (immediate, early, and delayed) on secondary stability and peri-implant bone density of single implants in the posterior maxilla.

Materials and Methods

Thirty-nine implants (Dentium, South-Korea) were placed in 39 patients. After placement, implant stability values (ISQ) and baseline peri-implant bone density values derived from cone-beam computed tomography were recorded. Thirteen implants were included randomly in each loading groups. The secondary ISQ values were recorded during follow-up visits. Peri-implant bone density values were measured 1 year after placement again. Data was statistically analyzed.

Results

Immediate-loaded group showed the lowest ISQ values, 1 month after placement. During the next follow-up visits, delayed-loaded group showed the lowest ISQ values while other groups showed comparable results. Early loading increased the peri-implant bone density greater than the other groups.

Conclusions

The peri-implant bone of early-loaded implants was significantly denser than that of immediate- and delayed-loaded implants, 1 year after placement. Density increment can be judged as the radiological findings of loaded-bone, which may also reduce the need for histomorphometric analysis of human biopsy to evaluate the bone reaction around the implants.

http://ift.tt/2pm9ZoK

Best reviewers award for 2016

http://ift.tt/2q4RJzr

WEO Newsletter

http://ift.tt/2q7ud2N

Issue Information - TOC

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The 93rd Congress of Japan Gastroenterological Endoscopy Society

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The 94th Congress of Japan Gastroenterological Endoscopy Society

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Cover Image

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SEDENTARY CONDITIONS AND ENHANCED RESPONSES TO GABA IN THE RVLM: ROLE OF THE CONTRALATERAL RVLM

A sedentary lifestyle is a major risk factor for cardiovascular disease, and both conditions are associated with overactivity of the sympathetic nervous system. Ongoing discharge of sympathetic nerves is regulated by the rostral ventrolateral medulla (RVLM), which in turn is modulated by the primary excitatory and inhibitory neurotransmitters glutamate and -amino-butyric acid (GABA), respectively. We reported previously that sedentary conditions enhance GABAergic modulation of sympathoexcitation in the RVLM, despite overall increased sympathoexcitation. Thus, the purpose of this study was to test the hypothesis that sedentary conditions increase responsiveness to GABA in RVLM. Male Sprague-Dawley rats performed either chronic wheeling running or remained sedentary for 12-15 weeks. Animals were instrumented to perform RVLM microinjections under Inactin anesthesia while recording mean arterial pressure (MAP) and splanchnic sympathetic nerve activity (SSNA). Unilateral microinjections of GABA (30 nl, 0.3-600 mM) into the RVLM produced dose-dependent decreases in MAP and SSNA; however, no group differences were observed. Inhibition of the contralateral RVLM (muscimol, 2 mM, 90 nl) caused decreases in MAP and SSNA that were not different between groups but enhanced decreases in SSNA to GABA in sedentary rats only. In sinoaortic denervated rats, GABA microinjections prior to or after inhibition of the contralateral RVLM caused decreases in MAP and SSNA that were not different between groups. Results suggest that contralateral RVLM plays an important role in buffering responses to inhibition of the ipsilateral RVLM under sedentary conditions. Enhanced sympathoinhibition may act to reduce already elevated sympathetic nervous system activity following sedentary conditions.

http://ift.tt/2qtRO0O

Role of Endothelial Nitric Oxide in Control of Peripheral Vascular Conductance During Muscle Metaboreflex Activation

Muscle metaboreflex activation during submaximal dynamic exercise, increases arterial pressure primarily via increases in cardiac output as there is little systemic vasoconstriction. Indeed, in normal animals we have often shown a small, but significant, peripheral vasodilation during metaboreflex activation, which is mediated, at least in part, by release of epinephrine and activation of vascular β₂ receptors. We tested whether this vasodilation is in part due to increased release of nitric oxide caused by the rise in cardiac output eliciting endothelium-dependent flow-mediated vasodilation. The muscle metaboreflex was activated via graded reductions in hindlimb blood flow during mild exercise with and without nitric oxide synthesis blockade (L-nitroarginine methyl ester (L-name); 5mg/kg). We assessed the role of increased cardiac output in mediating peripheral vasodilation via the slope of the relationship between the rise in non-ischemic vascular conductance (conductance of all vascular beds excluding hindlimbs) vs. the rise in cardiac output. L-name increased mean arterial pressure at rest and during exercise. The metaboreflex-induced increases in mean arterial pressure were unaltered by L-name; whereas, the increases in cardiac output and non-ischemic vascular conductance were attenuated. However, the slope of the relationship between non-ischemic vascular conductance and cardiac output was not affected by L-name indicating that the rise in cardiac output did not elicit vasodilation via increased release of nitric oxide. Thus, although nitric oxide is intrinsic to the vascular tonus, endothelial-dependent flow-mediated vasodilation plays little role in the small peripheral vasodilation observed during muscle metaboreflex activation.

http://ift.tt/2r488Cu

Enhanced insulin secretion and insulin sensitivity in young lambs with placental insufficiency-induced intrauterine growth restriction

Intrauterine growth restriction (IUGR) is associated with persistent metabolic complications, but information is limited for IUGR infants. We determined glucose-stimulated insulin secretion (GSIS) and insulin sensitivity in young lambs with placental insufficiency-induced IUGR. Lambs with hyperthermia-induced IUGR (n=7) were compared to control lambs (n=8). GSIS was measured at 8±1 days of age, and at 15±1 days body weight-specific glucose utilization rates were measured with radiolabeled D-glucose during a hyperinsulinemic-euglycemic clamp (HEC). IUGR lambs weighed 23% less (P<0.05) than controls at birth. Fasting plasma glucose and insulin concentrations were not different between IUGR and controls for either study. First-phase insulin secretion was enhanced 2.3-fold in IUGR lambs compared to controls. However, second-phase insulin concentrations, glucose-potentiated arginine-stimulated insulin secretion, and β-cell mass were not different, indicating that IUGR β-cells have an intrinsic enhancement in acute GSIS. Compared to controls, IUGR lambs had higher body weight-specific glucose utilization rates and greater insulin sensitivity at fasting (1.6-fold) and hyperinsulinemic periods (2.4-fold). Improved insulin sensitivity for glucose utilization was not due to differences in skeletal muscle insulin receptor and glucose transporters 1 and 4 concentrations. Plasma lactate concentrations during HEC were elevated in IUGR lambs compared to controls, but no differences were found for glycogen content or citrate synthase activity in liver and muscle. Greater insulin sensitivity for glucose utilization and enhanced acute GSIS in young lambs are predicted from fetal studies, but may promote conditions that exaggerate glucose disposal and lead to episodes of hypoglycemia in IUGR infants.

http://ift.tt/2qtQjQ9

Evidence for Intraventricular Secretion of Angiotensinogen and Angiotensin by the Subfornical Organ Using Transgenic Mice

Direct intracerebroventricular injection of angiotensin II causes increases in blood pressure, salt and water intake, presumably mimicking an effect mediated by an endogenous mechanism. The subfornical organ (SFO) is a potential source of cerebrospinal fluid (CSF) angiotensin-I (Ang-I) and angiotensin-II (Ang-II), and thus we hypothesized that the SFO has a secretory function. Endogenous levels of angiotensinogen (AGT) and renin are very low in the brain. We therefore examined the immunohistochemical localization of angiotensin peptides and AGT in the SFO, and AGT in the CSF in two transgenic models over-expressing either human AGT (A+ mice), or both human AGT and human renin (SRA mice) in the brain. Measurements were made at baseline and following volumetric depletion of CSF. Ultrastructural analysis with immunoelectron microscopy revealed that superficially located Ang-I/Ang-II and AGT immunoreactive cells in the SFO were vacuolated and opened directly into the ventricle. Withdrawal of CSF produced an increase in AGT in the CSF which was accompanied by a large decline in AGT immunoreactivity within SFO cells. Our data provide support for the hypothesis that the SFO is a secretory organ releasing AGT and possibly Ang-I/Ang-II into the ventricle at least under conditions when renin-angiotension system genes are overexpressed in mice.

http://ift.tt/2r3K1no

Intermittent Hypoxia Training Blunts Cerebrocortical Presenilin 1 Overexpression and Amyloid {beta} Accumulation in Ethanol-Withdrawn Rats

Abrupt cessation of chronic alcohol consumption triggers signaling cascades that harm vulnerable brain regions and produce neurobehavioral deficits. We have demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in rats prevents neurobehavioral impairment resulting from abrupt ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated protein kinase p38 and presenilin 1 (PS1), the -secretase component that produces the neurotoxic amyloid-β (Aβ) peptides, Aβ40 and Aβ42. We tested the hypotheses that (1) IHT limits EW-induced activation of the p38-PS1 axis, thereby attenuating -secretase activation and Aβ accumulation, and (2) EW disables heat shock protein 25 (HSP25), a p38 substrate, molecular chaperone and antioxidant, and provokes protein carbonylation in a manner suppressed by IHT. Adult male rats completed two cycles of 4 wk ethanol diet (0 or 6.5% w/v) and 3 wk EW. A 20 d IHT program of cyclic, 5-8 min exposures to 9.5-10% FIO₂ was administered during the first EW phase. PS1, phosphorylated p38 (P-p38) and HSP25 were analyzed by immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein carbonyl content by spectrometry, and Aβ40 and Aβ42 contents by enzyme-linked immunosorbent assay, in prefrontal cortical extracts. IHT attenuated the EW-associated increases in PS1, P-p38, Aβ40, Aβ42 and protein carbonyl contents, but not that of PS1 messenger RNA, while preserving functionally competent HSP25 dimers in EW rats. Collectively, these findings demonstrate that IHT attenuates EW-activation of the p38-PS1--secretase axis, thereby dampening Aβ accumulation, and prevents EW-induced oxidative protein damage.

http://ift.tt/2qu2fl3

Active Ingredients of Epimedii Folium and Ligustri Lucidi Fructus Balanced GR/HSP90 to Improve the Sensitivity of Asthmatic Rats to Budesonide

This study aimed to investigate the possible molecular mechanisms of active ingredients of Epimedii Folium (EF) and Ligustri Lucidi Fructus (LLF) combined with Budesonide (Bun) in asthmatic rats. Rats were divided into 5 groups, including normal group, asthma model group, Bun group, group of active ingredients of EL and LLF (EL), and group of coadministration of Bun with EL (Bun&EL). The asthmatic model was prepared by ovalbumin sensitizing and challenging. Lymphocyte apoptosis, GR protein and binding, and the protein and mRNA of GRα, GRβ, and HSP90 were tested. The results showed that Bun&EL ① markedly increased lymphocyte apoptosis, GR and HSP90 protein, and GR binding in BALF and ② enhanced the expressions of GRα and HSP90 and the ratio of GRα to GRβ or to HSP90 both in protein and in mRNA levels in lung, ③ while decrease occurred in GRβ mRNA and the mRNA ratio of GRβ to HSP90 compared with asthma or Bun group. Moreover, there was a significant correlation between GRα and GRβ in protein level, or between GRα and HSP90 both in protein and in mRNA levels. EL may effectively enhance the sensitivity of asthmatic rats to Bun via balancing GR/HSP90. And these findings will be beneficial for the treatment of asthma in the future.

http://ift.tt/2q728J1

From Human Mesenchymal Stem Cells to Insulin-Producing Cells: Comparison between Bone Marrow- and Adipose Tissue-Derived Cells

The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs), for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs), was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine. Conclusion. BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine.

http://ift.tt/2q4IlvT

Molecular Cloning, Expression Profiling, and Marker Validation of the Chicken Myoz3 Gene

Myozenin3 (Myoz3) has been reported to bind multiple Z-disc proteins and hence play a key role in signal transduction and muscle fiber type differentiation. The purpose of current study is to better understand the basic characteristics of Myoz3. Firstly, we cloned the ORF (open reading frame) of the Myoz3 gene. AA (amino acid) sequence analysis revealed that the Myoz3 gene encodes a 26 kDa protein which have 97% identities with that of turkey. Expression profiling showed that Myoz3 mRNA is mainly expressed in leg muscle and breast muscle. Furthermore, we investigated Myoz3 gene polymorphisms in two broiler breeds, the Yellow Bantam (YB) and the Avian. Five SNPs (single nucleotide polymorphisms) were identified in the YB breed and 3 were identified in the Avian breed. Genotypes and haplotype were constructed and their associations with carcass traits were analyzed. In the YB breed, c.516 C>T had a strong effect on both shank bone length and the value of breast muscle, and the H1H3 diplotype had the highest FC compared to other diplotypes. The markers identified in this study may serve as useful targets for the marker-assisted selection (MAS) of growth and meat quality traits in chickens.

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The Rush from Judgment

SEE RELATED ARTICLE, P. ■■■.

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Sclerema Neonatorum Treated Successfully with Parenteral Steroids: An Experience from a Resource Poor Country

Sclerema neonatorum is a form of panniculitides characterized by diffuse hardening of subcutaneous tissue with minimal inflammation. It usually affects ill and preterm neonates. Prognosis is usually poor in many cases despite aggressive management. Various treatment modalities (antibiotics, intravenous immunoglobulin, steroids, and exchange transfusion) have been explained in literature. Steroids due to its easy availability and low cost can prove to be lifesaving in such cases, especially in resource poor countries. Here, we report a case of sclerema neonatorum in a one-week preterm baby treated successfully with parenteral steroids and antibiotics.

http://ift.tt/2r1ThHR

Parotitis as an Initial Symptom of Kawasaki Disease

We report the case of a 13-month-old boy who developed right side parotitis as a first symptom of Kawasaki disease (KD). The data presented herein suggest that physicians should be aware that nonsuppurative parotitis is a possible manifestation of KD.

http://ift.tt/2pm2T3R

Perioperative COX-2 and {beta}-adrenergic blockade improves metastatic biomarkers in breast cancer patients in a phase-II randomized trial

Purpose: <br /> <p>Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients.</p> <br />Experimental Design: <br /> <p>In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a beta-adrenergic antagonist (propranolol) and a cyclooxygenase-2 (COX-2) inhibitor (etodolac), beginning five days before surgery. Excised tumors and sequential blood samples were assessed for pro-metastatic biomarkers.</p> <br /><br />Results: <br /> <p>Drugs were well tolerated with adverse event rates comparable to placebo. Transcriptome profiling of the primary tumor tested a priori hypotheses and indicated that drug treatment significantly (i) decreased epithelial-to-mesenchymal transition, (ii) reduced activity of pro-metastatic/proinflammatory transcription factors (GATA-1, GATA-2, early-growth-response-3/EGR3, signal transducer and activator of transcription-3/STAT-3), and (iii) decreased tumor-infiltrating monocytes while increasing tumor-infiltrating B cells. Drug treatment also significantly abrogated presurgical increases in serum interleukin-6 (IL-6) and C-reactive protein levels, abrogated perioperative declines in stimulated interleukin-12 and interferon-gamma production, abrogated postoperative mobilization of CD16^- "classical" monocytes, and enhanced expression of CD11a on circulating natural killer cells. </p> <br /><br />Conclusions:<br /> <p>Perioperative inhibition of COX-2 and b-adrenergic signaling provides a safe and effective strategy for inhibiting multiple cellular and molecular pathways related to metastasis and disease recurrence in early-stage breast cancer. 

http://ift.tt/2q7gfhf

Efficient Trial Design — FDA Approval of Valbenazine for Tardive Dyskinesia

A well-executed development program that addresses both regulatory and clinical requirements is critical for making novel therapeutics available as quickly as possible to patients with unmet medical needs. In the case of valbenazine, which was recently approved by the U.S. Food and Drug…

http://ift.tt/2qVj9sm

RET signaling in prostate cancer

Purpose: Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its co-receptor GFRα1, binds RET and activates downstream pro-oncogenic signaling. Since both GDNF and GFRα1 are secreted by nerves, we examined the role of RET signaling in prostate cancer. <p>Experimental Design: Expression of RET, GDNF and/or GFRα1 was assessed. The impact of RET signaling on proliferation, invasion and soft agar colony formation, perineural invasion and growth in vivo was determined. Cellular signaling downstream of RET was examined by Western blotting.</p> <p>Results: RET is expressed in all prostate cancer cell lines. GFRα1 is only expressed in 22Rv1 cells, which is the only line that responds to exogenous GDNF. In contrast, all cell lines respond to GDNF plus GFRα1. Conditioned medium from dorsal root ganglia contains secreted GFRα1 and promotes transformation related phenotypes, which can be blocked by anti-GFRα1 antibody. Perineural invasion in the dorsal root ganglion assay is inhibited by anti-GFRα antibody and RET knockdown. In vivo, knockdown of RET inhibits tumor growth. RET signaling activates ERK or AKT signaling depending on context, but phosphorylation of p70S6 kinase is markedly increased in all cases. Knockdown of p70S6 kinase markedly decreases RET induced transformed phenotypes. Finally, RET is expressed in 18% of adenocarcinomas and all three small cell carcinomas examined.</p> <p>Conclusions: RET promotes transformation associated phenotypes, including perineural invasion in prostate cancer via activation of p70S6 kinase. GFRα1, which is secreted by nerves, is a limiting factor for RET signaling, creating a perineural niche where RET signaling can occur.</p> <p> 

http://ift.tt/2q7nuWx

Genome-wide DNA methylation analysis reveals GABBR2 as a novel epigenetic target for EGFR 19 deletion lung adenocarcinoma with induction erlotinib treatment

Purpose: The last decade has witnessed the rapid development of personalized targeted therapies in lung cancer. It is still unclear whether epigenetic changes are involved in the response to tyrosine kinase inhibitor (TKI) treatment in epidermal growth factor receptor (EGFR) mutated lung cancer. <p>Experimental Design: Methyl-sensitive cut counting sequencing (MSCC) was applied to investigate the methylation changes in paired tissues before and after erlotinib treatment for 42 days with partial response (PR) from stage IIIa (N2) lung adenocarcinoma patients (N=2) with EGFR 19 deletion. The Sequenom EpiTYPER assay was used to validate the changed methylated candidate genes. Up- or downregulation of the candidate gene was performed to elucidate the potential mechanism in the regulation of erlotinib treatment response.</p> <p>Results: Sixty aberrant methylated genes were screened using MSCC sequencing. Two aberrant methylated genes, CBFA2T3 and GABBR2, were clearly validated. A same differential methylated region (DMR) between exon 2 and exon 3 of GABBR2 gene was confirmed consistently in both patients. GABBR2 was significantly downregulated in EGFR 19 deletion cells, HCC4006 and HCC827, but remained conserved in EGFR wild type A549 cells after erlotinib treatment. Upregulation of GABBR2 expression significantly rescued erlotinib-induced apoptosis in HCC827 cells. GABBR2 was significantly downregulated, along with the reduction of S6, p-p70 S6 and p-ERK1/2, demonstrating that GABBR2 may play an important role in EGFR signaling through the ERK1/2 pathway.</p> Conclusions: We demonstrated that GABBR2 gene might be a novel potential epigenetic treatment target with induction erlotinib treatment for stage IIIa (N2) EGFR 19 deletion lung adenocarcinoma.

http://ift.tt/2q4GF5s

Dual inhibition of EZH2 and EZH1 sensitizes PRC2-dependent tumors to proteasome inhibition

Purpose: <br /> <p>EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma (MM) and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on MM and prostate cancer.</p> <br /><br />Experimental Design: <br /> <p>In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in MM cell lines, primary patient cells and in a xenograft model. RNA-seq and ChIP-seq were performed to uncover the targets of UNC1999 in MM. The efficacy of the combination therapy was validated in prostate cancer cell lines.</p> <br /><br />Results:<br /> <p>Proteasome inhibitors repressed EZH2 transcription via abrogation of RB-E2F pathway, thereby sensitizing EZH2-dependent MM cells to EZH1 inhibition by UNC1999. Correspondingly, combination of proteasome inhibitors with UNC1999, but not with an EZH2-specific inhibitor, induced synergistic anti-myeloma activity in vitro. Bortezomib combined with UNC1999 remarkably inhibited the growth of myeloma cells in vivo. Comprehensive analyses revealed several direct targets of UNC1999 including the tumor suppressor gene NR4A1. Derepression of NR4A1 by UNC1999 resulted in suppression of MYC, which was enhanced by the combination with bortezomib, suggesting the cooperative blockade of PRC2 function. Notably, this combination also exhibited strong synergy in prostate cancer cells.</p> <br />Conclusions:<br /> <p>Our results identify dual inhibition of EZH2 and EZH1 together with proteasome inhibition as a promising epigenetics-based therapy for PRC2-dependent cancers.

http://ift.tt/2q4Bti6

A First-in-Human, Phase I, Dose-Escalation Study of TAK-117, a Selective PI3K{alpha} Isoform Inhibitor, in Patients with Advanced Solid Malignancies

Purpose: To evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of TAK-117 (MLN1117/INK1117), an investigational PI3Kα-selective inhibitor, in patients with advanced solid tumors. <p>Experimental Design: Seventy-one patients received oral TAK-117 once daily (QD, 100-300 mg [n = 24]), or 3 days per week (Mon-Wed-Fri [MWF], 200-1200 mg [n = 27]; Mon-Tue-Wed [MTuW], 200-900 mg [n = 20]), in 21-day cycles. Dose escalation proceeded via a 3+3 design.</p> <p>Results: TAK-117 QD dosing was associated with dose-limiting grade ≥3 alanine/aspartate aminotransferase (ALT/AST) elevations, resulting in a narrow range of tolerable doses (100-150 mg QD). With MWF/MTuW dosing, no dose-limiting ALT/AST elevations occurred until the MTD of 900 mg; total weekly dose was 2.6-fold that of 150 mg QD. Drug-related grade ≥3 adverse events occurred in 25%/22%/35% (including hyperglycemia in 0%/7%/15%) of QD/MWF/MTuW patients. TAK-117 (100-1200 mg) exhibited moderately fast oral absorption, a generally dose-proportional increase in exposure, and plasma half-life of ~11 hours. Total weekly exposures with 900 mg MWF/MTuW dosing were ~four times greater than with 150 mg QD. Skin pS6 expression was suppressed at ≥200 mg. There were 3/1/0 partial responses (QD/MWF/MTuW) and 5/7/5 patients had stable disease lasting ≥3 months (all PIK3CA mutated).</p> <p>Conclusion: Intermittent dosing of TAK-117 had an acceptable safety profile and enabled higher doses and total weekly exposures versus QD dosing. While the potential for TAK-117 as single-agent therapy appears limited, further evaluation in combination approaches for advanced solid tumors is warranted.

http://ift.tt/2q7lgqa

Accuracy of Blood Loss Measurement during Cesarean Delivery

AJP Rep 2017; 07: e93-e100
DOI: 10.1055/s-0037-1601382

Objective This study aims to compare the accuracy of visual, quantitative gravimetric, and colorimetric methods used to determine blood loss during cesarean delivery procedures employing a hemoglobin extraction assay as the reference standard. Study Design In 50 patients having cesarean deliveries blood loss determined by assays of hemoglobin content on surgical sponges and in suction canisters was compared with obstetricians' visual estimates, a quantitative gravimetric method, and the blood loss determined by a novel colorimetric system. Agreement between the reference assay and other measures was evaluated by the Bland–Altman method. Results Compared with the blood loss measured by the reference assay (470 ± 296 mL), the colorimetric system (572 ± 334 mL) was more accurate than either visual estimation (928 ± 261 mL) or gravimetric measurement (822 ± 489 mL). The correlation between the assay method and the colorimetric system was more predictive (standardized coefficient = 0.951, adjusted R2 = 0.902) than either visual estimation (standardized coefficient = 0.700, adjusted R2 = 00.479) or the gravimetric determination (standardized coefficient = 0.564, adjusted R2 = 0.304). Conclusion During cesarean delivery, measuring blood loss using colorimetric image analysis is superior to visual estimation and a gravimetric method. Implementation of colorimetric analysis may enhance the ability of management protocols to improve clinical outcomes.
[...]

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

http://ift.tt/2pyMjce

An Online Readability Analysis of Pathology-Related Patient Education Articles: An Opportunity for Pathologists to Educate Patients

Information for patients regarding their clinical conditions and treatment options is widely available online. The American Medical Association and National Institutes of Health recommend that online patient-oriented materials be written at no higher than a 7th grade reading level to ensure full comprehension by the average American. This study sought to determine whether online patient-oriented materials explaining common pathology procedures are written at appropriate reading levels. Ten pathology procedures that patients would likely research were queried into Google search, and plain text from the first 10 websites containing patient education materials for each procedure were analyzed using 10 validated readability scales.

http://ift.tt/2pz6bM9

Elastic staining – an rejuvenated method to reassess prognosis and serosal invasion in patients with pT3N0M0 gastric cancer

Prognosis of pT3N0M0 gastric cancer (GC) varies greatly, though the major factor conferring poor prognosis is unclear. Subserosal elastic lamina invasion (ELI+) is closely associated with poor outcomes in pT3 colorectal cancer, but related research on GC is unavailable. This study aimed to identify the influence of ELI+ on the prognosis of patients with pT3N0M0 GC and its relationship with serosal invasion using elastic staining. We retrospectively reviewed 94 and 28 patients with pT3N0M0 and pT4aN0M0 GC who underwent gastrectomy between 1994 and 2005.

http://ift.tt/2qVg4Zv

Comparison of clinicopathologic characteristics of gastric follicular lymphomas and duodenal follicular lymphomas

We compared the incidence, esophagogastroduodenoscopy (EGD) findings, and histopathologic characteristics of gastric and duodenal follicular lymphomas (FL). Of 626 FL cases, primary gastric FL and secondary gastric involvement of FL were observed in 1% and 5% of the cases, respectively, which were lower incidences than duodenal FL (10% and 9%, respectively). Gastric FL usually appeared as submucosal tumors (primary, 71%: secondary, 79%), whereas duodenal FL as granular lesions (primary, 92%: secondary, 87%).

http://ift.tt/2pyTssX

PTEN loss and p27 loss differ among morphologic patterns of prostate cancer, including cribriform

The presence and extent of cribriform pattern of prostate cancer portend recurrence and cancer death. Therelative expressions within this morphology of the prognostically adverse loss of PTEN, and the downstream inactivation of cell cycle inhibitor p27/Kip1 had been uncertain. In this study, we examined 52 cases of cribriform cancer by immunohistochemistry (IHC) for PTEN, p27, and CD44 variant (v)7/8, and a subset of 17 casesby chromogenic in situ hybridization (ISH) using probe for PTEN or CDKN1B (gene for p27).

http://ift.tt/2qUE4Mi

A novel fusion of HNRNPA1–ALK in inflammatory myofibroblastic tumor of urinary bladder

Here, we report an inflammatory myofibroblastic tumor (IMT) of the urinary bladder with a novel HNRNPA1–ALK fusion. To the best of our knowledge, this is the first case of a tumor with HNRNPA1–ALK fusion. A 42-year-old Japanese man underwent total cystectomy because of an invasive urinary bladder tumor. Grossly, the tumor had invaded the peribladder fat tissue. Histologically, it comprised spindle neoplastic cells with intermingled inflammatory cells. Immunohistochemically, it was positive for ALK, SMA, desmin, cytokeratin, and vimentin, consistent with the immunohistochemical characteristics of IMTs.

http://ift.tt/2pz6c2F

BRAF V600E Mutation in Pediatric Intracranial and Cranial Juvenile Xanthogranuloma

Juvenile xanthogranuloma (JXG) is a cutaneous form of non-Langerhans cell histiocytosis (LCH), primarily affecting children. The lesion is presumed to originate from either macrophages or dermal dendritic cells. JXG can rarely present as an isolated intracranial lesion and, in contrast to the dismal outcome of patients with systemic disease, cranial JXG has been shown to carry a more favorable prognosis. Here, we report for the first time 3 pediatric cases of JXG with a BRAF V600E mutation, 2 with intracranial lesions and one with cranial lesions.

http://ift.tt/2qUZKIj

ATOH1 promotes leptomeningeal dissemination and metastasis of Sonic Hedgehog subgroup medulloblastomas

Medulloblastoma (MB) arising from the cerebellum is the most common pediatric brain malignancy, with leptomeningeal metastases often present at diagnosis and recurrence associated with poor clinical outcome. In this study, we employed mouse MB models to explore the relationship of tumor pathophysiology and dysregulated expression of the Notch pathway transcription factor ATOH1, which is present in aggressive MB subtypes driven by aberrant Sonic Hedgehog/Patched (SHH/PTCH) signaling. In experiments with conditional Atoh1 mouse mutants crossed to Ptch1+/- mice which develop SHH-driven MB[63], animals with Atoh1 transgene expression developed highly penetrant MB at a young age with extensive leptomeningeal disease and metastasis to the spinal cord and brain, resembling xenografts of human SHH MB. Metastatic tumors retained abnormal SHH signaling like tumor xenografts. Conversely, Atoh1 expression was detected consistently in recurrent and metastatic SHH MB. ChIP-seq and gene expression profiling identified candidate ATOH1 targets in tumor cells involved in development and tumorigenesis. Among these targets specific to metastatic tumors, there was an enrichment in those implicated in extracellular matrix remodeling activity, cytoskeletal network and interaction with microenvironment, indicating a shift in transcriptomic and epigenomic landscapes during metastasis. Treatment with bone morphogenetic protein (BMP) or SHH pathway inhibitors decreased tumor cell proliferation and suppressed metastatic tumor growth, respectively. Our work reveals a dynamic ATOH1-driven molecular cascade underlying MB metastasis that offers possible therapeutic opportunities.

http://ift.tt/2q4R1Sj

CHK1 inhibition in small cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib

Effective targeted therapies for small cell lung cancer (SCLC), the most aggressive form of lung cancer, remain urgently needed. Here we report evidence of preclinical efficacy evoked by targeting the overexpressed cell cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacological blockade with the novel second-generation CHK1 inhibitor prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the effects of cisplatin or the PARP inhibitor olaparib, and improved the response of platinum-resistant models. Proteomic analysis identified CHK1 and MYC as top predictive biomarkers of LY2606368 sensitivity, suggesting that CHK1 inhibition may be especially effective in SCLC with MYC amplification or MYC protein overexpression. Our findings provide a preclinical proof of concept supporting the initiation of a clinical efficacy trial in patients with platinum-sensitive or platinum-resistant relapsed SCLC.

http://ift.tt/2pAUhCn

Three year cancer incidence in Blantyre, Malawi (2008-2010)

Abstract

In this paper we present incidence rates of different cancers calculated for the population of Blantyre, Malawi for the period 2008-2010, using data from the Malawi Cancer Registry. Active methods were used for case finding, with standard checks for accuracy and validity performed in CanReg 4. During this three year period, a total of 3,711 cases were registered comprising 1,643 men (an estimated age-standardized incidence rate (ASR) of 169.8 per 100,000) and 2,068 women (ASR 238.7 per 10⁵). Kaposi sarcoma (KS) was the most common cancer in men (40.5% of all cancers in men; ASR 54.0 per 10⁵) whilst cervical cancer was commonest in women (33.3%; ASR 88.6 per 10⁵). The incidence rates for oesophageal cancer remain one of the highest in the world (ASR 30.9 per 100,000 in men, 22.1 per 100,000 in women). Incidence of cancer of the prostate is relatively low in Blantyre (5.1%; ASR 16.4 per 10⁵), compared with elsewhere in Africa. In childhood, the cancer spectrum is dominated by Burkitt lymphoma (32.5% ASR 90.9 per 10⁶) followed by Wilms tumour (11.3%; ASR 35.9 per 10⁶) and pediatric KS (11.0%; ASR 31.1 per 10⁶). The overall percentage of cases with histological verification was 47.5%, a slight improvement from 42.4% in late 90's also indicating successful case finding outside laboratories. This article is protected by copyright. All rights reserved.

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Hyperglycaemia and aberrated insulin signalling stimulate tumour progression via induction of the extracellular matrix component hyaluronan

Abstract

Epidemiological studies have detected a higher incidence of various tumour entities in diabetic patients. However, the underlying mechanisms remain insufficiently understood. Glucose-derived pericellular and extracellular hyaluronan (HA) promotes tumour progression and development. In this study, we tested the hypothesis that a diabetic metabolic state, characterised by hyperglycaemia and concomitant aberrant insulin signalling, stimulates tumour progression via the induction of HA synthesis.

In a streptozotocin-induced diabetic nude mouse tumour xenograft model, hyperglycaemia and lack of insulin caused an increased formation of tumour-associated HA-matrix, which in turn accelerated tumour progression and neoangiogenesis. This process was effectively attenuated by treatment with 4-methylumbelliferone, a pharmacological inhibitor of HA-synthesis. To define the mechanisms behind these in vivo observations, we investigated the impact of hyperglycaemia and insulin on the glucose metabolism in oesophageal squamous cell cancer cells (ESCC). Hyperglycaemia induced HA synthesis while insulin diminished HA production by directing glucose metabolites to glycolysis. Vice versa, inhibition of glycolysis, either by knockdown of the glycolytic key enzyme phosphofructokinase or by an experimental abrogation of insulin signalling (knockdown of the insulin receptor, long-term treatment with insulin) augmented HA synthesis. Consequently, these processes induced invasion, anchorage-independent growth and adhesion of ESCC to endothelial cells in vitro.

Thus, the cellular shift in glucose usage from catabolism of glucose to anabolism of HA driven by hyperglycaemia and insulin resistance may represent an important link between diabetes and cancer progression. Hence, therapeutical inhibition of HA synthesis may represent a promising approach for tumour treatment in diabetic patients. This article is protected by copyright. All rights reserved.

http://ift.tt/2pAZslR

The SAFE-T Assessment Tool: Derivation and Validation of a Web-based Application for Point-of-care Evaluation of Gastroenterology Fellow Performance in Colonoscopy

Attending assessment is a critical part of endoscopic education for gastroenterology fellows. The aim of this study was to develop and validate a concise assessment tool to evaluate real-time fellow performance in colonoscopy administered via a web-based application.

http://ift.tt/2r3n6so

Endoscopic and Molecular Characterization of Colorectal Sessile Serrated Adenoma/polyps with Cytological Dysplasia

Sessile serrated adenoma/polyps (SSA/Ps), which are precursor lesions of colorectal cancer (CRC) with BRAF mutation and the CpG island methylator phenotype (CIMP), develop cytological dysplasia (CD) during the progression of colorectal tumorigenesis. In the present study, we aimed to clarify the endoscopic and molecular signatures of SSA/Ps, with and without CD.

http://ift.tt/2qtgYfK

Transmural Ablation of the Normal Porcine Common Bile Duct with Catheter-Directed Irreversible Electroporation is Feasible and Does Not Impact Duct Patency

http://ift.tt/2qtngMw

Su1626 What Do We Endoscopists Need for the Quality Control of Colonoscopy Exam?

The guidelines for colonoscopy present that the quality indicator should include cecal intubation rate (CIR), colonoscopy withdrawal time (WT), bowel preparation, and adverse events, in addition to the key indicator, adenoma detection rate. Small polyps less than 6 mm in diameter are diagnosed according to the narrow-band imaging international colorectal endoscopic (NICE) classification and usually followed up or removed without pathological exam. The purpose of this retrospective study is to demonstrate the clinical usefulness of PQ scope with passive bending (Olympus Medical Systems, Tokyo, Japan) and also analyze the related factors with high polyp detection rate (PDR) by using comprehensive health checkup data.

http://ift.tt/2r3LhXM

Does Vitamin D Status Correlate with Cardiometabolic Risk Factors in Adults with Growth Hormone Deficiency?

Horm Metab Res
DOI: 10.1055/s-0043-100114

Apart from being individually associated with cardiometabolic health, 25(OH)D and IGF-1 interplay with a positive correlation between them, which raises questions about the role of vitamin D for the adverse cardiovascular (CV) risk profile in hyposomatotropism. Thus, we aimed to investigate vitamin D status in GH deficiency (GHD) and the association between 25(OH)D and metabolic syndrome (MetS), its components, and other surrogate markers of CV risk. A total of 129 GHD adults (childhood-onset GHD, 41.9%) underwent blood testing (glucose, insulin, lipid profile, uric acid); blood pressure, anthropometric and bioelectrical-impedance measurements. Other CV risk markers were examined in a subsample of the initial population – hsCRP, adiponectin, and asymmetric dimethylarginine (n=88); carotid intima-media thickness (n=44). Total serum 25(OH)D, measured by electro-chemiluminescence binding assay, was used for vitamin D status assessment (adequate,≥30 ng/ml; insufficient, 20–29.9 ng/ml; deficient,<20 ng/ml). Data demonstrated high prevalence of hypovitaminosis D in GHD (deficiency 79.1%; insufficiency 14.7%), with lower 25(OH)D among adult-onset GHD subjects (14.0±7.2 vs. 16.8±8.0 ng/ml, p=0.039) and patients with MetS (11.8±4.5 vs. 16.3±8.1 ng/ml, p<0.0001). 25(OH)D correlated negatively and weakly with BMI, waist circumference, percent body fat, visceral fat area, and systolic BP. Regardless of whether vitamin D is a cause or a consequence of these metabolic abnormalities, 25(OH)D testing in hyposomatotropism is advisable. Normalization of vitamin D status is not proven to improve CV outcomes in general population, but it might have favorable effects in GHD, as its benefits might be restricted to patients with both low 25(OH)D and certain risk factors.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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

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Performance of Mycobacterium Growth Indicator Tube BACTEC 960 with Lowenstein–Jensen method for diagnosis of Mycobacterium tuberculosis at Ethiopian National Tuberculosis Reference Laboratory, Addis Ababa, Ethiopia

Bacteriological confirmed active case detection remains the corner stone for diagnosing tuberculosis. Non-radiometric liquid culture system Mycobacterium Growth Indicator Tube with automated interface had been re...

http://ift.tt/2r1EiNR

Effects of Exercise on Liver Fat and Metabolism in Alcohol Drinkers

Exercise is an important component of obesity associated disorders and has been shown to reduce markers of non-alcoholic fatty liver disease (NAFLD). However, little is known about how these effects are influenced by alcohol intake. We performed a randomized controlled trial to investigate the effects of exercise on hepatic triglyceride content (HTGC) and metabolism in overweight or obese patients who consume alcohol.

http://ift.tt/2r3E1uQ

Promising Modalities to Identify and Monitor Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is an allergen-mediated condition characterized by symptoms of esophageal dysfunction and histological evidence of intense eosinophilic inflammation involving the esophagus in absence of overlapping conditions such as gastroesophageal reflux disease. Since the initial description as a distinct entity about two decades ago, there has been a remarkable rise in the recognition of this clinico-pathologic entity.Current approach to diagnose and monitor EoE requires repeated esophagogastroduodenoscopies (EGDs), with associated sedation/anesthesia, to visualize mucosal abnormalities, and to obtain multiple biopsies for histologic assessment and to evaluate treatment response.

http://ift.tt/2qtc2rs

Glomus tumor of the stomach—a tumor that needs to be differentiated from gastrointestinal stromal tumor

http://ift.tt/2r3j2bm

High negative predictive value, low prevalence and spectrum effect: caution in the interpretation

http://ift.tt/2qthDOt

Multicenter External Validation of Risk Stratification Criteria for Patients With Variceal Bleeding

Early placement of a transjugular intrahepatic porto-systemic shunts (TIPS) is considered the treatment of choice for patients with acute variceal bleeding (AVB) and cirrhosis who have a high risk of death (Child-Pugh class B with active bleeding at endoscopy or Child-Pugh class C). It has been proposed that patients of Child-Pugh class B, even with active bleeding, should not be considered high risk. Alternative criteria have been proposed for identification of high-risk patients, such as Child-Pugh class C with plasma level of creatinine of 1 mg/dl or more (ChildC-C1) and a model for end-stage liver disease (MELD) score of 19 or more.

http://ift.tt/2r3nHdu

Biopsies from Allograft Liver Contain Histologic Features of Hepatitis C Virus Infection Following Virus Eradication

Most patients, even those who have received liver transplants, achieve a sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection. Little is known about the histologic features of liver biopsies collected following SVR, particularly in patients who have received liver transplants. We aimed to better characterize the histologic features of allograft liver biopsies from patients who achieved a SVR to anti-HCV therapy following liver transplantation.

http://ift.tt/2qt2Fb8

Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis

Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis

British Journal of Cancer 116, 1247 (9 May 2017). doi:10.1038/bjc.2017.67

Authors: Uwe Pelzer, Jean-Frédéric Blanc, Davide Melisi, Antonio Cubillo, Daniel D Von Hoff, Andrea Wang-Gillam, Li-Tzong Chen, Jens T Siveke, Yin Wan, Caitlyn T Solem, Marc F Botteman, Yoojung Yang, Floris A de Jong & Richard A Hubner

http://ift.tt/2nePFju

Evaluating wait times from screening to breast cancer diagnosis among women undergoing organised assessment vs usual care

Evaluating wait times from screening to breast cancer diagnosis among women undergoing organised assessment vs usual care

British Journal of Cancer 116, 1254 (9 May 2017). doi:10.1038/bjc.2017.87

Authors: Anna M Chiarelli, Derek Muradali, Kristina M Blackmore, Courtney R Smith, Lucia Mirea, Vicky Majpruz, Frances P O'Malley, May Lynn Quan & Claire MB Holloway

http://ift.tt/2onkRP4

Differential pattern of HIF-1α expression in HNSCC cancer stem cells after carbon ion or photon irradiation: one molecular explanation of the oxygen effect

Differential pattern of HIF-1α expression in HNSCC cancer stem cells after carbon ion or photon irradiation: one molecular explanation of the oxygen effect

British Journal of Cancer 116, 1340 (9 May 2017). doi:10.1038/bjc.2017.100

Authors: Anne-Sophie Wozny, Alexandra Lauret, Priscillia Battiston-Montagne, Jean-Baptiste Guy, Michael Beuve, Micaela Cunha, Yannick Saintigny, Emilie Blond, Nicolas Magne, Philippe Lalle, Dominique Ardail, Gersende Alphonse & Claire Rodriguez-Lafrasse

http://ift.tt/2nL6Deg

Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer

Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer

British Journal of Cancer 116, 1264 (9 May 2017). doi:10.1038/bjc.2017.95

Authors: C N Hurt, S Falk, T Crosby, A McDonald, R Ray, G Joseph, J Staffurth, R A Abrams, G Griffiths, T Maughan & S Mukherjee

http://ift.tt/2nHCnwI

Decreased levels of baseline and drug-induced tubulin polymerisation are hallmarks of resistance to taxanes in ovarian cancer cells and are associated with epithelial-to-mesenchymal transition

Decreased levels of baseline and drug-induced tubulin polymerisation are hallmarks of resistance to taxanes in ovarian cancer cells and are associated with epithelial-to-mesenchymal transition

British Journal of Cancer 116, 1318 (9 May 2017). doi:10.1038/bjc.2017.102

Authors: George E Duran, Yan C Wang, François Moisan, E Brian Francisco & Branimir I Sikic

http://ift.tt/2o2cDdU

Cetuximab in treatment of metastatic colorectal cancer: final survival analyses and extended RAS data from the NORDIC-VII study

Cetuximab in treatment of metastatic colorectal cancer: final survival analyses and extended RAS data from the NORDIC-VII study

British Journal of Cancer 116, 1271 (9 May 2017). doi:10.1038/bjc.2017.93

Authors: Tormod Kyrre Guren, Maria Thomsen, Elin H Kure, Halfdan Sorbye, Bengt Glimelius, Per Pfeiffer, Pia Österlund, Fridbjörn Sigurdsson, Inger Marie Bowitz Lothe, Astrid Marie Dalsgaard, Eva Skovlund, Thoralf Christoffersen & Kjell Magne Tveit

http://ift.tt/2o251rY

Serum inflammatory markers and colorectal cancer risk and survival

Serum inflammatory markers and colorectal cancer risk and survival

British Journal of Cancer 116, 1358 (9 May 2017). doi:10.1038/bjc.2017.96

Authors: Sundeep Ghuman, Mieke Van Hemelrijck, Hans Garmo, Lars Holmberg, Håkan Malmström, Mats Lambe, Niklas Hammar, Göran Walldius, Ingmar Jungner & Wahyu Wulaningsih

http://ift.tt/2nHyPe8

A phase 2 study of temozolomide in pretreated metastatic colorectal cancer with MGMT promoter methylation

A phase 2 study of temozolomide in pretreated metastatic colorectal cancer with MGMT promoter methylation

British Journal of Cancer 116, 1279 (9 May 2017). doi:10.1038/bjc.2017.109

Authors: M A Calegari, A Inno, S Monterisi, A Orlandi, D Santini, M Basso, A Cassano, M Martini, T Cenci, I de Pascalis, F Camarda, B Barbaro, L M Larocca, S Gori, G Tonini & C Barone

http://ift.tt/2oWwnln

Towards better dose individualisation: metabolic phenotyping to predict cabazitaxel pharmacokinetics in men with prostate cancer

Towards better dose individualisation: metabolic phenotyping to predict cabazitaxel pharmacokinetics in men with prostate cancer

British Journal of Cancer 116, 1312 (9 May 2017). doi:10.1038/bjc.2017.91

Authors: A Janssen, C P M Verkleij, A van der Vlist, R H J Mathijssen, H J Bloemendal & R ter Heine

http://ift.tt/2o2mTD5

Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study

Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multicentre study

British Journal of Cancer 116, 1287 (9 May 2017). doi:10.1038/bjc.2017.83

Authors: David L Phelps, Jane V Borley, Kirsty J Flower, Roberto Dina, Silvia Darb-Esfahani, Ioana Braicu, Jalid Sehouli, Christina Fotopoulou, Charlotte S Wilhelm-Benartzi, Hani Gabra, Joseph Yazbek, Jayanta Chatterjee, Jacey Ip, Harun Khan, Marina-Therese Likos-Corbett, Robert Brown & Sadaf Ghaem-Maghami

http://ift.tt/2nf3n5F

Predicting breast cancer response to neoadjuvant chemotherapy using pretreatment diffuse optical spectroscopic texture analysis

Predicting breast cancer response to neoadjuvant chemotherapy using pretreatment diffuse optical spectroscopic texture analysis

British Journal of Cancer 116, 1329 (9 May 2017). doi:10.1038/bjc.2017.97

Authors: William T Tran, Mehrdad J Gangeh, Lakshmanan Sannachi, Lee Chin, Elyse Watkins, Silvio G Bruni, Rashin Fallah Rastegar, Belinda Curpen, Maureen Trudeau, Sonal Gandhi, Martin Yaffe, Elzbieta Slodkowska, Charmaine Childs, Ali Sadeghi-Naini & Gregory J Czarnota

http://ift.tt/2o1g4q4

Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma—experience of the BriTROC consortium

Safety and utility of image-guided research biopsies in relapsed high-grade serous ovarian carcinoma—experience of the BriTROC consortium

British Journal of Cancer 116, 1294 (9 May 2017). doi:10.1038/bjc.2017.86

Authors: T Goranova, D Ennis, A M Piskorz, G Macintyre, L A Lewsley, J Stobo, C Wilson, D Kay, R M Glasspool, M Lockley, E Brockbank, A Montes, A Walther, S Sundar, R Edmondson, G D Hall, A Clamp, C Gourley, M Hall, C Fotopoulou, H Gabra, S Freeman, L Moore, M Jimenez-Linan, J Paul, J D Brenton & I A McNeish

http://ift.tt/2ontQji

Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis

Targeting of CCBE1 by miR-330-3p in human breast cancer promotes metastasis

British Journal of Cancer 116, 1350 (9 May 2017). doi:10.1038/bjc.2017.105

Authors: Aruz Mesci, Xiaoyong Huang, Samira Taeb, Sahar Jahangiri, Yohan Kim, Emmanouil Fokas, Jeff Bruce, Hon S Leong & Stanley K Liu

http://ift.tt/2o17oQt

Lithium enhances the antitumour effect of temozolomide against TP53 wild-type glioblastoma cells via NFAT1/FasL signalling

Lithium enhances the antitumour effect of temozolomide against TP53 wild-type glioblastoma cells via NFAT1/FasL signalling

British Journal of Cancer 116, 1302 (9 May 2017). doi:10.1038/bjc.2017.89

Authors: Sheng Han, Lingxuan Meng, Yang Jiang, Wen Cheng, Xinxin Tie, Junzhe Xia & Anhua Wu

http://ift.tt/2onne4v

Tyrosine kinase-targeting drugs-associated heart failure

Tyrosine kinase-targeting drugs-associated heart failure

British Journal of Cancer 116, 1366 (9 May 2017). doi:10.1038/bjc.2017.88

Authors: N Gronich, I Lavi, O Barnett-Griness, W Saliba, D R Abernethy & G Rennert

http://ift.tt/2o2mSiv

EM Nerd-An Addendum to The Case of the Incidental Bystander

The October 2016 NEJM publication of the PESIT trial by Prandoni et al set the world of social media ablaze (1). There were the standard fear mongering headlines noting that 1 in 6 patients admitted to the hospital following syncope had a pulmonary embolism. This was followed by a reactionary flurry of commentary by the […]

EMCrit by Rory Spiegel.

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'Internet of things' security introduction for EMS leaders

A cybersecurity expert offers a soup-to-nuts IoT security guide for every organization, individual and device with confidential data to protect

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Commentary on a case of body pushing and radiation exposure in screening of body packing

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Harnessing the DNA Dye-triggered Side Population Phenotype to Detect and Purify Cancer Stem Cells from Biological Samples

Methods allowing the characterization and isolation of stem cell populations from biological samples are critical for the advance of stem cell-targeted treatments in cancer and beyond. Here, we provide a detailed protocol for cancer stem cell isolation using the dye-triggered side population phenotype.

http://ift.tt/2qsHGFA

Dosimetric advantage of volumetric modulated arc therapy in the treatment of intraocular cancer

Abstract

Objective

The purpose of this study is to investigate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in the treatment of intraocular cancer by comparing it directly with three-dimensional conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT).

Methods

CRT plan, 7f-IMRT plan, and one-arc VMAT plan were generated for 14 intraocular cancer patients. Dosimetric and biological quality indices for target volume and organs at risks (OARs) were evaluated and compared.

Results

The target coverage presented by V95 for CRT, IMRT and VMAT were 95.02% ± 0.67%, 95.51% ± 2.25%, and 95.92% ± 3.05%, respectively. The homogeneity index (HI) for CRT, IMRT and VMAT were 0.15 ± 0.05, 0.23 ± 0.05, and 0.23 ± 0.06, respectively. IMRT and VMAT greatly decreased the dose to ipsilateral lens compared with CRT with a D1 of 2972.66 ± 1407.12 cGy, 3317.82 ± 915.28 cGy and 4809.54 ± 524.60 cGy for IMRT, VMAT and CRT, respectively. Similar results were observed for ipsilateral eyeballs. IMRT and VMAT also spared better on brainstem, optical nerves and optical chiasm compared CRT. However, CRT achieved lower dose to the eyeballs compared with IMRT and VMAT. VMAT and IMRT showed mixed results on target coverage and OAR sparing. The average MUs and delivery time of IMRT and VMAT were 531.25 ± 81.21 vs. 400.99 ± 61.49 and 5.05 ± 0.53 vs.1.71 ± 0.69 min, respectively.

Conclusions

Although no clear distinction on PTV coverage among CRT, IMRT and VMAT plans was observed in the treatment of intraocular cancer, VMAT and IMRT achieved better homogeneity and conformity for target volume, and delivered fewer doses to ipsilateral lens and eyeballs compared with CRT. However, VMAT and IMRT increased the low dose volume to the contralateral OARs. Although VMAT and IMRT showed mixed results on target coverage and OAR sparing, VMAT decreased MU and delivery time significantly compared with IMRT. VMAT is a promising and feasible external beam radiotherapy technique in the treatment of intraocular cancer patients.

http://ift.tt/2py2CWR

Diagnostic and treatment modalities for patients with cervical lymph node metastases of unknown primary site – current status and challenges

Abstract

Background and Purpose

This review aims to provide a comprehensive overview of the literature and elucidate open questions for future clinical trials concerning diagnostics and treatment modalities for cervical cancer of unknown primary (CUP).

Methods

A literature search for head and neck CUP was performed with focus on diagnostics and therapies as well as molecular markers.

Results

High level evidence on CUP is limited. However, it seems that a consensus exists regarding the optimal diagnostic procedures. The correct implementation of biomarkers for patient stratification and treatment remains unclear. An even greater dispute dominates about the ideal treatment with publications ranging from sole surgery to surgery with postoperative bilateral radiotherapy with inclusion of the mucosa and concomitant chemotherapy.

Conclusions

Cervical CUP represents a very heterogeneous malignant disease. On this account many aspects concerning treatment optimization remain unclear, despite a considerable number of publications in the past. Future research in form of prospective randomized trials is needed in order to better define patient stratification criteria and enable tailored treatment.

http://ift.tt/2pxQpkY

Hematological and serum biochemical alterations in buffalo with some digestive disorders

Abstract

Hematological and serum biochemical reference intervals are essential laboratory variables for optimal diagnostic purposes. The present study was delineated to provide an insight into the hemato-biochemical alterations as well as the measurement of selected acute phase proteins in buffaloes showing some digestive disorders. The present study included 40 native breed water buffalo showing various symptoms of digestive troubles. Based on competent case history, clinical and laboratory findings, the diseased buffaloes were allocated into four equal sized groups, namely stomatitis, acute traumatic reticuloperitonitis (TRP), acute rumen impaction, and enteritis. Ten apparently healthy buffaloes were randomly selected from the same animal population and considered as control group. Blood samples were drawn from all investigated animals for hematologic examination and measurements of a panel of serum biochemical variables. All diseased buffaloes showed statistically significant high values of total leucocytes (P ≤ 0.05) with significantly low values of total erythrocytes and hemoglobin concentration compared with controls (P ≤ 0.05). Serum magnesium, sodium, and iron showed a statistically (P ≤ 0.05) lower values in all studied buffaloes than those of controls; while serum calcium levels were significantly decreased (P ≤ 0.05) in buffaloes showing stomatitis and those with TRP compared with controls. Serum hepatic enzyme activities beside serum haptoglobin and C-reactive protein were significantly (P ≤ 0.05) higher in all diseased buffaloes than those of controls. The results herein concluded that diseased buffalo were associated with marked hematological and elemental alterations besides a distinct inflammatory reaction. Further studies are needed to explore the potential ameliorative value of using supplementary agents to help mitigate the associated biochemical and inflammatory reactions in buffaloes exhibiting digestive disorders.

http://ift.tt/2pliQqM

Effects of Salvia officinalis L. on 7, 12-dimethylbenz[a]anthracene-induced breast cancer in rats and mouse mammary carcinoma cells (4T1)

Abstract

The toxicity of Salvia officinalis L. on different cancer cell lines has been reported extensively, but an in vivo evaluation on breast cancer has not been conducted. Therefore, in vivo and in vitro studies of are evaluated in this study. The hydro-alcoholic extract of Salvia officinalis L. was studied in female Wistar rats in three groups: one control (Con) group (n = 7) and two 7, 12-dimethylbenz[a]anthracene cancer-induced groups (CI) that were gavaged either with distilled water (Con-CI) or 30 mg/kg sage hydro-alcoholic extract (SHE-CI) for 30 days (n = 34). A mammary gland whole mount was prepared, and the number of alveolar buds and lobules were scored. Histomorphometrical changes and apoptosis were examined in mammary gland sections. Chromatin condensation, cell viability, apoptosis, and toxicity induction were monitored in 4T1 mouse mammary carcinoma cells treated by different doses of SHE. IC₅₀ of the 4T1 cell-treated SHE were examined by MTT assay. A decrease in alveolar buds, number of ducts and lobules, ductal diameters, and epithelial cells was observed in whole mount and histological sections of mammary glands in SHE-CI compared to the Con-CI group. Apoptotic cells were increased in SHE-CI compared to the Con-CI group. A decrease in cell viability and increase in chromatin condensation were observed in a dose-dependent manner in SHE-treated cultures. MTT assay revealed IC₅₀ of the 4T1 cell-treated SHE reduced significantly compared to the NIH cell line from the fibroblast as a normal cell. Salvia officinalis might prevent breast cancer under both in vivo and in vitro conditions.

http://ift.tt/2r0Xbki

Giant fibroadenoma with massive infarction masquerading as malignancy: a case report

Abstract

Fibroadenoma is a common benign breast lesion that usually affects women in their second and third decade of life and usually present as small mobile painless lump. However, it is important to recognize that a small percentage have been shown to progress to giant fibroadenomas. Giant fibroadenomas can undergo infarction leading to significant morbidity and difficulty to distinguish from the more aggressive phyllodes tumors or carcinoma. We report an interesting case of giant fibroadenoma (17 × 11 × 7 cm) with massive infarction during lactation, further complicated by lactational mastitis with close resemblance to cystosarcoma phyllodes. Detailed clinical evaluation and proper investigation in the form of USG breast and PET–CT scan helped us to delineate the nature of pathology. Simple excision of lesion with curvilinear incision was done with excellent cosmetic outcome. Histopathologic features were consistent with fibroadenoma (giant) with large areas of infarction. Fibroadenoma breast has varied clinical presentations. The course of disease may be complicated by pregnancy, lactation and inflammatory processes. Massive infarction may make the picture more dubious and masquerade with malignant transformation altering our treatment decision. The presence of necrosis on core biopsy or intra-operative finding should be cautiously interpreted and is not itself a sign of malignancy. Detailed clinical evaluation and comprehensive workup should be done before embarking on radical treatment.

http://ift.tt/2r2IGgE

Evaluation of Analgesia, Tolerance, and the Mechanism of Action of Morphine-6-O-Sulfate Across Multiple Pain Modalities in Sprague-Dawley Rats.

BACKGROUND: Morphine-6-O-sulfate (M6S) is a mixed [mu]/[delta]-opioid receptor (OR) agonist and potential alternative to morphine for treatment of chronic multimodal pain. METHODS: To provide more support for this hypothesis, the antinociceptive effects of M6S and morphine were compared in tests that access a range of pain modalities, including hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold tests. RESULTS: Acutely, M6S was 2- to 3-fold more potent than morphine in HPT and PST tests, specifically, derived from best-fit analysis of dose-response relationships of morphine/M6S half-effective dose (ED50) ratios (lower, upper 95% confidence interval [CI]) were 2.8 (2.0-5.8) in HPT and 2.2 (2.1, 2.4) in PST tests. No differences in analgesic drug potencies were detected in the PPT test (morphine/M6S ED50 ratio 1.2 (95% CI, 0.8-1.4). After 7 to 9 days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all 3 pain tests. Morphine-tolerant rats were not crosstolerant to M6S. The antinociceptive effects of M6S were not sensitive to [kappa]-OR antagonists. However, the [delta]-OR antagonist, naltrindole, blocked M6S-induced antinociception by 55% +/- 4% (95% CI, 39-75) in the HPT test, 94% +/- 4% (95% CI, 84-105) in the PST test, and 5% +/- 17% (95% CI, -47 to 59) or 51% +/- 14% (95% CI, 14-84; 6 rats per each group) in the paw pressure threshold test when examined acutely or after 7 days of chronic treatment, respectively. CONCLUSIONS: Activity via [delta]-ORs thus appears to be an important determinant of M6S action. M6S also exhibited favorable antinociceptive and tolerance profiles compared with morphine in 3 different antinociceptive assays, indicating that M6S may serve as a useful alternative for rotation in morphine-tolerant subjects. (C) 2017 International Anesthesia Research Society

http://ift.tt/2pAukTz

Little Black Boxes: Noncardiac Implantable Electronic Medical Devices and Their Anesthetic and Surgical Implications.

Implanted electronic medical devices. or stimulators such as pacemakers and nerve stimulators have grown enormously in diversity and complexity over recent decades. The function and potential interaction of these devices with the perioperative environment is of increasing concern for anesthesiologists and surgeons. Because of the innate electromagnetic environment of the hospital (operating room, gastrointestinal procedure suite, and imaging suite), implanted device malfunction, reprogramming, or destruction may occur and cause physical harm (including nerve injury, blindness, deafness, burn, stroke, paralysis, or coma) to the patient. It is critical for the anesthesiologist and surgeon to be aware of the function and interaction of implanted devices, both with other implanted devices and procedures (such as magnetic resonance imaging and cardioversion) in the hospital environment. Because of these interactions, it is imperative that proper device function is assessed when the surgical procedure is complete. This review article will discuss these important issues for 12 different types of "little black boxes," or noncardiac implantable electronic medical devices. (C) 2017 International Anesthesia Research Society

http://ift.tt/2q48qed

Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants

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Pupillary Reflex for Evaluation of Thoracic Paravertebral Block: A Prospective Observational Feasibility Study.

BACKGROUND: Although thoracic paravertebral block (TPVB) is recommended in major breast surgery, there is no gold standard to assess the success of TPVB. Pupillary dilation reflex (PDR) is the variation of the pupillary diameter after a noxious stimulus. The objective was to evaluate the feasibility of recording the PDR to assess analgesia in an anesthetized thoracic dermatome after TPVB. METHODS: This prospective, observational, single-center study included 32 patients requiring breast surgery under general anesthesia and TPVB. TPVB was performed before surgery under ultrasound guidance with 20 mL of 0.75% ropivacaine. At the end of the surgery, remifentanil was stopped and the PDR was recorded after a 5-second tetanic stimulation (60 mA, 100 Hz) applied to the anterior chest wall. The PDR was defined as the maximal increase in pupil diameter after a standardized noxious stimulus, expressed as a percentage of the initial pupil diameter. The PDR was recorded twice in the same eye for each patient following a stimulus on both the TPVB and the control sides. Postoperative pain scores were recorded in a postanesthesia care unit. The primary outcome was the difference between the PDR on the TPVB and the control sides. RESULTS: The median (interquartile range) PDR was 9% (4%-13%) on the TPVB side and 41% (27%-66%) on the control side. There was a significant difference in the PDR between the TPVB and the control sides with a Hodges-Lehmann estimate of absolute difference of 37% points (95% confidence interval, 25-52, P

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Factors Influencing Quality of Pain Management in a Physician Staffed Helicopter Emergency Medical Service.

BACKGROUND: Pain is frequently encountered in the prehospital setting and needs to be treated quickly and sufficiently. However, incidences of insufficient analgesia after prehospital treatment by emergency medical services are reported to be as high as 43%. The purpose of this analysis was to identify modifiable factors in a specific emergency patient cohort that influence the pain suffered by patients when admitted to the hospital. METHODS: For that purpose, this retrospective observational study included all patients with significant pain treated by a Swiss physician-staffed helicopter emergency service between April and October 2011 with the following characteristics to limit selection bias: Age > 15 years, numerical rating scale (NRS) for pain documented at the scene and at hospital admission, NRS > 3 at the scene, initial Glasgow coma scale > 12, and National Advisory Committee for Aeronautics score 3 at hospital admission) was identified in 298 patients (38%). Factors associated with insufficient pain management were higher National Advisory Committee for Aeronautics scores, high NRS at the scene, nontrauma patients, no analgesic administration, and treatment by a female physician. In 16% (128 patients), despite ongoing pain, no analgesics were administered. Factors associated with this untreated persisting pain were short time at the scene (below 10 minutes), secondary missions of helicopter emergency service, moderate pain at the scene, and nontrauma patients. Sufficient management of severe pain is significantly better if ketamine is combined with an opioid (65%), compared to a ketamine or opioid monotherapy (46%, P = .007). CONCLUSIONS: In the studied specific Swiss cohort, nontrauma patients, patients on secondary missions, patients treated only for a short time at the scene before transport, patients who receive no analgesic, and treatment by a female physician may be risk factors for insufficient pain management. Patients suffering pain at the scene (NRS > 3) should receive an analgesic whenever possible. Patients with severe pain at the scene (NRS >= 8) may benefit from the combination of ketamine with an opioid. The finding about sex differences concerning analgesic administration is intriguing and possibly worthy of further study. (C) 2017 International Anesthesia Research Society

http://ift.tt/2pA01MR

Current Status of Cardiovascular Anesthesia in China.

High quality and safe cardiac anesthesia is a prerequisite for success in cardiac care. Cardiac surgery has developed rapidly over recent years in China. Because of language barriers, the current status of cardiac anesthesia in China is not well known to Western countries. To assess practice patterns, volume, workforce, and training requirements of Chinese cardiovascular anesthesiologists, we surveyed 92 major cardiovascular centers in China regarding their anesthesia practice, monitoring techniques, resources, staffing, and work hours. We aim to provide a review of the history, new developments, and a current cross section of cardiac anesthesia practice patterns in China. The goal is to allow Western readers to understand the unique achievements and challenges in Chinese cardiovascular anesthesiology, thus promoting further communications with Chinese cardiovascular anesthesiologists. (C) 2017 International Anesthesia Research Society

http://ift.tt/2q3Yu42

ING5 suppresses breast cancer progression and is regulated by miR-24

Abstract

Background

The inhibitor of growth (ING) gene family of tumor suppressors is involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is a new member of the ING family whose function and regulation remain largely unknown.

Methods

Quantitative real-time PCR and western blot were used to examine the expression levels of ING5 in breast cancer tissues. The miRNAs that potentially targeted ING5 were determined by bioinformatics analysis and luciferase reporter assay. Cell viability assay, transwell invasion and apoptosis assay were used to characterize the changes induced by overexpressing or knocking down miR-24 or ING5. Hematoxylin and eosin (H&E) staining and immunohistochemical staining for ING5 and Ki-67 were used for xenograft assays in BALB/c nude mice.

Results

We showed that the ING5 protein rather than the mRNA, was significantly downregulated in breast cancer tissues. We also investigated the potential function of ING5 in breast tumorigenesis and found that ING5 suppressed the proliferation and invasion of breast cancer cells and promoted their apoptosis. Furthermore, we explored the molecular mechanisms accounting for the dysregulation of ING5 in breast cancer cells and identified an oncomiR, miR-24, as a direct upstream regulator of ING5. We revealed that miR-24 had the opposite effects to those of ING5 on breast cancer cells and could accelerate xenografted tumor growth in vivo.

Conclusion

Our findings uncover the tumor-suppressive role of ING5 and the regulatory pathway of ING5 in breast cancer and may provide insights into the molecular mechanisms of breast carcinogenesis.

http://ift.tt/2pxGLyy

Thymic Epithelial Tumors phenotype relies on miR-145-5p epigenetic regulation

Abstract

Background

Thymoma and thymic carcinoma are the most frequent subtypes of thymic epithelial tumors (TETs). A relevant advance in TET management could derive from a deeper molecular characterization of these neoplasms. We previously identified a set of microRNA (miRNAs) differentially expressed in TETs and normal thymic tissues and among the most significantly deregulated we described the down-regulation of miR-145-5p in TET. Here we describe the mRNAs diversely regulated in TETs and analyze the correlation between these and the miRNAs previously identified, focusing in particular on miR-145-5p. Then, we examine the functional role of miR-145-5p in TETs and its epigenetic transcriptional regulation.

Methods

mRNAs expression profiling of a cohort of fresh frozen TETs and normal tissues was performed by microarray analysis. MiR-145-5p role in TETs was evaluated in vitro, modulating its expression in a Thymic Carcinoma (TC1889) cell line. Epigenetic transcriptional regulation of miR-145-5p was examined by treating the TC1889 cell line with the HDAC inhibitor Valproic Acid (VPA).

Results

Starting from the identification of a 69-gene signature of miR-145-5p putative target mRNAs, whose expression was inversely correlated to that of miR-145-5p, we followed the expression of some of them in vitro upon overexpression of miR-145-5p; we observed that this resulted in the down-regulation of the target genes, impacting on TETs cancerous phenotype. We also found that VPA treatment of TC1889 cells led to miR-145-5p up-regulation and concomitant down-regulation of miR-145-5p target genes and exhibited antitumor effects, as indicated by the induction of cell cycle arrest and by the reduction of cell viability, colony forming ability and migration capability. The importance of miR-145-5p up-regulation mediated by VPA is evidenced by the fact that hampering miR-145-5p activity by a LNA inhibitor reduced the impact of VPA treatment on cell viability and colony forming ability of TET cells. Finally, we observed that VPA was also able to enhance the response of TET cells to cisplatin and erlotinib.

Conclusions

Altogether our results suggest that the epigenetic regulation of miR-145-5p expression, as well as the modulation of its functional targets, could be relevant players in tumor progression and treatment response in TETs.

http://ift.tt/2qUjg7w

Increased pathologic complete response are expected in HER2-positive and triple-negative locally advanced breast cancers

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CD30 expression in extranodal natural killer/T-cell lymphoma, nasal type among 622 cases of mature T-cell and natural killer-cell lymphoma at a single institution in South China

Mature T-cell and natural killer (NK)-cell lymphomas compose a heterogeneous group of non-Hodgkin lymphomas, and extranodal NK/T-cell lymphoma, nasal type (ENKTL) is an aggressive subtype with sporadic CD30 ex...

http://ift.tt/2q6vpU7

Prospective pilot study of adoptive immunotherapy with autologous αβT cells for five cases of advanced and/or recurrent esophageal squamous cell carcinoma

Abstract

Background

Although several clinical trials of vaccination and cellular immunotherapy for esophageal cancer have been reported, clinical trials of anti-CD3-activated autologous αβT cell therapy for patients with esophageal squamous cell carcinoma are limited.

Method

A total of five patients with recurrent esophageal squamous cell carcinoma were enrolled in this prospective pilot study. Peripheral blood mononuclear cells from the patients were cultured with immobilized anti-CD3 antibody and interleukin-2 for approximately 14 days, and 5 × 10⁹ lymphocytes were harvested. Expanded lymphocytes were intravenously infused every 2 weeks for six courses. All patients were followed up until death. The treatment response was assessed by the number of lymphocytes, CD4/CD8 ratio, serum tumor markers, and computed tomography scan.

Results

A total of 23 courses of treatment were completed. Three of the five patients (cases 2, 3, and 4) completed six courses of cell therapy according to the protocol. However, case 1 quit treatment after three courses and case 5 quit treatment after two courses because of tumor progression. There were no adverse effects related to cell therapy. Although cases 1 and 5 did not show any treatment benefits, cases 2, 3, and 4 showed some treatment benefits. Cases 2 and 4 showed long-term survived for more than 1 year.

Conclusion

These results might suggest the safety and benefits of anti-CD3-activated autologous αβT cell therapy for the part of the patients with esophageal squamous cell carcinoma.

http://ift.tt/2pkZUIO

Assessment of Neuronal Viability Using Fluorescein Diacetate-Propidium Iodide Double Staining in Cerebellar Granule Neuron Culture

This protocol describes how to accurately measure neuronal viability using Fluorescein diacetate (FDA) and Propidium Iodide (PI) double staining in cultured cerebellar granule neurons, a primary neuronal culture used as an in vitro model in neuroscience and neuropharmacology research.

http://ift.tt/2pl3DGw

Complete response to anti-PD-1 nivolumab in massive skin metastasis from melanoma: efficacy and tolerability in an elderly patient.

The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma. The 30-40% of treated patients experience an objective tumour regression, with a significantly prolonged survival and an improved quality of life. Here, we report a case of a 75-year-old Caucasian woman affected by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced multiple relapses after surgery and repeated electrochemotherapy treatments. A poor response was observed after systemic therapy with ipilimumab, whereas a marked reduction in the lesion size was obtained during the treatment with nivolumab, with an objectively complete response after 6 months. Therapy was well tolerated, without immune-related side effects. During treatment, LDH levels decreased up to the standard values. Our experience confirms the good efficacy and the safety of anti-PD-1 nivolumab for the treatment of relapsed or refractory massive skin lesions, also in elderly patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2q6S5Uo

Report of two cases of acute cardiac adverse events in patients with colorectal carcinoma receiving oral capecitabine.

Capecitabine is an oral fluoropyrimidine chemotherapeutic agent, which, after oral administration, is metabolized to its active cytotoxic compound: 5-fluorouracil (5-FU). Cardiotoxicity is a recognized side effect of 5-FU, a closely related fluorinated pyrimidine antagonist. In the present report, we report on two patients who were admitted to our department after being treated with oral capecitabine for colorectal carcinoma and developed symptoms and signs of acute myocardial infarction that resolved after appropriate treatment and monitoring. The above two cases are discussed in the context of fluoropyrimidine, 5-FU, and capecitabine-induced cardiotoxicity; in addition, a detailed literature review of relevant cases and patient series reports is presented. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2qTWTz7

Imaging of the coracoglenoid ligament: a third ligament in the rotator interval of the shoulder

Abstract

Objective

The coracoglenoid ligament (CGL) forms part of the anterosuperior capsuloligamentous complex of the shoulder. Although it has received attention in the anatomical literature, it has not been investigated on imaging. The purpose of this study is to determine the percentage value and the interobserver agreement of identification and classification of the CGL on MR and MR arthrography (MRA) imaging.

Materials and methods

Retrospectively, 280 MR and 150 MRA examinations were evaluated for detection of the CGL by two musculoskeletal radiologists. On the MRA examinations the CGL configuration in relation to the superior glenohumeral (SGHL) and coracohumeral ligament (CHL) was classified into five types. Additionally, the percentage of intra-articular appearance of the CGL and its mean thickness value were calculated. Finally, a possible correlation between pathological condition and anatomical type was evaluated on MRA.

Results

The CGL could be identified in 56%/54% of MRI and in 76%/77% of MRA examinations. On MRA, the CGL was detected as distinct structures in 37%/35% of cases and it appeared fused (partially or totally) with the SGHL and/or CHL in 39%/42%; it was absent in 12%/12% and it appears undistinguishable in the remaining cases. The interobserver agreement was excellent (κ = 0.98 for detection on MRI; p = 0.927 for classification of anterosuperior anatomy on MRA; κ = 0.873 and 0.978 for identification on sagittal and axial external rotation MRA respectively; κ = 0.943 for classification as intra- or extra-articular on MRA).

Conclusions

The CGL can be reliably identified on MRI and MRA.

http://ift.tt/2qswyZl

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial

Abstract

Background

Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy.

Methods

Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded.

Results

The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = −0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE).

Conclusions

The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve.

Trial registration

This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry (http://ift.tt/1lXJedE, UMIN000004691).

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