Mechanisms of acute and chronic pain after surgery: update from findings in experimental animal models

Purpose of review Management of postoperative pain is still a major issue and relevant mechanisms need to be investigated. In preclinical research, substantial progress has been made, for example, by establishing specific rodent models of postoperative pain. By reviewing most recent preclinical studies in animals related to postoperative, incisional pain, we outline the currently available surgical-related pain models, discuss assessment methods for pain-relevant behavior and their shortcomings to reflect the clinical situation, delineate some novel clinical-relevant mechanisms for postoperative pain, and point toward future needs. Recent findings Since the development of the first rodent model of postoperative, incisional pain almost 20 years ago, numerous variations and some procedure-specific models have been emerged including some conceivably relevant for investigating prolonged, chronic pain after surgery. Many mechanisms have been investigated by using these models; most recent studies focussed on endogenous descending inhibition and opioid-induced hyperalgesia. However, surgical models beyond the classical incision model have so far been used only in exceptional cases, and clinical relevant behavioral pain assays are still rarely utilized. Summary Pathophysiological mechanisms of pain after surgery are increasingly discovered, but utilization of pain behavior assays are only sparsely able to reflect clinical-relevant aspects of acute and chronic postoperative pain in patients. Correspondence to Esther Pogatzki-Zahn, Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, A1, 48149 Münster, Germany. Tel: +49 251 8347261; fax: +49 251 88704; e-mail: pogatzki@anit.uni-muenster.de Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LdcxRi

Mise en ligne du N° 4, volume 63 (juillet 2018) de la revue 'Annales de chirurgie plastique esthétique'

Vol 63 - N°4 - juillet 2018 P. 277-362 © 2018, Elsevier Masson SAS

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Prostate cancer imaging: when the game gets tough, the hard one gets done!

https://ift.tt/2JDz3Nv

Glycine Protects the Liver from Reperfusion Injury following Pneumoperitoneum

Background: Experimental pneumoperitoneum induces ischemia/reperfusion injury (IRI) in the liver, most likely via Kupffer cell (KC)-dependent mechanisms. Glycine has been shown to ameliorate IRI in various animal models. Thus, this study was performed to assess the effects of glycine on the liver after pneumoperitoneum. Materials and Methods: Sprague-Dawley rats (220–250 g in weight) underwent CO₂ pneumoperitoneum (12 mm Hg) for 90 min. Some rats received i.v. glycine (1.5 mL, 300 mM) 10 min before pneumoperitoneum. Controls were given the same volume of Ringer's solution. Transaminases, hepatic microcirculation, and phagocytosis of latex beads indexing both liver injury and KC activation were examined following pneumoperitoneum. Analysis of variance (ANOVA), plus a subsequent t test or χ² test (or Fisher's exact test) were carried out as appropriate. Results are presented as mean ± SEM. Results: Glycine significantly decreased lactate dehydrogenase at 1 h and both aspartate aminotransferase and alanine aminotransferase at 2 h after pneumoperitoneum from 477 ± 43, 154 ± 17, and 60 ± 6 U/L in controls to 348 ± 25, 101 ± 11, and 34 ± 3 U/L, respectively (p #x3c; 0.05). In parallel, glycine significantly decreased both the rate of permanent adherence of leukocytes to the endothelium by up to 35% and the rate of phagocytosis by #x3e; 50% compared to the control group. Conclusion: Glycine decreased IRI after pneumoperitoneum, most likely via KC-dependent mechanisms.
Eur Surg Res 2018;59:91–99

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LUMBAR INTERBODY FUSION: A NEW APPROACH UTILIZING KAMBIN'S TRIANGLE

Publication date: Available online 19 July 2018

Source: Seminars in Spine Surgery

Author(s): William Tally

ABSTRACT

With advances of surgical techniques, a major focus is being directed to less traumatic delivery system for fusion hardware. The goal is to minimize the drawbacks of traditional open lumbar fusion by adopting less invasive approaches. However minimally invasive transforaminal, lateral transpsoas, and anterior lumbar fusion techniques are notorious for surgical complications that can be devastating and catastrophic.

In an attempt to find a safer access to the disc space, we have been utilizing the Kambin's triangle, which can be approached using muscle-preserving plane. This manuscript will further describe this technique, its advantages and limitations.

https://ift.tt/2JI36nc

Lumbar Interbody Fusion for Adjacent Segment Disease: An illustrative case of Anterolateral Retroperitoneal Psoas-Sparing (Anterior To Psoas; ATP) Approach

Publication date: Available online 19 July 2018

Source: Seminars in Spine Surgery

Author(s): Chadi Tannoury

ABSTRACT

Following prior lumbar arthrodesis, surgery for adjacent segment disease (ASD) is not uncommon. Many challenges exist due to scarring, laminectomy defects, retained hardware, and increased risks of various surgical morbidities. These include iatrogenic durotomy, neurologic injuries, wound infections, and ASD recurrence. The minimally invasive retroperitoneal anterolateral psoas-sparing (ATP) approach, unlike the transpsoas and transforaminal techniques, allows access to the T12-S1 segments, enabling unobstructed corridor to discectomy, endplate preparation, anterior column release, direct lumbar decompression, intervertebral height restoration, and sagittal lordosis correction. Despite the promising attributes of the ATP in managing ASD, high quality data is still lacking.

https://ift.tt/2L8VOOO

CRISPR-Cas13 Precision Transcriptome Engineering in Cancer.

Related Articles

CRISPR-Cas13 Precision Transcriptome Engineering in Cancer.

Cancer Res. 2018 Jul 18;:

Authors: Granados-Riveron JT, Aquino-Jarquin G

Abstract
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated genes (Cas) system has been rapidly harnessed to perform various genomic engineering tasks. Recently, it has been demonstrated that a novel RNA-targeting CRISPR effector protein, called Cas13, binds and cleaves RNA rather than DNA substrates analogously to the eukaryotic RNA interference system. The known Cas13a-Cas13d effectors are able to efficiently cleave complementary target single-stranded RNAs, which represent a potentially safer alternative to deoxyribonuclease Cas9, because it induces loss-of-function phenotypes without genomic loss of the targeted gene. Furthermore, through the improvement in Cas13 effector functionalities, a system called REPAIR has been developed to edit full-length transcripts containing pathogenic mutations, thus providing a promising opportunity for precise base editing. Moreover, advanced engineering of this CRISPR effector also permits nucleic acid detection, allowing the identification of mutations in cell-free tumor DNA through a platform termed Specific High Sensitivity Enzymatic Reporter Unlocking. All of these properties give us a glimpse about the potential of the CRISPR toolkit for precise transcriptome engineering, possibly leading to an expansion of CRISPR technologies for cancer therapeutics and diagnostics. Here, we examine previously unaddressed aspects of the CRISPR-based RNA-targeting approach as a feasible strategy for globally interrogating gene function in cancer in a programmable manner. Cancer Res; 78(15); 1-7. ©2018 AACR.

PMID: 30021724 [PubMed - as supplied by publisher]

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Immature particles and capsid-free viral RNA produced by Yellow fever virus-infected cells stimulate plasmacytoid dendritic cells to secrete interferons.

Related Articles

Immature particles and capsid-free viral RNA produced by Yellow fever virus-infected cells stimulate plasmacytoid dendritic cells to secrete interferons.

Sci Rep. 2018 Jul 18;8(1):10889

Authors: Sinigaglia L, Gracias S, Décembre E, Fritz M, Bruni D, Smith N, Herbeuval JP, Martin A, Dreux M, Tangy F, Jouvenet N

Abstract
Plasmacytoid dendritic cells (pDCs) are specialized in the production of interferons (IFNs) in response to viral infections. The Flaviviridae family comprises enveloped RNA viruses such as Hepatitis C virus (HCV) and Dengue virus (DENV). Cell-free flaviviridae virions poorly stimulate pDCs to produce IFN. By contrast, cells infected with HCV and DENV potently stimulate pDCs via short-range delivery of viral RNAs, which are either packaged within immature virions or secreted exosomes. We report that cells infected with Yellow fever virus (YFV), the prototypical flavivirus, stimulated pDCs to produce IFNs in a TLR7- and cell contact- dependent manner. Such stimulation was unaffected by the presence of YFV neutralizing antibodies. As reported for DENV, cells producing immature YFV particles were more potent at stimulating pDCs than cells releasing mature virions. Additionally, cells replicating a release-deficient YFV mutant or a YFV subgenomic RNA lacking structural protein-coding sequences participated in pDC stimulation. Thus, viral RNAs produced by YFV-infected cells reach pDCs via at least two mechanisms: within immature particles and as capsid-free RNAs. Our work highlights the ability of pDCs to respond to a variety of viral RNA-laden carriers generated from infected cells.

PMID: 30022130 [PubMed - in process]

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Improved Induction of Anti-Melanoma T Cells by Adenovirus-5/3 Fiber Modification to Target Human DCs.

Related Articles

Improved Induction of Anti-Melanoma T Cells by Adenovirus-5/3 Fiber Modification to Target Human DCs.

Vaccines (Basel). 2018 Jul 18;6(3):

Authors: Chondronasiou D, Eisden TTHD, Stam AGM, Matthews QL, Icyuz M, Hooijberg E, Dmitriev I, Curiel DT, de Gruijl TD, van de Ven R

Abstract
To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs in situ, represents an attractive vaccination strategy. In this study we made use of a full-length MART-1 expressing C/B-chimeric adenoviral vector, consisting of the Ad5 capsid and the Ad3 knob (Ad5/3), which we previously showed to selectively transduce DCs in human skin and lymph nodes. Our data demonstrate that chimeric Ad5/3 vectors encoding TAA, and able to target human DCs in situ, can be used to efficiently induce expansion of functional tumor-specific CD8⁺ effector T cells, either from a naïve T cell pool or from previously primed T cells residing in the melanoma-draining sentinel lymph nodes (SLN). These data support the use of Ad3-knob containing viruses as vaccine vehicles for in vivo delivery. "Off-the-shelf" DC-targeted Ad vaccines encoding TAA could clearly benefit future immunotherapeutic approaches.

PMID: 30022005 [PubMed]

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Absence of host NF-κB p50 induces murine glioblastoma tumor regression, increases survival, and decreases T-cell induction of tumor-associated macrophage M2 polarization

Abstract

High-grade gliomas harbor abundant myeloid cells that suppress anti-tumor immunity and support tumor growth. Targeting transcription factors, such as NF-κB p50, that mediate suppressive myeloid M2 polarization may prove therapeutic. GL261-Luc glioblastoma cells were inoculated into wild-type and p50^−/− mice, followed by analysis of tumor growth, survival, tumor myeloid cells, and T cells. The absence of host p50 slows tumor growth and enables regression in 30% of recipients, leading to prolonged survival. Tumors developing in p50^−/− mice possess a greater concentration of tumor-infiltrating myeloid cells (TIMs) than those in wild-type mice. TIMs are predominantly F4/80^hi macrophages which, along with tumor-associated microglia, express increased pro-inflammatory M1 and reduced immune-suppressive M2 markers. In p50^−/− mice, total tumor CD4 T cells are threefold more abundant, whereas CD8 T-cell numbers are unchanged, and both produce increased IFNγ and Granzyme B. Naïve splenic p50^−/− CD8 T cells manifest increased activation, whereas naïve p50^−/− and WT CD4 T cells show similar Th1, Th2, and Th17 polarization. Antibody targeting CD4, but not CD8, fully obviates the p50^−/− survival advantage. Combined CD4 and CD8 T-cell depletion reverses myeloid M2 polarization in wild-type hosts, without affecting myeloid M1 polarization in p50^−/− hosts. Finally, gliomas grow similarly in p50(f/f) and p50(f/f);Lysozyme-Cre mice, the latter having reduced p50 specifically in myeloid cells and tumor microglia. Thus, high-grade glioma T cells play a key role in directing M2 polarization of tumor myeloid cells, and reducing NF-κB p50 in both tumor myeloid cells and T cells may contribute to glioma therapy.

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CRISPR-Cas9 therapies in experimental mouse models of cancer

Future Oncology, Ahead of Print.


https://ift.tt/2mySiOU

Healthcare delay in breast cancer patients: a case study in a low-density population region from Mexico

Future Oncology, Ahead of Print.


https://ift.tt/2uQbPhB

Risk factors of birth asphyxia among newborns in public hospitals of Central Zone, Tigray, Ethiopia 2018

The aim of study was to identify risk factors of birth asphyxia among newborns in public hospitals of Central Zone Tigray, Ethiopia 2018.

https://ift.tt/2uSKwTZ

Rethinking urinary antibiotic breakpoints: analysis of urinary antibiotic concentrations to treat multidrug resistant organisms

The present study analyzed whether renally eliminated antibiotics achieve sufficient urinary concentrations based on their pharmacokinetic/pharmacodynamic principles to effectively eradicate organisms deemed r...

https://ift.tt/2mwAeFp

Detection of human bocavirus-1 in both nasal and stool specimens from children under 5 years old with influenza-like illnesses or diarrhea in Gabon

Human bocavirus (HBoV) is a viral pathogen which causes respiratory tract diseases and acute gastroenteritis worldwide. This virus mainly affected children under 5 years old. There is little information on HBo...

https://ift.tt/2zYyeiL

Absence of host NF-κB p50 induces murine glioblastoma tumor regression, increases survival, and decreases T-cell induction of tumor-associated macrophage M2 polarization

Abstract

High-grade gliomas harbor abundant myeloid cells that suppress anti-tumor immunity and support tumor growth. Targeting transcription factors, such as NF-κB p50, that mediate suppressive myeloid M2 polarization may prove therapeutic. GL261-Luc glioblastoma cells were inoculated into wild-type and p50^−/− mice, followed by analysis of tumor growth, survival, tumor myeloid cells, and T cells. The absence of host p50 slows tumor growth and enables regression in 30% of recipients, leading to prolonged survival. Tumors developing in p50^−/− mice possess a greater concentration of tumor-infiltrating myeloid cells (TIMs) than those in wild-type mice. TIMs are predominantly F4/80^hi macrophages which, along with tumor-associated microglia, express increased pro-inflammatory M1 and reduced immune-suppressive M2 markers. In p50^−/− mice, total tumor CD4 T cells are threefold more abundant, whereas CD8 T-cell numbers are unchanged, and both produce increased IFNγ and Granzyme B. Naïve splenic p50^−/− CD8 T cells manifest increased activation, whereas naïve p50^−/− and WT CD4 T cells show similar Th1, Th2, and Th17 polarization. Antibody targeting CD4, but not CD8, fully obviates the p50^−/− survival advantage. Combined CD4 and CD8 T-cell depletion reverses myeloid M2 polarization in wild-type hosts, without affecting myeloid M1 polarization in p50^−/− hosts. Finally, gliomas grow similarly in p50(f/f) and p50(f/f);Lysozyme-Cre mice, the latter having reduced p50 specifically in myeloid cells and tumor microglia. Thus, high-grade glioma T cells play a key role in directing M2 polarization of tumor myeloid cells, and reducing NF-κB p50 in both tumor myeloid cells and T cells may contribute to glioma therapy.

https://ift.tt/2O7Vmyb

Severity-Stratified Discrete Choice Experiment Designs for Health State Evaluations

Abstract

Background

Discrete choice experiments (DCEs) are increasingly used for health state valuations. However, the values derived from initial DCE studies vary widely. We hypothesize that these findings indicate the presence of unknown sources of bias that must be recognized and minimized. Against this background, we studied whether values derived from a DCE are sensitive to how well the DCE design spans the severity range.

Methods

We constructed an experiment involving three variants of DCE tasks for health state valuation: standard DCE, DCE-death, and DCE-duration. For each type of DCE, an experimental design was generated under two different conditions, enabling a comparison of health state values derived from current best practice Bayesian efficient DCE designs with values derived from 'severity-stratified' designs that control for coverage of the severity range in health state selection. About 3000 respondents participated in the study and were randomly assigned to one of the six study arms.

Results

Imposing the severity-stratified restriction had a large effect on health states sampled for the DCE-duration approach. The unstratified efficient design returned a skewed distribution of selected health states, and this introduced bias. The choice probability of bad health states was underestimated, and time trade-offs to avoid bad states were overestimated, resulting in too low values. Imposing the same restriction had limited effect in the DCE-death approach and standard DCE.

Conclusion

Variation in DCE-derived values can be partially explained by differences in how well selected health states spanned the severity range. Imposing a 'severity stratification' on DCE-duration designs is a validity requirement.

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Pembrolizumab for Previously Treated Advanced or Metastatic Urothelial Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

Pembrolizumab is an intravenously administered monoclonal antibody licensed for locally advanced or metastatic urothelial carcinoma after platinum-containing chemotherapy. This summary presents the perspective of Warwick Evidence, the Evidence Review Group (ERG) appointed by the National Institute of Health and Care Excellence (NICE) for the single technology appraisal of pembrolizumab for this indication. Pembrolizumab is manufactured by Merck, Sharp and Dohme (MSD). The major source of clinical effectiveness was the KEYNOTE-045 trial, where 542 patients received either pembrolizumab or clinician's choice of docetaxel, paclitaxel or vinflunine as a second-line treatment. No indirect treatment comparison was performed. The clinical effectiveness was assessed using hazard ratios for overall survival (OS) and progression-free survival (PFS) of the intention-to-treat (ITT) population, together with the subpopulations positive for programmed cell death 1 ligand 1 (PD-L1) expression (combined positive score [CPS] ≥ 1%) and strongly positive for PD-L1 expression (CPS ≥ 10%). In the ITT population, OS improved with pembrolizumab (HR 0.73, 95% CI 0.59–0.91) while PFS outcomes showed no difference (HR 0.98, 95% CI 0.81–1.19). Pembrolizumab demonstrated a better safety profile than its combined comparators, with fewer patients experiencing adverse events (60.9 vs 90.2%). Similar results were observed in populations expressing PD-L1. MSD estimated the cost effectiveness of pembrolizumab using a de novo partitioned survival model. The model had three health states: pre-progression, post-progression and death, where OS and PFS estimates excluded patients who received vinflunine. The largest uncertainty was over the selection of the parametric models used to extrapolate OS and PFS and the time point for when to begin their extrapolation. The company preferences for extrapolation were not well supported and the ERG disagreed with their selection for OS. Utility values were also contentious, with the company preferring to use pooled time-to-death–based utilities pooled across treatment arms, whilst the ERG preferred pooled progression-based utilities. The company preferred to use data from patients receiving vinflunine when calculating the utility values, which the ERG disagreed with as this is not recommended treatment within the UK. The company assumed a lifetime treatment effect for their model; however, the lack of evidence made it difficult to confidently provide a realistic estimate of treatment effect duration. Various durations were explored (3, 5 and 10 years). The first appraisal committee meeting concluded that pembrolizumab was not cost effective, largely due to uncertainty in the OS and PFS extrapolations. The company's second submission included an additional 4 months follow-up to survival data. The company in this new submission maintained their original assumptions in their base-case analysis, changing only the choice of parametric curve for PFS. This change resulted in the OS and PFS curves intersecting at 6 years in the pembrolizumab arm, at which point PFS identically followed OS. This resulted in no patients in the post-progression health state beyond this time point, and therefore, the majority of pembrolizumab's benefit came from pre-progression survival. Given the unclear PFS benefit, the ERG found this implausible and maintained their original base-case model assumptions. Considerable uncertainty remained over the specification of the extrapolations and the duration of treatment effect. Based on a new-value proposition submitted by the company, the appraisal committee concluded that pembrolizumab had plausible potential to be cost effective. Pembrolizumab was referred for funding through the Cancer Drugs Fund, so that further data could be collected with the aim of diminishing the outstanding uncertainties pertaining to its clinical effectiveness.

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Pharmacogenetics and cognitive symptoms in schizophrenia patients treated with antipsychotics

Pharmacogenomics, Ahead of Print.


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Clinical outcomes of CYP2C19 genotype-guided antiplatelet therapy: existing evidence and future directions

Pharmacogenomics, Ahead of Print.


https://ift.tt/2zXkKUq

Neuroimaging in the Kleine-Levin Syndrome

Abstract

Purpose of Review

The purpose was to review the most recent literature on neuroimaging in the Kleine-Levin syndrome (KLS). We aimed to investigate if frontotemporal and thalamic dysfunction are key KLS signatures, and if recent research indicates other brain networks of interest that elucidate KLS symptomatology and aetiology.

Recent Findings

In a comprehensive literature search, we found 12 original articles published 2013–2018. Most studies report deviations related to cerebral perfusion, glucose metabolism, or blood-oxygen-level-dependent responses in frontotemporal areas and/or the thalamus. Studies also report dysfunction in the temporoparietal junction and the oculomotor network that also were related to clinical parameters. We discuss these findings based on recent research on thalamocortical networks and brain stem white matter tracts.

Summary

The hypothesis of frontotemporal and thalamic involvement in KLS was confirmed, and additional findings in the temporoparietal junction and the oculomotor system suggest a broader network involvement, which can be investigated by future high-resolution and multimodal imaging.

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Disrupting Histidine Catabolism Reduces Methotrexate Sensitivity [Research Watch]

A CRISPR/Cas9 screen shows the histidine catabolism enzyme FTCD regulates methotrexate sensitivity.

https://ift.tt/2Nzx6UB

Targeting RXR Signaling May Delay Relapse in Melanoma [Research Watch]

A neural crest stem cell (NCSC) transcriptional state driven by RXRG underlies relapse in melanoma.

https://ift.tt/2O7k9SX

Ado-Trastuzumab Emtansine Achieves Responses in ERBB2-Mutant Lung Cancer [Research Watch]

Ado-trastuzumab emtansine achieves responses in 8 of 18 patients (44%) with ERBB2-mutant lung cancer.

https://ift.tt/2NAa4Nx

IDH Mutations Suppress T Cell-Mediated Antitumor Immunity [Research Watch]

IDH1 mutation-derived R-2-HG blocks T-cell activation and proliferation in gliomas.

https://ift.tt/2O5W0Mx

NT5C2 Mutations Drive Thiopurine Resistance via Distinct Mechanisms [Research Watch]

In patients with ALL the most common NT5C2 mutation class disrupted its switch-off mechanism.

https://ift.tt/2Nz4gDX

Tandem Duplicate Genes in Maize Are Abundant and Date to Two Distinct Periods of Time

Tandem duplicate genes are proximally duplicated and as such occur in similar genomic neighborhoods. Using the maize B73 and PH207 de novo genome assemblies, we identified thousands of tandem gene duplicates that account for ~10% of the annotated genes. These tandem duplicates have a bimodal distribution of ages, which coincide with ancient allopolyploidization and more recent domestication. Tandem duplicates are smaller on average and have a higher probability of containing LTR elements than other genes, suggesting origins in nonhomologous recombination. Within relatively recent tandem duplicate genes, ~26% appear to be undergoing degeneration or divergence in function from the ancestral copy. Our results show that tandem duplicates are abundant in maize, arose in bursts throughout maize evolutionary history under multiple potential mechanisms, and may provide a substrate for novel phenotypic variation.

https://ift.tt/2zWYrhH

Greening Vacant Land Improves Neighborhood Mental Health

FRIDAY, July 20, 2018 -- Fixing up blighted physical environments, particularly in resource-limited urban settings, may improve the mental health of residents living nearby, according to a study published in the July issue of JAMA Network...

https://ift.tt/2zXqOMA

Unfavorable Prepregnancy Lipid Levels Linked to Low Parity

FRIDAY, July 20, 2018 -- The risk of having no or only one child is elevated for women with an unfavorable prepregnancy lipid profile, according to a study published in the June issue of BMJ Open. Aleksandra Pirnat, from the University of Bergen in...

https://ift.tt/2uEfWOx

C.S. Mott Poll Addresses Child Safety at Amusement Parks

FRIDAY, July 20, 2018 -- One in five parents say they have not made plans with their children about what to do if they became separated at an amusement park or carnival, according to the C.S. Mott Children's Hospital National Poll on Children's...

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Increased Coverage in States With Medicaid Expansion

FRIDAY, July 20, 2018 -- Coverage rates and access to care are significantly higher in states with Medicaid expansion, compared with non-expansion states, according to a study published in the July issue of Health Affairs. Benjamin D. Sommers, M.D.,...

https://ift.tt/2uCHcwW

Bayer Stops U.S. Sale of Essure Birth Control Implant

FRIDAY, July 20, 2018 -- Amid lawsuits and plummeting sales for its Essure birth control device, Bayer announced Friday that it would cease U.S. sales of the product by the end of 2018. The announcement comes after years of claims by thousands of...

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CME Accreditation Page

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Forthcoming Issues

Infectious Disease Emergencies

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The Heme-Onc Tidal Wave: Are You Prepared?

The cancer population in the United States continues to grow and is projected to do so for the foreseeable future. Patients with hematologic and oncologic emergencies are presenting in increasing numbers to all types of emergency departments…academic, community, and rural. These patients bring a unique set of illnesses and complications, both of their primary disease and of its treatment. A functional understanding of some of the more frequently encountered emergencies in this unique population is mandatory for all practicing emergency providers.

https://ift.tt/2A3DGky

Rapid Fire

Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency, characterized by a constellation of hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia. The spectrum ranges from patients who are asymptomatic to those who go into cardiac arrest and die. Prompt recognition and initiation of treatment by emergency physicians are key, especially in the early stages of the syndrome. This case-based review presents an overview of the key points in pathophysiology, diagnosis, and management of TLS that are key to emergency physicians.

https://ift.tt/2uE3xdA

Anticoagulation Reversal

Today a variety of anticoagulants and antiplatelet agents are available on the market. Given the propensity for bleeding among patients prescribed these medications, the emergency medicine physician must be equipped with a working knowledge of hemostasis, and anticoagulant and antiplatelet reversal. This article reviews strategies to address bleeding complications occurring secondary to warfarin, low-molecular-weight heparin, and direct oral anticoagulant therapy.

https://ift.tt/2zY8nYb

Rapid Fire

Emergency providers are likely to encounter sickle cell disease–related emergencies. The pathophysiology of emergent complaints are usually related to either an acute anemia or a vasoocclusive crisis. Differentiating between the two is the first step in the workup. Anemic crises must then be differentiated by the source. Vasoocclusive crises must be appropriately treated with aggressive pain management, gentle hydration, and other appropriate adjuncts. Early recognition and treatment are key in providing excellent emergency care to those with sickle cell disease.

https://ift.tt/2uFlgkF

The Cancer Emergency Department—The Ohio State University James Cancer Center Experience

In 2015, The James Cancer Hospital's Emergency Department (ED) opened at The Ohio State University Wexner Medical Center's ED. Careful planning was undertaken to assure that the needs of patients with cancer would be addressed. Strong relationships between experts in hematology, oncology, and emergency medicine were built to maximize the positive impact. Ongoing reevaluation of operational needs facilitates optimal patient flow, resource use, and opportunities to build and develop new resources. The results are evident in improved patient satisfaction in the cancer ED and a much smoother flow of patients into the system.

https://ift.tt/2LDKnL9

Hematologic and Oncologic Emergencies

EMERGENCY MEDICINE CLINICS OF NORTH AMERICA

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Contributors

AMAL MATTU, MD

https://ift.tt/2A6SG15

Hematologic and Oncologic Emergencies

In the past two decades of practicing emergency medicine, there are probably only two major conditions that seem to have markedly increased in my practice: the number of elderly patients we care for and the number of patients with cancer (in their current or past history) that we care for. The increase in elderly patients in our practice has been strongly addressed in recent years in educational conferences, textbooks and journals, and national guidelines. But cancer still seems to be a relatively ignored clinical condition in emergency medicine.

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Copyright

ELSEVIER

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Contents

Amal Mattu

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Ginkgolide B inhibits platelet and monocyte adhesion in TNFα-treated HUVECs under laminar shear stress

Endothelial cells are sensitive to changes in both blood components and mechanical stimuli. Endothelial cells may undergo phenotypic changes, such as changes in adhesion protein expression, under different she...

https://ift.tt/2O5ktll

Case 22-2018: A 64-Year-Old Man with Progressive Leg Weakness, Recurrent Falls, and Anemia

Presentation of Case. Dr. Molly E. Wolf (Medicine): A 64-year-old man was admitted to this hospital because of progressive leg weakness, recurrent falls, and anemia. The patient had been in his usual state of health until 8 months before this admission, when fatigue on exertion and subjective leg…

https://ift.tt/2mwo67a

Cryptococcus neoformans Meningoencephalitis

A 36-year-old man presented to the emergency department with a 2-week history of fever, headache, drowsiness, and photophobia. He was previously healthy and was sexually active with men. The physical examination was notable for a temperature of 38.3°C and neck stiffness. Computed tomography of the…

https://ift.tt/2LwTXzt

2018 Hooley Awards winners named

Three individuals were named 2018 Hooley Awards winners at the 10th annual ImageTrend Connect Conference on July 19

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In This Issue

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1544-1545, July 2018.


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Publication schedule for 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1541-1541, July 2018.


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Introducing in AJMG Part A: Case reports in diverse populations

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1547-1548, July 2018.


https://ift.tt/2LbDN2h

Autosomal‐dominant biventricular arrhythmogenic cardiomyopathy in a large family with a novel in‐frame DSP nonsense mutation

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1622-1626, July 2018.


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Cover Image, Volume 176A, Number 7, July 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page i-i, July 2018.


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A novel FBXO28 frameshift mutation in a child with developmental delay, dysmorphic features, and intractable epilepsy: A second gene that may contribute to the 1q41‐q42 deletion phenotype

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1549-1558, July 2018.


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Table of Contents, Volume 176A, Number 7, July 2018

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1537-1540, July 2018.


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Ocular albinism with infertility and late‐onset sensorineural hearing loss

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1587-1593, July 2018.


https://ift.tt/2JFBGOS

Diagnostic clarity of exome sequencing following negative comprehensive panel testing in the neonatal intensive care unit

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1688-1691, July 2018.


https://ift.tt/2LA1hKQ

Molecular Signature at Birth Associated With Genetic Burden for Autism

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1543-1544, July 2018.


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Further delineation of Aymé‐Gripp syndrome and use of automated facial analysis tool

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1648-1656, July 2018.


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Hyperactive SHP2 Mutants Impair Chondrocyte Differentiation During Endochondral Bone Growth in Noonan Syndrome

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1546-1546, July 2018.


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Novel phenotype of achondroplasia due to biallelic FGFR3 pathogenic variants

American Journal of Medical Genetics Part A, Volume 176, Issue 7, Page 1675-1679, July 2018.


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Case 22-2018: A 64-Year-Old Man with Progressive Leg Weakness, Recurrent Falls, and Anemia

Presentation of Case. Dr. Molly E. Wolf (Medicine): A 64-year-old man was admitted to this hospital because of progressive leg weakness, recurrent falls, and anemia. The patient had been in his usual state of health until 8 months before this admission, when fatigue on exertion and subjective leg…

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Cryptococcus neoformans Meningoencephalitis

A 36-year-old man presented to the emergency department with a 2-week history of fever, headache, drowsiness, and photophobia. He was previously healthy and was sexually active with men. The physical examination was notable for a temperature of 38.3°C and neck stiffness. Computed tomography of the…

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Psychotic Disorders

The term "psychosis," which is derived from the Greek word for abnormal condition of the mind, has been used in many different ways in clinical medicine. Before 1980, the term "psychotic" was applied generically to persons whose mental functioning was sufficiently impaired to interfere with their…

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The Inevitable Math behind Entitlement Reform

The projected growth in Medicare and Medicaid spending, which exceeds projected aggregate economic growth, is pushing policymakers to seriously consider further entitlement reform. At some point, Americans will probably be unwilling to pay higher taxes or increase borrowing to fund public health…

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Evaluation of Medicare’s Bundled Payments Initiative for Medical Conditions

Episode-based payment holds promise for improving the quality and efficiency of care. The Center for Medicare and Medicaid Innovation (CMMI) launched the Bundled Payments for Care Improvement (BPCI) initiative in 2013. BPCI is a voluntary program, and hospitals that choose to participate may select…

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Case 22-2018: A 64-Year-Old Man with Progressive Leg Weakness, Recurrent Falls, and Anemia

Presentation of Case. Dr. Molly E. Wolf (Medicine): A 64-year-old man was admitted to this hospital because of progressive leg weakness, recurrent falls, and anemia. The patient had been in his usual state of health until 8 months before this admission, when fatigue on exertion and subjective leg…

https://ift.tt/2mwo67a

Cryptococcus neoformans Meningoencephalitis

A 36-year-old man presented to the emergency department with a 2-week history of fever, headache, drowsiness, and photophobia. He was previously healthy and was sexually active with men. The physical examination was notable for a temperature of 38.3°C and neck stiffness. Computed tomography of the…

https://ift.tt/2LwTXzt

Severe Mitral Stenosis

A 47-year-old man presented to the emergency department with a 6-month history of worsening exertional dyspnea. He had recently emigrated from Honduras and had a history of cardiac surgery as a child, but the initial diagnosis and specific procedure that had been performed were not known. The…

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Twitter Tailwinds — Little Capsules of Gratitude

Esther Choo, an emergency medicine physician at Oregon Health Sciences University, was at a mall in Portland, Oregon, waiting for her son to finish at a birthday party, when she fired off a tweet that briefly transformed medical Twitter: "When I first met B, he'd been dead for 20 min. We got him…

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Patterns of care and outcomes in oesophageal cancer

The optimal treatment for oesophageal cancer is a matter of debate. The aim of this study was to describe patterns of care and survival in a well-defined population for squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus.

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SYSTEMATIC REVIEW: FEATURES, DIAGNOSIS, MANAGEMENT AND PROGNOSIS OF HEPATIC HEMATOMA, A RARE COMPLICATION OF ERCP

Hepatic Hematoma (HH) is a rare but severe adverse event following endoscopic retrograde cholangiopancreatography (ERCP).

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Tipping Clonal Hematopoiesis into Transformation

Acute leukemias of various types are among the most serious blood disorders: leukemia causes severe illness, and the mortality rate is high. A better understanding of the causes of the various forms of leukemia could lead to earlier diagnosis and more effective treatment. The gene ASXL1 is often…

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A Phase 3 Trial of l-Glutamine in Sickle Cell Disease

Oxidative stress contributes to the complex pathophysiology of sickle cell disease. Nicotinamide adenine dinucleotide (NAD+) is a ubiquitous oxidation–reduction (redox) cofactor in red cells. NAD+ and its reduced form, NADH, play major roles in maintaining redox balance. Sickle red cells have a…

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l-Glutamine and the Dawn of Combination Therapy for Sickle Cell Disease

In 2017, the U.S. Food and Drug Administration approved l-glutamine (USAN, glutamine) for the prevention of acute vaso-occlusive pain events in persons with sickle cell disease who are older than 5 years of age — only the first drug to be approved for this indication in the 20 years since the…

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Burkitt lymphoma of the stomach in an immunocompetent patient

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Atrophy or cancer? That is the question

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Radiation Gastritis After Yttrium-90 Radioembolization

https://ift.tt/2NxJkgr

Disappearance of a tumor that completely covered the appendiceal orifice by endoloop-assisted endoscopic strangulation

https://ift.tt/2O7lOYD

Esophageal tuberculosis: a cause of dysphagia we should be aware of

https://ift.tt/2NxJi8j

Long-term recurrent bleeding risk after endoscopic therapy for definitive colonic diverticular bleeding: band ligation versus clipping

Very few prospective studies with over 100 samples have evaluated the long-term outcomes of endoscopic therapy for colonic diverticular bleeding (CDB). This study sought to elucidate the recurrent bleeding risk of endoscopic band ligation versus clipping for definitive CDB based on stigmata of recent hemorrhage (SRH).

https://ift.tt/2O2P96R

Underuse of Surgery Accounts for Racial Disparities in Esophageal Cancer Survival Times: A Matched Cohort Study

There are racial disparities in survival times of patients with esophageal cancer. We examined the sequential effects of characteristics and diagnosis and treatment-related factors on the disparity in survival times of black vs white patients with esophageal cancer.

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Endoscopic Therapy for Upper GI Bleeding on Antithrombotics – A Safe Option or Do Questions Remain?

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Improving Outcomes in Patients with Inflammatory Bowel Disease through Integrated Multi-Disciplinary Care— the Future of IBD Care

https://ift.tt/2mvh82d

Association Between Intestinal Microbiota Collected at Hospital Admission and Outcomes of Patients with Cirrhosis

Inpatients with cirrhosis are prone to develop acute-on-chronic liver failure (ACLF). ACLF is associated with dysbiosis of the intestinal microbiota, which might serve as a prognostic factor. We investigated whether features of the intestinal microbiota associate organ failure, transfer to intensive care, and mortality within 30 days in patients admitted to the hospital with cirrhosis.

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Levetiracetam

1 Therapeutic Reviews

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Next generation sequencing technologies for a successful diagnosis in a cold case of Leigh syndrome

Leigh Syndrome (LS, OMIM 256000) is an early-onset, progressive neurodegenerative disorder characterized by broad clinical and genetic heterogeneity; it is the most frequent disorder of mitochondrial energy pr...

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Antibiotic resistance in Swiss nursing homes: analysis of National Surveillance Data over an 11-year period between 2007 and 2017

We evaluated data from isolates of nursing home (NH) patients sent to the Swiss centre for antibiotic resistance (ANRESIS). We focussed on carbapenem-resistance (CR) among Gram-negative pathogens, extended-spe...

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Extended-spectrum β-lactamase prevalence and virulence factor characterization of enterotoxigenic Escherichia coli responsible for acute diarrhea in Nepal from 2001 to 2016

Multidrug-resistant (MDR) Gram-negative bacterial species are an increasingly dangerous public health threat, and are now endemic in many areas of South Asia. However, there are a lack of comprehensive data fr...

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Host cell-surface proteins as substrates of gingipains, the main proteases of Porphyromonas gingivalis

Journal Name: Biological Chemistry
Issue: Ahead of print


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Prognostic and predictive values of immune infiltrate in patients with head and neck squamous cell carcinoma

This study sought to determine whether the in situ tumor-infiltrating immune lymphocytes, as a novel companion to the Immunoscore analysis, could be a promising, valuable prognostic and predictive marker in patients with head and neck squamous cell carcinoma (HNSCC). Total (CD3+) and cytotoxic (CD8+) T lymphocytes were assessed using immunohistochemistry in tumor nests and stroma obtained from patient surgical specimens. The "Immunoscore" methodology has been defined to quantify the amount of in situ immune infiltrate (from I0 to I4).

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The role of acid sphingomyelinase and modulation of sphingolipid metabolism in bacterial infection

Journal Name: Biological Chemistry
Issue: Ahead of print


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BNIP3 contributes to the glutamine-driven aggressive behavior of melanoma cells

Journal Name: Biological Chemistry
Issue: Ahead of print


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Albuminuria and Allograft Failure, Cardiovascular Disease Events, and All-Cause Death in Stable Kidney Transplant Recipients: A Cohort Analysis of the FAVORIT Trial

Cardiovascular disease (CVD) is common and overall graft survival is suboptimal among kidney transplant recipients. Although albuminuria is a known risk factor for adverse outcomes among persons with native chronic kidney disease, the relationship of albuminuria with cardiovascular and kidney outcomes in transplant recipients is uncertain.

https://ift.tt/2JGDCqt

Hospice Among Hemodialysis Patients: Too Little, Too Late to Impact Care Delivery or Costs?

Patients with end-stage renal disease (ESRD) have high symptom burden1,2 and high risk for mortality.3 The 5-year survival rate for patients starting hemodialysis therapy in 2010 was 42%, lower than survival with many forms of cancer.4 Despite these realities, patients with ESRD receive more aggressive treatment at the end of life than patients with other life-limiting conditions. In a recent retrospective study of 57,753 decedents in the Veterans Affairs system, 32.3% of patients with ESRD died in an intensive care unit (ICU), compared to 13.4% of patients with cancer and 8.9% of patients with dementia.

https://ift.tt/2LnBb0G

Hypoglycemia-Related Hospitalizations and Mortality Among Patients With Diabetes Transitioning to Dialysis

Diabetic patients with declining kidney function are at heightened risk for hypoglycemia. We sought to determine whether hypoglycemia-related hospitalizations in the interval before dialysis therapy initiation are associated with post–end-stage renal disease (ESRD) mortality among incident patients with ESRD with diabetes.

https://ift.tt/2uQ1hPK

Prevalence and type-specific distribution of human papillomavirus infection among women in mid-western rural, Nepal- A population-based study

Cervical cancer is the most common cancer among women in Nepal. The prevalence of human papillomavirus (HPV) 16 and or HPV 18 among women with cervical pre-cancer and cancer is higher than the incidence of HPV...

https://ift.tt/2uRVgBY

Your dedication, our appreciation

New AT&T First Responder Appreciation offer gives local Law Enforcement, Fire, EMS exclusive discounts on AT&T Unlimited &More wireless plans, TV and Internet. Discounts available to eligible first responders include: 25% off the monthly plan charge on AT&T Unlimited &More wireless plans $15 off DIRECTV $15 off AT&T Internet Certain restrictions apply. Learn more about...

https://ift.tt/2LwHZtb

Visual Function Deficits Up in Developmental Dyslexia

FRIDAY, July 20, 2018 -- School-aged children with developmental dyslexia (DD) more frequently have visual function deficits than typically developing (TD) children, according to a study published online July 19 in JAMA Ophthalmology. Aparna...

https://ift.tt/2myXNgM

Lyme-Bearing Ticks More Widespread in U.S. Than Thought

FRIDAY, July 20, 2018 -- Ticks capable of transmitting Lyme disease and other tick-borne illnesses have been identified in dozens of places across the United States where the pests had never previously been recorded, according to a study published...

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Epinephrine Ups Survival in Out-of-Hospital Cardiac Arrest

FRIDAY, July 20, 2018 -- Epinephrine use results in improved 30-day survival versus placebo in patients with out-of-hospital cardiac arrest, according to a study published online July 18 in the New England Journal of Medicine. Gavin D. Perkins,...

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Complementary Medicine Use Ups Refusal of Usual Cancer Therapy

FRIDAY, July 20, 2018 -- Patients with cancer who receive complementary medicine (CM) are more likely to refuse conventional cancer treatment (CCT), according to a study published online July 19 in JAMA Oncology. Skyler B. Johnson, M.D., from the...

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FDA Proposes New Rule on Food Labeling in Vending Machines

FRIDAY, July 20, 2018 -- A new rule proposed by the U.S. Food and Drug Administration suggests that the type size on packaged foods sold in vending machines be at least 1.5 times the size of the net weight declaration on the front of the...

https://ift.tt/2zXNlcf

Patient Social Support Influential Factor for Transplant Providers

FRIDAY, July 20, 2018 -- For transplant providers, the second most influential factor determining a patient's suitability for transplantation is social support, according to a report published online June 28 in the Journal of Medical Ethics. Keren...

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Abstinence Rates for Substance Use Increasing Among Teens

FRIDAY, July 20, 2018 -- There have been substantial increases in complete abstinence from substance use reported by high school students over the past 40 years, according to a study published online July 19 in Pediatrics. Sharon Levy, M.D., M.P.H.,...

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Empagliflozin Doesn't Up Risk of Bone Fractures

FRIDAY, July 20, 2018 -- Empagliflozin does not increase the risk of bone fracture in patients with type 2 diabetes, according to a study published online June 15 in Diabetes Care. Sven Kohler, M.D., from Boehringer Ingelheim International in...

https://ift.tt/2zWv9iX

Valsartan-Containing Products: Update Health Professional and Consumer on Recent Recalled Products

[Posted 07/19/2018] AUDIENCE: Consumer, Health Professional, Pharmacy ISSUE: The investigation into valsartan-containing products is ongoing and the following list may change. We will update this statement as we have more information. There are...

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Tackling the quandary of the late-night call to increase retention

Our co-hosts discuss a recent article on the topic of late-night fatigue in EMS and how addressing those issues can lead to increased retention rates in the industry

https://ift.tt/2uRGQ53

Sudden hearing loss as an early detector of multiple sclerosis: a systematic review

OBJECTIVE: To evaluate whether Sudden Sensorineural Hearing Loss (S-SNHL) may be an early symptom of Multiple Sclerosis (MS).

MATERIALS AND METHODS: A systematic review was conducted using the following keywords: "Multiple sclerosis, hearing loss, sudden hearing loss, vertigo, tinnitus, magnetic resonance imaging, otoacoustic emission, auditory brainstem responses, white matter lesions, sensorineural hearing loss, symptoms of MS and otolaryngology, nerve disease and MS". Only the articles that included results of at least one auditory test and MRI were considered. We evaluated the prevalence of SNHL in patients with MS, the presence of different forms of SNHL (S-SNHL and Progressive SNHL (P-SNHL)) and their correlation with the stage of MS, the results of electrophysiological tests, and the location (if any) of MS lesions as detected by white matter hyperintensities in the MRI.

RESULTS: We reviewed a total of 47 articles, which included 29 case reports, 6 prospective studies, 6 cohort studies, 4 case-control studies, and 2 retrospective studies. 25% of patients suffered from SNHL. S-SNHL typically occurred in the early stage of the disease (92% of patients) and was the only presenting symptom in 43% of female subjects. Instead, P-SNHL occurred in the late stage of MS (88% of patients). Auditory Brainstem Responses (ABR) were abnormal in all MS patients with S-SNHL. When S-SNHL appeared during the early stage of the disease, MS lesions were found in the brain in 60% of patients and in the Internal Auditory Canal in 40% of patients. ABR remained abnormal after recovery.

CONCLUSIONS: S-SNHL can be an early manifestation of MS and should always be considered in the differential diagnosis of this condition, especially in women. The pathophysiology can be explained by the involvement of microglia attacking the central and/or peripheral auditory pathways as indicated by WMHs.

L'articolo Sudden hearing loss as an early detector of multiple sclerosis: a systematic review sembra essere il primo su European Review.

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Perioperative enteral supplementation with glutamine, fiber, and oligosaccharide reduces early postoperative surgical stress following esophagectomy for esophageal cancer

Abstract

Background

We clarified the effects of perioperative enteral supplementation with glutamine, fiber, and oligosaccharide (GFO) after an esophagectomy on preventing surgical stress.

Methods

Of 326 patients with esophageal cancer, 189 received GFO administration (GFO group) and 137 did not (control group). The propensity score matching method was used to identify 89 well-balanced pairs of patients to compare postoperative laboratory parameters and clinical and postoperative outcomes.

Results

The duration of the systemic inflammatory response syndrome (SIRS) was significantly shorter in the GFO group compared to the control group (p = 0.002). Moreover, the lymphocyte/neutrophil ratio (L/N ratio) had significantly recovered in the GFO group on postoperative day-3, and the CRP value was significantly lower in the GFO group than that in the control group on postoperative day-2.

Conclusions

Perioperative use of enteral supplementation with glutamine, fiber, and oligosaccharide likely contributes to a reduction in early surgical stress after an esophagectomy. These beneficial effects can bring about early recovery from postoperative immunosuppressive conditions after radical esophagectomy.

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Evaluation of volumetric wear of abutments on the retention loss of ball attachment systems in implant‐retained overdentures: An in vitro study

Clinical Implant Dentistry and Related Research, EarlyView.


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Mouse Study Links Immune Cells to Diarrhea Caused by Chemotherapy

A study in mice sheds light onto how some chemotherapies cause diarrhea. The findings could be the basis for developing new treatments for patients with cancer who develop gastrointestinal side effects from chemotherapy.

https://ift.tt/2zXzgeT

EUS-guided treatment of WON using lumen-apposing metal stents: protocol standardisation based on the occurrence of natural healing processes

We read with great interest the paper by Bang et al,1 which reported the results of a randomised controlled trial comparing endoscopic ultrasound (EUS)-guided placement of lumen-apposing metal stents (LAMS) (Hot Axios) versus plastic stents (PS) for the treatment of patients with walled-off pancreatic necrosis (WON). During the first phase of the study, a very high number of adverse events (AEs) (32.2%) occurred in the LAMS arm, including two patients with a buried stent, three with bleeding pseudoaneurysms that required coil embolisation and other three with stent-induced biliary stricture. All these AEs occurred within 6 weeks from stent placement, which was the time established to assess treatment response by an abdominal CT. Due to this high rate of AEs, the protocol was changed and follow-up CT anticipated at 3 weeks, resulting in a decrease of AEs to 6.5% in the subsequent patients treated with LAMS.

A high risk of bleeding due to...

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New smartwatch engages user and notifies first responders

The watch also has built-in GPS that alerts responders or a designated contact to the patient's exact location

https://ift.tt/2uCADKU

Valsartan-Containing Products: Update Health Professional and Consumer on Recent Recalled Products

[Posted 07/19/2018] AUDIENCE: Consumer, Health Professional, Pharmacy ISSUE: The investigation into valsartan-containing products is ongoing and the following list may change. We will update this statement as we have more information. There are...

https://ift.tt/2NsRCpV

MiR-124a inhibits proliferation and invasion of rheumatoid arthritis synovial fibroblasts

OBJECTIVE: To investigate the impact of miR-124Aa on the proliferation, invasion and cytokine excretion of rheumatoid arthritis synovial fibroblasts (RASFs) in patients with rheumatoid arthritis (RA).

PATIENTS AND METHODS: RASFs were separated for in-vitro culture, and transfected using lipidosome that connected with chemically synthesized miR-124a mimic or miR-124a inhibitor. Then, MTT, transwell chamber, and flow-cytometry were used to detect the impact on the proliferation, invasion, and apoptosis of RASFs; RT-PCR and Western-blotting were employed to measure the effect of miR-124a on the expressions of matrixmetalloproteinase3/13 (MMP3/13) and interleukin1β (IL-1β) of RASFs.

RESULTS: miR-124a significantly suppresses the proliferation of RASFs, while inhibits the invasion of RASFs. The flow cytometry indicated that miR-124a showed no significant effect on the apoptosis of RASFs. Finally, miR-124a downregulates the expressions of MMP3/13 and IL-1β.

CONCLUSIONS: MiR-124a is of great significance for the onset of RA by inhibiting the proliferation and invasion of RASFs possibly through downregulating the expression of MMP3/13 and IL-1β.

L'articolo MiR-124a inhibits proliferation and invasion of rheumatoid arthritis synovial fibroblasts sembra essere il primo su European Review.

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Is fatigue a cause of work disability in systemic lupus erythematosus? Results from a systematic literature review

OBJECTIVE: Fatigue affects the almost totality of Systemic Lupus Erythematous (SLE) patients impairing physical function and leading to a strong reduction of health-related quality of life (HRQoL). Similarly, SLE patients have an increased rate of work loss and work limitations. The aim of our paper was to systematically assess the relationship between fatigue and work disability in SLE.

MATERIALS AND METHODS: We performed a systematic review using the terms "fatigue" and "employment", "work disability", "work impairment", "presenteeism" and "absenteeism."

RESULTS: 19 studies were identified. Fatigue was involved in the development of work loss. In employed patients, fatigue led to impairment of work productivity and presenteeism with a parallel increase of both direct and indirect health costs. Fatigue also affected parenting and household productivity.

CONCLUSIONS: An adequate control of fatigue could improve physical and work performance in SLE patients thus reducing rates of work loss.

L'articolo Is fatigue a cause of work disability in systemic lupus erythematosus? Results from a systematic literature review sembra essere il primo su European Review.

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Evaluating Mediterranean diet and risk of chronic disease in cohort studies: an umbrella review of meta-analyses

Abstract

Several meta-analyses have been published summarizing the associations of the Mediterranean diet (MedDiet) with chronic diseases. We evaluated the quality and credibility of evidence from these meta-analyses as well as characterized the different indices used to define MedDiet and re-calculated the associations with the different indices identified. We conducted an umbrella review of meta-analyses on cohort studies evaluating the association of the MedDiet with type 2 diabetes, cardiovascular disease, cancer and cognitive-related diseases. We used the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) checklist to evaluate the methodological quality of the meta-analyses, and the NutriGrade scoring system to evaluate the credibility of evidence. We also identified different indices used to define MedDiet; tests for subgroup differences were performed to compare the associations with the different indices when at least 2 studies were available for different definitions. Fourteen publications were identified and within them 27 meta-analyses which were based on 70 primary studies. Almost all meta-analyses reported inverse associations between MedDiet and risk of chronic disease, but the credibility of evidence was rated low to moderate. Moreover, substantial heterogeneity was observed on the use of the indices assessing adherence to the MedDiet, but two indices were the most used ones [Trichopoulou MedDiet (tMedDiet) and alternative MedDiet (aMedDiet)]. Overall, we observed little difference in risk associations comparing different MedDiet indices in the subgroup meta-analyses. Future prospective cohort studies are advised to use more homogenous definitions of the MedDiet to improve the comparability across meta-analyses.

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Moderate neonatal hypoglycemia and adverse neurological development at 2–6 years of age

Abstract

To determine whether moderate neonatal hypoglycemia in otherwise healthy infants is associated with adverse neurodevelopmental outcome in pre-school children. Population-based cohort study with prospectively collected register data from Sweden. All singletons born July 1st 2008 through December 31st 2012 (n = 101,060) in the region were included. Infants with congenital malformations, infants treated in neonatal intensive care unit, infants with inborn errors of metabolism and infants to mothers with diabetes were excluded. Infants were followed-up until 2014, at 2–6 years of age. Exposure was neonatal moderate hypoglycemia. Main outcomes were a compiled neurological or neurodevelopmental outcome; any developmental delay; motor developmental delay; and cognitive developmental delay. In adjusted regression analyses, the odds ratio (OR) of any neurological or neurodevelopmental outcome was 1.48 (95% confidence interval: 1.17–1.88) in hypoglycemic compared to normoglycemic infants. The adjusted risk of any developmental delay was more than doubled (OR 2.53 [1.71–3.73]), the adjusted risk of motor developmental delay was almost doubled (OR: 1.91 [1.06–3.44]) and the adjusted risk of cognitive developmental delay was almost tripled (OR 2.85 [1.70–4.76]). Infants with early neonatal hypoglycemia (< 6 h) had a double risk (OR 1.94 [1.30–2.89]) of any neurological or neurodevelopmental outcome and a tripled risk of cognitive developmental delay (OR 3.17 [1.35–7.43]), compared to normoglycemic infants. In the first population-based study on this topic, we show that moderate neonatal hypoglycemia is associated with increased risks of impaired neurodevelopment. Current treatment routines for uncomplicated hypoglycemia should be followed.

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Scoring the tumor-stroma ratio in colon cancer: procedure and recommendations

Abstract

The tumor-stroma ratio (TSR) has been reported as a strong, independent prognostic parameter in colon cancer as well as in other epithelial cancer types, and may be implemented to routine pathology diagnostics. The TSR is an easy technique, based on routine hematoxylin and eosin stained histological sections, estimating the amount of stroma present in the primary tumor. It links tumors with high stromal content to poor prognosis. The analysis time is less than 2 min with a low inter-observer variation. Scoring of the TSR has been validated in a number of independent international studies. In this manuscript, we provide a detailed technical description of estimating the TSR in colon cancer, including examples, pitfalls, and recommendations.

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Preliminary study of Bim on the early diagnosis and prognosis of the elderly uremia with gastrointestinal nutrition combined with dialysis

OBJECTIVE: Elderly uremia frequently refers to the end stage of various chronic kidney diseases that threats the patients' health seriously. Enteral nutrition can reduce complications, while the molecular mechanism is still unclear. Mitochondrial protein Bim plays an essential role in regulating inflammation, restraining oxidative stress, and maintaining the balance of the mitochondrial membrane potential and energy production. This study aims to investigate the effect of Bim on the early diagnosis and prognosis of the elderly uremia with gastrointestinal nutrition combined with dialysis.

PATIENTS AND METHODS: Elderly patients with uremia in our hospital were selected and divided into parenteral nutrition group, enteral nutrition group, and regular treatment group. Healthy volunteers were chosen as the control group. Blood oxygen free radicals were tested by flow cytometry. Blood immune function parameter C-reactive protein and IL-6 levels were determined by Western blot. Bim expression in blood was evaluated by RT-PCR and Western blot. Correlation analysis was performed between Bim level and the prognosis of elderly patients with uremia who received gastrointestinal nutrition therapy.

RESULTS: Blood oxygen free radical level was significantly higher in parenteral nutrition group and regular treatment group compared with enteral nutrition group (p< 0.05). C-reactive protein and IL-6 contents were significantly reduced in parenteral nutrition group and regular treatment group compared to those in enteral nutrition group (p< 0.05). The expression of Bim at both mRNA and protein levels was declined in elderly patients with uremia after enteral nutrition combined with dialysis therapy to the normal level. The level of Bim was positively correlated with the severity of elderly uremia.

CONCLUSIONS: Bim is positively correlated with the severity of elderly uremia, which can be set as a potential specific biomarker, along with reactive oxygen radicals, CRP, IL-6, for the prognosis of elderly uremia.

L'articolo Preliminary study of Bim on the early diagnosis and prognosis of the elderly uremia with gastrointestinal nutrition combined with dialysis sembra essere il primo su European Review.

https://ift.tt/2JFUzRT

Liraglutide improves myocardial fibrosis after myocardial infarction through inhibition of CTGF by activating cAMP in mice

OBJECTIVE: To study the role and mechanism of liraglutide in myocardial fibrosis after myocardial infarction (MI).

MATERIALS AND METHODS: A total of 72 C57/BL male mice were randomly divided into sham operation group (Sham group), myocardial infarction group (MI group), and liraglutide intervention group (Lira group). The left anterior descending coronary artery (LAD) of the mice in MI group and Lira group was ligated to establish the MI model. One week after the operation, the mice in Lira group were intraperitoneally injected with 100 μg/kg of liraglutide once a day for 4 weeks. The mice in Sham group and MI group were injected with the equal volume of normal saline. At the 5th week after the operation, the cardiac morphologic indexes and cardiac function indexes were measured by echocardiography. After an ultrasound, the heart specimens of the mice were immediately harvested by thoracotomy, and histomorphological hematoxylin-eosin (HE) staining, collagen fiber Masson staining, and immunohistochemical staining were performed. The infarction zone and the non-infarction zone were isolated from another heart specimen; the cyclic adenosine monophosphate (cAMP) and hydroxyproline content were determined; and the expression levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting.

RESULTS: Liraglutide improved the cardiac function of mice after myocardial infarction. Liraglutide improved the myocardial fibrosis in mice after myocardial infarction. Liraglutide increased cAMP in myocardial cells of mice after myocardial infarction. Liraglutide did not change the TGF-β1 expressions while reduced the CTGF expressions in infarct and non-infarct area of mice after myocardial infarction.

CONCLUSIONS: Liraglutide, through increasing the level of cAMP, could decrease the deposition of collagen fibers in myocardial tissues of mice after MI, reduce the degree of infiltration of collagen fibers in the infarction zone into the myocardium in the non-infarction zone and inhibit the adverse ventricular remodeling in the non-infarction zone, thus improving the cardiac function after MI.

L'articolo Liraglutide improves myocardial fibrosis after myocardial infarction through inhibition of CTGF by activating cAMP in mice sembra essere il primo su European Review.

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Gestational weight gain as an independent risk factor for adverse pregnancy outcomes in women with gestational diabetes

OBJECTIVE: Obesity and gestational diabetes mellitus (GDM) are rising worldwide. This study retrospectively evaluated the role of excessive gestational weight gain (eGWG) in women with GDM and different pre-pregnancy body mass indices (BMIs).

PATIENTS AND METHODS: Optimal glycaemic control was defined as achieving glucose target thresholds in more than 80% of measurements. 283 women with GDM were categorized as underweight, normal weight, overweight or obese based on WHO's classification scheme. eGWG was defined as >18.0 kilograms for women who were underweight, >15.8 kilograms for those who were normal weight, >11.3 kilograms for those who were overweight and >9.0 kilograms for those who were obese. For the analysis, women were divided into two groups: normal and excessive GWG. The main outcomes measured were incidences of large/small for gestational age (LGA/SGA), macrosomia, preterm delivery, hypertensive disorders and caesarean sections (CS).

RESULTS: Excessive GWG was associated with higher birth weight and percentile (p<0.001), and with a higher prevalence of LGA (p<0.001), macrosomia (p=0.002) and hypertensive disorders (p=0.036). No statistical differences were found for the week of delivery, or prevalence of CS and SGA. The multivariate analysis highlighted both pre-pregnant BMI and eGWG as independent risk factors for LGA and macrosomia. Women with a pre-pregnant BMI of at least 25 and eGWG have a 5.43-fold greater risk of developing LGA (p=0.005).

CONCLUSIONS: When combined with an inadequate pre-pregnant BMI, eGWG acts as a "synergic risk factor" for a poor outcome. When obesity or GDM occur, an optimal GWG can guarantee a better pregnancy outcome.

L'articolo Gestational weight gain as an independent risk factor for adverse pregnancy outcomes in women with gestational diabetes sembra essere il primo su European Review.

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Comment on: MiR-877-5p suppresses cell growth, migration and invasion by targeting cyclin dependent kinase 14 and predicts prognosis in hepatocellular carcinoma

L'articolo Comment on: MiR-877-5p suppresses cell growth, migration and invasion by targeting cyclin dependent kinase 14 and predicts prognosis in hepatocellular carcinoma sembra essere il primo su European Review.

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MiR-7 regulates the PI3K/AKT/VEGF pathway of retinal capillary endothelial cell and retinal pericytes in diabetic rat model through IRS-1 and inhibits cell proliferation

OBJECTIVE: To investigate the role of miR-7 in diabetic retinopathy and the underlying mechanism.

MATERIALS AND METHODS: The rat model of diabetic retinopathy (DR) was established. After that, the endothelial cell (EC) and retinal pericyte (RP) were isolated. QRT-PCR was used to detect the expression of miR-7 and insulin receptor substrate-1 (IRS-1) in ECs and RPs cells while the protein level of IRS1 was detected by Western blot. miR-7 mimic and miR-7 inhibitor were transfected to achieve miR-7 overexpression or knockdown. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay after miR-7 overexpression or knockdown. Besides, the expression levels of PI3K, AKT, and VEGF were detected by Western Blot. The luciferase reporter assay was performed to investigate whether miR-7 could be combined with IRS-1. Conversely, whether miR-7 could affect IRS-1 was also verified.

RESULTS: miR-7 expression was significantly decreased in ECs and RPs of the experimental group compared with the control group, while the mRNA and protein levels of IRS-1 were increased. The CCK-8 assay showed that overexpression of miR-7 decreased the cell activity in ECs and RPs. In contrast, knock-down of miR-7 could increase the cell viability. Besides, Western blot showed that after overexpression of miR-7, the expressions of PI3K, AKT, and VEGF in ECs and RPs cells were down-regulated. Meanwhile, miR-7 knockdown upregulated the protein levels of PI3K, AKT, and VEGF. The luciferase reporter assay suggested that the 3'UTR region of IRS-1 could be combined with miR-7, which may be the downstream target gene for miR-7. Moreover, knockdown of IRS-1 could reverse the effect of the miR-7 inhibitor on cell proliferation in the diabetic model.

CONCLUSIONS: MiR-7 was lowly expressed in ECs and RPs cells. Overexpression of miR-7 can down-regulate the expression levels of PI3K, AKT, and VEGF by down-regulating its downstream target gene IRS-1, and ultimately inhibit the proliferation of retinal cells.

L'articolo MiR-7 regulates the PI3K/AKT/VEGF pathway of retinal capillary endothelial cell and retinal pericytes in diabetic rat model through IRS-1 and inhibits cell proliferation sembra essere il primo su European Review.

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MiR-129 is involved in the occurrence of uterine fibroid through inhibiting TET1

OBJECTIVE: To detect the expressions of micro ribonucleic acid (miR)-129 and its target gene in uterine fibroid tissues and to investigate the role of miR-129 in the occurrence of uterine fibroid.

PATIENTS AND METHODS: The expressions of miR-129 and its target gene ten-eleven translocation 1 (TET1) were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Dual-luciferase reporter gene and Western blotting were used to verify the regulatory relation between miR-129 and target gene. The effects of miR-129 on the proliferation, apoptosis, cycle and extracellular matrix (ECM) of uterine fibroid cells were investigated via transfection with miR-129 mimics and TET1 small-interfering RNA (siRNA).

RESULTS: MiR-129 was lowly expressed in uterine fibroid. The expression of miR-129 was regulated by sex hormones. The highly expressed miR-129 promoted apoptosis and inhibited proliferation through reducing the low expression of TET1. At the same time, miR-129 affected the accumulation of ECM.

CONCLUSIONS: The expression of miR-129 in uterine fibroid is lower, and the proliferation capacity of tumor cells is enhanced, thus promoting the occurrence and development of uterine fibroid.

L'articolo MiR-129 is involved in the occurrence of uterine fibroid through inhibiting TET1 sembra essere il primo su European Review.

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MicroRNA-551b expression profile in low and high-grade cervical intraepithelial neoplasia

OBJECTIVE: To evaluate the expression of microRNA (miR)-551b in patients with low and high grade cervical intraepithelial neoplasia (CIN) and to find an association with high-risk Human Papillomavirus (HR-HPV) infection-related prognostic biomarkers.

PATIENTS AND METHODS: The expression level of miR-551b was determined in 50 paraffin-embedded cervical specimens (10 normal squamous epithelium, 18 condylomas, 8 CIN1, and 14 CIN2-3) using quantitative Real-time polymerase chain reaction (qRT-PCR). χ2-test compared miR-551b expression in different diagnosis groups. An Ordered Logistic Regression and a Probit correlation were made to correlate miR-551b expression levels with the cervical tissue histological findings. The immunohistochemical distribution of p16 and Ki-67 according to histopathological findings was also assessed.

RESULTS: The distribution of the miR-551b expression profile was significantly lower in CIN1-3 samples compared to other histological diagnosis groups (condyloma and negative). The expression levels were inversely correlated to the cervical pathological grade, from negative to CIN2-3. A 1% increase in miR-551b expression level produced an increase of 19% to the probability of a minor histological grade diagnosis in a range from negative to CIN2-3 and an increase of 13% to the probability of a negative histological grade diagnosis. Among the cases with miR-551b expression < 0.02 (considered as cut-off value) a significant statistical correlation was found between p16 and Ki-67 expression and the diagnosis of CIN2-3.

CONCLUSIONS: Our data showed a significant inverse correlation between miR-551b expression and the histological grading of the lesions, suggesting a tumor suppressive function in the different stages of cervical dysplasia.

L'articolo MicroRNA-551b expression profile in low and high-grade cervical intraepithelial neoplasia sembra essere il primo su European Review.

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Long non-coding RNA LINP1 promotes the malignant progression of prostate cancer by regulating p53

OBJECTIVE: We aim to investigate the expression of long non-coding RNA-LINP1 (lncRNA LINP1) in prostate cancer (PCa) and its potential mechanism.

PATIENTS AND METHODS: The expression of lncRNA LINP1 in 74 pairs of PCa and normal tissues were detected by quantitative Real-time polymerase chain reaction (qRT-PCR); the relationship between its expression and the pathological features and prognosis of PCa was also analyzed. The expression of lncRNA LINP1 in the PCa cell line was verified by qRT-PCR. Knockdown of LINP1 was constructed by transfection of small interfering RNA (siRNA) in two PCa cell lines (Lncap and PC-3). The biological function of LINP1 was evaluated by cell counting kit-8 (CCK-8) assay, colony formation assay, migration and invasion assay, respectively. Finally, the potential mechanism of LINP1 was explored by Western blot and qRT-PCR.

RESULTS: qRT-PCR results showed a higher expression of LINP1 in PCa than that of normal tissues. Compared with PCa patients with a lower expression of LINP1, those with higher expression had a higher tumor stage, lymphatic metastasis and distant metastasis rate, and lower overall survival rate. Proliferation, invasion and metastasis in cells transfected with si-LINP1 were remarkably decreased than those transfected with negative control (si-NC). Moreover, the expressions of the key proteins in the p53 signaling pathway, including p53, PTEN, Akt and CDK2 were remarkably decreased in cells after knockdown of LINP1. In addition, a negative correlation between LINP1 and p53 was confirmed by rescue experiments.

CONCLUSIONS: Up-regulated LINP1 in PCa was correlated with a higher PCa stage, lymphatic metastasis, distant metastasis, and worse prognosis. Furthermore, LINP1 could promote the proliferative, migratory and invasive abilities of PCa by regulating the p53-signaling pathway.

L'articolo Long non-coding RNA LINP1 promotes the malignant progression of prostate cancer by regulating p53 sembra essere il primo su European Review.

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CA916798 affects growth and metastasis of androgen-dependent prostate cancer cells

OBJECTIVE: Abnormal activation of androgen receptor (AR) signaling pathway is a critical pathogenic mechanism and therapeutic target for prostate cancer (PCa). The CA916798 is a tumor-associated gene and may be regulated by the androgen-AR pathway. This study aims to investigate the function of CA916798 in the growth and metastasis of androgen-dependent PCa cells.

MATERIALS AND METHODS: CA916798 expression in PCa cell lines was investigated. LNCap cells were divided into 4 groups: LNCap, LNCap+ Dihydrotestosterone (DHT), LNCap+DHT+siCA916798, and LNCap+DHT+siRA group. CA916798 expressions in LNCap cells treated with siCA917698 or siAR were examined. The viability, apoptosis, migration, and invasion of PCa cells were examined. Dual luciferase and ChIP assays were used to examine the interaction between the AR and CA916798.

RESULTS: Endogenous CA916798 mRNA levels in PC3 cells were significantly higher than those in LNCap cells (p < 0.05). However, CA916798 was androgen-sensitive in LNCap cells, but not in PC-3 cells. Dual luciferase and ChIP assays showed that AR could specifically bind to the promoter regions of the CA916798. Knockdown of CA916798 (LNCap+DHT+siCA916798) and AR (LNCap+DHT+siAR) resulted in decreased cell viability, migration, and invasion, while it induced apoptosis and G1 cell cycle arrest in LNCap cells.

CONCLUSIONS: DHT could initiate the transcription of CA916798, which further mediates the androgen-AR signaling pathway-dependent cell growth and metastasis of the prostate cancer cell line LNCap.

L'articolo CA916798 affects growth and metastasis of androgen-dependent prostate cancer cells sembra essere il primo su European Review.

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KEAP1/NRF2 signaling pathway mutations in cervical cancer

OBJECTIVE: The aim of the present study was to explore the potential involvement of mutations in the KEAP1/NRF2 signaling pathway in Chinese samples with cervical cancer.

PATIENTS AND METHODS: 236 Chinese patients with various types of cervical cancer were recruited, and the coding exons and the corresponding intron-exon boundaries of the KEAP1 and NRF2 genes were analyzed for the potential mutations in the KEAP1/NRF2 signaling pathway.

RESULTS: A novel KEAP1 missense somatic mutation (c.1408C>T, p.R470C) and 5 NRF2 missense somatic mutations (c.72G>C, p.W24C; c.85G>T, p.D29Y; c.101G>A, p.R34Q; c.230A>C, p.D77A and c.242G>A p.G81D) were identified in 187 patients with cervical squamous cell carcinoma, respectively; no mutations were detected in other subtypes. All these mutations were heterozygous and predicted to be pathogenic by PolyPhen-2, MutationTaster programs, and evolutionary conservation analysis. Among these mutations, the KEAP1 (p.R470C) and 3 NRF2 mutations (p.D29Y, p.D77A, and p.G81D) were detected in cervical cancer for the first time. Also, no mutations were identified in our 21 adenosquamous carcinomas or 25 adenocarcinomas.

CONCLUSIONS: We identified 6 potential diseases causing mutations in the KEAP1/NRF2 signaling pathway in 187 (3.2%) Chinese cases with cervical squamous cell carcinoma, implicating KEAP1/NRF2 signaling pathway might play an active role in the pathogenesis of this subtype of cervical cancer. Furthermore, among these detected mutations, the KEAP1 and 3 NRF2 mutations were reported in cervical cancer for the first time.

L'articolo KEAP1/NRF2 signaling pathway mutations in cervical cancer sembra essere il primo su European Review.

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LncRNA EBIC promoted proliferation, metastasis and cisplatin resistance of ovarian cancer cells and predicted poor survival in ovarian cancer patients

OBJECTIVE: Ovarian cancer has the highest mortality rate cancer worldwide in women, and it is the second most common gynecologic malignancy in females, but the treatment remained unsatisfactory. Researches showed that lncRNA EBIC had played key roles in different cancer, but its role in ovarian cancer remains largely unclear.

PATIENTS AND METHODS: qRT-PCR was applied to detect the expression of lncRNA EBIC in ovarian cancer and adjacent tissue, and analysis was applied to explore the relationship between expression and clinical characteristic. Overall, the survival curves for the two groups were defined by the high and low expression level of EBIC in ovarian cancer patients. After that, CCK8 and transwell were used to detect the proliferation and metastasis ability of ovarian cancer, after suppression of lncRNA EBIC. The relative protein expression level in ovarian cancer cells after transfection with siRNA-NC or siRNA-EIBC was detected by Western blot.

RESULTS: qRT-PCR showed that lncRNA EIBC was highly expressed in ovarian cancer tissue, compared with adjacent tissue. Moreover, we found that expression of lncRNA EIBC was closely related to prognosis, tumor size and lymph node metastasis. We also found that the cell proliferation, invasion, migration and cisplatin resistance in ovarian cancer cells after transfection with siRNA-EBIC were significantly inhibited. Mechanistically, the relative protein expression level of β-catenin, vimentin and c-myc were significantly decreased and the relative expression of E-cadherin was significantly increased in ovarian cancer cells after transfection with siRNA-EBIC.

CONCLUSIONS: We found that overexpression of lncRNA EBIC could promote the proliferation, invasion and migration and improved cells cisplatin resistance by Wnt/β-catenin signaling pathway in ovarian cancer. LncRNA EBIC may be a potential target for the treatment of ovarian cancer patients.

L'articolo LncRNA EBIC promoted proliferation, metastasis and cisplatin resistance of ovarian cancer cells and predicted poor survival in ovarian cancer patients sembra essere il primo su European Review.

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Overexpressed microRNA-615-3p promotes progression of neonatal acute respiratory distress syndrome by inhibiting differentiation of mesenchymal stem cells to alveolar type II epithelial cells

OBJECTIVE: To explore whether microRNA-615-3p participates in the progression of neonatal acute respiratory distress syndrome (ARDS) by inhibiting differentiation of mesenchymal stem cells (MSCs) to alveolar type II epithelial cells (ATII) via Wnt/β-catenin pathway.

PATIENTS AND METHODS: Expression levels of microRNA-615-3p and inflammatory factors (IL-1, IL-6, IL-8, and TNF-α) in peripheral blood of 24 neonatal ARDS patients and 14 healthy newborns were detected by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction). MSCs were isolated from bone marrow of mice and identified by flow cytometry. The effect of microRNA-615-3p on regulating the differentiation of MSCs to ATII was analyzed. After altering expressions of microRNA-615-3p and DKK1 by plasmids transfection, Wnt/β-catenin pathway-related genes were detected by Western blot.

RESULTS: Higher expression levels of microRNA-615-3p and inflammatory factors (IL-1, IL-6, IL-8, and TNF-α) were observed in peripheral blood of neonatal ARDS patients than those of healthy newborns. ATII-specific genes were upregulated, and inflammatory factors were downregulated after the microRNA-615-3p knockdown in MSCs. Moreover, expressions of Wnt/β-catenin pathway-related genes were downregulated after the microRNA-615-3p overexpression, which was partially reserved by the DKK1 knockdown.

CONCLUSIONS: Overexpressed microRNA-615-3p promoted ARDS development through inhibiting differentiation of MSCs to ATII via Wnt/β-catenin pathway.

L'articolo Overexpressed microRNA-615-3p promotes progression of neonatal acute respiratory distress syndrome by inhibiting differentiation of mesenchymal stem cells to alveolar type II epithelial cells sembra essere il primo su European Review.

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CD11c + MHCII lo GM-CSF-bone marrow-derived dendritic cells act as antigen donor cells and as antigen presenting cells in neoepitope-elicited tumor immunity against a mouse fibrosarcoma

Abstract

Dendritic cells play a critical role in initiating T-cell responses. In spite of this recognition, they have not been used widely as adjuvants, nor is the mechanism of their adjuvanticity fully understood. Here, using a mutated neoepitope of a mouse fibrosarcoma as the antigen, and tumor rejection as the end point, we show that dendritic cells but not macrophages possess superior adjuvanticity. Several types of dendritic cells, such as bone marrow-derived dendritic cells (GM-CSF cultured or FLT3-ligand induced) or monocyte-derived ones, are powerful adjuvants, although GM-CSF-cultured cells show the highest activity. Among these, the CD11c⁺ MHCII^lo sub-set, distinguishable by a distinct transcriptional profile including a higher expression of heat shock protein receptors CD91 and LOX1, mannose receptors and TLRs, is significantly superior to the CD11c⁺ MHCII^hi sub-set. Finally, dendritic cells exert their adjuvanticity by acting as both antigen donor cells (i.e., antigen reservoirs) as well as antigen presenting cells.

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CD11c + MHCII lo GM-CSF-bone marrow-derived dendritic cells act as antigen donor cells and as antigen presenting cells in neoepitope-elicited tumor immunity against a mouse fibrosarcoma

Abstract

Dendritic cells play a critical role in initiating T-cell responses. In spite of this recognition, they have not been used widely as adjuvants, nor is the mechanism of their adjuvanticity fully understood. Here, using a mutated neoepitope of a mouse fibrosarcoma as the antigen, and tumor rejection as the end point, we show that dendritic cells but not macrophages possess superior adjuvanticity. Several types of dendritic cells, such as bone marrow-derived dendritic cells (GM-CSF cultured or FLT3-ligand induced) or monocyte-derived ones, are powerful adjuvants, although GM-CSF-cultured cells show the highest activity. Among these, the CD11c⁺ MHCII^lo sub-set, distinguishable by a distinct transcriptional profile including a higher expression of heat shock protein receptors CD91 and LOX1, mannose receptors and TLRs, is significantly superior to the CD11c⁺ MHCII^hi sub-set. Finally, dendritic cells exert their adjuvanticity by acting as both antigen donor cells (i.e., antigen reservoirs) as well as antigen presenting cells.

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Cancers, Vol. 10, Pages 238: Micelles Structure Development as a Strategy to Improve Smart Cancer Therapy

Cancers, Vol. 10, Pages 238: Micelles Structure Development as a Strategy to Improve Smart Cancer Therapy

Cancers doi: 10.3390/cancers10070238

Authors: Nemany A. N. Hanafy Maged El-Kemary Stefano Leporatti

Micelles as colloidal suspension have attracted considerable attention due to their potential use for both cancer diagnosis and therapy. These structures have proven their ability to deliver poorly water-soluble anticancer drugs, improve drug stability, and have good penetration and site-specificity, leading to enhance therapeutic efficacy. Micelles are composed of hydrophobic and hydrophilic components assembled into nanosized spherical, ellipsoid, cylindrical, or unilamellar structures. For their simple formation, they are widely studied, either by using opposite polymers attachment consisting of two or more block copolymers, or by using fatty acid molecules that can modify themselves in a rounded shape. Recently, hybrid and responsive stimuli nanomicelles are formed either by integration with metal nanoparticles such as silver, gold, iron oxide nanoparticles inside micelles or by a combination of lipids and polymers into single composite. Herein, through this special issue, an updated overview of micelles development and their application for cancer therapy will be discussed.

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The temporal and environmental context of early animal evolution: considering all the ingredients of an ‘explosion’

Abstract

Animals originated and evolved during a unique time in Earth history—the Neoproterozoic Era. This paper aims to discuss 1) when landmark events in early animal evolution occurred, and 2) the environmental context of these evolutionary milestones, and how such factors may have affected ecosystems and body plans. With respect to timing, molecular clock studies—utilizing a diversity of methodologies—agree that animal multicellularity had arisen by ∼800 million years ago (Ma) (Tonian period), the bilaterian body plan by ∼650 Ma (Cryogenian), and divergences between sister phyla occurred ∼560-540 Ma (late Ediacaran). Most purported Tonian and Cryogenian animal body fossils are unlikely to be correctly identified, but independent support for the presence of pre-Ediacaran animals is recorded by organic geochemical biomarkers produced by demosponges. This view of animal origins contrasts with data from the fossil record, and the taphonomic question of why animals were not preserved (if present) remains unresolved, although Neoproterozoic environments demanding small, thin body plans and lower abundance/rarity in populations may have played a role. Considering environmental conditions, geochemical data suggest that animals evolved in a relatively low-oxygen ocean. Here, we present new analyses of sedimentary total organic carbon contents in shales suggesting that the Neoproterozoic ocean may also have had lower primary productivity—or at least lower quantities of organic carbon reaching the seafloor—compared to the Phanerozoic. Indeed, recent modeling efforts suggest that low primary productivity is an expected corollary of a low-O₂ world. Combined with an inability to inhabit productive regions in a low-O₂ ocean, earliest animal communities would likely have been more food limited than generally appreciated, impacting both ecosystem structure and organismal behavior. In light of this, we propose the 'fire triangle' metaphor for environmental influences on early animal evolution. Moving towards consideration of all environmental aspects of the Cambrian radiation (fuel, heat, and oxidant) will ultimately lead to a more holistic view of the event.

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Communication through Playful Systems: Presenting scientific worlds the way a game might do

Abstract

More than ever, science is in the unenviable position of competing for the hearts and minds of the public against utterly false accounts of our world. These false accounts are often deeply spiritual, poetic, sublime — despite being false, they can leave a mark on the human imagination. It is difficult to convey scientific research in a way that leaves the audience with a comparable sense of awe or a personal connection to the subject matter. This is an area where games as a cultural form can offer some assistance and insight. A game can convey its complex inner workings with ease by engaging an audience through play. It is expressive communication that sows intuitive understanding and fosters a personal connection between the human player and the represented world. Games like Minecraft and Portal are thus increasingly being used in classrooms to teach math, physics, spatial reasoning, and even the scientific method. I discuss the process of designing interactive experiences in games as a model for effective communication. Drawing on examples from my own work at Double Fine Productions and the work of others, I offer insights from game design to address parallel challenges in scientific communication. I explore ways of introducing an audience to an unfamiliar world through narrative and play. For example, by setting up the rules of an unfamiliar world in an interactive way, especially through iterative problem solving, you can lead a novice audience to a nuanced understanding of that world's complexity without overloading information. These strategies can enhance communication of scientific research in any format.

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Editorial Board

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Contents

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Information for Authors and Readers

Clinical Gastroenterology and Hepatology is the go-to resource on a broad spectrum of themes in clinical gastroenterology and hepatology. The official clinical practice journal of the AGA Institute brings you the best original research in the field with a unique combination of reviews, editorials, podcasts, video abstracts, and outcomes research—all supporting clinical practice. Articles on education, policy, and practice management highlight issues pertinent to clinicians.

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Bile Acid Deficiency and Constipation

In a nicely performed study on a group of patients with constipation, Vijayvargiya et al1 showed reduced total (particularly dihydroxy secretory) fecal bile acids (BAs), along with the expected decrease in serum 7α-hydroxy-4-cholestene-3-one (a marker for bile acid synthesis) and increased fibroblast growth factor 19 (a factor involved in down-regulating bile acid synthesis). Vijayvargiya et al1 proposed that either "a decreased proportion of secretory fecal bile acids results in constipation" and/or "increased colonic transit time … results in increased passive absorption of fecal BAs and, hence, lower excretion of secretory BAs."

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Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is when there is a buildup of eosinophils (a type of white blood cell) in the esophagus (the tube that links your mouth and stomach). The buildup causes irritation and scarring. EoE is the result of an allergy to certain foods and is a lifelong health issue.

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Proximal Baseline Impedance Analysis Might be a Valuable Clue for Extraesophageal Reflux Diagnosis

We read the article written by Vaezi et al1 with great interest. They aimed to describe the developments in the field of extraesophageal reflux disease in their article based on expert opinion and relevant publications. We thank the authors for this review. However, we think that there is an issue that needs to be added.

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Reply

We thank Drs Crino and Larghi for their comments. We do agree that endoscopic ultrasound–guided fine-needle biopsy (EUS-FNB) is preferred over EUS-guided fine-needle aspiration (EUS-FNA) for tissue acquisition, except for the following: (1) when the patient is borderline coagulopathic or when anticoagulation cannot be discontinued but a tissue diagnosis still is desired (risk of bleeding may be higher with FNB), or (2) for sampling pancreatic cyst lesions (the risk of pancreatitis may be higher with FNB).

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EUS-Guided Fine Needle Tissue Acquisition for Pancreatic Solid Lesions: Are We at the End of Fine Needle Aspiration?

We read with interest the randomized controlled study by Bang et al,1 which compared endoscopic ultrasound (EUS) fine-needle aspiration (FNA) performed with a 22G needle with or without suction or with a 25G needle with or without suction in 352 patients with pancreatic solid lesions (PSLs). The primary outcome was diagnostic accuracy of cell-block, whereas secondary outcomes were the comparison of operating characteristics of rapid on-site cytopathology (ROSE) and EUS-FNA, the number of passes to establish onsite diagnostic adequacy, the specimen bloodiness, adverse events, and technical failure.

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Elsewhere in The AGA Journals

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An Inside View: AGA Advocacy Priorities

As Congress and the Trump administration struggle with efforts to reform the US health care system, we thought it would be timely to update you on the work AGA does in Washington, DC, to support the science and practice of gastroenterology.

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Correction

Meester RGS, Zauber AG, Doubeni CA, et al. Consequences of increasing time to colonoscopy examination after positive result from fecal colorectal cancer screening test. Clin Gastroenterol Hepatol 2016;14:1445–1451.

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Cover

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New Research From Clinical Psychological Science

Read about the latest research published in Clinical Psychological Science:

The Associations Among Callous-Unemotional Traits, Worry, and Aggression in Justice-Involved Adolescent Boys
Emily L. Robertson, Paul J. Frick, James V. Ray, Laura C. Thornton, Tina D. Wall Myers, Laurence Steinberg, and Elizabeth Cauffman

Callous-unemotional (CU) traits, characterized by a lack of empathy, affect, and guilt, have been related to psychopathy and antisocial behavior in youths, especially when associated with high anxiety. Robertson and colleagues explored the association between CU traits, anxiety, self-reported aggression, and official records of violent rearrests among more than 1,000 juvenile male first-time offenders, across 30 months. They collected measures of CU traits, anxiety (measured as trait worry), victimization, aggression, self-reported violent offending, and official arrest records. Results showed that both CU traits and anxiety predicted victimization, self-reported aggression, and violent offending. Moreover, self-reported violent offending was the highest in adolescents with high CU traits and high anxiety. However, arrests were predicted only by CU traits. These findings suggest that the additive effects of CU traits and anxiety in predicting violent behavior might be limited to self-report.

Mediators and Mechanisms
Warren W. Tryon

In psychotherapy research, mediators are usually thought to be mechanisms. However, mediation is to mechanism what correlation is to causation; that is, evidence of mediation is necessary but not sufficient to explain the mechanism. Thus, mechanisms need to meet criteria of causation and explanation. To fulfill these criteria, Tyron expanded on the proposal of an associative activation psychological mechanism by Otgaar and colleagues (2017). He shows how this mechanism involves parallel distributed processing (PDP) in connectionist neural network (CNN) models of memory, introduced by Rumelhart and McClelland (1986). According to CNN and PDP, information is organized in nodes that are connected in a network, and once one node is activated, activation automatically spreads to the linked nodes. Tyron provides analyses of the network dynamics and structure as a form of explanation of the mechanism and presents a simulation of personality that supports causation. He suggests the importance of using connectionist models to represent psychological mechanisms in psychotherapy and psychological research more generally.

Longitudinal Relations Between Depressive Symptoms and Executive Functions From Adolescence to Early Adulthood: A Twin Study
Naomi P. Friedman, Alta du Pont, Robin P. Corley, and John K. Hewitt

Major depressive disorder is usually associated with deficits in executive functions (EF) such as the cognitive control implied in goal-directed thoughts and actions. But what is the cause of these associations? Is it mostly genetic or mostly environmental? The authors tested twin pairs at ages 12, 17, and 23, using a diagnostic interview to assess depressive symptoms and EF tasks (response inhibition, working memory update, and mental set shifting). The results indicated that higher levels of depressive symptoms were associated with deficits in "common" EF, especially at 17 years old, and in "updating-specific" abilities at age 23, but not with "shifting-specific" abilities. The use of twin models allowed Friedman and colleagues to suggest that these associations can be almost entirely explained by shared genetics but not by environmental factors. In sum, the association between depressive symptoms and deficits in EF seems to result from shared genetic risk.

Identifying Core Deficits in a Dimensional Model of Borderline Personality Disorder Features: A Network Analysis
Matthew W. Southward and Jennifer S. Cheavens

Borderline personality disorder (BPD) is associated with three core deficits: emotion dysregulation, interpersonal problems, and self-identity disturbance. Southward and Cheavens used a network model to explore the associations between these deficits, or symptoms, and how they interact with each other. In network models of psychopathology, symptoms can be represented by nodes that are linked to each other. Depending on the number and strength of the connections between symptoms, they can be more or less central in the network. More than 4,000 participants with a range of BPD features completed measures of emotion regulation, interpersonal problems, and BPD assessment, and Southward and Cheavens conducted a network analysis. They found that loneliness, recklessness, and mood instability were the most central symptoms for participants high in BPD, whereas chronic emptiness, mood intensity, and mood instability were more central for those low in BPD. These results suggest that emotion dysregulation is central for both low- and high-BPD groups, but interpersonal problems are more central for the high-BPD group and self-identity disturbance is more central for the low-BPD group.

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