Turning Toxicants into Safe Therapeutic Drugs: Cytolytic Peptide−Photosensitizer Assemblies for Optimized In Vivo Delivery of Melittin

Advanced Healthcare Materials, EarlyView.


https://ift.tt/2Idj0VL

A controlled clinical trial on the effects of exercise on cognition and mobility in adults with multiple sclerosis

Objective To investigate the effects of a 6-month exercise program on cognition and mobility in participants with multiple sclerosis. Design Prospective, single blind, controlled clinical trial. Setting A community rehabilitation program within a large metropolitan health service. Participants Twenty-eight patients with multiple sclerosis, referred for outpatient rehabilitation. Interventions Participants were allocated to one of two groups and undertook a cognitive-motor exercise program or monitoring (control group). Main outcome measures Cognition and mobility. Cognition was evaluated using the Mini-Mental State Examination and the Frontal Assessment Battery. Mobility was assessed with the Timed Get-Up-and-Go-Test, applied with and without dual task distractors. Results The findings showed benefits provided by exercise on cognition and mobility. Differently, participants of the control group did not have significant changes in cognition scores after 6 months of follow-up, and had a worse performance in mobility tests. Conclusion Six months of exercise provided benefits to cognition and mobility in adults with multiple sclerosis. This trial was registered prospectively with the Brazilian Clinical Trials Register, ID: RBR-9gh4km, (https://ift.tt/2tsqhM3). All correspondence and requests for reprints should be addressed to: Gustavo Christofoletti, PhD, Institute of health, Universidade Federal de Mato Grosso do Sul, Av. Universitária, s/n, Caixa Postal 549, Campo Grande, MS, Brazil. Email: g.christofoletti@ufms.br Clinical Trial Identifier: RBR-9gh4km (https://ift.tt/2tsqhM3) Conflicts of interest: none. Financial disclosures: none. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2MKndDT

SHORT-TERM EFFECTS OF NORMOCAPNIC HYPERPNEA AND EXERCISE TRAINING IN COPD PATIENTS: A PILOT STUDY

Objective To evaluate the short-term physiologic effects of respiratory muscle training with normocapnic hyperpnea (NH) added to standard exercise training on respiratory muscle endurance/strength and exercise tolerance in COPD patients. Design Randomized controlled trial. Patients referred for rehabilitation were randomly assigned to 20 sessions (twice daily 5 days/week) of either NH (Group 1, n = 12) or sham maneuvers (Group 2, n = 10) in addition to individualized cycle training and abdominal, upper and lower limb muscle exercise. At baseline and end of study, patients underwent evaluation of respiratory muscle endurance, maximum voluntary ventilation (MVV), maximal inspiratory (MIP) and expiratory pressures (MEP), and 6-min walking distance (6MWD). Results Following training, a significant improvement was found only for Group 1 in respiratory muscle endurance time [by 654 (481) vs. 149 (216) sec for Group 2, P = 0.0108] and MIP [Group 1: from 81.2 (21.9) to 107.6 (23.0) cmH2O, P = 0.018 vs. Group 2: from 75.4 (13.8) to 81.3 (18.9) cmH2O, P = 0.139]. The difference between groups for 6MWD, MVV and MEP was not significant. Conclusions Short-term NH training added to standard exercise, compared to exercise training alone, improves respiratory muscle endurance and strength but not exercise tolerance in COPD patients. Correspondence to: Mara Paneroni, PT MSc, Department of Respiratory Rehabilitation, Istituti Clinici Scientifici Maugeri, IRCCS via Giuseppe Mazzini 129, 25065 Lumezzane (BS), Italy; email: mara.paneroni@icsmaugeri.it Authorship MP: Data collection, data analysis, statistics, writing, editing CS: Data collection, data analysis, writing, editing MS: Data collection, data analysis, writing DT, GFA, IS, GP: data collection NA: Review, editing MV: Protocol, editing All the Authors approved and critically revised the manuscript FUNDING The Research was supported by Institutional funding. CONFLICT OF INTEREST The Authors have no conflicts of interest to declare. ACKNOWLEDGMENTS The Authors thank Rosemary Allpress for the English revision of the paper and Laura Comini for editorial assistance. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2tjEdsG

Retinal Endovascular Surgery with Tissue Plasminogen Activator Injection for Central Retinal Artery Occlusion

Purpose: To report 2 cases of central retinal artery occlusion (CRAO) who underwent retinal endovascular surgery with injection of tissue plasminogen activator (tPA) into the retinal artery and showed a remarkable improvement in visual acuity and retinal circulation. Methods: Standard 25-G vitrectomy was performed under local anesthesia. Simultaneously, tPA (80,000 units/mL) solution was injected into the retinal artery of the optic disc for 2–3 min using a microneedle. Changes in visual acuity, fundus photography, optical coherence tomography (OCT), fluorescein angiography, and laser speckle flowgraphy (LSFG) results were examined. Results: Both cases could be treated within 12 h after the onset of CRAO. Case 1 was a 47-year-old woman. Her visual acuity improved from counting fingers before operation to 0.08 logMAR 1 month after the surgery. However, thinning of the retina at the macula was observed by OCT. Case 2 was a 70-year-old man. His visual acuity improved from counting fingers to 0.1 logMAR 2 months after the surgery. Both fluorescein angiography and LSFG showed improvement in retinal circulation after the surgery in case 2. Conclusions: Retinal endovascular surgery with injection of tPA into the retinal artery was feasible and may be a way to improve visual acuity and retinal circulation when performed in the acute phase of CRAO.
Case Rep Ophthalmol 2018;9:327–332

https://ift.tt/2lsH4Lz

Cancers, Vol. 10, Pages 211: Immunosenescence and Immunotherapy in Elderly Acute Myeloid Leukemia Patients: Time for a Biology-Driven Approach

Cancers, Vol. 10, Pages 211: Immunosenescence and Immunotherapy in Elderly Acute Myeloid Leukemia Patients: Time for a Biology-Driven Approach

Cancers doi: 10.3390/cancers10070211

Authors: Alessandro Isidori Federica Loscocco Marilena Ciciarello Giulia Corradi Mariangela Lecciso Darina Ocadlikova Sarah Parisi Valentina Salvestrini Sergio Amadori Giuseppe Visani Antonio Curti

Acute myeloid leukemia (AML) is a disease, which mainly affects the elderly population. Unfortunately, the prognosis of patients aged >65 years is dismal, with 1-year overall survival approaching 10% with conventional therapies. The hypothesis of harnessing the immune system against cancer, including leukemia, has been postulated for a long time, and several clinical attempts have been made in this field. In the last years, we increased our knowledge about the interplay between AML and immune cells, but no major improvement has been translated, up to now, from bench to bedside. However, the outstanding results coming from the modern immuno-oncology trials with new drugs have granted a new interest for immunotherapy in AML. Accordingly, the elderly population represents an ideal target, given the low percentage of patients eligible for allogeneic stem cell transplant. With that in mind, in the era of immunotherapy, we consider immunosenescence as the optimal background to start investigating a biology-driven approach to AML therapy in the elderly. By taking into account the physiological age-related changes of immune response, more personalized and tailored use of the new drugs and strategies harnessing the immune system against AML, has the potential to increase their efficacy and impact on clinical outcomes.

https://ift.tt/2ticlVM

Gestational changes in buprenorphine exposure: A physiologically‐based pharmacokinetic analysis

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2K6MG8P

The analgesic efficacy and pharmacokinetics of epidural oxycodone after gynaecological laparotomy: a randomized, double‐blind, double‐dummy comparison with intravenous administration

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2KbMj04

Patient involvement is essential in identifying drug‐related problems

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2K996q4

Genotype‐guided warfarin dosing vs. conventional dosing strategies: a systematic review and meta‐analysis of randomized controlled trials

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2K1IUla

Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open‐label clinical trial

British Journal of Clinical Pharmacology, EarlyView.


https://ift.tt/2IekjDO

Validation of multiple myeloma risk stratification indices in routine clinical practice: Analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies

Cancer Medicine, EarlyView.


https://ift.tt/2JYO7dJ

Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia

Abstract

To investigate the efficacy and safety of thalidomide in patients with thalassemia intermedia (TI). Patients with a confirmed diagnosis of TI who met the trial criteria and signed consent forms were prescribed oral thalidomide 50 mg qn for 3 months from February 2017. Complete blood counts, Hb analysis, and liver and kidney functions were monitored monthly during treatment and any differences were compared before and after treatment. Patients with Hb increments > 2.0 g/dL were termed main responders (MaR), and those with Hb increments between 1.0 and 2.0 g/dL as minor responders (MiR), otherwise they were termed non-responders. Relevance analysis was performed to explore parameters predicting Hb increments after treatment. Adverse effects during treatment were carefully recorded. The overall response rate (ORR = MaR + MiR) and MaR rates were 78.6 and 50% after 1 month of treatment, respectively, and 85.7 and 71.4% after 3 months treatment. At the end of the treatment period, Hb and HbF increased by 2.5 ± 1.8 g/dL and 2.5 ± 1.6 g/dL, while bilirubin, lactate dehydrogenase, and the nucleated red blood cell count (NRBC) were significantly decreased, while the reticulocyte count significantly increased. Correlation analysis showed that the Hb increments correlated significantly with the ratio of HbF before treatment (r = 0.683, P = 0.007) rather than age, Hb, reticulocyte count, and NRBC before treatment. Adverse events during treatment were mild, and drug reduction or withdrawal from the trial was not required. Thalidomide had rapid and significant effects in patients with TI, and also, it is safe and convenient. But larger scale clinical trials will be required to confirm our conclusions. Trial Registration: NCT02995707, https://www.clinicaltrials.gov/ct2/show/NCT03184844?term=thalidomide+thalassemia&rank=1.

https://ift.tt/2K2sRnr

The use of blue light flexible cystoscopy with hexaminolevulinate & the diagnosis of bladder cancer

Future Oncology, Ahead of Print.


https://ift.tt/2tj1dbl

Alkaline phosphatase in metastatic castration-resistant prostate cancer: reassessment of an older biomarker

Future Oncology, Ahead of Print.


https://ift.tt/2KaIFjY

Milestones over the development of SB3, a trastuzumab biosimilar

Future Oncology, Ahead of Print.


https://ift.tt/2MK8Mjg

Nivolumab and its use in the second-line treatment of metastatic urothelial cancer

Future Oncology, Ahead of Print.


https://ift.tt/2K8fiOW

Adaptive reconstruction for azimuth signal of multichannel HRWS SAR imaging system

The reconstruction of azimuth signal in multichannel synthetic aperture radar (SAR) for high-resolution and wide-swath (HRWS) imaging requires exact steering vectors. The information of ambiguities and system ...

https://ift.tt/2JXwbQp

Critical Care Management of Anti-N-Methyl-D-Asparate Receptor Encephalitis

Objectives: Anti-N-methyl-D-asparate receptor encephalitis is considered an immune-mediated form of encephalitis with paraneoplastic and nonparaneoplastic forms. Delay in recognition is common and patients typically present to the ICU without a diagnosis or with complications following a delayed diagnosis. The aim of this review is to provide a focused overview for the ICU clinician regarding presentation, diagnosis, and critical care management. Data Sources, Study Selection, and Data Extraction: PubMed database search with manual review of articles involving anti-N-methyl-D-asparate receptor encephalitis. Data Synthesis: Anti-N-methyl-D-asparate receptor encephalitis is increasingly encountered in the ICU. The cascade of events initiating anti-N-methyl-D-asparate receptor antibody formation may involve an infectious trigger particularly in the setting of teratoma. Following a prodrome, most patients develop psychiatric symptoms followed by movement disorder. Classical, psychiatric, and catatonic phenotypes may be distinguished based on the presence and severity of symptoms. Early immunotherapy and low initial cerebrospinal fluid inflammation are independent predictors of positive outcomes in ICU patients. Concomitant organ failure, status epilepticus, and the identification of a tumor did not influence outcome in critically ill patients. Supportive care in the ICU includes management of various manifestations of dyskinesia, status epilepticus, autonomic disorders, and the need for general sedation. Common treatment strategies and limitations are discussed including the emerging role of bortezomib. Conclusions: Intensivists should be familiar with the presentation and management of anti-N-methyl-D-asparate receptor encephalitis. Early diagnosis and immediate implementation of steroids, immunoglobulins, and/or plasmapheresis and immune therapy are associated with a good neurologic outcome although response may be delayed. The selection and timing of second-line immune therapy requires further study. Dr. Neyens disclosed off-label product use of IV immune globulin, rituximab, and bortezomib. Dr. Gaskill disclosed off-label product use of rituximab and bortezomib. Dr. Chalela has disclosed that he does not have any potential conflicts of interest. For information regarding this article, E-mail: Chalela@musc.edu Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

https://ift.tt/2yxgeeJ

Idiopathic Scoliosis Families Highlight Actin-Based and Microtubule-Based Cellular Projections and Extracellular Matrix in Disease Etiology

Idiopathic scoliosis (IS) is a structural lateral spinal curvature of ≥10 that affects up to 3% of otherwise healthy children and can lead to life-long problems in severe cases. It is well-established that IS is a genetic disorder. Previous studies have identified genes that may contribute to the IS phenotype, but the overall genetic etiology of IS is not well understood. We used exome sequencing to study five multigenerational families with IS. Bioinformatic analyses identified unique and low frequency variants (minor allele frequency ≤5%) that were present in all sequenced members of the family. Across the five families, we identified a total of 270 variants with predicted functional consequences in 246 genes, and found that eight genes were shared by two families. We performed GO term enrichment analyses, with the hypothesis that certain functional annotations or pathways would be enriched in the 246 genes identified in our IS families. Using three complementary programs to complete these analyses, we identified enriched categories that include stereocilia and other actin-based cellular projections, cilia and other microtubule-based cellular projections, and the extracellular matrix (ECM). Our results suggest that there are multiple paths to IS and provide a foundation for future studies of IS pathogenesis.

https://ift.tt/2tuswPb

Accuracy of a Novel Handheld Wireless Platform for Detection of Cardiac Dysfunction in Anthracycline-Exposed Survivors of Childhood Cancer

Purpose: Childhood cancer survivors are at risk for anthracycline-related cardiac dysfunction, often developing at a time when they are least engaged in long-term survivorship care. New paradigms in survivorship care and chronic disease screening are needed in this population. We compared the accuracy of a novel handheld mHealth platform (Vivio) as well as echocardiography for assessment of cardiac function [left ventricular ejection fraction (EF)] in childhood cancer survivors with cardiac magnetic resonance (CMR) imaging (reference).

Experimental Design: Cross-sectional study design was used. Concurrent evaluation of EF was performed using Vivio, two-dimensional (2D) echocardiography, and CMR. Differences in mean EF (2D echocardiography vs. CMR; Vivio vs. CMR) were compared using Bland–Altman plots. Linear regression was used to evaluate proportional bias.

Results: A total of 191 consecutive survivors participated [50.7% female; median time from diagnosis: 15.8 years (2–44); median anthracycline dose: 225 mg/m² (25–642)]. Echocardiography overestimated mean EF by 4.9% (P < 0.001); linear regression analysis confirmed a proportional bias, when compared with CMR (t = 3.1, P < 0.001). There was no difference between mean EF derived from Vivio and from CMR (–0.2%, P = 0.68). The detection of cardiac dysfunction via echocardiography was poor when compared with CMR [Echo EF < 45% (sensitivity 14.3%), Echo EF < 50% (sensitivity 28.6%)]. Sensitivity was substantially better for Vivio-based measurements [EF < 45% or EF < 50% (sensitivity 85.7%)].

Conclusions: This accessible technology has the potential to change the day-to-day practice of clinicians caring for the large number of patients diagnosed with cardiac dysfunction and heart failure each year, allowing real-time monitoring and management of their disease without the lag-time between imaging and interpretation of results. Clin Cancer Res; 1–7. ©2018 AACR.

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Editorial board

https://ift.tt/2K2OR1u

Inside front cover - Masthead

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Table of Contents

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In This Issue

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Interplay between ShcA signaling and PGC-1{alpha} triggers targetable metabolic vulnerabilities in breast cancer

The ShcA adaptor protein transduces oncogenic signals downstream of receptor tyrosine kinases. We show here that breast tumors engage the ShcA pathway to increase their metabolism. ShcA signaling enhanced glucose catabolism through glycolysis and oxidative phosphorylation, rendering breast cancer cells critically dependent on glucose. ShcA signaling simultaneously increased the metabolic rate and flexibility of breast cancer cells by inducing the PGC-1α transcription factor, a central regulator of mitochondrial metabolism. Breast tumors that engaged ShcA signaling were critically dependent on PGC-1α to support their increased metabolic rate. PGC-1α deletion drastically delayed breast tumor onset in an orthotopic mouse model, highlighting a key role for PGC-1α in tumor initiation. Conversely, reduced ShcA signaling impaired both the metabolic rate and flexibility of breast cancer cells, rendering them reliant on mitochondrial oxidative phosphorylation. This metabolic reprogramming exposed a targetable metabolic vulnerability, leading to a sensitization of breast tumors to inhibitors of mitochondrial complex I (biguanides). Genetic inhibition of ShcA signaling in the Polyoma virus middle T (MT) breast cancer mouse model sensitized mammary tumors to biguanides during the earliest stages of breast cancer progression. Tumor initiation and growth were selectively and severely impaired in MT/ShcA-deficient animals. These data demonstrate that metabolic reprogramming is a key component of ShcA signaling and serves an unappreciated yet vital role during breast cancer initiation and progression. These data further unravel a novel interplay between ShcA and PGC-1α in the coordination of metabolic reprogramming and demonstrate the sensitivity of breast tumors to drugs targeting oxidative phosphorylation.

https://ift.tt/2tprPYj

More Cash-Pay Patients Means Docs Need Billing Strategies

THURSDAY, June 21, 2018 -- More patients are paying for health care services with cash, and this means physician practices need a comprehensive billing policy, according to an article published in Medical Economics. High-deductible health plans and...

https://ift.tt/2txaV9o

BCG Vaccine Tied to Reduced Hyperglycemia in Type 1 Diabetes

THURSDAY, June 21, 2018 -- The Bacillus Calmette Guérin (BCG) vaccine is associated with a reduction in hyperglycemia among patients with type 1 diabetes with long-term disease, according to a study published online June 21 in npj Vaccines. Willem...

https://ift.tt/2ML8g4w

Few Receive All High-Priority Clinical Preventive Services

THURSDAY, June 21, 2018 -- Only 8 percent of U.S. adults aged 35 years and older receive all high-priority clinical preventive services, according to a report published in the June issue of Health Affairs. Amanda Borsky, Dr.P.H., from the Agency for...

https://ift.tt/2yDfrZM

Many Physicians Not Prepared for End-of-Life Talks With Patients

THURSDAY, June 21, 2018 -- While nearly all physicians say end-of-life conversations are important, many report lacking the training to have such conversations, according to a brief report published online May 23 in the Journal of the American...

https://ift.tt/2MLk86s

Medicaid Expansion Ups Preemptive Listing for Kidney Transplant

THURSDAY, June 21, 2018 -- The proportion of new preemptive listings for kidney transplantation with Medicaid coverage increased in states with Medicaid expansion in the post-expansion era, according to a study published online June 21 in the...

https://ift.tt/2ysh8ca

CD271+ cells are diagnostic and prognostic and exhibit elevated MAPK activity in SHH medulloblastoma

The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis and transcriptome data across 763 primary tumors. RNA sequencing of CD271+ and CD271- cells revealed molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling was upregulated in the CD271+ population, and inhibiting this pathway reduced endogenous CD271 levels, stem/progenitor cell proliferation, and cell survival as well as cell migration in vitro. Treatment with the MEK inhibitor selumetinib extended survival and reduced CD271 levels in vivo; whereas, treatment with vismodegib, a well-known smoothened (SMO) inhibitor currently in clinical trials for the treatment of recurrent SHH medulloblastoma, had no significant effect in our models. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells.

https://ift.tt/2K7l6by

Caenorhabditis elegans in high-throughput screens for anti-infective compounds

Nicholas D Peterson | Read Pukkila-Worley

https://ift.tt/2MI0EzI

Correction: Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells

Correction: Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells

Correction: Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells, Published online: 22 June 2018; doi:10.1038/s41416-018-0146-2

Correction: Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells

https://ift.tt/2MewLGk

Treponema denticola chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma

Treponema denticola chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma

<i>Treponema denticola</i> chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma, Published online: 22 June 2018; doi:10.1038/s41416-018-0143-5

Treponema denticola chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma

https://ift.tt/2Ke5giA

Rare case of severe acute pancreatitis following over‐the‐scope clip‐assisted duodenal endoscopic mucosal resection using a cap‐fitted endoscope in a patient with pancreas divisum

Digestive Endoscopy, EarlyView.


https://ift.tt/2Kgl9VI

Quality Improvement in Bariatric Surgery: The Impact of Reducing Postoperative Complications on Medicare Payments

Objective: To determine the temporal relationship between reducing surgical complications and costs, using the study population of bariatric surgery. Background: Understanding the relationship between quality and costs has significant implications for the business case of investing in performance improvement. An unprecedented focus on safety in bariatric surgery has led to substantial reductions in complication rates over time, making it an ideal patient population in which to examine this relationship. Methods: We performed a retrospective review of Medicare beneficiaries undergoing bariatric surgery in the years 2005 to 2006 and 2013 to 2014 (total N = 37,329 patients, 562 hospitals). Hospitals were ranked into quintiles based on their degree of improvement in risk and reliability-adjusted 30-day rates of serious complications across the time periods. Multivariable regression was used to calculate corresponding changes in average price-standardized payments for each quintile of hospitals. Results: We found a strong association between reductions in complications and decreased Medicare payments. The top 20% of hospitals had a decrease in average serious complication rate of 7.3% (10.0%–2.7%; P

https://ift.tt/2t6s49I

FDA Approves First Continuous Glucose Monitoring System with Fully Implantable Glucose Sensor

June 21, 2018 -- The U.S. Food and Drug Administration today approved the Eversense Continuous Glucose Monitoring (CGM) system for use in people 18 years of age and older with diabetes. This is the first FDA-approved CGM system to include a fully...

https://ift.tt/2lrBtoT

Both glypican-3/Wnt/β-catenin signaling pathway and autophagy contributed to the inhibitory effect of curcumin on hepatocellular carcinoma

The aim of this study is to investigate the role of Glypican-3(GPC3)/wnt/β-catenin signaling pathway and autophagy in the regulation of hepatocellular carcinoma (HCC) growth mediated by curcumin.

https://ift.tt/2yw9i1f

A real life comparison of the effectiveness of adalimumab and golimumab in moderate-to-severe ulcerative colitis, supported by Propensity Score analysis.

Adalimumab and golimumab are effective in the treatment of moderate to severe ulcerative colitis.

https://ift.tt/2loKnDp

Frontal EEG asymmetry in extremely low birth weight adult survivors: Links to antenatal corticosteroid exposure and psychopathology

The brain is particularly vulnerable to adverse environmental exposures during sensitive periods of development (Gluckman et al., 2008; Schlotz and Phillips, 2009). Infants born at extremely low birth weight (ELBW, <1000g) are exposed to significant perinatal adversity and provide a model that allows researchers to examine the impact of early life stress on neurodevelopment across the lifespan. While advances in neonatal care have significantly increased the number of ELBW infants surviving into adulthood (Stoll et al., 2015), relatively little is known about the long-term effects of preterm birth on the brain.

https://ift.tt/2K5OUoR

FDA approves first continuous glucose monitoring system with a fully implantable glucose sensor and compatible mobile app for adults with diabetes

June 21, 2018 -- The U.S. Food and Drug Administration today approved the Eversense Continuous Glucose Monitoring (CGM) system for use in people 18 years of age and older with diabetes. This is the first FDA-approved CGM system to include a fully...

https://ift.tt/2yyOTc0

Treponema denticola chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma

https://ift.tt/2lnynlI

Correction: Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells

https://ift.tt/2tt2yv9

SASH1, a potential therapeutic target for cancer

We read with interest the paper by Zhou et al. [1], reporting that downregulated SASH1 expression indicated poor clinical prognosis in gastric cancer. Xie et al. [2] also found that downregulation of SASH1 correlated with poor prognosis in cervical cancer. Chen et al. [3] investigated the effects of the SASH1 gene in A549 human lung cancer cells and found that SASH1 may inhibit A549 cell growth and proliferation. Similarly, the overexpression of SASH1 may also be related to the decreased migration of A549 human lung cancer cells.

https://ift.tt/2MfhtkH

Clinicopathological significance of PSF3 expression in uterine endometrial carcinomas

PSF3 (Partner of SLD Five 3) is a member of the heterotetrameric complex termed GINS. Previous studies have shown that PSF3 is up-regulated in several cancers and is associated with tumor malignancy. However, the clinicopathological significance of PSF3 expression in endometrial lesions is still poorly understood. To investigate whether PSF3 could serve as a useful biomarker for endometrial carcinomas, we performed immunohistochemical analysis of PSF3 expression. In 155 cases of endometrial carcinomas (ECs), the mean tumor proportion score (TPS) of PSF3 expression was 30.7% in G1 endometrioid carcinoma, 55.0% in G2 endometrioid carcinoma, 59.0% in G3 endometrioid carcinoma, and 58.9% in non-endometrioid carcinomas.

https://ift.tt/2JZGljG

Tumor budding is associated with poor prognosis of oral squamous cell carcinoma and histologically represents an epithelial–mesenchymal transition process

In this study, we aimed to identify whether tumor budding is associated with the progression and prognosis of oral squamous cell carcinoma (OSCC) and investigate the correlation between tumor budding and regulators of epithelial–mesenchymal transition (EMT). Fifty-six cases of OSCC were selected and their tumor budding status was reviewed using archived hematoxylin and eosin-stained slides. In addition, the expression of EMT regulators was evaluated by immunohistochemistry using antibodies against Snail and Twist.

https://ift.tt/2MfhXqH

Clinicopathological correlation of PD-L1 expression in primary and metastatic breast Cancer and infiltrating immune cells

Few studies have evaluated the expression of The Programmed cell death-1 and its ligand-1 (PD-L1) in breast cancer. In this study we correlated differential expression of PD-L1 in breast cancer (BC) and its microenvironment from a cohort of patients with BC, paired locally metastatic disease to regional lymph nodes (LN) and non-paired distantly metastatic disease (mets). PD-L1 expression was correlated with several pathologic and clinical parameters in tumor and tumor immune cells (ICs) (CD3, CD4, CD8, CD20 and CD68) using the Ventana antibody (SP263) in 41BC, 46 paired mets in LNs and 46 distant mets.

https://ift.tt/2JZGjs4

Are Corticosteroids Beneficial in the Treatment of Community-Acquired Pneumonia?

The search strategy initially yielded 4,273 potential studies. After review, 17 randomized controlled trials containing 2,264 patients were included in the meta-analysis. Thirteen randomized controlled trials (1,954 participants) studied adult participants and 4 (310 participants) investigated pediatric populations. Of the 4 pediatric studies, 2 trials investigated children with solely Mycoplasma pneumoniae, 1 trial included any cause of pneumonia, and 1 trial included children with respiratory syncytial virus.

https://ift.tt/2Ib1otO

A Comparative Effectiveness Study of Two Nontargeted HIV and Hepatitis C Virus Screening Algorithms in an Urban Emergency Department

We compare the effectiveness of 2 nontargeted HIV and hepatitis C virus screening protocols integrated consecutively into care in an urban emergency department: a nurse-order HIV/hepatitis C virus screening algorithm followed by an automated-laboratory-order HIV/hepatitis C virus screening algorithm programmed into the electronic health record.

https://ift.tt/2tfI4Xs

Multiple Bullae Associated with Human Parvovirus B19

A 2-year-old boy was admitted to the emergency department with acute swelling of both lower extremities. Two weeks prior, he had a fever of a duration of 3 days, which was followed by erythema on the cheeks and extremities. Physical examination revealed edematous erythema on both lower extremities with small vesicles, dominant on the left leg (Figure, A). Laboratory data showed a total white blood cell count of 8.2 × 109 /L and a C-reactive protein level of 3.2 mg/L. Initially, the patient received intravenous cefazolin for suspected bacterial cellulitis.

https://ift.tt/2yyeSjQ

Trajectories of Body Mass Index from Childhood to Young Adulthood among Patients with Type 1 Diabetes—A Longitudinal Group-Based Modeling Approach Based on the DPV Registry

To identify distinct longitudinal patterns of body mass index (BMI) z score in type 1 diabetes from childhood to young adulthood and secondly to determine sex differences as well as associated clinical covariates.

https://ift.tt/2tkuNgo

Guardians at the Gate: Pediatricians, Colic and Clinical Research

Descriptions of infant colic extend back to the time of Galen when reports about calming a fussy baby emerged. Academic reports describing colic and hypothesizing etiology date back to 1954, when Illingsworth and Wessel published 2 independent reports describing colic and possible causes as understood at the time.1,2 Infant colic continues to be a frustrating syndrome for parents and pediatricians despite numerous studies with several hypotheses for etiology and treatments. Treatment has included the use of opiates applied to the mother's nipples in the time of Galen to the use of prebiotics today.

https://ift.tt/2thcuJb

DNA Vaccine–Induced Long-Lasting Cytotoxic T Cells Targeting Conserved Elements of Human Immunodeficiency Virus Gag Are Boosted Upon DNA or Recombinant Modified Vaccinia Ankara Vaccination

Human Gene Therapy, Ahead of Print.


https://ift.tt/2lp7C08

New Recommendations Guide Arthritis Pain Management

THURSDAY, June 21, 2018 -- The European League Against Rheumatism has released recommendations -- published in the June issue of the Annals of the Rheumatic Diseases -- for health professionals to use in approaching pain management in inflammatory...

https://ift.tt/2tnwU3l

Parkinson's Medications Tied to Impulse Control Disorders

THURSDAY, June 21, 2018 -- For patients with Parkinson's disease (PD), dopamine agonist (DA) use is associated with incidence of impulse control disorders (ICDs) in a dose-effect relationship, according to a study published online June 20 in...

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Parents Say Cancer Prevention Best Reason for HPV Vaccination

THURSDAY, June 21, 2018 -- Parents view cancer prevention as the best reason for guideline-consistent human papillomavirus (HPV) vaccination, according to a study published online June 14 in Cancer Epidemiology, Biomarkers & Prevention. Melissa...

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Rate of Death Up in Year After Non-Fatal Opioid Overdose

THURSDAY, June 21, 2018 -- There is a marked excess of deaths among U.S. adults who experience a non-fatal opioid overdose, according to a study published online June 20 in JAMA Psychiatry. Mark Olfson, M.D., M.P.H., from Columbia University in New...

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No Causal Effect of 25(OH)D on Gestational HTN, Preeclampsia

THURSDAY, June 21, 2018 -- Vitamin D status does not have a causal effect on gestational hypertension or preeclampsia, according to research published online June 20 in The BMJ. Maria C. Magnus, Ph.D., from the University of Bristol in the United...

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ACA Provisions Tied to Change in Profile of Frequent ER Users

THURSDAY, June 21, 2018 -- Following implementation of several major coverage expansion provisions in the Affordable Care Act (ACA), the profile of frequent emergency department users changed, according to a study published in the June issue of...

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Educational Strategies Could Improve Cardiac Arrest Outcomes

THURSDAY, June 21, 2018 -- Addressing shortcomings in resuscitation educational efficiency and local implementation could improve outcomes after cardiac arrest, according to a scientific statement published online June 21 in Circulation. Noting that...

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User Ratings Didn't Catch Blood Pressure App Inaccuracies

THURSDAY, June 21, 2018 -- User reviews and ratings of a popular, yet inaccurate, blood pressure-measuring mobile app were largely positive, according to a study published online June 7 in the Journal of the American Medical Informatics...

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Valuing Gluten-Free Food Tied to Better Dietary Intake

THURSDAY, June 21, 2018 -- Young adults who value gluten-free food usually do so as part of a healthier dietary pattern, though they are also more likely to engage in unhealthy weight control activities, according to a study published online June 18...

https://ift.tt/2MKBfFK

Greater Satisfaction With Autologous Breast Reconstruction

THURSDAY, June 21, 2018 -- Patients undergoing autologous post-mastectomy breast reconstruction have greater satisfaction than those undergoing implant reconstruction, and the odds of developing complications are significantly higher for autologous...

https://ift.tt/2yv9KwF

Leaf Spray Mass Spectrometry: A Rapid Ambient Ionization Technique to Directly Assess Metabolites from Plant Tissues

Leaf spray mass spectrometry is a direct chemical analysis technique that minimizes the sample preparation and eliminates chromatography, allowing for the rapid detection of small molecules from plant tissues.

https://ift.tt/2MGn2tr

Mapping Metabolism: Monitoring Lactate Dehydrogenase Activity Directly in Tissue

We describe a protocol for mapping the spatial distribution of enzymatic activity for enzymes that generate nicotinatmide adenine dinucleotide phosphate (NAD(P)H) + H+ directly in tissue samples.

https://ift.tt/2Md4GyS

Diagonal Method to Measure Synergy Among Any Number of Drugs

In this protocol, we describe how to make Loewe additivity-based drug interaction measurements for pairwise and three-way drug combinations.

https://ift.tt/2MIE89Y

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry

Identification of genetic variants contributing to complex human disease allows us to identify novel mechanisms. Here, we demonstrate a multiplex genotyping approach to candidate genes or gene pathway analysis that maximizes the coverage at low cost and is amenable to cohort-based studies.

https://ift.tt/2ttriDF

Erratum

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Paediatric traumatic cardiac arrest: a Delphi study to establish consensus on definition and management

Aims

Paediatric traumatic cardiac arrest (TCA) is associated with low survival and poor outcomes. The mechanisms that underlie TCA are different from medical cardiac arrest; the approach to treatment of TCA may therefore also need to differ to optimise outcomes. The aim of this study was to explore the opinion of subject matter experts regarding the diagnosis and treatment of paediatric TCA, and to reach consensus on how best to manage this group of patients.

Methods

An online Delphi study was conducted over three rounds, with the aim of achieving consensus (defined as 70% agreement) on statements related to the diagnosis and management of paediatric TCA. Participants were invited from paediatric and adult emergency medicine, paediatric anaesthetics, paediatric ICU and paediatric surgery, as well as Paediatric Major Trauma Centre leads and representatives from the Resuscitation Council UK. Statements were informed by literature reviews and were based on elements of APLS resuscitation algorithms as well as some concepts used in the management of adult TCA; they ranged from confirmation of cardiac arrest to the indications for thoracotomy.

Results

73 experts completed all three rounds between June and November 2016. Consensus was reached on 14 statements regarding the diagnosis and management of paediatric TCA; oxygenation and ventilatory support, along with rapid volume replacement with warmed blood, improve survival. The duration of cardiac arrest and the lack of a response to intervention, along with cardiac standstill on ultrasound, help to guide the decision to terminate resuscitation.

Conclusion

This study has given a consensus-based framework to guide protocol development in the management of paediatric TCA, though further work is required in other key areas including its acceptability to clinicians.

https://ift.tt/2Icj9st

Effects of hallway/corridor and companions on clinical encounters: a possible explanation

All emergency medicine practitioners will have experienced the results of increased demand and exit block on our EDs. Crowded departments have made practising hallway/corridor-based medicine a daily occurrence. We already know that length of stay in hospital and mortality rates increase with crowding and that working in these conditions1 suggests patients are receiving substandard management. Certainly, there is the loss of privacy which all healthcare systems have gone to great lengths to protect and on which much of our medical teaching is premised.

Stoklosa et al2 describe two distinct non-private clinical encounters, one where the patient was seen and assessed in a hallway and the other when the patient was seen along with a companion. Both which are said to impinge on the physician's assessment of the patient. At closer reading, the premise of the survey is to determine if the assessing physician believes that...

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Abstracts from international Emergency Medicine journals

Editor's note: EMJ has partnered with the journals of multiple international emergency medicine societies to share from each a highlighted research study, as selected by their editors. This edition will feature an abstract from each publication.

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Emergency department overcrowding: a survey among European neurotrauma centres

Background

ED overcrowding is an increasing problem worldwide that may negatively affect quality of care and patient outcomes. We aimed to study ED overcrowding across European centres.

Methods

Questionnaires on structure and process of care, including crowding, were distributed to 68 centres participating in a large European study on traumatic brain injury (Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury).

Results

Of the 65 centres included in the analysis, 32 (49%) indicated that overcrowding was a frequent problem and 28 (43%) reported that patients were placed in hallways 'multiple times a day'; 27 (41%) stated that multiple times a day, there was no bed available when a patient needed to be admitted. Ambulance diversion rarely occurred in the participating centres.

Conclusion

Similar to reports from other parts of the world, ED crowding appears to be a considerable problem in Europe. More research is needed to determine effective ways to reduce overcrowding.

https://ift.tt/2IcUBj9

Essential medicines for emergency care in Africa

Objectives

Essential medicines lists (EMLs) are efficient means to ensure access to safe and effective medications. The WHO has led this initiative, generating a biannual EML since 1977. Nearly all countries have implemented national EMLs based on the WHO EML. Although EMLs have given careful consideration to many public health priorities, they have yet to comprehensively address the importance of medicines for treating acute illness and injury.

Methods

We undertook a multistep consensus process to establish an EML for emergency care in Africa. After a review of existing literature and international EMLs, we generated a candidate list for emergency care. This list was reviewed by expert clinicians who ranked the medicines for overall inclusion and strength of recommendation. These medications and recommendations were then evaluated by an expert group. Medications that reached consensus in both the online survey and expert review were included in a draft emergency care EML, which underwent a final inperson consensus process.

Results

The final emergency care EML included 213 medicines, 25 of which are not in the 2017 WHO EML, but were deemed essential for clinical practice by regional emergency providers. The final EML has associated recommendations of desirable or essential and is subdivided by facility level. Thirty-nine medicines were recommended for basic facilities, an additional 96 for intermediate facilities (eg, district hospitals) and an additional 78 for advanced facilities (eg, tertiary centres).

Conclusion

The 25 novel medications not currently on the WHO EML should be considered by planners when making rational formularies for developing emergency care systems. It is our hope that these resource-stratified lists will allow for easier implementation and will be a useful tool for practical expansion of emergency care delivery in Africa.

https://ift.tt/2JV3wvs

Highlights from this issue

Do EPs change their clinical behaviour in the hallway encounters or when a companion is present? A cross-sectional survey and the commentary by Jacky Hanson and Kirsten Walthall

Privacy is a key element in the process of undertaking a consultation with a patient, as it allows due care and attention to paid to the patient's condition and to their concerns.

This survey (see page 406) was conducted at the 2015 American College of Emergency Physicians Scientific Assembly, by inviting practising ED physicians into a booth at this meeting; participants were asked to consider 22 items to determine if seeing patients in the corridor ('hallway encounters') had any impact on practice including any delay or diagnostic failure, and if yes, then to provide greater detail about the associated problems encountered. Within this survey, physicians were also asked if the presence of a companion altered the nature of the consultation with the patient.

...

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Lower extremity pain and numbness

Clinical introduction

A 45-year-old man with no past medical history presents with bilateral lower extremity pain and perineal numbness after walking 10–15 min. The pain starts in his bilateral buttocks and radiates down into his thigh and into his toes. He has no back pain, fever, difficulty urinating or stooling, incontinence or trauma. Social history is positive for smoking. Physical examination was only remarkable for non-dopplerable lower extremity pulses, and he was unable to ambulate down the ED hallway without becoming symptomatic. Ultrasound of his abdominal aorta (figure 1) was performed.

Figure 1

Transverse view of distal abdominal aorta, just proximal to the bifurcation. (A) The aorta without Doppler. (B) The same image with Doppler mode activated.

Question

What is the most likely diagnosis based on the image?

A. Lumbar stenosis

B. Abdominal aortic aneurysm

C. Aortic thrombus

D. Aortic dissection

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Senior doctor triage (SDT), a qualitative study of clinicians views on senior doctors involvement in triage and early assessment of emergency patients

Introduction

Despite the focus during the last decade on introducing interventions such as senior doctor initial assessment or senior doctor triage (SDT) to reduce emergency department (ED) crowding, there has been little attempt to identify the views of emergency healthcare professionals on such interventions. The aim of this study was to gain an understanding of SDT from the perspective of emergency hospital staff. A secondary aim of this study was to develop a definition of SDT based on the interview findings and the available literature on this process.

Methods

Qualitative semi-structured telephone interviews were conducted with participants of different backgrounds including senior doctors, nurses, paramedics and ED managers. Textual data were analysed using a template analysis approach.

Results

27 participants from 13 EDs across England were interviewed. SDT was viewed as a safety mechanism and a measure to control patient flow. The most prominent positive aspect was the ability to initiate early investigations and treatment. Various shortcomings of SDT were described such as the lack of standardisation of the process and its cost implications. Participants identified a number of barriers to this process including insufficient resources and exit block, and called for solutions focused on these issues. A proposed definition of an 'ideal' SDT was developed where it is described as a systematic brief assessment of patients arriving at the ED by a senior doctor-led team, which takes place in a dedicated unit. The aim of this assessment is to facilitate early investigation and management of patients, early patient disposition and guide junior staff to deliver safe and high-quality clinical care.

Conclusion

This is the first national study to explore the opinions of various emergency and managerial staff on the SDT model. It revealed variable interpretations of this model and what it can and cannot offer. This has led to a standard definition of the SDT process, which can be useful for clinicians and researchers in emergency care.

https://ift.tt/2IbRuYM

End-tidal carbon dioxide output in manual cardiopulmonary resuscitation versus active compression-decompression device during prehospital quality controlled resuscitation: a case series study

Background

Active compression–decompression (ACD) devices have enhanced end-tidal carbon dioxide (ETCO₂) output in experimental cardiopulmonary resuscitation (CPR) studies. However, the results in out-of-hospital cardiac arrest (OHCA) patients have shown inconsistent outcomes, and earlier studies lacked quality control of CPR attempts. We compared manual CPR with ACD-CPR by measuring ETCO₂ output using an audiovisual feedback defibrillator to ensure continuous high quality resuscitation attempts.

Methods

10 witnessed OHCAs were resuscitated, rotating a 2 min cycle with manual CPR and a 2 min cycle of ACD-CPR. Patients were intubated and the ventilation rate was held constant during CPR. CPR quality parameters and ETCO₂ values were collected continuously with the defibrillator. Differences in ETCO₂ output between manual CPR and ACD-CPR were analysed using a linear mixed model where ETCO₂ output produced by a summary of the 2 min cycles was included as the dependent variable, the patient as a random factor and method as a fixed effect. These comparisons were made within each OHCA case to minimise confounding factors between the cases.

Results

Mean length of the CPR episodes was 37 (SD 8) min. Mean compression depth was 76 (SD 1.3) mm versus 71 (SD1.0) mm, and mean compression rate was 100 per min (SD 6.7) versus 105 per min (SD 4.9) between ACD-CPR and manual CPR, respectively. For ETCO₂ output, the interaction between the method and the patient was significant (P<0.001). ETCO₂ output was higher with manual CPR in 6 of the 10 cases.

Conclusions

This study suggests that quality controlled ACD-CPR is not superior to quality controlled manual CPR when ETCO₂ is used as a quantitative measure of CPR effectiveness.

Trial registration number

NCT00951704; Results.

https://ift.tt/2tee7HE

Sex differences in mortality among critically ill children in Pakistan

I read with interest the article on the outcomes of critically ill children in Pakistan.1 There are two surprising findings that the authors did not discuss. First, only 37% of the attending children were female. Second, 59% of all deaths were female. One can calculate the male death rate (8.2%) and the female death rate (20.1%). This means that the relative risk of dying for girls presenting as triage category 1 is 2.44 (2.23–2.76, p<0.0001). I find it perplexing that the authors' analysis of sex differences was limited to reporting a simple sex ratio.

An excess male population does not account for this huge difference in attendance between the sexes. The sex ratio in Pakistan is 1.05 males-to-females,2 equal to the natural sex ratio at birth.3 The male-to-female ratio among children aged 0–14 years is 1.06.2 If the attendance difference is because...

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Corrigendum to “Intelligent Techniques Using Molecular Data Analysis in Leukaemia: An Opportunity for Personalized Medicine Support System”

https://ift.tt/2K9yH5l

One Year of School Comes With an IQ Bump, Meta-Analysis Shows

A year of schooling leaves students with new knowledge, and it also equates with a small but noticeable increase to students' IQ, according to a systematic meta-analysis published in Psychological Science, a journal of the Association for Psychological Science.

"Our analyses provide the strongest evidence yet that education raises intelligence test scores," says psychological scientist Stuart J. Ritchie of the University of Edinburgh. "We looked at 42 datasets using several different research designs and found that, overall, adding an extra year of schooling in this way improved people's IQ scores by between 1 and 5 points."

Research has long shown that years of education and intelligence are correlated but it has been unclear whether this is because education boosts intelligence or because individuals who start off with higher IQ scores are likely to stay in school for longer.

Many individual studies on this question have now been published, and Ritchie and coauthor Elliot Tucker-Drob of the University of Texas at Austin saw an opportunity to clarify the nature of the schooling-IQ relationship:

"We felt the time was right to do a meta-analysis, combining all the previous studies to come up with an overall result for how much education boosts intelligence," Ritchie explains.

The researchers looked at three particular types of quasi-experimental studies from a variety of sources, including published articles, books, preprint articles, working papers, dissertations, and theses.

The first type of study includes data collected from individuals over time, with intelligence measurements obtained before and after individuals complete their education. This allows researchers to adjust for participants' prior intelligence level when examining the association between years of school and later intelligence.

The second type of study takes advantage of "natural experiments" in the form of policy changes that result in individuals staying in school for different lengths of time. In one study, for example, researchers examined data from the 1960s when Norway gradually enacted a new policy that increased the basic education requirement by 2 years, testing whether IQ scores were higher for students who'd been given more compulsory schooling.

In the third study type, researchers use school-admission age cutoffs to compare children who are similar in age but who have different levels of schooling due to their specific birth dates.

To be included in the meta-analysis, each data set had to provide cognitive scores obtained from objective measurement with participants who were 6 or older and cognitively healthy. This yielded 42 data sets from 28 studies collected from a total of 615,812 individuals.

In each of the three types of studies, the researchers found that an additional year of education was associated with an increase in IQ that ranged from 1.197 IQ points to 5.229 IQ points. In combination, the studies indicated that an additional year of education correlated with an average increase of 3.394 IQ points.

"The most surprising thing was how long-lasting the effects seemed to be, appearing even for people who completed intelligence tests in their 70s and 80s," Ritchie says. "Something about that educational boost seemed to be beneficial right across the lifespan."

The researchers note that each type of study has strengths and weaknesses, and the findings raise several new questions that future research will have to address. For example, does an additional year of school just make students better at taking tests or does it produce an underlying neurobiological change? What are the specific parts of the educational experience that are most responsible for the change? And what are the limits of education's effect?

"A crucial next step will be to uncover the mechanisms of these educational effects on intelligence in order to inform educational policy and practice," they conclude.

E.M. Tucker-Drob's contribution to this study was supported by National Institutes of Health (NIH) Research Grant R01HD083613. The Population Research Center at the University of Texas at Austin is supported by NIH Grant R24HD042849.

All meta-analytic data and all codebooks and analysis scripts (for Mplus and R) are publicly available via the Open Science Framework. The complete Open Practices Disclosure for this article is available online. This article has received the badge for Open Data.

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Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming

Single-cell RNA sequencing analysis of chemical reprogramming depicts its trajectory and highlights dynamic intermediate cellular programs resembling early embryonic signatures. Zhao et al. apply these insights to develop a faster reprogramming system.

https://ift.tt/2yti4NF

hPSC Modeling Reveals that Fate Selection of Cortical Deep Projection Neurons Occurs in the Subplate

Ozair et al. show that major classes of cortical DPNs can be specified from subplate neurons (SPNs) derived from hPSCs by modulating post-mitotic WNT signaling. The findings indicate that SPNs have evolved in primates as an important contributor to cortical lamination. These findings have implications for understanding neurodevelopmental disorders.

https://ift.tt/2lpWdNO

Chronic Liver Injury Induces Conversion of Biliary Epithelial Cells into Hepatocytes

Understanding cellular sources of hepatocyte regeneration is critical for developing effective therapies for chronic liver diseases. Xie and colleagues show that severe liver injuries can, without genetic interventions, induce biliary epithelial cells to significantly contribute to hepatocyte regeneration through direct lineage conversion.

https://ift.tt/2yvpmAq

Too Much Carrot and Not Enough Stick in New Stem Cell Oversight Trends

Regulators are now more often distinguishing between perceived good citizens and "bad actors" in stem cell and regenerative medicine clinical research, resulting in relatively more polar, carrot-and-stick oversight approaches. Here, I discuss why there may be too much carrot and not enough stick by regulators for effective enforcement.

https://ift.tt/2lqCMEy

Corrigendum to “The Therapeutic Effects of a Traditional Chinese Medicine Formula Wuzi Yanzong Pill for the Treatment of Oligoasthenozoospermia: A Meta-Analysis of Randomized Controlled Trials”

https://ift.tt/2K8AmoO

How do ED patients with criminal justice contact compare with other ED users? A retrospective analysis of ED visits in California

Objective

To assess the patterns of emergency department (ED) utilisation among those with and without criminal justice contact in California in 2014, comparing variation in ED use, visit frequency, diagnoses and insurance coverage.

Design

Retrospective, cross-sectional study.

Setting

Analyses included ED visits to all licensed hospitals in California using statewide data on all ED encounters in 2014.

Participants

Study participants included 3 757 870 non-elderly adult ED patients who made at least one ED visit in 2014.

Primary and secondary outcome measures

We assessed the patterns and characteristics of ED visits among those with criminal justice contact—patients who were either admitted to or discharged from the ED by a correctional institution—with patients who did not have criminal justice contact recorded during an ED visit.

Results

ED patients with criminal justice contact had higher proportions of frequent ED users (27.2% vs 9.4%), were at higher risk of an ED visit resulting in hospitalisation (26.6% vs 15.2%) and had higher prevalence of mental health conditions (52.8% vs 30.4%) compared with patients with no criminal justice contact recorded during an ED visit. Of the top 10, four primary diagnoses among patients with criminal justice contact were related to behavioural health conditions, accounting for 19.0% of all primary diagnoses in this population. In contrast, behavioural health conditions were absent from the top 10 primary diagnoses in ED patients with no observed criminal justice contact. Despite a high burden of disease, a lack of health insurance coverage was more common among those with criminal justice contact than those without (41.3% vs 14.1%).

Conclusions

Given that a large proportion of ED patients with criminal justice contact are frequent users with considerable mental health conditions, current efforts in California's Medicaid programme to identify individuals in need of coordinated services could reduce costly ED utilisation among this group.

https://ift.tt/2K5M86B

Improved correlation of urinary cytology specimens using The Paris System in biopsy‐proven upper tract urothelial carcinomas

Cancer Cytopathology, EarlyView.


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Variational Algorithms for Analyzing Noisy Multistate Diffusion Trajectories

Single-particle tracking offers a noninvasive high-resolution probe of biomolecular reactions inside living cells. However, efficient data analysis methods that correctly account for various noise sources are needed to realize the full quantitative potential of the method. We report algorithms for hidden Markov-based analysis of single-particle tracking data, which incorporate most sources of experimental noise, including heterogeneous localization errors and missing positions. Compared to previous implementations, the algorithms offer significant speedups, support for a wider range of inference methods, and a simple user interface.

https://ift.tt/2MMsN8L

Rhabdomyolysis: An Unusual Presentation of Mycoplasma pneumoniae Infection in an Adult—A Case Report and Literature Review

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia, and many extrapulmonary manifestations have been described, but rhabdomyolysis is infrequently reported in adults. Of the few cases that have been reported in adults, it was almost exclusively seen when pneumonia was present. We report a case of a 30-year-old male who came in with complaints of fever and myalgia for three days. Immunoglobulin M antibodies for Mycoplasma pneumoniae were positive and trending up, despite having no radiographic evidence of pneumonia on chest X-ray or CT scan. He was treated successfully with levofloxacin and intravenous hydration. Later, his condition was clinically and biochemically improved, and he was discharged. Our patient did not present with typical respiratory tract symptoms of a mycoplasma infection. In addition, there was an absence of pneumonia on imaging, suggesting that rhabdomyolysis secondary to mycoplasma might be underdiagnosed and go untreated in the setting of low clinical suspicion. Upon review of the literature, there is only one other case of mycoplasma infection where rhabdomyolysis occurred in the absence of pneumonia. However, the degree of rhabdomyolysis in our case was much more severe. Although rare, when faced with rhabdomyolysis, Mycoplasma pneumoniae should be kept as a differential diagnosis even in the absence of pneumonia on radiological imaging.

https://ift.tt/2KeZy0d

Cancers, Vol. 10, Pages 210: Genomic Landscapes of EBV-Associated Nasopharyngeal Carcinoma vs. HPV-Associated Head and Neck Cancer

Cancers, Vol. 10, Pages 210: Genomic Landscapes of EBV-Associated Nasopharyngeal Carcinoma vs. HPV-Associated Head and Neck Cancer

Cancers doi: 10.3390/cancers10070210

Authors: Hoi-Lam Ngan Lan Wang Kwok-Wai Lo Vivian Wai Yan Lui

: Epstein-Barr virus-positive nasopharyngeal carcinoma (EBV(+) NPC), and human papillomavirus-positive head and neck squamous cell carcinoma (HPV(+) HNSCC) are two distinct types of aggressive head and neck cancers with early age onsets. Their recently identified genomic landscapes by whole-exome sequencing (WES) clearly reveal critical roles of: (1) inflammation via NF-kB activation, (2) survival via PI3K aberrations, and perhaps (3) immune evasion via MHC loss in these cancers as summarized in this review. Immediate outcomes of these WES studies include the identification of potential prognostic biomarkers, and druggable events for these cancers. The impact of these genomic findings on the development of precision medicine and immunotherapies will be discussed. For both of these cancers, the main lethality comes from metastases and disease recurrences which may represent therapy resistance. Thus, potential curing of these cancers still relies on future identification of key genomic drivers and likely druggable events in recurrent and metastatic forms of these intrinsically aggressive cancers of the head and neck.

https://ift.tt/2K4iICh

A case of antiepiligrin cicatricial pemphigoid with extensive cutaneous erosions mimicking pemphigus vulgaris

Cicatricial pemphigoid (CP) is a chronic, autoimmune, subepidermal blistering disease with predominant mucosal involvement. In this article, we report a young patient with mucosal and extensive cutaneous involvement in the form of large erosions mimicking those of pemphigus vulgaris thus leading to diagnostic dilemma. We were unable to find any other previous reports with such extensive cutaneous erosions mimicking those of pemphigus vulgaris. Laminin 5 was the antigen found on knockout substrate testing. Antiepiligrin CP is a distinct subtype of CP with antibodies against laminin 5. This subtype is mostly associated with malignancy but no underlying malignancy was found in our case. Present report also highlights the importance of knockout substrate testing when immunoblot is not available.

https://ift.tt/2JXMFIs

Usual suspects: the foreign bodies of the aerodigestive tract

This case series is about four different foreign bodies lodged in different locations of the aerodigestive tract. All four cases had delayed diagnosis due to inconspicuous history. Radiology in the form of computed tomography aided the appropriate diagnosis in most of these cases. Though all four patients have been successfully managed by removal of foreign body, not all of them have identical outcomes. A brief discussion about predictive factors in the fish bone foreign body has been included. The authors also discuss certain critical aspects of the management, which may aid in reducing the morbidity. We emphasise on the high index of suspicion in peculiar cases and on the low threshold for radiological investigation in doubtful clinical scenarios.

https://ift.tt/2MbVyLa

Numb chin syndrome as a presenting symptom of diffuse large B-cell lymphoma with secondary myelofibrosis

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma that classically presents with rapidly enlarging lymph nodes. We present a 59-year-old man with unusual clinical presentation of numb chin syndrome (NCS) as the first symptom of disease. On evaluation, he was found to have diffuse extranodal skeletal involvement in the form of lytic-sclerotic lesions and minimal lymphadenopathy. Bone marrow biopsy revealed a poorly differentiated tumour with infarction and extensive myelofibrosis. This was subsequently proven to be DLBCL of germinal centre type on immunohistochemical stain. NCS should alarm the clinician to investigate for an advanced underlying malignancy. Extensive myelofibrosis, though described in carcinomas and low grade lymphomas, may also be seen in high grade DLBCL.

https://ift.tt/2JSK8PA

Acute renal artery embolisation: role of local catheter-based intra-arterial thrombolysis

A 45-year-old man without previous comorbidity presented to us with acute onset right-sided flank pain for last 14 hours. His general physical and systemic examination was unremarkable, and there were no clinical signs of peritonitis. The ultrasonography did not reveal any evidence of nephrolithiasis or hydronephrosis. His contrast-enhanced CT scan revealed hypoattenuated areas of right kidney and evidence of right renal artery thrombosis. He was immediately shifted to cardiac catheterisation lab, and his renal angiography showed thrombotic occlusion of right renal artery. The bolus dose of streptokinase (250 000 IU) was given locally in renal artery by right judkins catheter followed by systemic infusion of streptokinase (100 000 IU/hour) for 24 hours. After that he was started on low molecular weight heparin. Repeat renal angiography done after 5 days showed completely normal right renal artery. His cardiac and thrombophilia work up was negative, and he was discharged on antiplatelets, oral anticoagulants and statins.

https://ift.tt/2IcbwCx

An unusual case of leptomeningeal carcinomatosis in a patient with primary adenocarcinoma of the lung

A 72-year-old man was brought to the emergency department with acute onset confusion and haemoptysis. Chest X-ray showed a possible lung mass, while CT head showed a fluid-filled, space-occupying lesion (SOL) in the right frontal lobe of the brain. MRI head indicated that this SOL had spilt its contents into the subarachnoid and intraventricular spaces. Due to a fluctuating Glasgow Coma Scale (GCS), the patient underwent emergency debulking. Macroscopically, a frail-walled cystic tumour filled with straw-coloured fluid was noted; histology confirmed metastasis from a primary lung adenocarcinoma. Whole brain radiotherapy was given, with a view to commence systemic therapy. The patient, however, deteriorated and unfortunately passed away a few weeks after completing radiotherapy. This patient presented with leptomeningeal metastasis as the first presentation of a lung adenocarcinoma, and had a highly unusual mechanism by which leptomeningeal spread had occurred, with metastatic brain tumour spilling its contents into the meningeal spaces.

https://ift.tt/2JYL6Kc

Necrotising fasciitis as a complication of primary varicella infection in an immunocompetent child

Necrotising fasciitis (NF) is an infrequent yet significant complication of primary varicella infection in immunocompetent children. We report a case of a 4-year-old girl who presented three days into her chicken pox illness, with a rapidly progressing, severely tender erythematous rash surrounding one chicken pox lesion on her thigh. She required intravenous antibiotics, two surgical debridements, a skin graft and a prolonged stay in the paediatric intensive care unit, but ultimately we were able to save her life and limb. NF is a rare complication of chicken pox that has high morbidity and mortality that requires prompt and specific treatment.

https://ift.tt/2IedpPi

Heart transplant recipient with mycophenolate mofetil-induced colitis: the great imitator

In this article, we report a case of a 55-year-old male heart transplant recipient who presented with diarrhoea. An extensive workup for infectious diseases was negative. The patient had a colonoscopy with biopsies showing colitis that mimicked graft-versus-host disease on histopathology. After excluding other potential causes and excluding acute cellular rejection, mycophenolate mofetil was discontinued, and the patient had significant clinical improvement with increased appetite and weight gain.

https://ift.tt/2JXZzWG

Abscess originating from osteomyelitis as a cause of lower urinary tract symptoms (LUTS) and acute urinary retention

Lower urinary tract symptoms (LUTS) are a common complaint in the general population with great impact on the quality of life. Besides the classical pathologies, there are less common causes that must be considered in the treatment approach for patients with LUTS. We present the case of a 30-year-old patient with multiple emergency department episodes with dysuria, urinary frequency, suprapubic pain and an episode of acute urinary retention. The blood and urine tests only revealed increased systemic inflammatory parameters. The ultrasound examination showed thickening of the bladder wall, and the CT scan revealed a retropubic abscess originating from a pubic symphysis osteomyelitis. A percutaneous drainage was performed and, after empirical antibiotic therapy, there was complete resolution of the clinical picture.

https://ift.tt/2I9XYqY

Unilateral pulmonary vein atresia: diagnostic dilemma unfolded on imaging

Unilateral pulmonary vein atresia is a rare entity, usually congenital in origin. It is thought to result from failure of incorporation of common pulmonary vein to left atrium. Patients often present with recurrent chest infections and haemoptysis during infancy or early childhood. Associated anomalies are commonly present in these cases. Pulmonary angiography is generally used for definitive diagnosis; however, characteristic imaging findings on latest multislice CT can be virtually diagnostic.

https://ift.tt/2thl76n

Paraneoplastic cerebellar degeneration with bilateral facial palsy: a rare primary presentation of breast cancer

Paraneoplastic cerebellar degeneration is a rare dysfunction of the cerebellum associated with malignancy. Nevertheless, it is the most common paraneoplastic syndrome affecting the brain. A 50-year-old woman presented to the neurology outpatient department (OPD) with symptoms of cerebellar dysfunction since 4 months and complaints of a painless lump in the right breast and drooling from mouth since 1 month. Examination revealed classical signs of cerebellar dysfunction and a 5x5 cm lump in the right breast with a single right axillary lymph node. Serum anti-Yo antibody titre was strongly positive. The patient was referred to General Surgery OPD for opinion. After establishing the diagnosis of right breast carcinoma; she underwent a right modified radical mastectomy. She was referred to the oncologist for chemo/radiotherapy but because of poor performance status, only symptomatic treatment was pursued. Follow-up till now shows no improvement in the neurological dysfunction.

https://ift.tt/2MaZYSt

Oncocytoma of the adrenal gland in Birt-Hogg-Dube syndrome

A 32-year-old man was referred to our surgical unit with a left adrenal lesion. He was previously diagnosed with Birt-Hogg-Dube syndrome after presenting with a left pneumothorax and an incidental finding of a right apical lung mass. This syndrome is characterised commonly by benign skin hamartomas, recurrent pneumothoraces and an increased risk of renal tumours. He was unable to tolerate a biopsy of his lung lesion, however, this lung lesion was thought to be benign. Given the size of his adrenal lesion and radiological appearances, we performed a laparoscopic left adrenalectomy. Pathology confirmed that based on morphological appearances and immunohistochemical staining, this may represent an oncocytic tumour of the adrenal gland. This is only the third published case of an oncocytic tumour of the adrenal gland in a patient with Birt-Hogg-Dube syndrome.

https://ift.tt/2tgplv8

Wellens syndrome: a close call

We describe a case of a middle-aged man who presented to the emergency department with typical anginal chest pains and found to have new, deeply inverted T-waves on ECG consistent with Wellens' syndrome. Similar to the description by Wellens et al, a critical 99% stenosis of the proximal left anterior descending artery was indeed confirmed by coronary angiography and successfully treated with drug-eluting stent. It is very important that physicians recognise this ECG finding as a harbinger of a serious cardiovascular condition and the necessity for an early invasive cardiac catheterisation.

https://ift.tt/2IerZGe

Apprehension in patients mind: leading to myiasis

Description

A 65-year-old man had a history of acute urinary retention for which suprapubic catheterisation (SPC) was performed, following failed attempts at per urethral catheterisation by a local practitioner 3 months previously. He also had a history of hesitancy and intermittency for the past 1 year. He now presented with maggots discharging from the SPC site (figures 1 and 2). On taking a detailed history, he mentioned lack of local hygiene due to fear of dislodgement of SPC. There was no history of diabetes mellitus, surgical intervention or immune-compromised status.

Figure 1

Clinical photograph of the patient showing the suprapubic catheterisation site wound with maggots inside it.

Figure 2

Clinical photograph showing closer view of the suprapubic catheterisation site wound with maggots.

Per urethral catheterisation was attempted over a guide wire that was successful. Then his SPC was removed...

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Femoral nerve paralysis complicating a post-traumatic iliopsoas haematoma

Paralysis of the femoral nerve secondary to iliopsoas haematoma is a rare post-traumatic complication. Because of the large differential diagnosis, a high level of suspicion is required for its early recognition. Treatment modalities are controversial due to the rarity of this entity. An 18-year-old student presented with complete paralysis of the knee extensors and a sensory deficit on the anterior side of the thigh 5 weeks after a sport accident. MRI of the lesser pelvis showed an iliopsoas haematoma. Surgical decompression was performed and recovery was complete at 6 months of follow-up.

https://ift.tt/2IaiI23

Differential Expression of TXNIP Isoforms in the Peripheral Leukocytes of Patients with Acute Myocardial Infarction

Background. Acute myocardial infarction (AMI) is the most serious type of coronary atherosclerotic heart disease (CAD). The pathological changes are characterized by atherosclerosis. Oxidative stress plays an important role in atherosclerosis. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor and regulator of thioredoxin, could bind thioredoxin to regulate its expression and antioxidant activity negatively. The NCBI data show that there are two isoforms in TXNIP gene, namely, TXNIP1 and TXNIP2. Our previous studies have shown that TXNIP expression levels in patients with unstable angina pectoris (UAP) were increased compared with controls (CTR). However, no upregulation of TXNIP was detected in AMI patients. Methods. The leucocytes were isolated from peripheral venous blood, and total RNA of the leucocytes was extracted. Then, real-time quantitative PCR was performed. Results. mRNA levels of TXNIP2 in AMI were significantly increased compared with CTR (). However, the expression of TXNIP1 was downregulated in AMI, but the difference was not statistically significant (). Logistic regression analysis showed that TXNIP2 mRNA levels were significantly associated with AMI (OR = 2.207, ). Conclusions. The expression of TXNIP2, not TXNIP1, is upregulated in leukocytes of AMI patients, indicating that only TXNIP2 in circulating leucocytes may be involved in the pathogenesis of AMI.

https://ift.tt/2I8LujC

The Effects of the Honey-Roasting Process on the Pharmacokinetics of the Six Active Compounds of Licorice

A convenient UPLC-MS/MS method was established to determine the contents of six bioactive compounds, namely, liquiritin apioside, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and glycyrrhetinic acid, in rat plasma and their pharmacokinetics. By comparing the pharmacokinetic parameters of these compounds in rats by orally administering raw and honey-roasting licorice, the of isoliquiritin showed a significant decrease, while the showed no significant differences. The and of isoliquiritigenin were increased by 49.3% and 42.7% over those of the raw licorice group, respectively. These results indicate that the absorption of isoliquiritin in rats was reduced while the absorption of isoliquiritigenin was promoted in the honey-roasting process. These results may provide one explanation as to why licorice is more able to relieve cough, while honey-roasting licorice is better at invigorating qi and restoring pulse. Furthermore, the of glycyrrhetinic acid was increased, suggesting that it may enhance the tonic effect of licorice. Additionally, the amount of honey added in the honey-roasting process influenced the pharmacokinetic parameters of the six compounds whose absorption decreased when the 50% honey-roasting licorice water decoction was administered. These results provide an experimental basis for studying the influence of licorice processing on bioactive compound pharmacokinetics.

https://ift.tt/2K9HlRq

Issue Highlights

Barrett's esophagus is a known risk factor for esophageal adenocarcinoma. Current clinical practice guidelines recommend endoscopic surveillance for Barrett's esophagus patients to allow early detection of dysplasia or carcinoma, but endoscopic surveillance of Barrett's esophagus is inefficient. Risk stratification of patients might improve the effectiveness of surveillance. In this issue of Clinical Gastroenterology and Hepatology, Krishnamoorthi and colleagues1 reported results of a systematic review and meta-analysis of 20 cohort studies including approximately 75,000 patients and found increasing age, male gender, smoking, increasing Barrett's esophagus segment length, and low-grade dysplasia were associated with increase in risk of progression of Barrett's esophagus to high-grade dysplasia or esophageal adenocarcinoma.

https://ift.tt/2M7DpxU

Training the Endo-Athlete: An Update in Ergonomics in Endoscopy

As physicians, we work hard to take excellent care of our patients. Years of thoughtful practice and continuous learning allow us to deliver the best that medicine can provide. We often take poor care of ourselves, which can lead to burnout and physical injuries. As gastroenterologists, we spend substantial time performing endoscopic procedures that require repetitive motions such as flexion and extension on the wrist and fingers and torsional movements of the right hand, which may lead to overuse injuries.

https://ift.tt/2JTQUoc

Editorial Board

https://ift.tt/2K7JRED

Contents

https://ift.tt/2JTQNJi

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.

https://ift.tt/2MdjZYL

Reply

We welcome the interest by Fung et al1 in our systematic review and meta-analysis on the impact of race and ethnicity on phenotype and outcomes in patients with inflammatory bowel diseases (IBD) (Crohn's disease, ulcerative colitis) published in this journal.2 They raise a few different points. First, they suggest that the higher frequency of upper gastrointestinal tract involvement in Crohn's disease in Asian population may be due to greater use of upper gastrointestinal endoscopies in Asia compared with Western populations.

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Elsewhere in The AGA Journals

https://ift.tt/2MdjRIL

On the Visual Diagnosis of Human Taeniasis by Capsule Endoscopy

Le Mouel et al1 recently identified a case of human taeniasis caused by Taenia saginata by means of third-generation capsule endoscopy. The authors of the article provide 4 illustrative images of the tapeworm and, specifically, gravid proglottids containing a branched uterus are shown. Because after endoscopy no additional confirmatory diagnostic method is specified, we reckon that the images of this branched uterus were meaningful enough for the specific tapeworm identification. Capsule endoscopy is a diagnostic method with high sensitivity.

https://ift.tt/2MICBRr

Reply

We thank Parker et al1 for their interest in our study. The authors point out that subjects in our study had a high mortality in the control group as well as a higher survival in the experimental group1 than the reported literature.2 The systematic review by Parker et al provided details on mortality in alcoholic hepatitis. However, it did not present the median Maddrey's discriminant function scores in the included studies.2 For instance, in one study, pentoxifylline therapy was associated with short term mortality rate of 25% in patients with severe alcoholic hepatitis.

https://ift.tt/2MaNYAo

High Mortality in Control Group of Trial of Granulocyte Colony-Stimulating Factor in Alcoholic Hepatitis

We read with interest the report by Singh et al1 of their randomized, open-label trial of granulocyte colony-stimulating factor (GCSF), alone or in combination with N-acetylcysteine, in the treatment of acute severe alcoholic hepatitis.

https://ift.tt/2JXmaD1

Cover

https://ift.tt/2K2xV70

Response to Terlipressin in Hepatorenal Syndrome: Predict to Prognosticate!

I read with great interest the review article published recently by Mindikoglu et al1 and would like to congratulate the authors on their eloquent update on hepatorenal syndrome (HRS). As pointed out distinctly, HRS continues to be a significant problem faced by clinicians who are actively involved in managing patients with advanced liver disease with ascites. HRS type 1 is a type of rapidly progressive acute kidney injury and is associated with a median survival of only approximately 4 weeks. It thus becomes extremely crucial to predict the subset of patients who are likely to be nonresponsive to vasoconstrictor therapy, which would help treating clinicians to accurately prognosticate and counsel the patient and plan simultaneously for an early liver transplant.

https://ift.tt/2JUjHZP

Information for Authors

Clinical Gastroenterology and Hepatology (CGH) publishes clinical articles on all aspects of the digestive system, including the liver and pancreas. The types of articles Clinical Gastroenterology and Hepatology publishes include original papers, review articles, and special category manuscripts. Manuscripts must be prepared in accordance with the "Uniform Requirements for Manuscripts Submitted to Biomedical Journals" developed by the International Committee of Medical Journal Editors (ICMJE) (http://www.icmje.org).

https://ift.tt/2MaNFWg

Fatal Acinetobacter baumanii Necrotizing Fasciitis following Open Reduction Internal Fixation in a Polytrauma Patient

Necrotizing fasciitis is an uncommon and potentially fatal infection that can affect the epidermis, dermis, and more commonly the subcutaneous, fascia, and muscle layers. NF is usually caused by toxin-producing bacteria with a relatively fast progression associated with severe surrounding tissue destruction. Early diagnosis and management are crucial factors for survival. Broad-spectrum antibiotics along with surgical debridement, sometimes multiple, are needed in order to stop or slow down the progression of NF. Despite optimal care, necrotizing fasciitis remains a highly morbid condition with a high mortality rate. We present a case of a 28-year-old male patient with rapidly developing fatal A. baumannii associated with necrotizing fasciitis, after open reduction and internal fixation (ORIF) of multiple fractures after polytrauma.

https://ift.tt/2MFgD1D

Combined physiologic and excisional therapies improve cancer‐related lymphedema outcomes

CA: A Cancer Journal for Clinicians, EarlyView.


https://ift.tt/2K2xSIm

T-Synthase Deficiency Enhances Oncogenic Features in Human Colorectal Cancer Cells via Activation of Epithelial-Mesenchymal Transition

Background. Immature truncated O-glycans such as Tn antigen are frequently detected in human colorectal cancer (CRC); however, the precise pathological consequences of Tn antigen expression on CRC are unknown. T-synthase is the key enzyme required for biosynthesis of mature O-glycans. Here we investigated the functional roles of Tn antigen expression mediated by T-synthase deficiency in CRC cells. Methods. To knock out T-synthase, we used CRISPR-Cas9 technology to target C1GALT1, the gene encoding T-synthase, in a CRC cell line (HCT116). Deletion of T-synthase was confirmed by western blotting, and expression of Tn antigen was determined by flow cytometry in HCT116 cells. We then assessed the biological effects of T-synthase deficiency on oncogenic behaviors in HCT116 cells. Furthermore, we analyzed the mechanistic role of T-synthase deficiency in cancer cells by determining the epithelial-mesenchymal transition (EMT) pathway. Results. We showed that forced knockout of T-synthase in HCT116 cells significantly induced Tn antigen expression, which represented the occurrence of aberrant O-glycosylation. Loss of T-synthase significantly enhanced cell proliferation and adhesion, as well as migration and invasiveness in culture. More importantly, we demonstrated that T-synthase deficiency directly induced classical EMT characteristics in cancer cells. E-cadherin, a typical epithelial cell marker, was markedly decreased in T-synthase knockout HCT 116 cells, accompanied by an enhanced expression of mesenchymal markers including snail and fibronectin (FN). Conclusions. These findings indicate that T-synthase deficiency in CRC cells not only is responsible for aberrant O-glycosylation, but also triggers the molecular process of EMT pathway, which may translate to increased invasiveness and metastasis in cancers.

https://ift.tt/2KbGn7l

Breast‐conserving surgery followed by whole‐breast irradiation offers survival benefits over mastectomy without irradiation

BJS, EarlyView.


https://ift.tt/2I9FAie

Accuracy of printed casts generated from digital implant impressions versus stone casts from conventional implant impressions: A comparative in vitro study

Clinical Oral Implants Research, EarlyView.


https://ift.tt/2IaoS2l

Sphingolipid metabolism – an ambiguous regulator of autophagy in the brain

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2I8e04J

Pathological manifestations of Farber disease in a new mouse model

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2KbfHUi

Potential Antiproliferative Activity and Evaluation of Essential Oil Composition of the Aerial Parts of Tamarix aphylla (L.) H.Karst.: A Wild Grown Medicinal Plant in Jordan

Essential (volatile) oil from aerial parts of Tamarix aphylla (L.) H.Karst. (Tamaricaceae) grown wild in Jordan was hydrodistilled by Clevenger apparatus and analyzed by means of GC and GC-MS techniques. In vitro screening of potential cytotoxicity of the aqueous (AE) and ethanol (EE) extracts was also evaluated against human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (Caco-2), and pancreatic carcinoma (Panc-1) cancer cell lines as well as normal human fibroblasts. GC-MS analysis of T. aphylla EO revealed its richness in nonterpenoid nonaromatic hydrocarbons (52.39%), with predominance of 6,10,14-trimethyl-2-pentadecanone as the principal component. Biologically, the plant extracts exhibited cytotoxicity effects in dose-dependent manner against most of the tested cell lines, but potent effects were only predicted against MCF-7 cells with IC50 values of 2.17 ± 0.10 and 26.65 ± 3.09 μg/mL for T. aphylla AE and EE, respectively. T. aphylla AE demonstrated a comparable cytotoxic effect with that offered by the control drug cisplatin (IC50 value of 1.17 ± 0.13 μg/mL), even with higher safety profile against normal fibroblast cells (IC50 values of T. aphylla AE versus cisplatin: 79.99 ± 4.90 versus 9.08 ± 0.29 μg/mL). T. aphylla extracts could be a valuable source for cytotoxic agents with high safety and selective cytotoxicity profiles. Unfortunately, no antiproliferative potential against Caco-2 or Panc-1 cancer cell lines was detected at a concentration less than 30 μg/mL.

https://ift.tt/2I9zbmU

Anti-Inflammatory Effect of Gamisoyo-San in an Animal Model of Amyotrophic Lateral Sclerosis

Inflammation is considered a critical factor in the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to evaluate the effect of the herbal formula Gamisoyo-San (GSS) on the muscles of transgenic mice, a mouse model of ALS, by examining the tissue expression of inflammation- and oxidative stress-related proteins. The mice were randomly divided into three groups: nontransgenic mice (non-Tg, n = 4), transgenic mice (Tg, n = 4), and GSS-treated transgenic mice (Tg+GSS, n = 4). Eight-week-old female transgenic mice were fed GSS (1 mg/g body weight) for 6 weeks. Gastrocnemius (GA) tissues were analyzed for inflammatory proteins [CD11b and toll-like receptor 4 (TLR4)] and oxidative stress-related proteins [heme oxygenase 1 (HO1) and ferritin] by western blot analysis. Administration of GSS significantly reduced the level of inflammation- and oxidative stress-related proteins in transgenic mice. GSS ameliorated inflammation by downregulating TLR4 and CD11b expression and regulated iron homeostasis in the GA muscle of mice. GSS could help reduce inflammation by regulating immune reactions in patients with ALS. To the best of our knowledge, this is the first study to demonstrate the effect of GSS on muscle inflammation in an ALS animal model.

https://ift.tt/2Kbfvo2

Physical Injury, Health, and Well-Being: Role of Stress Perception

Publication date: Available online 20 June 2018
Source:Injury
Author(s): Irit Heruti, Sigal Levy, Ronit Avitsur
ObjectivePhysical injuries are common occurrences that can have substantial implications for mental health and well-being. Ample studies indicated that increased levels of perceived stress is associated with increased prevalence of general health problems, as well as reduced health-related quality of life. Thus, the goal of the present study was to examine the long-lasting association between bodily injuries and general health. In addition, the role of stress perception in moderating the association between injury and general health was assessed.MethodsTwo-hundred and forty victims of past injury and 251 non-injured participants completed a self-report health inventory questionnaire assessing illness prevalence during the six-month period prior to the study. In addition, they completed the short-form Medical Outcomes Survey (MOS SF-36) questionnaire and the Perceived Stress Scale.ResultsVictims of past injuries reported higher incidences of illness, mainly upper respiratory infections and fever, compared to non-injured participants. In addition, injured participants reported poorer perceived health status, including reduced general health, physical functioning, and health beliefs. Perceived stress levels were similar in injured and non-injured participants, however, correlations between perceived stress and self-reported medical outcomes were stronger in injured participants compared to non-injured controls.ConclusionsPast physical injuries are associated with increased incidence of general health concerns and poorer health-related well-being. Moreover, injured individuals do not report increased stress perception; however, when stressed, injured individuals are more affected and health-related quality of life is reduced. Promoting well-being in individuals who have suffered a significant injury is, thus, a clinical necessity and a pressing social priority. This study highlights the role of stress perception in the association between physical injury and health, and may assist in providing better multi-disciplinary care for the injured.



https://ift.tt/2yxeXUI

Response to the letter by Scorza et al

Acta Neurologica Scandinavica, EarlyView.


https://ift.tt/2tbD46r

In brief: Sudden unexpected death in Parkinson's disease

Acta Neurologica Scandinavica, EarlyView.


https://ift.tt/2yqqXY6

Pentameric last‐digit preference and stage border avoidance in pathology measurement

Histopathology, EarlyView.


https://ift.tt/2I9Xb9E

Norcantharidin enhances antitumor immunity of GM‐CSF prostate cancer cells vaccine by inducing apoptosis of regulatory T cells

Cancer Science, EarlyView.


https://ift.tt/2K9cFj7

Capabilities of the Monte Carlo Simulation Codes for Modeling of a Small Animal SPECT Camera

Abstract

Purpose

This study aims to compare Monte Carlo-based codes' characteristics in the determination of the basic parameters of a high-resolution single photon emission computed tomography (HiReSPECT) scanner.

Methods

The geometry of this dual-head gamma camera equipped with a pixelated CsI(Na) scintillator and lead hexagonal hole collimator were accurately described in the GEANT4 Application for the Tomographic Emission (GATE), Monte Carlo N-particle extended (MCNP-X), and simulation of imaging nuclear detectors (SIMIND) codes. We implemented simulation procedures similar to the experimental test for calculation of the energy spectra, spatial resolution, and sensitivity of HiReSPECT by using ^99mTc sources.

Results

The energy resolutions simulated by SIMIND, MCNP-X, and GATE were 17.53, 19.24, and 18.26%, respectively, while it was calculated at 19.15% in experimental test. The average spatial resolutions of the HiReSPECT camera at 2.5 cm from the collimator surface simulated by SIMIND, MCNP-X, and GATE were 3.18, 2.9, and 2.62 mm, respectively, while this parameter was reported at 2.82 mm in the experiment test. The sensitivities simulated by SIMIND, MCNP-X, and GATE were 1.44, 1.27, and 1.38 cps/μCi, respectively, on the collimator surface.

Conclusions

Comparison between simulation and experimental results showed that among these MC codes, GATE enabled to accurately model realistic SPECT system and electromagnetic physical processes, but it required more time and hardware facilities to run simulations. SIMIND was the most flexible and user-friendly code to simulate a SPECT camera, but it had limitations in defining the non-conventional imaging device. The most important characteristics like time and speed of simulation, preciseness of results, and user-friendliness should be considered during simulations.

https://ift.tt/2lpsJzk

Measurement of Peroxide Values in Oils by Triphenylphosphine/Triphenylphosphine Oxide (TPP/TPPO) Assay Coupled with FTIR‐ATR Spectroscopy: Comparison with Iodometric Titration

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2llg40u

Interactions Between Hammer Mill Crushing Variables and Malaxation Time During Continuous Olive Oil Extraction

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2tqbEsU

Quantification of Phorbol Esters in Jatropha curcas by HPLC‐UV and HPLC‐ToF‐MS with Standard Addition Method

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2lpzMbu

Identification of Phytyl Vaccinate as a Major Component of Wax Ester Fraction of Extra Virgin Olive Oil

European Journal of Lipid Science and Technology, EarlyView.


https://ift.tt/2tsBOuK

Optic disc vessel density in nonglaucomatous and glaucomatous eyes: an enhanced-depth imaging optical coherence tomography angiography study

https://ift.tt/2tqQWsB

Celastrol improves the therapeutic efficacy of EGFR-TKIs for non-small-cell lung cancer by overcoming EGFR T790M drug resistance

The development of resistance to therapy continues to be a serious clinical problem in lung cancer management. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is one of the most common chemotherapy drugs to treat non-small-cell lung cancer. However, almost all treatments fail after ∼1 year of treatment because of drug tolerance, probably occurring from the threonine 790 mutation (T790M) of the EGFR, resulting in overactivation of the EGFR. Celastrol is a natural compound that exhibits antiproliferative activity. In this study, we showed that celastrol combined with EGFR-TKIs significantly suppressed cell invasion of lung cancer cells with a T790M mutation by suppressing the EGFR pathway. Combined therapy with celastrol and EGFR-TKIs inhibited tumor growth in vivo. Together, these results suggested that combined therapy with EGFR-TKIs and celastrol may be a more effective treatment of patients with non-small-cell lung cancer with T790M mutations of the EGFR. * Ying Wang and Qiuyun Liu contributed equally to this article. Correspondence to Denghai Zhang, MD and Limin Xu, DSc, Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, 219 Miao Pu Road, Pudong New District, Shanghai 200135, China Tel: +86 021 5885 9398; fax: +86 021 3882 1635; e-mails: shanghai_zhang@163.com; 13564378807@163.com Received December 22, 2017 Accepted April 24, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2lm21HV

Comparison of Transferred Deep Neural Networks in Ultrasonic Breast Masses Discrimination

This research aims to address the problem of discriminating benign cysts from malignant masses in breast ultrasound (BUS) images based on Convolutional Neural Networks (CNNs). The biopsy-proven benchmarking dataset was built from 1422 patient cases containing a total of 2058 breast ultrasound masses, comprising 1370 benign and 688 malignant lesions. Three transferred models, InceptionV3, ResNet50, and Xception, a CNN model with three convolutional layers (CNN3), and traditional machine learning-based model with hand-crafted features were developed for differentiating benign and malignant tumors from BUS data. Cross-validation results have demonstrated that the transfer learning method outperformed the traditional machine learning model and the CNN3 model, where the transferred InceptionV3 achieved the best performance with an accuracy of 85.13% and an AUC of 0.91. Moreover, classification models based on deep features extracted from the transferred models were also built, where the model with combined features extracted from all three transferred models achieved the best performance with an accuracy of 89.44% and an AUC of 0.93 on an independent test set.

https://ift.tt/2K8MLvV

A Chemically Doped Naphthalenediimide‐Bithiazole Polymer for n‐Type Organic Thermoelectrics

Advanced Materials, EarlyView.


https://ift.tt/2KaZ5vU

A Simply Modified Lymphocyte for Systematic Cancer Therapy

Advanced Materials, EarlyView.


https://ift.tt/2I9p3L9

Quasi‐Solid‐State Single‐Atom Transistors

Advanced Materials, EarlyView.


https://ift.tt/2KaZ0s6

50 Years Ago in The Journal of Pediatrics

Glass AG, Hill JA, Miller RW. J Pediatr 1968;73:101-7.

https://ift.tt/2tiigtS

50 Years Ago in The Journal of Pediatrics

Weiss CF, Harris ST, Barrow WB, Buchanan RA. J Pediatr 1968;72:867-70

https://ift.tt/2tn2EEA

50 Years Ago in The Journal of Pediatrics

Fogel BJ, Arias D, Kung F, et al. J Pediatr 1968;73:108-10

https://ift.tt/2MJK0Qc

Subthreshold phototherapy during birth hospitalization may prevent readmission for phototherapy

Wickremasinghe AC, Kuzniewicz MW, McCulloch CE, Newman TB. Efficacy of Subthreshold Newborn Phototherapy During the Birth Hospitalization in Preventing Readmission for Phototherapy. JAMA Pediatr 2018;172:378-85.

https://ift.tt/2tsdPMx

Dental caries—something to sink your teeth into

In this volume of The Journal, Chen et al present some intriguing observations from the Kobe Offspring Study, comprising 71 069 children. The authors present analyses which may demonstrate an association between bedtime at 18 months and incidence of dental caries at 3 years, with increasing adjusted odds ratios for later bedtimes. This may have some biologic plausibility, since sleep and circadian rhythm may influence salivary flow, immune function, salivary amylase, and oral flora. On balance, though, this study raises as many questions as it seeks to answer.

https://ift.tt/2yvJAd7

Psychosocial factors and attrition from weight management

The progress of pediatric patients getting into and staying in treatment for obesity is complex and probably involves patient-specific factors, family factors, and clinical program factors. If patients are not able to engage in treatment and stay engaged, then it is likely that the outcomes will not be favorable.

https://ift.tt/2MEDmLf

No answers yet for the prevention of neonatal hypoglycemia

Prevention of neonatal hypoglycemia and the associated neonatal intensive care unit (NICU) admissions in asymptomatic newborn infants is important in order to limit the separation of mothers and infants after birth, to promote breastfeeding, and to limit potential complications of hypoglycemia. After the success of clinical trials of dextrose gel for infants with asymptomatic hypoglycemia (Cochrane Database Syst Rev 2016:CD011027), a logical next step would be to administer prophylactic treatment to infants with perinatal risk factors such as maternal diabetes.

https://ift.tt/2MLPaLB

Cardiac surgery and hearing loss

Hearing loss, which may occur for a variety of reasons in children, can be difficult to detect. When hearing loss is present, it can dramatically impact neurocognitive and language development. Early intervention is also important to be able to implement intervention strategies. Newborns who require intensive care are at risk of hearing loss and require expanded screening. It has been less clear if infants with congenital heart disease requiring complex surgery are at increased risk of hearing loss.

https://ift.tt/2ytX5Kj

Does learning or encouragement influence results for the 6-minute walk test?

The 6-minute walk test is a standard way to evaluate functional exercise capacity in both adults and children. In adults, both learning (experience with doing the test in the past) and encouragement improve the results of the test. This means that both learning and encouragement need to be standardized to get optimum results. These components have not been extensively studied in children.

https://ift.tt/2tq18lb

Corporal punishment associated with dating violence

Temple JR, Choi HJ, Reuter T, Wolfe D, Taylor CA, Madigan S, et al. Childhood Corporal Punishment and Future Perpetration of Physical Dating Violence. J Pediatr 2018;194:233-7.

https://ift.tt/2tf4I2t

Masthead

https://ift.tt/2yuC9mJ

Prenatal superior to postnatal myelomeningocele surgery

Farmer DL, Thom EA, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, et al. The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes. Am J Obstet Gynecol 2018;218:256.e1-256.e13.

https://ift.tt/2MLRrX5