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Τετάρτη 22 Αυγούστου 2018

Cancers, Vol. 10, Pages 283: CX-4945 Induces Methuosis in Cholangiocarcinoma Cell Lines by a CK2-Independent Mechanism

Cancers, Vol. 10, Pages 283: CX-4945 Induces Methuosis in Cholangiocarcinoma Cell Lines by a CK2-Independent Mechanism

Cancers doi: 10.3390/cancers10090283

Authors: Jomnarong Lertsuwan Kornkamon Lertsuwan Anyaporn Sawasdichai Nathapol Tasnawijitwong Ka Ying Lee Philip Kitchen Simon Afford Kevin Gaston Padma-Sheela Jayaraman Jutamaad Satayavivad

Cholangiocarcinoma is a disease with a poor prognosis and increasing incidence and hence there is a pressing unmet clinical need for new adjuvant treatments. Protein kinase CK2 (previously casein kinase II) is a ubiquitously expressed protein kinase that is up-regulated in multiple cancer cell types. The inhibition of CK2 activity using CX-4945 (Silmitasertib) has been proposed as a novel treatment in multiple disease settings including cholangiocarcinoma. Here, we show that CX-4945 inhibited the proliferation of cholangiocarcinoma cell lines in vitro. Moreover, CX-4945 treatment induced the formation of cytosolic vacuoles in cholangiocarcinoma cell lines and other cancer cell lines. The vacuoles contained extracellular fluid and had neutral pH, features characteristic of methuosis. In contrast, simultaneous knockdown of both the α and α′ catalytic subunits of protein kinase CK2 using small interfering RNA (siRNA) had little or no effect on the proliferation of cholangiocarcinoma cell lines and failed to induce the vacuole formation. Surprisingly, low doses of CX-4945 increased the invasive properties of cholangiocarcinoma cells due to an upregulation of matrix metallopeptidase 7 (MMP-7), while the knockdown of CK2 inhibited cell invasion. Our data suggest that CX-4945 inhibits cell proliferation and induces cell death via CK2-independent pathways. Moreover, the increase in cell invasion brought about by CX-4945 treatment suggests that this drug might increase tumor invasion in clinical settings.



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Infrared Thermographic Analysis of Surface Temperature of the Hands During Exposure to Normobaric Hypoxia

High Altitude Medicine &Biology, Ahead of Print.


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Typhoid fever: clinical presentation and associated factors in febrile patients visiting Shashemene Referral Hospital, southern Ethiopia

Although typhoid fever is a major public health problem in Ethiopia, data is not available in the study area. Therefore, this study aimed to determine the prevalence, clinical presentation at the time of diagn...

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Draft genome sequence of Bacillus pumilus strain EZ-C07 isolated from digested agricultural wastes

Bacillus species, belonging to the family Bacillaceae, are rod-shaped aerobic or facultative anaerobic Gram-positive bacteria that can be isolated from various environmental niches. Bacillus pumilus strains are r...

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Case 26-2018: A 48-Year-Old Man with Fever, Chills, Myalgias, and Rash

New England Journal of Medicine, Volume 379, Issue 8, Page 775-785, August 2018.


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Finding Better Ways to Prevent Postpartum Hemorrhage

New England Journal of Medicine, Volume 379, Issue 8, Page 790-792, August 2018.


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Immunotherapy for Melanoma Metastatic to the Brain

New England Journal of Medicine, Volume 379, Issue 8, Page 789-790, August 2018.


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Spur-Cell Anemia

nejmicm1714572_f1.jpeg

New England Journal of Medicine, Volume 379, Issue 8, Page 774-774, August 2018.


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Idiopathic Pulmonary Fibrosis

New England Journal of Medicine, Volume 379, Issue 8, Page 795-798, August 2018.


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Asteroid Hyalosis

nejmicm1712355_f1.jpeg

New England Journal of Medicine, Volume 379, Issue 8, August 2018.


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Free Drug Samples and the Opioid Crisis

New England Journal of Medicine, Volume 379, Issue 8, Page 793-794, August 2018.


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Lynch Syndrome–Associated Colorectal Cancer

New England Journal of Medicine, Volume 379, Issue 8, Page 764-773, August 2018.


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Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain

New England Journal of Medicine, Volume 379, Issue 8, Page 722-730, August 2018.


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Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery

New England Journal of Medicine, Volume 379, Issue 8, Page 731-742, August 2018.


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Cannabidiol in the Lennox–Gastaut Syndrome

New England Journal of Medicine, Volume 379, Issue 8, Page 794-795, August 2018.


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Outbreaks in a Rapidly Changing Central Africa — Lessons from Ebola

nejmp1807691_t1.jpeg

New England Journal of Medicine, Ahead of Print.


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Adolescents’ Use of “Pod Mod” E-Cigarettes — Urgent Concerns

nejmp1805758_f1.jpeg

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2PxUhR2

Case 26-2018: A 48-Year-Old Man with Fever, Chills, Myalgias, and Rash

New England Journal of Medicine, Volume 379, Issue 8, Page 775-785, August 2018.


https://ift.tt/2PweQNG

Finding Better Ways to Prevent Postpartum Hemorrhage

New England Journal of Medicine, Volume 379, Issue 8, Page 790-792, August 2018.


https://ift.tt/2wj574G

Immunotherapy for Melanoma Metastatic to the Brain

New England Journal of Medicine, Volume 379, Issue 8, Page 789-790, August 2018.


https://ift.tt/2wjxdwu

Spur-Cell Anemia

New England Journal of Medicine, Volume 379, Issue 8, Page 774-774, August 2018.


https://ift.tt/2Pqtia5

Idiopathic Pulmonary Fibrosis

New England Journal of Medicine, Volume 379, Issue 8, Page 795-798, August 2018.


https://ift.tt/2wrFAGD

Asteroid Hyalosis

New England Journal of Medicine, Volume 379, Issue 8, August 2018.


https://ift.tt/2Pv4WMl

Free Drug Samples and the Opioid Crisis

New England Journal of Medicine, Volume 379, Issue 8, Page 793-794, August 2018.


https://ift.tt/2PwWcFh

Lynch Syndrome–Associated Colorectal Cancer

New England Journal of Medicine, Volume 379, Issue 8, Page 764-773, August 2018.


https://ift.tt/2whxlN7

Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain

New England Journal of Medicine, Volume 379, Issue 8, Page 722-730, August 2018.


https://ift.tt/2Pv4Vbf

Tranexamic Acid for the Prevention of Blood Loss after Vaginal Delivery

New England Journal of Medicine, Volume 379, Issue 8, Page 731-742, August 2018.


https://ift.tt/2wikVEF

Cannabidiol in the Lennox–Gastaut Syndrome

New England Journal of Medicine, Volume 379, Issue 8, Page 794-795, August 2018.


https://ift.tt/2PxhK4X

Outbreaks in a Rapidly Changing Central Africa — Lessons from Ebola

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2wjxfo6

Adolescents’ Use of “Pod Mod” E-Cigarettes — Urgent Concerns

New England Journal of Medicine, Ahead of Print.


https://ift.tt/2PxUhR2

Disorders of Vergence Eye Movements

Abstract

Purpose of review

The purpose of this review is to summarize current understanding regarding disorders of gaze with comitant ocular misalignment at distance or near and a full range of extraocular movement. Emphasis is placed on clinical features that may be used to differentiate underlying neurologic disease from the more common benign causes. The approach to the diagnostic evaluation and treatment is discussed.

Recent findings

Randomized controlled trials and Cochrane review suggest the superiority of formal office-based vision therapy in treating convergence insufficiency in children. Divergence insufficiency in older adults is a common disorder caused by involution of connective tissues in the orbit. In contrast, divergence insufficiency in children may be a harbinger of central nervous system disease, particularly intracranial tumors.

Summary

Disorders of vergence are common in pediatric and aging adult populations. Benign causes are common but appropriate history and exam emphasizing ocular motility is essential to rule out more concerning diagnoses. Atypical presentations should prompt comprehensive evaluation including neuroimaging. Treatment of benign causes of vergence abnormalities should have a stepwise approach, beginning with the least invasive available intervention, though some patients may require surgery.



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Acute Symptomatic Seizures and Provoked Seizures: to Treat or Not to Treat?

Abstract

Purpose of review

Acute symptomatic and provoked seizures by definition occur in close proximity to an event and are considered to be situational. The treatment implications and likelihood of recurrence of acute symptomatic and provoked seizures differ from unprovoked seizures. In this article, the authors review the literature on acute symptomatic and provoked seizures with regard to therapeutic approach and risk of recurrence.

Recent findings

In the acute period, patients who suffer from acute symptomatic and provoked seizures have higher rates of morbidity and mortality. Patients with acute symptomatic seizures in the setting of certain conditions including subdural hemorrhage, traumatic penetrating injuries, cortical strokes, neurocysticercosis, venous sinus thrombosis, and viral encephalitis have a higher rate of seizure recurrence although the rate of recurrence of seizures is less than that of patients with unprovoked seizures.

Summary

In patients with acute symptomatic and provoked seizures, short-term treatment with anti-seizure medications is appropriate given the higher morbidity and mortality in the acute phase of illness. In patients with acute symptomatic seizures with persistent epileptiform activity on EEG and structural changes on imaging, longer-term treatment (i.e., a few months as opposed to 1 week) with anti-seizure medications can be considered due to high risk of seizure recurrence. If a patient subsequently has an unprovoked seizure, there is yet a higher risk of recurrence of seizures and likelihood of the development of epilepsy. In these patients, long-term seizure treatment can be considered, keeping in mind that although anti-seizure treatment may reduce risk of seizure recurrence in the short-term, it does not appear to influence long-term seizure remission rates.



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Correction to: Australia: regulating genomic data sharing to promote public trust

This article was inadvertently published under a draft title.



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Health State Utilities for Acute Myeloid Leukaemia: A Time Trade-off Study

Abstract

Objectives

Acute myeloid leukaemia (AML) is an aggressive haematological cancer associated with significant humanistic impact. The current study assessed how the general public in the United Kingdom (UK) values AML health states.

Methods

The composite time trade-off (cTTO) methodology was employed to elicit health state utilities in AML. Pertinent AML literature related to symptom and quality-of-life impact including physical, functional and emotional well-being, as well as the safety profile of AML treatments, were taken into consideration for drafting health state descriptions. Ten health states included in the study were newly diagnosed AML, induction, consolidation, maintenance, long-term follow-up, relapsed/refractory, stem-cell transplant (SCT) procedure, SCT recovery, SCT long-term follow-up with complications and SCT long-term follow-up without complications. The descriptions were validated by haematologists and nurse specialists for clinical accuracy and completeness. A total of 210 individuals from the general UK population participated in the cTTO interviews. Descriptive statistics were computed for health state utility values.

Results

The mean age of the participants was 44.0 years (standard deviation [SD] 14.9, range 18–81) and comprised 129 (61.4%) female participants. The utility values ranged from 0.94 (SD 0.13) for SCT long-term follow-up without complications to − 0.21 (SD 0.62) for the SCT procedure.

Conclusions

The study provides health utilities for a range of AML health states, with the SCT procedure health state being valued worse than death. The utilities obtained in this study can be employed as inputs in cost-effectiveness analyses of AML therapies.



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Radioimmunotherapy as a Novel Approach in HIV, Bacterial, and Fungal Infectious Diseases

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Biodistribution and Internal Radiation Dosimetry of 99mTc-IDA-D-[c(RGDfK)]2 (BIK-505), a Novel SPECT Radiotracer for the Imaging of Integrin αvβ3 Expression

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


https://ift.tt/2o24A3n

The Distribution and Imaging of 99mTc-nGO-PEG-FA in Human Patu8988 Tumor-Bearing Nude Mice

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Deletion of GIT1 Impacts eNOS Activity To Aggravate sFlt-1-Induced Preeclampsia Phenotype in Mice

Preeclampsia, a serious multisystem disorder specific to human pregnancy, remains a considerable burden of disease worldwide. Reduced nitric oxide bioavailability is proved to be crucial in the maternal and fetal pathophysiology of preeclampsia. G-protein-coupled Receptor Kinase Interactor-1 (GIT1) is a novel endothelial nitric oxide synthases (eNOS) interactor mediator. The aim of this paper is to investigate the effect of GIT1 on preeclampsia. Blood pressure (BP) was measured using a carotid catheter-calibrated eight-chamber tail-cuff system (CODA) at the same time daily. Urinary albumin excretion (UAE) was determined using Albuwell-M kits (Exocell Inc) and creatinine clearance (CCr) was determined by measuring urinary creatinine concentration with tandem liquid chromatography-mass spectrometry. The release of nitrite was analyzed to detect nitric oxide (NO) production using a Sievers Chemiluminescence NO Analyzer. NOS activity was examined by measuring the conversion of 3H-labeled l-arginine to 3H-labeled l-citrulline. BP was significantly increased in GIT1-/- mice with or without sFIT-1 treatment. In addition, GIT1-/- mice possessed higher UAE and lower CCr. Depletion of GIT1 impedes the NO production and placenta eNOS activity. Additional GIT1 attenuates sFlt-1-induced preeclampsia phenotypes. Our findings suggest that GIT1 significantly extenuates the sFlt-1-induced preeclampsia phenotypes by inhibiting eNOS activity, indicating a crucial role of GIT1 in the progression of preeclampsia.



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Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat

In this study we investigate the effects of parent of origin on complex traits in the laboratory rat, with a focus on coping style behavior in stressful situations. We develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We use this theory to investigate the effects on heritability of the parental origin of alleles in 798 outbred heterogeneous stock rats across 199 complex traits. Parent-of-origin-like heritability was on average 2.7-fold larger than classical additive heritability. Among the phenotypes with the most enhanced parent-of-origin heritability were 10 coping style behaviors, with average 3.2-fold heritability enrichment. To confirm these findings on coping behaviour, and to eliminate the possibility that the parent of origin effects are due to confounding with shared environment, we performed a reciprocal F1 cross between the behaviourally divergent RHA and RLA rat strains. We observed parent-of-origin effects on F1 rat anxiety/coping-related behavior in the Elevated Zero Maze test. Our study is the first to assess genetic parent-of-origin effects in rats, and confirm earlier findings in mice that such effects influence coping and impulsive behavior, and suggest these effects might be significant in other mammals, including humans.



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An Anopheles stephensi Promoter-Trap: Augmenting Genome Annotation and Functional Genomics

The piggyBac transposon was modified to generate gene trap constructs, which were then incorporated into the genome of the Asian malaria vector, Anopheles stephensi and remobilized through genetic crosses using a piggyBac transposase expressing line. A total of 620 remobilization events were documented, and 73 were further characterized at the DNA level to identify patterns in insertion site preferences, remobilization frequencies, and remobilization patterns. Overall, the use of the tetameric AmCyan reporter as the fusion peptide displayed a preference for insertion into the 5'-end of transcripts. Notably 183 - 44882 bp upstream of the An. stephensi v1.0 ab initio gene models, which demonstrated that the promoter regions for the genes of An. stephensi are further upstream of the 5'-proximal regions of the genes in the ab inito models than may be otherwise predicted. RNA-Seq transcript coverage supported the insertion of the splice acceptor gene trap element into 5'-UTR introns for nearly half of all insertions identified. The use of a gene trap element that prefers insertion into the 5'-end of genes supports the use of this technology for the random generation of knock-out mutants, as well as the experimental confirmation of 5'-UTR introns in An. stephensi.



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Antioxidant and anticancer activities of Trigonella foenum-graecum, Cassia acutifolia and Rhazya stricta

Here, we determined in vitro antioxidant activity, total phenols and flavonoids and evaluated antiproliferative activity of three medicinal plant extracts: Trigonella foenum-graecum (Fenugreek), Cassia acutifolia

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Tumor Antigen Escape from CAR T-cell Therapy [Mini Review]

Emerging data from chimeric antigen receptor (CAR) T-cell trials in B-cell malignancies demonstrate that a common mechanism of resistance to this novel class of therapeutics is the emergence of tumors with loss or downregulation of the target antigen. Antigen loss or antigen-low escape is likely to emerge as an even greater barrier to success in solid tumors, which manifest greater heterogeneity in target antigen expression. Potential approaches to overcome this challenge include engineering CAR T cells to achieve multispecificity and to respond to lower levels of target antigen and more efficient induction of natural antitumor immune responses as a result of CAR-induced inflammation. In this article, we review the evidence to date for antigen escape and downregulation and discuss approaches currently under study to overcome these obstacles.

Significance: Antigen escape and downregulation have emerged as major issues impacting the durability of CAR T-cell therapy. Here, we explore their incidence and ways to overcome these obstacles in order to improve clinical outcomes. Cancer Discov; 8(10); 1–8. ©2018 AACR.



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Extracellular HMGA1 promotes tumor Invasion and Metastasis in Triple-Negative Breast Cancer

Purpose: The study of the cancer secretome suggests that a fraction of the intracellular proteome could play unanticipated roles in the extracellular space during tumorigenesis. A project aimed at investigating the invasive secretome led us to study the alternative extracellular function of the nuclear protein high mobility group A1 (HMGA1) in breast cancer invasion and metastasis. Experimental Design: Antibodies against HMGA1 were tested in signalling, adhesion, migration, invasion and metastasis assays using breast cancer cell lines and xenograft models. Fluorescence microscopy was used to determine the subcellular localization of HMGA1 in cell lines, xenograft and patient-derived xenograft models. A cohort of triplenegative breast cancer (TNBC) patients was used to study the correlation between subcellular localization of HMGA1 and the incidence of metastasis. Results: Our data shows that treatment of invasive cells with HMGA1-blocking antibodies in the extracellular space impairs their migration and invasion abilities. We also prove that extracellular HMGA1 (eHMGA1) becomes a ligand for the Advanced glycosylation end product-specific receptor (RAGE), inducing pERK signalling and increasing migration and invasion. Using the cytoplasmic localization of HMGA1 as a surrogate marker of secretion, we showed that eHMGA1 correlates with the incidence of metastasis in a cohort of TNBC patients. Furthermore, we show that HMGA1 is enriched in the cytoplasm of tumor cells at the invasive front of primary tumors and in metastatic lesions in xenograft models. Conclusions: Our results strongly suggest that eHMGA1 could become a novel drug target in metastatic TNBC, and a biomarker predicting the onset of distant metastasis.



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FET PET in Primary Central Nervous System Vasculitis

imagePrimary central nervous system vasculitis is confined to the brain and spinal cord. While serological markers of inflammation are usually normal, conventional angiography may confirm the diagnosis. The diagnostic method of choice is central nervous system biopsy. A 57-year-old man suffered from a first generalized epileptic seizure. MRI revealed a contrast-enhancing lesion, and O-(2-[18F]fluoroethyl)-L-tyrosine amino acid PET displayed increased metabolic activity, both findings highly suggestive of a malignant glioma. Surprisingly, histology obtained following stereotactic biopsy revealed small-vessel vasculitis.

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Prognostic Value of FDG-PET/CT Metabolic Parameters in Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer

imagePurpose There are no standardized prognostication algorithms for metastatic radioiodine-refractory (RAI-R) differentiated thyroid cancer (DTC). We hypothesize that [18F]-FDG PET/CT may predict progression versus stability of disease based on quantitative analysis of metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Methods Retrospective study of 62 patients with metastatic RAI-R DTC to determine clinical outcomes with median follow-up from initial diagnosis of 11.1 years (8.38, 14.1) (range, 1.2–20 years). Baseline [18F]-FDG PET/CT scans were evaluated qualitatively for regional and distant metastases and quantitatively for tumor burden based on MTV and TLG obtained using gradient segmentation method. Results After diagnosis of metastatic RAI-R disease was established, the 5-year overall survival (OS) probability was 34%, and median OS was 3.56 years (2.87, infinity). The 5-year progression-free survival (PFS) probability was 19%, and median PFS was 1.31 years (1.03, 2.38). TSH-suppressed thyroglobulin (Tg) levels greater than 100 ng/mL and Tg doubling time (Tg-DT) less than 6 months were significantly associated with worse OS and PFS. Higher than median values of MTV and TLG were associated with worse OS (P = 0.06) and PFS (P = 0.007). Higher hazard of death was noted for higher values of log-MTV and log-TLG (HR, 1.17 [95% confidence interval, 0.99–1.39], P = 0.05, and HR, 1.14 [95% confidence interval, 1.00–1.31], P = 0.05, respectively). Conclusions [18F]-FDG PET/CT metabolic parameters can help define the volume and biologic variations of metastatic tumor burden. Metabolic tumor volume and TLG can be used for dynamic risk stratification of patients with metastatic RAI-R DTC regarding PFS and complement Tg-DT for prognosis of clinical disease course.

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Phenytoin Could Potentially Increase Hepatic Clearance of 99mTc-Sestamibi in Myocardial Perfusion Imaging

imageMyocardial perfusion imaging (MPI) is one of the most commonly used nuclear medicine imaging modalities for coronary artery disease evaluation and risk stratification. The authors present incidental image findings in a patient who underwent MPI twice because of development of seizures just before the first SPECT-MPI acquisition. The projection images for first MPI done without medication (phenytoin) showed the retention of hepatic tracer activity. After a few days from restarting of phenytoin, the repeat MPI showed complete hepatic clearance of tracer. This case highlights the possible pharmacokinetic interaction between phenytoin intake and 99mTc-sestamibi, resulting in faster hepatic clearance of the radiotracer.

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Amiodarone-Induced Thyrotoxicosis: Differential Diagnosis Using 99mTc-SestaMIBI and Target-to-Background Ratio (TBR)

imagePurpose of the Report Distinguishing between amiodarone-induced thyrotoxicosis (AIT) caused by excessive hormone synthesis (AIT-1) or by a destructive process (AIT-2) has important therapeutic implications, but is still difficult and debated. 99mTc-sestaMIBI thyroid scintigraphy (99m-STS) has been proposed as a tool for classifying the two forms. Material and Methods 30 AIT patients (11 females and 19 males) who underwent 99m-STS were retrospectively assessed for the present study. For each patient, a target-to-background ratio (TBR) was obtained on planar images. The TBR was then correlated with the qualitative assessment of the scans and the final clinical diagnosis. Results Considering clinical response to treatment as the gold standard for differential diagnosis, 14 cases of AIT-1, 12 of AIT-2, and 4 mixed forms were identified. 99m-STS was able to qualitatively identify all the mixed forms, while 1/14 AIT-1 and 6/12 AIT-2 cases were misdiagnosed as mixed forms. When the quantitative index (the TBR) was compared with the final clinical diagnosis, ROC curve analysis enabled us to identify an IBR of 0.482 during 99m-STS as a cut-off capable of discriminating between AIT-1 and AIT-2, with 100% specificity and 91.7% sensitivity (P

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Unusual Case of Metastatic Intracranial Hemangiopericytoma and Emphasis on Role of 68Ga-PSMA PET in Imaging

imageWe present a 53 year old woman initially diagnosed as hemangiopericytoma in the posterior fossa on the right side post excision with immunohistochemistry staining for CD34 being positive. Presently, the patient had difficulty in walking due to back pain and pain in left arm. Imaging with 18F-FDG PET showed low glucose avidity in disease sites but 68Ga-PSMA PET unequivocally demonstrated multiple skeletal and liver metastases with intense PSMA avidity. Patient received palliative radiotherapy to bone metastasis and was planned for chemotherapy. This report adds to the list of applications of 68Ga PSMA PET and a possible theranostic target.

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68Ga-NOTA-RM26 PET/CT in the Evaluation of Breast Cancer: A Pilot Prospective Study

imageBackground This prospective pilot study investigated the value of 68Ga-NOTA-RM26, an antagonist targeting gastrin-releasing peptide receptor, in evaluation of breast cancer. Methods Thirty-five women in suspicion of breast cancer based on mammography or ultrasonography were recruited with informed consent. They underwent PET/CT scans 30 minutes after intravenous injection of 68Ga-NOTA-RM26 in a dose of 1.85 MBq (0.05 mCi) per kilogram body weight within 1 week before surgery. The 68Ga-NOTA-RM26 uptake was correlated with the pathological and immunohistochemical findings. Results 68Ga-NOTA-RM26 positivity was found correlated with estrogen receptor (ER) expression (P = 0.006) and menstrual status (P = 0.019). In 34 patients diagnosed with breast cancer, the SUVmax was found significantly higher in the ER-positive breast cancer (4.97 ± 1.89) than in the ER-negative breast cancer (2.78 ± 0.65, P

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Primary Extragastrointestinal Stromal Tumor on FDG PET/CT

imagePrimary extragastrointestinal stromal tumor is very rare. We report a case of cervical paravertebral extragastrointestinal stromal tumor involving adjacent bones revealed by FDG PET/CT in a 66-year-old man without any gastrointestinal involvement.

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To Use or Not to Use 131I in Thyroid Cancer

Purpose The purpose of the following commentary is to discuss recent controversies in the use of radioactive iodine for differentiated thyroid cancer (DTC). Methods R. M. Tuttle (Thyroid 2010; 20:257–263), at Memorial Sloan Kettering Cancer Center, has enumerated the well-accepted goals of radioactive iodine therapy (RAIT) in DTC: (1) ablate residual thyroid to facilitate future surveillance, (2) "adjuvant therapy" for residual radioactive iodine–avid disease, and (3) a post-RAIT scan may reveal unknown local and/or distant metastases. Using these goals as a guide, the authors have critically reviewed a recent movement to decrease the use of RAIT in DTC that is being advocated by some investigators. Results As a result, a recent article has highlighted this new treatment philosophy. A 2017 publication in the Journal of Clinical Oncology (Molenaar et al, 2017 0:JCO.2017.75.0232) recommends that RAIT not be used in low- or intermediate-risk DTC. In this article, the authors claim that the RAIT risks in DTC, particularly leukemia, outweigh its potential benefits. This change, if adopted, in our opinion will have profound deleterious consequences on patient outcomes. We also have identified a major problem with the article of Molenaar et al. The authors use the American Thyroid Association's criteria for staging thyroid cancer. In our opinion, this method of staging is severely flawed. We also quantitatively compare the article's alleged risk of RAIT-induced leukemia with the benefits of RAIT for DTC. Conclusions In summary, this matter must be debated before eliminating RAIT in low- or intermediate-risk DTC. If RAIT is eliminated for these patients, many such patients will no longer benefit from the RAIT goals listed by R. M. Tuttle, including the critical advantage of potentially improved overall and event-free survival.

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Utility of 68Ga-PSMA-11 PET/CT in Imaging of Glioma—A Pilot Study

imageBackground Imaging of gliomas remains challenging. The aim of the study was to assess the feasibility of using 68Ga-PSMA-11 PET/CT for imaging gliomas. Methods Fifteen patients with glioma from 2 centers were included in the study. Ten patients were treated cases of glioblastoma with suspected recurrence. Two patients were sent for assessing the nature (primary lesion/metastasis) of space-occupying lesion in the brain; 3 patients were imaged immediately after surgery and before radiotherapy. Target-to-background ratios (TBR) for the brain lesions were calculated using contralateral cerebellar uptake as background. Results Among the 10 cases with suspected recurrence, scan was positive in 9, subsequent surgery was done, and histopathology proved it to be true recurrence. In the scan-negative case on follow-up, no evidence of disease could be made clinically or radiologically. Among the other cases the presence or absence of disease could be unequivocally identified on the 68Ga-PSMA-11 brain scan and correlated with the histopathology or other imaging. Apart from the visual assessment quantitative assessment of the lesions with TBR also showed a significantly high TBR value for those with true disease compared with those with no disease. Conclusions In the evaluation of gliomas, 68Ga-PSMA-11 PET/CT brain imaging is a potentially useful imaging tool. The use of 68Ga-PSMA-11 brain PET/CT in evaluation of recurrent glioma seems promising. Absence of physiological uptake of 68Ga-PSMA-11 in the normal brain parenchyma results in high TBR values and consequently better visualization of glioma lesions.

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FDG PET/CT of Metabolic Myopathy With Posttreatment Follow-up

imageA 38-year-old woman presented with extreme fatigue and multiple lung nodules. She was referred for a PET/CT, which demonstrated multiple FDG-avid pulmonary nodules and lymph nodes with intense uptake within multiple muscle groups predominantly involving the paraspinal muscles and muscles of mastication. Histopathology of a paraspinal muscle biopsy revealed increased skeletal muscle lipid stores and increased mitochondria with normal morphology. This abnormality is seen in metabolic myopathy due to a disorder of fatty acid oxidation. Transbronchial biopsy showed no evidence of sarcoidosis. The patient was commenced on carnitine and riboflavin supplementation, and a follow-up PET/CT was performed.

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Recurrent/Residual Intracranial Phosphaturic Mesenchymal Tumor Revealed on 68Ga-DOTATATE PET/CT

imagePhosphaturic mesenchymal tumors are benign tumors causing majority of tumor-induced osteomalacia. These tumors are most commonly located in the lower extremities followed by craniofacial regions. However, intracranial lesion is very rare. Here we describe 68Ga-DOTATATE PET/CT findings of a recurrent intracranial phosphaturic mesenchymal tumor in a 68 year old woman.

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18F-FDOPA PET/CT of Nonfunctioning Paraganglioma of the Gastroepiploic Pedicle

imageWe report the case of a 54-year-old woman with a nonfunctioning paraganglioma arising from the gastroepiploic pedicle demonstrated by 18F-FDOPA PET/CT. Because gastroepiploic arcade can be assimilated to the gastric mesentery, this tumor has been classified as a mesenteric paraganglioma (PGL). Neural crest cells are a multipotent population of cells characterized by effective migratory properties potentially explaining PGL atypical localization as in the mesentery. Mesenteric PGLs are often nonfunctioning and can mimic gastric, colic, or pancreatic primary tumor because of their anatomical boundaries, making more difficult the diagnosis on preoperative imaging.

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Ten-Year Survival After Peptide Receptor Radionuclide Therapy of a Metastatic Well-differentiated G3 Pancreatic Neuroendocrine Neoplasm

imageSubstantial molecular and clinical heterogeneity of high-grade neuroendocrine neoplasms (NENs) G3, all of which were previously referred to as neuroendocrine carcinomas, has been observed. Although data are still limited, somatostatin receptor expression in well-differentiated G3 NENs of the pancreas (according to the new WHO 2017 classification) may enable peptide receptor radionuclide therapy for these patients. We report our treatment experience of a G3 NEN patient with discordant Ki-67 proliferation indices (between primary tumor and the metastases), who had a long survival over a span of 10 years with excellent quality of life and no adverse effects after repeated cycles of PRRT.

https://ift.tt/2N9b4bA

Schwann cells augment cell spreading and metastasis of lung cancer

Although lungs are densely innervated by the peripheral nervous system (PNS), the role of the PNS in the progression of lung cancer is unknown. In this study, we report that mouse adult Schwann cells (SC), the principal glial cells of the PNS, can regulate the motility of lung cancer cells in vitro and the formation of metastases in vivo. SC promoted epithelial-mesenchymal transition (EMT) and the motility of two lung cancer cell lines by increasing expression of Snail and Twist in tumor cells; blocking of Snail and Twist expression abolished SC-induced motility of tumor cells. SC-derived CXCL5 was responsible for EMT in lung cancer cells, as the inhibition of CXCL5 or its receptor CXCR2 reduced SC-induced expression of Snail and Twist and reduced motility in tumor cells. CXCL5/CXCR2 binding activated the PI3K/AKT/GSK-3β/Snail-Twist signaling pathway in lung cancer cells, and the PI3K inhibitor blocked CXCL5-dependent phosphorylation of AKT and GSK-3β, reduced expression of Snail/Twist, and limited tumor cell invasiveness. SC conditioning of tumor cells prior to their injection into mice significantly increased the formation of metastases in the regional lymph nodes. In summary, SC can regulate the CXCL5/CXCR2/PI3K/AKT/GSK-3β/Snail-Twist pathway to promote EMT, invasiveness, and metastatic potential of lung cancer cells. Our results reveal a new role of the PNS in the functional organization of the tumor microenvironment and tumor progression.

https://ift.tt/2whd4Y7

Reduced expression of PROX1 transitions glioblastoma cells into a mesenchymal gene expression subtype

The homeodomain transcription factor PROX1 has been linked to several cancer types including gliomas, but its functions remain to be further elucidated. Here we describe a functional role and the prognostic value of PROX1 in glioblastoma. Low expression of PROX1 correlated with poor overall survival and the mesenchymal glioblastoma subtype signature. The latter finding was recapitulated in vitro where suppression or overexpression of PROX1 in glioma cell cultures transitioned cells to a mesenchymal or to a non-mesenchymal glioblastoma gene expression signature, respectively. PROX1 modulation affected proliferation rates that coincided with changes in protein levels of CCNA1 and CCNE1 as well as the cyclin inhibitors CDKN1A, CDKN1B, and CDKN1C. Overexpression of SOX2 increased PROX1 expression, but treatment with a CDK2 inhibitor subsequently decreased PROX1 expression, which was paralleled by decreased SOX2 levels. The THRAP3 protein was a novel binding partner for PROX1, and suppression of THRAP3 increased both transcript and protein levels of PROX1. Together these findings highlight the prognostic value of PROX1 and its role as a regulator of glioblastoma gene expression subtypes, intratumoral heterogeneity, proliferation, and cell cycle control.

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Dose and schedule determine distinct molecular mechanisms underlying the efficacy of the p53-MDM2 inhibitor HDM201

Activation of p53 by inhibitors of the p53-MDM2 interaction is being pursued as a therapeutic strategy in p53 wild-type cancers. Here we report distinct mechanisms by which the novel, potent, and selective inhibitor of the p53-MDM2 interaction HDM201 elicits therapeutic efficacy when applied at various doses and schedules. Continuous exposure of HDM201 led to induction of p21 and delayed accumulation of apoptotic cells. By comparison, high dose pulses of HDM201 were associated with marked induction of PUMA and a rapid onset of apoptosis. shRNA screens identified PUMA as a mediator of the p53 response specifically in the pulsed regimen. Consistent with this, the single high dose HDM201 regimen resulted in rapid and marked induction of PUMA expression and apoptosis together with down-regulation of Bcl-xL in vivo. Knockdown of Bcl-xL was identified as the top sensitizer to HDM201 in vitro, and Bcl-xL was enriched in relapsing tumors from mice treated with intermittent high doses of HDM201. These findings define a regimen-dependent mechanism by which disruption of MDM2-p53 elicits therapeutic efficacy when given with infrequent dosing. In an ongoing HDM201 trial, the observed exposure-response relationship indicates that the molecular mechanism elicited by pulse dosing is likely reproducible in patients. These data support the clinical comparison of daily and intermittent regimens of p53-MDM2 inhibitors.

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A Novel Microtubule Inhibitor Overcomes Multidrug Resistance in Tumors

Microtubule inhibitors as chemotherapeutic drugs are widely used for cancer treatment. However, the development of multidrug resistance (MDR) in cancer is a major challenge for microtubule inhibitors in their clinical implementation. From a high-throughput drug screen using cells transformed by oncogenic RAS, we identify a lead heteroaryl amide compound that blocks cell proliferation. Analysis of the structure-activity relationship indicated that this serial of scaffolds (exemplified by MP-HJ-1b) represents a potent inhibitor of tumor cell growth. MP-HJ-1b showed activities against a panel of more than 1000 human cancer cell lines with a wide variety of tissue origins. This compound depolymerized microtubules and affected spindle formation. It also induced the spike-like conformation of microtubules in vitro and in vivo, which is different from typical microtubule modulators. Structural analysis revealed that this serial of compounds bound the colchicine pocket at the intra-dimer interface, although mostly not overlapping with colchicine binding. MP-HJ-1b displayed favorable pharmacological properties for overcoming tumor MDR both in vitro and in vivo. Taken together, our data reveal a novel scaffold represented by MP-HJ-1b that can be developed as a cancer therapeutic against tumors with MDR.

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In reply:

We appreciate the comments and previous work by Drs. Calder and McDougall.1 Malpractice litigation is a complicated issue influenced by patient, provider, and environmental factors. Our work that examines factors associated with being named in a malpractice claim represents only a single view of factors associated with a malpractice claim in a single group of emergency physicians.2 Our data allowed us to examine several provider factors such as years in practice and operational factors, including length of stay and practice intensity at a macrolevel.

https://ift.tt/2MRpEYt

Young Man With Paraparesis

A 24-year-old man presented to our emergency department with paraparesis and urinary retention. The previous day, he had participated in his first beginner surfing lesson. Near the end of the 2-hour lesson, he experienced the acute onset of severe lower back pain when arching his back while attempting to stand to catch a wave. He had the strength to swim to shore, but within an hour he developed progressive bilateral lower-extremity numbness and weakness, and urinary retention. Physical examination was notable for bilateral lower-extremity weakness and hyperesthesia.

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Clinical Judgment and the Pediatric Emergency Care Applied Research Network Head Trauma Prediction Rules

We commend Babl et al1 for their well-designed subanalysis comparing clinical judgment with pediatric head trauma prediction rules to guide neuroimaging decisions, as few studies have explored such comparisons. The authors conclude that in settings with low computed tomography (CT) use such as theirs, prediction rules may have a limited influence on clinical decisionmaking in pediatric head trauma and may increase CT use. The authors note several caveats that merit further elaboration.

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Journal Performance Report

Once a year, we report our performance as a journal, along with important changes and achievements. This report covers July 2017 through June 2018.

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What's Coming in Annals ● October 2018



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Posttraumatic Stress Disorder in Emergency Medicine Residents: A Role for Moral Injury?

We read with interest the perspective piece on posttraumatic stress disorder in emergency medicine residents in the United States.1 The addition of the new exposure criteria to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,2 those of witnessing events or being exposed to aversive details of these traumatic events, would lead us to consider many emergency medicine and out-of-hospital care practitioners to be potentially at risk of posttraumatic stress disorder.

https://ift.tt/2NbhjeU

Woman With Pain and Deformity in Left Wrist

A 19-year-old woman presented with left wrist deformity. She had a history of shoulder "hypermobility" and a childhood left ulnar fracture treated nonoperatively. She was stretching her arms with fingers intertwined when she felt a "pop" and left wrist pain. On examination, she had a minimally tender volar deformity at the ulnar styloid, with inability to pronate, limited supination, and preserved wrist flexion and extension. Posteroanterior, lateral, and oblique radiographs were obtained.

https://ift.tt/2MMO7hs

Man With Abdominal Pain

A 78-year-old man with history of coronary artery disease, diabetes mellitus, and prostate cancer presented to the emergency department with abdominal pain for 1 day. Physical examination revealed diffuse abdominal tenderness and rebound tenderness. Computed tomography (CT) of the abdomen was obtained (Figures 1 and 2).

https://ift.tt/2Naitr4

Elderly Woman With Abdominal Pain

An 81-year-old woman was taken to the emergency department after a few days of worsening abdominal pain and deteriorating level of consciousness. She had extensive peripheral vascular disease and had recently required endarterectomy to salvage an acutely ischemic limb. On admission, she was profoundly hypotensive, tachypneic, and oliguric because of a state of circulatory shock, and the abdominal examination was characterized by generalized tenderness and reduced bowel sounds, without rebound or guarding.

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Information for Readers



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Whispers

An icy chill trickled into my chest and my lip curled when he told me why he was here. The triage note had read "51yo M: suicidal ideation." I thought it would be a quick medical clearance and a call to psych.

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Editors



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Beyond ATLS: Demystifying the Expert Resuscitationist

SEE RELATED ARTICLE, P. 289.

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Correction

Erratum to 'Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Suspected Acute Venous Thromboembolic Disease (Executive Summary)'

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Global Research Highlights

Editor's note: Annals has partnered with a small group of selected journals of international emergency medicine societies to share from each a highlighted research study, as selected monthly by their editors. Our goals are to increase awareness of our readership to research developments in the international emergency medicine literature, promote collaboration among the selected international emergency medicine journals, and support the improvement of emergency medicine world-wide, as described in the WAME statement at https://ift.tt/2dmKsCb.

https://ift.tt/2MJTQEM

Medical Practice Review and the Practice of Medicine

The American College of Emergency Physicians endorses the following principles in regard to medical opinions about the appropriateness or quality of medical care that are made for purposes other than the delivery of medical care:

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How to Not Kill Your Patients: An ER Doctor's Guide to Life After Residency

Many of us have encountered Dr. Sajid Khan's well-known and well-regarded book The Ultimate Emergency Medicine Guide: The Only EM Book You Need to Succeed. In his new book, How to Not Kill Your Patients: An ER Doctor's Guide to Life After Residency, Dr. Khan provides another practical tome to educate and enlighten the newly minted emergency physician. The latter part of the title, however, might lead the potential reader astray. To my overworked and very-much-appreciated residents, the subtitle may evoke algorithms on vacation scheduling, estate planning, and negotiating the politics of being in charge.

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Neurologic Emergencies: How to Do a Fast, Focused Evaluation of Any Neurologic Emergency

When deciding on my specialty 20-plus years ago in medical school, if anyone had told me, "The most exciting specialty 20 years in the future is going to be…neurology!" I would have assumed he or she was pulling my leg. Neurology's reputation as the most "diagnose and adios" of specialties was at that time historically solid. In a complete reversal, Ganti and Goldstein's Neurologic Emergencies: How to Do a Fast, Focused Evaluation of Any Neurologic Emergency comes at a time when acute and chronic neurologic conditions have significantly successful new treatments (with the DAWN, DEFUSE-3, and, most recently, ATTEST trials for stroke, monoclonal antibodies, and disease modifying therapies for multiple sclerosis) and research is giving new understanding of previously black-box conditions such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis and pointing new directions for treatment.

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Adolescents’ Use of "Pod Mod" E-Cigarettes — Urgent Concerns

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Adolescents' use of electronic cigarettes initially took the public health community by surprise. In 2011, less than 2% of U.S. high school students reported having used e-cigarettes in the previous month. But by 2015, the percentage had jumped to 16%. The following year, the U.S. Surgeon General…

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Outbreaks in a Rapidly Changing Central Africa — Lessons from Ebola

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West and Central Africa are experiencing explosive growth in urban populations, economic activities, and connectivity. The recent Ebola virus epidemic in West Africa demonstrated the vulnerability of the local health care infrastructure to newly emerging infectious diseases. Two key factors…

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Gym Class Memories Can Influence Adults' Exercise Habits

WEDNESDAY, Aug. 22, 2018 -- Memories of school gym class may affect a person's exercise habits today, according to a study published in the Aug. 15 issue of the Translational Journal of the American College of Sports Medicine. The study included...

https://ift.tt/2MIoZby

4 Experimental Ebola Therapies Approved for Use in Congo

WEDNESDAY, Aug. 22, 2018 -- Four more experimental treatments for Ebola virus have been approved by the Congo health ministry for use in an outbreak of the deadly infectious disease in the country's northeast. The treatments are ZMapp, Remdesivir,...

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Small Practices Also at Risk for Data Breaches

WEDNESDAY, Aug. 22, 2018 -- Data breaches can happen to small medical practices, but staff can take steps to prevent them, according to an article published in Medical Economics. For example, one five-provider group practice had a data breach that...

https://ift.tt/2MRaMcB

Nivolumab + Ipilimumab Shows Efficacy for Untreated Brain Mets

WEDNESDAY, Aug. 22, 2018 -- For patients with melanoma and untreated brain metastases, nivolumab combined with ipilimumab shows clinically meaningful efficacy, according to a study published in the Aug. 23 issue of the New England Journal of...

https://ift.tt/2NaFLNB

Prophylactic Tranexamic Acid Doesn't Cut Postpartum Bleeding

WEDNESDAY, Aug. 22, 2018 -- Prophylactic administration of tranexamic acid does not reduce postpartum hemorrhage among women with vaginal delivery receiving prophylactic oxytocin, according to a study published in the Aug. 23 issue of the New...

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Corrigendum to “Circulating Endocannabinoids and Insulin Resistance in Patients with Obstructive Sleep Apnea”



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Corrigendum to “Determination of Serum Lost Goodwill Target Proteome in Patients with Severe Traumatic Brain Injury”



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Current approaches for the management of Parkinson’s disease in Chinese hospitals: a cross-sectional survey

Chinese guidelines for management of Parkinson's disease (PD) have been issued and updated regularly since 2006. We undertook a cross-sectional survey to evaluate the impact of the latest edition (2014) on cur...

https://ift.tt/2Pswj9X

Multifocal motor neuropathy presenting as a post-infectious complication of dengue: a CASE report

Dengue infection is an endemic illness in the tropics and it is associated with a wide variety of post infectious complications. With the increasing prevalence of dengue infection in endemic regions, post-infe...

https://ift.tt/2w5TrTz

Retention outcomes and drivers of loss among HIV-exposed and infected infants in Uganda: a retrospective cohort study

Uganda's HIV Early Infant Diagnosis (EID) program rapidly scaled up testing of HIV-exposed infants (HEI) in its early years. However, little was known about retention outcomes of HEI after testing. Provision o...

https://ift.tt/2LiGFG2

Molecular characterization and epidemiology of carbapenem non-susceptible Enterobacteriaceae isolated from the Eastern region of Heilongjiang Province, China

The aim of this study was to elucidate the molecular epidemiology of carbapenem non-susceptible Enterobacteriaceae(CNSE) isolated in the Eastern region of Heilongjiang Province, China, and the mechanism of car...

https://ift.tt/2w7ZA1k

Intra-aural tick bite causing unilateral facial nerve palsy in 29 cases over 16 years in Kandy, Sri Lanka: is rickettsial aetiology possible?

Over the last two decades intra-aural tick infestation (otoacariasis) has been a common occurrence in the hilly central region in Sri Lanka. Very occasional detection of isolated unilateral facial nerve palsy ...

https://ift.tt/2LesGB3

Epidemiological analysis and rapid detection by one-step multiplex PCR assay of Haemophilus influenzae in children with respiratory tract infections in Zhejiang Province, China

Haemophilus influenzae (H. influenzae) is one of the most important pathogenic bacteria causing respiratory tract infection diseases in children. There are two main types of H. influenzae, encapsulated H. influen...

https://ift.tt/2w59voD

Computer-aided detection in chest radiography based on artificial intelligence: a survey

As the most common examination tool in medical practice, chest radiography has important clinical value in the diagnosis of disease. Thus, the automatic detection of chest disease based on chest radiography ha...

https://ift.tt/2Na9aHL

Alcohol and the risk of pneumonia: a systematic review and meta-analysis

Objective

A systematic review and meta-analysis to estimate the magnitude of the association between alcohol consumption and the risk of community-acquired pneumonia (CAP) in adults was undertaken.

Design

Systematic review and meta-analysis.

Methods

Comprehensive searches of Medline, Embase and Web of Science were carried out to identify comparative studies of the association between alcohol intake and CAP between 1985 and 2017. Reference lists were also screened. A random-effects meta-analysis was used to estimate pooled effect sizes. A dose–response meta-analysis was also performed.

Results

We found 17 papers eligible for inclusion in the review, of which 14 provided results which could be pooled. Meta-analysis of these 14 studies identified an 83% increased risk of CAP among people who consumed alcohol or in higher amounts, relative to those who consumed no or lower amounts of alcohol, respectively (relative risk=1.83, 95% CI 1.30 to 2.57). There was substantial between-study heterogeneity, which was attributable in part to differences in study continent, adjustment for confounders and pneumonia diagnosis (clinical vs death). Dose–response analysis found that for every 10–20 g higher alcohol intake per day, there was an 8% increase in the risk of CAP.

Conclusions

The findings suggest that alcohol consumption increases the risk of CAP. Therefore, strengthening policies to reduce alcohol intake would be likely to reduce the incidence of CAP.



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Characteristics associated with physical function trajectories in older adults with cancer during chemotherapy

Studies on physical function trajectories in older adults during chemotherapy remain limited.

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Third-Year Medical Students’ Reactions to Surgical Patients in Pain: Doubt, Distress and Depersonalization

Medical students have limited instruction about how to manage the interpersonal relationships required to care for patients in pain.

https://ift.tt/2o841oN

Defining adenoma detection rate benchmarks in average-risk male veterans

Veterans have higher prevalence of colorectal neoplasia than non-veterans; however, it is not known whether specific Veterans Affairs (VA) adenoma detection rate (ADR) benchmarks are required. We compared ADRs of a group of endoscopists for colonoscopies performed at a VA to their ADRs at a non-VA academic medical center.

https://ift.tt/2LlBs0h

Index colonoscopy-related risk factors for postcolonoscopy colorectal cancers

Postcolonoscopy colorectal cancers (PCCRCs) are those detected ≤10 years after an index colonoscopy negative for cancer, but modifiable risk factors are not well established in large, community-based populations.

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Chronic Abdominal Pain Caused by Collagenous Gastritis



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The Gut Microbiome in Pancreatic Disease

The gut microbiome is increasingly recognized for its role in human health and disease. Initial evidence indicates that gut microbial dysbiosis is associated with several pancreatic diseases. Although it is not known if these associations are causative, gut dysbiosis is hypothesized to mediate chronic pro-inflammatory changes in the pancreas. Further mechanistic and epidemiological studies of the microbiome are needed. Ultimately, targeted modulation of the microbiota could have therapeutic value.

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Small bowel paralytic ileus from Strongyloides stercoralis



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Is asymptomatic esophageal eosinophilia the same disease entity as eosinophilic esophagitis?



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Efficacy of High-dose, Rapid, Hepatitis A and B Vaccination Schedules in Patients With Cirrhosis



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Esophagogastroduodenoscopy-induced angina bullosa hemorrhagica of the aryepiglottic folds and arytenoid



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A case of Gastroduodenal Intussusception and Endoscopic Reduction (with Video)



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Amplitude-Integrated Electroencephalography for Early Recognition of Brain Injury in Neonates with Critical Congenital Heart Disease

To study perioperative amplitude-integrated electroencephalography (aEEG) as an early marker for new brain injury in neonates requiring cardiac surgery for critical congenital heart disease (CHD).

https://ift.tt/2N9VoEW

Ensuring Equity, Diversity, and Inclusion in Academic Surgery: An American Surgical Association White Paper

imageObjective: The leadership of the American Surgical Association (ASA) appointed a Task Force to objectively address issues related to equity, diversity, and inclusion with the discipline of academic surgery. Summary of Background Data: Surgeons and the discipline of surgery, particularly academic surgery, have a tradition of leadership both in medicine and society. Currently, we are being challenged to harness our innate curiosity, hard work, and perseverance to address the historically significant deficiencies within our field in the areas of diversity, equity, and inclusion. Methods: The ASA leadership requested members to volunteer to serve on a Task Force to comprehensively address equity, diversity, and inclusion in academic surgery. Nine work groups reviewed the current literature, performed primary qualitative interviews, and distilled available guidelines and published primary source materials. A work product was created and published on the ASA Website and made available to the public. The full work product was summarized into this White Paper. Results: The ASA has produced a handbook entitled: Ensuring Equity, Diversity, and Inclusion in Academic Surgery, which identifies issues and challenges, and develops a set of solutions and benchmarks to aid the academic surgical community in achieving these goals. Conclusion: Surgery must identify areas for improvement and work iteratively to address and correct past deficiencies. This requires honest and ongoing identification and correction of implicit and explicit biases. Increasing diversity in our departments, residencies, and universities will improve patient care, enhance productivity, augment community connections, and achieve our most fundamental ambition—doing good for our patients.

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Results of a Prospective, Multicenter Initiative Aimed at Developing Opioid-prescribing Guidelines After Surgery

imageObjective: The aim of this study was to conduct a prospective, multicenter survey of patients regarding postoperative opioid use to inform development of standardized, evidence-based, procedure-specific opioid prescribing guidelines. Summary of Background Data: Previous work has shown significant variation in the amount of opioids prescribed after elective procedures, calling for optimization of prescribing. Methods: Adults (n = 3412) undergoing 25 elective procedures were identified prospectively from 3 academic centers (March 2017 to January 2018) to complete a 29-question telephone interview survey 21 to 35 days post-discharge (n = 688 not contacted, n = 107 refused). Discharge opioids were converted into Morphine Milligram Equivalents (MMEs). Results: Of the 2486 patients who completed the survey, 91.2% received opioids at discharge [median 225 (interquartile range, IQR 125 to 381) MME]. A median of 43 (0 to 184) MMEs were consumed after discharge with 77.3% of patients having leftover opioids at the time of the survey. In total, 61.5% of prescribed opioids were unused; 31.4% of patients used no opioids, and 52.6% required

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An In Vivo Mouse Model to Measure Naïve CD4 T Cell Activation, Proliferation and Th1 Differentiation Induced by Bone Marrow-derived Dendritic Cells

Here, we present a protocol for the in vivo determination of naïve CD4 T cell (T cell) activation, proliferation, and Th1 differentiation induced by GM-CSF bone marrow (BM)-derived dendritic cells (DCs). In addition, this protocol describes BM and T-cell isolation, DC generation, and DC and T-cell adoptive transfer.

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Antioxidant and antidepressant-like effects of Eugenia catharinensis D. Legrand in an animal model of depression induced by corticosterone

Abstract

This work investigated the antioxidant and antidepressant-like effects of ethyl acetate extract from Eugenia catharinensis in mice treated with corticosterone (20 mg/Kg). The animals received saline or corticosterone (21 days) and, in the last 7 days, they were treated with the extract (50, 125, 200 or 250 mg/Kg) or vehicle. After 24 h, the mice were submitted to the open field and forced swimming tests, after which the hippocampus and cerebral cortex were removed. Our results showed that the extract decreased the immobility time of mice in the forced swimming test and that the extract was able to reverse the effect caused by corticosterone. Corticosterone pre-treatment generated oxidative stress, altering antioxidant enzymes in the nervous tissue. The extract increased the catalase and superoxide dismutase activities and reversed the effects of corticosterone. In the hippocampus, the extract increased superoxide dismutase activity and reversed the increase in catalase activity elicited by corticosterone. We propose that the effects elicited by the Eugenia catharinensis are dependent on the presence of phenolic compounds (gallic acid, protocatechuic acid, syringic acid, 4-hydroxy methylbenzoic acid, chlorogenic acid, salicylic acid, caffeic acid, vanillic acid, p-coumaric acid, isoquercetin, rutin, ferulic acid, aromadendrin, galangin and apigenin) in this extract, as demonstrated by HPLC-ESI-MS/MS.



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Computers in Abstraction/Representation Theory

Abstract

Recently, Horsman et al. (Proc R Soc Lond A 470:20140182, 2014) have proposed a new framework, Abstraction/Representation (AR) theory, for understanding and evaluating claims about unconventional or non-standard computation. Among its attractive features, the theory in particular implies a novel account of what is means to be a computer. After expounding on this account, I compare it with other accounts of concrete computation, finding that it does not quite fit in the standard categorization: while it is most similar to some semantic accounts, it is not itself a semantic account. Then I evaluate it according to the six desiderata for accounts of concrete computation proposed by Piccinini (Physical computation: a mechanistic account, Oxford University Press, Oxford, 2015). Finding that it does not clearly satisfy some of them, I propose a modification, which I call Agential AR theory, that does, yielding an account that could be a serious competitor to other leading account of concrete computation.



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Efficacy and safety of raltitrexed-based transarterial chemoembolization for colorectal cancer liver metastases

The liver is the most common site of colorectal cancer metastases. The present study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) with raltitrexed and oxaliplatin for colorectal liver metastases in a prospective, multicenter, single-arm trial conducted in 12 hospitals from different areas in China. A total of 90 patients with colorectal liver metastases were enrolled and treated by TACE with raltitrexed 4 mg and oxaliplatin 100 mg, followed by embolotherapy with 50 mg oxaliplatin and 5–20 ml lipiodol, administered every 28 days for four cycles. Patients were followed up every 3 months after the treatment and up to 12 months. The primary endpoint was time to progression. For the full analysis set (FAS), the median time to progression and overall survival were 9.1 and 17.8 months, respectively. The disease control rate in FAS was 71 (78.9%). Grade 3 or 4 adverse events were reported for 24 (26.7%) out of all 90 patients. Grade 3 thrombocytopenia, transglutaminase abnormality, and decreased neutrophil were observed in eight (8.9%), six (6.7%), and five (5.6%) patients, respectively. No unexpected adverse events or toxic deaths were observed. TACE with raltitrexed plus oxaliplatin is feasible, clinically beneficial, and well tolerated with low-grade toxicity for colorectal cancer patients with liver metastases. *Guoliang Shao and Ruibao Liu contributed equally to the writing of this article. Correspondence to Jianhua Wang, MD, PhD, Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032 China Tel: +86 136 1174 9557; fax: +86 216 403 8472; e-mail: wang.jianhua@zs-hospital.sh.cn Received April 13, 2018 Accepted July 30, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Cetirizine and thalidomide synergistically inhibit mammary tumorigenesis and angiogenesis in 7,12-dimethylbenz(a)anthracene-treated rats

Objective Cetirizine (CET) and thalidomide (THA) have been previously found to influence angiogenesis. The present study aimed to assess the ability of these drugs to influence mammary carcinogenesis in rats. Materials and methods Sixty Sprague-Dawley female rats, aged 8 weeks, received 15 mg of 7,12-dimethylbenz(a)anthracene (DMBA) intragastrically. CET and THA (1.0 and 3.0 mg/kg, respectively) were administered orally for 118 days after DMBA administration. At the end of the treatment period, mammary tumors were counted and weighed, and their morphology was analyzed using light microscopy. In tumor tissue, proliferation and apoptotic indices and microvessel density were determined using immunohistochemical techniques; the levels of angiogenic factors, vascular endothelial growth factor and basic fibroblast growth factor, were measured by western blotting. Results CET and THA, administered separately, failed to influence tumor formation and angiogenesis. In contrast, the drug combination decreased latency to first tumor (significant difference from vehicle-treated control and groups that received either drug alone, P

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Increased miR-203-3p and reduced miR-21-5p synergistically inhibit proliferation, migration, and invasion in esophageal cancer cells

Dysregulation of miR-203-3p and miR-21-5p has been identified in esophageal cancer (EC). The restoration of miR-203-3p and reduction of miR-21-5p were able to cause tumor suppression. Here, co-transfection of miR-203-3p mimics and miR-21-5p inhibitors led to an extraordinary increased expression of miR-203-3p and synergistically inhibited proliferation, migration, and invasion in EC cells. Moreover, we found that Ran GTPase (Ran) was dramatically inhibited in EC cells treated with the co-transfection of miR-203-3p mimics and miR-21-5p inhibitors. Finally, in-vivo studies showed that overexpression of miR-203-3p, combined with the suppression of miR-21-5p, significantly co-inhibited growth of tumors. The obtained data suggested that the development of miRNA-based combination therapeutics represents a promising cancer treatment strategy. Correspondence to Fang Zhang, PhD, College of Life Science and Bioengineering, Beijing University of Technology, 100 Pingleyuan, Chaoyang District, Beijing 100124, People's Republic of China Tel: +86 106 739 6212; fax: +86 106 739 2780; e-mail: zhangfang2000@bjut.edu.cn Received April 26, 2018 Accepted July 25, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Strategy Outlined for Shooter Incident in Health Care Facility

WEDNESDAY, Aug. 22, 2018 -- Adhering to a "secure, preserve, fight" strategy is recommended for health care professionals working with a vulnerable patient population, according to a Medicine and Society piece published in the Aug. 9 issue of the...

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Lower Long-Term Survival for In-Hospital Cardiac Arrests in Blacks

WEDNESDAY, Aug. 22, 2018 -- Older black survivors of in-hospital cardiac arrest (IHCA) have worse long-term survival than whites, according to a study published online Aug. 17 in Circulation. Lena M. Chen. M.D., from the University of Michigan in...

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National Provider Identifiers Are Vulnerable to Theft

WEDNESDAY, Aug. 22, 2018 -- National Provider Identifiers (NPIs) are vulnerable to identity theft, according to an article published in Physicians Practice. Thousands of health care providers' NPIs are stolen each year and are used for further...

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Teen Smoke Exposure Tied to Increase in Related Symptoms

WEDNESDAY, Aug. 22, 2018 -- Non-smoking adolescents with tobacco smoke exposure (TSE) have increased risk of TSE-related symptoms, according to a study published online Aug. 6 in Pediatrics. Ashley L. Merianos, Ph.D., from the University of...

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Paramedic-Led Intervention Cuts Ambulance Calls

WEDNESDAY, Aug. 22, 2018 -- For low-income older adults who live in subsidized housing, the Community Paramedicine at Clinic (CP@clinic), a paramedic-led, community-based health promotion program to prevent diabetes, cardiovascular disease, and...

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Advantages for HDHP Enrollees in Large Versus Small Firms

WEDNESDAY, Aug. 22, 2018 -- Workers in small firms are more likely to have higher deductible levels and lack employer contributions to help pay for out-of-pocket expenses compared to workers in larger firms, according to a study published in the...

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Similar Outcomes for Rural, Urban Cancer Patients in SWOG Trials

WEDNESDAY, Aug. 22, 2018 -- Rural and urban cancer patients with uniform care access through participation in a SWOG (formerly the Southwest Oncology Group) treatment trial have similar outcomes, according to a study published online Aug. 17 in JAMA...

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Spinal Manipulation Plus Exercise Effective for Teen Low Back Pain

WEDNESDAY, Aug. 22, 2018 -- Twelve weeks of spinal manipulative therapy (SMT) combined with exercise therapy (ET) is more effective than ET alone over a one-year period for adolescents with chronic low back pain (LBP), according to a study published...

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Detection of Viruses from Bioaerosols Using Anion Exchange Resin

An anion exchange resin-based method, adapted to liquid impingement-based bioaerosol sampling of viruses is demonstrated. When coupled with downstream molecular detection, the method allows for facile and sensitive detection of viruses from bioaerosols.

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Analysis of AtHIRD11 Intrinsic Disorder and Binding Towards Metal Ions by Capillary Gel Electrophoresis and Affinity Capillary Electrophoresis

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This protocol combines the characterization of a protein sample by capillary gel electrophoresis and a fast-binding screening for charged ligands by affinity capillary electrophoresis. It is recommended for proteins with a flexible structure, such as intrinsically disordered proteins, to determine any differences in binding for different conformers.

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Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization

Abstract

It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented.



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A Response to a Query Regarding a Recent Article: Always Follow Your Results Ulcerative Lesions and Night Sweats in an Intravenous Drug User

No abstract available

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Agarose-based Tissue Mimicking Optical Phantoms for Diffuse Reflectance Spectroscopy

Here, we demonstrate how agarose-based tissue-mimicking optical phantoms are made and how their optical properties are determined using a conventional optical system with an integrating sphere.

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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles

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Bicyclic aziridinium ions such as 1-azoniabicyclo[4.1.0]heptane tosylate were generated from 2-[4-tolenesulfonyloxybutyl]aziridine, which was utilized for the preparation of substituted piperidines and azepanes via regio- and stereospecific ring-expansion with various nucleophiles. This highly efficient protocol allowed us to prepare diverse azaheterocycles including natural products such as fagomine, febrifugine analogue and balanol.

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Probing the Limits of Egg Recognition Using Egg Rejection Experiments Along Phenotypic Gradients

This protocol provides guidelines for running egg rejection experiments: outlining techniques for painting experimental egg models to emulate the colors of natural bird eggs, conducting fieldwork, and analyzing the collected data. This protocol provides a uniform method for conducting comparable egg rejection experiments.

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Using Clinical Decision Support to Improve Referral Rates in Severe Symptomatic Aortic Stenosis: A Quality Improvement Initiative

Clinical decision support systems are used to ensure compliance with guidelines and can assist providers in improving quality of care. This quality improvement initiative was designed to evaluate the use of a clinical decision support system to improve specialist referral rate for patients with severe aortic stenosis. A clinical decision support system for cardiology and primary care providers was implemented to improve diagnosis of severe aortic stenosis. The ordering provider received an electronic medical record in-basket alert providing feedback and recommendations for referral to specialist for evaluation. The echocardiogram data were evaluated for change in specialist referral rate. Before clinical decision support system implementation, the referral rate was 72% for a 3-month period. All providers ordering echocardiograms received clinical decision support system notification if patient results met criteria based on valve severity (aortic valve area

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A Review of Measuring the Cognitive Workload of Electronic Health Records

The To Err Is Human report stated that 98 000 patients die yearly because of medical errors, and that medication errors kill more people than workplace injuries. The inadequate design and utilization of the electronic health record have been identified as major contributing factors to medical errors. Increased cognitive workload of clinicians has consistently been linked to the occurrence of medical errors. The purpose of this article was to synthesize the current state of the science on measuring clinicians' cognitive workload associated with using electronic health records in order to inform evidence-based guidelines. The major considerations identified in the literature involve the use of psychometric instruments, using efficiency as a proxy for cognitive workload, and eye tracking. The National Aeronautics and Space Administration Task Load Index was the most used psychometric instrument, but reliability measures were not reported. It is important to evaluate reliability of psychometric instruments because the consistency of the instrument can change when administered to different populations. Efficiency is an observable measure defined by the total time to complete a task and the total number of physical interactions with the user interface. Efficiency can allow the use of statistical modeling, but it does not directly evaluate the mental activity associated with using an electronic health record interface. Eye tracking has been used extensively in the literature to measure cognitive workload via changes in pupil size related to mental activity, but it is not often used to measure the cognitive workload associated with using the electronic health record. Eye tracking is very useful for continuous monitoring of cognitive workload. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Bryan A. Wilbanks, PhD, DNP, NB 545, 1720 2nd Ave S, Birmingham AL 35294 (BWilbanks@uab.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Enteral Nutrition Should Not Be Given to Patients on Vasopressor Agents

No abstract available

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Ultrasound Assessment of the Change in Carotid Corrected Flow Time in Fluid Responsiveness in Undifferentiated Shock

Objectives: Adequate assessment of fluid responsiveness in shock necessitates correct interpretation of hemodynamic changes induced by preload challenge. This study evaluates the accuracy of point-of-care Doppler ultrasound assessment of the change in carotid corrected flow time induced by a passive leg raise maneuver as a predictor of fluid responsiveness. Noninvasive cardiac output monitoring (NICOM, Cheetah Medical, Newton Center, MA) system based on a bioreactance method was used. Design: Prospective, noninterventional study. Setting: ICU at a large academic center. Patients: Patients with new, undifferentiated shock, and vasopressor requirements despite fluid resuscitation were included. Patients with significant cardiac disease and conditions that precluded adequate passive leg raising were excluded. Interventions: Carotid corrected flow time was measured via ultrasound before and after a passive leg raise maneuver. Predicted fluid responsiveness was defined as greater than 10% increase in stroke volume on noninvasive cardiac output monitoring following passive leg raise. Images and measurements were reanalyzed by a second, blinded physician. The accuracy of change in carotid corrected flow time to predict fluid responsiveness was evaluated using receiver operating characteristic analysis. Measurements and Main Results: Seventy-seven subjects were enrolled with 54 (70.1%) classified as fluid responders by noninvasive cardiac output monitoring. The average change in carotid corrected flow time after passive leg raise for fluid responders was 14.1 ± 18.7 ms versus –4.0 ± 8 ms for nonresponders (p

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Association Between Hospital Volume and Mortality in Status Epilepticus: A National Cohort Study

Objectives: In various medical and surgical conditions, research has found that centers with higher patient volumes have better outcomes. This relationship has not previously been explored for status epilepticus. This study sought to examine whether centers that see higher volumes of patients with status epilepticus have lower in-hospital mortality than low-volume centers. Design: Cohort study, using 2010–2015 data from the nationwide Case Mix Programme database of the U.K.'s Intensive Care National Audit and Research Centre. Setting: Greater than 90% of ICUs in United Kingdom, Wales, and Northern Ireland. Patients: Twenty-thousand nine-hundred twenty-two adult critical care admissions with a primary or secondary diagnosis of status epilepticus or prolonged seizure. Interventions: Annual hospital status epilepticus admission volume. Measurements and Main Results: We used multiple logistic regression to evaluate the association between hospital annual status epilepticus admission volume and in-hospital mortality. Hospital volume was modeled as a nonlinear variable using restricted cubic splines, and generalized estimating equations with robust SEs were used to account for clustering by institution. There were 2,462 in-hospital deaths (11.8%). There was no significant association between treatment volume and in-hospital mortality for status epilepticus (p = 0.54). This conclusion was unchanged across a number of subgroup and sensitivity analyses, although we lacked data on seizure duration and medication use. Secondary analyses suggest that many high-risk patients were already transferred from low- to high-volume centers. Conclusions: We find no evidence that higher volume centers are associated with lower mortality in status epilepticus overall. It is likely that national guidelines and local pathways in the United Kingdom allow efficient patient transfer from smaller centers like district general hospitals to provide satisfactory patient care in status epilepticus. Future research using more granular data should explore this association for the subgroup of patients with refractory and superrefractory status epilepticus. This work was performed at Queen Elizabeth Hospital Birmingham, University Hospital of Birmingham NHS trust. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/29S62lw). Dr. Whitehouse received a Queen Elizabeth Hospital Birmingham Charity Award for time spent on this study; he is also supported by Epilepsy Research UK unconditionally for this study; he disclosed that he is Chief Investigator for a National Institute for Health Research Efficacy and Mechanism Evaluation funded study into Septic Shock and Beta Blockade (STudy into the REversal of Septic Shock with Landiolol). Dr. Bion disclosed that he is a research advisor to Nestle, for which he receives an honorarium of less than £1,000 per year. Dr. Veenith received a Queen Elizabeth Hospital Birmingham Charity Award for time spent on this study, and he received support for article research from Queen Elizabeth hospital medical charities. For information regarding this article, E-mail: robert.goulden@doctors.org.uk Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Southern South Australian groundwater microbe diversity

ABSTRACT
Groundwater is increasingly used globally for domestic, industrial and agricultural production. While many studies have focused on groundwater as a resource, the diverse ecosystems within are often ignored. Here, we assess 54 Southern South Australian groundwater microbial communities from the populated part of the state to assess their status and dynamics in isolated groundwater systems. We observed a strong site-to-site individuality in groundwater bacterial communities, likely due to the isolated nature of groundwater bodies leading to unique ecosystems. Rank abundance analysis indicates bacterial diversity is maintained even at low abundances and that the distribution fits classical ecological models for strong competition in resource-limited environments. Combined, our data indicates that despite overrepresentation of pollutant-associated bacterial orders in and around the Adelaide metropolitan area, microbial communities remain diverse and show little evidence of converging on a common pollutant-effected community.

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Dependency of DNA extraction efficiency on cell concentration confounds molecular quantification of microorganisms in groundwater

ABSTRACT
Quantification of microbes in water systems is essential to industrial practices ranging from drinking water and wastewater treatment to groundwater remediation. While quantification using DNA-based molecular methods is precise, the accuracy is dependent on DNA extraction efficiencies. We show that the DNA yield is strongly impacted by the cell concentration in groundwater samples (r = −0.92, P < 0.0001). This has major implications for industrial applications using quantitative polymerase chain reaction (qPCR) to determine cell concentrations in water, including bioremediation. We propose a simple normalization method using a DNA recovery ratio, calculated with the total cell count and DNA yield. Application of this method to enumeration of bacteria and archaea in groundwater samples targeting phylogenetic markers (16S rRNA) demonstrated an increased goodness of fit after normalization (7.04 vs 0.94 difference in Akaike's information criteria). Furthermore, normalization was applied to qPCR quantification of functional genes and combined with DNA sequencing of archaeal and bacterial 16S rRNA genes to monitor changes in abundance of methanogenic archaea and sulphate-reducing bacteria in groundwater. The integration of qPCR and DNA sequencing with appropriate normalization enables high-throughput quantification of microbial groups using increasingly affordable and accessible techniques. This research has implications for microbial ecology and engineering research as well as industrial practice.

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A meta-analysis reveals universal gut bacterial signatures for diagnosing the incidence of shrimp disease

Abstract
Increasing evidence indicates that dysbiosis in the gut microbiota contributes to disease pathogenesis. However, whether certain taxa are universally indicative of diverse shrimp diseases is unclear thus far. We conducted a meta-analysis to explore the divergences in gut microbiota between healthy and diseased shrimp. The gut bacterial communities of healthy shrimp varied significantly (P < 0.05 in each comparison) over ontogenetic stages, and were distinct from the corresponding diseased cohorts at each life stage. Both phylogenetic-based mean nearest taxon distance analysis and multivariate dispersion testing revealed that shrimp disease weakened the relative importance of deterministic processes in governing the gut microbiota. Partitioning beta diversity analysis indicated that temporal turnover governed the gut microbiota as healthy shrimp aged, whereas this trend was retarded in disease cohorts, concurrent with an increased nestedness. After ruling out the age-discriminatory and disease-specific orders, a high diagnosed accuracy (85.9%) of shrimp health status was achieved by using the profiles of the 11 universal disease-discriminatory orders as independent variables. These findings improve current understanding of how disease alters the ecological processes that govern the shrimp gut microbiota assembly, and exemplifies the potential application of universal bacterial signatures to diagnose the incidence of diverse shrimp diseases, irrespective of causal pathogens.

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Microbial diversity along a gradient in peatlands treating mining-affected waters

ABSTRACT
Peatlands are used for the purification of mining-affected waters in Northern Finland. In Northern climate, microorganisms in treatment peatlands (TPs) are affected by long and cold winters, but studies about those microorganisms are scarce. Thus, the bacterial, archaeal and fungal communities along gradients of mine water influence in two TPs were investigated. The TPs receive waters rich in contaminants, including arsenic (As), sulfate (SO42−) and nitrate (NO3). Microbial diversity was high in both TPs, and microbial community composition differed between the studied TPs. Bacterial communities were dominated by Proteobacteria, Actinobacteria, Chloroflexi and Acidobacteria, archaeal communities were dominated by Methanomicrobia and the Candidate phylum Bathyarchaeota, and fungal communities were dominated by Ascomycota (Leotiomycetes, Dothideomycetes, Sordariomycetes). The functional potential of the bacterial and archaeal communities in TPs was predicted using PICRUSt. Sampling points affected by high concentrations of As showed higher relative abundance of predicted functions related to As resistance. Functions potentially involved in nitrogen and SO42− turnover in TPs were predicted for both TPs. The results obtained in this study indicate that (i) diverse microbial communities exist in Northern TPs, (ii) the functional potential of the peatland microorganisms is beneficial for contaminant removal in TPs and (iii) microorganisms in TPs are likely well-adapted to high contaminant concentrations as well as to the Northern climate.

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EMS Pioneers: Missouri paramedic says 'EMS chose me' 37 years ago

Sara Wainwright lauds ROSC progress, laments opioid epidemic

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A Western Blotting Protocol for Small Numbers of Hematopoietic Stem Cells

A standard Western blotting protocol was optimized for analyzing as few as 500 hematopoietic stem or progenitor cells. Optimization involves careful handling of the cell sample, limiting transfers between tubes, and directly lysing the cells in Laemmli sample buffer.

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Divergent brain gene expression patterns associate with distinct cell-specific tau neuropathology traits in progressive supranuclear palsy

Abstract

Progressive supranuclear palsy (PSP) is a neurodegenerative parkinsonian disorder characterized by tau pathology in neurons and glial cells. Transcriptional regulation has been implicated as a potential mechanism in conferring disease risk and neuropathology for some PSP genetic risk variants. However, the role of transcriptional changes as potential drivers of distinct cell-specific tau lesions has not been explored. In this study, we integrated brain gene expression measurements, quantitative neuropathology traits and genome-wide genotypes from 268 autopsy-confirmed PSP patients to identify transcriptional associations with unique cell-specific tau pathologies. We provide individual transcript and transcriptional network associations for quantitative oligodendroglial (coiled bodies = CB), neuronal (neurofibrillary tangles = NFT), astrocytic (tufted astrocytes = TA) tau pathology, and tau threads and genomic annotations of these findings. We identified divergent patterns of transcriptional associations for the distinct tau lesions, with the neuronal and astrocytic neuropathologies being the most different. We determined that NFT are positively associated with a brain co-expression network enriched for synaptic and PSP candidate risk genes, whereas TA are positively associated with a microglial gene-enriched immune network. In contrast, TA is negatively associated with synaptic and NFT with immune system transcripts. Our findings have implications for the diverse molecular mechanisms that underlie cell-specific vulnerability and disease risk in PSP.



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Editorial: Editorial for thematic issue on Archaea



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What's the link between vitamin D, gum health, and diabetes?

A new study finds that periodontitis and vitamin D insufficiency increase the risk of diabetes and make blood sugar levels more difficult to manage.

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LncRNA ANRIL regulates AML development through modulating the glucose metabolism pathway of AdipoR1/AMPK/SIRT1

Abstract

The long noncoding RNA ANRIL has been found to be abnormally expressed and play important roles in different cancers. However, the expression and function of ANRIL in acute myeloid leukemia (AML) remain to be declared. In this study, we found that ANRIL is up-regulated in AML patients at diagnosis and down-regulated in patients after complete remission (CR). Functional studies showed that knockdown of ANRIL expression resulted in a decline in glucose uptake and inhibition of AML cell maintenance in vitro and in vivo. Mechanically, ANRIL was found to repress the expression of Adiponectin receptor (AdipoR1), a key regulator of glucose metabolism. Both ANRIL and AdipoR1 knockdown reduced the expression levels of phosphorylation of AMPK and SIRT1, implying a previously unappreciated ANRIL-AdipoR1-AMPK/SIRT1 signaling pathway in regulating cell glucose metabolism and survival in AML. The study is the first to demonstrate that ANRIL promotes malignant cell survival and cell glucose metabolism to accelerate AML progression and is a potential prognostic marker and therapeutic target in AML treatment.



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LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway

Abstract

Background

Gastric cancer (GC) is a common malignancy and frequent cause of cancer-related death. Long non-coding RNAs (lncRNAs) have emerged as important regulators and tissue-specific biomarkers of multiple cancers, including GC. Recent evidence has indicated that the novel lncRNA LINC01133 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in GC remain largely unknown.

Methods

LINC01133 expression was detected in 200 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of LINC01133 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, quantitative PCR arrays, TOPFlash/FOPFlash reporter assay, luciferase assay, and rescue experiments.

Results

LINC01133 was downregulated in GC tissues and cell lines, and its low expression positively correlated with GC progression and metastasis. Functionally, LINC01133 depletion promoted cell proliferation, migration, and the epithelial–mesenchymal transition (EMT) in GC cells, whereas LINC01133 overexpression resulted in the opposite effects both in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-106a-3p was a direct target of LINC01133, which functioned as a ceRNA in regulating GC metastasis. Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/β-catenin pathway in an APC-dependent manner.

Conclusions

Our findings suggest that reduced expression of LINC01133 is associated with aggressive tumor phenotypes and poor patient outcomes in GC. LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.



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People Pick Gifts That Will “Wow” Rather Than Satisfy Recipients

Gift givers tend to focus on the "big reveal," leading them to choose whichever gift is more likely to surprise and delight the recipient in the moment – even when other options are more likely to bring recipients the greatest satisfaction, according to findings published in Psychological Science, a journal of the Association for Psychological Science.

"Our findings suggest that the pleasure that we can derive from others' display of emotions is more powerful than previously considered," says researcher Adelle Yang of the National University of Singapore, lead author on the research.

We commonly assume that other peoples' emotional displays are a representation of their internal state, such as their happiness and welfare, and we use these displays to guide our decision making. Yang and coauthor Oleg Urminsky of the Booth School of Business at the University of Chicago speculated that others' emotional displays may actually drive the decisions we make on their behalf.

Specifically, the researchers posited the "smile-seeking hypothesis," surmising that people would gravitate towards the gifts that they anticipate will elicit the most enthusiastic emotional responses, rather than those that the recipients themselves would prefer or would derive the most satisfaction from.

The researchers tested this hypothesis in a series of studies involving both real and imaginary gift-giving decisions.

In one online study, 357 participants imagined they were either part of a gift-receiving couple or one of the couple's gift-giving friends. They then saw pictures and descriptions of two similarly priced pairs of mugs – one set was personalized and the other had an ergonomic design. They rated how much they liked each option, which option they preferred, and predicted the emotional response and satisfaction that each option would elicit.

Regardless of whether they were giving or receiving the gift, participants anticipated that the personalized mugs would elicit a stronger emotional response than the ergonomic mugs would. Givers thought the couple would be equally satisfied with the two mug options and tended to prefer the personalized mugs, a preference driven by the emotional response they anticipated from the couple. Receivers, on the other hand, showed no preference for one option over the other.

In another online study, 295 participants in romantic relationships evaluated pairs of similarly priced Valentine's Day gifts. The choice pairs included one dozen roses in bloom or two dozen roses about to bloom, a bouquet of fresh flowers or a bonsai plant, and a heart-shaped basket containing cookies or fruit. Again, givers were more likely than receivers to choose the option that they thought would elicit the strongest immediate reaction, such as the bouquet of fresh flowers, over the option that was likely to deliver more long-term satisfaction, such as the bonsai plant.

Findings from additional studies revealed that givers' preference for gifts with a "wow" factor disappeared when they learned that they wouldn't be able to see the recipient's reaction.

When Yang and Urminsky asked people to think about gifts they had actually given or received, they found that people seem to derive the most enjoyment from receiving gifts, such as books and money, that givers often shy away from because they tend not to elicit strong emotional reactions.

Indeed, an online study examining real-life Christmas gifts showed that people derived the most enjoyment from giving those gifts that elicited the biggest reactions from recipients, especially if they were able to watch the recipient open it in person. The satisfaction that gifts would bring their recipients over the long term did not seem to influence gift-givers' enjoyment.

"These discrepant preferences are surprisingly 'stubborn,'" says Yang. "In this and other ongoing research, the data suggest that givers often report a different preference when imagining themselves as receivers, but that did not change their preference as givers."

Because this stubbornness is driven by strong motivational factors, asking givers to take the perspective of the recipient when choosing a gift is unlikely to sway their decision making. The researchers suspect that this same bias may influence decision making in even more consequential contexts:

"We expect that people tasked with making medical, financial, career, or consumption decisions for others are often influenced by anticipated interpersonal affective reactions, potentially at odds with their beliefs about the other person's long-term satisfaction or welfare," Yang and Urminsky conclude.

All data have been made publicly available via the Open Science Framework (OSF). The key materials necessary to reproduce the analyses have been uploaded on the OSF and Study 1 was preregistered. The complete Open Practices Disclosure for this article is online. This article has received the badges for Open Data, Open Materials, and Preregistration.



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