Nudt3 is an mRNA decapping enzyme that modulates cell migration [ARTICLE]

Removal of the 5'-end 7-methylguanosine cap structure is a critical step in the highly regulated process of mRNA decay. The Nudix hydrolase, Dcp2, was identified as a first decapping enzyme and subsequently shown to preferentially modulate stability of only a subset of mRNAs. This observation led to the hypothesis that mammalian cells possess multiple decapping enzymes that may function in distinct pathways. Here we report Nudt3 is a Nudix protein that possesses mRNA decapping activity in cells and is a modulator of MCF-7 breast cancer cell migration. Reduction of Nudt3 protein levels in MCF-7 cells promotes increased cell migration and corresponding enhanced filopodia extensions. Importantly, this phenotype was reversed by complementation with wild type, but not catalytically inactive Nudt3 protein indicating Nudt3 decapping activity normally functions to control cell migration. Genome-wide analysis of Nudt3 compromised cells identified elevated levels of transcripts involved in cell motility including integrin β6, lipocalin-2, and fibronectin. The observed increase in mRNA abundance was dependent on Nudt3 decapping activity where integrin β6 and lipocalin-2 were modulated directly through mRNA stability, while fibronectin was indirectly controlled. Moreover, increased cell migration observed in Nudt3 knockdown cells was mediated through the extracellular integrin β6 and fibronectin protein nexus. We conclude that Nudt3 is an mRNA decapping enzyme that orchestrates expression of a subset of mRNAs to modulate cell migration and further substantiates the existence of multiple decapping enzymes functioning in distinct cellular pathways in mammals.

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Correlates of the timed 25 foot walk in a multiple sclerosis outpatient rehabilitation clinic.

The Timed 25 Foot Walk (T25FW), a test of maximum walking speed on a short distance, is commonly used to monitor ambulation status and to assess treatment outcomes in multiple sclerosis (MS). The main aim of this study was to determine how walking speed on the T25FW correlates with other clinician-reported and patient-reported measures in an outpatient MS rehabilitation clinic. We analyzed cross-sectional data systematically collected during a physiatry evaluation for the management of spasticity and walking limitations. In addition to demographic variables and the Expanded Disability Status Scale (EDSS), measures of body functions [lower extremity manual muscle testing (LE MMT), lower extremity Modified Ashworth Scale, Fatigue Severity Scale, leg pain], and measures of activity and quality of life (reported frequency of falls, Incapacity Status Scale, Rivermead Mobility Index, EQ5D health questionnaire, and Patient Health Questionnaire-9 items) were administered. A multivariate regression analysis was carried out. 199 patients were included in the analysis [age 49.41 (9.89) years, disease duration 15.40 (10.22) years, EDSS score 5.6 (1.2), and T25FW speed 70.93 (44.13) cm/s]. Both EDSS and LE MMT were correlated significantly with T25FW speed (R2=0.692, P

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The emotional impact of a malpractice suit on physicians: Maintaining resilience

PHYSICIANS WHO HAVE BEEN involved in malpractice actions are all too familiar with the range of emotions they experience during the process. Anxiety, fear, frustration, remorse, self-doubt, shame,...

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When we need to remember that it is more than a job

"I am forever humbled." So said a heart failure...

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It is not the critic’s voice that should count

DURING MY 25 YEARS as a defense attorney, I have seen the traumatic impact that the allegation of medical malpractice can have on healthcare providers. And I have seen many times that in the...

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Dexmedetomidine for the Treatment of Hyperactive Delirium Refractory to Haloperidol in Nonintubated ICU Patients: A Nonrandomized Controlled Trial.

Objectives: To evaluate the clinical effectiveness, safety, and cost of dexmedetomidine for the treatment of agitated delirium refractory to haloperidol in nonintubated critically ill patients. Design: Nonrandomized, controlled trial. Setting: Intensive care department of a tertiary care nonprofit hospital. Patients: All consecutive admissions to a medical-surgical ICU with a diagnosis of agitated delirium. Interventions: Initial haloperidol titration: all patients received IV bolus doses of haloperidol until agitation was controlled (Richmond Agitation Sedation Scale scoring range, 0 to -2) or reaching the maximum daily dose. Group comparison: patient responders to haloperidol (control group) were compared with nonresponders (dexmedetomidine group). Measurements and Main Results: A total of 132 nonintubated patients were treated with haloperidol in the initial haloperidol titration phase. Forty-six patients (34.8%; 95% CI, 26.0-43.1%) did not respond to haloperidol, and 86 patients (65.2%; 95% CI, 56.3-73.0%) were responders. During the group comparison phase, dexmedetomidine achieved a higher percentage of time in satisfactory sedation levels than did haloperidol (92.7% [95% CI, 84.5-99.8%] vs 59.3% [95% CI, 48.6-69.3%], respectively; p = 0.0001). Haloperidol was associated with 10 cases (11.6% [95% CI, 6.5-21.2%]) of oversedation and two (2.0% [0.4-8%]) of corrected QT lengthening. Direct cost of dexmedetomidine was 17 times greater than haloperidol, but it achieved a mean savings of $4,370 per patient due to the reduction in length of ICU stay. Conclusions: In the study conditions, dexmedetomidine shows to be useful as a rescue drug for treating agitation due to delirium in nonintubated patients in whom haloperidol has failed, and it seems to have a better effectiveness, safety, and cost-benefit profile than does haloperidol. Copyright (C) by 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Measurement of CCT by ultrasonic pachymeter and oculus pentacam

Rashid RF, Farhood QK

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Retreatments after multifocal intraocular lens implantation: an analysis

Gundersen KG, Makari S, Ostenstad S, Potvin R

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Reduction of the Bethe–Salpeter wave function: Fermion–scalar case and scalar–scalar case

Abstract

In this paper, the general forms of the nonrelativistic Bethe–Salpeter wave functions for fermion–scalar bound state and scalar–scalar bound state are presented. Using the obtained normalization conditions and the corresponding Schrödinger equations for these bound states, the nonrelativistic Bethe–Salpeter wave functions can be calculated and can be used to compute the amplitude for the process involving these bound states.

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Hybrid synchronization of two independent chaotic systems on complex network

Abstract

The real network nodes are always interfered by other messages. So, how to realize the hybrid synchronization of two independent chaotic systems based on the complex network is very important. To solve this problem, two other problems should be considered. One is how the same network node of the complex network was affected by different information sources. Another is how to achieve hybrid synchronization on the network. In this paper, the theoretical analysis and numerical simulation on various complex networks are implemented. The results indicate that the hybrid synchronization of two independent chaotic systems is feasible.

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A cross-sectional internet-based patient survey of the management strategies for gout

Almost half of the patients with gout are not prescribed urate-lowering therapy (ULT) by their health care provider and >50 % use complementary and alternative therapies. Diet modification is popular among gou...

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BMS-754807 is cytotoxic to non-small cell lung cancer cells and enhances the effects of platinum chemotherapeutics in the human lung cancer cell line A549

Despite advances in targeted therapy for lung cancer, survival for patients remains poor and lung cancer remains the leading cause of cancer-related deaths worldwide. The type I insulin-like growth factor rece...

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The Medial Antebrachial Cutaneous Nerve - Everything You Need To Know - Dr. Nabil Ebraheim

Educational video describing the anatomy of the medial antebrachial cutaneous nerve.

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Health service provider education and/or training in infant male circumcision to improve short- and long-term morbidity outcomes: protocol for systematic review

There has been an expansion of circumcision services in Africa as part of a long-term HIV prevention strategy. However, the effect of infant male circumcision on morbidity and mortality still remains unclear. ...

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Comparing the coverage, recall, and precision of searches for 120 systematic reviews in Embase, MEDLINE, and Google Scholar: a prospective study

Previously, we reported on the low recall of Google Scholar (GS) for systematic review (SR) searching. Here, we test our conclusions further in a prospective study by comparing the coverage, recall, and precis...

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Do Cochrane summaries help student midwives understand the findings of Cochrane systematic reviews: the BRIEF randomised trial

Abstracts and plain language summaries (PLS) are often the first, and sometimes the only, point of contact between readers and systematic reviews. It is important to identify how these summaries are used and t...

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A historical glimpse into treating childhood hydrocephalus

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Erratum to: Posterior reversible encephalopathy syndrome (PRES): a rare condition after resection of posterior fossa tumors: two new cases and review of the literature

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Role of “major” and “minor” lambdoid arch sutures in posterior cranial fossa changes: mechanism of cerebellar tonsillar herniation in infants with multisutural craniosynostosis

Abstract

Purpose

This study aimed to explain the functional role of lambdoid arch sutures in the development of cerebellar tonsillar herniation. Posterior cranial fossa (PCF) changes were investigated in infants with premature synostosis of the major and minor sutures of the lambdoid arch without premature synostosis of the PCF synchondroses.

Methods

Morphometric and volumetric PCF measurements were performed on preoperative high-resolution CT studies in 12 infants with multisutural craniosynostosis involving the lambdoid arch and compared with those of 12 age-matched healthy subjects.

Results

All 12 patients had hypoplasia of PCF bone structures and normal volumes of the PCF and neural structures. PCF hypoplasia was related to exocciput length in infants with isolated involvement of major sutures, while it was related to posterior skull base hemifossae in infants with isolated involvement of minor lambdoid arch sutures. Foramen magnum AP diameter was reduced in babies with major suture involvement and tonsillar herniation, while foramen magnum AP and LL diameters were reduced in babies with minor suture involvement without tonsillar herniation. Right and left jugular foramen (JF) areas differed in all infants; however, the area of the smaller JF was significantly reduced only in infants with involvement of minor lambdoid arch sutures.

Conclusion

Hypoplasia of PCF bone structures due to sutural synostosis of the lambdoid arch is a required predisposing but not sufficient factor for the development of cerebellar tonsillar herniation through the foramen magnum. Normal PCF volume and foramen magnum anatomy may partly explain the development of cerebellar tonsil herniation in infants with lambdoid arch synostosis.

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Variation of the slope of the tentorium during childhood

Abstract

Background and purpose

Neural structures in the posterior fossa grow at different rates during development. While there are computationally intensive approaches to analyze growth of the cerebellum and brainstem, there is a paucity of information about summary measures of normal posterior fossa development suitable for real-time clinical use. The present study investigates changes in the trajectory of the tentorium as measured by the occipital and tentorial angles at different stages of development.

Methods

A retrospective study was conducted drawing from a Boston Children's Hospital database of over 1500 magnetic resonance imaging (MRI) studies. The imaging study population included fetuses older than 20 gestational weeks and children between the ages of 0 and 10 years. Two parameters were measured for all subjects: (1) the tentorial angle (the angle between the tentorium and a line from the internal occipital protuberance to the tuberculum sellae) and (2) the occipital angle (the angle between the tentorium and a line from the internal occipital protuberance to the opisthion). Descriptive statistics were used to analyze the study cohort.

Results

We reviewed 1510 brain MRI studies, and 367 studies met the inclusion criteria (125 fetal and 242 postnatal studies). During fetal development, the inclination of the tentorium showed an ascending course, while it plateaus after birth.

Conclusions

During the second and third trimesters, the tentorial and occipital angles steadily increase reflecting the dynamic growth of the posterior fossa structures. Postnatally, the tentorial angle decreases and the tentorium slopes downward and plateaus, possibly due to stabilization of posterior fossa development and ongoing growth of the cerebrum. Together, these findings suggest that the tentorial angle can serve as an imaging biomarker of posterior fossa development during the second half of fetal life.

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Drosophila Fed ARA and EPA Yields Eicosanoids, 15S-Hydroxy-5Z,8Z, 11Z, 13E-Eicosatetraenoic Acid, and 15S-Hydroxy-5Z,8Z,11Z,13E,17Z-Eicosapentaenoic Acid

Abstract

Drosophila melanogaster has been a widely used as a model system for its powerful genetic tools. However, it remains to be illustrated if Drosophila can be used to examine the biochemical and physiological metabolism of eicosanoids. Thus, the analysis on the metabolism of C20 polyunsaturated fatty acids (PUFA) in Drosophila was implemented with high performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS). Fatty acid (FA) analysis of the whole body, head, and thorax-abdomen in Drosophila showed C20 PUFA could only be found in Drosophila fed diets supplemented with eicosapentaenoic acid (EPA) and arachidonic acid (ARA), but not in Drosophila fed base diets. The C20 PUFA were found in abundance in the head. Drosophila fed ARA- and EPA-supplemented diets yielded 15S-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid [15(S)-HETE] and 15S-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid [15(S)-HEPE], respectively, while other sampled eicosanoids could not be detected. Similar results were obtained by incubating fly tissue supplemented with ARA or EPA. Furthermore, a genome sequence scan indicated that no gene encoding the key enzymes synthesizing eicosanoids were found in Drosophila. These findings demonstrate that Drosophila may possess a special lipid metabolic system, which is different from mammals.

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Brain stem herniation secondary to cerebrospinal fluid drainage in ruptured aneurysm surgery: a case report

A lumbar drainage catheter is frequently placed intra-operatively to decrease fluid pressure on the brain in aneurysmal subarachnoid cases. In rare cases, this catheter placement can lead to intracranial hypot...

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Saturation of electrical resistivity of solid iron at Earth’s core conditions

We report on the temperature dependence of the electrical resistivity of solid iron at high pressure, up to and including conditions likely to be found at the centre of the Earth. We have extended some of the ...

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