Παρασκευή, 20 Οκτωβρίου 2017

HIF-1α Promotes Breast Cancer Cell MCF-7 Proliferation and Invasion Through Regulating miR-210

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 297-301.


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PERK-Phosphorylated eIF2α Pathway Suppresses Tumor Metastasis Through Downregulating Expression of Programmed Death Ligand 1 and CXCL5 in Triple-Negative Breast Cancer

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 282-287.


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An Overview of Unfolded Protein Response Signaling and Its Role in Cancer

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 275-281.


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Imaging of Integrin αvβ3 Expression in Lung Cancers and Brain Tumors Using Single-Photon Emission Computed Tomography with a Novel Radiotracer 99mTc-IDA-D-[c(RGDfK)]2

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 288-296.


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Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to Activate Murine Dendritic Cells

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 302-308.


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HIF-1α Promotes Breast Cancer Cell MCF-7 Proliferation and Invasion Through Regulating miR-210

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 297-301.


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PERK-Phosphorylated eIF2α Pathway Suppresses Tumor Metastasis Through Downregulating Expression of Programmed Death Ligand 1 and CXCL5 in Triple-Negative Breast Cancer

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 282-287.


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An Overview of Unfolded Protein Response Signaling and Its Role in Cancer

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 275-281.


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Imaging of Integrin αvβ3 Expression in Lung Cancers and Brain Tumors Using Single-Photon Emission Computed Tomography with a Novel Radiotracer 99mTc-IDA-D-[c(RGDfK)]2

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 288-296.


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Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to Activate Murine Dendritic Cells

Cancer Biotherapy & Radiopharmaceuticals Oct 2017, Vol. 32, No. 8: 302-308.


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Effect of Myostatin SNP on muscle fiber properties in male Thoroughbred horses during training period

Abstract

Variants of the Myostatin gene have been shown to have an influence on muscle hypertrophy phenotypes in a wide range of mammalian species. Recently, a Thoroughbred horse with a C-Allele at the g.66493737C/T single-nucleotide polymorphism (SNP) has been reported to be suited to short-distance racing. In this study, we examined the effect of the Myostatin SNP on muscle fiber properties in young Thoroughbred horses during a training period. To investigate the effect of the Myostatin SNP on muscle fiber before training, several mRNA expressions were relatively quantified in biopsy samples from the middle gluteal muscle of 27 untrained male Thoroughbred horses (1.5 years old) using real-time RT-PCR analysis. The remaining muscle samples were used for immunohistochemical analysis to determine the population and area of each fiber type. All measurements were revaluated in biopsy samples of the same horses after a 5-month period of conventional training. Although the expressions of Myostatin mRNA decreased in all SNP genotypes, a significant decrease was found in only the C/C genotype after training. While, expression of VEGFa, PGC1α, and SDHa mRNAs, which relate to the biogenesis of mitochondria and capillaries, was significantly higher (54–82%) in the T/T than the C/C genotypes after training. It is suggested that hypertrophy of muscle fiber is directly associated with a decrease in Myostatin mRNA expression in the C/C genotype, and that increased expressions of VEGFa, PGC1α, and SDHa in the T/T genotype might be indirectly caused by the Myostatin SNP.



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Rifampicin Resistance and Multidrug-Resistant Tuberculosis Detection Using Xpert MTB/RIF in Wuhan, China: A Retrospective Study

Microbial Drug Resistance , Vol. 0, No. 0.


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Lessons From Team Nursing

When I hear discussions of or read about team-based care, I often think back to when I was in my BSN program, and team nursing was the relatively new model of care being implemented in hospital settings. As an integrated system of care, team nursing replaced the older functional models of nursing care. It was designed to accommodate multiple categories of hospital personnel to provide comprehensive care to groups of patients. I can still remember my senior clinical rotation (as well as the accompanying trepidation that my fellow students and I experienced) when it was our opportunity to be the team leaders and to be responsible for making the patient assignments, overseeing the development of care plans, scheduling team conferences, revising plans, and putting together a report for the next shift.

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Table of Contents



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Society



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Taking Care While Being Part of Something Bigger Than Ourselves

Nurses are the best caretakers. We give so much to others and that seems to double around the holiday season. As we leap with both feet into the season, I want to remind you to take care of yourself. If you work in the clinical setting like me, you are hitting the start of flu season. Patient volumes are up and breaks are short to nonexistent. On top of that, you're trying to finagle family time while covering your shift, call, or clinic obligations. My teammates and I attempt to give each other at least one 3-to-5–day stint off for family time around the holidays.

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Editorial Board



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States' Progress Toward Nurse Practitioner Full Practice Authority: Contemporary Challenges and Strategies

In 2017, South Dakota became the 22nd state to grant nurse practitioners (NPs) full practice authority (FPA; American Association of Nurse Practitioners, 2017a). Legislation for NP FPA introduced during 2017 in Arkansas, Illinois, Massachusetts, North Carolina, Oklahoma, and Pennsylvania resulted in varied outcomes. FPA legislation in Massachusetts, North Carolina, and Pennsylvania is still in progress. The goal of attaining NP FPA across the nation is steady albeit slow. NP advocates leading state FPA legislative campaigns are working diligently to address continually evolving challenges and gain support for FPA legislation.

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Information for Readers



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Pediatric Hip Pain: A Case Study

Hip pain in children can present a diagnostic challenge for the pediatric primary care provider. This case study examines an otherwise healthy 3-year-old girl with unilateral hip pain and intermittent refusal to bear weight on the affected side. Through history and physical examination, the provider was able to appropriately diagnose transient synovitis. This case study will summarize the care for hip pain in a child, including potential causes, a focused history and physical examination, appropriate diagnostic testing, and recommendations for home care and follow-up.

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Heterogeneous Patterns of Genetic Diversity and Differentiation in European and Siberian Chiffchaff (Phylloscopus collybita abietinus / P. tristis)

Identification of candidate genes for trait variation in diverging lineages and characterization of mechanistic underpinnings of genome differentiation are key steps towards understanding the processes underlying the formation of new species. Hybrid zones provide a valuable resource for such investigations since they allow for studying how genomes evolve as species exchange genetic material and for associating particular genetic regions with phenotypic traits of interest. Here we use whole-genome resequencing of both allopatric and hybridising populations of the European (Phylloscopus collybita abietinus) and the Siberian chiffchaff (P. tristis) - two recently diverged species which differ in morphology, plumage, song, habitat and migration - to quantify the regional variation in genome-wide genetic diversity and differentiation and to identify candidate regions for trait variation. We find that the levels of diversity, differentiation and divergence are highly heterogeneous with significantly reduced global differentiation and more pronounced differentiation peaks in sympatry than in allopatry. This pattern is consistent with regional differences in effective population size and recurrent background selection or selective sweeps reducing the genetic diversity in specific regions prior to lineage divergence, but the data also suggest that post-divergence selection has resulted in increased differentiation and fixed differences in specific regions. We find that hybridization and backcrossing is common in sympatry and that phenotype is a poor predictor of the genomic composition of sympatric birds. The combination of a differentiation scan approach with identification of fixed differences pinpoint a handful of candidate regions that might be important for trait variation between the two species.



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Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

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Effect of Stellate Ganglion Block on the Regional Hemodynamics of the Upper Extremity: A Randomized Controlled Trial

BACKGROUND: BACKGROUND:The success of stellate ganglion block (SGB) is traditionally determined on the basis of findings such as Horner's syndrome, temperature rise in the face, hyperemia of the tympanic membrane, and nasal congestion. However, decreases in vascular resistance and increases in blood flow in the arm may be more meaningful findings. To date, the effect of SGB on the regional hemodynamics of the arm has not been evaluated using pulsed-wave Doppler ultrasound. METHODS: METHODS:A total of 52 patients who were to undergo orthopedic surgery of the forearm were randomly assigned to either the mepivacaine group (SGB with 5 mL of 0.5% mepivacaine) or the saline group (SGB with 5 mL of normal saline). Before surgery, a single anesthesiologist performed a SGB under ultrasound guidance. The temperature of the upper extremity and the resistance index and blood flow in the brachial artery were measured before SGB, 15 and 30 minutes after SGB, and 1 hour after surgery. The severity of pain, requirement for rescue analgesics, and side effects of the local anesthetic agent were all documented. RESULTS: RESULTS:After SGB, the resistance index decreased significantly and the blood flow increased significantly in the brachial artery of members of the mepivacaine group (15 minutes: P = .004 and P

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Postoperative Outcomes in Obstructive Sleep Apnea Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis of Comparative Studies

BACKGROUND: BACKGROUND:Obstructive sleep apnea (OSA) is a common comorbidity in patients undergoing cardiac surgery and may predispose patients to postoperative complications. The purpose of this meta-analysis is to determine the evidence of postoperative complications associated with OSA patients undergoing cardiac surgery. METHODS: METHODS:A literature search of Cochrane Database of Systematic Reviews, Medline, Medline In-process, Web of Science, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL until October 2016 was performed. The search was constrained to studies in adult cardiac surgical patients with diagnosed or suspected OSA. All included studies must report at least 1 postoperative complication. The primary outcome is major adverse cardiac or cerebrovascular events (MACCEs) up to 30 days after surgery, which includes death from all-cause mortality, myocardial infarction, myocardial injury, nonfatal cardiac arrest, revascularization process, pulmonary embolism, deep venous thrombosis, newly documented postoperative atrial fibrillation (POAF), stroke, and congestive heart failure. Secondary outcome is newly documented POAF. The other exploratory outcomes include the following: (1) postoperative tracheal intubation and mechanical ventilation; (2) infection and/or sepsis; (3) unplanned intensive care unit (ICU) admission; and (4) duration of stay in hospital and ICU. Meta-analysis and meta-regression were conducted using Cochrane Review Manager 5.3 (Cochrane, London, UK) and OpenBUGS v3.0, respectively. RESULTS: RESULTS:Eleven comparative studies were included (n = 1801 patients; OSA versus non-OSA: 688 vs 1113, respectively). MACCEs were 33.3% higher odds in OSA versus non-OSA patients (OSA versus non-OSA: 31% vs 10.6%; odds ratio [OR], 2.4; 95% confidence interval [CI], 1.38–4.2; P = .002). The odds of newly documented POAF (OSA versus non-OSA: 31% vs 21%; OR, 1.94; 95% CI, 1.13–3.33; P = .02) was higher in OSA compared to non-OSA. Even though the postoperative tracheal intubation and mechanical ventilation (OSA versus non-OSA: 13% vs 5.4%; OR, 2.67; 95% CI, 1.03–6.89; P = .04) were significantly higher in OSA patients, the length of ICU stay and hospital stay were not significantly prolonged in patients with OSA compared to non-OSA. The majority of OSA patients were not treated with continuous positive airway pressure therapy. Meta-regression and sensitivity analysis of the subgroups did not impact the OR of postoperative complications for OSA versus non-OSA groups. CONCLUSIONS: CONCLUSIONS:Our meta-analysis demonstrates that after cardiac surgery, MACCEs and newly documented POAF were 33.3% and 18.1% higher odds in OSA versus non-OSA patients, respectively. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication August 16, 2017. Funding: The STOP-Bang tool is proprietary to University Health Network. This study is supported by University Health Network Foundation, and Department of Anesthesiology, University Health Network, University of Toronto. Conflicts of Interest: See Disclosures at the end of the article. 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 (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Frances Chung, MD, FRCPC, Department of Anesthesiology and Pain Medicine, Toronto Western Hospital, University Health Network, 399 Bathurst St, Toronto, Ontario, M5T 2S8, Canada. Address e-mail to frances.chung@uhn.ca. © 2017 International Anesthesia Research Society

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Physiology and Role of Intraocular Pressure in Contemporary Anesthesia

More than 26 million Americans suffer with cataracts, and with 3.6 million cataract extractions performed annually in the United States, it is the most common surgical procedure. The integrity of the delicate structures of the eye that mediate vision is dependent on the intraocular pressure (IOP). Yet, IOP acts to compress the vessels within the globe—akin to a Starling resistor—and is a key component that determines the ocular perfusion pressure, defined as the difference between arterial pressure and IOP. The retina is one of the most metabolically active tissues in the body, and its functional integrity is dependent on an adequate blood supply, with retinal function linearly related to the ocular perfusion pressure. Retinal cell death has been demonstrated at low perfusion pressures (below 50 mm Hg). Modern ophthalmic surgery involves globe irrigation, manipulation, and instrumentation, resulting in dynamic pressure fluxes within the eye. Marked elevations of IOP (up to 4–5 times the normal value) with consequent borderline retinal and optic disk perfusion pressures occur for prolonged periods during many ophthalmic procedures. General surgeries, including laparoscopic, spinal, and cardiac procedures, especially, with their demand for steep Trendelenburg or prolonged prone positioning and/or hypotensive anesthesia, can induce IOP changes and ocular perfusion imbalance. These rapid fluctuations in IOP, and so in perfusion, play a role in the pathogenesis of the visual field defects and associated ocular morbidity that frequently complicate otherwise uneventful surgeries. The exact etiology of such outcomes is multifactorial, but ocular hypoperfusion plays a significant and frequently avoidable role. Those with preexisting compromised ocular blood flow are especially vulnerable to intraoperative ischemia, including those with hypertension, diabetes, atherosclerosis, or glaucoma. However, overly aggressive management of arterial pressure and IOP may not be possible given a patient's comorbidity status, and it potentially exposes the patient to risk of catastrophic choroidal hemorrhage. Anesthetic management significantly influences the pressure changes in the eye throughout the perioperative period. Strategies to safeguard retinal perfusion, reduce the ischemic risk, and minimize the potential for expulsive bleeding must be central to the anesthetic techniques selected. This review outlines: important physiological principles; ophthalmic and general procedures most likely to develop damaging IOP levels and their causative factors; the effect of anesthetic agents and techniques on IOP; recent scientific evidence highlighting the significance of perfusion changes during surgery; and key aspects of postoperative visual loss and management approaches for high-risk patients presenting for surgery. Accepted for publication September 6, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Dermot J. Kelly, MRCPI, FFARCSI, DABA, Department of Anesthesia, Royal Victoria Eye and Ear Hospital, Adelaide Rd, Dublin 2, Ireland. Address e-mail to drdermotkelly@gmail.com. © 2017 International Anesthesia Research Society

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Insight Into Our Technology: Anesthesia Information Management Systems

Anesthesia information management systems (AIMS) have evolved from simple, automated intraoperative record keepers in a select few institutions to widely adopted, sophisticated hardware and software solutions that are integrated into a hospital's electronic health record system and used to manage and document a patient's entire perioperative experience. AIMS implementations have resulted in numerous billing, research, and clinical benefits, yet there remain challenges and areas of potential improvement to AIMS utilization. This article provides an overview of the history of AIMS, the components and features of AIMS, and the benefits and challenges associated with implementing and using AIMS. As AIMS continue to proliferate and data are increasingly shared across multi-institutional collaborations, visual analytics and advanced analytics techniques such as machine learning may be applied to AIMS data to reap even more benefits. Accepted for publication September 8, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Allan F. Simpao, MD, MBI, Department of Anesthesiology and Critical Care, Division of General Anesthesia, Perelman School of Medicine at the University of Pennsylvania and The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104. Address e-mail to simpaoa@email.chop.edu. © 2017 International Anesthesia Research Society

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Fatigue Risk Management: The Impact of Anesthesiology Residents’ Work Schedules on Job Performance and a Review of Potential Countermeasures

Long duty periods and overnight call shifts impair physicians' performance on measures of vigilance, psychomotor functioning, alertness, and mood. Anesthesiology residents typically work between 64 and 70 hours per week and are often required to work 24 hours or overnight shifts, sometimes taking call every third night. Mitigating the effects of sleep loss, circadian misalignment, and sleep inertia requires an understanding of the relationship among work schedules, fatigue, and job performance. This article reviews the current Accreditation Council for Graduate Medical Education guidelines for resident duty hours, examines how anesthesiologists' work schedules can affect job performance, and discusses the ramifications of overnight and prolonged duty hours on patient safety and resident well-being. We then propose countermeasures that have been implemented to mitigate the effects of fatigue and describe how training programs or practice groups who must work overnight can adapt these strategies for use in a hospital setting. Countermeasures include the use of scheduling interventions, strategic naps, microbreaks, caffeine use during overnight and extended shifts, and the use of bright lights in the clinical setting when possible or personal blue light devices when the room lights must be turned off. Although this review focuses primarily on anesthesiology residents in training, many of the mitigation strategies described here can be used effectively by physicians in practice. Accepted for publication September 8, 2017. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Keith J. Ruskin, MD, Department of Anesthesia and Critical Care, University of Chicago, 5841 S Maryland Ave, MC4028, Chicago, IL 60637. Address e-mail to ruskin@uchicago.edu. © 2017 International Anesthesia Research Society

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Noninfectious Fever in the Near-Term Pregnant Rat Induces Fetal Brain Inflammation: A Model for the Consequences of Epidural-Associated Maternal Fever

BACKGROUND: BACKGROUND:Women laboring with epidural analgesia experience fever much more frequently than do women who chose other forms of analgesia, and maternal intrapartum fever is associated with numerous adverse consequences, including brain injury in the fetus. We developed a model of noninfectious inflammatory fever in the near-term pregnant rat to simulate the pathophysiology of epidural-associated fever and hypothesized that it would produce fetal brain inflammation. METHODS: METHODS:Twenty-four pregnant Sprague-Dawley rats were studied at 20 days gestation (term: 22 days). Dams were treated by injection of rat recombinant interleukin (IL)-6 or vehicle at 90-minute intervals, and temperature was monitored every 30 minutes. Eight hours after the first treatment, dams were delivered of fetuses and then killed. Maternal IL-6 was measured at delivery. Fetal brains (n = 24) were processed and stained for ED-1/CD68, a marker for activated microglia, and cell counts in the lateral septal and hippocampal brain regions were measured. Fetal brains were also stained for cyclooxygenase-2 (COX-2), a downstream marker of neuroinflammation. Eight fetal brains were further analyzed for quantitative forebrain COX-2 by Western blotting compared to a β-actin standard. Maternal temperature and IL-6 levels were compared between treatments, as were cell counts, COX-2 staining, and COX-2 levels by Mann-Whitney U test, repeated-measures analysis of variance, or Fisher exact test, as appropriate. RESULTS: RESULTS:Injection of rat IL-6 at 90-minute intervals produced an elevation of maternal temperature compared to vehicle (P

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Multisensory modulation of experimentally evoked perceptual distortion of the face

Abstract

Background

Chronic orofacial pain patients often perceive the painful face area as 'swollen' without clinical signs, i.e., a perceptual distortion (PD). Local anesthetic (LA) injections in healthy participants are also associated with PD

Objective

The aim was to explore whether PD evoked by LA into the infraorbital region of could be modulated by adding mechanical stimulation (MS) to the affected area

Methods

MS was given with a brush and a 128 mN von Frey filament. First, sixty healthy participants were randomly divided into three groups: 1) LA control, 2) LA with MS, 3) Isotonic solution (ISO) with MS as an additional control condition. To further examine the role of a multisensory modulation an additional experiment was conducted. Twenty participants received LA with MS (filament) in addition to visual feedback of their distorted face. The results of the two experiments are presented together

Results

All three LA groups experienced PD, per contra PD was not reported in the ISO group. MS alone did not change the magnitude of PD: brush (p = 0.089), filament (p = 0.203). However, when the filament stimulation was combined with additional visual information of a distorted face there was observable decrease in PD (p = 0.002)

Conclusion

The findings indicate the importance of multisensory integration for PD, and represent a significant step forward in the understanding of the factors that may influence this common condition. Future studies are encouraged to investigate further the cortical processing for possible implications for PD in pain management.

This article is protected by copyright. All rights reserved.



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Oesophageal motor function in chronic intestinal idiopathic pseudo-obstruction: a study with high-resolution manometry

Chronic intestinal idiopathic pseudo-obstruction (idiopathic CIPO) is a rare heterogeneous condition for which the different phenotypes are difficult to be established. Oesophageal motility has shown to be impaired in patients with idiopathic CIPO at traditional manometry, whereas no studies have assessed it by high resolution manometry (HRM).

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Oesophageal motor function in chronic intestinal idiopathic pseudo-obstruction: a study with high-resolution manometry

Chronic intestinal idiopathic pseudo-obstruction (idiopathic CIPO) is a rare heterogeneous condition for which the different phenotypes are difficult to be established. Oesophageal motility has shown to be impaired in patients with idiopathic CIPO at traditional manometry, whereas no studies have assessed it by high resolution manometry (HRM).

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The spectrum of Charcot-Marie-Tooth disease due to myelin protein zero: An electrodiagnostic, nerve ultrasound and histological study

Charcot-Marie-Tooth disease (CMT) is the most frequent inherited neuromuscular disorder and encompasses heterogeneous motor-sensory length-dependent polyneuropathies. CMT manifests commonly in the first-second decade with moderate functional involvement and slow evolution. Variations in age of onset, from early infancy to late adulthood, and degree of severity, from an asymptomatic neuropathy to loss of the ambulatory autonomy, are not necessarily linked to specific genotypes. Clinical phenotypes, mode of inheritance and nerve conduction study (NCS) still address genetic tests in the Next-Generation Sequencing era (Rossor et al., 2016).

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Motor cortex excitability in seizure-free STX1B mutation carriers with a history of epilepsy and febrile seizures

Febrile seizures affect 2-4% of all children and have been related to strong genetic predisposition (Berg et al., 2013). Recently, mutations of the STX1B gene have been identified as a shared genetic mechanism implicated in the pathogenesis of febrile seizures with or without epilepsy (Schubert et al., 2014). STX1B encodes the presynaptic protein syntaxin-1B, a significant component of the soluble-N-ethylmaleimide sensitive factor attachment receptor (SNARE) complex, which tethers synaptic vesicles in the presynaptic membrane and mediates the vesicle exocytosis and release of neurotransmitters at the synapse (Kearney, 2015).

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Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study

Sleep is a natural occurring state of decreased arousal that is crucial for normal cardiovascular, immune and cognitive function (Rosenberg-Adamsen et al., 1996; Saper et al., 2010). However, the principal sedative drugs, most of which modulate the γ amino butyric acid A (GABAA) receptor, do not produce the neurophysiological oscillations of sleep (Akeju et al., 2017). Rather, they produce neurophysiological oscillations that reflect cortical circuit disruptions, which manifest as electroencephalogram frontal beta oscillations, frontal alpha oscillations, burst suppression and isoelectricity (Patat et al., 1994; Feinberg et al., 2000; van Lier et al., 2004; Purdon et al., 2013; Akeju et al., 2014a; Akeju et al., 2014b, Akeju et al., 2017).

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Cerebellar transcranial direct current stimulation improves adaptive postural control

Adaptive postural control is essential for almost all aspects of every day life. Impaired postural control results in substantial functional limitations in advanced age (Maki and McIlroy, 1996) and in pathological ageing conditions like stroke (Beyaert et al., 2015), Parkinson's disease (Schoneburg et al., 2013) or multiple sclerosis (Huisinga et al., 2012). Although rehabilitation and conditioning programs have shown promising results in recovery of postural control, those interventions are typically time and cost intensive and may only yield moderate effects (Howard-Wilsher et al., 2016; Smania et al., 2011; Yitayeh and Teshome, 2016).

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Early corticospinal tract damage in prodromal SCA2 revealed by EEG-EMG and EMG-EMG coherence

SCA2 is caused by a polyglutamine-coding CAG trinucleotide repeat expansion (>34) in the ataxin-2 gene (Pulst et al., 1996). The complex SCA2 phenotype results from multi-system degeneration, involving cerebellum, spinal cord, brainstem and thalamus (Rüb et al., 2013). The prodromal stage of SCA2 was defined here according to Maas et al. (2015) as individuals with already detectable central and/or peripheral nervous system changes but without or with only minimal signs of ataxia (Maas et al., 2015).

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Cervical vestibular evoked myogenic potential tuning properties of patients with recurrent peripheral vestibulopathy: Is it Meniere’s disease without hearing loss?

Clinicians often encounter patients who complain of episodic vertigo. Meniere's disease (MD) and vestibular migraine (VM) are representative diseases in this category. Recently, new diagnostic criteria for both of these diseases have been published (Lopez-Escamez et al., 2015; Lempert et al., 2012). MD patients exhibit auditory symptoms in association with episodic vertigo attacks, while VM patients also have migrainous symptoms in addition to these symptoms. However, many patients have episodic vertigo without auditory or migrainous symptoms.

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Natural and artificial radionuclides in a marine core. First results of 236U in North Atlantic Ocean sediments

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Publication date: Available online 20 October 2017
Source:Journal of Environmental Radioactivity
Author(s): M. Villa-Alfageme, E. Chamizo, F.J. Santos-Arévalo, J.M. López-Gutierrez, I. Gómez-Martínez, S. Hurtado-Bermúdez
There are very few data available of 236U in marine sediment cores. In this study we present the results from the first oceanic depth profile of 236U in a sediment core sampled in the North Atlantic Ocean, at the PAP site (4500 m depth, Porcupine Abyssal Plain (PAP) site, 49°0′ N, 16°30′ W). Additionally, the sediment core was radiologically characterized through the measurement of anthropogenic 137Cs, 239Pu, 240Pu, 129I and 14C and natural 210Pb, 40K and 226Ra.The measured 236U concentrations decrease from about 90·106 at g−1 at the seafloor down to 0.5·106 at g−1 at 6 cm depth. They are several orders of magnitude lower than the reported values for soils from the Northern Hemisphere solely influenced by global fallout (i.e. from 2700·106 to 7500·106 at g−1). 236U/238U atom ratios measured are at least three orders of magnitude above the estimated level for the naturally occurring dissolved uranium. The obtained inventories are 1·1012 at m−2 for 236U, 80 Bq m−2 for 137Cs, 45 Bq m−2 for 239+240Pu and 2.6·1012 at m−2 for 129I. Atomic ratios for 236U/239Pu, 137Cs/236U and 129I/236U, obtained from the inventories are 0.036, 0.11 and 2.5 respectively. Concentration profiles show mobilization probably due to bioturbation from the abundant detritivore holothurian species living at the PAP site sea-floor. The range of 236U, 137Cs, 239+240Pu and 129I values, inventories and ratios of these anthropogenic radionuclides are more similar to the values due to fall-out than values from a contribution from the Nuclear Fuel Reprocessing Plants dispersed to the south-west of the North Atlantic Ocean. However, signs of an additional source are detected and might be associated to the nuclear wastes dumped on the Eastern North Atlantic Ocean.



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Paramedic - UCHealth

At UCHealth, we do things differently Paramedic Testing & Interview Session, by invitation only, will be held on Monday, December 11, 2017. Applicants extended a contingent offer will need to clear pre-employment requirements by January 10th and will be expected to start in New Employee ...

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EMT- Intermediate and Basic - Community Care Ambulance Network

Please Visit www.ccan.org/careers to apply The EMT-basic is primarily responsible for providing basic life support to patients and/or assisting the paramedic in the delivery of advanced life support. Locations: Cuyahoga, Portage, Summit, Geauga, Ashtabula Counties 15228 Madison Rd, Middlefield, Ohio 44062, United States 115 E 24th St, Ashtabula, Ohio 44004, United States 830 W Main St, Geneva, Ohio ...

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EMS agency proposes ambulance chase car

The chase car would be available during a mass casualty event anywhere in the county; it could be provided to make up a BLS crew if all other avenues were exhausted

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Paramedics - Community Care Ambulance Network

The EMT-P is primarily responsible for providing patient care and customer service that meets or exceeds the national Standard of Care for Advanced Life Support personnel and all CCAN standards. The paramedic is ultimately responsible for all actions of the entire crew. Locations: Cuyahoga, Portage, Summit, Geauga, Ashtabula Counties 15228 Madison Rd, Middlefield, Ohio 44062, United States 115 E 24th ...

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What EMS leaders, educators can learn from continuing education data

An analysis of 8.7 million CAPCE continuing education records show how and when paramedics and EMTs earn CE for state and National Registry recertification

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Correction to: Effectiveness of Exercise Interventions to Improve Postural Control in Older Adults: A Systematic Review and Meta-Analyses of Centre of Pressure Measurements

Page 103, Table 1: The cell entry in the 'Terms used' column which previously read: "Centre of pressure OR center of pressure OR COP OR postural sway OR postural stability OR postural control OR balance OR force plat*".



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EMS credits WhatsApp with aiding in faster heart attack response

The messaging app is used to send diagnostic electrocardiograms directly to hospital cath labs

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Dallas officials reassure city that 911 problems are fixed

After two families claimed deaths due to 911 issues, Assistant Dallas Police Department Chief David Pughes said he is confident it will not happen again

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Pediatric population-specific disaster management

As we face more and different disasters, communities must consider the special needs of the pediatric portion that makes up one quarter of the population

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Ohio seeks technology ideas to solve national opioid crisis

Officials launched an $8 million effort to attract ideas for using technology to solve the national opioid addiction crisis that has touched scores of families

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In this issue



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Table of Contents, Volume 173A, Number 9, September 2017



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Cautious approach to genome editing urged



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Opitz award paper describes skeletal disorder



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Publication schedule for 2017



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Cover Image, Volume 173A, Number 11, November 2017

Thumbnail image of graphical abstract

The cover image, by Cristina M. Justice et al., is based on the Original Article A Variant Associated with Sagittal Nonsydromic Craniosynostosis Alters the Regulatory Function of a Non-Coding Element, DOI: 10.1002/ajmg.a.38392. Photo Credit: Blake Carrington (NIH/NHGRI).



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Association analysis of the SNP (rs345476947) in the FUT2 gene with the production and reproductive traits in pigs

Abstract

The FUT2 gene was considered as an important candidate for pathogenic infections, while the potential associations between this gene and the production and reproductive traits of pigs have not been explored. In this study, we detected the genetic variants of porcine FUT2 gene and analyzed the associations of the polymorphisms with FUT2 mRNA expression and production and reproductive traits (age at 100 kg, backfat thickness at 100 kg, eye muscle thickness, the number of newborn piglets, the number of weaned piglets, and birth weight) in 100 Large White sows. One single nucleotide polymorphism (SNP) (rs345476947, C→T) in the intron of FUT2 and three genotypes (TT, CT and CC) were determined. Association analysis revealed significant associations between this SNP with the number of newborn piglets and weaned piglets. Furthermore, individuals with the TT genotype had significantly higher numbers of newborn piglets and weaned piglets than those with the CC genotype (P < 0.05). Quantitative PCR analysis showed that FUT2 expression in individuals with CC genotype was significantly higher than those with TT and CT genotypes in the liver and lymph gland (P < 0.05) and higher than that of CT in the spleen, kidney, and duodenum (P < 0.05). These findings indicated that the TT genotype may be a favorable genotype for the reproductive traits of pigs. Our study revealed the genetic variants of the FUT2 gene and identified a promising candidate SNP (rs345476947) associated with the reproductive traits, which has the potential to be applied in selective breeding of pigs.



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Genes linked to species diversity in a sexually dimorphic communication signal in electric fish

Abstract

Sexually dimorphic behaviors are often regulated by androgens and estrogens. Steroid receptors and metabolism are control points for evolutionary changes in sexual dimorphism. Electric communication signals of South American knifefishes are a model for understanding the evolution and physiology of sexually dimorphic behavior. These signals are regulated by gonadal steroids and controlled by a simple neural circuit. Sexual dimorphism of the signals varies across species. We used transcriptomics to examine mechanisms for sex differences in electric organ discharges (EODs) of two closely related species, Apteronotus leptorhynchus and Apteronotus albifrons, with reversed sexual dimorphism in their EODs. The pacemaker nucleus (Pn), which controls EOD frequency (EODf), expressed transcripts for steroid receptors and metabolizing enzymes, including androgen receptors, estrogen receptors, aromatase, and 5α-reductase. The Pn expressed mRNA for ion channels likely to regulate the high-frequency activity of Pn neurons and for neuromodulator and neurotransmitter receptors that may regulate EOD modulations used in aggression and courtship. Expression of several ion channel genes, including those for Kir3.1 inward-rectifying potassium channels and sodium channel β1 subunits, was sex-biased or correlated with EODf in ways consistent with EODf sex differences. Our findings provide a basis for future studies to characterize neurogenomic mechanisms by which sex differences evolve.



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Perceived stress is associated with smaller hippocampal volume in adolescence

Abstract

Perceived stress has been associated with decreased hippocampal, amygdala, and prefrontal cortex volume, as well as decreased memory and executive functioning performance in adulthood. Parents' perceived stress has been linked to decreased hippocampal volume in young children. However, no studies have investigated the links between self-perceived stress and brain structure or function in adolescents. Additionally, findings from previous research with younger or older samples are inconsistent, likely in part due to inconsistencies in participants' age range. In this study, we investigated the associations among self-perceived stress, family socioeconomic factors (family income, parental education), subcortical (hippocampus, amygdala) volumes, prefrontal cortical thickness and surface area, and memory and executive functioning performance in adolescents. One hundred and forty-three participants (12–20 years old) were administered a cognitive battery, a questionnaire to assess perceived stress, and a structural MRI scan. Higher levels of perceived stress were associated with decreased adolescent hippocampal volume. This study provides empirical evidence of how experience may shape brain development in adolescence—a period of plasticity during which it may be possible to intervene and prevent negative developmental outcomes.



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Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection

Abstract

Background

Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1).

Methods

This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12).

Results

The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis.

Conclusions

G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.



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Hepatic Complications of Anorexia Nervosa

Abstract

Anorexia nervosa (AN) has the highest mortality rate of all psychiatric illnesses due to the widespread organ dysfunction caused by the underlying severe malnutrition. Starvation causes hepatocyte injury and death leading to a rise in aminotransferases. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases. Acute liver failure associated with coagulopathy and encephalopathy can rarely occur. Liver enzymes may also less commonly increase as part of the refeeding process due to hepatic steatosis and can be distinguished from starvation hepatitis by the finding of a fatty liver on ultrasonography. Individuals with AN and starvation-induced hepatitis are at increased risk of hypoglycemia due to depleted glycogen stores and impaired gluconeogenesis. Gastroenterology and hepatology consultations are often requested when patients with AN and signs of hepatitis are hospitalized. It should be noted that additional laboratory testing, imaging, or liver biopsy all have low diagnostic yield, are costly, and potentially invasive, therefore, not generally recommended for diagnostic purposes. While the hepatitis of AN can reach severe levels, a supervised increase in caloric intake and a return to a healthy body weight often quickly lead to normalization of elevated aminotransferases caused by starvation.



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MicroRNA-30a Inhibits Colorectal Cancer Metastasis Through Down-Regulation of Type I Insulin-Like Growth Factor Receptor

Abstract

Background

miR-30a expression is down-regulated and regulates tumor suppressors in various cancers.

Aim

We investigated the mechanisms underlying the biological role of miR-30a in CRC.

Methods

MicroRNA, mRNA, and protein expression were analyzed by quantitative real-time PCR and Western blot. The migration and invasion abilities of CRC were determined by wound healing assay, and trans-well migration and invasion. A luciferase reporter assay was used to confirm the targets of miR-30a.

Results

miR-30a expression was significantly down-regulated in CRC tissues and in CRC tissue with lymph node metastasis compared to CRC tissue without metastasis. Overexpression of miR-30a suppressed migration and invasion through insulin-like growth factor 1 receptor (IGF1R) in CRC cells. miR-30a suppresses IGF1R protein expression and inhibits β-catenin or p-AKT and increases E-cadherin expression. The IGF1R expression level is also up-regulated in CRC tumors and inversely correlated with miR-30a in CRC specimens.

Conclusions

miR-30a functions as a tumor-suppressive miRNA, which may provide a therapeutic strategy for metastasis of CRC.



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Heterogeneity of Outcomes Following Liver Transplantation for Primary Sclerosing Cholangitis: Age Matters



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Physiologic Management of Chronic Constipation: Let’s FEED It



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Black Is the New Black: Prolapsing Primary Anorectal Melanoma



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Chromoendoscopy, Narrow-Band Imaging or White Light Endoscopy for Neoplasia Detection in Inflammatory Bowel Diseases

Abstract

Background

Studies have confirmed an increased risk of colorectal cancer in patients with ulcerative colitis; hence, surveillance is recommended. Optional modalities include white light endoscopy (WLE) or dye-spray chromoendoscopy. However, narrow-band imaging (NBI) is still not considered comparable to chromoendoscopy.

Aim

The aim of this study was to compare the diagnostic yield (DY) of WLE, chromoendoscopy, NBI for detection of neoplasia in patients with inflammatory bowel disease (IBD) by performing a meta-analysis of the existing literature.

Methods

We searched databases for prospective studies. For each modality, we performed comparative per-lesion analysis (any neoplasia detection) and per-patient analysis (patient with neoplastic lesions). Meta-analysis was performed using fixed-effect model unless heterogeneity was high. Odds ratios (ORs) with 95% CIs were calculated and pooled.

Results

Five studies compared chromoendoscopy to WLE. Chromoendoscopy (n = 361) was superior to WLE (n = 358) with per-patient analysis OR 2.05 (95% CI 1.26, 3.35) and per-lesion analysis OR 2.79 (95% CI 2.08, 3.73). High-definition (HD) chromoendoscopy was superior to HD-WLE with per-lesion analysis OR 2.48 (95% CI 1.55, 3.97). In four studies comparing NBI to WLE (n = 305), no difference was found in per-patient analysis OR 0.97 (95% CI 0.62, 1.53) and per-lesion analysis OR 0.94 (95% CI 0.63, 1.4). In two studies comparing CE to NBI (n = 104), no difference was found in per-patient analysis OR 1.0 (95% CI 0.51, 1.95) and per-lesion analysis OR 1.29 (95% CI 0.69, 2.41).

Conclusion

Chromoendoscopy is superior to WLE for detection of dysplasia in IBD, even with HD endoscopy. No difference in DY could be demonstrated for NBI in comparison with other modalities.



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LncRNA-CCAT1 Promotes Migration, Invasion, and EMT in Intrahepatic Cholangiocarcinoma Through Suppressing miR-152

Abstract

Background

Increasing evidence has suggested that lncRNA CCAT1 is upregulated and functions as a potential tumor promoter in many cancers. However, the potential biological roles and regulatory mechanisms of CCAT1 in intrahepatic cholangiocarcinoma (ICC) remain unclear.

Methods

We used real-time PCR to measure CCAT1 expression in ICC tissues and the adjacent normal tissues. The statistical analyses were applied to evaluate the prognostic value and associations of CCAT1 expression with clinical parameters. The CCAT1 was silenced with siRNA in ICC cells. The migration and invasion of ICC cells were detected with Transwell assay. The expressions of epithelial–mesenchymal transition (EMT)-related proteins were evaluated to discover whether the process of EMT was involved.

Results

We found that CCAT1 expression was elevated in ICC tissues compared to the adjacent normal tissues. We also found that high CCAT1 expression is closely correlated with tumor progression in ICC patients. Furthermore, our results show that knockdown of CCAT1 significantly suppressed the migration and invasion of ICC cells. Additionally, CCAT1 silencing remarkably reverses the EMT phenotype of ICC cells. Moreover, bioinformatics analysis and luciferase reporter assay revealed that CCAT1 directly bound to the miR-152, which has been reported to serve as a tumor suppressor in variety cancers. Further investigation demonstrated that CCAT1 led to the metastasis and EMT activation of ICC cells through inhibiting miR-152.

Conclusions

Our results suggested that CCAT1 functions as an oncogenic lncRNA in ICC, which could serve as a potential diagnostic and therapeutic target for ICC patients.



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Rapid Fecal Calprotectin Test and Symptom Index in Monitoring the Disease Activity in Colonic Inflammatory Bowel Disease

Abstract

Background

Fecal calprotectin is a reliable surrogate marker for inflammatory activity in inflammatory bowel disease (IBD).

Aims

For the noninvasive monitoring of the activity of colonic inflammation, we validated a symptom index suitable for ulcerative colitis and colonic Crohn's disease. By combining the symptom index with a rapid semi-quantitative calprotectin test, we constructed a new activity index based on the highest AUCs, using histological remission as a reference. We also evaluated the correlation of the patient-reported influence of the IBD in the daily life, measured by a VAS, with the inflammation activity.

Methods

The disease activity of 72 patients with IBD of the colon was determined by endoscopic activity scores (SES-CD/UCEIS). The patients provided stool samples for determination of calprotectin and filled in a questionnaire about their symptoms during the last week.

Results

The results of the symptom index demonstrated a statistically significant correlation with the rapid calprotectin test, histological inflammation activity, and the VAS. No correlations were found between the VAS and calprotectin or the histological inflammation activity. The sensitivity of the combination index to detect active inflammation was slightly superior to fecal calprotectin alone.

Conclusion

The new symptom index and the combination index are simple, noninvasive means for distinguishing remission from active inflammation in colonic IBD. With the VAS, we can pick up patients who need psychosocial support because of the disease burden, even if their IBD is in remission.



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Long Non-coding RNAs in Gastric Cancer: A True Relationship or miR Chance?



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Longtime concerns of poor EMS working conditions to be improved at agency

By EMS1 Staff RICHLAND COUNTY, S.C. — Millions of dollars are being set aside to upgrade a county's embattled EMS services. WACH.com reported that Richland County Councilman Seth Rose started receiving complaints from EMS providers about poor working conditions a year ago. "People are leaving for higher paying jobs in other counties," Rose said. "We can't have that if we ...

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Utility of Genetics for Risk Stratification in Pediatric Hypertrophic Cardiomyopathy

Children with hypertrophic cardiomyopathy (HCM) experience sudden cardiac death (SCD) and other life-threatening events. We assessed if affected gene and variant burden predict outcomes. Patients <18 years old with primary HCM with a pathogenic variant or variant of uncertain significance in cardiomyopathy genes were included. Association of gene and variant number and type with freedom from major adverse cardiac events (MACE) i.e. ICD insertion, myectomy, aborted SCD, transplantation or death, was assessed by Cox regression. 98 of 155 gene-tested patients carried a non-benign variant. The primary affected gene was MYH7 in 35% (MYH7+) and MYBPC3 in 49% (MYBPC3+). MYH7+ patients had earlier disease onset and higher risk of MACE (hazard ratio 2.7, 95% CI 1.3 - 5.7). Risk of MACE was also higher in patients with multiple variants (n=16) (HR 2.5, CI: 1.1-5.9) compared to a propensity score-matched single variant subset, after adjustment for primary gene, and in patients with de novo (n=18) vs inherited variants (HR 5.7, CI: 2.6-12.7). Affected gene (e.g. MYH7), higher variant burden and de novo variant status are independently associated with earlier onset and higher frequency of adverse outcomes in pediatric HCM, highlighting the importance of genetic risk stratification in HCM.

Thumbnail image of graphical abstract

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Longtime concerns of poor EMS working conditions to be improved

By EMS1 Staff RICHLAND COUNTY, S.C. — Millions of dollars are being set aside to upgrade a county's embattled EMS services. WACH.com reported that Richland County Councilman Seth Rose started receiving complaints from EMS providers about poor working conditions a year ago. "People are leaving for higher paying jobs in other counties," Rose said. "We can't have that if we ...

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UK research: 1 in 5 witnesses do not perform CPR on victims

Researchers found that cardiac arrest survival rates remain low in the U.K. due to the lack of knowledge and skills to perform CPR

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Quality criteria of generation playgrounds Frank Amort

Introduction

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(Dis)advantaged childhoods and premature mortality: cumulative inequalities over the life-course Josephine Jackisch

Background

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Labour market position at age 18 and mental health related mortality up until ages 33 to 39 Josefin Sundin

Background

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‘Candy day’ in Finland and its association to consumption of sweets in 3- to 6-year-old children Laura Korpipää

Background

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The process of culture in implementation research: linking the clinic and the community in Stockholm Helle Mölsted Alvesson

Background

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‘Feeling threatened’ and self-reported health after terrorist attacks in Belgium. Are we prone to ‘terrorification’? Reginald Deschepper

Background

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Organisational actors who engage in Scottish e-cigarette policy debates: A mixed methods approach Shona Hilton

Electronic cigarettes have become subject to highly contested public and political debates, including the role of commercial actors in development and implementation of e-cigarette policy. There are concerns that e-cigarette debates provide opportunities for commercial actors to demonstrate alignment with public health interests, build reputation, and gain influence over policy processes. While previous research on commercial sector engagement in policymaking has enhanced understanding of its impact on public health, a striking research gap exists regarding commercial actors' engagement in e-cigarette debates.

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‘Models’ of Children’s Primary Care Michael Rigby

Primary care for children is provided in a number of different ways in the countries of Europe. Identifying a classification of models which is credible to the intended end readership of policy makers, professionals, and public is essential to give the work impact.

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Stockholm county councils health advisers in collaboration with the center of civic orientation Haibe Hussein

In collaboration with the The Center for Civic Orientation and as a part of the civic(social) orientation program, Stockholm County Council's health advisers offer all newly arrived immigrant participants of the program in Stockholm region an additional 12 hours long introduction to health promotional dialogue with the purpose of getting enhanced health impact. The collaboration between the health advisers and the Center for Civic orientation is strategic way of reaching all newly arrived refugees from 26 municipalities Stockholm region with essential health information. Stockholm County Councils Health advisers with in-depth knowledge and experience in health communications conduct a mother-tongue based group-dialogue sessions with the newly arrived refugees about range of topics including the impact of immigration on health and living habits. An external evaluation of the intervention has shown that the newly arrived refugees gained a new knowledge about health and had a new and improved healthy habits as a result a result of the group dialogue sessions. Collaboration between different authorities and organisations is thus essential to meet the complex needs of newly arrived refugees. The Collaboration is an innovative approach of giving needs based health information and knowledge to immigrants and refugee that would not have been possible otherwise. Establishing and developing and improving this type of multi-sectoral collaboration would be beneficial to refugees in whole of Sweden.

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“Inexperienced”? Exploring patterns in sexual activities among urban poor young adolescents Anna Kågesten

Background

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Workloads as mediator for the association between job requirement level and health of older workers Karolin Hiesinger

Background

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“One Good Year Added” for every citizen within a community Joachim Fischer

Enhancing and maintaining population health and well-being across the life-span is the ultimate goal of Public Health and preventive efforts. Achieving this goal has two key aspects: risk reduction, which involves ameliorating the health and economic impact of chronic and preventable diseases from earliest childhood on and resource strengthening, which focuses on raising healthy children and enabling them to participate as active citizens leading full and productive lives through adulthood and old age.

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Microbiological ascertainment in patients with pneumonia: is there room for improvement? Marianxhela Dajko

Background

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“Overweight” adults think they are “underweight”: a household survey in rural Zambia Yukiko Tateyama

Cardiovascular diseases (CVDs) are recent public health challenges in Sub-Saharan Africa (SSA). In Zambia, 8% of all mortality in 2012 is related to CVDs. The national adult overweight prevalence was 26.4% in 2010. Further increase of CVDs is predicted to continue with economic development; however, researches on CVDs are limited in Zambia, particularly in rural areas where urbanization is outpacing. We, therefore, aimed to investigate the prevalence and perception of overweight in rural Zambia through a cross-sectional study that employs a rigorous probability sampling. We recruited 690 male and female residents (48.6% and 51.4%, respectively) of Mumbwa district (ages 25-64) through a multistage, clustered, household sampling for the questionnaire survey, anthropometric, and biological measurements during May-July 2016. Data analysis took into account of complex sampling design. Mean age was 41.9 ± 0.55 (SE), 74.3% had only primary education and 47.4% earned ≦50USD per month. The prevalence of overweight (BMI≧25) was 26.8%, of which, 58.4% and 14.2% perceived themselves as "normal" and "underweight", respectively. Among all, 13.8% responded that they prefer to be overweight; the main reasons included "attractive" (78.6%), "looks wealthy/avoids to be seen poor" (49.7%), and "fears to be seen ill/looks healthy" (39.6%), of which, "fear to be seen as having HIV' was ranked as the top reason. We found that more than half of overweight participants perceived that they were normal weight and more than 10% of all participants prefer to be overweight. Such preference of overweight appeared to have been influenced by the culture, socioeconomic, and HIV stigma. Future interventions for CVDs in Zambia should address these culturally appropriate contexts and the influence of HIV endemic. The findings may also be beneficial for other SSA countries that are experiencing the same epidemiological transition.

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Post-traumatic stress symptoms and media exposure following the November 2015 Paris terror attacks Maëlle Robert

Background

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“Public Health Genomics in Cancer “in Cancer Control - Joint Action Policy Papers Marc Van Den Bulcke

Cancer control as a major public health issue and being a pathology strongly driven by genetic modification, is closely linked to a novel field in epidemiology wherein molecular data at population scale are integrated into new strategies both from a personalized medicine as a public health perspective. This domain is generally designated as 'Public Health genomics' (PHG).

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School tobacco policies, complex contagion and smoking inequalities among adolescents: a longitudinal study in seven European cities Pierre-Olivier Robert

Background

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1.A. Workshop: Public Landscapes for Public Health

Chair: George Morris, UK

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The effect of sleep apnea on type 2 diabetes and arterial hypertension Madalina Dumitru

Background

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1.B. Round Table: Upholding public health research, policy and practice in a future European Union

Chair: Dineke Zeegers Paget, EUPHA

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Defective ciliogenesis in INPP5E-related Joubert syndrome

Joubert syndrome is a neurodevelopmental disorder, characterized by malformation of the mid and hindbrain leading to the pathognomonic molar tooth appearance of the brainstem and cerebellum on axial MRI. Core clinical manifestations include hypotonia, tachypnea/apnea, ataxia, ocular motor apraxia, and developmental delay of varying degrees. In addition, a subset of patients has retinal dystrophy, chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly. Joubert syndrome exhibits genetic heterogeneity, with mutations identified in more than 30 genes, including INPP5E, a gene encoding inositol polyphosphate 5-phosphatase E, which is important in the development and stability of the primary cilium. Here, we report the detailed clinical phenotypes of two sisters with a novel homozygous variant in INPP5E (NM_019892.4: c.1565G>C, NP_063945.2: p.Gly552Ala), expanding the phenotype associated with Joubert syndrome type 1. Expression studies using patient-derived fibroblasts showed changes in mRNA and protein levels. Analysis of fibroblasts from patients revealed that a significant number of cells had shorter or no cilia, indicating defects in ciliogenesis, and cilia maintenance.



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Fitness-related differences in the rate of whole-body evaporative heat loss in exercising men are heat-load dependent

Abstract

The effect of aerobic fitness (defined as rate of peak oxygen consumption) on heat loss during exercise is thought to be related to the level of heat stress. However, it remains unclear at what combined exercise and environmental (net) heat load threshold these fitness-related differences occur. To identify this, we assessed whole-body heat exchange (dry and evaporative) by direct calorimetry in young (22 ± 3 years) men matched for physical characteristics with low (Low-fit) (39.8 ± 2.5 mLO2·kg−1·min−1), moderate (Mod-fit) (50.9 ± 1.2 mLO2·kg−1·min−1), and high (High-fit) (62.0 ± 4.4 mLO2·kg−1·min−1) aerobic fitness (each n = 8), during three 30-min bouts of cycling in dry heat (40°C, 12% relative humidity) at increasing rates of metabolic heat production of 300 (Ex1), 400 (Ex2), 500 W (Ex3), each followed by a 15-min recovery period. Each group was exposed to a similar net heat load (metabolic plus ∼100 W dry heat gain; P = 0.83) during each exercise bout (∼400 (Ex1), ∼500 (Ex2) and ∼600 W (Ex3); P < 0.01). However, while evaporative heat loss was similar between groups during Ex1 (P = 0.33), evaporative heat loss was greater in the High-fit [Ex2: 466 ± 21 W; Ex3: 557 ± 26 W] compared to the Low-fit [Ex2: 439 ± 22 W; Ex3: 511 ± 20 W] during Ex2 and Ex3 (P ≤ 0.03). Conversely, evaporative heat loss for the Mod-Fit did not differ from either the High-fit or Low-fit during all exercise bouts (≥ 0.09). We demonstrate that aerobic fitness modulates heat loss in a heat-load dependent manner, such that young highly-fit men display greater heat-loss capacity only at heat loads ∼≥500 W compared to their lesser trained counterparts.

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Advance in physiologically based pharmacokinetic modelling: from the organ level to sub-organ level based on experimental data

Abstract

Understanding the pharmacokinetics and target organ dosimetry properties of small molecular drugs and large molecular biologics is essential in the design of proper therapeutic regimens for disease treatments.

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Omecamtiv Mercabil and Blebbistatin modulate cardiac contractility by perturbing the regulatory state of the myosin filament

Abstract

Contraction of heart muscle is triggered by a transient rise in intracellular free calcium concentration linked to a change in the structure of the actin-containing thin filaments that allows the head or motor domains of myosin from the thick filaments to bind to them and induce filament sliding. It is becoming increasingly clear that cardiac contractility is also regulated through structural changes in the thick filaments, although the molecular mechanisms underlying thick filament regulation are still relatively poorly understood. Here we investigated those mechanisms using small molecules- Omecamtiv Mecarbil (OM) and Blebbistatin (BS) - that bind specifically to myosin and respectively activate or inhibit contractility in demembranated cardiac muscle cells. We measured isometric force and ATP utilization at different calcium and small-molecule concentrations in parallel with in situ structural changes determined using fluorescent probes on the myosin regulatory light chain in the thick filaments and on troponin C in the thin filaments. The results show that BS inhibits contractility and actin-myosin ATPase by stabilizing the OFF state of the thick filament in which myosin head domains are more parallel to the filament axis. In contrast, OM stabilizes the ON state of the thick filament, but inhibits contractility at high intracellular calcium concentration by disrupting the actin-myosin ATPase pathway. The effects of BS and OM on the calcium sensitivity of isometric force and filament structural changes suggest that the co-operativity of calcium activation in physiological conditions is due to positive coupling between the regulatory states of the thin and thick filaments.

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