Παρασκευή 24 Αυγούστου 2018

Knockdown of Long Noncoding RNA Plasmacytoma Variant Translocation 1 with Antisense Locked Nucleic Acid GapmeRs Exerts Tumor-Suppressive Functions in Human Acute Erythroleukemia Cells Through Downregulation of C-MYC Expression

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Knockdown of Long Noncoding RNA Plasmacytoma Variant Translocation 1 with Antisense Locked Nucleic Acid GapmeRs Exerts Tumor-Suppressive Functions in Human Acute Erythroleukemia Cells Through Downregulation of C-MYC Expression

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.


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Prevalence of Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacilli and Emergence of mcr-1 Colistin Resistance Gene in Lebanese Swine Farms

Microbial Drug Resistance, Ahead of Print.


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Relationship Between Biofilm Formation and Antimicrobial Resistance in Gram-Negative Bacteria

Microbial Drug Resistance, Ahead of Print.


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Bugs in inflammatory bowel disease- a questionable therapy



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Novel Biomarkers in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths and the fifth most common cancer worldwide. Most of these patients are seen with advanced disease at the time of presentation. In spite of its high prevalence, there are not many therapeutic options available for patients with advanced-stage HCC. There is an urgent need for improving early detection and prognostication of patients with HCC. In addition, the development of new therapies targeting specific pathways involved in the pathogenesis of HCC should be a major goal for future research, with the objective of improving outcomes of patients with HCC.

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HOXB9 inhibits proliferation in gastric carcinoma cells via suppression of phosphorylated-Akt and NF-κB-dependent Snail expression

HOXB9 is a homeobox transcription factor which plays an important role in carcinoma development. This protein has been shown to inhibit cancer cell proliferation. However, the mechanisms that underpin HOXB9-mediated inhibition of cellular proliferation remain to be elucidated.

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Low Back Pain in Persons with Lower Extremity Amputation: A Systematic Review of the Literature

Lower extremity amputation (LEA) is associated with elevated risk for development and progression of secondary health conditions. Low back pain (LBP) is one such condition adversely affecting function, independence, and quality of life.

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Comparative Effects of Different Assistance Force During Robot-Assisted Gait Training on Locomotor Functions in Patients with Subacute Stroke: An Assessor-Blind, Randomized Controlled Trial

Objective To compare the effects of progressive reducing assistance force (AF) versus full AF controlled robot-assisted gait training (RAGT) combined with conventional physiotherapy on locomotor functions in patients with subacute stroke. Design Inpatients with subacute stroke (N=29; 16 men; Functional Ambulation Category [FAC] score, 1±0.9) were randomly assigned to 1 of 2 groups: a progressive reducing AF group (n=15) or a full AF group (n=14). The progressive reducing AF group performed RAGT sessions from 100%-AF at the outset to 60%-AF at the end of the RAGT, while the full AF group received 100%-AF throughout the RAGT sessions. Both groups performed RAGT combined with conventional physiotherapy 5 days a week for 4 weeks. After intervention, all patients then underwent only conventional physiotherapy 5 days a week for 4-weeks of follow-up. Results The Mann-Whitney U test between-group comparisons showed that improvements were significantly greater in the progressive reducing AF group for the FAC, knee extensors torque, and Berg Balance Scale relative to the full AF group, both at post-intervention and at follow-up. Conclusion Progressive reducing AF control during RAGT combined with conventional physiotherapy may be more beneficial for improving locomotor functions in patients with subacute stroke. *Both first authors have equally contributed to this study as first author. Corresponding author: Yong-Il Shin, MD, PhD, Department of Rehabilitation Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea, Address: 20 Geumo-ro, Mulgeum-eup, Yangsan, Gyeongsangnam-do 50612, Republic of Korea. Mobile: +82-10-6535-0310. E-mail: rmshin01@gmail.com Author Disclosures: This manuscript has been submitted solely to this journal and has not been published or submitted elsewhere. No conflicts of interest have been reported by the authors or by any individual in control of the content of this manuscript. This research received no specific grant from any funding agency. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Physiatry, Pain Management and the Opioid Crisis: A Focus on Function Association of Academic Physiatrists Position Statement Addressing the Opioid Crisis

No abstract available

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Firefighter/Paramedic - Redmond fire and Rescue

#### **THE POSITION ** #### The successful candidate of this entry-level position will work a 48/96 work schedule, responding from one of Redmond Fire & Rescue's four fire stations. This position performs emergency medical services, firefighting, and fire prevention duties including preventing, combating, and extinguishing fires, and saving and protecting human life and property. #### **COMPENSATION ...

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Single cell analysis of Crohn’s disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties

Abstract

Background

Intestinal stem cells (ISCs) play indispensable roles in the maintenance of homeostasis, and also in the regeneration of the damaged intestinal epithelia. However, whether the inflammatory environment of Crohn's disease (CD) affects properties of resident small intestinal stem cells remain uncertain.

Methods

CD patient-derived small intestinal organoids were established from enteroscopic biopsy specimens taken from active lesions (aCD-SIO), or from mucosa under remission (rCD-SIO). Expression of ISC-marker genes in those organoids was examined by immunohistochemistry, and also by microfluid-based single-cell multiplex gene expression analysis. The ISC-specific function of organoid cells was evaluated using a single-cell organoid reformation assay.

Results

ISC-marker genes, OLFM4 and SLC12A2, were expressed by an increased number of small intestinal epithelial cells in the active lesion of CD. aCD-SIOs, rCD-SIOs or those of non-IBD controls (NI-SIOs) were successfully established from 9 patients. Immunohistochemistry showed a comparable level of OLFM4 and SLC12A2 expression in all organoids. Single-cell gene expression data of 12 ISC-markers were acquired from a total of 1215 cells. t-distributed stochastic neighbor embedding analysis identified clusters of candidate ISCs, and also revealed a distinct expression pattern of SMOC2 and LGR5 in ISC-cluster classified cells derived from aCD-SIOs. Single-cell organoid reformation assays showed significantly higher reformation efficiency by the cells of the aCD-SIOs compared with that of cells from NI-SIOs.

Conclusions

aCD-SIOs harbor ISCs with modified marker expression profiles, and also with high organoid reformation ability. Results suggest modification of small intestinal stem cell properties by unidentified factors in the inflammatory environment of CD.



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Systematic review with meta-analysis: real-world effectiveness and safety of vedolizumab in patients with inflammatory bowel disease

Abstract

Background

Selective patient recruitment can produce discrepancies between clinical trial results and real-world effectiveness.

Methods

A systematic literature review and meta-analysis were conducted to assess vedolizumab real-world effectiveness and safety in patients with ulcerative colitis (UC) or Crohn's disease (CD). MEDLINE, MEDLINE In-Process, EMBASE, and Cochrane databases were searched for real-world studies of vedolizumab in adult patients with UC/CD reporting clinical response, remission, corticosteroid-free remission, UC/CD-related surgery or hospitalization, mucosal healing, or safety published from May 1, 2014–June 22, 2017. Response and remission rates were combined in random-effects meta-analyses.

Results

At treatment week 14, 32% of UC patients [95% confidence interval (CI) 27–39%] and 30% of CD patients (95% CI 25–34%) were in remission; and at month 12, 46% for UC (95% CI 37–56%) and 30% for CD (95% CI 20–42%). For UC, the rates of corticosteroid-free remission were 26% at week 14 (95% CI 20–34%) and 42% at month 12 (95% CI 31–53%); for CD they were 25% at week 14 (95%, CI 20–31%) and 31% at month 12 (95%, CI 20–45%). At month 12, 33–77% of UC and 6–63% of CD patients had mucosal healing. Nine percent of patients reported serious adverse events.

Conclusions

Vedolizumab demonstrated real-world effectiveness in patients with moderate-to-severely active UC or CD, with approximately one-half and one-third of patients, respectively, in remission at treatment month 12. These findings are consistent with clinical trial data and support the long-term benefit–risk profile of vedolizumab.



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Bugs in inflammatory bowel disease- a questionable therapy



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Novel Biomarkers in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths and the fifth most common cancer worldwide. Most of these patients are seen with advanced disease at the time of presentation. In spite of its high prevalence, there are not many therapeutic options available for patients with advanced-stage HCC. There is an urgent need for improving early detection and prognostication of patients with HCC. In addition, the development of new therapies targeting specific pathways involved in the pathogenesis of HCC should be a major goal for future research, with the objective of improving outcomes of patients with HCC.

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HOXB9 inhibits proliferation in gastric carcinoma cells via suppression of phosphorylated-Akt and NF-κB-dependent Snail expression

HOXB9 is a homeobox transcription factor which plays an important role in carcinoma development. This protein has been shown to inhibit cancer cell proliferation. However, the mechanisms that underpin HOXB9-mediated inhibition of cellular proliferation remain to be elucidated.

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Sleep and Behavior Problems in Children With Epilepsy

We designed a cross-sectional study to examine the association between sleep and behavior problems in toddlers and preschool-age children with epilepsy. We found that 71 (78.9%) children slept less than 10 hours in a 24-hour period according to the actigraphy, with 75 (83.3%) children waking for more than an hour during nocturnal sleep. Twenty-five (27.8%) children usually or sometimes had an inconsistent bedtime, and 24 (26.7%) did not sleep the same amount each day. Twenty-nine (32.2%) and 18 (20.0%) children had an internalizing and externalizing problem in clinical range, respectively.

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Medical billing company works to create jobs in US

Fellow Health Partners strategically grew their business after listening to the majority of healthcare staff, who said they'd prefer a U.S. based billing manager

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Webinar: How can prehospital providers quickly identify and treat sepsis?

Learn how you can quickly assess and treat patients with sepsis as an EMS provider

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Priority Ambulance awarded for EMS innovation, safety efforts

The American Ambulance Association named Priority Ambulance the national AMBY Award winner in two categories

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How to transition from the apparatus to a power position

Our co-hosts answer an email from a listener asking for help in transitioning to a position of power from the fire truck

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Mid1ip1b modulates apical reorientation of non-centrosomal microtubule organizing center in epithelial cells

Publication date: Available online 24 August 2018

Source: Journal of Genetics and Genomics

Author(s): Xin Zhou, Chun Xiao, Yu Li, Yanna Shang, Dongqin Yin, Siying Li, Bo Xiang, Ran Lu, Yi Ji, Yang Wu, Wentong Meng, Hongyan Zhu, Jin Liu, Huozhen Hu, Xianming Mo, Hong Xu

Abstract

In most kinds of animal cells, the centrosome serves as the main microtubule organizing center (MTOC) that nucleates microtubule arrays throughout the cytoplasm to maintain cell structure, cell division and intracellular transport. Whereas in epithelial cells, non-centrosomal MTOCs are established in the apical domain for generating asymmetric microtubule (MT) fibers and cilia in epithelial cells for the organ morphogenesis during embryonic development. However, the mechanism by which MTOCs localize to the apical domain in epithelial cells remains largely unknown. Here, we show that Mid1ip1b has a close interaction with γ-tubulin protein, the central component of MTOC, and modulates lumen opening of the neural tube, gut, intestine, and kidney of zebrafish. Knockdown or dominant negative effect of Mid1ip1b resulted in failure of lumen formation of the organs as aforementioned. Moreover, the non-centrosomal MTOCs were unable to orientate to the apical domain in Mid1ip1b knockdown epithelial cells, and the centrosomal MTOCs were inaccurately placed in the apical domain, resulting in defective formation of asymmetric microtubules and misplacement of cilia in the apical domain. These data uncover a molecule that controls the proper localization of MTOCs in the apical domain in epithelial cells for organ morphogenesis during embryonic development.



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Genetic landscape of Gallbladder Cancer: Global overview

Publication date: Available online 23 August 2018

Source: Mutation Research/Reviews in Mutation Research

Author(s): Ravi Mehrotra, Sonam Tulsyan, Showket Hussain, Balraj Mittal, Sundeep Singh Saluja, Sandeep Singh, Pranay Tanwar, Milind Javle, Manal M. Hassan, Shubham Pant, Xabier De Aretxabala, Bhawna Sirohi, Preetha Rajaraman, Tanvir Kaur, G.K. Rath

Abstract

Gallbladder cancer (GBC) is a rare malignancy of biliary tract cancer (BTC) due to late presentation and poor prognosis. It exhibits wide geographical as well as ethnical variations. The development of GBC has been associated with several genetic and environmental factors. Although many studies have elucidated the role of genetic alterations in GBC, the etiopathogenesis of this carcinoma still has not been fully understood. This review aims to highlight the genetic landscape of GBC through various approaches, such as those of candidate genes; genome-wide association studies and high throughput sequencing. The literature on meta-analysis has also highlighted the significance of genetic aberrations in GBC carcinogenesis. Therefore, identification of the hotspot mutations which are involved in the etiopathogenesis of this cancer is necessary, before targeted therapies could be implemented clinically. This article is the first one to provide insights into the genetic heterogeneity of GBC along with somatic mutational data from Catalogue of Somatic Mutations in Cancer (COSMIC) database. In addition, this article throws light on the management of tumor heterogeneity as a therapeutic challenge. Furthermore, future prospects involve implications of liquid biopsy based research in clinical management.



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Real-world comparison of the effectiveness and safety of different bowel preparation agents

Clinical and Experimental Gastroenterology

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Association of T helper 1 cytokine gene single nucleotide polymorphisms with ulcerative colitis and Crohn’s disease

Digestive Diseases

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Association between allergic diseases and irritable bowel syndrome: A retrospective study

International Archives of Allergy and Immunology

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A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan

Neurogastroenterology & Motility

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Real-world outcomes of vedolizumab therapy in ulcerative colitis and Crohn’s disease at a tertiary referral center

Digestive Diseases

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Neutrophil extracellular traps in pediatric inflammatory bowel disease

Pathology International

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Long-term outcome of entecavir treatment of nucleos(t)ide analogue-naïve chronic hepatitis B patients in Japan

Journal of Gastroenterology

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Risk of esophageal adenocarcinoma after antireflux surgery in patients with gastroesophageal reflux disease in the nordic countries

JAMA Oncology

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Successful closure of a complicated duodenal ulcer perforation with an expandable esophageal stent

Asian Journal of Endoscopic Surgery, EarlyView.


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A statistical model for estimating the radiocesium transfer factor from soil to brown rice using the soil exchangeable potassium content

Publication date: Available online 23 August 2018

Source: Journal of Environmental Radioactivity

Author(s): Kohji Yamamura, Shigeto Fujimura, Takeshi Ota, Tetsuya Ishikawa, Takashi Saito, Yoshimitsu Arai, Takuro Shinano

Abstract

To reduce radiocesium uptake by rice, large amounts of potassium fertilizer have been applied to paddy fields contaminated by radiocesium released from the Fukushima Dai-ichi Nuclear Power Plant owned by the Tokyo Electric Power Company. The Fukushima Prefectural Government recommended maintenance of the soil exchangeable K content up to 200 mg K kg−1 before conventional fertilization in rice production. We constructed an equation to predict the transfer factor from soil to brown rice using the soil exchangeable K content. This equation was then used to calculate the appropriate soil exchangeable K content, which ensures a low risk (5%) of brown rice exceeding the standard limit (100 Bq kg−1 for grains) established in 2012. The equations were constructed using field data obtained by an investigation (measurement of the 137Cs concentrations in soil and brown rice and measurement of the soil exchangeable K content at harvest) that was performed from 2012 to 2015 in 321 paddy fields distributed all over Fukushima Prefecture. We found that the stochastic fluctuation of the transfer factor approximately follows a lognormal distribution under the given environmental conditions. Four factors are considered in predicting the logarithmic quantity of the transfer factor: (1) the linear influence of the logarithm of the exchangeable K content in soil, (2) the non-linear influence of the logarithm of the exchangeable K content in soil, (3) three districts in the Fukushima Prefecture and (4) the year. The linear model of the logarithm of exchangeable K content in soil was adopted by the RD criterion, which indicates the absolute goodness of models for prediction. The predictive ability of the model increased by 29% after including the logarithm of the exchangeable K content in soil (factor 1), while the predictive ability further increased by 10% after including spatial and temporal information (factors 3 and 4). The validity of the exchangeable K content recommended by the Fukushima Prefectural Government was re-examined using the proposed equations, which indicated that the conventional recommendation was appropriate at 2012 but is not fully appropriate under the current situation in which the radiocesium concentration in soil has decreased.



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5 tips to provide safe and effective ventilation

Assign someone to monitor the patient's airway visually and with capnography using these five tips

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5 tips to provide safe and effective ventilation

Assign someone to monitor the patient's airway visually and with capnography using these five tips

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Health Realization Community Coping Intervention for Somali Refugee Women

Abstract

Health Realization (HR) is a strengths-based stress and coping intervention used to promote the use of internal and external coping resources. Our three-arm comparison group trial examined the effects of a culturally adapted Somali HR intervention on coping and mental health outcomes in 65 Somali refugee women post-resettlement. Subjects participated one of three conditions: HR intervention, nutrition attention-control, and evaluation-control. The HR intervention significantly affected multiple dimensions of coping: WAYS-distancing (p = 0.038), seeking social support (p = 0.042), positive reappraisal (p = 0.001); and Refugee Appraisal and Coping Experience Scale-Internal subscale (p = 0.045). The HR intervention also demonstrated improvement in depression symptom ratings (p = 0.079). We discuss findings from the pilot, challenges encountered conducting a three-arm comparison group trial, and implications for further research involving the HR intervention with culturally diverse refugee communities.



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Cryotherapy reduces muscle spasticity but does not affect proprioception in ischemic stroke: a randomized sham-controlled crossover study

Objective To evaluate the immediate effects of cryotherapy (using an ice pack) on ankle joint position sense (JPS) and the degree of spasticity following chronic hemiparetic stroke. Design We used a sham-controlled crossover design. Sixteen chronic hemiparetic patients were randomly assigned to two groups: 1) those who received cryotherapy followed by a control intervention 15 days later (cryotherapy [CT] group) and 2) those who received the control intervention followed by cryotherapy 15 days later (control intervention [CI] group). Ankle JPS was measured on the paretic side using a Biodex Multi-joint System 3 dynamometer before and after 20 min of either application on the calf muscles. Lower absolute error scores were calculated for data analyses and were used to determine JPS. The degree of spasticity of the plantar flexor muscles was scored according to the Modified Ashworth scale. Results Sixteen patients completed the crossover experiment; however, data analysis was successfully conducted in 15 participants. Cryotherapy reduced the degree of spasticity of the plantar flexor muscles without altering ankle JPS. Conclusion Cryotherapy (using an ice pack) may reduce plantar flexor spasticity without influencing proprioception. *Both authors contributed equally to this study. Corresponding Author: Thiago Luiz de Russo and Luccas Cavalcanti Garcia, Laboratório de Pesquisa em Fisioterapia Neurológica. Departamento de Fisioterapia. Universidade Federal de São Carlos – UFSCar. São Carlos, SP, Brazil. Rodovia Washington Luís, Km 235. Zip Code: 13565-905. Telephone: +551633519578. E-mail: thiagoluizrusso@gmail.com or russo@ufscar.br Author Disclosures: This study was supported by the São Paulo Research Foundation – FAPESP (grants: 2013/25805-1, 2014/25845-6 and 2017/13655-6) and the National Council for Scientific and Technological Development – CNPq (funding: 442972/2014-8). The authors have no conflicts of interest to declare. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Benefits of maxillary expansion for a patient with spinal muscular atrophy type 2

This case report involves a 10-year-old boy diagnosed with spinal muscular atrophy type 2 who underwent nighttime mechanical ventilation with bi-level positive airway pressure. The oral examination revealed restricted mouth opening, lip interposition, dental crowding and maxillary compression. After maxillary expansion the upper airway volume increased 18.6%; 13 episodes of airway infections (20 days of hospitalization) were recorded in the 2 years prior to the maxillary expansion and only 4 episodes (no hospital admissions) in the 2 subsequent years. In conclusion, maxillary expansion in children with systemic disease that involves respiratory impairment may, in some cases, provide functional and clinical improvements, increase upper airway airflows and possibly decrease the number of respiratory infections Correspondence: Pedro Diz Dios, Special Needs Unit, School of Medicine and Dentistry, Santiago de Compostela University, 15782 Santiago de Compostela, Spain. Fax: +34981562226, Telephone: +34881562026. e-mail: pedro.diz@usc.es Author Disclosures: Authors declare no competing interests. No funding or grants or equipment have been provided for the project from any source. There aren´t financial benefits to the authors. Details of this case report have not been previously presented. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Letter to the Editor: Terminology and classification of clinically relevant muscle wasting disease

No abstract available

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Hypothesis testing in superiority, non-inferiority and equivalence clinical trials: Implications in Physical Medicine and Rehabilitation

Abstract: In medical research, it is important to be able to examine whether there is a significant difference between two samples. With this, establishing an appropriate hypothesis is a critical, basic step for correct interpretation of results in inferential statistical data analysis. It is important to note that the aim of hypothesis testing is not to "accept" or "reject" the null hypothesis but to gauge the likelihood that the observed difference is genuine if the null hypothesis is true. Traditionally, the null hypothesis assumes that there is no statistically significant difference between the two groups. As it has become more difficult to develop new treatments that are better than the standard of care. This review article summarizes and explains the methodology of the different types of clinical trials regarding the relevant basic statistical concepts and hypothesis testing. Corresponding Author: Dinesh Kumbhare, MD, PhD, FRCPC, FAAPMR, Department of Medicine, Division of Physical Medicine and Rehabilitation, University of Toronto, Toronto, Ontario, Canada. Email: dinesh.kumbhare@uhn.ca. Tel: 416-597-3422 x 4612 Funding Source: The authors received no funding for this work. Competing Interests of Authors: None declared Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Effects of the selective chymase inhibitor TEI‐F00806 on the intrarenal renin–angiotensin system in salt‐treated angiotensin I‐infused hypertensive mice

Experimental Physiology, Volume 0, Issue ja, -Not available-.


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The Role of the Midfoot in Drop Landings

Purpose The midfoot is instrumental to foot function; however, quantifying its roles in human movement have been difficult. A forceful dynamic activity like landing may help elucidate the midfoot's contribution to foot energetics and function. The main purpose of this study was to measure midtarsal joint kinematics and kinetics during a barefoot single-leg landing task. A secondary aim of this study was to explore the relationship between static foot posture and dynamic midfoot function. Methods In a cross-sectional study design, 48 females (age = 20.4 ± 1.8 yr, BMI = 21.6 ± 1.7 kg·m−1) performed drop landings from a height of 0.4 m onto split force platforms. Subjects hung from wooden rings and landed on their dominant leg. Midtarsal joint kinematic and kinetic data were recorded using a 14 camera optical motion capture system in conjunction with two in-ground force platforms and a custom kinetic 3-segment foot model. Foot structure was measuring using the Arch height index and the static midtarsal joint angle from motion capture. Results Kinematic data revealed an average sagittal plane midtarsal joint range of motion (ROM) of 27 degrees through the landing phase. Kinetic data showed that between 7% and 22% of the total lower extremity joint work during the landing was performed by the midtarsal joint. Both standing AHI and static midtarsal joint angle (static MA) were correlated with sagittal plane midtarsal joint ROM (standing AHI: r=-0.320, p=0.026; static MA: r=0.483, p

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Repetitive Head Impacts in Football Do Not Impair Dynamic Postural Control

Purpose The purpose of this study was to assess the effect of repetitive head impacts experienced by football players compared to non-contact athletes on dynamic postural control during both Single Task (ST) and Dual Task (DT) conditions. Methods Thirty four football players wearing accelerometer instrumented helmets and 13 cheerleaders performed a dynamic postural control battery, consisting of ST and DT gait initiation, gait, and gait termination, both prior to and following the football season. A 2 (group) x 2 (time) repeated measures ANOVA compared performance across 32 dynamic postural outcomes. A linear regression was performed on postural control change scores with common head impact kinematics serving as the independent variables. Results The football players experienced a mean of 538.1 + 409.1 head impacts in the season with a mean linear acceleration of 27.8 + 3.2 g's. There were no significant interactions for any of the ST or DT dynamic postural control tasks. There was a significant relationship between head impact kinematics and the lateral center of pressure displacement during the anticipatory postural adjustment phase (r2 = 0.26, p=0.010) and transitional phase (r2 = 0.511, p=0.042) during ST gait initiation. For both measures, the number of impacts exceeding 98 g's was the only significant predictor of decreased center of pressure displacement. Conclusions A single competitive football season did not adversely affect dynamic postural control when comparing football players to cheerleaders who do not experience repetitive head impacts. Furthermore, there were limited relationships with head impact kinematics suggesting that a single season of football does not adversely affect most outcome measures of instrumented dynamic postural control. These findings are consistent with most studies which fail to identify clinical differences related to repetitive head impacts. Corresponding Author: Thomas Buckley, Ed.D., ATC, Associate Professor, Department of Kinesiology and Applied Physiology, University of Delaware, 541 South College Ave, Newark, DE 19716, (P) 302.831.4783, (F) 302.831.3693, TBuckley@udel.edu This study was funded, in part, by a grant from the National Institute of Health/Neurological Disorders and Stroke (1R15NS070744). The funding agency had no role in the development of this manuscript or the decision to submit to Medicine and Science in Sports and Exercise. The authors have no relationships with companies or manufacturers who will benefit from the results of the present study. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Submitted for publication March 2018. Accepted for publication August 2018. © 2018 American College of Sports Medicine

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Physical Activity Patterns and Mortality: The Weekend Warrior and Activity Bouts

PURPOSE This study aimed to examine how accelerometer-assessed physical activity accumulation patterns (e.g., is activity performed daily or only one or two days a week or is activity accrued in bouts) may affect the association with mortality. METHODS Adults (N = 3438), aged 40 years and older, who wore an accelerometer (ActiGraph 7164), were drawn from the longitudinal follow-up of the National Health and Nutritional Examination Survey (NHANES, 2003-2006), a population-based survey of the United States. Accelerometer-assessed moderate-to-vigorous physical (MVPA) was described by activity patterns. Participants engaging in the majority of their activity on only one or two days a week were classified as 'weekend warriors'. Activity bouts were defined as a period of at least moderate intensity lasting at least 10 minutes. Bout characteristics included bout frequency and length. Mortality was assessed through National Death Index matching through 2013. Mortality rates were compared among groups with different activity patterns. RESULTS Over an average follow-up of 77.4 months, 394 deaths occurred. Compared to participants with

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In Response

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Intrinsic Plan B Airway for Patients Undergoing Bronchial Thermoplasty

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Anesthesia in High-Risk Patients, 1st ed

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71st World Health Assembly, Geneva, Switzerland 2018

No abstract available

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Oxygen Reserve Index: Validation of a New Variable

BACKGROUND: Pulse oximetry–derived oxygen saturation is typically >97% in normoxia and hyperoxia, limiting its clinical use. The new Oxygen Reserve Index (ORi), a relative indicator of the partial pressure of oxygen dissolved in arterial blood (PaO2) in the range of 100–200 mm Hg, may allow additional monitoring of oxygen status. METHODS: In this prospective validation intervention study, 20 healthy volunteers were breathing standardized oxygen concentrations ranging from mild hypoxia (fraction of inspired oxygen = 0.14) to hyperoxia (fraction of inspired oxygen = 1.0) via a tight-fitting face mask. ORi was measured noninvasively by multiwavelength pulse co-oximetry using 2 finger sensors. These ORi values (unitless scale, 0.00–1.00) were compared with measured PaO2 values. Repeated-measurements correlation analysis was performed to assess the ORi/PaO2 relationship. ORi trending ability was assessed using a 4-quadrant plot. The area under the receiver operating characteristics curve was calculated to assess the prediction of hypoxia (low-ranged PaO2,

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Dexmedetomidine Pharmacokinetics and a New Dosing Paradigm in Infants Supported With Cardiopulmonary Bypass

BACKGROUND: Dexmedetomidine is increasingly used off-label in infants and children with cardiac disease during cardiopulmonary bypass (CPB) and in the postoperative period. Despite its frequent use, optimal dosing of dexmedetomidine in the setting of CPB has not been identified but is expected to differ from dosing in those not supported with CPB. This study had the following aims: (1) characterize the effect of CPB on dexmedetomidine clearance (CL) and volume of distribution (V) in infants and young children; (2) characterize tolerance and sedation in patients receiving dexmedetomidine; and (3) identify preliminary dosing recommendations for infants and children undergoing CPB. We hypothesized that CL would decrease, and V would increase during CPB compared to pre- or post-CPB states. METHODS: Open-label, single-center, opportunistic pharmacokinetics (PK) and safety study of dexmedetomidine in patients ≤36 months of age administered dexmedetomidine per standard of care via continuous infusion. We analyzed dexmedetomidine PK data using standard nonlinear mixed effects modeling with NONMEM software. We compared model-estimated PK parameters to those from historical patients receiving dexmedetomidine before anesthesia for urologic, lower abdominal, or plastic surgery; after low-risk cardiac or craniofacial surgery; or during bronchoscopy or nuclear magnetic resonance imaging. We investigated the influence of CPB-related factors on PK estimates and used the final model to simulate dosing recommendations, targeting a plasma concentration previously associated with safety and efficacy (0.6 ng/mL). We used the Wilcoxon rank sum test to evaluate differences in dexmedetomidine exposure between infants with hypotension or bradycardia and those who did not develop these adverse events. RESULTS: We collected 213 dexmedetomidine plasma samples from 18 patients. Patients had a median (range) age of 3.3 months (0.1–34.0 months) and underwent CPB for 161 minutes (63–394 minutes). We estimated a CL of 13.4 L/h/70 kg (95% confidence interval, 2.6–24.2 L/h/70 kg) during CPB, compared to 42.1 L/h/70 kg (95% confidence interval, 38.7–45.8 L/h/70 kg) in the historical patients. No specific CPB-related factor had a statistically significant effect on PK. A loading dose of 0.7 µg/kg over 10 minutes before CPB, followed by maintenance infusions through CPB of 0.2 or 0.25 µg/kg/h in infants with postmenstrual ages of 42 or 92 weeks, respectively, maintained targeted concentrations. We identified no association between dexmedetomidine exposure and selected adverse events (P = .13). CONCLUSIONS: CPB is associated with lower CL during CPB in infants and young children compared to those not undergoing CPB. Further study should more closely investigate CPB-related factors that may influence CL. Accepted for publication June 27, 2018. Funding: K.O.Z. is funded by grant KL2TR001115-03 from the Duke Clinical and Translational Science Awards and K23 grant HD091398 from the National Institutes of Health (NIH). H.W. received salary support from grant K23HD0785891 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) for completion of this project. M.L. receives support from the US government for work in neonatal clinical pharmacology, clinical trials, and cohort studies including Food and Drug Administration (FDA) R01 FD005101, Prinicipal Investigator (PI) M.L.; National Heart, Lung and Blood Institute (NHLBI) R34 HL124038, PI M.L.; the NIH Office of the Director, Environmental Influences on Child Health Outcomes (ECHO) Coordinating Center U2C OD023375, PI P.B.S., Duke University School of Medicine; the NICHD Pediatric Trials Network Government Contract HHSN267200700051C, PI Daniel Benjamin Jr, Duke University School of Medicine; and as the satellite site PI for the NICHD Neonatal Research Network NICHD U10 HD040492, PI C. Michael Cotten, Duke University School of Medicine. R.G.G. receives salary support for research from the NIH training grants (5T32HD043029-13), NIH awards (HHSN 275201000003I, HHSN 272201300017I), and from the FDA (HHSF223201610082C). P.B.S. receives salary support for research from the NIH (NIH-1R21HD080606-01ª1) and the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the NICHD (HHSN275201000003I), and the FDA (1R18-FD005292-01). C.P.H. receives salary support for research from the National Center for Advancing Translational Sciences of the NIH (UL1TR001117) and the US government for his work in pediatric and neonatal clinical pharmacology (Government Contract HHSN267200700051C, PI: Daniel Benjamin Jr under the Best Pharmaceuticals for Children Act). M.C.-W. receives support for research from the NIH (1R01-HD076676-01A1), the National Institute of Allergy and Infectious Disease (HHSN272201500006I and HHSN272201300017I), the NICHD (HHSN275201000003I), the Biomedical Advanced Research and Development Authority (HHSO100201300009C), and industry for drug development in adults and children (https://ift.tt/2PAHZY8). K.M.W. receives support from the Pediatric Critical Care and Trauma Scientist Development Program (5K12HD047349) and the NICHD (1K23HD075891) for his work in pediatric clinical pharmacology. The authors declare no conflicts of interest. 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/KegmMq). Reprints will not be available from the authors. Address correspondence to Kanecia O. Zimmerman, MD, MPH, Department of Pediatrics, Duke University School of Medicine, Box 3850, Durham, NC 27710. Address e-mail to Kanecia.obie@dm.duke.edu. © 2018 International Anesthesia Research Society

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When Laryngeal Masks Fail

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Process Optimization and Digital Quality Improvement to Enhance Timely Initiation of Epidural Infusions and Postoperative Pain Control

BACKGROUND: Although intraoperative epidural analgesia improves postoperative pain control, a recent quality improvement project demonstrated that only 59% of epidural infusions are started in the operating room before patient arrival in the postanesthesia care unit. We evaluated the combined effect of process and digital quality improvement efforts on provider compliance with starting continuous epidural infusions during surgery. METHODS: In October 2014, we instituted 2 process improvement initiatives: (1) an electronic order queue to assist the operating room pharmacy with infusate preparation; and (2) a designated workspace for the storage of equipment related to epidural catheter placement and drug infusion delivery. In addition, we implemented a digital quality improvement initiative, an Anesthesia Information Management System–mediated clinical decision support, to prompt anesthesia providers to start and document epidural infusions in pertinent patients. We assessed anesthesia provider compliance with epidural infusion initiation in the operating room and postoperative pain-related outcomes before (PRE: October 1, 2012 to September 31, 2014) and after (POST: January 1, 2015 to December 31, 2016) implementation of the quality improvement initiatives. RESULTS: Compliance with starting intraoperative epidural infusions was 59% in the PRE group and 85% in the POST group. After adjustment for confounders and preintervention time trends, segmented regression analysis demonstrated a statistically significant increase in compliance with the intervention in the POST phase (odds ratio, 2.78; 95% confidence interval, 1.73–4.49; P

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Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Amisulpride as Treatment of Established Postoperative Nausea and Vomiting in Patients Who Have Had No Prior Prophylaxis

BACKGROUND: Postoperative nausea and vomiting (PONV) occurs commonly in surgical patients despite widespread prophylactic antiemetic use. Rescue options are currently limited. 5HT3 antagonists are most frequently used for prophylaxis, but if they fail, additional doses are not effective as rescue medication. Intravenous (IV) amisulpride, a well-studied D2/D3 antagonist, has been shown in trials to prevent PONV. This study was designed to determine if amisulpride could be used to treat established PONV in patients at low-to-moderate risk of PONV who had not received any prior prophylaxis. METHODS: Men and women aged over 18 years were permitted to enroll if they were to undergo general inhalational anesthesia, expected to last at least 1 hour, for an outpatient or inpatient surgical procedure. Patients who then suffered PONV were randomized equally to 1 of 3 single-dose IV regimens: placebo or 5 or 10 mg amisulpride. The primary end point was complete response, defined as no emesis in the period 30 minutes to 24 hours after study drug treatment and no use of rescue medication in the entire 24-hour period. RESULTS: One thousand nine hundred eighty-eight patients were enrolled preoperatively, of whom 560 were randomized to a treatment arm. Complete response occurred in 39 of 181 patients (21.5%) in the placebo group compared to 60 of 191 patients (31.4%; P = .016) and 59 of 188 patients (31.4%; P = .016) in the amisulpride 5 and 10 mg groups, respectively. The adverse event profile of amisulpride at either dose was similar to placebo. CONCLUSIONS: IV amisulpride at 5 and 10 mg was safe and efficacious in the treatment of established PONV in surgical patients undergoing general anesthesia with no prior PONV prophylaxis. Accepted for publication July 3, 2018. Funding: This work was supported by Acacia Pharma Ltd, Cambridge, United Kingdom. Conflicts of Interest: See Disclosures at the end of the article. Clinical trial registry number: ClinicalTrials.gov NCT2449291. Reprints will not be available from the authors. Address correspondence to Keith A. Candiotti, MD, Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami, Jackson Memorial Hospital, (C-302), 1611 NW 12th Ave, Miami, FL 33136. Address e-mail to kcandiotti@miami.edu. © 2018 International Anesthesia Research Society

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In Response

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Update on Perioperative Acute Kidney Injury

Acute kidney injury (AKI) in the perioperative period is a common complication and is associated with increased morbidity and mortality. A standard definition and staging system for AKI has been developed, incorporating a reduction of the urine output and/or an increase of serum creatinine. Novel biomarkers may detect kidney damage in the absence of a change in function and can also predict the development of AKI. Several specific considerations for AKI risk are important in surgical patients. The surgery, especially major and emergency procedures in critically ill patients, may cause AKI. In addition, certain comorbidities, such as chronic kidney disease and chronic heart failure, are important risk factors for AKI. Diuretics, contrast agents, and nephrotoxic drugs are commonly used in the perioperative period and may result in a significant amount of in-hospital AKI. Before and during surgery, anesthetists are supposed to optimize the patient, including preventing and treating a hypovolemia and correcting an anemia. Intraoperative episodes of hypotension have to be avoided because even short periods of hypotension are associated with an increased risk of AKI. During the intraoperative period, urine output might be reduced in the absence of kidney injury or the presence of kidney injury with or without fluid responsiveness. Therefore, fluids should be used carefully to avoid hypovolemia and hypervolemia. The Kidney Disease: Improving Global Outcomes guidelines suggest implementing preventive strategies in high-risk patients, which include optimization of hemodynamics, restoration of the circulating volume, institution of functional hemodynamic monitoring, and avoidance of nephrotoxic agents and hyperglycemia. Two recently published studies found that implementing this bundle in high-risk patients reduced the occurrence of AKI in the perioperative period. In addition, the application of remote ischemic preconditioning has been studied to potentially reduce the incidence of perioperative AKI. This review discusses the epidemiology and pathophysiology of surgery-associated AKI, highlights the importance of intraoperative oliguria, and emphasizes potential preventive strategies. Accepted for publication July 17, 2018. Funding: A.Z. received lecture fees from Baxter, Astute Medical, Fresenius, Braun, and Ratiopharm and unrestricted research grants from Fresenius, German Research Foundation, Astellas, and Astute Medical. J.L.K. reports receiving consulting fees from Astute Medical, Sphingotec, and Pfizer and research funds from Astute Medical, Bioporto, Nxstage, Satellite Healthcare, and the National Institutes of Health. J.A.K. reports consulting fees and grant support from Astute Medical. E.A.J.H. received a travel grant from AM Pharma, a speaker's fee from Astute Medical, and a research grant from Bellco. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Alexander Zarbock, MD, Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Bldg A1, 48149 Münster, Germany. Address email to zarbock@uni-muenster.de. © 2018 International Anesthesia Research Society

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Anesthesia

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Postoperative Care in Thoracic Surgery: What’s New

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Anesthesiologists’ Overconfidence in Their Perceived Knowledge of Neuromuscular Monitoring and Its Relevance to All Aspects of Medical Practice: An International Survey

BACKGROUND: In patients who receive a nondepolarizing neuromuscular blocking drug (NMBD) during anesthesia, undetected postoperative residual neuromuscular block is a common occurrence that carries a risk of potentially serious adverse events, particularly postoperative pulmonary complications. There is abundant evidence that residual block can be prevented when real-time (quantitative) neuromuscular monitoring with measurement of the train-of-four ratio is used to guide NMBD administration and reversal. Nevertheless, a significant percentage of anesthesiologists fail to use quantitative devices or even conventional peripheral nerve stimulators routinely. Our hypothesis was that a contributing factor to the nonutilization of neuromuscular monitoring was anesthesiologists' overconfidence in their knowledge and ability to manage the use of NMBDs without such guidance. METHODS: We conducted an Internet-based multilingual survey among anesthesiologists worldwide. We asked respondents to answer 9 true/false questions related to the use of neuromuscular blocking drugs. Participants were also asked to rate their confidence in the accuracy of each of their answers on a scale of 50% (pure guess) to 100% (certain of answer). RESULTS: Two thousand five hundred sixty persons accessed the website; of these, 1629 anesthesiologists from 80 countries completed the 9-question survey. The respondents correctly answered only 57% of the questions. In contrast, the mean confidence exhibited by the respondents was 84%, which was significantly greater than their accuracy. Of the 1629 respondents, 1496 (92%) were overconfident. CONCLUSIONS: The anesthesiologists surveyed expressed overconfidence in their knowledge and ability to manage the use of NMBDs. This overconfidence may be partially responsible for the failure to adopt routine perioperative neuromuscular monitoring. When clinicians are highly confident in their knowledge about a procedure, they are less likely to modify their clinical practice or seek further guidance on its use. Accepted for publication July 3, 2018. A. F. Kopman is now retired. Funding: S.J.B. has received research funding from Merck & Co, Inc (Kenilworth, NJ) (funds to Mayo Clinic). 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 (https://ift.tt/KegmMq). M. Naguib and S. J. Brull contributed equally to this work and share first authorship. Reprints will not be available from the authors. Address correspondence to Mohamed Naguib, MD, MSc, FCARCSI, Department of General Anesthesia, Anesthesiology Institute, Cleveland Clinic, 9500 Euclid Ave, NE6-306, Cleveland, OH 44195. Address e-mail to naguibm@ccf.org. © 2018 International Anesthesia Research Society

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