Πέμπτη 4 Οκτωβρίου 2018

Evidence for Stabilizing Selection Driving Mutational Turnover of Short Motifs in the Eukaryotic Complementary Sex Determiner (Csd) Protein

Short linear motifs (SLiMs) can play pivotal functional roles in proteins, such as targeting proteins to specific subcellular localizations, modulating the efficiency of translation and tagging proteins for degradation. Until recently we had little knowledge about SLiM evolution. Only a few amino acids in these motifs are functionally important, making them likely to evolve ex nihilo and suggesting that they can play key roles in protein evolution. Several reports now suggest that these motifs can appear and disappear while their function in the protein is preserved, a process sometimes referred to as "turnover". However, there has been a lack of specific experiments to determine whether independently evolved motifs do indeed have the same function, which would conclusively determine whether the process of turnover actually occurs. In this study, we experimentally detected evidence for such a mutational turnover process for nuclear localization signals (NLS) during the post-duplication divergence of the Complementary sex determiner (Csd) and Feminizer (Fem) proteins in the honeybee (Apis mellifera) lineage. Experiments on the nuclear transport activity of protein segments and those of the most recent common ancestor (MRCA) sequences revealed that three new NLS motifs evolved in the Csd protein during the post-duplication divergence while other NLS motifs were lost that existed before duplication. A screen for essential and newly evolved amino acids revealed that new motifs in the Csd protein evolved by one or two missense mutations coding for lysine. Amino acids that were predating the duplication were also essential in the acquisition of the C1 motif suggesting that the ex nihilo origin was constrained by preexisting amino acids in the physical proximity. Our data support a model in which stabilizing selection maintains the constancy of nuclear transport function but allowed mutational turnover of the encoding NLS motifs.



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Automated functional upper limb evaluation of patients with Friedreich ataxia using serious games rehabilitation exercises

Friedreich ataxia (FRDA) is a disease with neurological and systemic involvement. Clinical assessment tools commonly used for FRDA become less effective in evaluating decay in patients with advanced FRDA, part...

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Regional Anesthesia and Readmission Rates After Total Knee Arthroplasty

BACKGROUND: Total knee arthroplasty is a commonly performed procedure and an important contributor to national health care spending. Reducing the incidence of readmission could have important consequences for patient well-being and relevant financial implications. Whether regional anesthesia techniques are associated with decreased readmission rates and costs among privately insured patients remains unknown. METHODS: Using administrative claims data, we identified 138,362 privately insured patients 18–64 years of age who underwent total knee arthroplasty between 2002 and 2013. We then examined whether the use of a nerve block was associated with decreases in readmission rates and related costs during the 90 days after discharge. Our analyses were adjusted for potential confounding variables including medical comorbidities and previous use of opioids and other medications. RESULTS: After adjusting for patient demographics, comorbidities, and preoperative medication use, the adjusted 90-day readmission rate was 1.8% (95% confidence interval [CI], 1.1–2.4) among patients who did not receive a block compared to 1.7% (95% CI, 1.1–2.4) among patients who did (odds ratio, 0.99; 95% CI, 0.91–1.09; P = .85). The adjusted readmission-related postoperative cost for patients who did not receive a block was $561 (95% CI, 502–619) and $574 (95% CI, 508–639) for patients who did (difference, $13; 95% CI, −75 to 102; P = .74). This lack of statistically significant differences held for subgroup and sensitivity analyses. CONCLUSIONS: Nerve blocks were not associated with improved measures of long-term postoperative resource use in this younger, privately insured study population. Accepted for publication August 24, 2018. Funding: E.C.S. was supported by the National Institute on Drug Abuse (K08DA042314). 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). This work was presented at the Medical Student Anesthesia Research Fellowship (MSARF) symposium at the annual American Society of Anesthesiologists meeting, Boston, MA, October 22, 2017. Reprints will not be available from the authors. Address correspondence to Eric C. Sun, MD, PhD, Department of Anesthesiology, Perioperative and Pain Medicine, H3580, Stanford University Medical Center, Stanford, CA 94305. Address e-mail to esun1@stanford.edu. © 2018 International Anesthesia Research Society

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Predicting the Size of a Left Double-Lumen Tube for Asian Women Based on the Combination of the Diameters of the Cricoid Ring and Left Main Bronchus: A Randomized, Prospective, Controlled Trial

BACKGROUND: There are limited data about how to choose the correct size of a double-lumen tube (DLT). It is especially difficult to select an appropriate DLT for Asian women because of their small stature. The primary aim of this study was to compare the overall accuracy of the DLT selected based on the combination of transverse diameter of cricoid ring and the equivalent diameter of the left main bronchus (ED-LMB) with that based on the ED-LMB alone for Asian women. METHODS: In this study, 80 consecutive and blinded female patients were assigned randomly to 2 groups. The overall accuracy of the selection of DLT was compared between the Combined group and LMB group. The accuracy of the selection of tracheal segment and bronchial segment was also compared between the 2 groups. The postoperative hoarseness and sore throat were investigated by blinded assessors. RESULTS: The overall accuracy of selection of the DLTs was higher in the Combined group than that in the LMB group (87.5% vs 60.0%; P = .010). The accuracy of selection of tracheal segment was also higher in the Combined group (92.5% vs 67.5%; P = .010). The accuracy of selection of bronchial segment was similar between the groups (95.0 % vs 86.1%; P = .246). The severity of sore throat was higher in the LMB group at 24 hours after the operation (P = .001). CONCLUSIONS: The correct size of DLT for Asian women should be selected based on the combination of transverse diameter of cricoid ring and the ED-LMB. Accepted for publication August 29, 2018. Funding: None. The authors declare no conflicts of interest. Clinical trial number and registry URL: ChiCTR-INR-17013040, https://ift.tt/2IBXrA2. Reprints will not be available from the authors. Address correspondence to Dong Youjing, PhD, Shengjing Hospital, China Medical University, No. 36 Sanhao St, Heping District, 110004 Shenyang, China. Address e-mail to dongyj@sj-hospital.org. © 2018 International Anesthesia Research Society

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Predosing Chemical Stability of Admixtures of Propofol, Ketamine, Fentanyl, and Remifentanil

Admixtures of propofol–ketamine, propofol–ketamine–fentanyl, and propofol–ketamine–remifentanil were subjected to various clinically relevant conditions to study their chemical stability. A novel high-performance liquid chromatography-mass spectrometry method revealed no degradation of any compound by incubation at 37°C, constant mixing, or table-top storage for 6- and 24-hour time periods, except variable recovery of both propofol and fentanyl in the admixtures of propofol–ketamine–fentanyl suggesting possible degradation. Accepted for publication August 1, 2018. Funding: US Army Medical Research and Materiel Command. The authors declare no conflicts of interest. The views expressed in this article are those of the authors and do not reflect the official policy of the Uniformed Services University, Departments of the Army, Navy, or Air Force, Department of Defense, Department of Veterans Affairs, or the US Government. Reprints will not be available from the authors. Address correspondence to Peter Bedocs, MD, PhD, Defense and Veterans Center for Integrative Pain Management, Henry M. Jackson Foundation, 11300 Rockville Pike, Suite 709, Rockville, MD 20852. Address e-mail to peter.bedocs.ctr@usuhs.edu. © 2018 International Anesthesia Research Society

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Resident Competency and Proficiency in Combined Spinal–Epidural Catheter Placement Is Improved Using a Computer-Enhanced Visual Learning Program: A Randomized Controlled Trial

BACKGROUND: Physician educators must balance the need for resident procedural education with clinical time pressures as well as patient safety and comfort. Alternative educational strategies, including e-learning tools, may be beneficial to orient novice learners to new procedures and speed proficiency. We created an e-learning tool (computer-enhanced visual learning [CEVL] neuraxial) to enhance trainee proficiency in combined spinal–epidural catheter placement in obstetric patients and performed a randomized controlled 2-center trial to test the hypothesis that use of the tool improved the initial procedure performed by the anesthesiology residents. METHODS: Anesthesiology residents completing their first obstetric anesthesiology rotation were randomized to receive online access to the neuraxial module (CEVL group) or no access (control) 2 weeks before the rotation. On the first day of the rotation, residents completed a neuraxial procedure self-confidence scale and an open-ended medical knowledge test. Blinded raters observed residents performing combined spinal–epidural catheter techniques in laboring parturients using a procedural checklist (0–49 pts); the time required to perform the procedure was recorded. The primary outcome was the duration of the procedure. RESULTS: The CEVL group had significantly shorter mean (±standard deviation) procedure time compared to the control group 22.5 ± 4.9 vs 39.5 ± 7.1 minutes (P

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Red Blood Cell Transfusion in Pediatric Orthotopic Liver Transplantation: What a Difference a Few Decades Make

BACKGROUND: Liver transplantation in children is often associated with coagulopathy and significant blood loss. Available data are limited. In this observational retrospective study, we assessed transfusion practices in pediatric patients undergoing liver transplantation at a single institution over the course of 9 years. METHODS: Data were retrospectively collected from patient medical records at the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center. All patients who underwent liver transplantation from January 2008 to June 2017 were included. Primary and secondary outcomes were volume of red blood cells (RBCs) transfused and mortality, respectively. RESULTS: From January 2008 to June 2017, there were 278 liver transplants in 271 patients. The number of primary transplants were 259, second retransplants 15, and third retransplants 4. Average age at transplantation was 6.9 years. Biliary atresia, maple syrup urine disease, urea cycle defect, and liver tumor were the leading indications accounting for 66 (23.7%), 45 (16.2%), 24 (8.6%), and 23 (8.3%) of transplants, respectively. Seventy-six cases (27.3%) did not require RBC transfusions. Among those transfused, 181 (89.6%) of the cases required 12 months of age (0.12 BV). By diagnosis, the group requiring the highest median volume transfusion was patients with total parenteral nutrition–related liver failure (3.41 BV) followed by patients undergoing repeat transplants (0.6 BV). Comparison of primary versus repeat transplants shows a trend toward higher volume transfusions in third transplants (median, 2.71 BV), compared to second transplants (0.43 BV) and primary transplants (0.18 BV). Four of 271 patients (1.5%) died during admission involving liver transplantation. Nine of 271 patients (3.3%) died subsequently. Total mortality was 4.8%. CONCLUSIONS: In contrast to historically reported trends, evaluation of current transfusion practices reveals that most patients undergoing liver transplantation receive

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Real-Time Measurement of Xenon Concentration in a Binary Gas Mixture Using a Modified Ultrasonic Time-of-Flight Anesthesia Gas Flowmeter: A Technical Feasibility Study

BACKGROUND: Xenon (Xe) is an anesthetic gas licensed for use in some countries. Fractional concentrations (%) of gases in a Xe:oxygen (O2) mixture are typically measured using a thermal conductivity meter and fuel cell, respectively. Speed of sound in such a binary gas mixture is related to fractional concentration, temperature, pressure, and molar masses of the component gases. We therefore performed a study to assess the feasibility of developing a novel single sterilizable device that uses ultrasound time-of-flight to measure both real-time flowmetry and fractional gas concentration of Xe in O2. METHODS: For the purposes of the feasibility study, we adapted an ultrasonic time-of-flight flowmeter from a conventional anesthetic machine to additionally measure real-time fractional concentration of Xe in O2. A total of 5095 readings of Xe % were taken in the range 5%–95%, and compared with simultaneous measurements from the gold standard of a commercially available thermal conductivity Xe analyzer. RESULTS: Ultrasonic measurements of Xe (%) showed agreement with thermal conductivity meter measurements, but there was marked discontinuity in the middle of the measurement range. Bland-Altman analysis (95% confidence interval in parentheses) yielded: mean difference (bias) 3.1% (2.9%–3.2%); lower 95% limit of agreement −4.6% (−4.8% to −4.4%); and upper 95% limit of agreement 10.8% (10.5%–11.0%). CONCLUSIONS: The adapted ultrasonic flowmeter estimated Xe (%), but the level of accuracy is insufficient for clinical use. With further work, it may be possible to develop a device to perform both flowmetry and binary gas concentration measurement to a clinically acceptable degree of accuracy. Accepted for publication August 17, 2018. Funding: None. Conflicts of Interest: See Disclosures at the end of the article. Some preliminary data from the first part of this study were presented as a poster at the European Society of Anaesthesia Annual Conference, Geneva, Switzerland, June 5, 2017. Reprints will not be available from the authors. Address correspondence to David J. Williams, FRCA, Department of Anaesthetics, Morriston Hospital, Swansea SA6 6NL, United Kingdom. Address e-mail to davidjwilliams@doctors.org.uk. © 2018 International Anesthesia Research Society

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Statistical Versus Clinical Significance in Subclavian Vein Cross-Sectional Area: Is a 0.10-cm2 Difference Really Meaningful or Just an Example of False Precision?

No abstract available

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P111 A case of persistent hypertransaminasemia



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Disparities in Tdap Vaccination and Vaccine Information Needs Among Pregnant Women in the United States

Abstract

Objectives The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that pregnant women receive the Tdap vaccine during every pregnancy. The objectives of this paper are to evaluate disparities in Tdap vaccination among pregnant women in the U.S., and to assess whether race/ethnicity and other characteristics are associated with factors that inform pregnant women's decisions about Tdap vaccination. Methods We conducted a nationwide cross-sectional web-based survey of pregnant women in the U.S. during June–July 2014. The primary outcome was self-reported vaccination status with Tdap during pregnancy, categorized as vaccinated, unvaccinated with intent to be vaccinated during the current pregnancy, and unvaccinated with no intent to be vaccinated during the current pregnancy. Secondary outcomes included factors that influenced women's decisions about vaccination and information needs. We used multivariable logistic regression models to estimate odds ratios for associations between race/ethnicity and the outcomes. Results Among pregnant women who completed the survey, 41% (95% CI 36–45%) reported that they had received Tdap during the current pregnancy. Among those women in the third trimester at the time of survey, 52% (95% CI 43–60%) had received Tdap during the current pregnancy. Hispanic women had higher Tdap vaccination than white women and black women (53%, p < 0.05, compared with 38 and 36%, respectively). In logistic regression models adjusting for maternal age, geographic region, education, and income, Hispanic women were more likely to have been vaccinated with Tdap compared with white women (aOR 2.29, 95% CI 1.20–4.37). Higher income and residing in the western U.S. were also independently associated with Tdap vaccination during pregnancy. Twenty-six percent of surveyed women had not been vaccinated with Tdap yet but intended to receive the vaccine during the current pregnancy; this proportion did not differ significantly by race/ethnicity. The most common factor that influenced women to get vaccinated was a health care provider (HCP) recommendation. The most common reason for not getting vaccinated was a concern about safety of the vaccine. Conclusions This study found that some disparities exist in Tdap vaccination among pregnant women in the U.S., and HCPs have an important role in providing information and recommendations about the maternal Tdap recommendation to pregnant women so they can make informed vaccination decisions.



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Mentoring and mental health: What's new in EMS

Our co-hosts are joined by EMS1 contributor Amy Eisenhauer to discuss her thoughts on professional development, mentoring and mental health in the industry

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Distinct patterns of fiber type adaptation in rat hindlimb muscles 4 weeks after hemorrhagic stroke

Objective The aim of this study was to evaluate adaptations in soleus (SOL) and tibialis anterior (TA) muscles in a rat model 4 weeks after hemorrhagic stroke. Design Young adult Sprague-Dawley rats were randomly assigned to two groups: stroke (STR) and control (CTRL), with 8 SOL and 8 TA muscles per group. Hemorrhagic stroke was induced in the right caudoputamen of the STR rats. CTRL rats had no intervention. Neurologic status was evaluated in both groups pre-stroke, and four weeks post-stroke. Muscles were harvested after post-stroke neurologic testing. Muscle fiber types and cross-sectional areas were determined in SOL and TA using immunohistochemical labeling for myosin heavy chain (MHC). Results No generalized fiber atrophy was found in any of the muscles. Fiber types shifted from faster to slower in the TA of the STR group, but no fiber type shifts occurred in the SOL muscles of STR animals. Conclusion Since slower MHC fiber types are associated with weaker contractile force and slower contractile speed, this faster-to-slower fiber type shift in TA muscles may contribute to weaker and slower muscle contraction in this muscle after stroke. This finding may indicate potential therapeutic benefit from treatments known to influence fiber type plasticity. Corresponding author: L. Snow, MMC 388, 420 Delaware St. SE, Minneapolis, MN 55455, Phone: 612-626-5782, FAX: 612-625-4274, Email: snow0018@umn.edu Disclosures: Funding: NIH-K08HD049459 Competing interests and financial benefits to authors: none The results of this study have not been previously presented at any professional association meeting. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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More Than Just a Game: The Public Health Impact of Sport and Physical Activity for People With Disabilities (The 2017 DeLisa Lecture)

Although people with disabilities make up a large proportion of our global population and are known to be disproportionately impacted by sedentary lifestyles leading to chronic disease, programs promoting physical activity often fail to address their unique needs. Both environmental and attitudinal factors also act as barriers to full participation. In this context, increasing evidence shows the positive impact of physical activity and sport on outcomes related to physical health, mental health, community participation, and, in some cases, neurorecovery for people with disabilities. Thus, participation should be seen not only as a medical intervention, but also as a rights-based issue. We, as physiatrists, can be agents of change by promoting concepts of universal design and inclusion in physical activity and sport programs. Corresponding Author: Cheri A. Blauwet, MD, Assistant Professor of PM&R, Harvard Medical School, Director, Kelley Adaptive Sports Research Institute, Spaulding Rehabilitation Hospital, 300 1st Avenue, Charlestown, MA 02129, Office: 617 732 9702, Fax: 617 732 9576, cblauwet@bwh.harvard.edu Acknowledgements The lead author would like to thank Peter Wilson-Braun for assistance in manuscript formatting and figure development. This work was supported by funds from the Kelley Adaptive Sports Research Institute. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Intra- and Interrater Reliability and Concurrent Validity of a New Tool for Assessment of Breast Cancer related Lymphedema of the Upper Extremity (CLUE)

Publication date: Available online 4 October 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Bryan Spinelli, Michael J. Kallan, Xiaochen Zhang, Andrea Cheville, Andrea Troxel, Joy Cohn, Lorraine Dean, Kathleen Sturgeon, Margaret Evangelista, Zi Zhang, David Ebaugh, Kathryn H. Schmitz

Abstract
Objective

The goal of this study was to develop and assess intra and inter-rater reliability and validity of a clinical evaluation tool for breast cancer related lymphedema, for use in the context of outcome evaluation in clinical trials

Design

Blinded repeated measures observational study.

Setting

Outpatient research laboratory.

Participants

Breast cancer survivors with and without lymphedema (N=71).

Interventions

Not applicable.

Main outcome measure

The assessment of Intraclass Correlations (ICCs) for the Breast Cancer related Lymphedema in the Upper Extremity (CLUE) standardized clinical evaluation tool.

Results

Intra-rater reliability for the CLUE tool was ICC: 0.88 (95% CI: 0.71, 0.96). Inter-rater reliability for the CLUE tool was ICC: 0.90 (95% CI: 0.79, 0.95). Concurrent validity of the CLUE score (Pearson's r) was 0.79 with perometric inter-limb difference, and 0.53 with the Norman Lymphedema overall score.

Conclusions

The CLUE tool shows excellent inter- and intra-rater reliability. The overall CLUE score for the upper extremity also shows moderately strong concurrent validity with objective and subjective measures. This newly developed clinical, physical assessment of upper extremity lymphedema provides standardization and a single score that accounts for multiple constructs. Next steps include evaluation of sensitivity to change, which would establish usefulness to evaluate intervention efficacy.



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Skilled Nursing Facility Participation in Medicare’s Bundled Payments for Care Improvement Initiative: A Retrospective Study

Publication date: Available online 4 October 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lianna Weissblum, Peter Huckfeldt, José Escarce, Pinar Karaca-Mandic, Neeraj Sood

Abstract
Objective

To investigate differences in facility characteristics, patient characteristics, and outcomes between skilled nursing facilities (SNFs) that participated in Medicare's voluntary Bundled Payments for Care Improvement (BPCI) initiative and non-participants, prior to BPCI.

Design

Retrospective, cross-sectional comparison of BPCI participants and non-participants.

Setting

SNFs

Participants

All Medicare-certified SNFs (n = 15,172) and their 2011-2012 episodes of care for chronic obstructive pulmonary disease, congestive heart failure, femur and hip/pelvis fracture, hip and femur procedures, lower extremity joint replacement, and pneumonia (n = 873,739).

Interventions

Participation in a bundled payment program that included taking financial responsibility for care within a 90 day episode.

Main Outcome Measures

This study investigates the characteristics of bundled payment participants and their patient characteristics and outcomes relative to non-participants prior to BPCI, to understand the implications of a broader implementation of bundled payments.

Results

SNFs participating in BPCI were more likely to be in urban areas (80.8-98.4% versus 69.5%) and belong to a chain or system (73.8-85.5% versus 55%), and were less likely to be located in the south (13.1-20.2% versus 35.4%). Quality performance was similar or higher in most cases for SNFs participating in BPCI relative to non-participants. In addition, BPCI participants admitted higher socioeconomic status patients with similar clinical characteristics. Initial SNF length of stay was shorter and hospital readmission rates were lower for BPCI patients compared to non-participant patients.

Conclusions

We found that SNFs participating in the second financial risk-bearing phase of BPCI represented a diversity of SNF types, regions, and levels of quality and the results may provide insight into a broader adoption of bundled payment for post-acute providers.



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Data: How often does EMS respond to injured football players

ePCR data from more than 1,000 EMS agencies filtered to understand frequency and type of football players injuries

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Detection of radon with biosensors based on the lead(II)-induced conformational change of aptamer HTG and malachite green fluorescence probe

Publication date: December 2018

Source: Journal of Environmental Radioactivity, Volume 195

Author(s): Shiya Li, Hongwen Liu, Guiying Yang, Shimeng Liu, Ran Liu, Changyin Lv

Abstract

The aim of this paper is to assemble a new biosensor for detecting the accumulated radon dose in the environment to achieve rapid monitor of radon. Based on the correlation between radon and its stable decay daughter 210Pb, a biosensor using the lead-induced specific aptamer HTG conformational changes, and the organic dye malachite green (MG) as a fluorescent probe was assembled. In these studies, we explored a novel, sensitive, label-free, fluorescence biosensing method for the detection of both radon and lead. The fluorescence intensity difference has a linear relationship with Pb2+ and the accumulated radon concentration from 6.87 × 103 Bq·h/m3 to 3.49 × 105 Bq·h/m3. The lead and radon detection limits of this method are 6.7 nmol/L and 2.06 × 103 Bq·h/m3, respectively. The student's t-test results indicated that the new method was reliable and stable. The detection method is sensitive, accurate, easy to operate, has a wide linear range and is highly selective. In the sampling and determination processes of radon, the radiation harm to human health can be effectively avoided.

Graphical abstract

Image 1



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Dabigatran Reduces Liver Fibrosis in Thioacetamide-Injured Rats

Abstract

Background

Liver fibrosis can progress to cirrhosis, hepatocellular carcinoma, or liver failure. Unfortunately, the antifibrotic agents are limited. Thrombin activates hepatic stellate cells (HSCs). Therefore, we investigated the effects of a direct thrombin inhibitor, dabigatran, on liver fibrosis.

Methods

Adult male Sprague–Dawley rats were injected intraperitoneally with thioacetamide (TAA, 200 mg/kg twice per week) for 8 or 12 weeks to induce liver fibrosis. The injured rats were assigned an oral gavage of dabigatran etexilate (30 mg/kg/day) or vehicle in the last 4 weeks of TAA administration. Rats receiving an injection of normal saline and subsequent oral gavage of dabigatran etexilate or vehicle served as controls.

Results

In the 8-week TAA-injured rats, dabigatran ameliorated fibrosis, fibrin deposition, and phosphorylated ERK1/2 in liver, without altering the transcript expression of thrombin receptor protease-activated receptor-1. In vitro, dabigatran inhibited thrombin-induced HSC activation. Furthermore, dabigatran reduced intrahepatic angiogenesis and portal hypertension in TAA-injured rats. Similarly, in the 12-week TAA-injured rats, a 4-week treatment with dabigatran reduced liver fibrosis and portal hypertension.

Conclusions

By inhibiting thrombin action, dabigatran reduced liver fibrosis and intrahepatic angiogenesis. Dabigatran may be a promising therapeutic agent for treatment of liver fibrosis.



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5 ways to eliminate dosing errors

Remain consistent once you've established the patient's weight, ensure you know what's in your containers and practice dosing calculations to prevent errors

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A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1, followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer: Results of the KDOG1001 trial

Gastric Cancer

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Dual Red Imaging Maintains Clear Visibility During Colorectal Endoscopic Submucosal Dissection

Abstract

Background

The endoscopic lens becomes clouded and its visibility reduces during colorectal endoscopic submucosal dissection (ESD), especially in cases with submucosal fatty tissue. Dual red imaging (DRI) is a novel image-enhanced endoscopic technique that improves endoscopic visibility.

Aims

This study aimed to evaluate the predictive factors of submucosal fatty tissue and the clinical usefulness of DRI in maintaining clear visibility during colorectal ESD.

Methods

The study participants included 586 consecutive patients with 645 colorectal tumors who underwent ESD between January 2014 and July 2017. First, the degree of submucosal fatty tissue was evaluated by reviewing recorded images, and the clinical characteristics of the patients and tumors related to severe submucosal fatty tissue were evaluated. Second, 34 tumors resected using DRI were propensity score-matched in a 1:1 ratio to other resected tumors using white light imaging (WLI), and the degree of endoscope lens cloudiness and clinical outcomes were evaluated.

Results

The proportion of tumors located in the right side of the colon, body mass index (≥ 25, BMI), and hemoglobin A1c (≥ 6.5%, HbA1c) were significantly higher in patients with severe submucosal fatty tissue. The visibility in the DRI group was significantly better than in the WLI group. Treatment outcomes in the DRI group were as good as those in the WLI group.

Conclusions

Tumor location in the right side of the colon, BMI (≥ 25), and HbA1c (≥ 6.5%) are the predictive factors of severe submucosal fatty tissue. DRI is useful in maintaining clear visibility during colorectal ESD, especially with submucosal fatty tissue.



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High Trophinin-Associated Protein Expression Is an Independent Predictor of Poor Survival in Liver Cancer

Abstract

Background

Trophinin-associated protein (TROAP) is a cytoplasmic protein that functions as an adhesion molecule in processes such as embryo implantation, spindle formation, and cancer.

Objective

To evaluate the relationship of TROAP expression in hepatocellular carcinoma (HCC) tissue with clinicopathologic parameters and survival time in liver cancer patients based on an analysis of The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data.

Methods

RNA-sequencing (RNA-Seq) expression data and clinical information were downloaded for the TCGA-LIHC cohort. Associations between TROAP expression in HCC tissues and clinical parameters were evaluated by Chi-square tests. Differences in survival between high and low expression groups (median expression cutoff) from Cox regression analysis were compared, and P values were calculated by a log-rank test. Kaplan–Meier curves were compared with the log-rank test.

Results

Analysis of RNA-Seq gene expression data for 373 patients with primary tumors revealed overexpression of TROAP in liver cancer. High TROAP expression was associated with survival status (P = 0.015), T stage (P = 0.049), clinical stage (P = 0.048), and gender (P = 0.033). Patients with high TROAP-expressing liver cancers had a shorter median overall survival of 3.83 years compared with 5.80 years for patients with low TROAP-expressing liver cancers (P = 0.00422). Multivariate analysis identified TROAP expression as an independent prognostic variable for overall survival in liver cancer patients.

Conclusion

TROAP expression is an independent predictor of poor survival in liver cancer.



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Clinical Significance of the Thioredoxin System and Thioredoxin-Domain-Containing Protein Family in Hepatocellular Carcinoma

Abstract

Background

Oxidative stress occurs due to the excessive generation of cellular reactive oxygen species and antioxidant system dysfunction. The thioredoxin (TXN) system and TXN-domain-containing protein (TXNDC) family form networks maintaining the cellular reducing environment. Recently, the importance of these genes in the tumor environment has been emphasized.

Aim

To investigate the clinical significance of TXNs and TXNDC family members in HCC.

Methods

Genomic data from 367 hepatocellular carcinoma (HCC) patients who underwent hepatic resections were analyzed to determine genetic alterations in mRNA and protein levels between patients and healthy controls. In addition, functional enrichment and survival analyses were performed.

Results

HCC patients were shown to have enhanced expression of TXN, TXNRD1, and TXNDC7/9/14 mRNA and protein compared with controls. In accordance with the survival analyses, strong associations were found that patients with TXN, TXNRD1, and TXNDC1/7/9 alterations were proven to have poor prognosis in overall survival. Moreover, gene set enrichment analysis and network analyses revealed that positive correlations were found in mRNA expression of TXN, TXNRD1, and TXNDC7/9 genes with upregulation of the tumor-promoting genes, specifically mTORC1, E2F targets, and Myc targets. On the other hand, elevated expressions of TXNIP and TXNDC11 genes were correlated with suppression of the above tumor-promoting genes.

Conclusions

TXN system and TXNDC family gene panel obtained from the resected tissue of the HCC patients could be used to predict survival prognosis of HCC, and these genes could be considered as potential therapeutic targets for improving HCC survival.



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Confirmation of spondylo‐epi‐metaphyseal dysplasia with joint laxity, EXOC6B type

American Journal of Medical Genetics Part A, EarlyView.


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Impairments of emotional face processing in schizophrenia patients: Evidence from P100, N170 and P300 ERP components in a sample of auditory hallucinators

Publication date: Available online 4 October 2018

Source: International Journal of Psychophysiology

Author(s): Dhrasti Shah, Verner Knott, Ashley Baddeley, Hayley Bowers, Nicola Wright, Allen Labelle, Charles Collin

Abstract

Patients with schizophrenia show impaired face and emotional expression processing that may be due to early perceptual deficits or late impairments in higher-order emotional facial recognition. This study examined event-related potentials (ERPs) in 23 patients with schizophrenia who experience auditory hallucinations and 19 healthy controls. EEG activity was recorded from 32 scalp sites positioned according to the 10-10 placement system. Linked left and right electrodes at the mastoids served as the reference. The P100, N170 and P300 were measured during an emotional facial identification task, which included neutral, joyful, sad, angry and fearful facial expressions and non-face stimuli (chairs). P100 was measured at O1/2 and P7/8. N170 was measured at P7/8. P300 was measured at Pz. Patients with schizophrenia were slower at identifying all facial expressions, including neutral ones. They also showed less positive P100 amplitude to sad, angry and fearful facial expressions. N170 amplitudes were smaller in patients in response to neutral, joyful, sad, angry, and fearful facial expression. Patients showed less positive P300 mean amplitudes to all facial expressions, including neutral ones. Within-group comparisons showed that patients exhibited a different pattern of ERP modulation across facial expressions than controls for P100 and N170, but not for P300. Our findings are compatible with the idea that behavioural and electrophysiological face-processing deficits in schizophrenia arise from early-stage deficits in visual processing.



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Ultrasound-guided lumbar plexus block using three different techniques: a comparison of ultrasound image quality

Abstract

Purpose

The purpose of this study was to compare the ultrasound image quality at three different transducer positions for ultrasound-guided lumbar plexus block (LPB).

Methods

This prospective comparative study included 30 patients who underwent total hip arthroplasty under general anesthesia in combination with LPB. Using the same ultrasound machine settings for each patient, a transverse view of the lumbar plexus (LP) at the L3–4 vertebral level was obtained with a convex transducer placed at three different positions: immediately lateral to the dorsal midline (medial position), almost 5 cm lateral to the dorsal midline (paravertebral position), and at the abdominal transverse flank (shamrock position). Ultrasound-guided LPB with catheter insertion was performed via in-plane needle insertion with the transducer randomly assigned to one of the three positions. The echo intensity (EI) ratio of the LP to psoas major muscle (PMM), the EI of the LP and PMM, and the ultrasound visibility score of the needle, local anesthetic, and catheter were recorded.

Results

The LP/PMM EI ratio was significantly higher at paravertebral position (1.4 ± 0.2) than at medial position (1.2 ± 0.2; p = 0.003) and shamrock position (1.3 ± 0.2; p = 0.040). The EI of the LP and PMM was highest at shamrock position (p < 0.001). During the block procedure, the ultrasound visibility score of the needle and local anesthetic was significantly higher at paravertebral position than at medial position.

Conclusion

Under the conditions of this study, the contrast between LP and PMM is significantly higher at paravertebral position than at medial position and at the abdominal transverse flank (shamrock position). LP and PMM at the shamrock position appear significantly brighter among the three probe positions in sonograms.



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Predictors for sustained new-onset atrial fibrillation in critically ill patients: a retrospective observational study

Abstract

Purpose

Although new-onset atrial fibrillation (AF) is frequently observed in the intensive care unit (ICU), the incidence and predictors for sustained new-onset AF have not been investigated, except for cardiac surgery patients. We have evaluated potential predictors for sustained new-onset AF in a mixed ICU.

Methods

In this retrospective observational study, we screened non-cardiac surgery patients who were admitted to the ICU between January 2010 and December 2013 and had been hospitalized for > 24 h in the ICU. We collected information about heart rhythm 6 h after the onset of AF. We compared detailed patient characteristics between patients with sinus rhythm (SR) and those with sustained AF at 6 h after the onset of AF. Additionally, we applied variable selection using backward elimination based on Akaike's Information Criterion (AIC). Calibration was performed based on the Hosmer–Lemeshow test.

Results

New-onset AF occurred in 151 of 1718 patients and 99 patients converted to SR at 6 h. Backward elimination identified predictors as follows (AIC = 175.3): CHADS2 score, elective surgery, infection on ICU admission, serum potassium > 4.0 mmol/L, male sex, mechanical ventilation, and diagnostic grouping. The model showed good calibration for sustenance of AF at 6 h after the onset using the Hosmer–Lemeshow Chi-square value of 4.36 (degrees of freedom = 4, p = 0.360) indicating a good fit.

Conclusions

These predictors might be useful in future interventional studies to identify patients who are likely to sustain new-onset AF.



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In vitro changes in the proportion of protein-unbound-free propofol induced by valproate

Abstract

Purpose

It has been reported that oral valproate (VPA) reduces the dose of propofol required for sedation. As  a potential reason for this, it is considered that VPA displaces serum protein-bound propofol and increases the proportion of protein-unbound-free propofol. To examine this hypothesis, the present in vitro study investigated the influence of VPA on the proportion of protein-unbound-free propofol in human serum samples.

Methods

Serum samples were collected from 10 healthy volunteers, who were not taking any medication. VPA (final concentration: 0.05, 0.1 or 1 mg/mL) and propofol (final concentration: 1 or 5 µg/mL) were mixed with serum samples with normal (4.0 g/dL) or low (2.5 g/dL) albumin concentrations. Then, protein-unbound-free propofol was extracted from the samples, and its concentration was measured using high-performance liquid chromatography. We compared the proportion of protein-unbound-free propofol in each of the VPA-containing samples with that in serum samples without VPA (control).

Results

In the serum samples with normal albumin concentrations, 1 mg/mL VPA significantly increased the proportion of protein-unbound-free propofol at 1 and 5 µg/mL propofol. Furthermore, in the serum samples with low albumin concentrations, the proportion of protein-unbound-free propofol was significantly increased by both 0.1 and 1 mg/mL VPA at propofol concentrations of 1 and 5 µg/mL.

Conclusion

VPA might increase the proportion of protein-unbound-free propofol in human serum via displacement reactions.



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Clinical significance of hepatic steatosis according to coronary plaque morphology: assessment using controlled attenuation parameter

Abstract

Background

Nonalcoholic fatty liver disease (NAFLD) plays a significant role in coronary atherosclerosis, independent of shared metabolic risk factors. The measurement of the controlled attenuation parameter (CAP) has shown to allow early and noninvasive detection of NAFLD at subclinical stage. We evaluated the significance of CAP-defined NAFLD in association with the presence of any type of coronary plaques and different plaque compositions.

Methods

We conducted a retrospective cohort of apparently healthy subjects who had liver Fibroscan and coronary computed tomography during health screening exams.

Results

A greater number of subjects with CAP-defined NAFLD was found in group with coronary plaques (61.3% vs. 73.5%, p = 0.005 without vs. with any type of plaque). From multivariate regression model, CAP ≥ 222 dB/m was an independent and significant parameter associated with the presence of coronary plaques, after adjusting possible confounders (OR 1.624, 95% 1.047–2.518, p = 0.030). Interestingly, CAP ≥ 222 dB/m was significantly associated with non-calcified plaque (adjusted OR 3.528, 95% CI 1.463–8.511, p = 0.005), whereas it was not significant in calcified plaques (p = 0.171).

Conclusion

CAP-defined NAFLD is independently associated with coronary plaques, especially non-calcified plaques. The association between NAFLD and non-calcified plaques suggests that particular attention should be given to the subjects with NAFLD for primary prevention.



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Elevation of extracellular osmolarity improves signs of myotonia congenita in vitro: A preclinical animal study

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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The central amygdala to periaqueductal gray pathway comprises intrinsically distinct neurons differentially affected in a model of inflammatory pain

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Visual response properties of neurons in the superficial layers of superior colliculus of awake mouse

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Structural and copy number chromosome abnormalities in canine cutaneous mast cell tumours

Abstract

Mast cell tumours (MCTs) are the most common skin tumours in dogs. Their clinical behaviour is variable and their aetiology remains largely unknown. We performed a metaphase fluorescence in situ hybridisation (FISH) with whole chromosome painting probes, and interphase FISH with BAC probes for 14 cancer-related genes to reveal clonal structural chromosome rearrangements and copy number variants (CNVs) in canine cutaneous MCTs. The metaphase FISH performed in three MCTs revealed several clonal monosomies and trisomies and two different chromosome rearrangements. No centric fusions were detected. The interphase FISH showed a variety of low frequency CNVs for the individual cancer-related genes. The heterogeneous character of the detected abnormalities indicates increased chromosome instability in canine MCTs. The clonal gain of chromosome 11 was detected in 81% (13/16) of the MCTs. Further research is needed to evaluate the significance of this abnormality as prognostic factor for the survival time or recurrence risk assessments in canine cutaneous MCTs.



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Homozygous 2p11.2 deletion supports the implication of ELMOD3 in hearing loss and reveals the potential association of CAPG with ASD/ID etiology

Abstract

Autism spectrum disorder (ASD) is a set of neurodevelopmental conditions characterized by early-onset difficulties in social communication and unusually restricted, repetitive behavior and interests. Parental consanguinity may lead to higher risk of ASD and to more severe clinical presentations in the offspring. Studies of ASD families with high inbreeding enable the identification of inherited variants of this disorder particularly those with an autosomal recessive pattern of inheritance. In our study, using copy number variants (CNV) analysis, we identified a rare homozygous deletion in 2p11.2 region that affects ELMOD3, CAPG, and SH2D6 genes in a boy with ASD, intellectual disability (ID), and hearing impairment (HI). This deletion may reveal a new contiguous deletion syndrome in which ELMOD3, known to be implicated in autosomal recessive deafness underlies the HI of the proband and CAPG, member of actin regulatory proteins involved in cytoskeletal dynamic, an important function for brain development and activity, underlies the ASD/ID phenotype. A possible contribution of SH2D6 gene, as a part of a chimeric gene, to the clinical presentation of the patient is discussed. Our result supports the implication of ELMOD3 in hearing loss and highlights the potential clinical relevance of 2p11.2 deletion in autism and/or intellectual disability.



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An extremely rare case who underwent total remnant pancreatectomy due to recurrent pancreatic metastasis of intraductal tubulopapillary neoplasm

Abstract

We describe a rare case of recurrent pancreatic metastasis of intraductal tubulopapillary neoplasm (ITPN). A 53-year-old woman diagnosed with an intraductal papillary mucinous neoplasm (IPMN) and a pancreatic ductal adenocarcinoma (PDAC) of the pancreatic body underwent a distal pancreatectomy. The tumor was composed of cuboidal, high-grade dysplastic cells proliferating in a tubulopapillary growth pattern without mucin production; hence, the final diagnosis was ITPN. A follow-up computed tomography scan revealed an enhanced 2 cm mass of the pancreatic head 3 years after the surgery. From workup investigations, the patient was diagnosed with PDAC or a recurrent ITPN of the remnant pancreas. A total remnant pancreatectomy was then performed. Histopathological findings revealed that the new ITPN had the same features as the prior ITPN. In IPMNs, the presence of an invasive component and high-grade dysplasia can lead to progression to a recurring IPMN and the development of PDAC. Because there have been few reports of recurrent ITPN developing into PDAC, the risk factors for ITPN have not been investigated. Because of the uncertain clinicopathological characteristics of ITPN, more data should be gathered to assess the long-term outcome and malignant potential of ITPN.



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Transcranial Direct Current Stimulation (tDCS) Reduces Nociceptive Behavior in an Orofacial Pain Model

Journal of Oral Rehabilitation, Volume 0, Issue ja, -Not available-.


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The efficacy of nasal airway stent (Nastent) on obstructive sleep apnea and prediction of treatment outcomes

Journal of Oral Rehabilitation, Volume 0, Issue ja, -Not available-.


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Time for a Different Approach to Anterior Cruciate Ligament Injuries: Educate and Create Realistic Expectations

Abstract

Following an anterior cruciate ligament (ACL) injury, patients are often reassured that timely surgery followed by intensive physiotherapy will "fix their knee". Not only does this message create a false perception of uncomplicated return to sport (RTS), it also ignores the large body of evidence demonstrating a high RTS re-injury rate following ACL reconstruction. In this article, we propose an individualised approach to the management of ACL injuries that targets a shift away from early surgery and towards conservative management, with surgery 'as needed' and rehabilitation tailored to the patient's RTS goals. Education on the natural history of ACL injuries will ensure patients are not misguided into thinking surgery and intensive rehabilitation guarantees great outcomes. Further, understanding that conservative management is not inferior to surgery—and not more likely to cause knee osteoarthritis—will help the patient make an informed decision. For patients who opt for surgical management, rehabilitation must target strength and functional performance, avoid rapid increases in training load, and be guided by an RTS timeframe that is no shorter than 9 months. The content of rehabilitation should be similar for patients who opt for non-operative management, although the RTS timeframe will likely be shorter. All patients should receive education on the relationship between injury risk and training load, and understand that a home-exercise program is not inferior to intensive physiotherapist-led exercise.



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