Παρασκευή, 30 Νοεμβρίου 2018

Football Compared with Usual Care in Men with Prostate Cancer (FC Prostate Community Trial): A Pragmatic Multicentre Randomized Controlled Trial

Abstract

Background

Physical activity has been shown to mitigate the unwanted psychological and physiological side effects of prostate cancer treatments, but sustainable exercise possibilities are limited.

Objective

Our objective was to examine whether football in a real-world setting (i.e., local football clubs) was safe and feasible in practice and could improve quality of life, mitigate decline in muscle mass and bone density, and increase fat mass in patients with prostate cancer.

Methods

In this pragmatic, multicentre, parallel randomized controlled trial, men diagnosed with prostate cancer were recruited from five Danish urological departments. Men (N = 214) diagnosed with prostate cancer were randomly allocated, using random generated lists (block size 4–8) stratified for center and androgen-deprivation therapy status, to either 1 h of football twice weekly in a local football club or to usual care, which was a 15- to 30-min telephone session covering their options for physical activity or free-of-charge rehabilitation delivered as standard in Denmark. Allocation was concealed from the trial investigator performing the randomization, but—given the nature of the intervention—this was not possible for personnel and participants. Assessments were performed at baseline, 12 weeks, and 6 months. The primary outcome was mean change difference in prostate cancer-specific quality of life at 12 weeks. Secondary outcomes were body composition, 12-Item Short Form Health Survey (SF-12) physical and mental health, and safety—reported as fractures, falls, and serious adverse events.

Results

Attrition was 1 and 3% at 12 weeks, and 5% and 5% at 6 months for the usual care and football groups, respectively. Prostate cancer-specific quality of life was equal between groups at 12 weeks (mean difference + 1.9 points, 95% confidence interval [CI] –1.0–4.8; P = 0.20) and at 6 months (+ 0.5 points, 95% CI –2.8–3.8; P = 0.76). Fractures were equally distributed, with two fractures in the usual care group and one in the football group. Likewise, body composition outcomes were equal. Mental health improved after 6 months of football (mean difference + 2.7 points, 95% CI 0.8–4.6; P = 0.006).

Conclusions

In this trial, community-based football was a feasible exercise strategy for men with prostate cancer. Football did not improve prostate cancer-specific quality of life but did improve mental health; the clinical significance of this is unclear.

Trial registration

ClinicalTrials.gov: NCT02430792.



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Genetic Diversity Analysis of Mupirocin-Resistant Staphylococcus aureus Clinical Isolates in Tehran Hospitals, Iran

Microbial Drug Resistance, Ahead of Print.


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Efficient Homologous Recombination in Mice Using Long Single Stranded DNA and CRISPR Cas9 Nickase

The CRISPR/Cas9 nickase mutant is less prone to off-target double-strand (ds)DNA breaks than wild-type Cas9 because to produce dsDNA cleavage it requires two guide RNAs to target the nickase to nearby opposing strands. Like wild-type Cas9 lesions, these staggered lesions are repaired by either non-homologous end joining or, if a repair template is provided, by homologous recombination (HR). Here, we report very efficient (up to 100%) recovery of heterozygous insertions in Mus musculus produced by long (>300 nt), single-stranded DNA donor template-guided repair of paired-nickase lesions.



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Effects of deep brain stimulation on the primary motor cortex: Insights from transcranial magnetic stimulation studies

Movement disorders are characterized by hyperkinetic or hypokinetic movements. Abnormal neuronal activities in the cortex and other regions related to disturbances in the basal ganglia nuclei is a major cause of many movement disorders (Lang and Lozano, 1998a; Lozano and Lipsman, 2013). Modulation of disordered circuits within basal ganglia-thalamo-cortical pathways is a critical therapeutic strategy in various movement disorders. Although a pharmacological approach to correct disordered circuits is useful, potential exposure of all neurons in the brain to a drug may make the therapy less attractive in some patient populations (Lang and Lozano, 1998b).

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Development of a collaborative model of low back pain: report from the 2017 NASS consensus meeting

Low back pain (LBP) is a multifactorial problem with complex interactions among many biological, psychological and social factors. It is difficult to fully appreciate this complexity because the knowledge necessary to do so is distributed over many areas of expertise that span the biopsychosocial domains.

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PREDICTION OF MECHANICAL COMPLICATIONS IN ADULT SPINAL DEFORMITY SURGERY – THE GAP SCORE VERSUS THE SCHWAB CLASSIFICATION

– Surgery for adult spinal deformity (ASD) is a challenging and complex procedure with high reported complication (8.4-42%) and revision rates (9-17.6%). Failure to achieve or maintain adequate postoperative sagittal alignment has been reported to be the main cause of mechanical complications. In order to define appropriate surgical targets, the Scoliosis Research Society (SRS)-Schwab classification and the Global Alignment and Proportion (GAP) score were established. In the literature, no study has yet compared these classification systems with respect to the risk of developing mechanical complications.

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Editorial announcement

Publication date: December 2018

Source: Journal of Human Evolution, Volume 125

Author(s): Mike Plavcan, David M. Alba, Sarah Elton



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Scapular anatomy of Paranthropus boisei from Ileret, Kenya

Publication date: December 2018

Source: Journal of Human Evolution, Volume 125

Author(s): David J. Green, Habiba Chirchir, Emma Mbua, John W.K. Harris, David R. Braun, Nicole L. Griffin, Brian G. Richmond

Abstract

KNM-ER 47000A is a new 1.52 Ma hominin scapular fossil belonging to an associated partial skeleton from the Koobi Fora Formation, Kenya (FwJj14E, Area 1A). This fossil effectively doubles the record of Early Pleistocene scapulae from East Africa, with KNM-WT 15000 (early African Homo erectus) preserving the only other known scapula to date. KNM-ER 47000A consists of a complete glenoid cavity preserving a portion of the scapular spine and neck, the proximal half of the acromion, and a majority of the axillary border. A sufficient amount of anatomy is preserved to compare KNM-ER 47000A with scapulae of several Australopithecus species, extinct Homo, and living hominoids. The glenohumeral joint of KNM-ER 47000A is more laterally oriented than those of great apes and Australopithecus, aligning it closely with KNM-WT 15000 and modern humans. While this morphology does not imply a strong commitment to arboreality, its scapular spine is obliquely oriented—as in gorillas and some Australopithecus fossils—particularly when compared to the more horizontal orientation seen in KNM-WT 15000 and modern humans. Such a spine orientation suggests a narrow yet long infraspinous region, a feature that has been attributed to suspensory taxa. Accordingly, the morphology of KNM-ER 47000A presents conflicting behavioral implications. Nonetheless, a multivariate consideration of the available scapular traits aligns KNM-ER 47000A and Australopithecus with great apes, whereas KNM-WT 15000 resembles modern humans. The scapular morphology of KNM-ER 47000A is unique among fossil and extant hominoids and its morphological differences from KNM-WT 15000 strengthen the attribution of KNM-ER 47000 to Paranthropus boisei as opposed to early Homo. As the first evidence of scapular morphology in P. boisei, KNM-ER 47000A provides important new information on variation in hominin shoulder and upper limb anatomy from this critical period of hominin evolutionary history.



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Editorial Board

Publication date: December 2018

Source: Journal of Human Evolution, Volume 125

Author(s):



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EEG analysis in anti-NMDA receptor encephalitis: description of typical patterns

Publication date: Available online 29 November 2018

Source: Clinical Neurophysiology

Author(s): S. Jeannin-Mayer, N. André-Obadia, S. Rosenberg, C. Boutet, J. Honnorat, J.C. Antoine, L. Mazzola

Abstract
Objective

To describe different electroencephalogram (EEG) patterns and epileptic features in patients with anti- N-methyl-D-aspartate receptor encephalitis (anti-NMDARE), their timeline in the course of the disease, their correlation with clinical data and outcome.

Methods

We retrospectively analyzed EEG recordings between November 2007 and June 2016 in 24 consecutive patients.

Results

Three EEG patterns were described: Excessive Beta Activity range 14-20 Hz (EBA) in 71% of patients, Extreme Delta Brush (EDB) in 58% and Generalized Rhythmic Delta Activity (GRDA) in 50%. They followed a chronological organization in the course of the disease: EBA appeared first, followed by EDB and then GRDA, as the median time of appearance for EBA, EDB and GRDA was respectively 10, 16.5 and 21.5 days. The presence of GRDA was strongly associated with concomitant abnormal movements (p<0.001).

Conclusion

This study focuses on EEG and epileptic abnormalities in anti-NMDARE. Beyond EDB that were already reported (Schmitt et al., 2012), GRDA seems to be a very frequent pattern. Its rhythmic aspect should not be misinterpreted as seizure or status epilepticus, to avoid antiepileptic treatments intensification.

Significance

This study comforts the importance of EEG in anti-NMDARE, with a better description of EEG abnormalities for a better treatment management.



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Behavioural and electrophysiological effects of tDCS to prefrontal cortex in patients with disorders of consciousness

Publication date: Available online 29 November 2018

Source: Clinical Neurophysiology

Author(s): Marianna Cavinato, Clara Genna, Emanuela Formaggio, Caterina Gregorio, Silvia F. Storti, Paolo Manganotti, Emanuela Casanova, Roberto Piperno, Francesco Piccione

Abstract
Objectives

Left dorsolateral prefrontal cortex anodal transcranial direct current stimulation (tDCS) was applied in a group of patients with disorders of consciousness to determine the effects of modulation of spontaneous oscillatory brain activity.

Methods

12 patients in an unresponsive wakefulness syndrome (UWS) and 12 in a minimally conscious state (MCS) underwent 2-weeks active and 2-weeks sham tDCS. Neurophysiological assessment was performed with EEG power spectra and coherence analysis directly before and after each session

Results

An increase of power and coherence of the frontal and parietal alpha and beta frequency bands and significant clinical improvements were seen after the active tDCS in MCS patients. In contrast, UWS patients showed some local frontal changes in the slow frequencies. No treatment effect was observed after sham.

Conclusions

tDCS could induce changes in cortical EEG oscillations, modulating the travel of alpha and beta waves between anterior and posterior brain areas when some cognitive functions were preserved. This plays an important role in consciousness by integrating cognitive-emotional processing with the state of arousal. In unresponsive people, brain integration seems to be lost.

Significance

Our results further support the critical role of long-range fronto-parietal connections in consciousness and show the potential therapeutic utility of tDCS.



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Coregulatory long non-coding RNA and protein-coding genes in serum starved cells

Publication date: Available online 29 November 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Fan Wang, Rui Liang, Benjamin Soibam, Jin Yang, Yu Liu

Abstract

Serum starvation is widely used in cell biology to trigger cell cycle arrest, apoptosis, autophagy, and metabolic adaptations. Serum starvation-related molecular events have been well characterized at protein level but not at transcript level: how long non-coding RNAs contribute to the regulation of protein-coding genes is largely unknown. Here, we captured the lncRNA transcriptome in serum starved mouse embryonic fibroblasts and identified three main modes of action: cis-acting/coregulatory, trans-acting, and "miRNA-carrier". Whole-genome and individual gene level analyses support that our annotation provides an important platform for understanding lncRNA/protein-coding gene coregulatory mechanisms in serum starvation.



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Severe vitamin D deficiency is a prognostic biomarker in autoimmune hepatitis

Alimentary Pharmacology and Therapeutics

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Depression in cirrhosis – A prospective evaluation of the prevalence, predictors and development of a screening nomogram

Alimentary Pharmacology and Therapeutics

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Hepatitis B virus relapse rates in chronic hepatitis B patients who discontinue either entecavir or tenofovir

Alimentary Pharmacology and Therapeutics

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Comprehensive study on the technical aspects of sampling, transporting and measuring radon-in-water

Publication date: February 2019

Source: Journal of Environmental Radioactivity, Volume 197

Author(s): Viktor Jobbágy, Heiko Stroh, Gerd Marissens, Mikael Hult

Abstract

The European Commission's Joint Research Centre organizes proficiency tests (PT) on radon-in-water measurements. In order to optimize sampling, transport and measurement methods many tests and small scale proficiency tests have been performed. The waters from natural springs, wells were sampled on-site in glass bottles then transported cooled to the JRC and collaborating laboratories. For the material characterization standard measurement methods based on gamma-ray spectrometry, emanometry and liquid scintillation counting were used. The influence of sampling, transport and sample handling on radon-loss was tested and quantified. It was observed that parameters like container material, filling height, storage temperature and handling can lead to substantial measurement bias due to radon-loss. This high risk for radon-loss from samples can potentially be a general radioprotection problem as doses to the public may be underestimated. Regular air and road transport can be considered adequate means of transport as they have little influence on radon-loss if a suitable glass sample container with flexible cap is used and that it is completely filled. On the basis of this work, modifications to the related standard as best practices are also proposed.



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Correction to: Inequality and Innovation: Barriers and Facilitators to 17P Administration to Prevent Preterm Birth among Medicaid Participants

The original version of this article unfortunately contained a mistake in the order of authors. The co-author "Sarah Benatar" should be the second author and "Brigette Courtot" should be the third author of the article.



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Micronutrient status of populations and preventive nutrition interventions in South East Asia

Abstract

Objectives Since the 1990s, programs for the control of micronutrient deficiencies became a public health priority for many governments, including the countries partnering the project "Sustainable Micronutrient Interventions to Control Deficiencies and Improve Nutritional Status and General Health in Asia" (SMILING): Cambodia, Indonesia, Laos-PDR, Thailand and Vietnam. The aim of this study was to map which micronutrient deficiencies have been addressed and which interventions were in place in the SMILING countries. Methods The mapping covered the period up to 2012. Updated information from relevant surveys after 2012 is included in this paper after the completion of the SMILING project. The mapping of micronutrient status was limited to either national or at least large-scale surveys. Information on nutrition interventions obtained through a systematic mapping of national programs combined with a snowball collection from various sources. Results Among the five SMILING countries, Thailand differed historically by an early implementation of a nationwide community-based nutrition program, contributing to reductions in undernutrition and micronutrient deficiencies. For Cambodia, Indonesia, Laos PDR, and Vietnam, some national programs addressing micronutrients have been implemented following adjusted international recommendations. National surveys on micronutrient status were scattered and inconsistent across the countries in design and frequency. Conclusion for practice In conclusion, some micronutrient deficiencies were addressed in national interventions but the evidence of effects was generally lacking because of limited nationally representative data collected. Improvement of intervention programs to efficiently reduce or eliminate micronutrient deficiencies requires more systematic monitoring and evaluation of effects of interventions in order to identify best practices.



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The Gut Microbiome: A Difficult Target for Translational Studies of Clostridium Difficile Colonization

No abstract available

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Conceptual Model of Lean Body Mass in Pediatric Inflammatory Bowel Disease

Youth with Inflammatory Bowel Disease (IBD) demonstrate deficits in lean body mass (LM) placing them at increased risk for future health problems, including reduction of bone mass and impaired bone architecture. Research suggests that deficits in LM are multifactorial, including influences from the disease and its treatment, as well as health behaviors such as diet and physical activity. Based on a systematic literature review examining factors related to LM deficits in IBD, this paper presents a conceptual model to explain the development of LM in youth with IBD. The model considers predictors of LM across four domains: (1) demographic; (2) medical; (3) diet; and (4) physical activity. Much existing research is cross-sectional, but suggests multiple factors work together to promote or inhibit LM accrual in youth with IBD. The conceptual model, developed based on empirical findings to date, can be used to understand and further elucidate the process through which LM is developed and maintained, to inform the development of empirically-supported clinical interventions, and to guide future research objectives and priorities. Address correspondence and reprint requests to Margaux J. Barnes, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, McWane Suite 5604, Birmingham, AL 35294 (e-mail: mbarnes@peds.uab.edu). Received 11 June, 2018 Accepted 14 October, 2018 This work has been supported in part by the Nutrition and Obesity Research Center Pilot and Feasibility Program as well as the Kaul Pediatric Research Institute. No competing interests, personal or financial, exist for any authors. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Abnormal Liver Enzymes in Fat or Lean Children Should Always Be a Cautionary Tale

No abstract available

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Lean NAFLD: Should it be considered in Lean Adolescents with Elevated Liver Enzymes?

No abstract available

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Colombian school children with functional GI disorders respond differently to family stress than healthy children

Our objective is to compare coping methods, stress responses, and resilience in children with and without functional gastrointestinal disorders (FGIDs) in response to common sources of stress. We performed a case-control study. Children meeting criteria for FGIDs and matched controls completed measures of response to stress (Peer Stress, Family Stress, Academic Problems, and Recurrent Abdominal Pain versions of the Response to Stress Questionnaire) and resilience (Connor-Davidson Resilience Scale 10). We included 134 children with a FGID (57 with functional constipation and 74 with an abdominal pain-predominant FGID) and 135 controls. Children with FGIDs were more likely to take action (p 

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Complementary and alternative medicine use in children with inflammatory bowel disease

Complementary and Alternative Medicine (CAM) consists of products and practices that are not considered to be a part of conventional medicine. This article reviews pediatric studies on CAM in Inflammatory Bowel Disease (IBD) along with relevant adult studies. Prevalence of CAM use ranges from 22 to 84% in children with IBD all over the world. CAM use in IBD includes diet changes, supplements, herbals, botanicals and mind-body therapies. Common reasons for using CAM include severe disease and concern for adverse effects of conventional medicines. Despite widespread use, there are limited studies on efficacy and safety of CAM in children. Small studies suggest a favorable evidence for use of probiotics, fish oil, marijuana and mind-body therapy in IBD. Adverse effects of CAM are reported but are rare. The article provides current state of knowledge on the topic and provides guidance to physicians to address CAM use in pediatric patients with IBD. Address correspondence and reprint requests to Dinesh S. Pashankar, MD, MRCP, Department of Pediatrics, Yale University, School of Medicine, 333 Cedar Street, PO Box 208064, LMP 4091A, New Haven, CT 06520 (e-mail: dinesh.pashankar@yale.edu). Received 7 August, 2018 Accepted 6 November, 2018 Financial Disclosure Statement: The authors have no financial relationship relevant to this article to disclose. Funding Source: None Conflict of interest Statement: The authors have no conflicts of interest relevant to this article to disc. Abbreviations: CAM-complementary and alternative medicine, IBD-Inflammatory bowel disease, CD – Crohn's disease, UC – Ulcerative colitis Author role: Dr Phatak conceptualized the review, drafted the initial manuscript, reviewed and revised the manuscript and approved the final manuscript as submitted. Dr Alper reviewed and revised the manuscript, and approved the final manuscript as submitted Dr Pashankar conceptualized the review, reviewed and revised the manuscript, and approved the final manuscript as submitted. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Giant Portomesenteric Venous Thrombosis Associated With Rectal Bleeding In A Child

No abstract available

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Changing Epidemiology of Liver Involvement in Children with Celiac Disease

Objectives: Available data indicate that liver involvement is present in a significant proportion of children with celiac disease (CD) at the diagnosis (elevated transaminases 15–57%, autoimmune liver disease 1–2%). We sought to evaluate prevalence, clinical course, and risk factors for liver involvement in a large cohort of children with CD. Methods: Children (age 0–18 years) diagnosed with CD from March 2010 to April 2016 were enrolled. Liver involvement was considered to be present when ALT levels were >40 U/L (hypertransaminasemia, HTS). Patients with HTS were re-evaluated after at least 12 months of a gluten-free diet (GFD). Results: CD was diagnosed in 806 patients during the study period; of these, ALT levels were available for 700 patients (86.9%), and were elevated in 27 (3.9%, HTS group); median ALT and AST levels in the HTS group were 57 U/L (IQR 49–80 U/L) and 67 U/L (IQR 53–85 U/L), respectively. Younger age, malabsorption symptoms, and low hemoglobin or ferritin were significantly more common in the HTS group at univariate analysis. At multivariate analysis, only age ≤4.27 years correlated with risk of liver involvement (OR 3.73; 95% CI: 1.61 - 8.66). When retested on a GFD, all but three patients normalized ALT levels; of these, one was diagnosed with sclerosing cholangitis. Conclusions: Liver involvement in celiac children is now less frequent than previously reported, possibly due to changing CD epidemiology. Younger age is the only risk factor. Associated autoimmune liver disease is rare. Address correspondence and reprint requests to Samuele Naviglio, MD, Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'Istria 65/1, 34137, Trieste, Italy (e-mail: samuele.naviglio@gmail.com). Received 18 August, 2018 Accepted 5 November, 2018 Elisa Benelli and Samuele Naviglio contributed equally to this work. Conflicts of Interest and Source of Funding: This study was supported by the European Union - European Regional Development Fund (Interreg Central Europe "Focus in CD" project N° CE11). All Authors declare no conflict of interests. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Πέμπτη, 29 Νοεμβρίου 2018

Comment on: “The Use of Microtechnology to Quantify the Peak Match Demands of the Football Codes: A Systematic Review”



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Authors’ Reply to Carling et al: Comment on: “The Use of Microtechnology to Quantify the Peak Match Demands of the Football Codes: A Systematic Review”



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Intracholecystic papillary-tubular neoplasm of the gallbladder originating in the cystic duct with extensive intraepithelial progress in the common bile duct

Abstract

A 59-year-old man with anorexia who had a history of cholecystectomy was referred to our hospital. Imaging examinations revealed a contrast-enhanced tumor in the residual cystic duct and a part of the common bile duct. Endoscopic retrograde cholangiopancreatography and peroral-cholangioscopy showed a papillary tumor with movement and a change in the shape. Under a diagnosis of primary cystic duct cancer, subtotal stomach-preserving pancreaticoduodenectomy was performed. The microscopic examination of a resected specimen revealed intracholecystic papillary-tubular neoplasm located in the residual cystic duct, forming a polypoid protrusion to the common bile duct and extensive intraepithelial progress in the common bile duct.



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Genetic diversity and population structure of Lychnis wilfordii (Caryophyllaceae) with newly developed 17 microsatellite markers

Abstract

Lychnis wilfordii (Regel) Maxim. is a perennial plant designated as an endangered species by the Korean government because of rapid reduction in its population size. Thus, a population genetic study of this species is needed to establish the strategy for management and conservation based on scientific evidences. The goals of this study were to develop useful microsatellite markers for L. wilfordii and to understand current genetic status of L. wilfordii in Korean peninsula. Seventeen microsatellite markers were identified using next-generation sequencing and bioinformatic analysis and then analyzed genetic diversity in one hundred forty-five individuals from Korea (KI1, KI2, and KP), China (CX, CF) and Russia (RP). Analysis of molecular variance (AMOVA), principal coordinates analysis (PCoA) and STRUCTURE results consistently showed discontinuity among L. wilfordii populations. AMOVA showed that the percentage of variation among populations was 53%, which was higher than the variation within populations (19%). PCoA showed that the populations were divided into three genetic clusters, (1) Chinese (CX, CF), (2) Russian (RP) populations and Korean populations (KI1, KI2) excluding KP, and (3) the KP population. In particular, KP, the most southern population on the Korean peninsula, showed significantly lower observed and expected heterozygosity, number of effective alleles, and Shannon index (I) than those of KI1 and KI2. L. wilfordii showed high differentiation between populations with low genetic diversity within populations. Among Korean populations, KP is likely to be affected by genetic drift due to small population size, low genetic diversity and limited gene flow.



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Association between CD53 genetic polymorphisms and tuberculosis cases

Abstract

Background

Tetraspanin proteins are expressed in various immune cells, and they play an important role in tuberculosis formation. CD53 is a protein in the tetraspanin family that is expressed in many white blood cells. In particular, it plays an important role in cytokine regulation and interaction between natural killer (NK) cells and antigen-presenting cells (APCs).

Objectives

The purpose of this study was to investigate whether the single nucleotide polymorphisms (SNPs) difference of CD53 gene could affect TB case.

Methods

In this study, we investigated the effects of genetic polymorphism of CD53 on the pathogenesis of tuberculosis based on Korean Association Resource (KARE) data. Logistic regression analysis was used to determine the effect of SNPs of the CD53 gene on tuberculosis in TB cases and control groups. We also examined the effect of SNPs on tuberculosis in gene expression.

Results

Eight SNPs of CD53 were found to be associated with TB case. The SNP showing the greatest significance in this association was rs4839583 (odds ratio = 0.83, 95% confidence interval 0.72–0.96, p = 0.010). These genetic variants might be involved in cytokine regulation through the Jun pathway, and are thought to affect the immune responses and pathogenesis of TB.

Discussion

CD53 is a type of tetraspanin that is expressed on various immune cells. In this study, we identified eight statistically significant SNPs in CD53 gene, confirming that it could be involved in the regulation of CD53 gene expression.

Conclusion

Associations between genetic variants and tuberculosis facilitated better understanding of the differences in the incidence of tuberculosis in various populations.



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Contents



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Editorial Board



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Acknowledgement to Reviewers



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SNZ3 Encodes a PLP Synthase Involved in Thiamine Synthesis in Saccharomyces cerevisiae

Pyridoxal 5'-phosphate (the active form of vitamin B6) is a cofactor that is important for a broad number of biochemical reactions and is essential for all forms of life. Organisms that can synthesize pyridoxal 5'-phosphate use either the deoxyxylulose phosphate-dependent or -independent pathway, the latter is encoded by a two-component pyridoxal 5'-phosphate synthase. Saccharomyces cerevisiae contains three paralogs of the two-component SNZ/SNO pyridoxal 5'-phosphate synthase. Past work identified the biochemical activity of Snz1p, Sno1p and provided in vivo data that SNZ1 was involved in pyridoxal 5'-phosphate biosynthesis. Snz2p and Snz3p were considered redundant isozymes and no growth condition requiring their activity was reported. Genetic data herein showed that either SNZ2 or SNZ3 are required for efficient thiamine biosynthesis in Saccharomyces cerevisiae. Further, SNZ2 or SNZ3 alone could satisfy the cellular requirement for pyridoxal 5'-phosphate (and thiamine), while SNZ1 was sufficient for pyridoxal 5'-phosphate synthesis only if thiamine was provided. qRT-PCR analysis determined that SNZ2,3 are repressed ten-fold by the presence thiamine. In total, the data were consistent with a requirement for PLP in thiamine synthesis, perhaps in the Thi5p enzyme, that could only be satisfied by SNZ2 or SNZ3. Additional data showed that Snz3p is a pyridoxal 5'-phosphate synthase in vitro and is sufficient to satisfy the pyridoxal 5'-phosphate requirement in Salmonella enterica when the medium has excess ammonia.



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PlayBionic: Game-Based Interventions to Encourage Patient Engagement and Performance in Prosthetic Motor Rehabilitation

Prosthetic motor rehabilitation usually relies on the highly repetitive training of movements. Patients might drop out of training because the rehabilitation process is long and often discouraging. Game-based interventions provide a potentially useful alternative to standard myoelectric (electromyographic [EMG]) training and can increase engagement with training.

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Editorial Board



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Control Mechanisms of Static and Dynamic Balance in Adults With and Without Vestibular Dysfunction in Oculus Virtual Environments

Deficits in sensory integration and fear of falling in complex environments contribute to decreased participation of adults with vestibular disorders. With recent advances in virtual reality technology, head-mounted displays are affordable and allow manipulation of the environment to test postural responses to visual changes.

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Academy News – November PM&R

As the primary medical society for the specialty of PM&R, your Academy is focused on moving the specialty and you forward. Our mission is to lead the advancement of physiatry's impact throughout health care. Your Academy will ensure that:

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Copyright Page



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Table of Contents



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Barriers, Facilitators and Interventions to Support Virtual Reality Implementation in Rehabilitation: A Scoping Review

Virtual reality and active video games (VR/AVGs) are promising rehabilitation tools because of their potential to facilitate abundant, motivating, and feedback-rich practice. However, clinical adoption remains low despite a growing evidence base and the recent development of clinically accessible and rehabilitation-specific VR/AVG systems. Given clinicians' eagerness for resources to support VR/AVG use, a critical need exists for knowledge translation (KT) interventions to facilitate VR/AVG integration into clinical practice.

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Virtual Reality and Noninvasive Brain Stimulation in Stroke: How Effective Is Their Combination for Upper Limb Motor Improvement?—A Meta-Analysis

Efforts to augment post-stroke upper limb (UL) motor improvement include the use of newer interventions such as noninvasive brain stimulation (NIBS) and task practice in virtual reality environments (VEs). Despite increasing interest in using a combination of these 2 interventions, the effectiveness of this combination to enhance UL motor improvement outcomes has not been examined.

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Virtual Reality in Rehabilitation—Using Technology to Enhance Function

Virtual reality (VR) in rehabilitation capitalizes on rapidly evolving technologies to maximize function and quality of life. Virtual Reality Environments (VEs) have been suggested to be the closest human equivalent of enriched environments [1,2], which are known to be invaluable in promoting recovery, an idea first suggested in 1996 [3]. The use of VR allows designing personalized training environments combining elements such as practice intensity, variability, and task-specificity, in addition to motivation and feedback.

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Three Epidural Steroid Techniques

A 32-year-old man presents to your clinic with 6-week onset of left-sided low back pain radiating down his left posterolateral leg to the top of his left foot. His symptoms include painful shooting electrical sensations, numbness and tingling, and mild weakness in raising his foot. His deep tendon reflexes are normal and he has a positive slump sit test result on the left lower extremity. His primary care physician prescribed gabapentin and a course of oral steroids (methylprednisolone), with minimal benefit.

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Spanish Translated Abstracts



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Simplified follow-up of patients with mild chronic hepatitis C in areas with limited access to antiviral therapy

In some areas of the world, antiviral therapy for chronic hepatitis C (CHC) is not available for all patients. The optimal interval for liver stiffness measures (LSM) and noninvasive scores to assess fibrosis progression has not been studied. We evaluated the usefulness of consecutive LSM, APRI, FIB-4 and Forns scores to predict disease progression.

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Coronary flow reserve is an innovative tool for the early detection of cardiovascular dysfunction in primary biliary cholangitis patients



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Engineered periosteum-bone biomimetic bone graft enhances posterolateral spine fusion in a rabbit model

Bone marrow derived mesenchymal stem cells (BMSCs) and periosteum-derived cells (PDCs) have shown great viability in terms of osteogenic potential and have been considered the major cellular source for skeletal tissue engineering. Using a PDCs-impregnated cell sheet to surround a BMSCs-impregnated tricalcium phosphate (TCP) scaffold might create a periosteum-bone biomimetic bone graft substitute to enhance spine fusion.

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Behavioural and electrophysiological effects of tDCS to prefrontal cortex in patients with disorders of consciousness



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EEG analysis in anti-NMDA receptor encephalitis: description of typical patterns

Anti-N-methyl D-aspartate receptor encephalitis (anti-NMDARE) is the most frequent human autoimmune encephalitis and is primarily directed against the NR1 subunit of the NMDAR (Dalmau et al., 2008). Clinical symptoms are initially marked by psychiatric manifestations, impaired cognition and seizures followed by movement disorders, loss of consciousness, and dysautonomia (Dalmau et al., 2011, 2008; Irani et al., 2010; Titulaer et al., 2013) The association of one of these symptoms and anti-NMDAR IgG antibodies detection made a definite diagnosis (Graus et al., 2016).

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The value of genetic testing for family health history of adopted persons

The value of genetic testing for family health history of adopted persons

The value of genetic testing for family health history of adopted persons, Published online: 29 November 2018; doi:10.1038/s41576-018-0080-4

The lack of family health history experienced by most adopted persons can represent a marked disadvantage for these individuals. Genetic testing has the potential to reliably and usefully fill informational gaps, but considerable challenges need to be addressed to assemble an economic case for affordability.

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Short rare minisatellite variant of BORIS -MS2 is related to bladder cancer susceptibility

Abstract

Background

BORIS/CTCFL, a paralog of CTCF and member of the cancer-testicular antigen family, is abnormally activated in multiple cancers.

Objective

We investigated the relationship between polymorphic variants of the BORIS minisatellite 2 (BORIS-MS2), located within the 5′ upstream promoter region of BORIS, and bladder cancer.

Methods

We used case-control study with 516 controls and 113 bladder cancer patients. To evaluate whether minisatellite variants play a role in BORIS expression, we examined the transcript levels of a reporter gene linked to these minisatellites in cell lines. We also examined BORIS expression in cancerous and non-cancerous bladder tissue.

Results

A statistically significant association was identified between the short rare allele (13-repeat) and bladder cancer incidence (odds ratio (OR) 2.97, 95% confidence interval (CI) [1.14, 7.74]; P = 0.020). In particular, short rare alleles in the younger group (aged < 65) were associated with statistically significant increase in bladder cancer risk (OR 5.38, CI [1.32, 21.87]; P = 0.01). The BORIS-MS2 region acted as a negative regulator, and the expression level of the luciferase reporter in bladder cancer cells was less effectively inhibited than in normal cells. Furthermore, the expression of BORIS mRNA significantly differed (P < 0.05) between normal and cancerous muscle-invasive bladder cancer tissues, and relationship to clinical parameters was observed.

Conclusions

The short rare allele of BORIS-MS2 could be used to identify bladder cancer risk. BORIS expression levels have been shown to increase with the progression of bladder cancer, could be used as a biomarker for its progression.



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Heterotopic chondroid tissue of the main bile duct mimicking Klatskin tumor: case report and review of the literature

Abstract

Heterotopic tissue in the bile duct is a very rare condition. There are a few case reports of heterotopic tissue including gastric and pancreatic cells. However, we could not find any data regarding heterotopic chondroid tissue obstructing the common bile duct in the literature. A 56-year-old woman was admitted to our hospital with complaints of progressive jaundice and pruritus. Laboratory test results were within the normal limits except bilirubin and alkaline phosphatase which were 10.8 mg/dL and 256 IU/L, respectively. Endoscopic retrograde cholangiography (ERCP) and computed tomography (CT) revealed a biliary stricture confined to the upper part of the common bile duct. The patient was operated as soon as the bilirubin level dropped below 5 mg/dL by percutaneous transhepatic cholangiography. Despite the lack of a precise confirmation, the patient was prepared for operation considering the possibility of a malignant biliary tumor since the radiographic mass findings together with hyperbilirubinemia were highly suggestive of malignancy. The patient underwent total extrahepatic bile duct resection and Roux-en-Y hepaticojejunostomy, and was discharged without any postoperative complications. Histologic examination of the bile duct and the nodule revealed the presence of a well-demarcated chondroid tissue within the subepithelial connective tissue. Herein, we presented the first case, to our knowledge, of heterotopic chondroid tissue of the common bile duct in the literature. It is a benign condition that should be considered in the differential diagnosis of stricture and mass-forming lesions of the bile duct.



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Emanuel Donchin (1935–2018)



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Issue Information



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The value of genetic testing for family health history of adopted persons



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Calcineurin/AKAP interactions: therapeutic targeting of a pleiotropic enzyme with a little help from its friends

Abstract

The ubiquitous Ca2+/calmodulin‐dependent phosphatase calcineurin is a key regulator of pathological cardiac hypertrophy whose therapeutic targeting in heart disease has been elusive due to its role in other essential biologic processes. Calcineurin is targeted to diverse intracellular compartments by association with scaffold proteins, including by multivalent A‐kinase anchoring proteins (AKAPs) that bind PKA and other important signaling enzymes determining cardiac myocyte function and phenotype. Calcineurin anchoring by AKAPs confers specificity to calcineurin function in the cardiac myocyte. Targeting of calcineurin "signalosomes" may provide a rationale for inhibiting the phosphatase in disease.

Proposed targeting of Calcineurin/AKAP complexes. By using peptide displacement to compete for Calcineurin binding to AKAPs, we may be able to prevent its downstream functions including induction of cardiac disease.

This article is protected by copyright. All rights reserved



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Inhibition of non‐receptor tyrosine kinase Src induces phosphoserine 256‐independent aquaporin‐2 membrane accumulation

Key Points

Aquaporin‐2 (AQP2) is crucial for water homeostasis, and vasopressin (VP) induces AQP2 membrane trafficking by increasing intracellular cAMP, activating PKA, and causing phosphorylation of AQP2 at serine 256, 264 and 269 residues and dephosphorylation of serine 261 residue on the AQP2 c‐terminus. It is thought that serine 256 is the master regulator of AQP2 trafficking, and its phosphorylation has to precede the change of phosphorylation state of other serine residues. We found that Src inhibition causes serine 256 independent AQP2 membrane trafficking and induces phosphorylation of serine 269 independent of serine 256. This targeted phosphorylation of serine 269 is important for Src inhibition induce AQP2 membrane accumulation. Without serine 269, Src inhibition exerts no effect on AQP2 trafficking. This result helps us better understand the independent pathways that can target different AQP2 residues, and design new strategies to induce or sustain AQP2 membrane expression when VP signaling is defective.

Abstract

Aquaporin‐2 (AQP2) is essential for water homeostasis. Upon stimulation by vasopressin, AQP2 is phosphorylated at serine 256 (S256), S264 and S269, and dephosphorylated at S261. It is thought that S256 is the master regulator of AQP2 trafficking and membrane accumulation, and that its phosphorylation has to precede phosphorylation of other serine residues. In this study, we found that VP reduces Src kinase phosphorylation: by suppressing Src using the inhibitor dasatinib and siRNA, we could increase AQP2 membrane accumulation in cultured AQP2‐expressing cells and in kidney collecting duct principal cells. Src inhibition increased exocytosis and inhibited clathrin‐mediated endocytosis of AQP2, but exerted its effect in a cAMP, PKA and S256 phosphorylation (pS256) independent manner. Despite the lack of S256 phosphorylation, dasatinib increased phosphorylation of S269, even in S256A mutant cells in which S256 phosphorylation cannot occur. To confirm the importance of pS269 in AQP2 re‐distribution, we expressed an AQP2 S269A mutant in LLC‐PK1 cells, and found that dasatinib no longer induced AQP2 membrane accumulation. In conclusion, Src inhibition causes phosphorylation of S269 independently of pS256, and induces AQP2 membrane accumulation by inhibiting clathrin‐mediated endocytosis and increasing exocytosis. We conclude that S269 can be phosphorylated without pS256, and pS269 alone is important for AQP2 apical membrane accumulation under some conditions. These data increase our understanding of the independent pathways that can phosphorylate different residues in the AQP2 c‐terminus, and suggest new strategies to target distinct AQP2 serine residues to induce membrane expression of this water channel when VP signaling is defective.

This article is protected by copyright. All rights reserved



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Oxygen is rocket fuel for the human brain; a radical perspective!



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The role of submaximal exercise‐induced skeletal muscle remodeling in HFrEF patients



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A randomized controlled trial comparing efficacy of early video capsule endoscopy with standard of care in the approach to non-hematemesis GI bleeding (with videos)

Gastrointestinal Endoscopy

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Demographic and comorbidity predictors of adherence to diagnostic colonoscopy in the Danish Colorectal Cancer Screening Program: A nationwide cross-sectional study

Clinical Epidemiology

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Proton pump inhibitors use and risk of chronic kidney disease in diabetic patients

Diabetes Research and Clinical Practice

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Association Between Breastfeeding and Childhood Cardiovascular Disease Risk Factors

Abstract

Introduction The immediate benefits of breastfeeding are well-established but the long-term health benefits are less well-known. West Virginia (WV) has a higher prevalence of cardiovascular disease (CVD) and lower breastfeeding rates compared to national averages. There is a paucity of research examining the relationship between breastfeeding and subsequent childhood CVD risk factors, an issue of particular relevance in WV. Methods This study used longitudinally linked data from three cross-sectional datasets in WV (N = 11,980). The information on breastfeeding was obtained retrospectively via parental recall when the child was in the fifth grade. The outcome variables included blood pressure measures [systolic blood pressure (SBP), diastolic blood pressure (DBP)] and lipid profile [total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), non-HDL, and triglycerides (TG)]. Multiple regression analyses were performed, adjusting for childhood body mass index (BMI) and additional covariates. Results Only 43% of mothers self-reported ever breastfeeding. The unadjusted analysis showed that children who were ever vs. never breastfed had significantly lower SBP (b = − 1.39 mmHg; 95% CI − 1.97, − 0.81), DBP (b = − 0.79 mmHg; 95% CI − 1.26, − 0.33), log-TG (b = − 0.08; 95% CI − 0.1, − 0.05), and higher HDL (b = 0.95 mg/dL; 95% CI 0.33, 1.56). After adjustment for the child's BMI, socio-demographic and lifestyle factors, log-TG remained significantly associated with breastfeeding (b = − 0.04; 95% CI − 0.06, − 0.01; p = 0.01). Conclusion The observed protective effect of any breastfeeding on childhood TG level was small but significant. This finding provides some support for a protective effect of breastfeeding on later CVD risk.



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The influence of humic substances on uranium biomineralization induced by Bacillus sp. dwc-2

Publication date: February 2019

Source: Journal of Environmental Radioactivity, Volume 197

Author(s): Hong Tu, Tu Lan, Guoyuan Yuan, Changsong Zhao, Jun Liu, Feize Li, Jijun Yang, Jiali Liao, Yuanyou Yang, Dongqi Wang, Ning Liu

Abstract

In this paper, the influence of humic acid (HA) and fulvic acid (FA) on biomineralization behaviour was evaluated. The results showed HA and FA did not obviously inhabit or promote the precipitation of U-phosphate minerals. The data from molecular dynamic simulation indicated that the free energy for the dissociation of uranyl the PO43− -uranyl was 202.49 kJ/mol, which was much larger than that form HA-uranyl (88.3 kJ/mol). These simulated results revealed the less competitiveness of HA and FA with PO43− for uranyl and explained why HA and FA had less impacted on the formation of U-phosphate minerals. However, the influence of HA/FA on the morphology was obvious, the microstructure of the bio-minerals changed from small particles to lamellar stacking structure with the addition of HA or FA. The findings of this study are helpful for us to gain a better understanding natural U-phosphate biomineralization behaviour.



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Exposure to ionizing radiation affects the growth of ectomycorrhizal fungi and induces increased melanin production and increased capacities of reactive oxygen species scavenging enzymes

Publication date: February 2019

Source: Journal of Environmental Radioactivity, Volume 197

Author(s): David Kothamasi, Jean Wannijn, May Van Hees, Robin Nauts, Axel Van Gompel, Nathalie Vanhoudt, Hildegarde Vandenhove

Abstract

Ectomycorrhizal (EM) fungi form symbioses with dominant tree families in boreal, temperate and tropical ecosystems and are important drivers of ecosystem function. EM fungal hyphae extend over a large area making them susceptible to enhanced radiation levels from naturally occurring or anthropogenically originating radioisotopes in the rhizosphere. In this study, the in-vitro effects of ionizing radiation on the growth and biomass of EM fungi Suillus luteus, S. bovinus and Rhizopogon luteolus were investigated. EM fungal cultures were exposed to gamma radiation from a 137Cs source for 137 h in darkness at 21 °C at dose rates of 404, 108.5 and 54.9 mGy h−1 resulting in total absorbed doses of 55.21, 14.82 and 7.50 Gy respectively. Cultures grown in the dark at 21 °C but not exposed to the 137Cs source served as the control. Our results show that EM fungi vary in their sensitivity to ionizing radiation. EM fungi used in this study produced melanin and reactive oxygen species scavenging enzymes such as catalase and superoxide dismutase as a response to ionizing radiation.

Graphical abstract

Image 1



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Editorial Board

Publication date: December 2018

Source: Gene Expression Patterns, Volume 30

Author(s):



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Characterization of PI3KCA and BRAF mutations in gastric adenocarcinoma: An approach to a personalized targeted therapy for Moroccan HER2 overexpressed patients

Publication date: Available online 28 November 2018

Source: Arab Journal of Gastroenterology

Author(s): Hanaa Amrani Hassani Joutei, Nabila Marchoudi, Wafaa Mahfoud, Ilham Sadaoui, Taoufiq Fechtali, Hakima Benomar

Abstract
Background and study aims

Targeted therapies have an increasing importance in digestive oncology. To our knowledge, we are the first to report the distribution of PI3KCA and BRAF mutations in Moroccan HER2 overexpressed patients, in order to introduce targeted therapy in the arsenal of therapeutic modalities for management in Morocco.

Patients and methods

98 gastric adenocarcinoma tissue samples were collected. Further histological and immunohistochemical examinations were carried out at the Laboratory of Anatomy Pathology in Pasteur Institute-Morocco, in order to select HER2 positive cases. Out of 98 cases, 16 were found to be HER2-positive. The molecular study was performed for 55 good quality tissue samples including the HER2-positive ones, and activating mutations in H1047R PI3KCA and V600E BRAF were analyzed by Cast-PCR and Real-time PCR, respectively, at the Department of Molecular Biology, ANOUAL Specialized Center-Casablanca, Morocco. Statistical analyses were performed using the Epi-info software (version 6.09).

Results

Pi3KCA mutation was present in 8 cases (14,54%). BRAF mutation was present in 4 cases (7,27%) and 3 cases showed concomitant mutations. In total, 9 cases (16,36%) had PI3KCA and/or BRAF mutations.

Conclusion

The association between HER2 expression and PI3KCA alteration in gastric adenocarcinoma is most probably necessary to identify trastuzumab responders. Consequently, the 83,64% rate of HER2-positive patients harboring wild-type mutations possibly represents the portion of patients responding to trastuzumab while the 16,36% rate of patients carrying at least one of the studied mutations represents the portion of potentially non responsive patients to the targeted therapy, and thus may be considered as good candidates for multi-drug targeted therapy.



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Analysis of 17 948 pediatric patients undergoing procedural sedation with a combination of intranasal dexmedetomidine and ketamine

Summary

Background

Intranasal procedural sedation using dexmedetomidine is well described in the literature. The combination of intranasal dexmedetomidine and ketamine is a novel approach for which there are little data on the rate of successful sedation or adverse events.

Objectives

The aim of this study is to evaluate the rate of successful sedation and adverse events of intranasal procedural sedation using a combination of dexmedetomidine and ketamine for diagnostic examination in children.

Methods

This was a retrospective study and data were collected after ethics approval. A total of 17 948 pediatric patients (7718 females, 10 230 males) in a tertiary hospital in China were evaluated. Patients received a combination of 2 μg kg−1 of dexmedetomidine and 1 mg kg−1 of ketamine intranasally for procedural sedation. The level of sedation and recovery was assessed by the Modified Observer Assessment of Alertness/Sedation scale and the Modified Aldrete Score.

Results

The rate of intranasal sedation success was 93% (16691/17948), intranasal sedation rescue was 1.8% (322/17948), and intranasal sedation failure was 5.2% (935/17948). Sedation success was defined as successful completed the diagnostic examination and obtained adequate diagnostic‐quality images and reports. Intranasal sedation success, rescue and failure were respectively defined as sedation success with intranasal a single dose, additional bolus dose and the need for intravenous (IV) medications/inhalation agents. Median sedation time was 62 min (interquartile range: 55‐70 min), median time for onset of sedation was 15 min (interquartile range: 15‐20 min), and median sedation recovery time was 45 min (interquartile range: 38‐53 min). Incidence of adverse events was low (0.58%; 105/17948), with major and minor adverse event being reported in 0.02% (4/17948) and 0.56% (101/17948) patients, respectively. Postoperative nausea and vomiting was the most common (0.3%; 53/17948) minor adverse event.

Conclusion

Procedural sedation using a combination of intranasal dexmedetomidine and ketamine is associated with acceptable effectiveness and low rates of adverse events.



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Three-Dimensional Take-off Step Kinetics of Long Jumpers with and without a Transtibial Amputation

Purpose The loads applied on the musculo-skeletal system during the long jump take-off step are not well established for non-amputee athletes or athletes with a lower extremity amputation. Information on joint loading and potential injury mechanisms is important for improving training or rehabilitation protocols, prosthetic design and the general understanding of the long jump. Methods Three-dimensional take-off step kinematics and kinetics were used for inverse dynamic model calculations on three male athletes with and seven male athletes without a below the knee amputation (BKA). Athletes with BKA used their affected leg as their take-off leg. Results Despite equivalent long jump performance, ground reaction force application characteristics were widely different and calculated joint loads were significantly lower in athletes with BKA compared to non-amputee athletes during the take-off step. The take-off step of the long jump for athletes with BKA seems to be dominated by sagittal plane movements, while for non-amputee athletes it involves sagittal plane movement and compensatory joint work in the frontal plane. Conclusions Coaches and athletes should adapt training protocols to the unique musculo-skeletal loading patterns of long jumpers with or without a BKA. Specifically, non-amputee athletes should strengthen the muscles responsible for hip and knee extension, as well as for frontal plane stabilization, early in the season to avoid injuries. The presented data enables clinicians to identify potential causes of pain or injury more differentially in both groups of athletes and might stimulate future research in the field of robotics and prosthetic components. Furthermore, the altered joint mechanics of athletes with BKA versus non-amputees serves as an explanation for their previously described more effective take-off step. Corresponding author: Johannes Funken, MSc, German Sport University Cologne, Institute of Biomechanics and Orthopaedics, Am Sportpark Müngersdorf 6, 50933 Cologne, Germany. Email: j.funken@dshs-koeln.de. Phone: +49(0)22149827662 Funding was provided by the Japan Broadcasting Cooperation (NHK). JF was funded by a graduate fellowship of the German Sport University Cologne. HH was funded by JSPS KAKENHI Grant Number 26702027. AMG's contribution to this project was also partially supported by the BADER Consortium, a US Department of Defense Congressionally Directed Medical Research Programs cooperative agreement (W81XWH-11-2-0222). None of the authors had any conflict of interest associated with the study. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sports Medicine. Accepted for publication November 2018. © 2018 American College of Sports Medicine

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Aerobic Exercise Improves Microvascular Function in Older Adults

Microvascular function is reduced with age, disease, and inactivity. Exercise is well known to improve vascular health and has the potential to improve microvascular function in aging and disease. Purpose The study aimed to assess changes in peripheral microvascular function in sedentary older adults following aerobic exercise training. Methods Twenty-three, sedentary older adults (67±5 yrs, BMI=29±5, mean±SD) successfully completed a randomized 12-week graded treadmill walking intervention. The exercise group (EX) performed 40 minutes of uphill walking 4 days a week at 70% heart rate reserve. The control group (CON) maintained a sedentary lifestyle for 12 weeks. MRI measured blood-oxygen-level dependent (BOLD) responses of the soleus were used to evaluate microvascular function; brief (1s) maximal plantar flexion contractions were performed. Separately, blood flow in the popliteal artery was measured by ultrasound following brief contraction. Phosphorus magnetic resonance spectroscopy of the calf was used to examine muscle oxidative capacity and whole body peak oxygen consumption (V[Combining Dot Above]O2peak) was used to confirm training induced cardiorespiratory adaptations. Results Peak post-contraction BOLD response increased by 33% in EX (PRE:3.3±1.0%, POST:4.4±1.4%) compared to CON (PRE:3.0±1.3%, POST:3.2±1.5%), p

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Morning vs Evening Aerobic Training Effects on Blood Pressure in Treated Hypertension

Introduction The acute blood pressure (BP) decrease is greater after evening than morning exercise, suggesting that evening training may have a greater hypotensive effect. Objective To compare the hypotensive effect of aerobic training performed in the morning versus evening in treated hypertensives. Methods Fifty treated hypertensive men were randomly allocated to 3 groups: morning training (MT); evening training (ET); and control (C). Training groups cycled for 45min at moderate-intensity (progressing from the heart rate of the anaerobic threshold to 10% below the heart rate of the respiratory compensation point), while C stretched for 30 min. Interventions were conducted 3 times/week for 10 weeks. Clinic and ambulatory BP, hemodynamic, and autonomic mechanisms were evaluated before and after the interventions. Clinic assessments were performed in the morning (7-9a.m.) and evening (6-8p.m.). Between-within ANOVAs were used (P≤0.05). Results Only ET decreased clinic systolic BP differently from C and MT (morning assessment -5±6 mmHg and evening assessment -8±7 mmHg, P

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Analytical validity of a genotyping assay for use with personalized antihypertensive and chronic kidney disease therapy

Hypertension and chronic kidney disease are inextricably linked. Hypertension is a well-recognized contributor to chronic kidney disease progression and, in turn, renal disease potentiates hypertension. A generalized approach to drug selection and dosage has not proven effective in managing these conditions, in part, because patients with heterogeneous kidney disease and hypertension etiologies are frequently grouped according to functional or severity classifications. Genetic testing may serve as an important tool in the armamentarium of clinicians who embrace precision medicine. Increasing scientific evidence has supported the utilization of genomic information to select efficacious antihypertensive therapy and understand hereditary contributors to chronic kidney disease progression. Given the wide array of antihypertensive agents available and diversity of genetic renal disease predictors, a panel-based approach to genotyping may be an efficient and economic means of establishing an individualized blood pressure response profile for patients with various forms of chronic kidney disease and hypertension. In this manuscript, we discuss the validation process of a Clinical Laboratory Improvement Amendments-approved genetic test to relay information on 72 genetic variants associated with kidney disease progression and hypertension therapy. These genomic-based interventions, in addition to routine clinical data, may help inform physicians to provide personalized therapy. ✠Deceased. Correspondence to Michael T. Eadon, MD, 950 W Walnut St. E202, Indianapolis, IN 46202, USA Tel: +1 317 274 2502; fax: +1 317 274 8575; e-mail: meadon@iupui.edu Received May 29, 2018 Accepted October 11, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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CYP2D6 haplotypes with enhancer single-nucleotide polymorphism rs5758550 and rs16947 (*2 allele): implications for CYP2D6 genotyping panels

Introduction CYP2D6 metabolizes ∼25% of all clinically used drugs, with numerous genetic polymorphisms affecting enzyme activity and drug response. Clinical utility of current CYP2D6 genotyping is partially compromised the unresolved complex haplotype structure of the CYP2D6 locus. We have identified a distal enhancer single-nucleotide polymorphism rs5758550 that robustly increases CYP2D6 expression, whereas rs16947 (CYP2D6*2), previously considered inert, reduces correct mRNA splicing and expression, thereby affecting presumed activity of other alleles on the *2 haplotype. Objective This study aims to determine the structure and frequency of haplotypes containing either rs5758550 or rs16947, or both, together with other relevant CYP2D6 alleles, assigning predictive enzyme activity scores to each, and addressing ambiguities in estimating diplotypes in different populations. Methods The structure and frequency of haplotypes containing rs5758550 and/or rs16947 in different populations were determined by using phased genotype data from 'The 1000 Genomes Project'. The assigned haplotype–phenotype relationship was tested by associating assigned CYP2D6 activity score with CYP2D6 enzyme activity in a cohort of 122 human liver microsomes. Results Addition of enhancer single-nucleotide polymorphism rs5758550 and *2 to a CYP2D6 panel improves prediction of CYP2D6 activity. Moreover, the haplotype containing rs5758550 and rs16947 predict extensive CYP2D6 activity more accurately than CYP2D6*2A, a surrogate marker for extensive activity. Conclusion With further studies, the results support possible incorporation of rs5758550 and rs16947 into CYP2D6 biomarker panels for more accurate prediction of CYP2D6 metabolizer status. Correspondence to Danxin Wang, MD, PhD, Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, 1345 Center Drive MSB PG-05B, Gainesville, FL 32610, USA Tel: +1 352 273 7673; fax: +1 352 273 6121; e-mail: danxin.wang@cop.ufl.edu Received June 13, 2018 Accepted November 10, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Effect of tacrolimus dispositional genetics on acute rejection in the first 2 weeks and estimated glomerular filtration rate in the first 3 months following kidney transplantation

Background CYP3A4/5 and P-glycoprotein (P-gp, ABCB1) affect tacrolimus (TAC) exposure in T cells and kidney cells. Genetic variability of these genes has been widely studied for effects on acute rejection and kidney function after transplantation, but findings remain contradictory. In addition, cytochrome P450 reductase (POR) is important for CYP3A4/5 activity, and the pregnane X receptor (NR1I2) regulates CYP3A4/5 and P-gp expression. However, the relationship between POR and NR1I2 genetics and acute rejection and kidney function has not been extensively investigated. Objective The aim of this study was to investigate the effect of ABCB1 (61A>G, 1199G>A, 1236C>T, 2677G>T, 3435C>T), CYP3A4*22, CYP3A5*3, NR1I2 (8055C>T, 63396C>T) and POR*28 genotypes/haplotypes on acute rejection and kidney function in the first 3 months after transplant. Participants and methods The study included 165 kidney transplant recipients, who received TAC, mycophenolate and prednisolone, and 129 donors. TAC dose was adjusted to target trough blood concentrations of 8–15 ng/ml by therapeutic drug monitoring. Recipient and donor genotype/haplotype differences in acute rejection incidence within the first 2 weeks after transplant were assessed by logistic regression, adjusting for induction therapy, human leucocyte antigen mismatches, kidney transplant number, peak panel-reactive antibodies and donor type. Recipient and donor genotype/haplotype differences in estimated glomerular filtration rate in the first 3 months after transplant were assessed by linear mixed effects analysis, adjusting for acute rejection, delayed graft function and donor type. Results No genetic factors significantly affected acute rejection or estimated glomerular filtration rate after correction for multiple comparisons (P>0.004). Conclusion Recipient and donor dispositional genetics had no significant effect on short-term clinical outcomes in kidney transplant patients receiving TAC therapeutic drug monitoring. Correspondence to Rong Hu, MSc, Discipline of Pharmacology, Level 3, Helen Mayo South Building, The University of Adelaide, SA 5005, Australia Tel: +61 883 136 035; e-mail: rong.hu@adelaide.edu.au Received August 29, 2018 Accepted November 4, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Transcriptomic analysis of cells in response to EV71 infection and 2A pro as a trigger for apoptosis via TXNIP gene

Abstract

Background

Enterovirus 71 (EV71) is the main pathogen of hand-foot-mouth disease (HFMD) and sometimes causes several neurological complications. However, the underlying mechanism of the host response to the virus infection remains unclear.

Objective

To reveal the cell-specific transcriptional response of cultured RD cells following infection with EV71, and better understand the molecular mechanisms of virus-host interactions.

Methods

The RD cells were infected with or without EV71 for 24 h, and then transcriptome sequencing and qRT-PCR were performed to analyze the transcriptome difference of functional genes.

Results

More than 15000 genes were identified in transcriptome sequencing. In comparison with uninfected RD cells, 329 DEGs were identified in cells infected with EV71. GO and KEGG pathway enrichment analysis showed that most of the DEGs were related to DNA binding, transcriptional regulation, immune response and inflammatory response, apoptosis inducing factors and enriched in JAK-STAT and MAPK signaling pathways. TXNIP (thioredoxin-interacting protein) gene was further demonstrated to play an important role participating in cellular apoptosis induced by EV71, and the apoptosis and death mediated by TXNIP during EV71 infection was triggered by viral 2A protease (2Apro), not 3C protease (3Cpro).

Conclusion

Our study demonstrated that RD cells have a significant response to EV71 infection, including immune response and apoptosis. 2Apro might be a key inducer relative to the cellular apoptosis and death mediated by TXNIP during EV71 infection. These data would contribute to preferably understand the process at the molecular level and provide theoretical foundation for diagnosis and treatment of EV71-related diseases.



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Τετάρτη, 28 Νοεμβρίου 2018

Does the Current American Society of Anesthesiologists Physical Status Classification Represent the Chronic Disease Burden in Children Undergoing General Anesthesia?

No abstract available

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Pain Management: A Problem-Based Learning Approach

No abstract available

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Handbook of Sepsis

No abstract available

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A Comparison of Spinal Anesthesia Versus Monitored Anesthesia Care With Local Anesthesia in Minimally Invasive Fetal Surgery

BACKGROUND: Minimally invasive fetal surgery is commonly performed to treat twin-to-twin transfusion syndrome with selective fetoscopic laser photocoagulation and twin-reversed arterial perfusion sequence using radiofrequency ablation. Although an increasing number of centers worldwide are performing these procedures, anesthetic management varies. Both neuraxial anesthesia and monitored anesthesia care with local anesthesia are used at different institutions. We sought to determine the efficacy and outcomes of these 2 anesthetic techniques for fetal procedures at our institution. METHODS: All patients undergoing minimally invasive fetal surgery for twin-to-twin transfusion syndrome or twin-reversed arterial perfusion sequence over a 6-year time period (2011–2016) were reviewed. Patients receiving monitored anesthesia care with local anesthesia were compared with those receiving spinal anesthesia in both selective fetoscopic laser photocoagulation and radiofrequency ablation fetal procedures. The primary outcome examined between the monitored anesthesia care and spinal anesthesia groups was the difference in conversion to general anesthesia using a noninferiority design with a noninferiority margin of 5%. Secondary outcome measures included use of vasopressors, procedure times, intraoperative fluids administered, maternal complications, and unexpected fetal demise within 24 hours of surgery. RESULTS: The difference in failure rate between monitored anesthesia care and spinal was −0.5% (95% CI, −4.8% to 3.7%). Patients receiving monitored anesthesia care plus local anesthesia were significantly less likely to need vasopressors, had a shorter presurgical operating room time, and received less fluid (P

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Speaker Gender Representation at the American Society of Anesthesiology Annual Meeting: 2011–2016

The American Society of Anesthesiologists (ASA) Annual Meeting is the primary venue for anesthesiologists to present research, share innovations, and build networks. Herein, we describe gender representation for physician speakers at the Annual Meeting relative to the specialty overall. Details of ASA Annual Meeting presentations for individuals and panels were abstracted from the ASA archives for 2011–2016. Observed speaker gender composition was compared to expected composition based on the gender distribution of members of the ASA. There were 5167 speaker slots across 2025 presentations and panels. Of the speaker slots, 3874 were assigned to men and 1293 to women. Speaker slot gender composition was relatively consistent between 2011 and 2016 (annual percentage 22.3%–27.7% women, trend test P = .062). ASA membership composition of women increased slightly over the study period (24%–28%). The overall observed number of women in speaker slots over the study period did not differ significantly from what would be expected based on the ASA membership composition (25.0% observed vs 25.9% expected; P = .153). However, the percentage of single speakers who were women was significantly less than would be expected based on the ASA gender distribution (20.2% observed vs 25.9% expected; P

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General Anesthesia Alters the Diversity and Composition of the Intestinal Microbiota in Mice

Dysbiosis of the intestinal microbiota has been shown to result in altered immune responses and increased susceptibility to infection; as such, the state of the intestinal microbiome may have profound implications in the perioperative setting. In this first-in-class study, we used 16s ribosomal RNA sequencing and analysis in a mouse model of general anesthesia to investigate the effects of volatile anesthetics on the diversity and composition of the intestinal microbiome. After 4-hour exposure to isoflurane, we observed a decrease in bacterial diversity. Taxonomic alterations included depletion of several commensal bacteria including Clostridiales. These data identify volatile anesthetics as potential contributors to microbial dysbiosis in the postoperative patient. Accepted for publication October 17, 2018. Funding:This work was supported by grants from the National Institutes of Health (R01 GM120519-01). 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 Cyrus D. Mintz, MD, PhD, The Johns Hopkins University School of Medicine, 720 Rutland Ave, Ross Bldg 370, Baltimore, MD 21205. Address e-mail to Cmintz2@jhmi.edu. © 2018 International Anesthesia Research Society

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The Impact of Postoperative Intensive Care Unit Admission on Postoperative Hospital Length of Stay and Costs: A Prespecified Propensity-Matched Cohort Study

BACKGROUND: In this prespecified cohort study, we investigated the influence of postoperative admission to the intensive care unit versus surgical ward on health care utilization among patients undergoing intermediate-risk surgery. METHODS: Of adult surgical patients who underwent general anesthesia without an absolute indication for postoperative intensive care unit admission, 3530 patients admitted postoperatively to an intensive care unit were matched to 3530 patients admitted postoperatively to a surgical ward using a propensity score based on 23 important preoperative and intraoperative predictor variables. Postoperative hospital length of stay and hospital costs were defined as primary and secondary end points, respectively. RESULTS: Among patients with low propensity for postoperative intensive care unit admission, initial triage to an intensive care unit was associated with increased postoperative length of stay (incidence rate ratio, 1.69 [95% CI, 1.59–1.79]; P

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Remote Surveillance Technologies: Realizing the Aim of Right Patient, Right Data, Right Time

The convergence of multiple recent developments in health care information technology and monitoring devices has made possible the creation of remote patient surveillance systems that increase the timeliness and quality of patient care. More convenient, less invasive monitoring devices, including patches, wearables, and biosensors, now allow for continuous physiological data to be gleaned from patients in a variety of care settings across the perioperative experience. These data can be bound into a single data repository, creating so-called data lakes. The high volume and diversity of data in these repositories must be processed into standard formats that can be queried in real time. These data can then be used by sophisticated prediction algorithms currently under development, enabling the early recognition of patterns of clinical deterioration otherwise undetectable to humans. Improved predictions can reduce alarm fatigue. In addition, data are now automatically queriable on a real-time basis such that they can be fed back to clinicians in a time frame that allows for meaningful intervention. These advancements are key components of successful remote surveillance systems. Anesthesiologists have the opportunity to be at the forefront of remote surveillance in the care they provide in the operating room, postanesthesia care unit, and intensive care unit, while also expanding their scope to include high-risk preoperative and postoperative patients on the general care wards. These systems hold the promise of enabling anesthesiologists to detect and intervene upon changes in the clinical status of the patient before adverse events have occurred. Importantly, however, significant barriers still exist to the effective deployment of these technologies and their study in impacting patient outcomes. Studies demonstrating the impact of remote surveillance on patient outcomes are limited. Critical to the impact of the technology are strategies of implementation, including who should receive and respond to alerts and how they should respond. Moreover, the lack of cost-effectiveness data and the uncertainty of whether clinical activities surrounding these technologies will be financially reimbursed remain significant challenges to future scale and sustainability. This narrative review will discuss the evolving technical components of remote surveillance systems, the clinical use cases relevant to the anesthesiologist's practice, the existing evidence for their impact on patients, the barriers that exist to their effective implementation and study, and important considerations regarding sustainability and cost-effectiveness. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication October 18, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Jeanine P. Wiener-Kronish, MD, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, GRB 4–444, Boston, MA 02114. Address e-mail to jwiener-kronish@partners.org. © 2018 International Anesthesia Research Society

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Optimal Muscle Selection for OnabotulinumtoxinA Injections in Post-stroke Lower-Limb Spasticity: A Randomized Trial

OBJECTIVE To identify optimal muscle selection patterns for onabotulinumtoxinA treatment of post-stroke lower-limb spasticity (PSLLS). DESIGN Adults with PSLLS (ankle Modified Ashworth Scale [MAS] ≥3) were randomized to onabotulinumtoxinA (300 U, mandatory ankle plantar flexors; ≤100 U, optional lower-limb muscles) or placebo. Post hoc analysis assessed the impact of muscle selection patterns on ankle MAS and physician-assessed Clinical Global Impression of Change (CGI) based on change from baseline to average of weeks 4/6 versus placebo. RESULTS Among 468 patients randomized, onabotulinumtoxinA improved ankle MAS (–0.81 vs –0.61; P=0.01) and CGI (0.86 vs 0.65; P=0.012) versus placebo. Injection of mandatory muscles alone was not sufficient in improving ankle MAS (P=0.255) or CGI (P=0.576) versus placebo but was adequate ≤24 months post-stroke (MAS, –1.13 vs –0.62, P=0.019; CGI, 1.24 vs 0.68, P=0.006). Additional injections into toe muscles (flexor digitorum longus, flexor hallucis longus) improved ankle MAS (–0.98 vs –0.52; P=0.002) and CGI (0.80 vs 0.38; P=0.023) versus placebo regardless of time since stroke. OnabotulinumtoxinA was well tolerated, with no new safety findings. CONCLUSIONS Post hoc analyses suggested additional injections of onabotulinumtoxinA into toe flexors improved ankle MAS and CGI scores versus mandatory muscles alone overall and with treatment initiation >24 months post-stroke. Address correspondence to: Alberto Esquenazi, MD, Department of Physical Medicine and Rehabilitation, MossRehab Gait and Motion Analysis Laboratory, 60 Township Line Road, Elkins Park, PA 19027. Phone: 215-663-6676. Fax: 215-663-6686. aesquena@einstein.edu Disclosures: Competing Interests: Alberto Esquenazi, MD: Dr Esquenazi has received research support from and acted as a consultant for Allergan and Ipsen. Theodore H. Wein, MD, FRCPC: Dr Wein has received research funds from Allergan plc, Merz, National Institutes of Health, Accorda, and Boehringer Ingelheim; acted as a consultant for Allergan plc and Ispen; and received honoraria for accredited CME from Bayer and Boehringer Ingelheim. Anthony B. Ward, MD, FRCP: Dr Ward is a speaker and consultant for Allergan plc and Ipsen. Carolyn Geis, MD: Dr Geis has received research support from and is a speaker/consultant for Allergan plc. Chengcheng Liu, PhD, and Rozalina Dimitrova, MD, MPH, are employees of Allergan plc and Rozalina Dimitrova holds stock in the company. Study funding: This study and analysis were sponsored by Allergan plc (Dublin, Ireland). The study sponsor was involved in the study design, data collection, data analysis, data interpretation, and writing of the article. Assistance with medical writing was provided by Complete Healthcare Communications, LLC (West Chester, PA). Details of Previous Presentations: The REFLEX Study subanalysis on muscle selection patterns for onabotulinumtoxinA has been presented at the following conferences: Wein T, Esquenazi A, Ward A, Geis C, Liu C, Dimitrova R. Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients With Post-Stroke Lower-Limb Spasticity Influence Outcome: Results From a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. American Academy of Neurology 2016 - 68th Annual Meeting. 2016. Wein T, Esquenazi A, Ward A, Geis C, Liu C, Dimitrova R. Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients With Post-Stroke Lower-Limb Spasticity Influence Outcome: Results From a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. World Federation for NeuroRehabilitation - 9th World Congress for NeuroRehabilitation. 2016. Wein T, Esquenazi A, Ward A, Geis C, Liu C, Dimitrova R. Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients With Post-Stroke Lower-Limb Spasticity Influence Outcome: Results From a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. Movement Disorder Society - 20th International Congress of Parkinson's Disease and Movement Disorder. 2016. Wein T, Esquenazi A, Ward A, Geis C, Liu C, Dimitrova R. Muscle Selection Patterns for Injection of OnabotulinumtoxinA in Adult Patients With Post-Stroke Lower-Limb Spasticity Influence Outcome: Results From a Double-Blind, Placebo-Controlled Phase 3 Clinical Trial. American Academy of Physical Medicine and Rehabilitation. 2016. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Letter to the Editor Re: Comorbidities and Mobility in Lower Limb Prosthesis Users

No abstract available

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ANALYSIS OF CELL VIABILITY AND GENE EXPRESSION AFTER CONTINUOUS ULTRASOUND THERAPY IN L929 FIBROBLAST CELLS

Objective This study aimed to analyze cell viability and gene expression IL-6 (interleukin-6) and VEGF (vascular endothelial growth factor) after continuous ultrasound therapy of 1 and 3 MHz on L929 fibroblast cells. Design The L929 cells were cultivated in 12-well plates and divided into 5 groups: G1: non-irradiated, G2: 0.2 W/cm2-1 MHz, G3: 0.5 W/cm2-1 MHz, G4: 0.2 W/cm2-3 MHz and G5: 0.5 W/cm2-3 MHz. The cells were irradiated at 24 hours and 48 hours. Cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The gene expression analysis was assessed using real-time PCR. Results The G2 and G3 groups showed a decrease in cell viability when compared to the G1 at 48 hours (p

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Effects of Carbohydrate Mouth Rinse on Cycling Time Trial Performance: A Systematic Review and Meta-Analysis

Abstract

Background

Despite the growing number of studies reporting carbohydrate mouth rinse effects on endurance performance, no systematic and meta-analysis review has been conducted to elucidate the level of evidence of carbohydrate mouth rinse effects on cycling trial performance such as time-, work-, and distance-based trials.

Objectives

The objective of this study were to establish the effect of a carbohydrate mouth rinse on cycling performance outcomes such as mean power output and time to complete a trial, together with the risk of bias in the cycling-carbohydrate mouth rinse literature.

Methods

We systematically reviewed randomized placebo-controlled trials that assessed carbohydrate mouth rinse effects on mean power output and time to complete the trial. A random-effects meta-analysis assessed the standardized mean difference between carbohydrate and placebo mouth rinses.

Results

Thirteen studies (16 trials) were qualitatively (systematic review) and quantitatively (meta-analysis) analyzed with regard to mean power output (n = 175) and time to complete the trial (n = 151). Overall, the reviewed studies showed a low risk of bias and homogeneous results for mean power output (I2 = 0%) and time to complete the trial (I2 = 0%). When compared with placebo, the carbohydrate mouth rinse improved mean power output (standardized mean difference = 0.25; 95% confidence interval 0.04–0.46; p = 0.02), but not the time to complete the trial (standardized mean difference = − 0.13; 95% confidence interval − 0.36 to 0.10; p = 0.25).

Conclusion

The present systematic and meta-analytic review supports the notion that a carbohydrate mouth rinse has the potential to increase mean power output in cycling trials, despite showing no superiority over placebo in improving time to complete the trials.



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Prevalence and Clinical Features of Community-Acquired Pneumonia Caused by Macrolide-Resistant Mycoplasma pneumoniae Isolated from Adults in Jeju Island

Microbial Drug Resistance, Ahead of Print.


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Increasing Prevalence of Group III Penicillin-Binding Protein 3 Mutations Conferring High-Level Resistance to Beta-Lactams Among Nontypeable Haemophilus influenzae Isolates from Children in Korea

Microbial Drug Resistance, Ahead of Print.


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Modified FOLFIRINOX versus CisGem first-line chemotherapy for locally advanced non resectable or metastatic biliary tract cancer (AMEBICA) − PRODIGE 38: study protocol for a randomized controlled multicenter phase II/III study

Combination of cisplatine and Gemcitabine (CisGem) is the reference 1 st line Chemotherapy in patients with advanced biliary cancer. FOLFIRINOX demonstrated an overall survival superiority when compared to gemcitabine in 1 st line for patients with metastatic pancreatic adenocarcinoma. Because of similarities between pancreatic and biliary cancers, we proposed a randomized trial comparing mFOLFIRINOX and CisGEm.

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Chronic Hepatitis C Infection — Noninvasive assessment of Liver Fibrosis in the era of Direct Acting Antivirals

Significant advancements in the diagnosis and treatment of chronic hepatitis C infection and its associated fibrosis have revolutionized treatment of these patients over the last several years. Liver biopsy, the gold standard diagnostic method for evaluating liver fibrosis level, was routinely used prior to initiation of hepatitis C therapy, placing patients at an inherent risk of adverse events. The recent advent of noninvasive serologic and nonserologic measures of hepatic fibrosis level has reduced the need for liver biopsy significantly, thereby minimizing its associated risks.

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A RARE CASE OF SUBMUCOSAL GASTRIC TUMOR.



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Prolonged depression of knee‐extensor torque complexity following eccentric exercise

Experimental Physiology Prolonged depression of knee‐extensor torque complexity following eccentric exercise

New Findings

What is the central question of this study?

Does eccentric exercise leading to prolonged knee‐extensor torque depression also result in a prolonged loss of knee‐extensor torque complexity?

What is the main finding and its importance?

The recovery of the loss of torque complexity after eccentric exercise took 24 h, whereas after acute muscle fatigue it took 10 min. The depression of torque complexity after eccentric exercise was prolonged.

Abstract

Neuromuscular fatigue reduces the temporal structure, or complexity, of muscle torque output. Exercise‐induced muscle damage reduces muscle torque output for considerably longer than high‐intensity fatiguing contractions. We hypothesized that muscle‐damaging eccentric exercise would lead to a persistent decrease in torque complexity, whereas fatiguing exercise would not. Ten healthy participants performed five isometric contractions (6 s contraction, 4 s rest) at 50% maximal voluntary contraction (MVC) before, immediately after and 10, 30 and 60 min and 24 h after eccentric (muscle‐damaging) and isometric (fatiguing) exercise. These contractions were also repeated 48 h and 1 week after eccentric exercise. Torque and surface EMG signals were sampled throughout each test. Complexity and fractal scaling were quantified using approximate entropy (ApEn) and the detrended fluctuation analysis α exponent (DFA α). Global, central and peripheral perturbations were quantified using MVCs with femoral nerve stimulation. Complexity decreased after both eccentric [ApEn, mean (SD), from 0.39 (0.10) to 0.20 (0.12), P < 0.001] and isometric exercise [from 0.41 (0.13) to 0.09 (0.04); P < 0.001]. After eccentric exercise, ApEn and DFA α required 24 h to recover to baseline levels, but after isometric exercise they required only 10 min. The MVC torque remained reduced [from 233.6 (74.2) to 187.5 (64.7) N m] 48 h after eccentric exercise, with such changes evident only up to 60 min after isometric exercise [MVC torque, from 246.1 (77.2) to 217.9 (71.8) N m]. The prolonged depression in maximal muscle torque output is therefore accompanied by a prolonged reduction in torque complexity.



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