Πέμπτη, 31 Ιανουαρίου 2019

A novel WDR62 missense mutation in microcephaly with abnormal cortical architecture and review of the literature

Abstract

Autosomal recessive primary microcephaly (MCPH) is a group of rare neurodevelopmental diseases with severe microcephaly at birth. One type of the disorder, MCPH2, is caused by biallelic mutations in the WDR62 gene, which encodes the WD repeat–containing protein 62. Patients with WDR62 mutation may have a wide range of malformations of cortical development in addition to congenital microcephaly. We describe two patients, a boy and a girl, with severe congenital microcephaly, global developmental delay, epilepsy, and failure to thrive. MRI showed hemispherical asymmetry, diffuse pachygyria, thick gray matter, indistinct gray-white matter junction, and corpus callosum and white matter hypoplasia. Whole exome sequencing revealed the same novel homozygous missense mutation, c.668T>C, p.Phe223Ser in exon 6 of the WDR62 gene. The healthy parents were heterozygous for this mutation. The mutation affects a highly conserved region in one of the WD repeats of the WDR62 protein. Haplotype analysis showed genetic relatedness between the families of the patients. Our findings expand the spectrum of mutations randomly distributed in the WDR62 gene. A review is also provided of the brain malformations described in WDR62 mutations in association with congenital microcephaly.



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Genomic Resources for Goniozus legneri, Aleochara bilineata and Paykullia maculata, Representing Three Independent Origins of the Parasitoid Lifestyle in Insects

Parasitoid insects are important model systems for a multitude of biological research topics and widely used as biological control agents against insect pests. While the parasitoid lifestyle has evolved numerous times in different insect groups, research has focused almost exclusively on Hymenoptera from the Parasitica clade. The genomes of several members of this group have been sequenced, but no genomic resources are available from any of the other, independent evolutionary origins of the parasitoid lifestyle. Our aim here was to develop genomic resources for three parasitoid insects outside the Parasitica. We present draft genome assemblies for Goniozus legneri, a parasitoid Hymenopteran more closely related to the non-parasitoid wasps and bees than to the Parasitica wasps, the Coleopteran parasitoid Aleochara bilineata and the Dipteran parasitoid Paykullia maculata. The genome assemblies are fragmented, but complete in terms of gene content. We also provide preliminary structural annotations. We anticipate that these genomic resources will be valuable for testing the generality of findings obtained from Parasitica wasps in future comparative studies.



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Evaluation of InSeq To Identify Genes Essential for Pseudomonas aeruginosa PGPR2 Corn Root Colonization

The reciprocal interaction between rhizosphere bacteria and their plant hosts results in a complex battery of genetic and physiological responses. In this study, we used insertion sequencing (INSeq) to reveal the genetic determinants responsible for the fitness of Pseudomonas aeruginosa PGPR2 during root colonization. We generated a random transposon mutant library of Pseudomonas aeruginosa PGPR2 comprising 39,500 unique insertions and identified genes required for growth in culture and on corn roots. A total of 108 genes were identified as contributing to the fitness of strain PGPR2 on roots. The importance in root colonization of four genes identified in the TnSeq screen was verified by constructing deletion mutants in the genes and testing them for the ability to colonize corn roots singly or in competition with the wild type. All four mutants were affected in corn root colonization, displaying 5- to 100-fold reductions in populations in single inoculations, and all were outcompeted by the wild type by almost 100-fold after seven days on corn roots in mixed inoculations of the wild type and mutant. The genes identified in the screen had homology to genes involved in amino acid catabolism, stress adaptation, detoxification, signal transduction, and transport. INSeq technology proved a successful tool to identify fitness factors in P. aeruginosa PGPR2 for root colonization.



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Factors affecting quality of life in children and adolescents with hypermobile Ehlers‐Danlos syndrome/hypermobility spectrum disorders

Hypermobile Ehlers‐Danlos syndrome (hEDS) is a hereditary disorder of connective tissue, often presenting with complex symptoms can include chronic pain, fatigue, and dysautonomia. Factors influencing functional disability in the pediatric hEDS population are incompletely studied. This study's aims were to assess factors that affect quality of life in children and adolescents with hEDS. Individuals with hEDS between the ages 12–20 years and matched parents were recruited through retrospective chart review at two genetics clinics. Participants completed a questionnaire that included the Pediatric Quality of Life Inventory (PedsQL™), PedsQL Multidimentional Fatigue Scale, Functional Disability Inventory, Pain‐Frequency‐Severity‐Duration Scale, the Brief Illness Perception Questionnaire, measures of anxiety and depression, and helpful interventions. Survey responses were completed for 47 children and adolescents with hEDS/hypermobility spectrum disorder (81% female, mean age 16 years), some by the affected individual, some by their parent, and some by both. Clinical data derived from chart review were compared statistically to survey responses. All outcomes correlated moderately to strongly with each other. Using multiple regression, general fatigue and pain scores were the best predictors of the PedsQL total score. Additionally, presence of any psychiatric diagnosis was correlated with a lower PedsQL score. Current management guidelines recommend early intervention to prevent disability from deconditioning; these results may help identify target interventions in this vulnerable population.



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Ectodermal dysplasias: Classification and organization by phenotype, genotype and molecular pathway

Abstract

An international advisory group met at the National Institutes of Health in Bethesda, Maryland in 2017, to discuss a new classification system for the ectodermal dysplasias (EDs) that would integrate both clinical and molecular information. We propose the following, a working definition of the EDs building on previous classification systems and incorporating current approaches to diagnosis: EDs are genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands. Genetic variations in genes known to be associated with EDs that affect only one derivative of the ectoderm (attenuated phenotype) will be grouped as non‐syndromic traits of the causative gene (e.g., non‐syndromic hypodontia or missing teeth associated with pathogenic variants of EDA "ectodysplasin"). Information for categorization and cataloging includes the phenotypic features, Online Mendelian Inheritance in Man number, mode of inheritance, genetic alteration, major developmental pathways involved (e.g., EDA, WNT "wingless‐type," TP63 "tumor protein p63") or the components of complex molecular structures (e.g., connexins, keratins, cadherins).



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Comment on: “Equity in Physical Activity: A Misguided Goal”



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Reply to Williams et al.: Comment on: “Equity in Physical Activity: A Misguided Goal”



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Comparison of Naturally Occurring Resistance-Associated Substitutions Between 2008 and 2016 in Chinese Patients with Chronic Hepatitis C Virus Infection

Microbial Drug Resistance, Ahead of Print.


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The combined effects of salivas and occlusal indicators on occlusal contact forces

Abstract

Background

Some occlusal detection products are designed for use on dry teeth, but this is not always achieved. Others are suited for dry and wet applications.

Objective

The objective of this study is to assess the combined effects, on occlusal contact forces, of two previously studied affecting variables – occlusal detection products and saliva.

Methods

We used a full arch dentiform with 3 occlusal detection products (an articulating film, an articulation paper and T‐Scan) in combination with human (HS) and an artificial saliva. The maxillary arch assembly, weighing ~54 N (the maximum bite force), was lowered onto (occlusion) and lifted off (disclusion) of the mandibular arch through 10 cycles by a mechanical testing machine. The forces and moments acting on the mandibular arch were continuously recorded by a load cell that supported it.

Results

The maximum values of Flateral (the in‐occlusal plane component of the occlusal contact force) were analyzed by occlusion/disclusion separately using one‐way ANOVA, with factor for group type to identify the significant effect of salivas on products, effect of products, effect of salivas with products, effect of human saliva. A difference in occlusion and/or in disclusion was considered different.

Statistical differences (p < 0.0001) in Flateral were found in: dry product vs. product + HS, dry product vs. product + artificial saliva (with articulating film and T‐Scan) and HS vs. product + HS (with articulation paper and T‐Scan).

Conclusion

All products were affected by the salivas, except articulation paper by artificial saliva.

This article is protected by copyright. All rights reserved.



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Interoceptive accuracy predicts nonplanning trait impulsivity

Abstract

Influential theories concerning personality argue that many impulsive individuals show physiological underarousal at rest. This interoceptive state is proposed to be egodystonic, motivating impulsive maladaptive actions to enhance arousal. However, there is little empirical research on this matter. The current study tested the relationship between physiological markers of arousal, measures of interoceptive (in)sensitivity, and trait impulsivity in a nonclinical sample of young adults. Experiment 1 investigated whether individuals (N = 31) with high trait impulsivity show decreased resting measures of arousal (indexed from heart rate, heart rate variability, and sympathetic electrodermal activity). Experiment 2 assessed whether trait impulsivity is linked to interoceptive abilities (N = 60). Overall, our results do not provide any compelling support for the underarousal theory of impulsivity. However, impaired interoceptive (cardiac discrimination) accuracy predicted the degree of Barratt nonplanning impulsivity, such that individuals with a better ability to distinguish between internal (bodily) and external signals manifest lower levels of nonplanning trait impulsivity. These findings open an avenue for potential novel interventions aimed at improving planning abilities via better interoceptive discrimination.



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Electroencephalography-based endogenous brain–computer interface for online communication with a completely locked-in patient

Brain–computer interfaces (BCIs) have demonstrated the potential to provide paralyzed individuals with new means of communication, but an electroencephalography (EEG)-based endogenous BCI has never been succes...

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Exploring the relationship between social deprivation and domestic radon levels in the East Midlands, UK

Publication date: April 2019

Source: Journal of Environmental Radioactivity, Volumes 199–200

Author(s): Antony R. Denman, Robin G.M. Crockett, Christopher J. Groves-Kirkby, Paul S. Phillips, Gavin K. Gillmore

Abstract

The natural radioactive gas radon is widely present in the built environment and at high concentrations is associated with enhanced risk of lung-cancer. This risk is significantly enhanced for habitual smokers. Although populations with higher degrees of social deprivation are frequently exposed to higher levels of many health-impacting pollutants, a recent study suggests that social deprivation in the UK is associated with lower radon concentrations.

The analysis reported here, based on published data on social deprivation and domestic radon in urban and rural settings in the English East Midlands, identifies a weak association between increasing deprivation and lower radon areas. This is attributed to the evolution of the major urban centres on low-permeability, clay-rich alluvial soils of low radon potential. In addition, the predominance of high-rise dwellings in towns and cities will further reduce average exposure to radon in populations in those areas.



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The Accuracy of Acquiring Heart Rate Variability from Portable Devices: A Systematic Review and Meta-Analysis

Abstract

Background

Advancements in wearable technology have provided practitioners and researchers with the ability to conveniently measure various health and/or fitness indices. Specifically, portable devices have been devised for convenient recordings of heart rate variability (HRV). Yet, their accuracies remain questionable.

Objective

The aim was to quantify the accuracy of portable devices compared to electrocardiography (ECG) for measuring a multitude of HRV metrics and to identify potential moderators of this effect.

Methods

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles published before July 29, 2017 were located via four electronic databases using a combination of the terms related to HRV and validity. Separate effect sizes (ESs), defined as the absolute standardized difference between the HRV value recorded using the portable device compared to ECG, were generated for each HRV metric (ten metrics analyzed in total). A multivariate, multi-level model, incorporating random-effects assumptions, was utilized to quantify the mean ES and 95% confidence interval (CI) and explore potential moderators.

Results

Twenty-three studies yielded 301 effects and revealed that HRV measurements acquired from portable devices differed from those obtained from ECG (ES = 0.23, 95% CI 0.05–0.42), although this effect was small and highly heterogeneous (I2 = 78.6%, 95% CI 76.2–80.7). Moderator analysis revealed that HRV metric (p <0.001), position (p = 0.033), and biological sex (β = 0.45, 95% CI 0.30–0.61; p <0.001), but not portable device, modulated the degree of absolute error. Within metric, absolute error was significantly higher when expressed as standard deviation of all normal–normal (R–R) intervals (SDNN) (ES = 0.44) compared to any other metric, but was no longer significantly different after a sensitivity analysis removed outliers. Likewise, the error associated with the tilt/recovery position was significantly higher than any other position and remained significantly different without outliers in the model.

Conclusions

Our results suggest that HRV measurements acquired using portable devices demonstrate a small amount of absolute error when compared to ECG. However, this small error is acceptable when considering the improved practicality and compliance of HRV measurements acquired through portable devices in the field setting. Practitioners and researchers should consider the cost–benefit along with the simplicity of the measurement when attempting to increase compliance in acquiring HRV measurements.



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mTOR-S6K1 pathway mediates cytoophidium assembly

Publication date: Available online 31 January 2019

Source: Journal of Genetics and Genomics

Author(s): Zhe Sun, Ji-Long Liu

Abstract

CTP synthase (CTPS), the rate-limiting enzyme in de novo CTP biosynthesis, has been demonstrated to assemble into evolutionarily conserved filamentous structures, termed cytoophidia, in Drosophila, bacteria, yeast and mammalian cells. However, the regulation and function of the cytoophidium remain elusive. Here, we provide evidence that the mechanistic target of rapamycin (mTOR) pathway controls cytoophidium assembly in mammalian and Drosophila cells. In mammalian cells, we find that inhibition of mTOR pathway attenuates cytoophidium formation. Moreover, CTPS cytoophidium assembly appears to be dependent on the mTOR complex 1 (mTORC1) mainly. In addition, knockdown of the mTORC1 downstream target S6K1 can inhibit cytoophidium formation, while overexpression of the constitutively active S6K1 reverses mTOR knockdown-induced cytoophidium disassembly. Finally, reducing mTOR protein expression results in a decrease of the length of cytoophidium in Drosophila follicle cells. Therefore, our study connects CTPS cytoophidium formation with the mTOR signaling pathway.



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Treatment of Veterans with Psychiatric Diagnoses Nationally in the Veterans Health Administration: A Comparison of Service Delivery by Mental Health Specialists and Other Providers

Abstract

Patients with psychiatric disorders are treated by both mental health specialists and non-specialists. We use national data from the Veterans Health Administration to evaluate changing proportions of patients seen exclusively by non-specialists during the study year (FY 2012) limit as well as differences in socio-demographic, clinical and service use characteristics. There has been a five-fold increase in veterans with mental disorders seen by non-specialists over 20 years from 7 to 38%, findings similar to those in non-VA settings. Veterans treated by mental health specialists were younger, more likely to have been homeless and disabled, and had more severe and more numerous psychiatric diagnoses. There is a need to maintain specialty services and to strengthen non-specialty care through education and research.



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Allocation Concealment And Intention-To-Treat Analysis Do Not Influence The Treatment Effects Of Physical Therapy Interventions In Low Back Pain Trials: A Meta-Epidemiological Study

Publication date: Available online 31 January 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Matheus Oliveira de Almeida, Bruno Tirotti Saragiotto, Chris Maher, Leonardo Oliveira Pena Costa

Abstract
Objective

To evaluate if allocation concealment and intention-to-treat (ITT) analysis influence the treatment effects of physical therapy interventions in low back pain trials.

Data sources

We searched on PubMed, Embase, Cochrane Database of Systematic Reviews, PEDro and CINAHL up to February 2017.

Study selection

We included low back pain trials that compared physical therapy interventions to placebo or no intervention or minimal intervention with pain or disability outcomes.

Data extraction

Information about allocation concealment and ITT analysis was extracted from PEDro and pain and disability outcomes converted to a 0-100 scale. A meta-regression was performed to evaluate the influence of these methodological features of interest on treatment effects. Other covariates included in the meta-regression were sample size and sequence generation.

Data Synthesis

We identified 128 eligible trials (pooled n = 20555 participants). A total of 44.5% of the trials achieved allocation concealment, while 32% performed ITT analysis. Meta regression analyses showed no influence of allocation concealment on treatment effects for pain (regression coefficient 0.009; 95% CI -2.91 to 2.91) and disability (regression coefficient 1.13; 95% CI -1.35 to 3.62), and no influence of ITT analysis for pain (regression coefficient 1.38; 95% CI -1.73 to 4.50) or disability (regression coefficient 1.27; 95% CI -1.39 to 3.64). For the other covariates, there was also no clinically significant influence on the treatment effects.

Conclusion

There is no influence of allocation concealment and/or ITT analysis on treatment effects of physical therapy interventions for pain and disability in low back pain trials.



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Returning to Activity After a Concussion

Publication date: Available online 30 January 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Nick Reed, Noah D. Silverberg, Mary Alexis Iaccarino, Michael McCrea, Karen L. McCulloch, William Panenka, Emma Gregory, Kristen Dams-O'Connor, Grant L. Iverson, Chris Weyer Jamora, Heather Belanger, Gary McKinney, Alison M. Cogan, Christine Provvidenza



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Aging, effort, and stereotyping: The evidence for the moderating role of self-involvement

Publication date: Available online 30 January 2019

Source: International Journal of Psychophysiology

Author(s): Gabriela Czarnek, Małgorzata Kossowska, Michael Richter

Abstract

A study with young and older adults (N = 91) investigated the effect of self-involvement on stereotyping tendency and effort mobilization. We hypothesized that the impact of self-involvement varies as a function of age: increased self-involvement should lead older adults to engage in more effortful information processing and decreased stereotyping, whereas increased self-involvement should have no impact on effort mobilization and stereotyping tendency in younger adults. Young and older adults read narratives under low and high-self-involvement conditions before performing a recognition test that measured their stereotyping tendency. Effort was assessed as cardiovascular responses. We found that older adults in the high-self-involvement condition presented low stereotyping tendency (similar to that of young people) in comparison to older adults in the low-self-involvement condition. Furthermore, older adults in the high-self-involvement condition had decreased high-frequency heart rate variability in comparison to the other conditions, but only during the recognition test; this suggests increased effort mobilization. These findings indicate that self-involvement decreases older adults' stereotyping tendency, possibly through effort mobilization.



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Preventing Nerve Injury with Pedicle Screw Testing

Publication date: Available online 31 January 2019

Source: Clinical Neurophysiology

Author(s): Marc R. Nuwer



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Neuronal spiking activity highlights a gradient of epileptogenicity in human tuberous sclerosis lesions

Publication date: Available online 30 January 2019

Source: Clinical Neurophysiology

Author(s): Elodie Despouy, Jonathan Curot, Marie Denuelle, Martin Deudon, Jean-Christophe-Sol, Jean-Albert Lotterie, Leila Reddy, Lionel G. Nowak, Jérémie Pariente, Simon J. Thorpe, Luc Valton, Emmanuel J. Barbeau

Abstract
Objective

The mechanisms underlying epileptogenicity in tuberous sclerosis complex (TSC) are poorly understood.

Methods

We analysed neuronal spiking activity (84 neurons), fast ripples (FRs), local field potentials and intracranial electroencephalogram during interictal epileptiform discharges (IEDs) in the tuber and perituber of a patient using novel hybrid electrodes equipped with tetrodes.

Results

IEDs were recorded in the tuber and perituber. FRs were recorded only in the tuber and only with the microelectrodes. A larger proportion of neurons in the tuber (57%) than in the perituber (17%) had firing-rates modulated around IEDs.

Conclusions

A multi-scale analysis of neuronal activity, FRs and IEDs indicates a gradient of epileptogenicity running from the tuber to the perituber.

Significance

We demonstrate, for the first time in vivo, a gradient of epileptogenicity from the tuber to the perituber, which paves the way for future models of epilepsy in TSC. Our results also question the extent of the neurosurgical resection, including or not the perituber, that needs to be made in these patients.



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Widespread interictal epileptic discharge more likely than focal discharges to unveil the seizure onset zone in EEG-fMRI

Publication date: Available online 30 January 2019

Source: Clinical Neurophysiology

Author(s): Tomohiro Yamazoe, Nicolás von Ellenrieder, Hui Ming Khoo, Yao-Hsien Huang, Natalja Zazubovits, François Dubeau, Jean Gotman

Abstract
Objective

We hypothesized that the number of interictal epileptic discharges (IEDs) during scan and their spatial extent are contributing factors in obtaining appropriate activations that reveal the seizure onset zone (SOZ) in EEG-fMRI.

Methods

157 IED types, each corresponding to one EEG scalp distribution, in 64 consecutive EEG-fMRI studies from 64 patients with refractory localization-related epilepsy were reviewed. To determine reliable activation, we used the threshold corresponding to corrected whole-brain topological false discovery rate (FDR). The location with maximum activation was compared to the presumed SOZ as defined by a comprehensive evaluation for each patient.

Results

The number of IEDs was significantly higher in the types with t-value above FDR than with t-value below FDR. The presumed SOZ could be delineated in 30 of the 64 patients. Among these patients, the types of IED concordant with the SOZ had significantly larger extent on scalp EEG than the IED types discordant with the SOZ.

Conclusions

The number of IEDs is important factor in obtaining reliable activations in EEG-fMRI. IEDs with larger spatial extent are more likely to reveal, on maximum BOLD, accurate location of the SOZ.

Significance

Widespread discharges are more likely to yield a reliable activation for SOZ in EEG-fMRI.



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Τετάρτη, 30 Ιανουαρίου 2019

Antimicrobial Resistance and Biofilm Formation in Enterococcus spp. Isolated from Humans and Turkeys in Poland

Microbial Drug Resistance, Ahead of Print.


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Machine Learning for Prediction of Sustained Opioid Prescription After Anterior Cervical Discectomy and Fusion

The severity of the opioid epidemic has increased scrutiny of opioid prescribing practices. Spine surgery is a high-risk episode for sustained postoperative opioid prescription.

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Assessment of changes in the micro-nano environment of intervertebral disc degeneration based on Pfirrmann grade

Pfirrmann grading can be used to assess intervertebral disc degeneration (IVDD) . There is growing evidence that IVDD is not simply a structural disorder but also involves changes to the substructural characteristics of the disc. Whether Pfirrmann grade can accurately represent these micro-nano environmental changes remains unclear.

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Isolated Teres Minor Injury in a Dragon Boat Racer

No abstract available

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Geographic Inequities in Coverage of Maternal and Child health Services in Haryana State of India

Abstract

Introduction India aims to achieve universal health coverage, with a focus on equitable delivery of services. There is significant evidence on extent of inequities by income status, gender and caste. In this paper, we report geographic inequities in coverage of reproductive, maternal and child health (MCH) services in Haryana state of India. Methods Cross-sectional data on utilization of maternal, child health and family planning services were collected from 12,191 women who had delivered a child in the last one year, 10314 women with 12–23 months old child, and 45864 eligible couples across all districts in Haryana state. Service coverage was assessed based on eight indicators − 6 for maternal health, one for child health and one for family planning. Inter- and intra-district inequalities were compared based on four and three indicators respectively. Results Difference in coverage of full ante-natal care, full immunization and contraceptive prevalence rate between districts performing best and worst was found to be 54%, 65% and 63% respectively. More than one-thirds of the sub-centres (SCs) in Panchkula, Ambala, Gurgaon and Mewat districts had their ante-natal care coverage less than 50% of the respective district average. Similarly, a significant proportion of SCs in Mewat, Panipat and Hisar districts had full immunization rate below 50% of the district average. Conclusion Widespread inter- and intra-district inequities in utilization of MCH services exist. A comprehensive geographical targeting to identify poor performing districts, community development blocks and SCs could result in significant equity gains, besides contributing to quick achievement of sustainable development goals.



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Early Menstrual Factors Are Associated with Adulthood Cardio-Metabolic Health in a Survey of Mexican Teachers

Abstract

Objectives To evaluate whether age at menarche and time to menstrual regularity were related to cardio-metabolic risk factors in Mexican women. Methods The study population comprised 54,921 women from the 2008–2010 wave of the Mexican Teacher's Cohort. A modified Poisson approach was used; exposures were age at menarche and time to menstrual regularity (< 1 year vs. ≥1 year), and outcomes were prevalent obesity, type 2 diabetes, high blood pressure, and high cholesterol. Results Mean (SD) age of women was 42.1 (7.6) years, and mean (SD) menarcheal age was 12.5 (1.5) years. Compared to women with menarche age 13 years, those with menarche < 9 years had a 65% (95% CI 43–90%); 27% (95% CI 4–55%); and 23% (95% CI 1–49%) higher prevalence of obesity, high blood pressure, and high cholesterol, respectively. For diabetes, there was a U-shaped association; compared to menarche age 13 years, those with menarche < 9 years had an 89% higher prevalence of diabetes (95% CI 39–156%), and those with menarche ≥ 17 years had a 65% higher prevalence (95% CI 16–134%). Among women with regular cycles (n = 43,113), a longer time to menstrual regularity was associated with diabetes (PR = 1.11 with 95% CI 1.02–1.22), high blood pressure (PR = 1.11 with 95% CI 1.06–1.17), and high cholesterol (PR = 1.09 with 95% CI 1.04–1.14). Conclusions for practice Mexican women with earlier and later ages at menarche and/or longer time to menstrual regularity may have higher risk of cardio-metabolic disease in adulthood.



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Recent advances in rehabilitation for Parkinson’s Disease with Exergames: A Systematic Review

The goal of this contribution is to gather and to critically analyze recent evidence regarding the potential of exergaming for Parkinson's disease (PD) rehabilitation and to provide an up-to-date analysis of t...

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The combined effects of acute irradiation and food supply on survival and fertility in Daphnia magna

Publication date: April 2019

Source: Journal of Environmental Radioactivity, Volumes 199–200

Author(s): Elena I. Sarapultseva, Kseniya Ustenko, Yuri E. Dubrova

Abstract

The results of recent studies have provided strong evidence for the combined effects of diet restriction and exposure to chemical on the survival and reproduction of aquatic organisms. However, the combined effects of diet restriction and exposure to ionizing radiation remain poorly understood. To establish whether parental irradiation and diet restriction can affect the survival and fertility of directly exposed crustaceans and their progeny, Daphnia magna were given 10, 100 and 1000 mGy of acute γ-rays either during chronic diet restriction or normal food supply. Acute exposure to 1000 mGy significantly compromised the viability of irradiated Daphnia and their first-generation progeny, but did not affect the second-generation progeny. Similarly acute exposure to 100 and 1000 mGy also significantly compromised the fertility of F0 and F1Daphnia and did not affect the F2 generation. Low level of food supply compromised the viability of non-exposed and irradiated Daphnia, whereas their fertility was substantially affected by all diets. The dose-response for the effects of irradiation on viability and fertility of Daphnia received different food supply were practically similar, thus implying that the level of nutrition and acute exposure to ionizing radiation independently affect the life history traits in crustacean.



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Large area decontamination after a radiological incident

Publication date: April 2019

Source: Journal of Environmental Radioactivity, Volumes 199–200

Author(s): Jaleh Semmler, Wenxing Kuang, Konstantin Volchek, Arshad Toor, Anthony Snaglewski, Zahid Khan, Pervez Azmi

Abstract

Effective decontamination of large-scale areas such as roads and parking lots after an accidental or intentional radiological incident is important in order to contain the spread of contamination and avoid the need for long-term evacuation of urban areas. As a simulation, large coupons (surface area 3600 cm2) made of concrete patio stone and aged asphalt (from a parking lot) were contaminated with either 60Co or 137Cs solutions and then decontaminated. The decontamination process consisted of a six-component water-based chemical formulation applied using a common house-hold carpet cleaner. Tests were carried out to compare the effectiveness of decontamination using deionized water (simulating rain fall) and chemical formulation. Test results showed that rain fall prior to decontamination lowered the effectiveness of a subsequent decontamination regardless of the surface type or radionuclide. Tests were also carried out to determine if the decontamination effectiveness increased with multiple applications. Using multiple applications of the chemical formulation, the removal of 60Co from concrete patio stone and aged asphalt were 65 ± 2% and 70 ± 3%, respectively, while the removal of 137Cs was 53 ± 3% from asphalt surfaces and 21 ± 8% from concrete patio stone. This paper summarizes the work carried out to prepare for the tests, presents the test results and compares the process to several other processes in terms of effectiveness and suitability for application on a large scale.



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Institutional Guidelines for Resistance Exercise Training in Cardiovascular Disease: A Systematic Review

Abstract

Background

Institutional position stands are useful for practitioners when designing exercise routines for specific populations. Resistance training has been included in programs for patients with cardiovascular disease.

Objective

The objective of this systematic review was to analyze institutional guidelines providing recommendations for resistance training applied to cardiovascular disease.

Methods

PubMed, Web of Science, and Scopus databases were searched from inception until 30 April, 2018.

Results

Of 994 articles initially found, 13 position stands were retained. Consensual indications occurred only for number of sets (one to three sets) and training frequency (two to three sessions/week). Recommendations concerning other major training variables were discordant regarding workload (none or loads ranging from < 30% up to 80% 1 repetition maximum) and exercise order (none or vaguely indicating alternation of muscle groups or circuit format), or insufficient regarding intervals between sets and exercises or number and type of exercises. Overall, guidelines lack recommendations of specific procedures for each type of disease at different severity levels, cardiovascular risk during exercise, or criteria for training progression.

Conclusions

Recommendations provided by institutional guidelines appear to be insufficient to support adequate resistance training prescription in the context of cardiovascular disease.



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Hallmarks of HPV carcinogenesis: The role of E6, E7 and E5 oncoproteins in cellular malignancy

Publication date: Available online 29 January 2019

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

Author(s): Diogo Estêvão, Natália Rios Costa, Rui M. Gil da Costa, Rui Medeiros

Abstract

Human papillomavirus (HPV) is the most common sexually transmitted infectious agent worldwide, being also responsible for 5% of all human cancers. The integration and hypermethylation mechanisms of the HPV viral genome promote the unbalanced expression of the E6, E7 and E5 oncoproteins, which are crucial factors for the carcinogenic cascade in HPV-induced cancers. This review highlights the action of E6, E7 and E5 over key regulatory targets, promoting all known hallmarks of cancer. Both well-characterized and novel targets of these HPV oncoproteins are described, detailing their mechanisms of action. Finally, this review approaches the possibility of targeting E6, E7 and E5 for therapeutic applications in the context of cancer.



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Defining gene networks controlling the maintenance and function of the differentiation niche by an in vivo systematic RNAi screen

Publication date: Available online 30 January 2019

Source: Journal of Genetics and Genomics

Author(s): Yuan Gao, Ying Mao, Rong-Gang Xu, Ruibao Zhu, Ming Zhang, Jin Sun, Da Shen, Ping Peng, Ting Xie, Jian-Quan Ni

Abstract

In the Drosophila ovary, escort cells (ECs) extrinsically control germline stem cell (GSC) maintenance and progeny differentiation. However, the underlying mechanisms remain poorly understood. In this study, we identified 173 EC genes for their roles in controlling GSC maintenance and progeny differentiation by using an in vivo systematic RNAi approach. Of the identified genes, 10 and 163 are required in ECs to promote GSC maintenance and progeny differentiation, respectively. The genes required for progeny differentiation fall into different functional categories, including transcription, mRNA splicing, protein degradation, signal transduction and cytoskeleton regulation. In addition, the GSC progeny differentiation defects caused by defective ECs are often associated with BMP signaling elevation, indicating that preventing BMP signaling is a general functional feature of the differentiation niche. Lastly, exon junction complex (EJC) components, which are essential for mRNA splicing, are required in ECs to promote GSC progeny differentiation by maintaining ECs and preventing BMP signaling. Therefore, this study has identified the major regulators of the differentiation niche, which provides important insights into how stem cell progeny differentiation is extrinsically controlled.



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Vascular responses to hypoxia are not impaired in obstructive sleep apnoea patients free of overt cardiovascular disease

New Findings

What is the central question of this study?

Does treatment of obstructive sleep apnoea (OSA) with nocturnal oxygen or continuous positive airway pressure (CPAP) improve hypoxic vascular responses, which are reportedly impaired in OSA?

What is the main finding and its importance?

Cerebrovascular and cardiovascular hypoxic responses were not impaired in OSA patients free of overt cardiovascular disease and known risk factors, and were not altered by nocturnal oxygen or CPAP treatment. We conclude that this OSA patient phenotype has normal vascular responses to hypoxia and are unlikely to obtain long term cardiovascular benefits from nocturnal oxygen or CPAP therapy.

Abstract

Cerebral blood flow (CBF) and cardiovascular responses to hypoxia are reportedly impaired in obstructive sleep apnoea (OSA) patients and corrected by continuous positive airway pressure (CPAP); beneficial effects that are ascribed to correction of OSA‐related intermittent hypoxia (IH). However, CPAP corrects both IH and ancillary OSA features (i.e., intermittent hypercapnia, sympathetic activation, blood pressure surges, negative intrathoracic pressure swings and sleep fragmentation). Whether correction of these ancillary OSA features contribute to CPAP's beneficial effects on vascular hypoxic responses is unknown. Nocturnal oxygen corrects OSA‐induced IH, but apnoeas and ancillary features persist. Thus, we examined the effects of nocturnal oxygen and CPAP on cerebrovascular and cardiovascular hypoxic responses in untreated OSA patients. Responses were assessed in 52 OSA patients free of overt cardiovascular disease and known risk factors at baseline, after 2‐weeks of nocturnal oxygen (n = 26) or no treatment (n = 26), and after ∼4‐weeks of CPAP treatment (n = 40). Twenty‐two age‐matched controls were assessed at baseline and follow‐up visits. Resting, isocapnic‐euoxia mean blood pressure was decreased following nocturnal oxygen (‐3.6 ± 6.0 mmHg; p = 0.006) and CPAP (‐4.5 ± 7.5 mmHg; p < 0.001) while cerebrovascular conductance was increased with CPAP (p = 0.001). However, these changes were not different from controls. Unexpectedly, OSA patients and controls had similar hypoxic vascular responses at baseline that were not changed by either nocturnal oxygen or CPAP. We conclude that, OSA patients free of overt cardiovascular disease and known risk factors did not have impaired cerebrovascular or cardiovascular responses to hypoxia and are unlikely to obtain long term cardiovascular benefits from nocturnal oxygen or CPAP therapy.

This article is protected by copyright. All rights reserved



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The effect of short duration resistance training on insulin sensitivity and muscle adaptations in overweight men

New Finding

What is the central question of this study?

What is the timecourse of muscular adaptations to short duration resistance exercise training.

What is the main finding and its importance?

Short duration resistance training results in early and progressive increases in muscle mass and function and an increase in insulin sensitivity.

Abstract

Objectives

The aim of the current study was to investigate the effects of six weeks of resistance exercise training, compromised of one set of each exercise to voluntary failure, on i) insulin sensitivity and ii) the time‐course of adaptations in muscle strength/mass.

Methods

Ten overweight men (age: 36 ± 8 years; height 175 ± 9 cm; weight 89 ± 14 kg; BMI 29 ± 3 kg.m2) were recruited to the study. Resistance exercise training involved three sessions per week for six weeks. Each session involved one set, of nine exercises, performed at 80% of 1 repetition maximum (1RM) to volitional failure. Sessions lasted 15–20 minutes. Oral glucose tolerance tests were performed at baseline and post intervention. Vastus lateralis muscle thickness, knee extensor maximal isometric torque and rate of torque development (RTD – measured between 0–50 ms, 0–100 ms, 0–200 ms and 0–300 ms) were measured at baseline, each week of the intervention, and after the intervention.

Results

Resistance training resulted in a 16.3 ± 18.7% (P < 0.05) increase in insulin sensitivity (Cederholm index). Muscle thickness, maximal isometric torque and 1RM increased with training ending the intervention 26.9 ± 8.3%, 10.3 ± 2.5%, 18.3 ± 4.5 higher (P < 0.05 for both) than baseline, respectively. RTD50ms and 100 ms, but not RTD200ms and 300 ms, increased (P < 0.05) over the intervention period.

Conclusions

Six weeks of single set resistance exercise to failure results in improvements in insulin sensitivity and increases in muscle size and strength in young overweight men.

This article is protected by copyright. All rights reserved



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Blood Flow Restriction Only Increases Myofibrillar Protein Synthesis with Exercise

Purpose Combining blood flow restriction (BFR) with exercise can stimulate skeletal muscle hypertrophy. Recent observations in an animal model suggest that BFR performed without exercise can also induce anabolic effects. We assessed the impact of BFR performed both with and without low-load resistance-type exercise (LLRE) on in vivo myofibrillar protein synthesis rates in young men. Methods Twenty healthy young men (age: 24±1 y, BMI: 22.9±0.6 kg/m2) were randomly assigned to remain in resting condition (REST+/-BFR; n=10), or to perform LLRE (LLRE+/-BFR at 20%1RM; n=10), combined with two 5-min cycles of single leg BFR. Myofibrillar protein synthesis rates were assessed during a 5-h post-BFR period by combining a primed continuous L-[ring-13C6]phenylalanine infusion with the collection of blood samples, and muscle biopsies from the BFR leg and the contralateral control leg. Phosphorylation status of anabolic signaling (mTOR pathway) and metabolic stress (ACC) related proteins, as well as mRNA expression of genes associated with skeletal muscle mass regulation were assessed in the collected muscle samples. Results Under resting conditions, no differences in anabolic signaling or myofibrillar protein synthesis rates were observed between REST+BFR and REST (0.044±0.004 vs 0.043±0.004 %/h, respectively; P=0.683). In contrast, LLRE+BFR increased myofibrillar protein synthesis rates by 10±5% compared with LLRE (0.048±0.005 vs 0.043±0.004 %/h, respectively; P=0.042). Furthermore, compared with LLRE, LLRE+BFR showed higher phosphorylation status of ACC and 4E-BP1 as well as elevated mRNA expression of MuRF1 (all P

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Metabolic Implications of Diet and Energy Intake during Physical Inactivity

Purpose Physical inactivity is associated with disruptions in glucose metabolism and energy balance, whereas energy restriction may blunt these adverse manifestations. During hypocaloric feeding, higher-protein intake maintains lean mass which is an important component of metabolic health. This study determined whether mild energy restriction preserves glycemic control during physical inactivity and whether this preservation is more effectively achieved with a higher-protein diet. Methods Ten adults (24±1 year) consumed a control (64% carbohydrate, 20% fat, 16% protein) and higher-protein diet (50% carbohydrate, 20% fat, 30% protein) during two ten-day inactivity periods (>10,000→~5,000 steps/day) in a randomized cross-over design. Energy intake was decreased by ~400 kcal/d to account for reduced energy expenditure associated with inactivity. A subset of subjects (n=5) completed ten days of inactivity while consuming 35% excess of their basal energy requirements, which served as a positive control condition (overfeeding+inactivity). Results Daily steps were decreased from 12,154±308 to 4,275±269 steps/day (P0.05). Overfeeding+inactivity increased body weight, body fat, HOMA-IR, and 2-hour postprandial glucose and insulin concentrations (P

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Exercise Arrangement Is Associated with Physical and Mental Health in Older Adults

Purpose Although exercising with others might have health benefits, no previous study has comprehensively examined associations of exercise arrangement with physical activity (PA), physical function (PF), and mental health (MH). We examined whether PA, PF, and MH are better when exercising with others than when exercising alone or not exercising. Methods We analyzed cross-sectional data from 7,759 (4,007 men and 3,752 women) non-disabled residents aged 65-84 years. PA, PF, and MH were assessed with the International Physical Activity Questionnaire-Short Form (PA sufficiency defined as ≥150 min/week of moderate-to-vigorous PA), Motor Fitness Scale (higher PF defined as total score ≥12 in men and ≥10 in women), and World Health Organization-Five Well-Being Index (better MH defined as a total score ≥13), respectively. Exercise arrangement was classified as "non-exerciser," "exercising alone," and "exercising with others." Using multilevel logistic regression analyses, we examined independent associations of exercise arrangement with PA, PF, and MH. Results Compared with exercising alone, the multivariate-adjusted odds ratios (95% confidence interval) among non-exercisers and those exercising with others were 0.21 (0.17-0.25) and 1.32 (1.04-1.67), respectively, for PA sufficiency, 0.47 (0.40-0.57) and 1.12 (0.94-1.34) for higher PF, and 0.69 (0.58-0.82) and 1.45 (1.17-1.79) for better MH, respectively, in men. In women, the corresponding odds ratios were 0.37 (0.30-0.46) and 1.31 (1.01-1.70) for PA sufficiency, 0.66 (0.54-0.80) and 1.08 (0.88-1.32) for higher PF, and 0.70 (0.58-0.85) and 1.27 (1.03-1.56) for better MH, respectively. Conclusions Exercising alone and with others were better than no exercise for maintaining better PA, PF, and MH in both sexes. Although exercise arrangement had little effect on maintaining PF, exercising with others appears to enhance PA levels and MH in both sexes. 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. Address of corresponding author: Satoshi Seino, PhD, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae, Itabashi, Tokyo, 173-0015, Japan, Phone: +81 (3) 3964-3241 ext. 4252, E-mail: seino@tmig.or.jp This study was supported by grants from Ota City. We declare that the results of the present study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and do not constitute endorsement by the American College of Sports Medicine. CONFLICT OF INTERESTS: The authors declare that they have no competing interests. Accepted for Publication: 2 January 2019 © 2019 American College of Sports Medicine

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Histamine-Receptor Antagonists Slow 10-km Cycling Performance in Competitive Cyclists

Histamine is released within skeletal muscle during exercise. In humans, antihistamines have no effect on speed, power output, or time-to-completion of short-duration high-intensity exercise. In mice, blocking histamine's actions decreases speed and duration of endurance tasks. It is unknown if these opposing outcomes are the result of differences in histamine's actions between species or are related to duration and/or intensity of exercise, as blocking histamine during endurance exercise has not been examined in humans. Purpose Determine the effects of histamine-receptor antagonism on cycling time-trial performance in humans, with and without a preceding bout of sustained steady-state exercise. Methods Eleven (3F) competitive cyclists performed six 10-km time-trials on separate days. The first two time-trials served as familiarization. The next four time-trials were performed in randomized-block order, where two were preceded by 120 min of seated rest (Rest) and two by 120 min of cycling exercise (Exercise) at 50% VO2peak. Within each block, subjects consumed either combined histamine H1 and H2 receptor antagonists (Blockade) or Placebo, prior to the start of the 120-min Rest/Exercise. Results Blockade had no discernible effects on hemodynamic or metabolic variables during Rest or Exercise. However, Blockade increased time-to-completion of the 10-km time-trial compared to Placebo (+10.5 ± 3.7 s, P

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Regulation of Hepatic Follistatin Expression at Rest and during Exercise in Mice

Introduction Follistatin (FST) is a protein with numerous biological roles, and was recently identified as an exercise inducible hepatokine; however, the signals that regulate this are not well understood. The purpose of this study was to delineate potential endocrine factors that may regulate hepatic FST at rest and during exercise. Methods This study used four experiments. First, male and female C57BL/6J mice remained sedentary or were subjected to a single bout of exercise at moderate or exhaustive intensity with liver collected immediately post. Second, mice were injected with glucagon (1 mg/kg, 60 min), epinephrine (2 mg/kg, 30 min), glucagon then epinephrine, or saline. Third, mice were pre-treated with propranolol (20-60 mg/kg, 30 min) prior to epinephrine injection. Fourth, glucagon receptor wild type (Gcgr+/+) or knockout (Gcgr-/-) mice were pre-treated with saline or propranolol (20 mg/kg, 30 min) and were subjected to a single bout of exhaustive exercise with liver collected immediately post or after 2 hours recovery. In all experiments liver FST mRNA expression was measured, and in experiment four FST protein content was measured. Results A single bout of treadmill exercise performed at an exhaustive but not moderate intensity increased FST expression, as did injection of glucagon or epinephrine alone and when combined. Pre-treatment of mice with propranolol attenuated the epinephrine induced increase in FST expression. The exercise-induced increase in FST expression was attenuated in Gcgr-/- mice, with no effect of propranolol. Gcgr-/- mice had higher protein content of FST, but there was no effect of exercise or propranolol. Conclusion These data suggest that both glucagon and epinephrine regulate hepatic FST expression at rest; however, only glucagon is required for the exercise-induced increase. These authors contributed equally, Willem T. Peppler, Laura N. Castellani Corresponding author: David C. Wright, PhD, Rm. 334 Animal Science Nutrition Building, Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada, N1G 2W1, Phone: 519 824 4120 ext 56751, Email: dcwright@uoguelph.ca, Fax: 519-763-5902 This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (DCW). DCW is a Tier II Canada Research Chair in Lipids, Metabolism, and Health. The Ontario Graduate Scholarship program supported WTP and LNC. An NSERC postgraduate scholarship, Dairy Farmers of Ontario Doctoral Research Assistantship, and the Ontario Graduate Scholarship Program supported LKT. The Ontario Graduate Scholarship program, and subsequently, a NSERC Canada Graduate Scholarship supported SFC. REKM was supported by a post-doctoral fellowship from the Alzheimer's Society of Canada. The results of the present study do not constitute endorsement by ACSM, and the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Competing Interests: The authors declare no competing interests. Accepted for Publication: 3 January 2019 © 2019 American College of Sports Medicine

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Novel Approach to Characterize Heterogeneity in an Aerobic Exercise Intervention

Purpose Exercise intervention studies for brain health can be difficult to interpret due to heterogeneity in exercise intensity, exercise duration, and in adherence to the exercise intervention. This study aimed to characterize heterogeneity in these components in a cohort of healthy middle-aged and older adults who participated in a prescribed six-month supervised aerobic exercise intervention as part of the Brain in Motion (BIM) study. Methods and Results Group-based multi-trajectory analysis (GBMTA) was used to characterize variation in the trajectory of exercise intensity and duration for male and female participants in the first three-months of the exercise program. The GBMTA for males and females revealed two distinct trajectory subgroups, namely, "High-Increasing" (HI) and "Low-Increasing" (LI). Logistic regression was used to assess the association between the identified latent subgroups and i) demographic characteristics, ii) physiological characteristics including cardiovascular and cerebrovascular function, iii) genetic characteristics, and IV) adherence with American College of Sports Medicine (ACSM) guidelines on exercise for older adults. Of the 196 participants, 54.1% met the ACSM aerobic exercise targets for intensity and duration during the intervention. Aerobic fitness (V[Combining Dot Above]O2max; OR=1.27, p

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Activity Tracker to Prescribe Various Exercise Intensities in Breast Cancer Survivors

Purpose To prescribe different physical activity (PA) intensities using activity trackers to increase PA, reduce sedentary time and improve health outcomes among breast cancer survivors. The maintenance effect of the interventions on study outcomes was also assessed. Methods The Breast Cancer and Physical Activity Level (BC-PAL) pilot trial randomized 45 breast cancer survivors to a home-based, 12-week lower (300 minutes/week at 40-59% of heart rate reserve) or higher (150 minutes/week at 60-80% of heart rate reserve) intensity PA, or no PA intervention/control. Both intervention groups received Polar A360® activity trackers. Study outcomes assessed at baseline, 12- and 24-weeks included PA and sedentary time (ActiGraph GT3X+), health-related fitness (e.g. body composition, cardiopulmonary fitness/VO2max) and patient-reported outcomes (e.g. quality of life). Intention-to-treat analyses were conducted using linear mixed models and adjusted for baseline outcomes. Results Increases in moderate-vigorous intensity PA (least squares adjusted group difference (LSAGD)= 0.6 (95% confidence interval (CI)= 0.1, 1.0)) and decreases in sedentary time (LSAGD= -1.2 (95% CI= -2.2, -0.2)) were significantly greater in the lower intensity PA group versus control at 12-weeks. Increases in VO2max at 12-weeks in both interventions groups were significantly greater than changes in the control group (lower intensity PA group LSAGD= 4.2 (95% CI= 0.5, 8.0 ml/kg/min); higher intensity PA group LSAGD= 5.4 (95% CI= 1.7, 9.1 ml/kg/min)). Changes in PA and VO2max remained at 24-weeks, but differences between the intervention and control groups were no longer statistically significant. Conclusion Increases in PA time and cardiopulmonary fitness/VO2max can be achieved with both lower- and higher-intensity PA interventions in breast cancer survivors. Reductions in sedentary time were also noted in the lower intensity PA group. Send correspondence and reprint requests to: Jessica McNeil, Ph.D., Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Holy Cross Centre, Room 508B, Box ACB, 2210 2nd street SW, Calgary, Alberta, Canada, T2S 3C3, Phone: 1-403-698-8163, Fax: 1-403-264-2654, E-mail: Jessica.McNeil2@albertahealthservices.ca Dr. McNeil is a recipient of Postdoctoral Fellowship Awards from the Canadian Institutes of Health Research and Alberta Innovates-Health Solutions. Dr. Brenner was supported by a Capacity Development Award in Cancer Prevention from the Canadian Cancer Society (#703917). Ms. Stone was supported by the Queen Elizabeth II (Province of Alberta) Scholarship. Dr. Vallance holds a Tier II Canada Research Chair. Dr. Courneya holds a Tier I Canada Research Chair. Dr. Friedenreich was supported by a Health Senior Scholar Award from Alberta Innovates-Health Solutions and the Alberta Cancer Foundation Weekend to End Women's Cancers Breast Cancer Chair. The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. CONFLICTS OF INTEREST AND SOURCES OF FUNDING: The authors declare no conflicts of interest. Pilot data collection for the BC-PAL Trial was funded by a Catalyst Grant from the O'Brien Institute for Public Health, University of Calgary and the Carole May Yates Memorial Endowment for Cancer Research Fund, administered through the Arnie Charbonneau Cancer Institute, University of Calgary. Accepted for Publication: 2 January 2019 © 2019 American College of Sports Medicine

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Physical Activity, Sleep, and Symptoms of Depression in Adults—Testing for Mediation

Purpose Physical activity, sleep problems and symptoms of depression contribute to overall wellbeing. The factors are reciprocally associated, but the nature of these associations remains unclear. The present study examined whether sleep problems mediated the association between physical activity and depressive symptoms. Methods The eligible population (n = 3596) consisted of adults from the ongoing, population-based Cardiovascular Risk in Young Finns Study started in 1980. Participants' leisure-time physical activity was assessed with physical activity index (2007) and sleep problems with Jenkins' Sleep Questionnaire (JSQ) in 2007 and 2011. Depressive symptoms were measured using modified Beck Depression Inventory (BDI-II) in 2007 and 2012, from which the items reflecting sleep problems were excluded. Mediation analyses, through which the associations between the variables were examined, were adjusted for sex and a set of health-related covariates assessed in 2007 and 2011. Results Physical activity was associated with decreased levels of sleep problems and depressive symptoms (P 0.05). Conclusion Physical activity's favorable contribution to depressive symptoms was mediated partly by sleep, but the mediation effect disappeared after adjusting for the previous depressive symptoms in adulthood. Corresponding Author: Kaisa Kaseva, Department of Psychology and Logopedics, P.O. Box 9, 00014 University of Helsinki, Finland. E-mail: kaisa.kaseva@helsinki.fi, tel: +35844307773 The present study was funded by Academy of Finland (grant no. 258578), Ministry of Education and Culture, Kone Foundation and Urheiluopistosäätiö. CONFLICTS OF INTEREST: The authors have no conflicts of interest to declare. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the study do not constitute endorsement by American College of Sports Medicine. Accepted for Publication: 7 January 2019 © 2019 American College of Sports Medicine

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Machine Learning in Modeling High School Sport Concussion Symptom Resolve

Introduction Concussion prevalence in Sport is well-recognized; so too is the challenge of clinical and return-to-play management for an injury with an inherent indeterminant time course of resolve. Clear, valid insight to the anticipated resolution time could assist in planning treatment intervention. Purpose This study implemented a supervised machine learning-based approach in modeling estimated symptom resolve time in high school athletes who incurred a concussion during sport activity. Methods We examined the efficacy of 10 classification algorithms using machine learning for prediction of symptom resolution time (within seven, fourteen, or twenty-eight days), with a dataset representing three years of concussions suffered by high school student-athletes in football (most concussion incidents) and other contact sports. Results The most prevalent sport-related concussion reported symptom was headache (94.9%), followed by dizziness (74.3%) and difficulty concentrating (61.1%). For all three category thresholds of predicted symptom resolution time, single-factor ANOVAs revealed statistically significant performance differences across the ten classification models for all learners at a 95% confidence level (P=0.000). Naïve Bayes and Random Forest with either 100 or 500 trees were the top-performing learners with an area under the ROC curve performance ranging between 0.666 and 0.742 (0.0-1.0 scale). Conclusions Considering the limitations of these data specific to symptom presentation and resolve, supervised machine learning demonstrated efficacy, while warranting further exploration, in developing symptom-based prediction models for practical estimation of sport-related concussion recovery in enhancing clinical decision support. Corresponding author: Michael F. Bergeron, Ph.D., FACSM, SIVOTEC Analytics, Boca Raton Innovation Campus, 4800 T-Rex Avenue, Suite 315, Boca Raton, FL 33431, e-mail: mbergeron@sivotecanalytics.com, (706) 284-7142 The NATION project was funded by the National Athletic Trainers' Association Research & Education Foundation and Central Indiana Corporate Partnership Foundation in cooperation with BioCrossroads. Content of this report is solely the responsibility of the authors and does not necessarily reflect the views of any of the funding organizations. The authors declare that the results of this 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: 9 January 2019 © 2019 American College of Sports Medicine

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Cerebral Blood Flow during Exercise in Heart Failure: Impact of Ventricular Assist Devices

Introduction In healthy individuals cerebral blood flow (CBF) increases during exercise, but few studies have compared changes in CBF during exercise in patients with heart failure (HF) to healthy controls (CTRL), or assessed the effects of left ventricular assist devices (LVADs). We hypothesised that subjects implanted with LVADs would exhibit impaired cerebrovascular responses to cycle exercise when compared to age- and sex-matched healthy CTRL subjects, but enhanced responses relative to subjects with HF. Methods Internal carotid artery [ICA] blood flow, and intra-cranial middle [MCAv] and posterior cerebral [PCAv] artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental submaximal cycle ergometer exercise protocol in 9 LVAD participants (58±15yrs; 87±16kg; 172±8 cm, 6♂), 9 age- and sex-matched subjects with HF (58±8yrs; 84±11kg;177±6cm), and 9 CTRL (55±14yrs; 74±16kg;168±10cm). Results At rest, ICA hemodynamics (velocity, shear rate and flow) were greater in CTRLs and LVADs than HF (p

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Fast Running Does Not Contribute More to Cumulative Load than Slow Running

Purpose As running speed increases there are concomitant changes in loads associated with tibial stress fracture risk. Runners often include multiple speeds in their training, but the effect of speed distribution on load accumulation is unknown. We studied how running at different proportions of speed within a given running distance affects the cumulative loading of the vertical average loading rate, cumulative peak absolute tibial free moment, and cumulative peak axial tibial load. These loads were compared between two proportions of speed: running all distance at normal self-selected speed, and running the same distance at a combination of slow/fast speeds with the same average speed as normal. Also, the contributions of slow and fast running to the combined condition were compared. Methods 43 recreational runners (age 18-49y, 29 female, 14 male) ran around a 50-m indoor track for three laps each at self-selected slow, normal, and fast speeds. Per-step peak loads and cumulative loads per kilometer were calculated at each speed and for each speed distribution, respectively. Results Only cumulative vertical average loading rate was lower at normal speed compared to the slow/fast speed combination. The contribution of fast speed running to cumulative tibial load was less than the contribution of slow speed running. Conclusion Running at a combination of slow and fast speeds, rather than a single moderate speed, increased cumulative vertical average loading rate but not cumulative tibial load or free moment. Fast running can be included in a training program without necessarily increasing the cumulative load. Total distance and average speed may not be sufficient information to estimate cumulative load from running training. Corresponding author: Jessica G. Hunter, 4200 Valley Drive, University of Maryland, College Park, MD, USA 20742. Phone: 786.218.6022. Email: jghunter@umd.edu This study was supported by a grant from Maryland Technology Enterprises Institute. Conflict of interest: The authors have no conflicts of interest. The results of this study do not constitute endorsement by the ACSM. The results of this study are presented clearly and honestly without fabrication, falsification, or inappropriate data manipulation. Accepted for publication: 3 January 2019. © 2019 American College of Sports Medicine

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Physical Activity and Sedentary Time: Association with Metabolic Health and Liver Fat

Introduction/Purpose To investigate whether a) lower levels of daily physical activity (PA) and greater sedentary time accounted for contrasting metabolic phenotypes (higher liver fat/presence of metabolic syndrome [MetS+] vs lower liver fat/absence of metabolic syndrome [MetS-]) in individuals of similar BMI and b) the association of sedentary time on metabolic health and liver fat. Methods Ninety-eight habitually active participants (53 female, 45 male; age 39±13 years; BMI 26.9±5.1 kg/m2), underwent assessments of PA (SenseWear armband; wear time ~98%), cardio-respiratory fitness (V[Combining Dot Above]O2 peak), body composition (MRI and MRS) and multi-organ insulin sensitivity (OGTT). We undertook a) cross-sectional analysis comparing four groups: non-obese or obese, with and without metabolic syndrome (MetS+ vs MetS-) and b) univariate and multivariate regression for sedentary time and other levels of PA in relation to liver fat. Results Light, moderate and vigorous PA did not account for differences in metabolic health between individuals, whether non-obese or obese, although MetS+ individuals were more sedentary, with a higher number, and prolonged bouts (~1-2 hours). Overall, sedentary time, average daily METS and V[Combining Dot Above]O2 peak were each independently associated with liver fat percentage. Each additional hour of daily sedentary time was associated with a 1.15% (95% CI, 1.14–1.50%) higher liver fat content. Conclusions Greater sedentary time, independent of other levels of PA, is associated with being metabolically unhealthy; even in habitually active people, lesser sedentary time, and higher cardio-respiratory fitness and average daily METS is associated with lower liver fat. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Corresponding author: Kelly A. Bowden Davies, Institute of Ageing & Chronic Disease, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK; kdavies@liverpool.ac.uk; +44 (0)151 794 9141 Original funding support by Diabetes UK (grant number 13/0004719) with additional support from the MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) and internal funding from Institute of Ageing and Chronic Disease, University of Liverpool. Andrew Irwin (Obesity and Endocrinology, University Hospital Aintree, UK) for clinical assistance and Val Adams for radiographic expertise at LiMRIC. Conflict of Interest: The authors declare that there is no conflict of interest associated with this manuscript. MH has support from NIHR Leicester BRC. The results of the study to not constitute endorsement by ACSM and are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for publication: 28 December 2018. © 2019 American College of Sports Medicine

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Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients

Abstract

Purpose

Intermittent hypoxia training/treatment (IHT) is an emerging therapeutic approach to alleviate chronic diseases, such as diabetes. The present study investigated the effects of IHT on blood leucocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and its relationship with the changes in blood insulin level.

Methods

Seven adult healthy volunteers and 11 prediabetic patients participated in this study. A 3-week course of IHT consisted of a 40-min session of 4 cycles of 5-min 12% O2 and 5-min room air breathing per day, 3 sessions per week for 3 weeks (i.e., total 9 sessions of IHT). Plasma insulin levels and leukocyte PDK-1 mRNA expression were determined at various time points either under fasting condition or following oral glucose tolerance test (OGTT). Correlation between the IHT-induced changes in PDK-1 mRNA and insulin or glucose levels in the same serological samples was analyzed.

Results

At pre-IHT baseline, PDK-1 mRNA expression was two times higher in prediabetes than control subjects. IHT resulted in significant augmentation in PDK-1 mRNA expression (> twofold) in prediabetes at the end of 3-week IHT and remained elevated 1 month after IHT, which was correlated with a significantly reduced insulin release and lower blood glucose after glucose loading with OGTT.

Conclusion

IHT can trigger beneficial effects in normalizing blood insulin levels in prediabetic patients under oral glucose load, which were closely correlated with an enhanced mRNA expression of PDK-1 in leukocytes. Further clinical trials are warranted to validate the utility of IHT as a non-invasive complementary therapy against diabetes-associated pathologies.



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A case of broken bones and systems: The threat of irresponsible testimony

A 2‐month‐old healthy baby presented to the emergency room with an arm that was not moving and was found to have multiple and extensive fractures of her long bones. An extensive medical work‐up was done, and the hospital's multidisciplinary child abuse team was consulted, including child protection, genetics, radiology, and general pediatrics. It was determined that the history, clinical findings, radiographic findings, and laboratory findings were consistent with child abuse. Child protection services removed the child from the home, and for the next 10 months, the infant was well, and did not sustain a single new fracture. At a civil proceeding to determine the infant's custody, an expert witness for the defense concluded that the child had hypermobile Ehlers‐Danlos syndrome and low vitamin D. He stated that because of these conditions, the baby was vulnerable to fractures with routine handling. This is a personal story of a clinical geneticist who explored fracture fact versus fracture fiction and learned about the difference between responsible and irresponsible testimony. This story gives insight into how physicians can prepare to transition from the clinic to the courtroom. It is also a story about how medical experts must and should remain unbiased, evidence‐based, and committed to accuracy and truth.



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Τρίτη, 29 Ιανουαρίου 2019

Glucose control in the ICU

Purpose of review Critically ill patients usually develop hyperglycemia, which is associated with adverse outcome. Controversy exists whether the relationship is causal or not. This review summarizes recent evidence regarding glucose control in the ICU. Recent findings Despite promising effects of tight glucose control in pioneer randomized controlled trials, the benefit has not been confirmed in subsequent multicenter studies and one trial found potential harm. This discrepancy could be explained by methodological differences between the trials rather than by a different case mix. Strategies to improve the efficacy and safety of tight glucose control have been developed, including the use of computerized treatment algorithms. Summary The ideal blood glucose target remains unclear and may depend on the context. As compared with tolerating severe hyperglycemia, tight glucose control is well tolerated and effective in patients receiving early parenteral nutrition when provided with a protocol that includes frequent, accurate glucose measurements and avoids large glucose fluctuations. All patient subgroups potentially benefit, with the possible exception of patients with poorly controlled diabetes, who may need less aggressive glucose control. It remains unclear whether tight glucose control is beneficial or not in the absence of early parenteral nutrition. Correspondence to Greet Van den Berghe, MD, PhD, Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, B-3000, Leuven, Belgium. Tel: +32 16 344021; fax +32 16 344015; e-mail: greet.vandenberghe@kuleuven.be Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Thoracic trauma in military settings: a review of current practices and recommendations

Purpose of review To examine current literature on thoracic trauma related to military combat and to explore its relevance to the civilian population. Recent findings Damage control resuscitation (DCR) has improved the management of hemorrhaging trauma patients. Permissive hypotension below 110 mmHg and antifibrinolytic use during DCR is widely accepted, whereas the use of freeze-dried plasma and whole blood is gaining popularity. The Modified Physiologic Triaging Tool can be used for primary triage and it may have applications in civilian trauma systems. Although Tactical Combat Casualty Care protocol recommends the Cric-Key device for surgical cricothyroidotomies, other devices may offer comparable performance. Recommendations for regional anesthesia after blunt trauma are not well defined. Increasing amounts of evidence favor the use of extracorporeal membrane oxygenation for refractory hypoxemia and resuscitative endovascular balloon occlusion of the aorta (REBOA) for severe hemorrhage. REBOA outcomes are potentially improved by partial occlusion and small 7 Fr catheters. Summary The Global War on Terror has provided opportunities to better understand and treat thoracic trauma in military settings. Trauma registries and other data sources have contributed to significant advancements in the management of thoracic trauma in military and civilian populations. Correspondence to Robert Mansky, 545 First Ave, Apt 8I, New York, NY 10016, USA. Tel: +1 516 672 5589; e-mail: rmansky@gmail.com Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Noninvasive ventilation versus oxygen therapy in patients with acute respiratory failure

Purpose of review High-flow nasal cannula oxygen therapy (HFOT) is becoming an alternative to noninvasive ventilation (NIV) and standard oxygen in management of patients with acute respiratory failure. Recent findings Patients with de novo acute respiratory failure should be managed with HFOT rather than NIV. Indeed, the vast majority of patients with de novo respiratory failure meet the criteria for ARDS, and NIV does not seem protective, as patients generate overly high tidal volume that may worsen underlying lung injury. However, NIV remains the first-line oxygenation strategy in postoperative patients and those with acute hypercapnic respiratory failure when pH is equal to or below 7.35. During preoxygenation, NIV also seems to be more efficient than standard oxygen using valve-bag mask to prevent profound oxygen desaturation. In postoperative cardiothoracic patients, HFOT could be an alternative to NIV in the management of acute respiratory failure. Summary Recent recommendations for managing patients with acute respiratory failure have been established on the basis of studies comparing NIV with standard oxygen. Growing use of HFOT will lead to new studies comparing NIV versus HFOT in view of more precisely defining the appropriate indications for each treatment. Correspondence to Jean-Pierre Frat, Médecine Intensive Réanimation, CHU de Poitiers, 2 rue la Milétrie, 86021 Poitiers Cedex, France. Tel: +33 5 49 44 40 07; e-mail: jean-pierre.frat@chu-poitiers.fr Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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The effectiveness of noise interventions in the ICU

Purpose of review Excessive noise has direct adverse physiological and psychological effects, and may also have indirect negative health consequences by reducing sleep quality and quantity. This review presents a synthesis of the epidemiology of noise in the ICU, and the potential interventions designed to attenuate noise and protect patients. Recent findings Noise increases cortisol release, oxygen consumption, and vasoconstriction. ICU noise levels are excessive throughout the 24-h cycle, irrespective of level of intervention or whether the patient is in a side room or open ward. Direct measurement suggests that noise is a substantial contributor to poor sleep quantity and quality in the ICU and is frequently recalled by survivors of critical illness as a negative experience of ICU admission. Noise abatement, environmental masking and pharmacological interventions may all reduce the impact of noise on patients. However, the sustainability of behavioural interventions remains uncertain and high-quality evidence demonstrating the benefit of any intervention on patient-centered outcomes is lacking. Summary Noise levels in the ICU are consistently reported to reach levels likely to have both direct and indirect adverse health consequences for both patients and staff. Noise reduction, abating the transmission of noise and pharmacological modulation of the adverse neural effects of noise are all potentially beneficial strategies, although definitive evidence of improved patient-centered outcomes is lacking. Correspondence to Lori Delaney, MIHM, MN, PGD Crit Care, PGC Ed, Faculty of Nursing, Queensland University of Technology, Kelvin Grove, QLD 4059, Australia. E-mail: Lori.delaney@qut.edu.au Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Telemedicine in the ICU: clinical outcomes, economic aspects, and trainee education

Purpose of review The evidence base for telemedicine in the ICU (tele-ICU) is rapidly expanding. The last 2 years have seen important additions to our understanding of when, where, and how telemedicine in the ICU adds value. Recent findings Recent publications and a recent meta-analysis confirm that tele-ICU improves core clinical outcomes for ICU patients. Recent evidence further demonstrates that comprehensive tele-ICU programs have the potential to quickly recuperate their implementation and operational costs and significantly increase case volumes and direct contribution margins particularly if additional logistics and care standardization functions are embedded to optimize ICU bed utilization and reduce complications. Even though the adoption of tele-ICU is increasing and the vast majority of today's medical graduates will regularly use some form of telemedicine and/or tele-ICU, telemedicine modules have not consistently found their way into educational curricula yet. Tele-ICU can be used very effectively to standardize supervision of medical trainees in bedside procedures or point-of-care ultrasound exams, especially during off-hours. Lastly, tele-ICUs routinely generate rich operational data, as well as risk-adjusted acuity and outcome data across the spectrum of critically ill patients, which can be utilized to support important clinical research and quality improvement projects. Summary The value of tele-ICU to improve patient outcomes, optimize ICU bed utilization, increase financial performance and enhance educational opportunities for the next generation of providers has become more evident and differentiated in the last 2 years. Correspondence to Christian D. Becker, MD, PhD, Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. Tel: +1 914 493 1040; fax: +1 914 493 8373; e-mail: christian.becker@wmchealth.org Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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In Vitro Activity of Tedizolid in Comparison with Other Oral and Intravenous Agents Against a Collection of Community-Acquired Methicillin-Resistant Staphylococcus aureus (2014–2015) in the United States

Microbial Drug Resistance, Ahead of Print.


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Prevalence and Genetic Characteristics of Methicillin-Resistant Staphylococcus aureus and Coagulase-Negative Staphylococci Isolated from Oral Cavity of Healthy Children in Japan

Microbial Drug Resistance, Ahead of Print.


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TP901-1 Phage Recombinase Facilitates Genome Engineering in Drosophila melanogaster

Molecular biology techniques have a large impact on biomedical research and the availability of diverse tools to perform genome manipulations advances the ease of executing complicated genetic research. Here, we introduce in the fruit fly another such tool by harnessing the phage recombinase TP901-1 to perform site-directed recombination that leads to recombinase-mediated cassette exchange (RMCE). The TP901-1 system complements already existing recombination systems and enhances genome engineering in the fruit fly and other organisms.



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Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed

Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (Canis lupus familiaris), and has been associated with glaucoma and blindness. Goniodysgenesis and early-onset glaucoma initially emerged in Border Collies in Australia in the late 1990s and has subsequently been found in this breed in Europe and the USA. The objective of the present study was to determine the genetic basis of goniodysgenesis in Border Collies. Clinical diagnosis was based on results of examinations by veterinary ophthalmologists of affected and unaffected dogs from eleven different countries. Genotyping using the Illumina high density canine single nucleotide variant genotyping chip was used to identify a candidate genetic region. There was a highly significant peak of association over chromosome 17, with a p-value of 2 x 10–13. Expression profiles and evolutionary conservation of candidate genes were assessed using public databases. Whole genome sequences of three dogs with glaucoma, three severely affected by goniodysgenesis and three unaffected dogs identified a missense variant in the olfactomedin like 3 (OLFML3) gene in all six affected animals. This was homozygous for the risk allele in all nine cases with glaucoma and 12 of 14 other severely affected animals. Of 67 reportedly unaffected animals, only one was homozygous for this variant (offspring of parents both with goniodysgenesis who were also homozygous for the variant). Analysis of pedigree information was consistent with an autosomal recessive mode of inheritance for severe goniodysgenesis (potentially leading to glaucoma) in this breed. The identification of a candidate genetic region and putative causative variant will aid breeders to reduce the frequency of goniodysgenesis and the risk of glaucoma in the Border Collie population.



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Cross-cultural Adaptation of the Neck Pain and Disability Scale: A Methodological Systematic Review

Neck pain is a common and uncomfortable symptom, adversely affecting the work and life of those affected. The Neck Pain and Disability Scale (NPDS) is widely used in neck pain assessment. It has been cross-culturally adapted into several languages to extend its reach to non-English-speaking countries. The aim of this study was to comprehensively evaluate the translation procedures and measurement properties of cross-cultural adaptations of the NPDS.

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Comparison of the history and physical examination for hip osteoarthritis and lumbar spinal stenosis

Leg pain associated with walking is sometimes incorrectly attributed to hip osteoarthritis (OA) or lumbar spinal stenosis (LSS).

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Gypsy moth genome provides insights into flight capability and virus-host interactions [Genetics]

Since its accidental introduction to Massachusetts in the late 1800s, the European gypsy moth (EGM; Lymantria dispar dispar) has become a major defoliator in North American forests. However, in part because females are flightless, the spread of the EGM across the United States and Canada has been relatively slow over...

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Whole-chromosome paints in maize reveal rearrangements, nuclear domains, and chromosomal relationships [Genetics]

Whole-chromosome painting probes were developed for each of the 10 chromosomes of maize by producing amplifiable libraries of unique sequences of oligonucleotides that can generate labeled probes through transcription reactions. These paints allow identification of individual homologous chromosomes for many applications as demonstrated in somatic root tip metaphase cells, in...

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Paternal comeback in mitochondrial DNA inheritance [Genetics]

Since the discovery of mtDNA in 1963 (1), it has been a common notion that inheritance of this small, but very essential, piece of DNA occurs in a strict maternal manner. One reason for this is that the paternal contribution of sperm mitochondria to the fertilized egg is about 1,000-fold...

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Opinion: To curate the molecular past, museums need a carefully considered set of best practices [Anthropology]

Biomolecular research has sparked a methodological revolution in the field of anthropology, and museums are now faced with the curatorial challenge of conserving and evaluating materials for these new methods. Since 2010, hundreds of genome-wide datasets from ancient human samples have been published, and thousands more have been generated; doubling...

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A Qualitative Exploration of Mothers’ Experiences Receiving Mental Health Services in a Supermarket Setting

Abstract

Objectives Innovative mental health care delivery models have been proposed as a method to address disparities in access and utilization. The aim of this study is to characterize patients' perspectives and experiences of participating in one such innovative delivery model, group cognitive behavioral therapy within a supermarket setting. Methods In this qualitative study, 16 mothers were interviewed to explore their experiences and perspectives of receiving group-based cognitive behavioral therapy in a supermarket setting, as part of their participation in an academic-community research collaborative whose mission is to address mental health needs within low-resourced communities. Data from semi-structured interviews were analyzed using inductive coding. Results Five themes related to receiving mental health services in a supermarket setting emerged from the data: (1) Participants reported a convergence of life stressors and their introduction to supermarket-based services; (2) Participants perceived the supermarket setting as convenient; (3) Participants perceived the supermarket setting as less stigmatizing; (4) Participants perceived services in the supermarket as an acceptable form of mental health treatment; and (5) Participants described the program staff as an influential component of their treatment experience. Conclusions Understanding patient experiences of various service delivery models is critical to improving access to treatment and addressing disparities in mental health service utilization and outcomes. This study supports the use of innovative delivery models to increase access to mental health services in low-resourced communities.



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Rat mesenteric small artery neurogenic dilation is predominantly mediated by β1‐adrenoceptors in vivo

Key points

The prevailing dogma about neurogenic regulation of vascular tone consists of major vasodilation caused by CGRP (and possibly substance P) released from sensory‐motor nerves and vasoconstriction caused by noradrenaline, ATP and NPY release from sympathetic nerves. Most studies on perivascular nerve mediated vasodilation are made in vitro. We here provide evidence that in vivo electrical perivascular nerve stimulation in rat mesenteric small arteries causes a large β1‐adrenoceptor mediated vasodilation, which contrasts with a smaller vasodilation caused by endogenous CGRP, which is only visible after inhibition of Y1 NPY receptors. Mesenteric arteries are densely innervated and the nerves are important regulators of vascular tone and hence blood pressure and blood flow . Perivascular sensory‐motor nerves have been shown to cause vasodilation in vitro. However, less is known about their function in vivo. Male Wistar rats (10‐12 weeks old; n = 72) were anaesthetized with ketamine (3 mg kg−1) and xylazine (0.75 mg kg−1) or pentobarbital (60 mg kg−1). After a laparotomy, a section of 2nd order mesenteric artery was visualized in an organ bath after minimal removal of perivascular adipose tissue. The effects of electrical field stimulation (EFS) and drugs on artery diameter and blood flow were recorded with intravital microscopy and laser speckle imaging. EFS caused vasodilation in arteries constricted with 1 μm U46619 in the presence of 140 μm suramin and 1 μm prazosin. The vasodilation was inhibited by 1 μm tetrodotoxin and 5 μm guanethidine but not by the 1 μm of the CGRP receptor antagonist BIBN4096bs. In the presence of 0.3 μm of the Y1 receptor antagonist BIBP3226, BIBN4096bs partly inhibited the vasodilation. One μm atenolol inhibited the vasodilation while 0.1 μm of the β2‐adrenoceptor selective antagonist ICI‐118,551 had no effect. Increasing the extracellular [K+] to 20 mm caused vasodilation but vasoconstriction in the presence of 1 μm BIBN4096bs, and constriction to 30 mm potassium was potentiated by BIBN4096bs. Atenolol but not BIBN4096bs increased contraction to EFS in the absence of suramin and prazosin. In mesenteric small arteries of anaesthetized rats, EFS failed to stimulate major dilation via sensory‐motor nerves but induced sympathetic β1‐adrenoceptor mediated dilation.

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