Παρασκευή 18 Ιανουαρίου 2019
Propofol TCI Reductions Do Not Attenuate Significant Falls in Cardiac Output Associated With Anesthesia Induction and Knee-Chest Positioning in Spinal Surgery
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Journal Club
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Cognitive Prehabilitation: Supercharged Mind or Wishful Thinking?
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Dynamic Changes of Cardiac Repolarization Instability during Exercise Testing
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Dynamic Interactions Between the Genome and an Endogenous Retrovirus: Tirant in Drosophila simulans Wild-Type Strains
All genomes contain repeated sequences that are known as transposable elements (TEs). Among these are endogenous retroviruses (ERVs), which are sequences similar to retroviruses and are transmitted across generations from parent to progeny. These sequences are controlled in genomes through epigenetic mechanisms. At the center of the epigenetic control of TEs are small interfering RNAs of the piRNA class, which trigger heterochromatinization of TE sequences. The tirant ERV of Drosophila simulans displays intra-specific variability in copy numbers, insertion sites, and transcription levels, providing us with a well-suited model to study the dynamic relationship between a TE family and the host genome through epigenetic mechanisms. We show that tirant transcript amounts and piRNA amounts are positively correlated in ovaries in normal conditions, unlike what was previously described following divergent crosses. In addition, we describe tirant insertion polymorphism in the genomes of three D. simulans wild-type strains, which reveals a limited number of insertions that may be associated with gene transcript level changes through heterochromatin spreading and have phenotypic impacts. Taken together, our results participate in the understanding of the equilibrium between the host genome and its TEs.
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Effect of spinal decompression on back pain in lumbar spinal stenosis: A Canadian Spine Outcomes Research Network (CSORN) study
Surgical decompression is usually offered for improvement of neurogenic claudication in patients with symptomatic lumbar canal stenosis. These patients often have associated low back pain (LBP) and little is known about the effect of decompression on this symptom.
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Comparison of pre-oxygenation using spontaneous breathing through face mask and high-flow nasal oxygen: A prospective randomised crossover controlled study in healthy volunteers
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Central venous-to-arterial PCO2 difference, arteriovenous oxygen content and outcome after adult cardiac surgery with cardiopulmonary bypass: A prospective observational study
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Programmed intermittent bolus infusion versus continuous infusion of 0.2% levobupivacaine after ultrasound-guided thoracic paravertebral block for video-assisted thoracoscopic surgery: A randomised controlled trial
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Pre-operative ultrasonographic evaluation of inferior vena cava collapsibility index and caval aorta index as new predictors for hypotension after induction of spinal anaesthesia: A prospective observational study
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Imaging of Progressive Neuropathic Arthropathy of the Shoulder
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Evidence in Rehabilitation Medicine: Between Facts and Prejudices
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Is Aerobic Exercise Training Beneficial for Adults With Fibromyalgia?: A Cochrane Review Summary with Commentary
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A Controlled Clinical Trial on the Effects of Exercise on Cognition and Mobility in Adults With Multiple Sclerosis
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Integrated Rehabilitation for Breast Cancer Survivors
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Effect of Exercise on Risk Factors of Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis
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Comment on “Efficacy of Armeo Robotic Therapy Versus Conventional Therapy on Upper Limb Function in Children With Hemiplegic Cerebral Palsy”
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Morphological Differences in the Upper Trapezius Muscle Between Female Office Workers With and Without Trapezius Myalgia: Facts or Fiction?: A Cross-Sectional Study
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Cochrane Corners to Enhance Access to Evidence-Based Physiatry
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Functional Outcome Scores With Standard Myoelectric Prostheses in Below-Elbow Amputees
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The Incidence of Physiatry-Relevant Complications in Trauma Patients Admitted to an Urban Canadian Trauma Center
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Impact of Vascular Disease, Amputation Level, and the Mismatch Between Balance Ability and Balance Confidence in a Cross-Sectional Study of the Likelihood of Falls Among People With Limb Loss: Perception Versus Reality
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When the Injury's Healing Process Meets the Needs of a Top-Level Volleyball Player: A Nonconventional Treatment of a Mallet Fracture Reinjury
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The Effect of Static Stretching of Peroneal and Tibialis Anterior Muscles on Reaction Time: A Randomized Controlled Study
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Predatory Open-Access Medical Publishers “Caveat Emptor”
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Effects of Twitch Contraction Induced by Magnetic Stimulation on Expression of Skeletal Muscle Fibrosis Related Genes and Limited Range of Motion in Rats
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Ultrasound Imaging for Dorsal Radiolunotriquetral Ligament Possibly Causing Wrist Impingement
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Subcostal approach to anterior quadratus lumborum block for pain control following open urological procedures
Abstract
In the case of open urological surgeries, analgesic coverage at mid thoracic dermatomal levels is required. As shown in cadaveric studies, the site of QL block injection is an important determinant of the extent of dye spread and presumably local anesthetic dermatomal coverage. In this case series, we evaluated dermatomal blockade and analgesic efficacy of a subcostal approach to anterior QL block following open urological surgeries. Twenty-two adult patients undergoing renal transplant surgery (60%) and open nephrectomy (40%) received unilateral ultrasound-guided subcostal anterior QL block with catheter insertion. Sensory level, pain score (numeric rating scale, NRS), local anesthetic consumption, and opioid consumption (morphine equivalent dose, MED) were assessed daily for 3 days. The block achieved sensory blockade between T6-7 and L1-2. The most frequently affected dermatomes were T8 -T12 and the number of blocked segments was 3 (mean 2.8). The median (interquartile range Q1, Q3) of NRS pain score was 3.7 (2.8–5.5), 3.3 (2.4–4.7), 2.9 (1.9–3.6), and 2.3 (1.0–4.2) on POD0, POD1, POD2, and POD3, respectively. Our preliminary data showed that the subcostal approach to anterior QL block provides appropriate thoracic dermatome level needed for analgesia following open urological surgical procedures between T6-7 and L1-2.
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Repeatability of exercise‐induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle
New Findings
What is the central question of this study?
Are individual changes in exercise‐induced mRNA expression repeatable (i.e. representative of the true response to exercise rather than random error)?
What is the main finding and its importance?Changes in mRNA expression are not repeatable even under identical experimental conditions.
The lack of repeatability is not explained by technical error arising from major gene analysis steps, highlighting sources of technical error and/or biological variability originating directly within the muscle.
Fibre‐type distribution is highly variable in two portions of the same muscle biopsy.
The substantial random error in exercise‐induced mRNA expression challenges its use as a biomarker of adaptive potential and/or individual responsiveness to exercise.
Abstract
It remains unknown if: 1) the observed change in mRNA expression reflects an individual's true response to exercise or random (technical and/or biological) error, and 2) the individual responsiveness to exercise is protocol‐specific. We examined the repeatability of skeletal muscle PGC‐1α, PDK4, NRF‐1, VEGF‐A, HSP72, and p53 mRNA expression following two identical endurance exercise (END) bouts (END‐1, END‐2; 30 minutes of cycling at 65% of peak work rate [WRpeak], n = 11) and inter‐individual variability in PGC‐1α and PDK4 mRNA expression following END and sprint interval training (SIT; 8 × 20‐second cycling intervals at ∼170% WRpeak, n = 10) in active young males. The repeatability of key gene analysis steps (RNA extraction, reverse transcription, qPCR) and within‐sample fibre‐type distribution (n = 8) was also determined to examine potential sources of technical error in our analyses. Despite highly repeatable exercise bout characteristics (work rate, heart rate, blood lactate; ICCs > 0.71; CVs < 10%; r > 0.85, p < 0.01), gene analysis steps (ICCs > 0.73; CVs < 24%; r > 0.75, p < 0.01), and similar group‐level changes in mRNA expression, individual changes in PGC‐1α, PDK4, VEGF‐A, and p53 mRNA expression were not repeatable (ICCs < 0.22; CVs > 20%; r < 0.21). Fibre‐type distribution in two portions of the same muscle biopsy was highly variable and not significantly related (ICC = 0.39; CV = 26%; r = 0.37, p = 0.37). Since individual changes in mRNA expression following identical exercise bouts were not repeatable, inferences regarding individual responsiveness to END or SIT were not made. Substantial random error exists in changes in mRNA expression following acute exercise, thereby challenging the use of mRNA expression for analyzing individual responsiveness to exercise.
This article is protected by copyright. All rights reserved
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Novel Point Mutations in cyp51A and cyp51B Genes Associated with Itraconazole and Posaconazole Resistance in Aspergillus clavatus Isolates
Microbial Drug Resistance, Ahead of Print.
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Caffeine affects children’s ERPs and performance in an equiprobable go/no‐go task: Testing a processing schema
Abstract
Caffeine's stimulant properties were used to test a proposed processing schema for children's processing stages in the equiprobable auditory go/no‐go task. Active control‐related ERP components were hypothesized to be differentially enhanced by caffeine. Caffeine (80 mg) was administered in a counterbalanced, randomized, double‐blind, placebo‐controlled, cross‐over study of 24 children, aged 8–12 years. Four blocks of an equiprobable auditory go/no‐go task were completed on each of two occasions, while on or off caffeine. ERP data sets from each condition (caffeine/go, placebo/go, caffeine/no‐go, placebo/no‐go) were subjected to separate temporal PCAs with extraction and varimax rotation of all components. Caffeine significantly reduced reaction time and go omission errors, and enhanced go PN, N2c, and P3b, and no‐go N1‐1 and N2b. This selective enhancement of different go/no‐go components by caffeine matched the predicted amplification of biomarkers of children's active control processing in this task. Some unexpected findings also support further refinements in the child processing schema.
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Out and about: Subsequent memory effect captured in a natural outdoor environment with smartphone EEG
Abstract
Spatiotemporal context plays an important role in episodic memory. While temporal context effects have been frequently studied in the laboratory, ecologically valid spatial context manipulations are difficult to implement in stationary conditions. We investigated whether the neural correlates of successful encoding (subsequent memory effect) can be captured in a real‐world environment. An off‐the‐shelf Android smartphone was used for wireless mobile EEG acquisition and stimulus presentation. Participants encoded single words, each of which was presented at a different location on a university campus. Locations were approximately 10–12 m away from each other, half of them with striking features (landmarks) nearby. We predicted landmarks would improve recall performance. After a first free recall task of verbal stimuli indoors, participants performed a subsequent recall outdoors, in which words and locations were recalled. As predicted, significantly more words presented at landmark locations as well as significantly more landmark than nonlandmark locations were recalled. ERP analysis yielded a larger posterior positive deflection during encoding for hits compared to misses in the 400–800 ms interval. Likewise, time‐frequency analysis revealed a significant difference during encoding for hits compared to misses in the form of stronger alpha (200–300 ms) and theta (300–400 ms) power increases. Our results confirm that a vibrant spatial context is beneficial in episodic memory processing and that the underlying neural correlates can be captured with unobtrusive smartphone EEG technology. The advent of mobile EEG technology promises to unveil the relevance of natural physical activity and natural environments on memory.
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Cluster‐based permutation tests of MEG/EEG data do not establish significance of effect latency or location
Abstract
Cluster‐based permutation tests are gaining an almost universal acceptance as inferential procedures in cognitive neuroscience. They elegantly handle the multiple comparisons problem in high‐dimensional magnetoencephalographic and EEG data. Unfortunately, the power of this procedure comes hand in hand with the allure for unwarranted interpretations of the inferential output, the most prominent of which is the overestimation of the temporal, spatial, and frequency precision of statistical claims. This leads researchers to statements about the onset or offset of a certain effect that is not supported by the permutation test. In this article, we outline problems and common pitfalls of using and interpreting cluster‐based permutation tests. We illustrate these with simulated data in order to promote a more intuitive understanding of the method. We hope that raising awareness about these issues will be beneficial to common scientific practices, while at the same time increasing the popularity of cluster‐based permutation procedures.
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Syllables constitute proximate units for Mandarin speakers: Electrophysiological evidence from a masked priming task
Abstract
Languages may differ regarding the primary mental unit of phonological encoding in spoken production, with models of speakers of Indo‐European languages generally assuming a central role for phonemes, but spoken Chinese production potentially attributing a more prominent role to syllables. In the present study, native Mandarin Chinese speakers named objects that were preceded by briefly presented and masked prime words, which were form related and either matched or mismatched concerning their syllabic structure, or were unrelated. Behavioral results showed a previously reported interaction between prime and target syllable type. Concurrently recorded EEG also exhibited this interaction and further revealed that syllable overlap modulated ERPs mainly in the time window of 300–400 ms after picture onset. By contrast, phonemic overlap modulated ERPs from 500 ms to 600 ms. This pattern might suggest that speakers retrieved syllables before phonemes and strengthens the claim that for Chinese individuals syllables constitute primary functional representations ("proximate units").
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Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort
Abstract
Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography–tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1–2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1–2% lower estrogen (E1, E2, E3) levels, but 1–2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4–18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1–2% higher (no difference in estrogens). Androgen concentrations were 18–30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.
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Learned Helplessness After Anterior Cruciate Ligament Reconstruction: An Altered Neurocognitive State?
Abstract
Traumatic knee injuries, such as anterior cruciate ligament (ACL) sprains, have detrimental effects on long-term health as they initiate a cycle of chronic pain, physical inactivity, and disability. Alterations in strength and neural activity are factors that contribute to rehabilitation failure after ACL reconstruction (ACLR); however, psychological deficits also hinder rehabilitative success. Neural impairments observed following injury and ACLR may be associated with psychological dysfunction, a phenomenon defined as learned helplessness (LH). The proposed framework establishes the link between depressed neural activity and psychological dysfunction after ACL injury using foundational evidence from neuroscience and psychology to support the integration of LH into recovery.
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Impact of Ad Libitum Versus Programmed Drinking on Endurance Performance: A Systematic Review with Meta-Analysis
Abstract
Background
Debate continues on how athletes should hydrate during exercise. Several studies have recently been published comparing the effect of ad libitum (ALD) and programmed drinking (PD) on endurance performance (EP).
Objective
This work examined whether one drinking strategy offers an EP advantage over the other.
Design
Systematic review and meta-analysis of crossover controlled trials.
Data Sources
PubMed and SPORTDiscus database searches.
Eligibility Criteria for Selecting Studies
Key criteria were (1) experiments performed under controlled settings; (2) exercise lasting ≥ 1 h; (3) exercise initiated in an euhydrated state; (4) fluid intake during PD > ALD; (5) fluid composition matched for electrolytes; and (6) carbohydrate intake varied by > 25% between conditions when the exercise was 1 h and matched for exercise > 1 h.
Results
Seven publications, producing eight effect estimates, including cycling and running exercises and representing 82 subjects, were included. Mean (± standard deviation) ambient temperature, exercise intensity and duration of the experiments were 28 ± 6 °C, 81 ± 12% of maximal heart rate and 96 ± 25 min, respectively. Mean rate of fluid consumption for the PD and ALD conditions was 1073 ± 247 mL/h and 505 ± 156 mL/h, respectively. Mean change in body mass for the PD and ALD conditions was − 1.0 ± 0.5% and − 2.1 ± 0.7%, respectively. Compared with PD, ALD improved EP by 0.98 ± 0.44% (95% confidence interval 0.11–1.84%). The greater EP conferred by ALD is likely trivial.
Conclusions
Despite ALD being associated with an hourly rate of fluid consumption half as much as PD, and resulting in a dehydration level considered sufficient to impair EP, both strategies were found to similarly impact 1–2 h cycling or running performances conducted at moderate to high intensity and under temperate to warm ambient conditions.
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Revised Approach to the Role of Fatigue in Anterior Cruciate Ligament Injury Prevention: A Systematic Review with Meta-Analyses
Abstract
Background
Causes of anterior cruciate ligament (ACL) injuries are multifactorial. Anterior cruciate ligament injury prevention should thus be approached from a multifactorial perspective as well. Training to resist fatigue is an underestimated aspect of prevention programs given that the presence of fatigue may play a crucial role in sustaining an ACL injury.
Objectives
The primary objective of this literature review was to summarize research findings relating to the kinematic and kinetic effects of fatigue on single-leg landing tasks through a systematic review and meta-analysis. Other objectives were to critically appraise current approaches to examine the effects of fatigue together with elucidating and proposing an optimized approach for measuring the role of fatigue in ACL injury prevention.
Methods
A systematic literature search was conducted in the databases PubMed (1978–November 2017), CINAHL (1992–November 2017), and EMBASE (1973–November 2017). The inclusion criteria were: (1) full text, (2) published in English, German, or Dutch, (3) healthy subjects, (4) average age ≥ 18 years, (5) single-leg jump landing task, (6) evaluation of the kinematics and/or kinetics of the lower extremities before and after a fatigue protocol, and (7) presentation of numerical kinematic and/or kinetic data. Participants included healthy subjects who underwent a fatigue protocol and in whom the effects of pre- and post-fatigue on three-dimensional lower extremity kinematic and kinetics were compared. Methods of data collection, patient selection, blinding, prevention of verification bias, and study design were independently assessed.
Results
Twenty studies were included, in which four types of single-leg tasks were examined: the single-leg drop vertical jump, the single-leg drop landing, the single-leg hop for distance, and sidestep cutting. Fatigue seemed to mostly affect initial contact (decreased angles post-fatigue) and peak (increased angles post-fatigue) hip and knee flexion. Sagittal plane variables at initial contact were mostly affected under the single-leg hop for distance and sidestep cutting conditions whilst peak angles were affected during the single-leg drop jump.
Conclusions
Training to resist fatigue is an underestimated aspect of prevention programs given that the presence of fatigue may play a crucial role in sustaining an ACL injury. Considering the small number of variables affected after fatigue, the question arises whether the same fatigue pathways are affected by the fatigue protocols used in the included laboratory studies as are experienced on the sports field.
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The Muscle Protein Synthetic Response to Meal Ingestion Following Resistance-Type Exercise
Abstract
Protein ingestion following resistance-type exercise stimulates muscle protein synthesis rates and consequently enhances the skeletal muscle adaptive response to prolonged training. Ingestion of ~ 20 g of quickly digestible protein isolate optimizes muscle protein synthesis rates during the first few hours of post-exercise recovery. However, the majority of daily protein intake is consumed as slower digestible, nutrient-rich, whole-food protein sources as part of mixed meals. Therefore, the muscle protein synthetic response to the ingestion of protein supplements and typical foods or mixed meals may differ substantially. In addition, the muscle protein synthetic response to feeding is not only determined by acute nutrient intake but is also likely modulated by habitual energy and nutrient intake and nondietary factors such as habitual physical activity, body composition, age, and/or sex. Therefore, nutritional recommendations to maximize the muscle protein synthetic response to exercise depend on the type of meal (e.g., protein supplements vs. mixed meals) and the time until the next feeding opportunity (e.g., feeding before overnight sleep) and, therefore, need to be personalized to the individual athlete.
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Associations Between Maternity Care Practices and 2-Month Breastfeeding Duration Vary by Race, Ethnicity, and Acculturation
Abstract
Objectives This study examines the associations between specific maternity care practices and breastfeeding duration for Spanish-speaking Hispanic, English-speaking Hispanic, non-Hispanic Native American, and non-Hispanic White women. Methods We analyzed data from the 2012–2014 New Mexico Pregnancy Risk Assessment Monitoring System. We used survey language as a proxy measure of acculturation and categorized women as Spanish-speaking Hispanic, English-speaking Hispanic, non-Hispanic Native American, and non-Hispanic White. We conducted bivariate analyses to compare rates of breastfeeding at 2 months and experiences of maternity care practices and logistic regression analysis to estimate the effects of these practices on breastfeeding duration for each group. Results Hispanic women were less likely than non-Hispanic women to breastfeed for at least 2 months (67.9% vs. 76.6%; p = 0.000); however, this varied significantly by acculturation level: 78.1% of Spanish-speaking Hispanic women compared to 66.1% of English-speaking Hispanic women breastfed for at least 2 months (p = 0.000). The effects of specific maternity care practices on duration varied across groups. Among non-Hispanic White, Native American, and English-speaking Hispanic women, breastfeeding while at the hospital had the strongest effect (AOR 2.09, 95% CI 1.67–2.61; AOR 2.71, 95% CI 2.08–3.52; and AOR 1.99, 95% CI 1.76–2.25, respectively). Among Spanish-speaking Hispanic women, being encouraged to breastfeed on demand had the strongest effect (AOR 5.179, 95% CI 3.86–6.94). Conclusions for Practice The effects of maternity care practices on breastfeeding duration vary by race, ethnicity, and acculturation level. Health care systems must acknowledge the diversity of their patient populations when seeking to develop and implement breastfeeding-friendly practices.
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Comparison between cuff-based and radial tonometry exercise-induced central blood pressure
Abstract
Purpose
Non-invasive central blood pressure assessed during exercise may provide better cardiovascular prognostic than measurements taken at rest. Radial tonometry is the only technique validated to perform this type of assessment; however, it relies on the experience of the tester. Cuff-based devices have been developed to avoid operator dependency, although these systems have yet to be validated during exercise. The purpose of this study was to compare exercise-induced central blood pressure estimations between a cuff-based device and radial tonometry.
Methods
Twenty young healthy subjects were recruited to perform a three-workload steady-state exercise test at blood lactate levels of < 2, 2–4, and > 4 mmol/L, respectively. Central systolic and diastolic blood pressure (cSBP and cDBP, respectively), central pulse pressure (cPP), and augmentation index (AIx) were assessed at rest and during each workload with a cuff-based device and radial tonometry. Statistical analysis included Bland–Altman analysis for agreement between techniques. Agreement was considered when 95% of the data set for each central blood pressure parameter was within 1.96 standard deviations from the mean difference. Significance was considered at α = 0.05.
Results
Central blood pressure measurements with the cuff device were obtained only at rest and during low-intensity exercise. During low-intensity exercise, all measurements showed agreement between both devices (cSBP 95% CI [− 6.0 to 10.7], cDBP 95% CI [− 4.5 to 6.3], cPP 95% CI [− 4.7 to 8.3], and AIx (95% CI [− 20.1 to 22.2]).
Conclusion
A cuff-based device can estimate central blood pressure at low-intensity exercise, without operator dependency, and showing agreement to radial tonometry.
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Readers of the m6A epitranscriptomic code
Publication date: Available online 17 January 2019
Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Soizik Berlivet, Jérémy Scutenaire, Jean-Marc Deragon, Cécile Bousquet-Antonelli
Abstract
N6-methyl adenosine (m6A) is the most prevalent and evolutionarily conserved, modification of polymerase II transcribed RNAs. By post-transcriptionally controlling patterns of gene expression, m6A deposition is crucial for organism reproduction, development and likely stress responses. m6A mostly mediates its effect by recruiting reader proteins that either directly accommodate the modified residue in a hydrophobic pocket formed by their YTH domain, or otherwise have their affinity positively influenced by the presence of m6A. We firstly describe here the evolutionary history, and review known molecular and physiological roles of eukaryote YTH readers. In the second part, we present non YTH-proteins whose roles as m6A readers largely remain to be explored. The diversity and multiplicity of m6A readers together with the possibility to regulate their expression and function in response to various cues, offers a multitude of possible combinations to rapidly and finely tune gene expression patterns and hence cellular plasticity. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Soller Matthias and Dr. Fray Rupert.
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Difficulties and challenges in the development of precision medicine
The rapid development of precision medicine is introducing a new era of significance in medicine. However, attaining precision medicine is an ambitious goal that is bound to encounter some challenges. Here, we have put forward some difficulties or questions that should be addressed by the progress in this field. The proposed issues include the long road to precision medicine for all types of diseases as the unknown domains of the human genome hinder the development of precision medicine. The challenges in the acquisition and analysis of large amounts of omics data, including difficulties in the establishment of a library of biological samples and large‐scale data analysis, as well as the challenges of informed consent and medical ethics in precision medicine, must be overcome to attain the goals of precision medicine. To date, precision medicine programmes have accomplished many preliminary achievements and will help to drive a dramatic revolution in clinical practices for the medical community. Through these advances, the diagnosis and treatment of many diseases will achieve many breakthroughs. This project is just beginning and requires a great deal of time and money. Precision medicine also requires extensive collaboration. Ultimately, these difficulties can be overcome. We should realize that precision medicine is good for patients, but there is still a long way to go.
This article is protected by copyright. All rights reserved.
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CLINICAL AND MOLECULAR DIAGNOSIS OF NON‐PMM2 N‐LINKED CONGENITAL DISORDERS OF GLYCOSYLATION IN SPAIN
The congenital disorders of glycosylation (CDG) are defects in glycoprotein and glycolipid glycan synthesis and attachment. They affect multiple organ/systems but non‐specific symptoms render the diagnosis of the different CDG very challenging. PMM2‐CDG is the most common CDG, but advances in genetic analysis have shown others to occur more commonly than previously thought. The present work reports the clinical and mutational spectrum of 25 non‐PMM2 CDG patients. The most common clinical symptoms were hypotonia (80%), motor or psychomotor disability (80%) and craniofacial dysmorphism (76%). Based on their serum transferrin isoform profile eighteen were classified as CDG‐I and seven as CDG‐II. Pathogenic variations were found in 16 genes (ALG1, ALG6, ATP6V0A2, B4GALT1, CCDC115, COG7, DOLK, DPAGT1, DPM1, GFPT1, MPI, PGM1, RFT1, SLC35A2, SRD5A3, SSR4). Overall, 27 variants were identified, 12 of which are novel. The results highlight the importance of combining genetic and biochemical analyses for the early diagnosis of this heterogeneous group of disorders.
This article is protected by copyright. All rights reserved.
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Newly identified set of obesity‐related genotypes and abdominal fat influence the risk of insulin resistance in a Korean population
We aimed to identify obesity‐related single nucleotide polymorphism (SNP) loci in a Korean population and construct an obesity genetic risk score (GRS) to examine the association of the genetic predisposition to obesity with insulin resistance (IR). In total, 9,675 subjects were included, and 7,666 of these subjects were used for replication. A GRS was constructed using the SNP loci that overlapped in both cohort sets. The subjects showed a trend toward an increase in body mass index, waist circumference, systolic/diastolic blood pressure, homeostatic model assessment (HOMA)‐IR, HOMA‐B, and levels of insulin, triglyceride, and alanine aminotransferase across the tertiles of obesity GRS, while the adiponectin level showed a trend toward a decrease with increasing GRS. The associations between the obesity GRS and the measures of fasting insulin, HOMA‐IR, and adiponectin were significant after adjusting for confounding factors. Moreover, a significant association between obesity GRS and HOMA‐IR was observed in subjects with abdominal obesity. The present results indicate that a predisposition to obesity may affect IR in the Korean population and that abdominal fat may alter or modify the genetic effects. Furthermore, the set of obesity‐related genotypes and abdominal fat may play interactive roles in determining the risk of IR.
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Assessment of preimplantation genetic testing for embryo aneuploidies: a SWOT analysis
The recently re‐named preimplantation genetic testing for determining embryo aneuploidies (PGT‐A) is presently very popular although its acceptance by the scientific community is controversial. This approach still encounters drawbacks. This paper uses a SWOT (strengths, weaknesses, opportunities and threats) analysis to discuss salient points to be considered when examining the PGT‐A strategy in order to gather information from a range of perspectives. One of the strength associated with the procedure is represented by an increase in implantation rate although data from the highest level of evidence do not support an increase in cumulative pregnancy rates. The current difficulty in the management of mosaicisms represents a weakness of PGT‐A. The application of the strategy represents an opportunity to favor the single embryo transfer while other advantages such as reduction of time to pregnancy and emotional distress are controversial. Potential important threats, at present still undefined, are represented by the biopsy‐related damage to the blastocyst and the impact on neonatal and long term outcomes.
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Brown adipose tissue remodeling induced by corticosterone in Wistar male rats
New Findings
What is the central question of this study?
Brown adipose tissue is centrally involved in energy metabolism. The aim of this work was to test the hypothesis that glucocorticoids excess disrupts BAT phenotype and function.
What is the main finding and its importance?
This work highlights that glucocorticoids might be an important modulator of brown fat physiology. Furthermore, it suggests a role for brown adipose tissue on pathophysiology of metabolic disturbances induced by glucocorticoid excess.
Abstract
In mammals, brown adipose tissue (BAT) is centrally involved in energy metabolism. To test the hypothesis that glucocorticoids excess disrupts BAT phenotype and function, male Wistar rats were treated with corticosterone in drinking water for 21 days. To confirm induction of glucocorticoid excess and metabolic disturbances, adrenals weight, corticotrophin releasing hormone mRNA levels, corticosterone serum levels, glucose tolerance test and serum triacylglycerol analyses were performed. Adipose tissue deposits were excised, weighed and evaluated by a set of biochemical, histological and molecular procedures, such as: thin‐layer chromatography, histochemistry, immunohistochemistry, quantitative real‐time polymerase chain reaction, high‐resolution oxygraphy, ATP synthesis and enzymatic activity measurements. The approach was successful in induction of glucocorticoid excess and metabolic disturbances. Lower body weight and increased adiposity were observed in corticosterone‐treated rats. Interscapular brown adipose tissue (iBAT) showed higher sensitivity to glucocorticoids than other fat deposits. The treatment induced lipid accumulation, unilocular rearrangement, increased collagen content and decreased innervation in iBAT. Furthermore, expression of Prdm16 (P < 0.05), Ucp1 (P < 0.05) and Slc7a10 (P < 0.05) decreased, while expression of Fasn (P < 0.05) and Lep (P < 0.05) mRNA increased in brown adipose tissue. Also, the levels of UCP1 diminished (P < 0.001, 2.5‐fold). Finally, lower oxygen consumption (P < 0.05), ATP synthesis (P < 0.05) and mitochondrial content (P < 0.05) were observed in iBAT of GCs‐treated rats. Glucocorticoid excess induced an extensive remodeling of interscapular brown adipose tissue, resulting in a white‐like phenotype in association with metabolic disturbances.
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Hepatocyte‐specific and extra‐hepatocyte actions of Perilipin‐2 during fatty liver disease: Benefits of being extra
Oral thermosensing by murine trigeminal neurons: modulation by capsaicin, menthol, and mustard oil
Key points
Orosensory thermal trigeminal afferent neurons respond to cool, warm, and nociceptive hot temperatures with the majority activated in the cool range. Many of these thermosensitive trigeminal orosensory afferent neurons also respond to capsaicin, menthol and/or mustard oil (allyl isothiocyanate, AITC) at concentrations found in foods and spices. There is significant but incomplete overlap between afferent trigeminal neurons that respond to heat and to the above chemesthetic compounds. Capsaicin sensitizes warm trigeminal thermoreceptors and orosensory nociceptors; menthol attenuates cool thermoresponses.
Abstract
When consumed with foods, mint, mustard and chili peppers generate pronounced oral thermosensations. Here we recorded responses in mouse trigeminal ganglion neurons to investigate interactions between thermal sensing and the active ingredients of these plants — menthol, allyl isothiocyanate (AITC), and capsaicin, respectively — at concentrations found in foods and commercial hygiene products. We carried out in vivo confocal calcium imaging of trigeminal ganglia in which neurons express GCaMP3 or GCAMP6s and recorded their responses to oral stimulation with thermal and the above chemesthetic stimuli. In the V3 (oral sensory) region of the ganglion, thermoreceptive neurons accounted for ∼10% of imaged neurons. We categorized them into 3 distinct classes: cool‐responsive and warm‐responsive thermosensors, and nociceptors (responsive only to temperatures ≥43‐45o). Menthol, AITC, and capsaicin also elicited robust calcium responses that differed markedly in their latencies and durations. Most of the neurons that responded to these chemesthetic stimuli were also thermosensitive. Capsaicin and AITC increased the numbers of warm‐responding neurons and shifted the nociceptor threshold to lower temperatures. Menthol attenuated the responses in all classes of thermoreceptors. Our data show that while individual neurons may respond to a narrow temperature range (or even bimodally), taken collectively, the population is able to report on graded changes of temperature. Our findings also substantiate an explanation for the thermal sensations experienced when one consumes pungent spices or mint.
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Oral manifestations in patients and dogs with mucopolysaccharidosis Type VII
Mucopolysaccharidosis Type VII (MPS7, also called β‐glucuronidase deficiency or Sly syndrome; MIM 253220) is an extremely rare autosomal recessive lysosomal storage disease, caused by mutations in the GUSB gene. β‐glucuronidase (GUSB) is a lysosomal hydrolase involved in the stepwise degradation of glucuronic acid‐containing glycosaminoglycans (GAGs). Patients affected with MPS VII are not able to completely degrade glucuronic acid‐containing GAGs, including chondroitin 4‐sulfate, chondroitin 6‐sulfate, dermatan sulfate, and heparan sulfate. The accumulation of these GAGs in lysosomes of various tissues leads to cellular and organ dysfunctions. Characteristic features of MPS VII include short stature, macrocephaly, hirsutism, coarse facies, hearing loss, cloudy cornea, short neck, valvular cardiac defects, hepatosplenomegaly, and dysostosis multiplex. Oral manifestations in patients affected with MPS VII have never been reported. Oral manifestations observed in three patients consist of wide root canal spaces, taurodontism, hyperplastic dental follicles, malposition of unerupted permanent molars, and failure of tooth eruption with malformed roots. The unusual skeletal features of the patients include maxillary hypoplasia, hypoplastic midface, long mandibular length, mandibular prognathism, hypoplastic and aplastic mandibular condyles, absence of the dens of the second cervical vertebra, and erosion of the cortex of the lower border of mandibles. Dogs affected with MPS VII had anterior and posterior open bite, maxillary hypoplasia, premolar crowding, and mandibular prognathism. Unlike patients with MPS VII, the dogs had unremarkable mandibular condyles. This is the first report of oral manifestations in patients affected with MPS VII.
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Effects of emotions on heart rate asymmetry
Abstract
Heart rate asymmetry (HRA) is an index that accounts for an uneven contribution of decelerations and accelerations to the heart rate variability (HRV). Clinical studies indicated that HRA measures have additive clinical value over the more frequently used HRV indexes. Despite the abundance of studies on psychological influences on HRV, little is known whether psychological factors influence HRA. Based on previous research regarding HRA and stress, we expected that negative emotions compared to positive emotions would decrease the contribution of decelerations to HRV. Thirty female participants watched three clips that produced negative emotions, positive emotions, and neutral affect. Besides electrocardiogram, we measured several physiological and behavioral responses to ascertain the affective impact of the clips. Using the RR interval time series, we calculated HRV and HRA indexes. We found that HRA differentiated between positive emotions and negative emotions reactivity. Positive emotions produced a higher number of decelerations in short‐term variability to the total short‐term variability (C1 d) compared to negative emotions. Moreover, C1 d correlated with subjective ratings of affect. In sum, the results of this study indicated that HRA is sensitive to psychological influences. HRA indexes are likely to contribute to a more nuanced physiological differentiation between emotions.
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