Vertebrate behaviours are produced by neuroglial networks that evolved from a common set of ancestral (homologous) traits, as well as unique specializations that created opportunities for new behaviours and exploitation of novel environments.
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Our purpose was to study the effects of aerobic, resistance, and mixed (aerobic and resistance) training programs on blood pressure, both at rest and during submaximal exercise in healthy people.
We randomized 39 physically active, healthy participants into aerobic, resistance, and mixed (aerobic and resistance) exercise groups, and a control group. The exercise groups trained for 60 min three times/week for 6 weeks, and a submaximal cycle ergometer test was performed before and after training, and 3 weeks after detraining. Continuous blood pressure was determined before and during the test.
At the submaximal test, both systolic and diastolic blood pressures decreased significantly (p < 0.05) after detraining in the exercise groups. However, between pre-training and detraining, we found significant reductions at rest only in the mixed exercise group (p < 0.05).
Although all exercise had similar effects on blood pressure during submaximal exercise, the mixed aerobic and resistance exercise may be optimal for blood pressure reduction, by the addition of diverse physiological pathways.
Our aim was to compare the effects of a single exercise training mode (resistance exercise) with a combined exercise training (resistance and plyometric exercise) mode on satellite cell activity and anabolic signaling at the molecular level.
Eighteen male weight lifters (20 ± 4 years, BMI 27 ± 6 kg/m2) were randomly assigned to either a series of resistance exercise or a series of combined exercise group. The intensity of the exercise was set at 60% of their 1 RM weight and subjects completed three sets each of six repetitions. The combined exercise group performed three different types of resistance exercise alternating with three different types of plyometric exercise, whereas the resistance exercise group performed only the three different types of resistance exercise which was repeated twice. Muscle biopsies were obtained the vastus lateralis muscle immediately before and 3 h after one bout of exercise.
Exercise induced increases in satellite cell activation and myofibrillar protein synthesis following both exercise modes, but the resistance exercise group was superior compared to the combined exercise group in satellite cell activity expressed by Ki67/CD56 (165 vs 232%) and PI3K/Akt protein expression (121 vs 157%), mTOR protein expression (117 vs 288%), p70S6K protein expression (253 vs 809%), and 4E-BP1 protein expression (70 vs 139%) of anabolic signaling pathway.
These results suggest that the previous findings showing a greater effect of combined as opposed to a single exercise mode could be the effect of a greater training volume rather than a true-training effect of a combined exercise program.
The mechanisms governing the control of musculoskeletal redundancy remain to be fully understood. The hand is highly redundant, and shows different functional role of extensors according to its configuration for a same functional task of finger flexion. Through intermuscular coherence analysis combined with hand musculoskeletal modelling during maximal isometric hand contractions, our aim was to better understand the neural mechanisms underlying the control of muscle force coordination and agonist–antagonist co-contraction.
Thirteen participants performed maximal isometric flexions of the fingers in two configurations: power grip (Power) and finger-pressing on a surface (Press). Hand kinematics and force/moment measurements were used as inputs in a musculoskeletal model of the hand to determine muscular tensions and co-contraction. EMG–EMG coherence analysis was performed between wrist and finger flexors and extensor muscle pairs in alpha, beta and gamma frequency bands.
Concomitantly with tailored muscle force coordination and increased co-contraction between Press and Power (mean difference: 48.08%; p < 0.05), our results showed muscle-pair-specific modulation of intermuscular coupling, characterized by pair-specific modulation of EMG–EMG coherence between Power and Press (p < 0.05), and a negative linear association between co-contraction and intermuscular coupling for the ECR/FCR agonist–antagonist muscle pair (r = − 0.65; p < 0.05).
This study brings new evidence that pair-specific modulation of EMG–EMG coherence is related to modulation of muscle force coordination during hand contractions. Our results highlight the functional importance of intermuscular coupling as a mechanism contributing to the control of muscle force synergies and agonist–antagonist co-contraction.
Increased variability in cerebral blood flow (CBF) predisposes to adverse cerebrovascular events. Oscillations in arterial blood pressure and PaCO2 induce CBF variability. Less is known about how heart rate (HR) variability affects CBF. We experimentally reduced respiration-induced HR variability in healthy subjects, hypothesizing that CBF variability would increase.
Internal carotid artery (ICA) blood velocity was recorded by Doppler ultrasound in ten healthy subjects during baseline, control-mode, non-invasive mechanical ventilation (NIV), i.e., with fixed respiratory rate, hypovolemia induced by lower body negative pressure, and combinations of these. ICA beat volume (ICABV) and ICA blood flow (ICABF) were calculated. HR, mean arterial blood pressure (MAP), respiratory frequency (RF), and end-tidal CO2 were recorded. Integrals of power spectra at each subject's RF ± 0.03 Hz were used to measure variability. Phase angle/coherence measured coupling between cardiovascular variables.
Control-mode NIV reduced HR variability (−56%, p = 0.002) and ICABV variability (−64%, p = 0.006) and increased ICABF variability (+140%, p = 0.002) around RF. NIV + hypovolemia reduced variability in HR and ICABV by 70–80% (p = 0.002) and doubled ICABF variability (p = 0.03). MAP variability was unchanged in either condition. Respiration-induced HR and ICABV oscillations were in inverse phase and highly coherent (coherence >0.9) during baseline, but this coherence decreased during NIV, in normovolemia and hypovolemia (p = 0.01).
Controlling respiration in awake healthy humans reduced HR variability and increased CBF variability in hypovolemia and normovolemia. We suggest respiration-induced HR variability to be a mechanism in CBF regulation. Maintaining spontaneous respiration in patients receiving ventilatory support may be beneficial also for cerebral circulatory purposes.
This study aimed to examine the reliability of extended field-of-view (EFOV) ultrasound imaging to evaluate the cross-sectional area (CSA) and echo intensity of abdominal skeletal muscles.
Twenty-seven healthy young males (age 18.6 ± 1.0 years, body mass index 20.9 ± 2.8 kg/m2, waist circumference 75.0 ± 7.9 cm, body fat 16.6 ± 5.9%) visited the laboratory on 2 days. EFOV ultrasound images of the rectus abdominis, abdominal oblique, and erector spinae muscles were acquired at the height of the third lumbar vertebra with the subject lying on a bed. We then analyzed CSA and echo intensity using ImageJ software and calculated intra-class correlation coefficients (ICC) and the standard error of measurement (SEM).
No significant differences (p = 0.149–0.679) were observed in CSA or echo intensity values for each skeletal muscle between days. ICC and SEM values in CSA for each skeletal muscle ranged between 0.944 and 0.958 and 4.9% and 7.3%, respectively. The corresponding values for echo intensity were 0.851–0.945 for ICC and 5.3–9.7% for SEM.
The present results indicate that EFOV ultrasound imaging has high repeatability for measuring CSA and echo intensity of abdominal skeletal muscle groups in healthy college-aged males.
To compare the effects of self-paced high-intensity interval and continuous cycle training on health markers in premenopausal women.
Forty-five inactive females were randomised to a high-intensity interval training (HIIT; n = 15), continuous training (CT; n = 15) or an inactive control (CON; n = 15) group. HIIT performed 5 × 5 min sets comprising repetitions of 30-s low-, 20-s moderate- and 10-s high-intensity cycling with 2 min rest between sets. CT completed 50 min of continuous cycling. Training was completed self-paced, 3 times weekly for 12 weeks.
Peak oxygen uptake (16 ± 8 and 21 ± 12%), resting heart rate (HR) (−5 ± 9 and −4 ± 7 bpm) and visual and verbal learning improved following HIIT and CT compared to CON (P < 0.05). Total body mass (−0.7 ± 1.4 kg), submaximal walking HR (−3 ± 4 bpm) and verbal memory were enhanced following HIIT (P < 0.05), whereas mental well-being, systolic (−5 ± 6 mmHg) and mean arterial (−3 ± 5 mmHg) blood pressures were improved following CT (P < 0.05). Participants reported similar levels of enjoyment following HIIT and CT, and there were no changes in fasting serum lipids, fasting blood [glucose] or [glucose] during an oral glucose tolerance test following either HIIT or CT (P > 0.05). No outcome variable changed in the CON group (P > 0.05).
Twelve weeks of self-paced HIIT and CT were similarly effective at improving cardiorespiratory fitness, resting HR and cognitive function in inactive premenopausal women, whereas blood pressure, submaximal HR, well-being and body mass adaptations were training-type-specific. Both training methods improved established health markers, but the adaptations to HIIT were evoked for a lower time commitment.
Cross-education (CE) of strength is a well-known phenomenon whereby exercise of one limb can induce strength gains in the contralateral untrained limb. The only available meta-analyses on CE, which date back to a decade ago, estimated a modest 7.8% increase in contralateral strength following unilateral training. However, in recent years new evidences have outlined larger contralateral gains, which deserve to be systematically evaluated. Therefore, the aim of this meta-analysis was to appraise current data on CE and determine its overall magnitude of effect.
Five databases were searched from inception to December 2016. All randomized controlled trials focusing on unilateral resistance training were carefully checked by two reviewers who also assessed the eligibility of the identified trials and extracted data independently. The risk of bias was assessed using the Cochrane Risk-of-Bias tool.
Thirty-one studies entered the meta-analysis. Data from 785 subjects were pooled and subgroup analyses by body region (upper/lower limb) and type of training (isometric/concentric/eccentric/isotonic–dynamic) were performed. The pooled estimate of CE was a significant 11.9% contralateral increase (95% CI 9.1–14.8; p < 0.00001; upper limb: + 9.4%, p < 0.00001; lower limb: + 16.4%, p < 0.00001). Significant CE effects were induced by isometric (8.2%; p = 0.0003), concentric (11.3%; p < 0.00001), eccentric (17.7%; p = 0.003) and isotonic–dynamic training (15.9%; p < 0.00001), although a high risk of bias was detected across the studies.
Unilateral resistance training induces significant contraction type-dependent gains in the contralateral untrained limb. Methodological issues in the included studies are outlined to provide guidance for a reliable quantification of CE in future studies.
(1) To examine the comparability, i.e., discriminatory power, in a preschooler test (PREFIT 20-m shuttle-run test) and the 20mSRT-Original in 5–6-year-olds; (2) to provide an equation to estimate VO2max from the 20mSRT-PREFIT.
138 participants aged 5–6 years performed the 20mSRT-PREFIT and the 20mSRT-Original in a counterbalanced order. Total test duration, completed stages, maximum speed and maximum heart rate were registered.
Participants finished stages from 2–10 in the 20mSRT-PREFIT, whereas stages 1–5 were completed in the 20mSRT-Original and a null was registered, showing the original version a lower discriminatory power. We also observed that the higher the cardiorespiratory fitness level the more comparable were the tests, i.e., − 0.04 km h−1 difference between tests in the fittest participants (i.e., maximum speed ≥ 9.5 km h−1). Using the original equation proposed by Leger and colleagues in 1988 and based on the estimation regression of maximum speed in the 20mSRT-Original from the PREFIT version, we computed a new equation to estimate VO2max from the 20mSRT-PREFIT: Y = 44.657 + 1.795X 1 − 2.601X 2 + 0.0852X 1X 2 (r = 0.77; r 2 = 0.59; SEE = 1.25 ml kg−1 min−1 or 2.59% of estimated mean VO2max = 48.38 ml kg−1 min−1), where X 1 is the 20mSRT-PREFIT maximum speed (km h−1) and X 2 is the age of participants. The 20mSRT-PREFIT resulted in a significantly higher maximum heart rate than the 20mSRT-Original.
The 20mSRT-PREFIT has higher discriminatory power than the 20mSRT-Original. Our study provides for the first time an opportunity to estimate VO2max in preschoolers and children based on the 20mSRT-PREFIT maximum speed and the age of participants.
Exercise-induced muscle damage (EIMD) has been shown to reduce endurance exercise performance. This study examined the effects of EIMD on critical torque (CT) and the sum of the torque integral above CT during (∫T total) during a 5-min all-out, intermittent isometric knee extension exercise.
CT was determined in eight participants prior to and 48-h following EIMD. EIMD was induced using electrically stimulated eccentric knee extensions until maximal voluntary strength (MVC) was reduced by 40%. EIMD was assessed by changes in MVC and ratings of muscle soreness using a VAS scale. EMG and near-infrared spectroscopy (NIRS) were collected from the vastus lateralis and vastus medialis, respectively, during the CT test to assess neuromuscular electrical activity and microvascular circulation.
MVC decreased 22% (p = 0.006) and soreness increased from 2.1 ± 1.9 to 50.4 ± 31.5 mm (p = 0.002) 48-h following eccentric exercise. CT declined from 61.6 ± 17.8 to 52.0 ± 14.1 Nm (−14%; p = 0.005) post-EIMD. ∫T total declined 33% (p = 0.0006) post-EIMD. No changes were observed in neuromuscular electrical activity (p = 0.95 for EMG RMS and p = 0.57 for EMG median frequency) or any parameter of microvascular circulation (p = 0.60 for tissue saturation index, p = 0.27 for total hemoglobin and myoglobin, p = 0.51 for oxyhemoglobin, and p = 0.26 for deoxyhemoglobin) between conditions.
Our finding that EIMD-reduced CT may explain the decrements in endurance performance following EIMD observed in the previous studies. The disproportionate reduction in ∫T total compared to MVC and CT is suggestive of a more rapid depletion of anaerobic energy stores and/or accumulation of metabolic by-products leading to fatigue following EIMD.
The performance and physiological effects of isomaltulose and maltodextrin consumed intermittently during prolonged soccer-specific exercise were investigated.
University soccer players (n = 22) performed 120 min of intermittent exercise while consuming 8% carbohydrate–electrolyte drinks (equivalent to ~ 20 g h−1) containing maltodextrin (Glycaemic Index: 90–100), isomaltulose (Glycaemic Index: 32) or a carbohydrate-energy-free placebo in a manner replicating the practices of soccer players (i.e., during warm-up and half-time). Physical (sprinting, jumping) and technical (shooting, dribbling) performance was assessed.
Blood glucose and plasma insulin (both P < 0.001) concentrations varied by trial with isomaltulose maintaining > 13% higher blood glucose concentrations between 75 and 90 min versus maltodextrin (P < 0.05). A decline in glycaemia at 60 min in maltodextrin was attenuated with isomaltulose (−19 versus −4%; P = 0.015). Carbohydrates attenuated elevations in plasma epinephrine concentrations (P < 0.05), but isomaltulose proved most effective at 90 and 120 min. Carbohydrates did not attenuate IL-6 increases or reductions in physical or technical performances (all P > 0.05). Ratings of abdominal discomfort were influenced by trial (P < 0.05) with lower values for both carbohydrates compared to PLA from 60 min onwards.
Although carbohydrates (~ 20 g h−1) did not attenuate performance reductions throughout prolonged soccer-specific exercise, isomaltulose maintained higher blood glucose at 75–90 min, lessened the magnitude of the exercise-induced rebound glycaemic response and attenuated epinephrine increases whilst maintaining similar abdominal discomfort values relative to maltodextrin. When limited opportunities exist to consume carbohydrates on competition-day, low-glycaemic isomaltulose may offer an alternative nutritional strategy for exercising soccer players.
We investigated the combined effect of cardiorespiratory fitness and the clustered score of inflammatory biomarkers (InflaScore) on the cardiometabolic risk score in adolescents.
This is a cross-sectional analysis with 529 adolescents (267 girls) aged 12–18 years. The shuttle run test was used to assess cardiorespiratory fitness. Continuous scores of clustered inflammatory biomarkers (high sensitivity C-reactive protein, complement factors C3 and C4, fibrinogen and leptin); cardiometabolic risk score (systolic blood pressure, triglycerides, ratio total cholesterol/HDL, HOMA-IR and waist circumference) were computed.
Adolescents with a higher inflammatory profile had the highest cardiometabolic risk score; adolescents with high InflaScore and low fitness had the highest odds of having a high cardiometabolic risk (OR 16.5; 95% CI 7.8–34.5), followed by adolescents with a higher InflaScore but fit (OR 7.5; 95% CI 3.7–8.4), and then by adolescents with a low InflaScore and unfit (OR 3.7; 95% CI 1.6–8.4) when compared to those with low InflaScore and fit, after adjustments for age, sex, pubertal stage, adherence to a Mediterranean dietary pattern and socioeconomic status.
The findings of our study suggest that the combination of high inflammatory state and low cardiorespiratory fitness is synergistically associated with a significantly higher cardiometabolic risk score and thus supports the relevance of early targeted interventions to promote physical activity and preservation as part of primordial prevention.
In the nematode Caenorhabditis elegans, RNA interference (RNAi) triggered by double-stranded RNA (dsRNA) spreads systemically to cause gene silencing throughout the organism and its progeny. We confirm that Caenorhabditis nematode SID-1 orthologs have dsRNA transport activity and demonstrate that the SID-1 paralog CHUP-1 does not transport dsRNA. Sequence comparison of these similar proteins, in conjunction with analysis of loss-of-function missense alleles identifies several conserved 2-7 amino acid microdomains within the extracellular domain that are important for dsRNA transport. Among these missense alleles, we identify and characterize a sid-1 allele, qt95, which causes tissue-specific silencing defects most easily explained as a systemic RNAi export defect. However, we conclude from genetic and biochemical analyses that sid-1(qt95) disrupts only import and speculate that the apparent export defect is caused by the cumulative effect of sequentially impaired dsRNA import steps. Thus, consistent with previous studies, we fail to detect a requirement for sid-1 in dsRNA export, but demonstrate for the first time that SID-1 functions in the intestine to support environmental RNAi.
The common bean is a tropical facultative short day legume that is now grown in tropical and temperate zones. This observation underscores how domestication and modern breeding can change the adaptive phenology of a species. A key adaptive trait is the optimal timing of the transition from the vegetative to the reproductive stage. This trait is responsive to genetically controlled signal transduction pathways and local climatic cues. A comprehensive characterization of this trait can be started by assessing the quantitative contribution of the genetic and environmental factors, and their interactions. This study aimed to locate significant QTL (G) and environmental (E) factors controlling time-to-flower in the common bean, and to identify and measure G x E interactions. Phenotypic data were collected from a bi-parental [Andean x Mesoamerican] recombinant inbred population (F11:14, 188 genotypes) grown at five environmentally distinct sites. QTL analysis using a dense linkage map revealed 12 QTL, five of which showed significant interactions with the environment. Dissection of G x E interactions using a linear mixed-effect model revealed that temperature, solar radiation, and photoperiod play major roles in controlling common bean flowering time directly, and indirectly by modifying the effect of certain QTLs. The model predicts flowering time across five sites with an adjusted r-square of 0.89 and root-mean square error of 2.52 days. The model provides the means to disentangle the environmental dependencies of complex traits, and presents an opportunity to identify in-silico QTL allele combinations that could yield desired phenotypes under different climatic conditions.
Postural changes impair the ability of the cerebrovasculature to buffer against dynamic pressure fluctuations, but the mechanisms underlying this impairment have not been elucidated. We hypothesized that autoregulatory impairment may reflect the impact of static central volume shifts on hemodynamic factors other than arterial pressure (AP). In 14 young volunteers, we assessed the relation of fluctuations in cerebral blood flow (CBF) to those in AP, cardiac output, and CO2, during oscillatory lower body pressure (LBP) (±20 mmHg at 0.01 and 0.06 Hz) at three static levels (-20, 0, and +20 mmHg). Static and dynamic changes in AP, cardiac output, and CO2 explained over 70% of the variation in CBF fluctuations. However, their contributions were different across frequencies and levels: dynamic AP changes explained a substantial proportion of the variation in faster CBF fluctuations (partial R2=0.75, standardized β=0.83, p<0.01), whereas those in CO2 explained the largest portion of the variation in slow fluctuations (partial R2=0.43, β=0.51, p<0.01). There was, however, a major contribution of slow dynamic AP changes during negative (β=0.43), but not neutral (β=0.05) or positive (β=-0.07) LBP. This highlights the differences in contributions of systemic variables to dynamic and static autoregulation, and has important implications for understanding orthostatic intolerance.
Coronary microvascular function and blood flow responses during acute exercise are impaired in the aged heart, but can be restored by exercise training. Coronary microvascular resistance is directly dependent on vascular smooth muscle function in coronary resistance arterioles; therefore, we hypothesized that age impairs contractile function and alters the phenotype of vascular smooth muscle in coronary arterioles. We further hypothesized that exercise training restores contractile function and reverses age-induced phenotypic alterations of arteriolar smooth muscle. Young and old Fischer 344 rats underwent 10 weeks of treadmill exercise training or remained sedentary. At the end of training or cage-confinement, contractile responses, vascular smooth muscle proliferation, and expression of contractile proteins were assessed in isolated coronary arterioles. Both receptor- and non-receptor-mediated contractile function were impaired in coronary arterioles from aged rats. Vascular smooth muscle shifted from a differentiated, contractile phenotype to a secretory phenotype with associated proliferation of smooth muscle in the arteriolar wall. Expression of smooth muscle myosin heavy chain 1 (SM1) was decreased in arterioles from aged rats; whereas expression of phospho-histone H3 and of the synthetic protein, ribosomal protein S6 (rpS6), were increased. Exercise training improved contractile responses, reduced smooth muscle proliferation and expression of rpS6, and increased expression of SM1 in arterioles from old rats. Thus, age-induced contractile dysfunction of coronary arterioles and emergence of a secretory smooth muscle phenotype may contribute to impaired coronary blood flow responses, but arteriolar contractile responsiveness and a younger smooth muscle phenotype can be restored with late-life exercise training.
Clinical assessment of right ventricular (RV) contractility in diseases such as pulmonary arterial hypertension (PAH) has been hindered by the lack of a robust methodology. Here, a novel clinically-viable single-beat method was developed to assess end-systolic elastance (Ees), a measure of RV contractility. We hypothesized that this novel approach reduces uncertainty and interobserver variability in the estimation of the maximum isovolumic pressure (Piso), the key step in single-beat methods. The new method was designed to include a larger portion of the RV pressure data and minimize subjective adjustments by the operator. Data were obtained from right heart catheterization of PAH patients in a multicenter prospective study (Dataset 1) and a single-center retrospective study (Dataset 2). To obtain Piso, three independent observers used an established single-beat method (based on the first derivative of the pressure waveform) and the novel method (based on the second derivative). Interobserver variability analysis included paired t-test, one-way ANOVA, inter-class correlation (ICC) analysis and a modified Bland-Altman analysis. The Piso values obtained from two methods were linearly correlated for both Dataset 1 (R2 = 0.74) and Dataset 2 (R2 = 0.91). Compared to the established method, the novel method resulted in smaller interobserver variability (p < 0.001), nonsignificant differences between observers, and a narrower confidence interval. By reducing uncertainty and interobserved variability, this novel approach may pave the way for more effective clinical management of PAH.
The human arterial vascular tree can be described by multi-compartment models using electrical components. Being first introduced in the 1960s by Noordergraaf and Westerhof these hardware-based approaches required several simplifications. We were able to remove the restrictions using modern software simulation tools and improve overall model quality considerably. While the original Westerhof model consisted of 121 Windkessel elements, the refined model has 711 elements and gives realistic pulse waveforms of the aorta, brachial and radial arteries with realistic blood pressures. Moreover, novel insights concerning the formation of the physiological aortic-radial transfer function were gained. Its being potentially due to the coupling of many small resonant elements gives new impetus to the discussion of arterial pressure wave reflection. The individualized transfer function derived from our improved model incorporates distinct patient characteristics and can potentially be used for estimation of central blood pressure values.
The reason for increased sleep disordered breathing with predominance of central apneas in the elderly is unknown. We hypothesized that the propensity to central apneas is increased in older adults, manifested by a reduced carbon-dioxide (CO2) reserve in older compared to young adults during non-REM (NREM) sleep. Methods: 10 elderly and 15 young healthy adults underwent multiple brief trials of nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation (MV) resulted in hypocapnic central apnea or hypopnea. The CO2 reserve was defined as the difference in PETCO2 between eupnea and the apneic threshold, where the apneic threshold was the end-tidal CO2 (PETCO2) that demarcated the central apnea closest to the eupneic PETCO2. For each MV trial, the hypocapnic ventilatory response (controller gain) was measured as the change in minute ventilation (VE) during the MV trial for a corresponding change in PETCO2. Results: The eupneic PETCO2 was significantly lower in elderly vs. young adults. Compared to young adults, the elderly had a significantly reduced CO2 reserve (-2.6±0.4 vs. -4.1±0.4 mmHg, p=0.01) and a higher controller gain (2.3±0.2 vs. 1.4±0.2 L/min/mmHg, p=0.007), indicating increased chemoresponsiveness in the elderly. Thus, elderly adults are more prone to hypocapnic central apneas owing to increased hypocapnic chemoresponsiveness during NREM sleep.
Publication date: Available online 12 October 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Eunsun Jung, Youngmo Seong, Bohyun Jeon, Hoseok Song, Young-Soo Kwon
Among the four Argonaute family members in mammals, only AGO2 protein retains endonuclease activity and facilitates cleavage of target RNAs base-pairing with highly complementary guide RNAs. Despite the deeply conserved catalytic activity, only a small number of targets have been reported to extensively base pair with cognate miRNAs to be cleaved by AGO2. Here, we analyzed AGO2-bound RNAs by CrossLinking ImmunoPrecipitation (CLIP) of genetically modified cells that express epitope-tagged AGO2 from the native genomic locus. We found that HMGA2 mRNA is cleaved by AGO2 loaded with let-7 and miR-21. In contrast to the generally accepted notion, the base-pairing from the seed region to the cleavage site, rather than perfect or near perfect complementarity, was required for cleavage of the target mRNA in cells. Non-templated addition of nucleotides at the 3′ end of the cleaved RNA was observed, further supporting the AGO2-mediated cleavage. Based on the observation that the limited complementarity is the minimum requirement for cleavage, we found that AGO2-mediated cleavage of targets is more common than previously thought. Our result may explain the vital role of endonuclease activity in controlling miRNA-mediated gene regulation.
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Emotional enhancement of free recall can be context dependent. It is readily observed when emotional and neutral scenes are encoded and recalled together in a "mixed" list, but diminishes when these scenes are encoded separately in "pure" lists. We examined the hypothesis that this effect is due to differences in allocation of attention to neutral stimuli according to whether they are presented in mixed or pure lists, especially when encoding is intentional. Using picture stimuli that were controlled for semantic relatedness, our results contradicted this hypothesis. The amplitude of well-known electrophysiological markers of emotion-related attention—the early posterior negativity (EPN), the late positive potential (LPP), and the slow wave (SW)—was higher for emotional stimuli. Crucially, the emotional modulation of these ERPs was insensitive to list context, observed equally in pure and mixed lists. Although list context did not modulate neural markers of emotion-related attention, list context did modulate the effect of emotion on free recall. The apparent decoupling of the emotional effects on attention and memory, challenges existing hypotheses accounting for the emotional enhancement of memory. We close by discussing whether findings are more compatible with an alternative hypothesis, where the magnitude of emotional memory enhancement is, at least in part, a consequence of retrieval dynamics.
Dipyrone has analgesic, spasmolytic, and antipyretic effects and is used to treat pain. Due to a possible risk of agranulocytosis with the use of dipyrone, it has been banned in a number of countries. The most commonly used data for the use of dipyrone are related to adults. Information relating to the use of dipyrone in children is scarce. Given the potential added value of dipyrone in the treatment of pain, a review of the literature was conducted to obtain more insight into the analgesic efficacy of dipyrone in children as well as the safety of dipyrone in terms of adverse events. A literature search was done for original articles (in English, German, or Spanish language) which met the following criteria: the use of dipyrone for pain and children up to the age of 17 years old. All titles and abstracts retrieved were reviewed, independently, by two of the authors, for their suitability for inclusion. The references of the selected articles were also checked for additional relevant papers. The publications were categorized into case reports, observational studies, or randomized controlled trials. To assess the methodological quality of the studies, the Jadad score was used. In the limited available data, the analgesic efficacy of intravenous dipyrone appears similar to that of intravenous paracetamol. Evidence is lacking to support the claim that dipyrone is equivalent or even superior to Non-Steroid-Anti-Inflammatory-Drugs in pediatric pain. While the absolute risk of agranulocytosis with dipyrone in children, based on available literature, cannot be determined, case reports suggest that this risk is not negligible.
The precise mechanisms governing the central distribution of macromolecules from the cerebrospinal fluid (CSF) to the brain and spinal cord remain poorly understood, despite their importance for physiological processes such as antibody trafficking for central immune surveillance as well as several ongoing intrathecal clinical trials. Here, we clarify how immunoglobulin G (IgG) and smaller single-domain antibodies (sdAb) distribute throughout the whole brain in a size-dependent manner after intrathecal infusion in rats using ex vivo fluorescence and in vivo 3D magnetic resonance imaging. Antibody distribution was characterized by diffusion at the brain surface and widespread distribution to deep brain regions along perivascular spaces of all vessel types, with sdAb accessing 4–7 times greater brain area than IgG. Perivascular transport involved blood vessels of all caliber and putative smooth muscle and astroglial basement membrane compartments. Perivascular access to smooth muscle basement membrane compartments also exhibited size-dependence. Electron microscopy was used to show stomata on leptomeningeal coverings of blood vessels in the subarachnoid space as potential access points for substances in the CSF to enter the perivascular space. Osmolyte co-infusion significantly enhanced perivascular access of the larger antibody from the CSF, with intrathecal 0.75 m mannitol increasing the number of perivascular profiles per slice area accessed by IgG by approximately 50%. Our results reveal potential distribution mechanisms for endogenous IgG, one of the most abundant proteins in the CSF, as well as provide new insights needed to understand and improve drug delivery of macromolecules to the central nervous system via the intrathecal route.
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Impairment of neuromuscular function in neurological disorders leads to reductions in muscle force, which may lower quality of life. Rehabilitation robots that are equipped with sensors are able to quantify th...
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Postural balance and gait training is important for treating persons with functional impairments, however current systems are generally not portable and are unable to train different types of movements.
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The masculine reproductive phenotype varies significantly across vertebrates. As a result, biologists have long recognized that many of the mechanisms that support these phenotypes—particularly the androgenic system—is evolutionarily labile, and thus susceptible to the effects of selection for different traits. However, exactly how androgenic signaling systems vary in a way which results in dramatically different functional outputs, remain largely unclear. We explore this topic here by outlining four key—but non-mutually exclusive—hypotheses that propose how the mechanisms of androgenic signaling might change over time to potentiate the emergence of phenotypical variation in masculine behavior and physiology. We anchor this framework in a review of our own studies of a tropical bird called the golden-collared manakin (Manacus vitellinus), which has evolved an exaggerated acrobatic courtship display that is heavily androgen-dependent. The result is an example of how the cellular basis of androgenic action can be modified to support a unique reproductive repertoire. We end this review by highlighting a broad pathway forward to further pursue the intricate ways by which the mechanisms of hormone action evolve to support processes of adaptation and animal design.
The study aim was to compare the influence of an auditory stimulus (AS) on anticipatory postural adjustments (APAs) between young and older adults during a choice step reaction.
Sixteen young and 19 older adults stepped forward in response to a visual imperative stimulus of an arrow. We used a choice reaction time (CRT) task and a Simon task which consisted of congruent and incongruent conditions. The direction of the presented arrow and its spatial location matched in the congruent condition while they did not in the incongruent condition. The AS was presented randomly and simultaneously with the visual stimulus. Incorrect weight shifts before lifting off the foot, termed APA errors, stepping errors, temporal parameters, and APA amplitudes were analyzed.
The APA error rate was higher in trials with than without AS in all task conditions for the older group, while this increase occurred only in the incongruent condition for the young group. The stepping error rate was also increased in the presence of AS in the incongruent condition for the older group. Reaction times were faster with AS in both groups. The APA amplitude of erroneous APA trials became larger with AS in the incongruent condition for both groups, and this effect appeared greater for the older group.
The effect of AS on APAs is larger in the elderly during a choice step reaction. In the presence of incongruent visual information, this effect becomes even greater, potentially inducing not only APA errors but also stepping errors.
BACKGROUND CONTEXT: The use of occipital condyle screws in occipitocervical fixation is a recent development, and was originally described by Uribe et al. Occipital condyle screw placement is a salvage technique when an occipital plate cannot be placed or fails to provide adequate fixation. Detailed knowledge of the dimensions of the occipital condyle and the surrounding anatomy of the occipitocervical junction is critical when placing occipital condyle screws.
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BACKGROUND CONTEXT: Kinematic magnetic resonance imaging (kMRI) provides multi-positional MRI, multiplanar capability, and excellent soft tissue contrast. Various studies analyzed cervical spine pathologies using kMRI, however there is no study comparing the reliability of kMRI measurement to dynamic plain radiograph.
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BACKGROUND CONTEXT: Proximal junctional kyphosis (PJK) is a difficult complication in adult spinal deformity. While several risk factors for PJK have been identified, there is concern that osteoporotic bone can contribute to the development of PJK. To date, there is no cumulative risk calculation that correlates with PJK development. The Fracture Risk Assessment Tool (FRAX) is a well-validated risk model that predicts the 10-year probability of significant osteoporotic fracture. Because the FRAX tool is a comprehensive osteoporotic fracture risk assessment, we believe that it will be a useful surrogate in predicting the development of PJK after ASD surgery.
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BACKGROUND CONTEXT: Computer-assisted three-dimensional navigation may guide spinal instrumentation. The utility of intraoperative navigation is most evident in minimally-invasive (MIS) and deformity-correcting procedures, where anatomic landmarks are less readily identifiable. A novel optical topographic imaging (OTI) system for spinal navigation has been developed and described separately. While it offers comparable accuracy and significantly faster registration relative to current navigation systems, OTI to date has been applied only to open posterior exposures.
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BACKGROUND CONTEXT: Cervical disc arthroplasty (CDA) is a potential substitute for anterior cervical decompression and fusion (ACDF) with the hope that maintenance of motion may decrease the likelihood of adjacent segment disease and avoid other morbidities associated with cervical fusion. The Bryan® cervical disc has been studied with over 10 years of data currently being reported.
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BACKGROUND CONTEXT: While sagittal correction for adult spinal deformity (ASD) is proven to correlate with improvement in Health-Related Quality of Life scores (HRQOL) using standard instrumentation, data were still sparse regarding simultaneous translation on two rods techniquePatients surgically treated for ADS were enrolled in an international study which aimed to compare long term treatment outcomes of surgical correction of adult spinal deformity by quality of life (QOL) and sagittal alignment indices.
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BACKGROUND CONTEXT: Two independent clinical trials have concluded that cervical disc arthroplasty (CDA) is as safe and effective as anterior cervical discectomy and fusion (ACDF) for treating symptomatic cervical disc disease (SCDD) at one and two levels.
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BACKGROUND CONTEXT: Surgical treatment of spinal deformity in cerebral palsy patients has been found to be very beneficial. Previous studies of surgery in these patients have shown a higher risk of revisions and failures than in AIS patients. Current surgical techniques and implants seem to have decreased both revisions and other complications. We studied the rate of revisions with modern surgical techniques at minimum 5 years.
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BACKGROUND CONTEXT: While cervical disc arthroplasty (CDA) has been used for the treatment of cervical disc disease with radiculopathy or myelopathy, concerns remain about the appropriateness of CDA to treat patients with myelopathy.
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BACKGROUND CONTEXT: Lumbar TDR for DDD is increasingly recommended by leading health technology assessment groups and professional societies as the evidence base expands. NASS recommends coverage for lumbar TDR on the basis of two and five-year data demonstrating that TDR is at least as safe and efficacious as spinal fusion for discogenic back pain. Despite such recommendations, some US payers do not yet cover this technology, citing that lumbar TDR is experimental and investigational, with long-term data needed.
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BACKGROUND CONTEXT: Dysphagia is a common complication in the setting of ACDF surgery. Controversy exists in the literature regarding the effectiveness of local intraoperative corticosteroids (LICs) in reducing postoperative dysphagia. This study aims to evaluate the effectiveness of LICs in decreasing the severity of swallowing difficulty following ACDF.
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BACKGROUND CONTEXT: Surgery is evolving from open to MIS techniques. Anatomic anomalies, or other patient factors such as deformity or degeneration, may affect pedicle screw accuracy, particularly in the two-dimensional visualization system of fluoroscopic-based MIS. Proper screw placement is associated with improved fixation, which has led to use of free hand navigation, and subsequently, robot guidance systems. Presently, robotic systems which differ in their mechanical set-up, have not been adequately compared to traditional MIS techniques.
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BACKGROUND CONTEXT: Dysphagia and dysphonia are the most common complications following anterior cervical discectomy and fusion (ACDF). Fortunately, most post–ACDF dysphagia is mild and transient, but in the limited number of patients who develop severe dysphagia, it will have profound effects on overall health and surgical outcomes. Severe dysphagia places the patient at higher risk for dehydration, malnutrition, social isolation, aspiration, pneumonia and death. Previous studies have demonstrated that intravenous (IV) and local steroids can decrease prevertebral soft-tissue swelling; however, no standardized studies have compared the efficacy of local steroid application to controls during ACDF on postoperative dysphagia and dysphonia.
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BACKGROUND CONTEXT: Current clinical research relies on statistical models to identify independent risk factors of postoperative complications. However, complex interplay between risk factors is rarely accounted for, which can lead to inaccurate patient morbidity and mortality. Neural network is a machine learning classification system inspired by the human brain. Each network contains a large cluster of neurons which collectively but uniquely weigh the importance of input variables. Optimization of each individual neuron allows for the system to "learn" through repetitive epochs and minimizes error.
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BACKGROUND CONTEXT: While recommendations for caudal "end level" in posterior cervical reconstruction remain highly variable, the benefits of routine extension of posterior cervical fusions into the thoracic spine remain unclear.
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BACKGROUND CONTEXT: The United States Food and Drug Administration (FDA) issued a warning in 2008 against the use of recombinant bone morphogenetic protein (BMP). Patient demographics and economic data associated with the insertion of BMP are critical to understanding and improving health care utilization. Given the increasing focus on health care utilization and value-based care, it is essential to understand the demographic and economic data surrounding utilization of BMP.
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BACKGROUND CONTEXT: Degenerative changes in the cervical spine may result in cervical stenosis and spinal cord compression, which can become clinically symptomatic as cervical spondylotic myelopathy. Though cervical spondylotic myelopathy (CSM) can follow various courses, patients commonly exhibit a slow, progressive stepwise decline in their neurological function. The most common manifestation of CSM is gait disturbance. During the human gait cycle, the magnitude and direction of the force each foot imparts on the ground (measured as the ground reaction force [GRF]) varies in a controlled fashion to propel the body's center of mass forward.
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BACKGROUND CONTEXT: Kyphoplasty, a minimally invasive vertebral augmentation procedure for fracture reduction and stabilization, has been used to minimize pain from vertebral compression fractures (VCFs), while also restoring vertebral height and local spinal lordosis. Although several studies have suggested the efficacy of kyphoplasty for the treatment of painful VCFs, kyphoplasty remains a controversial treatment modality for VCFs. Interestingly, no studies have analyzed kyphoplasty in the clinically distinct workers' compensation (WC) population.
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BACKGROUND CONTEXT: Numerous studies have attempted to delineate the normative value for the T1 slope-cervical lordosis (T1S-CL) as a marker for both cervical deformity and as a goal for correction similar to how pelvic incidence-lumbar lordosis (PI-LL) mismatch informs decision making in thoracic lordosis (TL) adult spine deformity (ASD).
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BACKGROUND CONTEXT: Degenerative lumbar spinal stenosis (DLS) is characterized as a narrowing of the spinal canal, compressing the neural elements and leading to symptoms of radiculopathy or neurogenic claudication. Conservative care is commonly recommended for the initial treatment of DLS, but in refractory cases, surgical intervention is considered. During the initial management of patients with DLS, the use of opiates has become increasingly common. Findings from previous studies show that 33%-70% of patients undergoing spine surgery are on opioid therapy despite the evidence that preoperative opioid use has a negative impact on spine surgery outcomes.
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As the primary medical society for the specialty of PM&R, your Academy is focused on moving the specialty and you forward. Academy membership supports initiatives to assist our members with:
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As clinicians working in rehabilitation, we treat patients from various cultural, ethnic, linguistic, and religious backgrounds. Some of these cultural factors may impact the way that information is communicated, goals are negotiated, and medical decisions are made. The terms cultural competence, cultural humility, cultural sensitivity, cultural respect, and, more generally, diversity, often are used to discuss the aspects of practice that address cultural factors in health care delivery. Kleinman and Benson [1] have written eloquently in their article, "Anthropology in the Clinic: The Problem of Cultural Competency and How to Fix It," that culture matters in the clinic, but addressing it cannot be reduced to a technical skill.
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The study by Silver et al [1] in this issue of PM&R is research long overdue. The Harvard group must be commended for shedding a bright light on the important topic of gender disparities in medicine, a phenomenon not unique to physiatry.
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