Τετάρτη 4 Απριλίου 2018

Subtle Perturbations of the Maize Methylome Reveal Genes and Transposons Silenced by Chromomethylase or RNA-Directed DNA Methylation Pathways

DNA methylation is a chromatin modification that can provide epigenetic regulation of gene and transposon expression. Plants utilize several pathways to establish and maintain DNA methylation in specific sequence contexts. The chromomethylase (CMT) genes maintain CHG (where H = A, C or T) methylation. The RNA-directed DNA methylation (RdDM) pathway is important for CHH methylation. Transcriptome analysis was performed in a collection of Zea mays lines carrying mutant alleles for CMT or RdDM-associated genes. While the majority of the transcriptome was not affected, we identified sets of genes and transposon families sensitive to context-specific decreases in DNA methylation. Many of the genes that are up-regulated in CMT mutant lines have high levels of CHG methylation, while genes that are differentially expressed in RdDM mutants are enriched for having nearby mCHH islands, implicating context-specific DNA methylation in the regulation of expression for a small number of genes. Many genes regulated by CMTs exhibit natural variation for DNA methylation and transcript abundance in a panel of diverse inbred lines. Transposon families with differential expression in the mutant genotypes show few defining features, though several families up-regulated in RdDM mutants are preferentially in endosperm tissue, highlighting the potential importance for this pathway during reproduction. Together, our findings suggest that while the number of genes and transposon families whose expression are reproducibly affected by mild perturbations in context-specific methylation is small, there are distinct patterns for loci impacted by RdDM and CMT mutants.



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Comparative Sonographic and Magnetic Resonance Images of an Acute Pronator Teres Full-Thickness Tear



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Benefits of hippotherapy and horse riding simulation exercise on healthy older adults: a systematic review

To provide an up-to-date research analysis on equine-assisted therapies and horse riding simulation exercise in older adults, and to suggest future directions in clinical practice and research.

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Effects of whole body vibration on tibia strength and structure of competitive adolescent swimmers: A randomized controlled trial

Swimming has no effect on bone mass or structure. Therefore, adolescent swimmers present similar bone strength values when compared to normo-active controls, and lower values when compared to weight-bearing athletes. It thus seems necessary to try to improve bone structure and strength of adolescent swimmers through a weight-bearing intervention in order to reduce the risk of suffering osteoporosis later in life.

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Comparing the Effects of Dual-task Gait Testing in New and Established Ambulators with Lower Extremity Amputations

Gait is a complex process that involves coordinating motor and sensory systems through higher-order cognitive processes. Walking with a prosthesis after lower extremity amputation challenges these processes. However, the factors that influence the cognitive-motor interaction in gait among lower extremity amputees has not been evaluated. To assess the interaction of cognition and mobility, individuals must be evaluated using the dual-task paradigm.

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Genicular Radiofrequency Ablation for the Treatment of Post-Traumatic Knee Pain: A Case Presentation

This is the first reported case presentation utilizing cooled genicular radiofrequency ablation (C-RFA) for the treatment of post-traumatic knee pain. The patient is a 29 year old male who sustained open right femoral and tibial fractures following two motor vehicle collisions. He was deemed too young to undergo TKA by Orthopedic Surgery. It was recommended he trial diagnostic genicular nerve blocks followed by C-RFA. The procedure provided a >50% reduction in average pain with an increase in activity tolerance lasting 9 months.

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Dynamic sonographic visualization of an occult posterior lateral meniscocapsular separation: A case report

Meniscocapsular separation describes detachment of the meniscus from the knee joint capsule. Diagnosis is challenging with conventional examination and imaging methods. We report a case of an 18-year-old female softball catcher with unrevealing MRI despite continued left knee locking and discomfort with deep squatting. Meniscocapsular separation was revealed only on dynamic sonographic exam, where knee flexion revealed a 3.1 mm gap that developed between the capsule and peripheral meniscus. Arthroscopy confirmed the sonographic findings, and repair resulted in complete resolution of symptoms.

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In silico identification and computational characterization of endogenous small interfering RNAs from diverse grapevine tissues and stages

Abstract

Small interfering RNAs (siRNAs) are effectors of regulatory pathways underlying plant development, metabolism, and stress- and nutrient-signaling regulatory networks. The endogenous siRNAs are generally not conserved between plants; consequently, it is necessary and important to identify and characterize siRNAs from various plants. To address the nature and functions of siRNAs, and understand the biological roles of the huge siRNA population in grapevine (Vitis vinifera L.). The high-throughput sequencing technology was used to identify a large set of putative endogenous siRNAs from six grapevine tissues/organs. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed to classify the target genes of siRNA. In total, 520,519 candidate siRNAs were identified and their expression profiles exhibited typical temporal characters during grapevine development. In addition, we identified two grapevine trans-acting siRNA (TAS) gene homologs (VvTAS3 and VvTAS4) and the derived trans-acting siRNAs (tasiRNAs) that could target grapevine auxin response factor (ARF) and myeloblastosis (MYB) genes. Furthermore, the GO and KEGG analysis of target genes showed that most of them covered a broad range of functional categories, especially involving in disease-resistance process. The large-scale and completely genome-wide level identification and characterization of grapevine endogenous siRNAs from the diverse tissues by high throughput technology revealed the nature and functions of siRNAs in grapevine.



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Effect of low-intensity versus high-intensity resistance training on the functioning of the institutionalized frail elderly

Frailty has emerged as an important risk factor for disability. Age-related declines in physical and physiological function lead to increased risk of loss of independence and poor quality of life. Recent evidence has shown the effectiveness of physical exercise programmes in preventing or reversing frailty. The aim of this study was to evaluate changes in the functioning of frail elderly individuals after undergoing resistance training for 3 days a week for 8 weeks. The effectiveness of exercise training was investigated in 48 frail elderly individuals who were randomly assigned to the following intervention groups: high-intensity (HI; n=16; age: 69–96 years) or low-intensity (LI; n=16; age: 77–93 years) strength training groups or a control group (n=16; age: 76–93 years) with no specific exercise programme. Participants were assessed for muscle strength, physical function, activities of daily living, depression and quality of life. The HI group had significantly better results (P0.05). The study showed that LI exercise was as effective as HI exercise for most parameters tested. Exercise training is useful for the prevention or treatment of frailty, as it improves functioning by contributing positively to muscle strength, gait, balance and quality of life. Correspondence to Ulku K. Sahin, MSc, Department of Physical Therapy and Rehabilitation, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey Tel: +90 312 305 1576; fax: +90 312 305 2012; e-mail: ulkuertan@hacettepe.edu.tr Received February 11, 2018 Accepted March 14, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Analysis of sulphur and chlorine induced DNA cytosine methylation alterations in fresh corn ( Zea mays L. saccharata and rugosa ) leaf tissues by methylation sensitive amplification polymorphism (MSAP) approach

Abstract

DNA (cytosine) methylation mechanism is another way through which plants respond to various cues including soil fertility amendments and abiotic stresses, and the mechanism has been used to infer some physiological, biochemical or adaptation processes. Despite numerous studies on global DNA methylation profiling in various crop species, however, researches on fresh corn (Zea mays L. saccharata or rugosa) remain largely unreported. The study aimed at investigating sulphur and chlorine induced DNA methylation changes in the fresh corn leaves of field-grown plants at the milk stage. Methylation sensitive amplification polymorphism (MSAP) technique was used to profile sulphur (S) and chlorine (Cl) induced DNA methylation patterns, levels and polymorphism alterations at the CCGG sites in fresh corn leaves of TDN21, JKN2000 and JKN928 hybrid cultivars. Twelve primer pairs used effectively detected 325 MSAP bands, exhibiting differentially methylated sites in the genomic DNA of all the three cultivars, with control showing higher (48.9–56.3%) type I bands as compared to sulphur (34.8–44.9%) and chlorine (40.9–47.4%) treatment samples. Consequently, total methylation levels were greater in S and Cl treatment samples than control; accounting for 43.7–59.7, 51.1–65.2 and 46.8–55.1% of total sites in TDN21, JKN2000 and JKN928, respectively. Full methylation of the internal cytosine was greater than hemi-methylation. Further, demethylation polymorphic loci significantly exceeded methylation polymorphic loci, being greater in S than Cl and control samples in all cultivars. Sulphur and chlorine have a profound influence on DNA methylation patterns and levels at the milk stage, principally by increasing the demethylation loci in the internal cytosine of the fresh corn genome. We speculate that these methylation alterations play an integral role in photosynthates assimilation and physiochemical pathways regulating quality parameters in kernels, as well as abiotic stress responses in fresh corn.



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Size as an Important Determinant of Chest Blow–induced Commotio Cordis

Purpose Commotio cordis is sudden cardiac death caused by a relatively innocent blow to the left chest wall. Adolescents account for the majority of the cases; whether this is due to the higher frequency of adolescents playing ball sports or whether there is some maturational reduction of risk is not known. Methods In a swine model of commotio cordis, the effect of body weight/size (directly related to age) to the susceptibility of chest impact induced ventricular fibrillation (VF) is examined. Methods Ball impacts were delivered at escalating velocities from 48.3 to 96.9 km/hr (30 to 60 mph) to 128 swine ranging from 5 to 54 kg. Results VF occurred in 29% of impacts to the smallest animals compared to 34% in 14-23.9 kg group, 27% in 24-33.9 kg group, 30% in 34-43 kg group and 15% in the 44-54 kg animals. The highest weight group was associated with a significantly lower incidence of VF compared to other weights (p = 0.002). In a multivariate logistic regression analysis, controlling for repeated measures, 4 variables predicted VF: body weight (p=0.0008), velocity (p 44 kg have a lower susceptibility. An increase in size of the individual, rather than reduced play of ball sports is the likely reason for the decreased commotio cordis incidence in older individuals. Address for Correspondence: Mark S. Link, MD, UTSouthwestern Medical Center, 5939 Harry Hines BLVD, POB 1, Dallas, TX 75390, Email: mark.link@UTSouthwestern.edu Study supported by the National Operating Committee on Standards for Athletic Equipment (NOCSAE), Overland Park, KS. Mark S Link has research support from NOCSAE. No other author has any disclosures. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 14 March 2018 © 2018 American College of Sports Medicine

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Physiological and Functional Alterations after Spaceflight and Bed Rest

Introduction Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits. Methods A test battery comprised of 7 functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 days of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included Control and Exercise groups to examine the effects of exercise during bed rest. Results Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased heart rate to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function, however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects. Conclusion Bed rest data indicates that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the Exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular function, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is required to maintain functional performance. Corresponding Author: Jacob J. Bloomberg, Ph.D. Neuroscience Laboratories, Biomedical Research and Environmental, Sciences Division, NASA-Johnson Space Center, Mail Code: SK272, Houston, TX 77058, USA. jacob.j.bloomberg@nasa.gov There are no conflicts of interest for all authors. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. This study was conducted with the support from NASA's Human Research Program and the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences, National Institutes of Health. Accepted for Publication: 7 February 2018 © 2018 American College of Sports Medicine

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Effects of Branched-Chain Amino Acid Supplementation on Spontaneous Seizures and Neuronal Viability in a Model of Mesial Temporal Lobe Epilepsy

Background: The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine have recently emerged as a potential novel treatment for medically refractory epilepsy. Blood-derived BCAAs can readily enter the brain, where they contribute to glutamate biosynthesis and may either suppress or trigger acute seizures. However, the effects of BCAAs on chronic (ie, spontaneous recurrent) seizures and epilepsy-associated neuron loss are incompletely understood. Materials and Methods: Sixteen rats with mesial temporal lobe epilepsy were randomized into 2 groups that could drink, ad libitum, either a 4% solution of BCAAs in water (n=8) or pure water (n=8). The frequency and relative percent of convulsive and nonconvulsive spontaneous seizures were monitored for a period of 21 days, and the brains were then harvested for immunohistochemical analysis. Results: Although the frequency of convulsive and nonconvulsive spontaneous recurrent seizures over a 3-week drinking/monitoring period were not different between the groups, there were differences in the relative percent of convulsive seizures in the first and third week of treatment. Moreover, the BCAA-treated rats had over 25% fewer neurons in the dentate hilus of the hippocampus compared with water-treated controls. Conclusions: Acute BCAA supplementation reduces seizure propagation, whereas chronic oral supplementation with BCAAs worsens seizure propagation and causes neuron loss in rodents with mesial temporal lobe epilepsy. These findings raise the question of whether such supplementation has a similar effect in humans. T.E. and R.D. are supported by grants from the National Institutes of Health (NIH): NINDS R01 NS070824. S.E.G. is supported by grants from the Foundation for Anesthesia Education and Research (FAER) and the NIH: T32 GM086287. This work was also made possible by a grant from the National Center for Advancing Translational Sciences (NCATS; UL1 TR000142), a component of the NIH and the NIH Roadmap for Medical Research. The authors have no conflicts of interest to disclose. Address correspondence to: Tore Eid, MD, PhD, Department of Laboratory Medicine, 330 Cedar St., P.O. Box 208035, Yale School of Medicine, New Haven, CT 06520 (e-mail: tore.eid@yale.edu). Received November 28, 2017 Accepted February 23, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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New Zealand blackcurrant extract enhances fat oxidation during prolonged cycling in endurance-trained females

Abstract

Purpose

New Zealand blackcurrant (NZBC) extract has previously been shown to increase fat oxidation during prolonged exercise, but this observation is limited to males. We examined whether NZBC intake also increases fat oxidation during prolonged exercise in females, and whether this was related to greater concentrations of circulating fatty acids.

Methods

In a randomised, crossover, double-blind design, 16 endurance-trained females (age: 28 ± 8 years, BMI: 21.3 ± 2.1 kg·m−2, VO2max: 43.7 ± 1.1 ml·kg−1·min−1) ingested 600 mg·day−1 NZBC extract (CurraNZ) or placebo (600 mg·day−1 microcrystalline cellulose) for 7 days. On day 7, participants performed 120 min cycling at 65% VO2max, using online expired air sampling with blood samples collected at baseline and at 15 min intervals throughout exercise for analysis of glucose, NEFA and glycerol.

Results

NZBC extract increased mean fat oxidation by 27% during 120 min moderate-intensity cycling compared to placebo (P = 0.042), and mean carbohydrate oxidation tended to be lower (P = 0.063). Pre-exercise, plasma NEFA (P = 0.034) and glycerol (P = 0.051) concentrations were greater following NZBC intake, although there was no difference between conditions in the exercise-induced increase in plasma NEFA and glycerol concentrations (P > 0.05). Mean fat oxidation during exercise was moderately associated with pre-exercise plasma NEFA concentrations (r = 0.45, P = 0.016).

Conclusions

Intake of NZBC extract for 7 days elevated resting concentrations of plasma NEFA and glycerol, indicative of higher lipolytic rates, and this may underpin the observed increase in fat oxidation during prolonged cycling in endurance-trained females.



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Make it easier! Evaluation of the ‘vagal-sympathetic effect’ in different conditions with R–R intervals monitoring



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Authors’ reply to Medeiros et al.: Make it easier! Evaluation of the ‘vagal-sympathetic effect’ in different conditions with R–R intervals monitoring



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Differential expression of primary pair-rule genes during bidirectional regeneration in Perionyx excavatus

Abstract

The earthworm Perionyx excavatus is a species highly capable of bidirectional regeneration. Pair-rule genes are thought to have an ancestral function in arthropod segmentation. However, orthologs in annelids (i.e. Capitella teleta) do not exhibit segmental expression in the ectoderm or mesoderm. Their role in regeneration is currently unclear. Here, we report the expression profile of primary pair-rule genes (Pex-EvxA, Pex-EvxB, Pex-RuntA, Pex-RuntB, Pex-Hes1A, Pex-Hes1B, Pex-Hes4A, and Pex-Hey) found in P. excavatus using semi-quantitative reverse transcription-polymerase chain reaction. Our results indicated these genes showed variable expression during bidirectional regeneration. Six of these genes might play diverse and potentially critical roles in head and/or tail regeneration.



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Economic Impact of Multisystemic Therapy for Child Abuse and Neglect

Abstract

This study evaluated the economics of Multisystemic Therapy for Child Abuse and Neglect (MST-CAN) by applying the Washington State Institute for Public Policy (WSIPP) cost-benefit model to data from a randomized effectiveness trial with 86 families (Swenson et al. in JFP 24:497–507, 2010b). The net benefit of MST-CAN, versus enhanced outpatient treatment, was $26,655 per family at 16 months post-baseline. Stated differently, every dollar spent on MST-CAN recovered $3.31 in savings to participants, taxpayers, and society at large. Policymakers and public service agencies should consider these findings when making investments into interventions for high-need families involved with child protective services.



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Oral Health Practices, Beliefs and Dental Service Utilization of Albanian Immigrants in Milwaukee, Wisconsin: A Pilot Study

Abstract

There is limited information on the oral health of Albanian immigrant population residing in the U.S. This creates a hinderance to developing and implementing appropriate dental care programs for the population. This study investigated oral health practices, beliefs, dental visits and associated factors of Albanian adults living in Milwaukee, Wisconsin. Purposive and snowball sampling methods were employed. Self-administered questionnaires were used to collect data on oral health practices, beliefs, dental visits and socio-demographic information. Descriptive and multivariable logistics regression were conducted. Overall, 266 adults were recruited, 54% male, 56% have lived 10 or more years in the U.S., 95% rated their oral health as excellent/good and 87% reported having a dental visit in the last year. Age, ability to speak English, having a usual source of dental care, and reporting excellent/good oral health were associated with having a dental visit in the last year. A substantial number of Albanians adult reported a dental visit in the last year and those that did not write or read in English had lower odds of reporting a dental visit.



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Human evolution: Archaic admixture with Denisovans

Human evolution: Archaic admixture with Denisovans

Human evolution: Archaic admixture with Denisovans, Published online: 04 April 2018; doi:10.1038/nrg.2018.18

Human evolution: Archaic admixture with Denisovans

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Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees

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Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Giuseppe Granata, Riccardo Di Iorio, Roberto Romanello, Francesco Iodice, Stanisa Raspopovic, Francesco Petrini, Ivo Strauss, Giacomo Valle, Thomas Stieglitz, Paul Čvančara, David Andreu, Jean-Louis Divoux, David Giraud, Loic Wauters, Arthur Hiairrassary, Winnie Jensen, Silvestro Micera, Paolo Maria Rossini
ObjectiveThe aim of the paper is to objectively demonstrate that amputees implanted with intraneural interfaces are truly able to feel a sensation in the phantom hand by recording "phantom" somatosensory evoked potentials from the corresponding brain areas.MethodsWe implanted four transverse intrafascicular multichannel electrodes, available with percutaneous connections to a multichannel electrical stimulator, in the median and ulnar nerves of two left trans-radial amputees. Two channels of the implants that were able to elicit sensations during intraneural nerve stimulation were chosen, in both patients, for recording somatosensory evoked potentials.ResultsWe recorded reproducible evoked responses by stimulating the median and the ulnar nerves in both cases. Latencies were in accordance with the arrival of somatosensory information to the primary somatosensory cortex.ConclusionOur results provide evidence that sensations generated by intraneural stimulation are truly perceived by amputees and located in the phantom hand. Moreover, our results strongly suggest that sensations perceived in different parts of the phantom hand result in different evoked responses.SignificanceSomatosensory evoked potentials obtained by selective intraneural electrical stimulation in amputee patients are a useful tool to provide an objective demonstration of somatosensory feedback in new generation bidirectional prostheses.



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Rapid exhaustion of auditory neural conduction in a prototypical mitochondrial disease, Friedreich ataxia

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Publication date: June 2018
Source:Clinical Neurophysiology, Volume 129, Issue 6
Author(s): Fabrice Giraudet, Perrine Charles, Thierry Mom, Odile Boespflug-Tanguy, Alexandra Dürr, Paul Deltenre, Paul Avan
ObjectivesIn patients with Friedreich ataxia (FRDA), mitochondrial failure leads to impaired cellular energetics. Since many FRDA patients have impaired hearing in noise, we investigated the objective consequences on standard auditory brainstem-evoked responses (ABRs).MethodsIn 37 FRDA patients, among whom 34 with abnormal standard ABRs, hearing sensitivity, speech-in-noise intelligibility and otoacoustic emissions were controlled. ABR recordings were split into four consecutive segments of the total time frame used for data collection, thus allowing the dynamics of ABR averaging to be observed.ResultsMost ears showed features of an auditory neuropathy spectrum disorder with flattened ABRs and impaired speech-in-noise intelligibility contrasting with near-normal hearing sensitivity and normal preneural responses. Yet split-ABRs revealed short-lived wave patterns in 26 out of 68 ears with flattened standard ABRs (38%). While averaging went on, the pattern of waves shifted so that interwave latencies increased by 35% on average.ConclusionsIn FRDA, the assumption of stationarity used for extracting standard ABRs is invalid. The preservation of early split-ABRs indicates no short-term dyssynchrony of action potentials. A large decrease in conduction velocity along auditory neurons occurs within seconds, attributed to fast energetic failure.SignificanceThis model of metabolic sensory neuropathy warns against exposure of metabolically-impaired patients to sustained auditory stimulation.



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Radon-222 related influence on ambient gamma dose

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Publication date: September 2018
Source:Journal of Environmental Radioactivity, Volume 189
Author(s): A. Melintescu, S.D. Chambers, J. Crawford, A.G. Williams, B. Zorila, D. Galeriu
Ambient gamma dose, radon, and rainfall have been monitored in southern Bucharest, Romania, from 2010 to 2016. The seasonal cycle of background ambient gamma dose peaked between July and October (100–105 nSv h−1), with minimum values in February (75–80 nSv h−1), the time of maximum snow cover. Based on 10 m a.g.l. radon concentrations, the ambient gamma dose increased by around 1 nSv h−1 for every 5 Bq m−3 increase in radon. Radon variability attributable to diurnal changes in atmospheric mixing contributed less than 15 nSv h−1 to the overall variability in ambient gamma dose, a factor of 4 more than synoptic timescale changes in air mass fetch. By contrast, precipitation-related enhancements of the ambient gamma dose were 15–80 nSv h−1. To facilitate routine analysis, and account in part for occasional equipment failure, an automated method for identifying precipitation spikes in the ambient gamma dose was developed. Lastly, a simple model for predicting rainfall-related enhancement of the ambient gamma dose is tested against rainfall observations from events of contrasting duration and intensity. Results are also compared with those from previously published models of simple and complex formulation. Generally, the model performed very well. When simulations underestimated observations the absolute difference was typically less than the natural variability in ambient gamma dose arising from atmospheric mixing influences. Consequently, combined use of the automated event detection method and the simple model of this study could enable the ambient gamma dose "attention limit" (which indicates a potential radiological emergency) to be reduced from 200 to 400% above background to 25–50%.



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Human evolution: Archaic admixture with Denisovans



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