Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children

Summary

Background

Children often starve for longer than recommended by current preoperative fasting guidelines.

Aims

We studied the effects of implementing a more lenient fasting regimen on the duration of clear fluid fasting, as well as the incidence of extended fasting in children.

Methods

Preoperative duration of clear fluid fasting was recorded for patients scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This group was compared with a cohort in the same unit 1 year after transitioning to a 6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen has been implemented for over a decade was also studied for comparison.

Results

Patients fasting according to the 6-4-2 fasting regimen (n = 66) had a median fasting time for clear fluids of 4.0 h and a 33.3% incidence of fasting more than 6 h. After transitioning to the 6-4-0 fasting regimen (n = 64), median duration of fasting for clear fluids decreased to 1.0 h, and the incidence of fasting more than 6 h decreased to 6.3%. In the second unit (n = 73), median fasting time was 2.2 h and the proportion of patients fasting more than 6 h was 21.9%.

Conclusion

The introduction and implementation of the 6-4-0 fasting regimen reduces median fluid fasting duration and the number of children subjected to extended fasting.

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Biallelic mutations in NALCN: Expanding the genotypic and phenotypic spectra of IHPRF1

Loss-of function mutations in NALCN on chromosome 13q, a sodium leak channel that maintains baseline neuronal excitability, cause infantile hypotonia with psychomotor retardation and characteristic faces 1 (IHPRF1, OMIM #615419). Here, we document two individuals with early onset hypotonia with poor feeding and intellectual disability who were compatible with a diagnosis of IHPRF1. The two patients had bi-allelic mutations in NALCN through two different genetic mechanisms: Patient 1 had bi-allelic splice site mutations, that is c.1267-2A>G, derived from heterozygous parents, while Patient 2 had a partial maternal uniparental isodisomy that harbored a frameshift mutation, that is c.2022_2023delAT, in chromosome 13 that was detected through a dedicated algorithm for homozygosity data mapping in whole exome sequencing. The delineation of the exact pattern of inheritance provided vital information regarding the risk of recurrence. In animal models with Nalcn mutations, two behavioral phenotypes, that are, postnatal dyspnea and sleep disturbance, have been reported. Our observations of the two patients with postnatal dyspnea and one patient with sleep disturbance support an association between these two behavioral phenotypes and NALCN mutations in humans. The routine use of a detection algorithm for homozygosity data mapping might improve the diagnostic yields of next-generation sequencing.

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Novel STRA6 null mutations in the original family described with Matthew–Wood syndrome

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Single suture craniosynostosis: Identification of rare variants in genes associated with syndromic forms

We report RNA-Sequencing results on a cohort of patients with single suture craniosynostosis and demonstrate significant enrichment of heterozygous, rare, and damaging variants among key craniosynostosis-related genes. Genetic burden analysis identified a significant increase in damaging variants in ATR, EFNA4, ERF, MEGF8, SCARF2, and TGFBR2. Of 391 participants, 15% were found to have damaging and potentially causal variants in 29 genes. We observed transmission in 96% of the affected individuals, and thus penetrance, epigenetics, and oligogenic factors need to be considered when recommending genetic testing in patients with nonsyndromic craniosynostosis.

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Congenital limb deficiencies and major associated anomalies in Alberta for the years 1980–2012

There is a wide range of the proportion of congenital anomalies associated with limb deficiencies reported in the literature. This variation is primarily attributed to methodology and classification differences. The distribution of associated anomalies among cases with congenital limb deficiencies in Alberta born between January 1, 1980 and December 31, 2012 is described. Of the 170 cases identified, most were live born (75.3%), male (61.8%), had longitudinal limb deficiencies (78.8%), and had associated anomalies outside the musculoskeletal system (77.6%). Significant associations between the preaxial longitudinal group and the central nervous, gastrointestinal, and cardiovascular systems are reported as well as between the postaxial longitudinal group and congenital hip and foot anomalies. Probable and possible syndrome diagnoses are described for cases with recognized malformation patterns.

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Interdependent feedback regulation of breathing by the carotid bodies and the retrotrapezoid nucleus

Abstract

The retrotrapezoid nucleus, RTN, regulates breathing in a CO₂ and state-dependent manner. RTN neurons are glutamatergic and innervate principally the respiratory pattern generator; they regulate multiple aspects of breathing, including active expiration, and maintain breathing automaticity during non-REM sleep. RTN neurons encode arterial PCO₂ /pH via cell-autonomous and paracrine mechanisms, and via input from other CO₂-responsive neurons. In short, RTN neurons are a pivotal structure for breathing automaticity and arterial PCO₂ homeostasis.

The carotid bodies stimulate the respiratory pattern generator directly and, indirectly, by activating RTN via a neuronal projection originating within the solitary tract nucleus. The indirect pathway operates under normo- or hypercapnic conditions; under respiratory alkalosis (e.g. hypoxia) RTN neurons are silent and the excitatory input from the carotid bodies is suppressed. Also, silencing RTN neurons optogenetically quickly triggers a compensatory increase in carotid body activity. Thus, in conscious mammals, breathing is subject to a dual and interdependent feedback regulation by chemoreceptors. Depending on the circumstance, the activity of the carotid bodies and that of RTN vary in the same or the opposite direction, producing additive or countervailing effects on breathing. These interactions are mediated either via changes in blood gases or by brainstem neuronal connections but their ultimate effect is invariably to minimize arterial PCO₂ fluctuations.

We discuss the potential relevance of this dual chemoreceptor feedback to cardiorespiratory abnormalities present in diseases in which the carotid bodies are hyperactive at rest, e.g. essential hypertension, obstructive sleep apnea and heart failure.

This article is protected by copyright. All rights reserved

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Direct Testing for Allele-Specific Expression Differences Between Conditions

Allelic imbalance (AI) indicates the presence of functional variation in cis regulatory regions. Detecting cis regulatory differences using AI is widespread, yet there is no formal statistical methodology that tests whether AI differs between conditions. Here we present a novel model and formally test differences in AI across conditions using Bayesian credible intervals. The approach tests AI by environment (GxE) interactions and can be used to test AI between environments, genotypes, sex, and any other condition. We incorporate bias into the modeling process. Bias is allowed to vary between conditions, making the formulation of the model general. As gene expression affects power for detection of AI, and as expression may vary between conditions, the model explicitly takes coverage into account. The proposed model has low type I and II error under several scenarios, and is robust to large differences in coverage between conditions. We reanalyze RNA-seq data from a Drosophila melanogaster population panel, with F1 genotypes, to compare levels of AI between mated and virgin female flies and we show that AI*genotype interactions can also be tested. To demonstrate the use of the model to test genetic differences and interactions, a formal test between two F1's was performed, showing the expected 20% difference in AI. The proposed model allows a formal test of GxE and GxG and reaffirms a previous finding, that cis regulation is robust between environments.

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Reference Assembly and Annotation of the Pyrenophora teres f. teres Isolate 0-1

Pyrenophora teres f. teres, the causal agent of net form net blotch (NFNB) of barley, is a destructive pathogen in barley growing regions throughout the world. Typical yield losses due to NFNB range from 10-40%, however, complete loss has been observed on highly susceptible barley lines where environmental conditions favor the pathogen. Currently, genomic resources for this economically important pathogen are limited to a fragmented draft genome assembly and annotation with limited RNA support of the P. teres f. teres isolate 0-1. This research presents an updated 0-1 reference assembly facilitated by long read sequencing and scaffolding with the assistance of genetic linkage maps. Additionally, genome annotation was mediated by RNAseq analysis using three infection time points and a pure culture sample resulting in 11,541 high-confidence gene models. The 0-1 genome assembly and annotation presented here now contains the majority of the repetitive content of the genome. Analysis of the 0-1 genome revealed classic characteristics of a 'two-speed' genome, being compartmentalized into GC-equilibrated and AT-rich compartments. The assembly of repetitive AT-rich regions will be important for future investigation of genes known as effectors which often reside in close proximity to repetitive regions. These effectors are responsible for manipulation of the host defense during infection. This updated P. teres f. teres isolate 0-1 reference genome assembly and annotation provides a robust resource for the examination of the barley-P. teres f. teres host-pathogen co-evolution.

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Restorer-of-Fertility Mutations Recovered in Transposon-Active Lines of S Male-Sterile Maize

Mitochondria execute key pathways of central metabolism and serve as cellular sensing and signaling entities - functions that depend upon interactions between mitochondrial and nuclear genetic systems. This is exemplified in cytoplasmic male sterility type S (CMS-S) of Zea mays, where novel mitochondrial open reading frames are associated with a pollen collapse phenotype, but nuclear restorer-of-fertility (restorer) mutations rescue pollen function. To better understand these genetic interactions, we screened Activator-Dissociation (Ac-Ds), Enhancer/Suppressor-mutator (En/Spm) and Mutator (Mu) transposon-active CMS-S stocks to recover new restorer mutants. The frequency of restorer mutations increased in transposon-active stocks compared to transposon-inactive stocks, but most mutants recovered from Ac-Ds and En/Spm stocks were unstable, reverting upon backcrossing to CMS-S inbred lines. Ten independent restorer mutations recovered from CMS-S Mu transposon stocks were, however, stable upon back crossing. Many restorer mutations condition seed-lethal phenotypes that provide a convenient test for allelism. Eight such mutants recovered in this study included one pair of allelic mutations that were also allelic to the previously described rfl2-1 mutant. Targeted analysis of mitochondrial proteins by immunoblot identified two features that consistently distinguished restored CMS-S pollen from comparably staged, normal-cytoplasm, non-mutant pollen - increased abundance of nuclear-encoded alternative oxidase relative to mitochondria-encoded cytochrome oxidase and decreased abundance of mitochondria-encoded ATP synthase subunit 1 compared to nuclear-encoded ATP synthase subunit 2. CMS-S restorer mutants thus revealed a metabolic plasticity in maize pollen, and further study of these mutants will provide new insights into mitochondrial functions critical to pollen and seed development.

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Tactile Perception of the Roughness of 3D-Printed Textures

Surface roughness is one of the most important qualities in haptic perception. Roughness is a major identifier for judgments of material composition, comfort and friction, and is tied closely to manual dexterity. Some attention has been given to the study of roughness perception in the past, but it has typically focused on non-controllable natural materials or on a narrow range of artificial materials. The advent of high-resolution 3D printing technology provides the ability to fabricate arbitrary 3D textures with precise surface geometry to be used in tactile studies. We used parametric modeling and 3D printing to manufacture a set of textured plates with defined element spacing, shape, and arrangement. Using active touch and two-alternative forced choice protocols, we investigated the contributions of these surface parameters to roughness perception in human subjects. Results indicate that large spatial periods produce higher estimations of roughness (with Weber fraction = 0.19), small texture elements are perceived as rougher than large texture elements of the same wavelength, perceptual differences exist between textures with the same spacing but different arrangements, and roughness equivalencies exist between textures differing along different parameters. We posit that papillary ridges serve as tactile processing units, and neural ensembles encode the spatial profiles of the texture contact area to produce roughness estimates. The stimuli and the manufacturing process may be used in further studies of tactile roughness perception and in related neurophysiological applications.

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The impact of spatio-temporal calcium dynamics within presynaptic active zones on synaptic delay at the frog neuromuscular junction

The spatio-temporal calcium dynamics within presynaptic neurotransmitter release sites (active zones, AZs) at the time of synaptic vesicle fusion is critical for neurotransmitter release. Specifically, the relative arrangement and density of voltage gated calcium channels (VGCCs) as well as the concentration of calcium buffering proteins can play a large role in the timing, magnitude and plasticity of release by shaping the AZ calcium profile. However, a high-resolution understanding of the role of AZ structure on the spatiotemporal calcium dynamics and how that may contribute to functional heterogeneity at an adult synapse is currently lacking. We demonstrate that synaptic delay varies considerably across, but not within, individual synapses at the frog neuromuscular junction (NMJ). To determine how elements of the AZ could contribute to this variability, we performed a parameter search using a spatially realistic diffusion-reaction based computational model of a frog NMJ active zone (Dittrich et al., 2013, Ma et al., 2015). We demonstrate using our model that synaptic delay is sensitive to significant alterations in the spatio-temporal calcium dynamics within an AZ at the time of release caused by manipulations to the density and organization of VGCCs or by the concentration of calcium buffering proteins. Further, our data provide a framework for understanding how AZ organization and structure is important for understanding presynaptic function and plasticity.

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LEARNING-INDUCED MODULATION OF THE EFFECT OF ENDOCANNABINOIDS ON INHIBITORY SYNAPTIC TRANSMISSION

Endocannabinoids are key modulators that regulate central brain functions and behaviours, including learning and memory. At the cellular and molecular levels, endocannabinoids are potent modulators of excitatory and inhibitory synaptic function. Most effects of cannabinoids are thought to be mediated via G protein-coupled cannabinoids receptors. In particular, cannabinoids released from post-synaptic neurons are suggested to act as retrograde messengers, activating presynaptic Type-1 Cannabinoid receptors (CB1R), thereby inducing suppression of synaptic release. Another central mechanism of cannabinoids-induced action requires activation of astroglial CB1R. CB1R are also implicated in self-modulation of cortical neurons. Rats that are trained in a particularly difficult olfactory-discrimination task show a dramatic increased ability to acquire memories of new odors. The memory of the acquired high skill acquisition, termed 'rule learning' or 'learning set' lasts for many months. Using this behavioural paradigm, we show a novel function of action for CB1R; supporting long-term memory by maintaining persistent enhancement of inhibitory synaptic transmission. Long-lasting enhancement of inhibitory synaptic transmission is blocked by a CB1R inverse agonist. This effect is mediated by a novel purely post-synaptic mechanism, obtained by enhancing the single GABAA channel conductance that is PKA-dependent. The significant role that CB1R has in maintaining learning-induced long-term strengthening of synaptic inhibition suggests that endocannabinoids have a key role in maintaining long-term memory by enhancing synaptic inhibition.

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The Modulation of Hippocampal Theta Rhythm by the Vestibular System.

The vestibular system is a sensory system that has evolved over millions of years to detect acceleration of the head, both rotational and translational, in three dimensions. One of its most important functions is to stabilize gaze during unexpected head movement; however, it is also important in the control of posture and autonomic reflexes. Theta rhythm is a 3-12 Hz oscillating EEG signal that is intimately linked to self-motion and is also known to be important in learning and memory. Many studies over the last two decades have shown that selective activation of the vestibular system, either using natural rotational or translational stimulation, or electrical stimulation of the peripheral vestibular system, can induce and modulate theta activity. Furthermore, inactivation of the vestibular system has been shown to significantly reduce theta in freely moving animals, which may be linked to its impairment of place cell function as well as spatial learning and memory. The pathways through which vestibular information modulate theta rhythm remain debatable. However, vestibular responses have been found in the pedunculopontine tegmental nucleus (PPTg) and activation of the vestibular system causes an increase in acetylcholine release into the hippocampus, probably from the medial septum. Therefore, a pathway from the vestibular nucleus complex and/or cerebellum to the PPTg, supramammillary nucleus, posterior hypothalamic nucleus and the septum, to the hippocampus, is likely. The modulation of theta by the vestibular system may have implications for vestibular effects on cognitive function and the contribution of vestibular impairment to the risk of dementia.

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Prefrontal cortical specific differences in behavior and synaptic plasticity between adolescent and adult mice

Adolescence is a highly vulnerable period for the emergence of major neuropsychological disorders and is characterized by decreased cognitive control and increased risk-taking behavior and novelty seeking. The prefrontal cortex (PFC) is involved in the cognitive control of impulsive and risky behavior. Although the PFC is known to reach maturation later than other cortical areas, little information is available regarding the functional changes from adolescence to adulthood in PFC , particularly compared to other primary cortical areas. This study aims to understand the development of PFC-mediated, compared to non PFC-mediated, cognitive functions. Towards this aim, we performed cognitive behavioral tasks in adolescent and adult mice, and subsequently investigated synaptic plasticity in two different cortical areas. Our results showed that adolescent mice exhibit impaired performance in PFC-dependent cognitive tasks compared to adult mice, while their performance in non-PFC dependent tasks is similar to that of adults. Furthermore, adolescent mice exhibited decreased long-term potentiation (LTP) within upper layer synapses of the PFC, but not the barrel cortex (BC). Blocking GABA_A receptor function significantly augments LTP in both the adolescent and adult PFC. No change in intrinsic excitability of PFC pyramidal neurons was observed between adolescent and adult mice. Finally, increased expression of the NR2A subunit of the NMDA receptors is found only in the adult PFC, a change that could underlie the emergence of LTP. In conclusion, our results demonstrate physiological and behavioral changes during adolescence that are specific to the PFC and could underlie the reduced cognitive control in adolescents.

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Perceptual Decisions Based on Previously Learned Information are Independent of Dopaminergic Tone

Both cognitive and motor symptoms in people with Parkinson's disease (PD) arise from either too little or too much dopamine (DA). Akinesia stems from DA neuronal cell loss and dyskinesia often stems from an overdose of DA medication. Cognitive behaviors typically associated with frontal cortical function such as working memory and task switching are also affected by too little or too much DA in PD. Whether motor and cognitive circuits overlap in PD is unknown. Here, we show that whereas motor performance improves in people with PD when on dopaminergic medication compared to off medication, memory-based decision-making performance remains impaired whether on or off medications. To rule out effects of long-term DA treatment and dopaminergic neuronal loss as occur in PD, we also tested a group of people with dopa-unresponsive focal dystonia - a disease that involves primarily the basal ganglia like PD, but has motor symptoms that are insensitive to dopamine treatment and is not thought to involve frontal cortical DA circuits, unlike PD. We found that people with focal dystonia showed intact perceptual decision-making performance, but impaired memory-based decision-making performance, similar to people with PD. Together, the results show a dissociation between motor and cognitive performance in people with PD and reveal a novel cognitive impairment, independent of sensory and motor impairment, in people with focal dystonia. The combined results from people with PD and people with focal dystonia provide mechanistic insights into the role of basal ganglia non-dopaminergic circuits in memory-based perceptual decision-making.

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Diagnosing Kernohan-Woltman notch phenomenon by Somatosensory Evoked Potentials in Intensive Care Unit

Kernohan-Woltman notch phenomenon can occur after hemispheric brain lesions with severe midline herniation. This is clinically defined by the existence of false-localizing signs (such as an ipsilateral hemiparesis) due to a contralateral mesencephalon compression by the tentorial edge, without contralateral hemiparesis by temporal lobe herniation (Codd et al., 2013). Repetitive somatosensory evoked potential (SEP) recordings have been used to help assessing secondary injury related to severe herniation on the intensive care unit (ICU), even if they were not brought to evidence by intracranial pressure (ICP) monitoring (Stocchetti et al., 2014).

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Multisession anodal transcranial direct current stimulation induces motor cortex plasticity enhancement and motor learning generalization in an aging population

Transcranial direct-current stimulation (tDCS) is a non-invasive technique of cortical brain neuromodulation with potential therapeutic effects. Using a constant and low intensity direct current that flows between two electrodes over the scalp (Webster et al., 2006, Fregni et al., 2007), this technique influences trans-membrane neuronal potentials and modifies the level of cortical excitability in the targeted brain region (Priori et al., 1998, Fregni et al., 2007, Nitsche et al., 2008, Bastani et al., 2012).

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Introduction to special issue: Body mass estimation — Methodological issues and fossil applications

Publication date: Available online 22 November 2017
Source:Journal of Human Evolution
Author(s): Christopher B. Ruff, Markku Niskanen




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A Pilot Quality Improvement Collaborative to Improve Safety Net Dental Access for Pregnant Women and Young Children

Abstract

Objectives To determine acceptability and feasibility of a quality improvement (QI) collaborative in safety net dental practices, and evaluate its effects on financial stability, access, efficiency, and care for pregnant women and young children. Methods Five safety net dental practices participated in a 15-month learning collaborative utilizing business assessments, QI training, early childhood oral health training, and prenatal oral health training. Practices collected monthly data on: net revenue, no-show rates, total encounters, and number of encounters for young children and pregnant women. We analyzed quantitative data using paired t-tests before and after the collaborative and collected supplemental qualitative feedback from clinic staff through focus groups and directed email. Results All mean measures improved, including: higher monthly revenue ($28,380–$33,102, p = 0.37), decreased no-show rate (17.7–14.3%, p = 0.11), higher monthly dental health encounters (283–328, p = 0.08), and higher monthly encounters for young children (8.8–10.5, p = 0.65), and pregnant women (2.8–9.7, p = 0.29). Results varied by practice, with some demonstrating largest increases in encounters for young children and others pregnant women. Focus group participants reported that the collaborative improved access for pregnant women and young children, and that QI methods were often new and difficult. Conclusion for practice Participation by safety net dental practices in a QI collaborative is feasible and acceptable. Individual sites saw greater improvements in different outcomes areas, based on their own structures and needs. Future efforts should focus on specific needs of each dental practice and should offer additional QI training.

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A Multilevel Approach to Breastfeeding Promotion: Using Healthy Start to Deliver Individual Support and Drive Collective Impact

Abstract

Purpose Breastfeeding has been linked to a host of positive health effects for women and children. However, disparities in breastfeeding initiation and duration prevent many low-income and African-American women from realizing these benefits. Existing breastfeeding promotion efforts often do not reach women who need support the most. In response, the Westside Healthy Start program (WHS), located in Chicago, Illinois, developed an ongoing multilevel approach to breastfeeding promotion. Description Key elements of our WHS breastfeeding model include individual education and counseling from pregnancy to 6 months postpartum and partnership with a local safety-net hospital to implement the Baby-Friendly Hospital Initiative and provide lactation support to delivering patients. Assessment In the year our model was implemented, 44.6% (49/110) of prenatal WHS participants reported that they planned to breastfeed, and 67.0% (183/273) of delivered participants initiated. Among participants reaching 6 months postpartum, 10.5% (9/86) were breastfeeding. WHS also had 2667 encounters with women delivering at our partner hospital during breastfeeding rounds, with 65.1% of contacts initiating. Community data was not available to assess the efficacy of our model at the local level. However, WHS participants fared better than all delivering patients at our partner hospital, where 65.0% initiated in 2015. Conclusion Healthy Start programs are a promising vehicle to improve breastfeeding initiation at the individual and community level. Additional evaluation is necessary to understand barriers to duration and services needed for this population.

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House Parties: An Innovative Model for Outreach and Community-Based Health Education

Abstract

Purpose To connect low resource communities to innovative services that address gaps in health access and knowledge. Description We describe the house party model, as a community-based workshop approach to health education developed by the Westside Healthy Start program (WHS) in Chicago, Illinois. Key elements of the WHS house party model include use of community health workers as facilitators, collaboration with participants and community-based organizations, referrals to health care and social services, and engagement strategies such as interactive activities, personal stories, and discussion. Assessment In 2014 and 2015, WHS completed 23 house parties with 271 participants, delivering education on relevant maternal and child health (MCH) topics. Participants demonstrated improvements in knowledge of several health-related areas. About half of participants were able to identify causes or signs of preterm labor prior to the house party, compared to over 80% after. In addition, 94% of participants rated the house party workshops "excellent" or "good". Conclusion House parties are a promising strategy for increasing knowledge about MCH topics and linking hard-to-reach populations to resources in the community.

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Inaccuracies in caffeine intake quantification and other important limitations in recent publication by Goncalves et al.

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CORRIGENDUM

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It is time to investigate acute and chronic perceptual responses to eccentric cycling

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Reply to Drs. Nuzzo and Barry

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Muscle Oxygen content at exercise in patients with claudication

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Editorial makes unsubstantiated claims about high-load resistance training

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Reply to Areta et al.: Time to withdraw and let the myth rest

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Reply to Drs. Pageaux et al.: Cognitive demand of eccentric versus concentric cycling

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Reply to Drs. Henni and Abraham: Muscle oxygen content at exercise in patients with claudication

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Last Word on Viewpoint: Origin of the forward-going "backward" wave

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Origin of the forward-going "backward" wave

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UBC-Nepal Expedition: acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea level and high altitude

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g., shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that 1) at rest, SNA would be elevated and FMD would be reduced at HA compared with sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344 m) and HA (5,050 m) in 14 participants during mild lower-body negative pressure (LBNP; –10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n = 5). Our findings were 1) at rest, SNA was elevated (P < 0.01), and absolute FMD was reduced (P = 0.024), but relative FMD remained unaltered (P = 0.061), at HA compared with SL; and 2) despite significantly altering SNA with LBNP (+60.3 ± 25.5%) and LBPP (–37.2 ± 12.7%) (P < 0.01), FMD was unaltered at SL (P = 0.448) and HA (P = 0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA.

NEW & NOTEWORTHY The role of the sympathetic nervous system on endothelial function remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic nervous activity at sea level and high altitude and measured brachial endothelial function via flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no effect on endothelial function.

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Commentaries on Viewpoint: Origin of the forward-going "backward" wave

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Effects of anti-inflammatory (NSAID) treatment on human tendinopathic tissue

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat tendinopathy, but evidence for this treatment is lacking, and little is known regarding effects of NSAIDs on human tendinopathic tendon. This study investigated the effects of NSAID treatment (ibuprofen) on human tendinopathic tendon, with changes in gene expression as the primary outcome, and tendon pain, function, and blood flow as secondary outcomes. Twenty-six adults (16 men, 10 women), diagnosed with chronic Achilles tendinopathy, were randomized to 1-wk treatment with ibuprofen (600 mg x3/day) (n = 13) or placebo (n = 13) (double-blinded). Ibuprofen content in blood, visual analog scale score for tendon pain at rest and activity, Victorian Institute of Sports Assessment-Achilles (VISA-A) scores for tendon function, tendon thickness (with ultrasonography), and color Doppler were measured before and 1 h after treatment. After the last posttreatment test, a full-width tendon biopsy was taken from the affected area. Real-time-RT-PCR was used to assess expression of collagen I, collagen III, transforming growth factor (TGF-β) isoforms, cyclooxygenase-2 (COX-2), angiopoietin-like 4 (ANGPTL4), and cyclic AMP-dependent transcription factor (ATF3) in tendon tissue. Expression of collagens and TGF-β isoforms showed relatively low variation and was unaffected by ibuprofen treatment. Further, no changes were seen in tendon thickness or VISA-A score. The placebo treatment reduced the color Doppler (in tendon plus surrounding tissue) compared with the ibuprofen group and also increased the perception of pain at rest. In conclusion, there was no indication that short-term ibuprofen treatment affects gene expression in human chronic tendinopathic tendon or leads to any clear changes in tendon pain or function.

NEW & NOTEWORTHY Nonsteroidal anti-inflammatory drugs are widely used in the treatment of tendinopathy, but little is known of the effects of these drugs on tendon tissue. We find that 1 wk of ibuprofen treatment has no effect on gene expression of collagen and related growth factors in adult human tendinopathic tendon in vivo (in spite of relatively low levels of variation in gene expression), suggesting that tendinopathic cells are not responsive to ibuprofen.

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Measuring high-altitude adaptation

High altitudes (>8,000 ft or 2,500 m) provide an experiment of nature for measuring adaptation and the physiological processes involved. Studies conducted over the past ~25 years in Andeans, Tibetans, and, less often, Ethiopians show varied but distinct O₂ transport traits from those of acclimatized newcomers, providing indirect evidence for genetic adaptation to high altitude. Short-term (acclimatization, developmental) and long-term (genetic) responses to high altitude exhibit a temporal gradient such that, although all influence O₂ content, the latter also improve O₂ delivery and metabolism. Much has been learned concerning the underlying physiological processes, but additional studies are needed on the regulation of blood flow and O₂ utilization. Direct evidence of genetic adaptation comes from single-nucleotide polymorphism (SNP)-based genome scans and whole genome sequencing studies that have identified gene regions acted upon by natural selection. Efforts have begun to understand the connections between the two with Andean studies on the genetic factors raising uterine blood flow, fetal growth, and susceptibility to Chronic Mountain Sickness and Tibetan studies on genes serving to lower hemoglobin and pulmonary arterial pressure. Critical for future studies will be the selection of phenotypes with demonstrable effects on reproductive success, the calculation of actual fitness costs, and greater inclusion of women among the subjects being studied. The well-characterized nature of the O₂ transport system, the presence of multiple long-resident populations, and relevance for understanding hypoxic disorders in all persons underscore the importance of understanding how evolutionary adaptation to high altitude has occurred.

NEW & NOTEWORTHY Variation in O₂ transport characteristics among Andean, Tibetan, and, when available, Ethiopian high-altitude residents supports the existence of genetic adaptations that improve the distribution of blood flow to vital organs and the efficiency of O₂ utilization. Genome scans and whole genome sequencing studies implicate a broad range of gene regions. Future studies are needed using phenotypes of clear relevance for reproductive success for determining the mechanisms by which naturally selected genes are acting.

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Qualitative Evaluation of a Peer Navigator Program for Latinos with Serious Mental Illness

Abstract

Peer navigator programs (PNP) may help reduce physical health disparities for ethnic minorities with serious mental illness (SMI). However, specific aspects of PNP that are important to peer navigators and their clients are under-researched. A qualitative study explored the perspectives of service users (n = 15) and peer navigators (n = 5) participating in a randomized controlled trial of a PNP for Latinos with SMI. Results show PN engagement with service users spans diverse areas and that interactions with peers, trust, and accessibility are important from a service user perspective. PNs discussed needs for high-quality supervision, organizational support, and additional resources for undocumented Latinos.

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Locomotor recovery after lumbar spinal cord injury: fact or fancy?

Abstract

A recent global survey reported that the prevalence of spinal cord injury (SCI) ranges from 250 to 900 per million.

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