Blood flow restriction late in recovery after heavy resistance exercise hampers muscle recuperation

Abstract

Purpose

This study aimed to examine the effect of acute blood flow restriction during the late recovery phase between two resistance exercise bouts on muscular endurance and oxygenation.

Methods

Amateur male middle- and long-distance runners performed two bouts of one-leg dynamic plantar flexion exercise to failure with the load equivalent to 75% of maximum. Subjects were randomly assigned into two experimental groups with thigh occlusion pressure between bouts at either 120 or 200 mmHg with 20 min of passive rest in between, and two control groups without any blood flow restriction separated by either 5 or 20 min of rest. Blood flow restriction in the experimental groups was implemented during the last 15 min of recovery. Calf arterial blood flow and muscle oxygenation were measured by venous occlusion plethysmography and near-infrared spectroscopy, respectively.

Results

Decrease of muscular oxygenation and blood flow during recovery between exercise bouts depended on the applied occlusion pressure. When compared with bout 1, work capacity in the experimental groups during bout 2 was reduced by 9.3 ± 2.2% with 120 mmHg and by 10.5 ± 3.1% (p < 0.05) with 200 mmHg occlusion pressure. In the control groups, work capacity was restored after 20 min (− 3.9 ± 3.2%, p > 0.05) but not after 5-min recovery (− 20.0 ± 1.8%, p < 0.05).

Conclusions

Blood flow restriction late in recovery after a heavy resistance exercise bout decreased muscle oxygenation and work capacity during the subsequent heavy resistance exercise bout.

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Androgen and estrogen sensitivity of bird song: a comparative view on gene regulatory levels

Abstract

Singing of songbirds is sensitive to testosterone and its androgenic and estrogenic metabolites in a species-specific way. The hormonal effects on song pattern are likely mediated by androgen receptors (AR) and estrogen receptor alpha (ERα), ligand activated transcription factors that are expressed in neurons of various areas of the songbirds' vocal control circuit. The distribution of AR in this circuit is rather similar between species while that of ERα is species variant and concerns a key vocal control area, the HVC (proper name). We discuss the regulation of the expression of the cognate AR and ERα and putative splice variants. In particular, we suggest that transcription factor binding sites in the promoter of these receptors differ between bird species. Further, we suggest that AR- and ERα-dependent gene regulation in vocal areas differs between species due to species-specific DNA binding sites of putative target genes that are required for the transcriptional activity of the receptors. We suggest that species differences in the distribution of AR and ERα in vocal areas and in the genomic sensitivity to these receptors contribute to species-specific hormonal regulation of the song.

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A 12.3 kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3

Von Willebrand Disease (VWD) type 3 is a serious and sometimes fatal hereditary bleeding disorder. In pigs, the disease has been known for decades and affected animals are used as models for the human disease. Due to the recessive mode of inheritance of VWD type 3, severe bleeding is typically seen in homozygous individuals. We sequenced the complete porcine VWF (Von Willebrand Factor) cDNA and detected a tandem duplication of exons 17 and 18, causing a frameshift and a premature termination codon (p.Val814LeufsTer3) in the affected pig. Subsequent next generation sequencing on genomic DNA proved the existence of a 12.3 kb tandem duplication associated with VWD. This duplication putatively originates from porcine SINE elements located within VWF introns 16 and 18 with high identity. The premature termination truncates the VWF open reading frame by a large part, resulting in an almost entire loss of the mature peptide. It is therefore supposed to account for the severe VWD type 3. Our results further indicate the presence of strong, nonsense-mediated decay in VWF mRNA containing the duplication, which was supported by the almost complete absence of the complete VWF protein in immunohistochemistry analysis of the VWD-affected pig. In the past, differentiation of wildtype and heterozygous pigs in this VWD colony had to rely on clinical examinations and additional laboratory methods. The present study provides the basis to distinguish both genotypes by performing a rapid and simple genetic analysis.

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Cell-Type Transcriptomes of the Multicellular Green Alga Volvox carteri Yield Insights into the Evolutionary Origins of Germ and Somatic Differentiation Programs

Germ-soma differentiation is a hallmark of complex multicellular organisms, yet its origins are not well understood. Volvox carteri is a simple multicellular green alga that has recently evolved a simple germ-soma dichotomy with only two cell types: large germ cells called gonidia and small terminally differentiated somatic cells. Here, we provide a comprehensive characterization of the gonidial and somatic transcriptomes of Volvox to uncover fundamental differences between the molecular and metabolic programming of these cell types. We found extensive transcriptome differentiation between cell types, with somatic cells expressing a more specialized program overrepresented in younger, lineage-specific genes and gonidial cells expressing a more generalist program overrepresented in more ancient genes that shared striking overlap with stem-cell-specific genes from animals and land plants. Directed analyses of metabolic pathways revealed a strong dichotomy between cell types with gonidial cells expressing growth-related genes and somatic cells expressing an altruistic metabolic program geared towards the assembly of flagella, which support organismal motility, and the conversion of storage carbon to sugars, which act as donors of extracellular matrix glycoproteins whose secretion enables massive organismal expansion. Volvox orthologs of Chlamydomonas diurnally controlled genes were analyzed for cell-type distribution and found to be strongly partitioned, with expression of dark-phase genes overrepresented in somatic cells and light-phase genes overrepresented in gonidial cells, a result that is consistent with cell type programs in Volvox arising by cooption of temporal regulons in a unicellular ancestor. Together our findings reveal fundamental molecular, metabolic, and evolutionary mechanisms that underlie the origins of germ-soma differentiation in Volvox and provide a template for understanding the acquisition of germ-soma differentiation in other multicellular lineages.

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Transcriptional Profiling of Saccharomyces cerevisiae Reveals the Impact of Variation of a Single Transcription Factor on Differential Gene Expression in 4NQO, Fermentable, and Non-fermentable Carbon Sources

Cellular metabolism can change the potency of a chemical's tumorigenicity. 4-nitroquinoline-1-oxide (4NQO) is a tumorigenic drug widely used on animal models for cancer research. Polymorphisms of the transcription factor, Yrr1, confer different levels of resistance to 4NQO in Saccharomyces cerevisiae. To study how different Yrr1 alleles regulate gene expression leading to resistance, transcriptomes of three isogenic S. cerevisiae strains carrying different Yrr1 alleles were profiled via RNA sequencing (RNA-Seq) and chromatin immunoprecipitation coupled with sequencing (ChIP-Seq) in presence and absence of 4NQO. In response to 4NQO, all alleles of Yrr1 drove the expression of SNQ2 (multidrug transporter), which was the highest in the presence of 4NQO resistance conferring alleles, and overexpression of SNQ2 alone was sufficient to overcome 4NQO sensitive growth. Using shape metrics to refine the ChIP-seq peaks, Yrr1 strongly associated with three loci including SNQ2. In addition to a known Yrr1 target, SNG1, Yrr1 also bound upstream of RPL35B; however, overexpression of these genes did not confer 4NQO resistance. RNA-seq data also implicated nucleotide synthesis pathways including the de novo purine pathway, and the ribonuclease reductase pathways were downregulated in response to 4NQO. Conversion of a 4NQO sensitive allele to a 4NQO resistant allele by a single point mutation mimicked the 4NQO resistant allele in phenotype and while the 4NQO resistant allele increased the expression of the ADE genes in the de novo purine biosynthetic pathway, the mutant Yrr1 increased expression of ADE genes even in the absence of 4NQO. These same ADE genes were only increased in the wild-type alleles in the presence of 4NQO, indicating the point mutation activated Yrr1 to upregulate a pathway normally only activated in response to stress. The various Yrr1 alleles also influenced growth on different carbon sources by altering the function of the mitochondria. Hence, the complement to 4NQO resistance was poor growth on non-fermentable carbon sources, which in turn varied depending on the allele of Yrr1 expressed in the isogenic yeast. The oxidation state of the yeast affected the 4NQO toxicity by altering the reactive oxygen species (ROS) generated by cellular metabolism. The integration of RNA-Seq and ChIP-Seq elucidated how Yrr1 regulates global gene transcription in response to 4NQO and how various Yrr1 alleles confer differential resistance to 4NQO. This study provides guidance for further investigation into how Yrr1 regulates cellular responses to 4NQO, as well as transcriptomic resources for further analysis of transcription factor variation on carbon source utilization.

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Optimizing Genomic Methods for Mapping and Identification of Candidate Variants in ENU Mutagenesis Screens Using Inbred Mice

Positional cloning of ENU-induced mutations has traditionally relied on analysis of polymorphic variation between two strains.  In contrast, the application of whole genome sequencing (WGS) has enabled gene discovery in mutant lines maintained on an inbred genetic background.  This approach utilizes genetic variation derived from ENU-induced variants for mapping, and reduces the likelihood of phenotypic variation, making it an ideal method for genetic modifier screening.  Here, we describe the results of such a screen, wherein we determined the minimal number of mutant genomic DNA samples to include in our analyses, and improved the sensitivity of our screen by individually barcoding each genomic DNA library.  We present several unique cases to illustrate this approach's efficacy, including the discovery of two distinct mutations that generate essentially identical mutant phenotypes, the ascertainment of a non-ENU-induced candidate variant through homozygosity mapping, and an approach to the identification of putative dominant genetic modifiers.

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Whole Genome Sequencing of Hulunbuir Short-Tailed Sheep for Identifying Candidate Genes Related to the Short-Tail Phenotype

The Hulunbuir short-tailed sheep (Ovis aries) is a breed native to China, in which the short-tail phenotype is the result of artificial and natural selection favoring a specific set of genetic mutations. Here, we analyzed the genetic differences between short-tail and normal-tail phenotypes at the genomic level. Selection signals were identified in genome-wide sequences. From 16 sheep, we identified 72,101,346 single nucleotide polymorphisms. Selection signals were detected based on the fixation index and heterozygosity. Seven genomic regions under putative selection were identified, and these regions contained nine genes. T was related to vertebral development; however, a non-synonymous mutation at c.G334T resulted in p.G112W substitution. We inferred that the c.G334T mutation in T leads to functional changes in Brachyury-encoded by this gene-resulting in the short-tail phenotype. Our findings provide a valuable insight into the development of the short-tail phenotype in sheep and other short-tailed animals.

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Clinically significant pedicle screw malposition is an underestimated cause of radiculopathy

Instrumented fusion of the lumbosacral spine has been credited with improved rates of solid arthrodesis, but it also carries a small risk of neurological, vascular, and intestinal injury. Indeed, King [1] recognized in 1948 that pedicle screws could cause postoperative radiculitis.

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The Functional Impairments in a Patient with Morvan’s Syndrome: A Case Report

A 48 year-old man with lung squamous cell carcinoma was admitted to acute care with cognitive impairment after recent chemotherapy. He developed myoclonus, ataxia, agitation, and visual hallucinations. Morvan's Syndrome, a rare voltage-gated potassium channel antibody disorder characterized by neuromyotonia with central nervous system dysfunction, was eventually diagnosed. He received plasmapheresis and was admitted to inpatient rehabilitation, where he safely participated in therapies. By focusing on neuromuscular rehabilitation, balance training, fine motor skills, and cognitive retraining emphasizing skills relevant to the patient's premorbid cognitive activities, the patient demonstrated significant functional improvement, decreasing the burden of care of his caregivers.

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Changes of Oxygen Consumption and Heart Rate after Acute Myocardial Infarction during 6-Month Follow-up

Exercise intensity is a particularly important determinant of physiological responses to exercise training in patients with acute myocardial infarction. Heart rate (HR) is commonly used as a practical way of prescribing and monitoring exercise as specific intensities based on linear relationship between the percentage of maximum heart rate (%HRmax) and the percentage of maximum oxygen consumption (%VO2max) regardless of age, sex or exercise mode.

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Aprotinin and coronary artery bypass surgery

No abstract available

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Procedural sedation and analgesia for adults in Europe: Safety first

No abstract available

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Predictive models for acute kidney injury after cardiac surgery

No abstract available

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European Society of Anaesthesiology and European Board of Anaesthesiology guidelines for procedural sedation and analgesia in adults

No abstract available

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Safety and quality of procedural sedation and analgesia practice for adult patients throughout Europe: A step forward

No abstract available

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Fibrinogen on Admission in Trauma score: Early prediction of low plasma fibrinogen concentrations in trauma patients

BACKGROUND Early recognition of low fibrinogen concentrations in trauma patients is crucial for timely haemostatic treatment and laboratory testing is too slow to inform decision-making. OBJECTIVE To develop a simple clinical tool to predict low fibrinogen concentrations in trauma patients on arrival. DESIGN Retrospective cohort study. SETTING Three designated level 1 trauma centres in the Paris Region, from January 2011 to December 2013. PATIENTS Patients admitted in accordance with national triage guidelines for major trauma and plasma fibrinogen concentration testing on admission. INTERVENTION Construction of a clinical score [Fibrinogen on Admission in Trauma (FibAT) score] in a derivation cohort to predict fibrinogen plasma concentration 1.5 g l−1 or less after multiple regressions. One point was given for each predictive factor. The score was the sum of all. Validation was performed in a separate validation cohort. MAIN OUTCOME MEASURE Predictive accuracy of FibAT score. RESULTS In total, 2936 patients were included, 2124 in the derivation cohort and 812 in the validation cohort. In the derivation cohort, a multivariate logistic model identified the following predictive factors for plasma fibrinogen concentrations 1.5 g l−1 or less: age less than 33 years, prehospital heart rate more than 100 beats per minute, prehospital SBP less than 100 mmHg, blood lactate concentration on admission more than 2.5 mmol l−1, free intraabdominal fluid on sonography, decrease in haemoglobin concentration from prehospital to admission of more than 2 g dl−1, capillary haemoglobin concentration on admission less than 12 g dl−1 and temperature on admission less than 36°C. The FibAT score had an area under the receiver operating characteristic curve of 0.87 [95% confidence interval (0.86 to 0.91)] in the derivation cohort and of 0.82 (95% confidence interval (0.86 to 0.91)] in the validation cohort to predict a low plasma fibrinogen. CONCLUSION The FibAT score accurately predicts plasma fibrinogen levels 1.5 g l−1 or less on admission in trauma patients. This easy-to-use score could allow early, goal-directed therapy to trauma patients.

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High versus low PEEP for abdominal surgery

No abstract available

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Blood glucose concentrations in prehospital trauma patients with traumatic shock: A retrospective analysis

BACKGROUND Deranged glucose metabolism after moderate to severe trauma with either high or low concentrations of blood glucose is associated with poorer outcome. Data on prehospital blood glucose concentrations and trauma are scarce. OBJECTIVES The primary aim was to describe the relationship between traumatic shock and prehospital blood glucose concentrations. The secondary aim was to determine the additional predictive value of prehospital blood glucose concentration for traumatic shock when compared with vital parameters alone. DESIGN Retrospective analysis of the predefined, observational database of a nationwide Helicopter Emergency Medical Service (34 bases). SETTING Emergency trauma patients treated by Helicopter Emergency Medical Service between 2005 and 2013 were investigated. PATIENTS All adult trauma patients (≥18 years) with recorded blood glucose concentrations were enrolled. OUTCOMES Primary outcome: upper and lower thresholds of blood glucose concentration more commonly associated with traumatic shock. Secondary outcome: additional predictive value of prehospital blood glucose concentrations when compared with vital parameters alone. RESULTS Of 51 936 trauma patients, 20 177 were included. In total, 220 (1.1%) patients died on scene. Hypoglycaemia (blood glucose concentration 2.8 mmol l−1 or less) was observed in 132 (0.7%) patients, hyperglycaemia (blood glucose concentration exceeding 15 mmol l−1) was observed in 265 patients (1.3%). Blood glucose concentrations more than 10 mmol l−1 (n = 1308 (6.5%)) and 2.8 mmol l−1 or less were more common in patients with traumatic shock (P 

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Dobutamine and its haemodynamic effects in pleural effusion

No abstract available

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Median effective dose of intranasal dexmedetomidine sedation for transthoracic echocardiography examination in postcardiac surgery and normal children: An up-and-down sequential allocation trial

BACKGROUND Dexmedetomidine (DEX) has been used for sedation in young infants and children undergoing transthoracic echocardiography (TTE). The median effective dose of intranasal DEX has not been described for postcardiac surgery children. Postcardiac surgery children could require more DEX to achieve satisfactory sedation for TTE examination than children suspected of congenital heart disease. OBJECTIVES To study whether postcardiac surgery children need a larger dose of DEX for TTE than normal children. DESIGN A double-blind sequential allocation trial with doses determined by the Dixon and Massey up-and-down method. SETTING A tertiary care teaching hospital from 25 October to 30 November 2016. PATIENTS Children under the age of 3 years requiring intranasal DEX for TTE. INTERVENTIONS Children were allocated to a postcardiac surgery group (n = 20) or a normal group (n = 19). The first patient in both groups received intranasal DEX (2 μg kg−1): using the up-and-down method of Dixon and Massey, the next dose was dependent on the previous patient's response. MAIN OUTCOME MEASURES Median effective dose was estimated from the up-and-down method of Dixon and Massey and probit regression. A second objective was to study haemodynamic stability and adverse events with these doses. RESULTS The median effective dose (95% confidence interval) of intranasal DEX was higher in postcardiac surgery children than in normal children, 3.3 (2.72 to 3.78) μg kg−1 versus 1.8 (1.71 to 2.04) (μg kg-1), respectively (P 

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Reply to: alveolar recruitment manoeuvres after cardiac surgery

No abstract available

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Clinical signs and electroencephalographic patterns of emergence from sevoflurane anaesthesia in children: An observational study

BACKGROUND Few studies have systematically described relationships between clinical–behavioural signs, electroencephalographic (EEG) patterns and age during emergence from anaesthesia in young children. OBJECTIVE To identify the relationships between end-tidal sevoflurane (ETsevoflurane) concentration, age and frontal EEG spectral properties in predicting recovery of clinical–behavioural signs during emergence from sevoflurane in children 0 to 3 years of age, with and without exposure to nitrous oxide. The hypothesis was that clinical signs occur sequentially during emergence, and that for infants aged more than 3 months, changes in alpha EEG power are correlated with clinical–behavioural signs. DESIGN An observational study. SETTING A tertiary paediatric teaching hospital from December 2012 to August 2016. PATIENTS Ninety-five children aged 0 to 3 years who required surgery below the neck. OUTCOME MEASURES Time–course of, and ETsevoflurane concentrations at first gross body movement, first cough, first grimace, dysconjugate eye gaze, frontal (F7/F8) alpha EEG power (8 to 12 Hz), frontal beta EEG power (13 to 30 Hz), surgery-end. RESULTS Clinical signs of emergence followed an orderly sequence of events across all ages. Clinical signs occurred over a narrow ETsevoflurane, independent of age [movement: 0.4% (95% confidence interval (CI), 0.3 to 0.4), cough 0.3% (95% CI, 0.3 to 0.4), grimace 0.2% (95% CI, 0 to 0.3); P > 0.5 for age vs. ETsevoflurane]. Dysconjugate eye gaze was observed between ETsevoflurane 1 to 0%. In children more than 3 months old, frontal alpha EEG oscillations were present at ETsevoflurane 2.0% and disappeared at 0.5%. Movement occurred within 5 min of alpha oscillation disappearance in 99% of patients. Nitrous oxide had no effect on the time course or ETsevoflurane at which children showed body movement, grimace or cough. CONCLUSION Several clinical signs occur sequentially during emergence, and are independent of exposure to nitrous oxide. Eye position is poorly correlated with other clinical signs or ETsevoflurane. EEG spectral characteristics may aid prediction of clinical–behavioural signs in children more than 3 months.

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Reply to: predictive models for acute kidney injury after cardiac surgery

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Estimating and reporting error rates, and detecting improvements

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Reply to: high versus low positive end-expiratory pressure for abdominal surgery

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Reply to: estimating and reporting rates, and detecting improvements

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Reply to: aprotinin and coronary artery bypass surgery

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Alveolar recruitment manoeuvres after cardiac surgery

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Reply to: dobutamine and its haemodynamic effects in pleural effusion

No abstract available

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Extraction and quantification system for environmental radioxenon sample analysis

Publication date: February 2018
Source:Journal of Environmental Radioactivity, Volume 182
Author(s): M. Sabzian, M.N. Nasrabadi, M. Haji-Hosseini
A xenon dynamic adsorption setup based on granular activated carbon packed column was developed. The adsorption behavior of xenon under different experimental conditions was studied and the results used to design an appropriate adsorber column for specific conditions. The resulting radioxenon gas extraction and quantification setup was evaluated based on an inter-comparison exercise and standard sample analysis results. The results showed that the quantification setup achieves experimental rules with uncertainty of ±3%.



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Tracking the genome-wide outcomes of a transposable element burst over decades of amplification [Genetics]

To understand the success strategies of transposable elements (TEs) that attain high copy numbers, we analyzed two pairs of rice (Oryza sativa) strains, EG4/HEG4 and A119/A123, undergoing decades of rapid amplification (bursts) of the class 2 autonomous Ping element and the nonautonomous miniature inverted repeat transposable element (MITE) mPing. Comparative...

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Reply to Liu et al.: Yin and yang of PTEN regulation [Biological Sciences]

In a letter to the editor, Liu et al. (1) find that PTEN contains some transcript variants that are polyadenylated and prematurely terminated in the first intron of PTEN. These transcripts are suggested to be 5′-UTR–containing promoter-spanning and to encode for three small RNAs (sRNAs), with one of these (sRNA3)...

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Transcription start site-associated small RNAs in the PTEN gene [Biological Sciences]

The PTEN gene is inactivated in various cancers. PTEN has a pseudogene in the human genome, PTENpg1, which up-regulates PTEN expression by acting as a miRNA sponge. Interestingly, one of the antisense RNAs from the PTENpg1 locus, PTENpg1 asRNA α, is found to epigenetically down-regulate PTEN transcription by recruitment of...

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Germline Cas9 expression yields highly efficient genome engineering in a major worldwide disease vector, Aedes aegypti [Genetics]

The development of CRISPR/Cas9 technologies has dramatically increased the accessibility and efficiency of genome editing in many organisms. In general, in vivo germline expression of Cas9 results in substantially higher activity than embryonic injection. However, no transgenic lines expressing Cas9 have been developed for the major mosquito disease vector Aedes...

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Drosophila protein phosphatases 2A B' Wdb and Wrd regulate meiotic centromere localization and function of the MEI-S332 Shugoshin [Genetics]

Proper segregation of chromosomes in meiosis is essential to prevent miscarriages and birth defects. This requires that sister chromatids maintain cohesion at the centromere as cohesion is released on the chromatid arms when the homologs segregate at anaphase I. The Shugoshin proteins preserve centromere cohesion by protecting the cohesin complex...

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Muscle Fiber and Performance Changes after Fast Eccentric Complex Training

Introduction The purpose of this study was to examine the effects of a short-term fast eccentric and ballistic complex training program on muscle power, rate of force development (RFD), muscle fiber composition and cross-sectional area (CSA). Methods Sixteen male physical education students were randomly assigned to either a training group (TG, n=8) or a control group (C, n=8). The TG followed a 6-week low volume training program, including fast eccentric squat training with an individually optimized load of 74±7% of maximal half-squat strength (1RM) twice per week and a ballistic training session with loaded (30% 1RM) and unloaded jump squats, once per week, all combined with unloaded plyometric jumps. Results Half squat 1RM was increased in the TG from 1.87±0.28 to 2.14±0.31 kg.kg-1 body mass (14.4±9.3%, p=0.01). The percentage of type I, IIA and IIX fibers were similar in the two groups at pre testing and did not change after the intervention period (p=0.53-0.89). Muscle fiber CSA increased in all fiber types by 8.3 to 11.6% (p=0.02 to 0.001) in TG only. Countermovement jump height and peak power measured at five different external loads (0-65% of 1RM) only increased in the TG by ~20-36% (p

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Protocol for Objective Measurement of Infants’ Physical Activity using Accelerometry

Purpose To evaluate methods for infants' physical activity measurement based on accelerometry, including the minimum number of measurement days and placement of a wrist or ankle device. We also evaluated the acceptability of the device among infants and mothers. Methods A cross-sectional mixed-methods study was conducted on a convenience sample of 90 infants. Physical activity was measured using the Actigraph GT3X+ accelerometer placed on the wrist and/or ankle for seven consecutive days (worn for 24 hours), and a qualitative interview was performed to verify acceptability. The intraclass correlation coefficient method and the Bland and Altman's dispersion diagram were used to verify the minimum number of measurement days. All analyses were stratified by walking status. Results The mean age was 12.9 months (SD 1.70); the mean acceleration varied between 25.8 mg (95% CI 14.3-52.7) to 27.3 mg (95% CI 17.9-44.5) using the wrist placement; and between 24.9 mg (95% CI 10.6-48.4) to 26.2 mg (95% CI 11.7-65.6) using the ankle placement. The ICC results showed a lower acceleration variability between days among infants incapable of walking; they achieved the ICC=0.80 with one day of measurement in both placements. Among those capable of walking, the minimum number of days to achieve ICC=0.80 were two days measured at the wrist (0.85; 95% CI 0.71-0.93) and three days measured at the ankle (0.92; 95% CI 0.84-0.96). The qualitative results pointed to the wrist placement as the preferred placement among the overall sample. Conclusion Two and three measurement days with the accelerometer placed on the wrist and ankle, respectively, seemed to adequately represent a week of measurement. The accelerometer placed on the wrist had better acceptance by the infants and mothers. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Corresponding author: Luiza Isnardi Cardoso Ricardo, Marechal Deodoro, 1160 (3rd floor) Pelotas, RS - Brazil, CEP: 96020-220 – phone/fax: +55 (53) 3284 - 1300. E-mail: luizaicricardo@gmail.com Ms. Luiza Ricardo and Ms. Rafaela Martins are funded by the CAPES PhD scholarship, and Ms. Andrea Wendt is funded by a CNPq PhD scholarship. This work was supported by the Wellcome Trust (Grant number: 095582/Z/11/Z). The results of the present study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation; and do not constitute endorsement by the authors or the ACSM. Accepted for Publication: 23 November 2017 © 2017 American College of Sports Medicine

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Effect of Beta-blocker Treatment on VO2peak in Patients with Heart Failure

ABSTRACT Purpose In addition to prolong life and reduce hospitalization rates, it is currently unclear whether beta-blocker (BB) treatment modulates peak oxygen consumption (VO2peak), a hallmark of exercise capacity, in patients with heart failure (HF). The main aim of this study is to determine the effect of BB treatment on VO2peak in HF patients. Methods We conducted a systematic search of MEDLINE, Scopus and Web of Science since their inceptions until March 2017 for randomized controlled trials (RCTs) assessing the effect of BB treatment on VO2peak in chronic HF patients. A meta-analysis was performed to ascertain the standardized mean difference (SMD) between the effect of BB versus placebo treatment on VO2peak. Secondary outcomes included peak exercise performance and New York Health Association (NYHA) functional class. Subgroup and meta-regression analyses assessed potential moderating factors. Results Fourteen RCTs met the inclusion criteria (overall n=616). Interventions comprised BB (n=324) or placebo (n=292) administration lasting 3 to 24 months. Concomitant reported medication did not differ between HF patients assigned to BB and placebo groups. After data pooling, VO2peak was preserved with BB compared with placebo treatment (SMD=-0.04, 95 % CI=-0.20, 0.12; P=0.61); heterogeneity among studies was not detected (I2=0 %, P=0.88). Peak exercise performance was not altered (SMD=0.02, 95 % CI=-0.16, 0.20; P=0.85), whereas NYHA functional class was reduced with BB compared with placebo (SMD=-0.54, 95 % CI=-0.90, -0.18; P=0.003). Conclusion According to evidence from RCTs, prolonged BB (B1-selective or non-selective) treatment do not affect VO2peak yet improves functional status in HF patients. Correspondence: Dr. David Montero, University Heart Center, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland. Tel.: + 41 44 255 33 53, Fax: +41 44 255 48 59. Email: david.monterobarril@usz.ch The results of the present study do not constitute endorsement by ACSM. The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. DM receives research salary from the Forschungskredit Award, Faculty of Medicine, University of Zurich. The authors have no conflicts of interest to disclose. Accepted for Publication: 27 November 2017 © 2017 American College of Sports Medicine

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Three Weeks of Overload Training Increases Resting Muscle Sympathetic Activity

Purpose Overload training is hypothesized to alter autonomic regulation, though interpretations using indirect measures of heart rate variability are conflicting. The aim of the present study was to examine the effects of overload training on muscle sympathetic nerve activity (MSNA), a direct measure of central sympathetic outflow, in recreational endurance athletes. Methods Measurements of heart rate variability, cardiac baroreflex sensitivity (BRS), MSNA (microneurography), and sympathetic BRS were obtained in seventeen healthy triathletes and cyclists after 1-week of reduced training (baseline) and following 3-weeks of either regular (CON, n=7) or overload (OL, n=10) training. Results Following training, the changes ([INCREMENT]) in peak power output (10 ± 10 vs. -12 ± 9 W, P 0.05). Conclusions Overload training increased MSNA and attenuated increases in cardiac BRS and heart rate variability observed with regular training. These results support neural adaptations following overload training and suggest that increased central sympathetic outflow may be linked with decreased exercise performance. Address for Correspondence: Jamie F. Burr, Animal Science and Nutrition, 50 Stone Road E., University of Guelph, Guelph, ON, Canada, N1G 2W1, Phone 519-824-4120 x 52591. Email: burrj@uoguelph.ca This research was supported by a Natural Science and Engineering Research Council (NSERC) of Canada Discovery Grant (P.J.M. #06019; J.F.B. #03974), the Ontario Ministry of Research, Innovation, Science (P.J.M. #34379; J.F.B. 460597), and the Canada Foundation for Innovation (P.J.M.#34379; J.F.B. 460597). A.M.C. was supported by a Ontario Graduate Scholarship. A.V.I. and C.J.D. were supported by Queen Elizabeth II Graduate Scholarships in Science and Technology. J.D.S. was supported by a NSERC Undergraduate Student Research Award. The authors have no conflicts of interest to declare. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 28 November 2017 © 2017 American College of Sports Medicine

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The Interplay between Genes and Psychosocial Home Environment on Physical Activity

ABSTRACT Introduction Genetic factors contribute to individual differences in physical activity, but it remains uncertain whether the magnitude of the genetic effects is modified by variations in home environments. We aimed to examine to what extent the psychosocial home environment in childhood and adolescence modifies the genetic influences on leisure-time physical activity in young adulthood. Methods Participants were Finnish twins (N=3,305) who reported their leisure-time physical activity at age 24. The psychosocial home environment was assessed by twins at ages 12, 14 and 17, as well as by their parents when the twins were age 12. Gene–environment interaction modeling was performed with OpenMx software. Results Parental ratings of positive home atmosphere as well as the twins' ratings of both positive home atmosphere at age 14 and lower relational tensions at ages 12 and 14 predicted higher leisure-time physical activity levels in young adulthood (regression coefficients 0.33–0.64). Parental perceptions as well as the twins' perceptions of positive home atmosphere at ages 14 and 17 increased the additive genetic variation (moderation effects 0.60, 95% CI 0.26–1.05; 0.55, 95% CI 0.29–0.80 and 0.52, 95%CI 0.19–0.87, respectively). The twins' ratings of positive home atmosphere at age 12 and lower relational tensions at ages 12 and 14 increased the unique environmental variation of their subsequent physical activity (moderation effects 0.46, 95% CI 0.19–0.60; 0.48, 95% CI 0.29–0.64 and 0.85, 95% CI 0.12–0.95, respectively). Conclusions A psychosocial home environment that is warm and supportive in childhood and adolescence not only increases the mean level of subsequent leisure-time physical activity in young adulthood, but also modifies the genetic and environmental variances in leisure-time physical activity. Corresponding author: Sari Aaltonen Ph.D., Institute for Molecular Medicine (FIMM), University of Helsinki, P.O. Box 20 (Tukholmankatu 8 B), FIN-00014 University of Helsinki, Helsinki, Finland. E-mail: sari.s.aaltonen@helsinki.fi The research work has been supported by the Academy of Finland (grant 266592 to S.A. and K.S., grants 100499, 205585, 141054, 265240, 263278 and 264146 to J.K.), the Finnish Ministry of Education and Culture (to S.A., U.M.K. and K.S.), the Juho Vainio Foundation (to S.A., U.M.K. and K.S.), and the Finnish Cultural Foundation (to S.A.). Data collection of the FinnTwin12 study has also been supported by the U.S. National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R.J.R.). The authors declare no conflict of interest. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The authors state that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 21 November 2017 © 2017 American College of Sports Medicine

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Perceptual Responses to High- and Moderate-Intensity Interval Exercise in Adolescents

ABSTRACT Purpose High-intensity continuous exercise is proposed to evoke unpleasant sensations as predicted by the dual mode theory (DMT), and may negatively impact on future exercise adherence. Previous studies support unpleasant sensations in affective responses during continuous high-intensity exercise, but the affect experience during high-intensity interval exercise (HIIE) involving brief bursts of high-intensity exercise separated by low-intensity activity is poorly understood in adolescents. We examined the acute affective, enjoyment and perceived exertion responses to HIIE compared to moderate-intensity interval exercise (MIIE) in adolescents. Methods Thirteen adolescent boys (mean±SD; age 14.0±0.5 years) performed two counterbalanced exercise conditions: 1) HIIE: 8 x 1-minute work intervals at 90% maximal aerobic speed; and 2) MIIE: between 9-12 x 1-minute work intervals at 90% ventilatory threshold where the number of intervals performed were distance-matched to HIIE. HIIE and MIIE intervals were interspersed with 75 s active recovery at 4 km·h−1. Affect, enjoyment and rating of perceived exertion (RPE) were recorded before, during and after exercise. Results Affect responses declined in both conditions but the fall was greater in HIIE than MIIE (P0.64). Conclusions Despite elevated RPE, HIIE did not elicit prominent unpleasant feelings as predicted by DMT and was associated with greater post-exercise enjoyment responses than MIIE. This study demonstrates the feasibility of the application of HIIE as an alternative form of PA in adolescents. Corresponding author: Dr Alan R. Barker, Children's Health and Exercise Research Centre, Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, St Luke's Campus, Exeter, EX1 2LU, Tel: 44 (0)1392 722766 Adam Abdul Malik is financially supported by the Government of Malaysia for the funding under the academic staff training scheme (USM/PPSP(Pent)/L2/bJld.XV). The results of the present study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of this study also do not constitute endorsement by the American College of Sports Medicine. The authors have no conflicts of interest to disclose. Accepted for Publication: 27 November 2017 © 2017 American College of Sports Medicine

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Acute Inflammatory Responses to Exercise in Patients with Abdominal Aortic Aneurysm

ABSTRACT Purpose Inflammation and extracellular matrix degeneration contribute to abdominal aortic aneurysm (AAA) development. We aimed to assess the effect of exercise intensity on circulating biomarkers of inflammation and extracellular matrix degeneration in patients with AAA and healthy older adults. Methods Twenty patients with AAA (74±6y) and twenty healthy males (72±5y) completed moderate-intensity cycling at 40% peak power output (PPO), higher-intensity intervals at 70% PPO, and control (rest) on separate days. Circulating matrix metalloproteinase-9 (MMP-9), transforming growth factor beta 1 (TGF-β1), interleukin-6 (IL-6), IL-10 and tumour necrosis factor alpha (TNF-α) were analysed at rest, and 0 to 90 min post. Results Biomarkers at baseline were similar between groups. IL-6 responses to exercise were similar between groups, with a greater increase in ΔIL-6 after moderate-intensity compared to higher-intensity exercise (P

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Link between Physical Activity Type in Adolescence and Body Composition in Adulthood

ABSTRACT PURPOSE We investigated whether type of physical activity (PA) (sports, running, fitness/dance) engaged in during adolescence is associated with body composition in late adolescence or early adulthood. METHODS Data were drawn from 631 participants in the Nicotine Dependence in Teens study, a prospective investigation of students ages 12–13 years at inception. Self-report PA data were collected at baseline, in Grade 7, and every 3-4 months thereafter during the 5 years of high school (1999–2005). Anthropometric indicators (height, weight, waist circumference, triceps and subscapular skinfold thickness) were measured at ages 12, 16 and 24 years. Based on prior exploratory factor analysis, PA were categorized into one of three types (sports, running, fitness/dance). Regression models estimated the association between number of years participating in each PA type (0-5 years) during high school and body composition measures in later adolescence or early adulthood. RESULTS In multivariable models accounting for age, sex, and parent education, more years participating in running during adolescence was associated with lower body mass index (BMI), waist circumference, and skinfold thickness in later adolescence and early adulthood (all p

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Association between Physical Activity and Adiposity in Adolescents with Down Syndrome

Purpose Obesity is highly prevalent among adolescents with Down syndrome (DS); however, reported associations between body composition and moderate-to-vigorous physical activity (MVPA) have been small and non-significant. The purpose of this study to compare group differences between adolescents with and without DS, including dual-energy x-ray absorptiometry (DXA) measured body composition and accelerometer-measured physical activity, and then examine associations within adolescents with DS. Methods Thirty-nine adolescents (22 with DS and 17 typically developing controls), aged 12-18 years participated in the study. Groups had similar distributions of age, sex, and Tanner pubertal stage. Body composition was assessed by DXA, BMI, and BMI percentile. MVPA was measured with Actigraph GT3X+ accelerometers. Results Adolescents with DS had significantly higher BMI, BMI percentile, and DXA-derived percent body fat (BF%), as well as lower MVPA compared to controls (p .05). Conclusions Our findings suggest that MVPA is associated with adiposity when measured with DXA among adolescents with DS. Corresponding Author: E. Andrew Pitchford, Iowa State University, 534 Wallace Rd. Ames, IA 50011-1160, Office: 515-294-3136, Fax: 515-294-8740, Email: eapitch@iastate.edu This study was supported by funding from the National Institutes of Health (F31HD079227) and SHAPE America. Preparation of the manuscript was supported, in part, by the U.S. Department of Education (H325D110003). The authors have no conflicts of interest to declare. The results of the present study do not constitute an endorsement by ACSM. The authors declare that results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 20 November 2017 © 2017 American College of Sports Medicine

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The perioperative significance of systemic arterial diastolic hypertension in adults

Purpose of review Hypertension affects approximately one third of the U.S. population and is the most common preventable medical reason that surgical cases are postponed or cancelled. However, subtypes of hypertension and their perioperative risks are poorly studied and understood. We will review the natural history and pathophysiology of essential hypertension and discuss the perioperative significance of diastolic blood pressure elevation. Recent findings There is evidence that elevated preoperative diastolic blood pressures are associated with an increased perioperative risk of cardiovascular and cerebrovascular events and increased postoperatively 30-day mortality. However, lower preoperative diastolic blood pressures were found, in one study, to be associated with renal injury. Summary Diastolic hypertension and hypotension both carry perioperative risk. Further study needs to be dedicated to elucidating the risks and developing strategies for acute and chronic management of diastolic blood pressure changes in order to improve perioperative safety. Correspondence to Edwin G. Avery IV, MD, Chief Anesthesia Officer, Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA. Tel: +1 216 844 7334; fax: +1 216 844 3781; e-mail: edwin.avery@uhhospitals.org Copyright © 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Perioperative pulmonary thromboembolism: current concepts and treatment options

Purpose of review Anesthesiologists are familiar with pulmonary emboli prophylaxis paradigms and many have witnessed acute intraoperative embolization. Clinicians must balance conservative anticoagulation and aggressive intervention in perioperative submassive pulmonary emboli, yet the bulk of the literature excludes surgery as a relative contraindication. This review will summarize the current treatment options for acute pulmonary emboli, drawing attention to special considerations in perioperative submassive pulmonary emboli, and discuss right ventricular monitoring to improve assessment of intervention efficacy. Recent findings Recent reviews have identified the elevated risk and inadequacy of treatment of pulmonary embolism in intra and postoperative patients, in part because of the risks of systemic anticoagulation. Early studies of catheter-directed therapies have shown promising efficacy with a reduction in bleeding risk, which is especially important for perioperative patients. Success relies on defining endpoints, yet the practice of measuring mean pulmonary artery pressure alone to assess intervention efficacy is flawed. Summary Identifying submassive pulmonary emboli that requires treatment and optimizing therapy remains difficult. Researchers must consider avoiding systemic anticoagulation and focus on designing trials that evaluate intervention efficacy in surgical patients. The success of catheter-directed therapy in early trials warrants further investigation into using these therapies in the treatment of perioperative submassive pulmonary emboli. Correspondence to Paul M. Heerdt, MD, PhD, Division of Applied Hemodynamics, Department of Anesthesiology, Yale University School of Medicine, 333 Cedar Street B425, New Haven, CT 06520, USA. E-mail: paul.heerdt@yale.edu Copyright © 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Surgery and discontinuation of angiotensin converting enzyme inhibitors: current perspectives

Purpose of review The current article reviews the current evidence for continuing or discontinuing angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) during the perioperative period. Recent findings In patients undergoing treatment of hypertension with ACEIs or ARBs, there are both benefits associated with continuing these medications during the perioperative period and higher risk for perioperative hypotension and its complications. Summary Since the introduction of ACEIs and ARBs into clinical practice, their use during the perioperative period has been controversial. Although these medications increase the risk of serious hypotension immediately after induction and maintenance of anesthesia, their use has numerous benefits, making it reasonable to continue them during perioperative period. Correspondence to Nikola Bradic, MD, Department of Cardiovascular Anesthesiology and Cardiac Intensive Medicine, Clinic of Anesthesiology, Resuscitation and Intensive Care Medicine, University Hospital Dubrava, Gojko Susak Avenue No. 6, 10000 Zagreb, Croatia. e-mail: nbradic@kbd.hr Copyright © 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Drug-induced sleep endoscopy: from obscure technique to diagnostic tool for assessment of obstructive sleep apnea for surgical interventions

Purpose of review Provide a practical update on drug-induced sleep endoscopy (DISE) for anesthesia providers, which can also serve as a reference for those preparing to establish a DISE program. Recent findings New developments in surgical approaches to OSA and the growing global incidence of the condition have stimulated increased interest and demand for drug-induced sleep endoscopy. New techniques include transoral robotic surgery and hypoglossal nerve stimulation. Recent DISE literature has sought to address numerous debates including relevance of DISE findings to those during physiologic sleep and the most appropriate depth and type of sedation for DISE. Propofol and dexmedetomidine have supplanted midazolam as the drugs of choice for DISE. Techniques based on pharmacokinetic models of propofol are superior to empiric dosing with regard to risk of respiratory compromise and the reliability of dexmedetomidine to achieve adequate conditions for a complete DISE exam is questionable. Summary The role of DISE in surgical evaluation and planning for treatment of OSA continues to develop. Numerous questions as to the optimal anesthetic approach remain unanswered. Multicenter studies that employ a standardized approach using EEG assessment, pharmacokinetic–pharmacodynamic modelling, and objectively defined clinical endpoints will be helpful. There may be benefit to undertaking DISE studies in non-OSA patients. Correspondence to Joshua H. Atkins, Associate Professor of Anesthesiology & Critical Care, Associate Professor of Otorhinolaryngology: Head & Neck Surgery, Department of Anesthesiology & Critical Care, Perelman School of Medicine at the University of Pennsylvania, 680 Dulles Building, 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel: +1 215 203 4781; e-mail: Joshua.Atkins@uphs.upenn.edu Copyright © 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Immediate effects of simultaneous application of transcutaneous electrical nerve stimulation and ultrasound phonophoresis on active myofascial trigger points: a randomized controlled trial

Objective was to investigate the efficacy of phonophoresis with combined therapy (PH-CT) on active myofascial trigger points (MTrPs). Participants One hundred participants with acute mechanical neck pain and at least one active MTrP in the upper trapezius were randomly assigned into 4 equal groups. Intervention Groups consisted of; diclofenac PH-CT; diclofenac phonophoresis (PH); ultrasound (US) with coupling gel and sham-US; applied for 10 minutes over MTrP. Measurements included pressure pain threshold (PPT) and active cervical lateral flexion. Results There were statistically significant improvements in post-intervention PPT and range of motion (ROM) values in treatment groups (P<.0001 as for the sham-us no significant difference was found between pre- and post-intervention values>.05). Bonferroni correction test revealed that there was a significant difference between all the four groups in PPT values (P<.0001 however it was non-significant>0.05) for ROM. Conclusion Diclofenac PH-CT, PH, and US were all effective in increasing PPT values and ROM. Additionally, PH-CT was shown to be superior over PH, and PH was superior over US in terms of reducing pain sensitivity. However, none of the treatment groups were found to be superior over the other in increasing ROM. Correspondence (for publication) for contact purposes: Name-Mary Kamal Nassif Takla, Department-Basic Sciences for Physical Therapy, Institution-Faculty of Physical Therapy, Cairo University, Country-Egypt. Email-marynassif@pt.cu.edu.eg Ethics approval: The Board Council of Higher Education of the School of Physical Therapy, the Institutional Review Board of Higher Education and Research of Cairo University, and the Supreme Council of Universities at Egypt approved this study. The study is prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616001677493). All participants gave written informed consent before data collection began. Conflict of interests: None Source(s) of support and Funding: None Pervious presentation or publication: None Financial benefits to the authors: None Acknowledgements: None Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Lean Mass and Functional Recovery in Men With Hip Fracture: A Short-Term Prospective Pilot Study

ABSTRACT OBJECTIVE To assess the capability of different definitions of low appendicular lean mass (aLM) to predict the short-term functional recovery in hip-fracture men. DESIGN We investigated 80 of 95 men with hip fracture admitted consecutively to a rehabilitation hospital. Body composition was assessed by dual-energy x-ray absorptiometry. Functional recovery after inpatient rehabilitation was evaluated using Barthel Index scores. RESULTS The patients with aLM above the cut-off value of 19.75kg indicated by the Foundation for the National Institutes of Health (FNIH) had significantly higher Barthel Index scores than those with aLM below the cut-off value(p=0.002). Patients' categorization according to the same threshold (aLM=19.75kg) was significantly associated with a Barthel Index score ≥85 after adjustment for age, cognitive impairment, hip-fracture type, comorbidities, and medications (odds ratio = 7.17; 95% CI 1.43-35.94; p = 0.017). Conversely, patients' categorization according to neither Baumgartner's cut-off value (7.26kg/m2) for aLM/height2 nor FNIH cut-off value(0.789) for aLM divided by body mass index (BMI) was significantly associated with the Barthel Index scores. CONCLUSIONS Categorization according to the FNIH threshold for aLM, but not to the FNIH threshold for aLM/BMI or Baumgartner's threshold for aLM/height2, was associated with the short-term recovery in activities of daily living following a hip-fracture in men. CORRESPONDING AUTHOR: Dr. Marco Di Monaco, Osteoporosis Research Center, Division of Physical Medicine and Rehabilitation, Presidio Sanitario San Camillo, Strada Santa Margherita 136, 10131, Torino, Italy. Tel. 0039 011 8199411; Fax 0039 011 8193012; Email Marco.di.monaco@alice.it,m.di-monaco@h-sancamillo.to.it DISCLOSURES: All the authors have no conflicts of interest. The study was not funded. The authors had no financial benefits for the study. The results have not been previously presented. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Minimally invasive esophagectomy: a propensity score-matched analysis of semiprone versus prone position

Abstract

Background

The preferred surgical approach for esophageal cancer is a minimally invasive transthoracic esophagectomy with a two-field lymph node dissection. The thoracoscopic phase may be performed either in prone- or in left lateral decubitus (LLD) position. Prone positioning has been associated with better pulmonary outcomes compared to LLD positioning; however, conversion to a classic thoracotomy is more difficult. The semiprone position has been proposed as an alternative approach.

Methods

A retrospective review of a prospectively maintained database (2008–2014) was performed to compare postoperative complications, surgical radicality, and lymph node yield between patients who underwent three-stage minimally invasive transthoracic esophagectomy in either the prone or semiprone position. Comparative analyses were conducted before and after propensity score matching.

Results

One hundred and twenty-one patients were included. In total, 82 patients underwent minimally invasive esophagectomy (MIE) in semiprone position and 39 patients in prone position. After propensity score matching, both groups consisted of 39 patients. The operative time in the semiprone group was longer (368 vs. 225 min, P < 0.001) and in this group the lymph node yield was significantly higher (16 (range 6–80) vs. 13 (range 3–33), P = 0.019). There were no statistically significant differences regarding radical resections, postoperative complications, and hospital stay.

Conclusion

The use of semiprone positioning in MIE is safe, feasible, and at least comparable to MIE in prone position in terms of oncological clearance and postoperative complications.

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App warns users when drugs are laced with fentanyl

Bad Batch Alert is an anonymous texting service that uses data to track fentanyl overdose hotspots and points users in the direction of harm reduction services

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Copy number variation arising from gene conversion on the human Y chromosome

Abstract

We describe the variation in copy number of a ~ 10 kb region overlapping the long intergenic noncoding RNA (lincRNA) gene, TTTY22, within the IR3 inverted repeat on the short arm of the human Y chromosome, leading to individuals with 0–3 copies of this region in the general population. Variation of this CNV is common, with 266 individuals having 0 copies, 943 (including the reference sequence) having 1, 23 having 2 copies, and two having 3 copies, and was validated by breakpoint PCR, fibre-FISH, and 10× Genomics Chromium linked-read sequencing in subsets of 1234 individuals from the 1000 Genomes Project. Mapping the changes in copy number to the phylogeny of these Y chromosomes previously established by the Project identified at least 20 mutational events, and investigation of flanking paralogous sequence variants showed that the mutations involved flanking sequences in 18 of these, and could extend over > 30 kb of DNA. While either gene conversion or double crossover between misaligned sister chromatids could formally explain the 0–2 copy events, gene conversion is the more likely mechanism, and these events include the longest non-allelic gene conversion reported thus far. Chromosomes with three copies of this CNV have arisen just once in our data set via another mechanism: duplication of 420 kb that places the third copy 230 kb proximal to the existing proximal copy. Our results establish gene conversion as a previously under-appreciated mechanism of generating copy number changes in humans and reveal the exceptionally large size of the conversion events that can occur.

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Rebuttal from Y. C. Tzeng and R. B. Panerai

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CrossTalk opposing view: dynamic cerebral autoregulation should be quantified using induced (rather than spontaneous) blood pressure fluctuations

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CrossTalk proposal: dynamic cerebral autoregulation should be quantified using spontaneous blood pressure fluctuations

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Rebuttal from David Simpson and Jurgen Claassen

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The Risk of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers without a First-Degree Relative with Breast Cancer

ABSTRACT

The objective of this study was to estimate the lifetime risk of breast cancer in women with a BRCA1 or BRCA2 mutation with and without at least one first-degree relative with breast cancer. A total of 2835 women with a BRCA1 or BRCA2 mutation were followed. Age- and gene-specific breast cancer rates were calculated. The relative risks of breast cancer for subjects with a family history of breast cancer, compared to no family history were calculated. The mean age at baseline was 41.1 years, and they were followed for a mean of 6.0 years. The estimated penetrance of breast cancer to age 80 years was 60.8% for BRCA1 and 63.1% for BRCA2. For all BRCA carriers, the penetrance of breast cancer to age 80 for those with no first-degree relative with breast cancer was 60.4%, and was 63.3% for those with at least one first-degree relative with breast cancer. The risk of breast cancer for BRCA carriers with no first-degree relative with breast cancer is substantial, and as a result, clinical management for these women should be the same as those for women with an affected relative.

Penetrance of breast cancer for BRCA2 carriers by subjects with or without first degree relative with breast cancer

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Improved methods for acrylic-free implants in nonhuman primates for neuroscience research

Traditionally, head fixation devices and recording cylinders have been implanted in nonhuman primates (NHP) using dental acrylic despite several shortcomings associated with acrylic. The use of more biocompatible materials such as titanium and PEEK is becoming more prevalent in NHP research. We describe a cost-effective set of procedures that maximizes the integration of headposts and recording cylinders with the animal's tissues while reducing surgery time. Nine rhesus monkeys were implanted with titanium headposts, and one of these was also implanted with a recording chamber. In each case, a three-dimensional printed replica of the skull was created based on computerized tomography scans. The titanium feet of the headposts were shaped, and the skull thickness was measured preoperatively, reducing surgery time by up to 70%. The recording cylinder was manufactured to conform tightly to the skull, which was fastened to the skull with four screws and remained watertight for 8.5 mo. We quantified the amount of regression of the skin edge at the headpost. We found a large degree of variability in the timing and extent of skin regression that could not be explained by any single recorded factor. However, there was not a single case of bone exposure; although skin retracted from the titanium, skin also remained adhered to the skull adjacent to those regions. The headposts remained fully functional and free of complications for the experimental life of each animal, several of which are still participating in experiments more than 4 yr after implant.

NEW & NOTEWORTHY Cranial implants are often necessary for performing neurophysiology research with nonhuman primates. We present methods for using three-dimensional printed monkey skulls to form and fabricate acrylic-free implants preoperatively to decrease surgery times and the risk of complications and increase the functional life of the implant. We focused on reducing costs, creating a feasible timeline, and ensuring compatibility with existing laboratory systems. We discuss the importance of using more biocompatible materials and enhancing osseointegration.

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Social experience alters socially induced serotonergic fluctuations in the inferior colliculus

Past social experience and current social context shape the responses of animals to social signals. The serotonergic system is one potential mechanism by which both experiential and contextual factors could be conveyed to sensory systems, such as the auditory system, for multiple reasons. 1) Many features of the serotonergic system are sensitive to social experience. 2) Elevations in serotonergic activity are triggered by social partners, and variations in socially triggered serotonergic responses reflect behavioral differences among social encounters. 3) Serotonin is an auditory neuromodulator, altering how auditory neurons respond to sounds including conspecific vocalizations. In this study, we tested how social experience influences the socially triggered serotonergic response in the inferior colliculus, an auditory midbrain region with an important role in vocalization processing. We used carbon fiber voltammetry to measure serotonin during social interactions of male mice (Mus musculus) from different social backgrounds: 4 weeks of grouped or individual housing. When paired with an unfamiliar male, both group-housed and individually housed males demonstrated elevations in serotonin; however, individually housed males exhibited socially triggered serotonergic responses with delayed time courses compared with the group-housed males. Furthermore, group-housed males displayed previously described correlations between the socially triggered serotonergic response and behaviors such as social investigation. In contrast, individually housed males did not show these serotonin-behavior relationships. These results suggest that social experience gained via social housing may shape the ability of the central serotonergic system to encode social context in sensory regions.

NEW & NOTEWORTHY We demonstrate that past social experience influences the fidelity with which the serotonergic system represents social context in an auditory region. Social experience altered the time course of socially triggered serotonergic responses and changed how the serotonergic system reflects behavioral variations among social encounters of the same context. These findings are significant to the study of communication, suggesting that centralized neuromodulatory systems potentially convey integrated information regarding past experience and current context to primary sensory regions.

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Methodological considerations for a chronic neural interface with the cuneate nucleus of macaques

While the response properties of neurons in the somatosensory nerves and anterior parietal cortex have been extensively studied, little is known about the encoding of tactile and proprioceptive information in the cuneate nucleus (CN) or external cuneate nucleus (ECN), the first recipients of upper limb somatosensory afferent signals. The major challenge in characterizing neural coding in CN/ECN has been to record from these tiny, difficult-to-access brain stem structures. Most previous investigations of CN response properties have been carried out in decerebrate or anesthetized animals, thereby eliminating the well-documented top-down signals from cortex, which likely exert a strong influence on CN responses. Seeking to fill this gap in our understanding of somatosensory processing, we describe an approach to chronically implanting arrays of electrodes in the upper limb representation in the brain stem in primates. First, we describe the topography of CN/ECN in rhesus macaques, including its somatotopic organization and the layout of its submodalities (touch and proprioception). Second, we describe the design of electrode arrays and the implantation strategy to obtain stable recordings. Third, we show sample responses of CN/ECN neurons in brain stem obtained from awake, behaving monkeys. With this method, we are in a position to characterize, for the first time, somatosensory representations in CN and ECN of primates.

NEW & NOTEWORTHY In primates, the neural basis of touch and of our sense of limb posture and movements has been studied in the peripheral nerves and in somatosensory cortex, but coding in the cuneate and external cuneate nuclei, the first processing stage for these signals in the central nervous system, remains an enigma. We have developed a method to record from these nuclei, thereby paving the way to studying how sensory information from the limb is encoded there.

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Corticospinal excitability of the biceps brachii is shoulder position dependent

The purpose of this study was to examine the effect of shoulder position on corticospinal excitability (CSE) of the biceps brachii during rest and a 10% maximal voluntary contraction (MVC). Participants (n = 9) completed two experimental sessions with four conditions: 1) rest, 0° shoulder flexion; 2) 10% MVC, 0° shoulder flexion; 3) rest, 90° shoulder flexion; and 4) 10% MVC, 90° shoulder flexion. Transcranial magnetic, transmastoid electrical, and Erb's point stimulation were used to induce motor-evoked potentials (MEPs), cervicomedullary MEPs (CMEPs), and maximal muscle compound potentials (M_max), respectively, in the biceps brachii in each condition. At rest, MEP, CMEP, and M_max amplitudes increased (P < 0.01) by 509.7 ± 118.3%, 113.3 ± 28.3%, and 155.1 ± 47.9%, respectively, at 90° compared with 0°. At 10% MVC, MEP amplitudes did not differ (P = 0.08), but CMEP and M_max amplitudes increased (P < 0.05) by 32.3 ± 10.5% and 127.9 ± 26.1%, respectively, at 90° compared with 0°. MEP/M_max increased (P < 0.01) by 224.0 ± 99.1% at rest and decreased (P < 0.05) by 51.3 ± 6.7% at 10% MVC at 90° compared with 0°. CMEP/M_max was not different (P = 0.22) at rest but decreased (P < 0.01) at 10% MVC by 33.6 ± 6.1% at 90° compared with 0°. EMG increased (P < 0.001) by 8.3 ± 2.0% at rest and decreased (P < 0.001) by 21.4 ± 4.4% at 10% MVC at 90° compared with 0°. In conclusion, CSE of the biceps brachii was dependent on shoulder position, and the pattern of change was altered within the state in which it was measured. The position-dependent changes in M_max amplitude, EMG, and CSE itself all contribute to the overall change in CSE of the biceps brachii.

NEW & NOTEWORTHY We demonstrate that when the shoulder is placed into two common positions for determining elbow flexor force and activation, corticospinal excitability (CSE) of the biceps brachii is both shoulder position and state dependent. At rest, when the shoulder is flexed from 0° to 90°, supraspinal factors predominantly alter CSE, whereas during a slight contraction, spinal factors predominantly alter CSE. Finally, the normalization techniques frequently used by researchers to investigate CSE may under- and overestimate CSE when shoulder position is changed.

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ImageTrend and CrewSense announce new offering

LAKEVILLE, Minn. and GRANTS PASS, Ore. — ImageTrend, Inc., a leading EMS ePCR (electronic patient care records), fire RMS (records management system) and reporting solutions provider, and CrewSense, an employee scheduling, overtime distribution and resource management platform for the public safety industry - announce today a bundled integration. Both technology offerings will work together seamlessly ...

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Clinical sequencing: from raw data to diagnosis with lifetime value

Abstract

High-throughput sequencing (HTS) has revolutionized genetics by enabling the detection of sequence variants at hitherto unprecedented large scale. Despite these advances, however, there are still remaining challenges in the complete coverage of targeted regions (genes, exome or genome) as well as in HTS data analysis and interpretation. Moreover, it is easy to get overwhelmed by the plethora of available methods and tools for HTS. Here, we review the step-by-step process from the generation of sequence data to molecular diagnosis of Mendelian diseases. Highlighting advantages and limitations, this review addresses the current state of (i) HTS technologies, considering targeted, whole-exome, and whole-genome sequencing on short- and long-read platforms; (ii) read alignment, variant calling and interpretation; as well as (iii) regulatory issues related to genetic counseling, reimbursement, and data storage.

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Retropharyngeal Dissection by Parker Flex-Tip Nasal Endotracheal Tube.

Retropharyngeal Dissection by Parker Flex-Tip Nasal Endotracheal Tube.

Anesth Prog. 2017;64(4):240-243

Authors: Terumitsu M, Hirahara M, Seo K

Abstract
Possible complications of nasotracheal intubation include injury to the nasal or pharyngeal mucosa. Dissection of the retropharyngeal tissue by the endotracheal tube is one of the rarer of the more severe complications. Previous studies have indicated that the Parker Flex-Tip (PFT) tracheal tube (Parker Medical, Highlands Ranch, Colo) reduces the incidence of mucosal injury. We experienced a case involving inadvertent retropharyngeal placement of a PFT tube in a 29-year-old patient during nasotracheal intubation under general anesthesia for elective dental treatment. Despite thermosoftening the PFT tube, expanding the nasal meatus, and ensuring gentle maneuvering, the tube intruded into the left retropharyngeal mucosa. However, the injury was not severe, and the only required treatment was the administration of antibiotics and corticosteroids. Even when a PFT tube is utilized, pharyngeal dissection is possible. When resistance is felt during passing of the PFT tube through the nasopharynx, an alternative method to overcome this resistance should be utilized.

PMID: 29200373 [PubMed - in process]

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Fourteen-Year Anti-TNF Therapy in Crohn’s Disease Patients: Clinical Characteristics and Predictive Factors

Abstract

Background

Crohn's disease (CD) is an intractable disease that requires long-term treatment. Tumor necrosis factor (TNF) inhibitors have strong efficacy and are widely used for CD treatment. However, a loss of response is one of the issues in long-term TNF therapy. To identify the factors affecting the efficacy of long-term CD treatment with TNF inhibitors, we conducted a retrospective study of treatment outcomes and clinical factors using clinical data over a 14-year period.

Methods

Clinical characteristics and factors for surgery, hospitalization, and TNF inhibitor treatment discontinuation were examined in 219 biologic-naïve patients who were treated with TNF inhibitors at our hospital before October 2014.

Results

Treatment persistence rates with no hospitalization, surgery, or dose escalation were 60.7, 25.9, and 17.3% for 1, 5, and 10 years, respectively; these rates did not differ between infliximab (IFX) and adalimumab. In patients receiving IFX dose escalation, 1- and 5-year persistence rates were approximately 90.4 and 65.1%, respectively. Previous surgery (OR = 1.45, P = 0.043) was identified as a risk factor for surgery, male sex (OR = 0.70, P = 0.044) and previous surgery (OR = 1.51, P = 0.03) were risk factors for hospitalization, and perianal fistula (OR = 1.39, P = 0.049) was the risk factor for TNF inhibitor treatment discontinuation.

Conclusions

The durability of anti-TNF therapy in CD patients remains a problem, and treatment optimization that includes dose escalation should be carefully examined depending on patient characteristics and the timing of optimization.

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Perioperative management of gastrostomy tube placement in Duchenne muscular dystrophy adolescent and young adult patients: A role for a perioperative surgical home

Summary

Background

In past decades, Duchenne muscular dystrophy patients have been living longer and as the disease advances, patients experience multisystemic deterioration. Older patients often require gastrostomy tube placement for nutritional support. For optimizing the perioperative care, a practice of multidisciplinary team can better anticipate, prevent, and manage possible complications and reduce the overall perioperative morbidity and mortality.

Aims

The aim of this study was to review our experience with perioperative care of adolescent and young adults with Duchenne muscular dystrophy undergoing gastrostomy by various surgical approaches in order to identify challenges and improve future perioperative care coordination to reduce morbidity.

Methods

We retrospectively examined cases of gastrostomy tube placement in patients of ages 15 years and older between 2005 and 2016. We reviewed preoperative evaluation, anesthetic and surgical management, and postoperative complications.

Results

Twelve patients were identified; 1 had open gastrostomy, 3 laparoscopic gastrostomies, 5 percutaneous endoscopic guided, and 3 radiologically inserted gastrostomy tubes. All patients had preoperative cardiac evaluation with 6 patients demonstrating cardiomyopathy. Nine patients had preoperative pulmonary consultations and the pulmonary function tests reported forced vital capacity of ≤36% of predicted. Eight patients were noninvasive positive pressure ventilation dependent. General anesthesia with tracheal intubation was administered in 8 patients, and intravenous sedation in 4 patients; 1 received sedation supplemented with regional anesthesia and 3 received deep sedation. One patient had a difficult intubation that resulted in trauma and prolonged tracheal intubation. Three patients developed postoperative respiratory complications. Two patients' procedures were postponed due to inadequate preoperative evaluation and 1 because of disagreement between anesthesia and procedural services as to the optimal approach for airway management.

Conculsion

Optimal management of the perioperative care of Duchenne muscular dystrophy patients requires input from relevant medical specialists, proceduralist and anesthesiologist. This complexity of care coordination presents an opportunity for anesthesiologists to lead a collaborative perioperative team in management of advanced Duchenne patients coming for gastrostomy.

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Ultrasound-guided lower forearm median nerve block in open surgery for trigger thumb in 1- to 3-year-old children: A randomized trial

Summary

Background and Aim

Trigger thumb is a common hand disability in children and is primarily treated with open surgery. A conscious median nerve block can usually meet the requirements for trigger thumb-releasing surgery in adults; however, its effectiveness in children requires further clarification. The present study aims to demonstrate whether ultrasound-guided lower forearm median nerve blockade is a viable option for children undergoing open surgery for trigger thumb.

Methods

A prospective randomized study was designed to compare median nerve blocks guided by ultrasonography with those guided by anatomic landmarks. Following induction of general anesthesia, the children received a median nerve block performed either by ultrasound-guided block of the lower forearm (group U) or landmark-based blocking at the proximal wrist crease level (group T) with a 0.2% ropivacaine injection. The success rates were compared between groups as the primary endpoint; additional sufentanil and propofol administration, anesthesia recovery time, and other secondary endpoints were also compared.

Results

A total of 100 children (age 1-3 years) with ASA status I who were scheduled for open surgery for trigger thumb were included in this study (n = 50 per group). Thirty-seven children in group T and 50 children in group U underwent successful blocks. The rate of unsuccessful blockade was significantly lower in group U than group T (0% and 26%, respectively), and rate of additional sufentanil and propofol administration was also lower in group U than in group T.

Conclusion

Ultrasound-guided lower forearm median nerve block can provide more effective analgesia, a higher success rate, and lower general and local anesthetic dosages than the anatomic landmark-based blocking method in children undergoing open surgery for trigger thumb.

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Ultrasound-guided pudendal nerve block in children: A new technique of ultrasound-guided transperineal approach

Summary

Background

Transperineal pudendal nerve block guided by nerve stimulator is used in pediatric anesthesia as an alternative to caudal analgesia in perineal surgery. The risk of rectal puncture or intravascular injection is inherent to this blinded technique. We described a new technique of transperineal pudendal nerve block, with ultrasound guidance, to improve safety of the technique.

Aims

The first goal of this study was to describe this new technique and to test its feasibility. The second objective was to evaluate intra operative effectiveness and postoperative pain control.

Methods

After parental and children consent, this prospective descriptive study included children aged 1-15 years, ASA status I-III, scheduled for general anesthesia associated with bilateral pudendal nerve block for an elective perineal surgery. After standardized general anesthesia, the anesthesiologist performed pudendal nerve block under ultrasound guidance with "out of plane" approach and evaluated the visualization of anatomical structures (ischial tuberosity, rectum, and pudendal artery), of the needle and of the local anesthetic spread. Pudendal nerve block failure was defined as an increase in mean arterial blood pressure or heart rate more than 20% compared to baseline values after surgical incision. In the postoperative period, the need for rescue analgesia was noted.

Results

During the study period, 120 blocks were performed in 60 patients, including 59 boys. Quality of the ultrasonographic image was good in 81% of blocks, with easy visualization of ischium and rectum in more than 95% of cases. Localization of the tip of the needle was possible for all pudendal nerve blocks, directly or indirectly. The spread of local anesthetic was seen in 79% of cases. The block was effective in 88% of cases.

Conclusion

The new technique of ultrasound-guided pudendal nerve block, described in this study, seems to be easy to perform with a good success rate, and probably improves safety of the puncture and of the injection by real-time visualization of anatomical structures and local anesthetic spread.

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Prospective analysis of serious cardiorespiratory events in children during ophthalmic artery chemotherapy for retinoblastoma under a deep standardized anesthesia

Summary

Background and Objective

Serious adverse cardiorespiratory events complicate super selective ophthalmic artery chemotherapy for retinoblastoma in anesthetized children. Their mechanism remains unclear but may be attributed to an autonomic nervous reflex induced by the catheter close to the ophthalmic artery. Inadequate depth of anesthesia during catheter stimulation might be an aggravating factor. Thus, we tested whether deep general anesthesia reduced the incidence of serious cardiorespiratory events.

Methods

Children were prospectively included in this observational study. Standardized deep general anesthesia with sevoflurane, rocuronium, and sufentanil was administered. Sevoflurane MAC was kept between 1.5 and 1.7 and additional sufentanil administered. Serious cardiorespiratory event criteria were predefined and included arterial hypotension, bradycardia, and severe decrease in lung compliance. They were recorded and the factors influencing their occurrence were investigated.

Results

One hundred fifteen procedures were performed on 32 children. The median MAC of sevoflurane was 1.5 and median BIS value was 44. Serious cardiorespiratory events occurred in 20% of procedures and were mainly severe decrease in lung compliance (83% of events). All of them required active treatment. One procedure was aborted due to cardiorespiratory compromise and required an epinephrine infusion. All severe decreases in lung compliance occurred within 2 minutes after catheter insertion in the ophthalmic artery. No recorded demographic and endovascular characteristics were associated with serious cardiorespiratory events.

Conclusion

Serious cardiorespiratory events occur commonly during super selective ophthalmic artery chemotherapy. Standardized deep anesthesia with analgesia did not appear to be protective. No predictive factors were identified, but these events systematically arose within 2 minutes after ophthalmic artery catheter insertion. Anesthetists and neuroradiologists should be prepared to manage these serious complications and parents should be informed of the risks.

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Cerebrovascular blood pressure autoregulation monitoring and postoperative transient ischemic attack in pediatric moyamoya vasculopathy

Summary

Background

Children with moyamoya vasculopathy are at high risk of perioperative cerebral ischemia or hyperperfusion. Maintaining blood pressure within the range of functional cerebrovascular blood pressure autoregulation might reduce the risk of perioperative neurologic injury.

Aims

We tested whether blood pressure autoregulation is associated with postoperative transient ischemic attack in a study of patients with pediatric moyamoya vasculopathy.

Methods

We conducted an observational study of 15 pediatric patients undergoing surgical revascularization with pial synangiosis. Nine patients had bilateral moyamoya and 6 had unilateral moyamoya. We measured autoregulatory vasoreactivity intraoperatively and during the first postoperative night with the hemoglobin volume index, a value derived from near-infrared spectroscopy. We also identified the optimal mean arterial blood pressure at which autoregulation was most robust in each patient.

Results

Of the 15 children monitored, 3 with bilateral moyamoya and one with unilateral moyamoya experienced a transient ischemic attack. Poorer autoregulation during surgery was associated with postoperative transient ischemic attack among those with bilateral vasculopathy (P = .048, difference in hemoglobin volume index medians: 0.023, 95% confidence interval: 0.003-0.071). This relationship was not observed with postoperative autoregulation. The optimal mean arterial blood pressure was identifiable during surgery in all monitored patients, varied among patients, and often differed between the intraoperative and postoperative periods.

Conclusion

Dysfunctional intraoperative autoregulation may increase the risk of TIA in patients with pediatric moyamoya vasculopathy. The blood pressure range that supports autoregulation appears to vary among patients. Using autoregulation monitoring to guide individualized blood pressure goals should be studied as a potential method to reduce perioperative neurologic morbidity in pediatric patients with moyamoya.

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Fluid replacement modulates oxidative stress- but not nitric oxide-mediated cutaneous vasodilation and sweating during prolonged exercise in the heat

The roles of nitric oxide synthase (NOS), reactive oxygen species (ROS), and angiotensin II type 1 receptor (AT₁R) activation in regulating cutaneous vasodilation and sweating during prolonged (≥60 min) exercise are currently unclear. Moreover, it remains to be determined whether fluid replacement (FR) modulates the above thermoeffector responses. To investigate, 11 young men completed 90 min of continuous moderate intensity (46% Vo_2peak) cycling performed at a fixed rate of metabolic heat production of 600 W (No FR condition). On a separate day, participants completed a second session of the same protocol while receiving FR to offset sweat losses (FR condition). Cutaneous vascular conductance (CVC) and local sweat rate (LSR) were measured at four intradermal microdialysis forearm sites perfused with: 1) lactated Ringer (Control); 2) 10 mM N^G-nitro-l-arginine methyl ester (l-NAME, NOS inhibition); 3) 10 mM ascorbate (nonselective antioxidant); or 4) 4.34 nM losartan (AT₁R inhibition). Relative to Control (71% CVC_max at both time points), CVC with ascorbate (80% and 83% CVC_max) was elevated at 60 and 90 min of exercise during FR (both P < 0.02) but not at any time during No FR (all P > 0.31). In both conditions, CVC was reduced at end exercise with l-NAME (60% CVC_max; both P < 0.02) but was not different relative to Control at the losartan site (76% CVC_max; both P > 0.19). LSR did not differ between sites in either condition (all P > 0.10). We conclude that NOS regulates cutaneous vasodilation, but not sweating, irrespective of FR, and that ROS influence cutaneous vasodilation during prolonged exercise with FR.

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The plateau in the NIRS-derived [HHb] signal near the end of a ramp incremental test does not indicate the upper limit of O2 extraction in the vastus lateralis

This study aimed to examine, at the level of the active muscles, whether the plateau in oxygen (O₂) extraction normally observed near the end of a ramp incremental (RI) exercise test to exhaustion is caused by the achievement of an upper limit in O₂ extraction. Eleven healthy men (27.3 ± 3.0 yr, 81.6 ± 8.1 kg, 183.9 ± 6.3 cm) performed a RI cycling test to exhaustion. O₂ extraction of the vastus lateralis (VL) was measured continuously throughout the test using the near-infrared spectroscopy (NIRS)-derived deoxygenated hemoglobin [HHb] signal. A leg blood flow occlusion was performed at rest (LBF_OCC1) and immediately after the RI test (LBF_OCC2). The [HHb] values during the resting occlusion (108.1 ± 21.7%; LBF_OCC1) and the peak values during exercise (100 ± 0%; [HHb]_plateau) were significantly greater than those observed at baseline (0.84 ± 10.6% at baseline 1 and 0 ± 0% at baseline 2) (P < 0.05). No significant difference was found between LBF_OCC1 and [HHb]_plateau (P > 0.05) or between the baseline measurements (P > 0.05). [HHb] values at LBF_OCC2 (130.5 ± 19.7%) were significantly greater than all other time points (P < 0.05). These results support the existence of an O₂ extraction reserve in the VL muscle at the end of a RI cycling test and suggest that the observed plateau in the [HHb] signal toward the end of a RI test is not representative of an upper limit in O₂ extraction.

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Comparative NMR and NIRS analysis of oxygen-dependent metabolism in exercising finger flexor muscles

Muscle contraction requires the physiology to adapt rapidly to meet the surge in energy demand. To investigate the shift in metabolic control, especially between oxygen and metabolism, researchers often depend on near-infrared spectroscopy (NIRS) to measure noninvasively the tissue O₂. Because NIRS detects the overlapping myoglobin (Mb) and hemoglobin (Hb) signals in muscle, interpreting the data as an index of cellular or vascular O₂ requires deconvoluting the relative contribution. Currently, many in the NIRS field ascribe the signal to Hb. In contrast, ¹H NMR has only detected the Mb signal in contracting muscle, and comparative NIRS and NMR experiments indicate a predominant Mb contribution. The present study has examined the question of the NIRS signal origin by measuring simultaneously the ¹H NMR, ³¹P NMR, and NIRS signals in finger flexor muscles during the transition from rest to contraction, recovery, ischemia, and reperfusion. The experiment results confirm a predominant Mb contribution to the NIRS signal from muscle. Given the NMR and NIRS corroborated changes in the intracellular O₂, the analysis shows that at the onset of muscle contraction, O₂ declines immediately and reaches new steady states as contraction intensity rises. Moreover, lactate formation increases even under quite aerobic condition.

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A new paradigm of sodium regulation in inflammation and hypertension

Dysregulation of sodium (Na⁺) balance is a major cause of hypertensive cardiovascular disease. The current dogma is that interstitial Na⁺ readily equilibrates with plasma and that renal excretion and reabsorption is sufficient to regulate extracellular fluid volume and control blood pressure. These ideas have been recently challenged by the discovery that Na⁺ accumulates in tissues without commensurate volume retention and activates immune cells, leading to hypertension and autoimmune disease. However, objections have been raised to this new paradigm, with some investigators concerned about where and how salt is stored in tissues. Further concerns also include how Na⁺ is mobilized from tissue stores and how it interacts with various organ systems to cause hypertension and end-organ damage. This review assesses these two paradigms of Na⁺ regulation in the context of inflammation-mediated hypertension and cardiovascular disease pathogenesis. Also highlighted are future perspectives and important gaps in our understanding of how Na⁺ is linked to inflammation and hypertension. Understanding mechanisms of salt and body fluid regulation is the sine qua non of research efforts to identify therapeutic targets for hypertension and cardiovascular disease.

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