Cognitive rehabilitation is advantageous in terms of fatigue and independence in pediatric cancer treatment: a randomized-controlled study

This study aimed to investigate the effect of task-oriented inpatient cognitive rehabilitation on fatigue perception and independence in daily activities. Forty (22 males, 18 females) children with pediatric cancer were randomized to either study [n=22; 10.81 (1.33) years] or control [n=18; 10.16 (1.24) years] groups. The study group received a cognitive rehabilitation intervention in addition to a routine therapy program, and the control group received a routine therapy program for 15 sessions. Cognitive status, fatigue, and daily life activity outcomes were assessed by blinded assessors in before and after interventions in the hospital setting. The study group showed a significant decrease in fatigue (P values for fatigue before, during, and after activity: P

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Analysis of Genetic Diversity and Population Structure in Three Forest Musk Deer Captive Populations with Different Origins

Musk deer (Moschidae), whose secretion is an expensive and irreplaceable component of traditional medicine, have become endangered in the wild due to habitat fragmentation and over-exploitation. In recent years, China has had success in the artificial breeding of forest musk deer, thus relieving the pressure on wild populations. However, many farmed populations are experiencing degradation, and little genetic information is available for conservation management. In this study, we selected 274 individuals from three typical captive populations (originated from the Ta-pa Mountains (Tp), the midrange of the Qinling Mountains (Ql) and the Western Sichuan Plateau (WS), respectively) to evaluate the genetic variations. A total of more than 3.15 billion high-quality clean reads and 4.37 million high-quality SNPs were generated by RAD sequencing. Based on the analysis, we found that captive forest musk deer populations exhibit a relatively low level of genetic diversity. Ql displayed a higher level of genetic diversity than the Tp and WS populations. Tp and WS had experienced population bottlenecks in the past as inferred from the values of Tajima's D. There were high levels of heterozygote deficiency caused by inbreeding within the three populations. Population structure analysis suggested that the three populations have evolved independently, and a moderate amount of genetic differentiation has developed, although there was a low level of gene flow between the Ql and Tp populations. Furthermore, the average quantities of musk secreted by musk deer in the Tp and WS populations were significantly higher than that in the Ql population. The present genetic information should be considered in management plans for the conservation and utilization of musk deer from captive breeding.

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Bidirectional Selection for Body Weight on Standing Genetic Variation in a Chicken Model

Experimental populations of model organisms provide valuable opportunities to unravel the genomic impact of selection in a controlled system. The Virginia body weight chicken lines represent a unique resource to investigate signatures of selection in a system where long-term, single-trait, bidirectional selection has been carried out for more than 60 generations. At 55 generations of divergent selection, earlier analyses of pooled genome resequencing data from these lines revealed that 14.2% of the genome showed extreme differentiation between the selected lines, contained within 395 genomic regions. Here, we report more detailed analyses of these data exploring the regions displaying within- and between-line genomic signatures of the bidirectional selection applied in these lines. Despite the strict selection regime for opposite extremes in body weight, this did not result in opposite genomic signatures between the lines. The lines often displayed a duality of the sweep signatures, where an extended region of homozygosity in one line, in contrast to mosaic pattern of heterozygosity in the other line. These haplotype mosaics consisted of short, distinct haploblocks of variable between-line divergence, likely the results of a complex demographic history involving bottlenecks, introgressions and moderate inbreeding. We demonstrate this using the example of complex haplotype mosaicism in the growth1 QTL. These mosaics represent the standing genetic variation available at the onset of selection in the founder population. Selection on standing genetic variation can thus result in different signatures depending on the intensity and direction of selection.

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Biomechanical effects on the intermediate segment of noncontiguous hybrid surgery with cervical disc arthroplasty and anterior cervical discectomy and fusion: a finite element analysis

Surgery for cervical degenerative disc disorder (CDDD) at two noncontiguous segments is infrequent. Few studies have explored the biomechanical effects on the intermediate adjacent segment of anterior cervical discectomy and fusion (ACDF) or cervical disc arthroplasty (CDA) in this situation. No study has examined biomechanical differences between ACDF and hybrid surgery (HS) constructs for noncontiguous CDDD. Differences in the biomechanical changes between the intermediate and adjacent segments are unknown.

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Cost-effectiveness of microdiscectomy versus endoscopic discectomy for lumbar disc herniation

Microdiscectomy is a standard technique for the surgical treatment of lumbar disc herniation (LDH). Endoscopic discectomy (ED) is another surgical option that has become popular owing to reports of shorter hospitalization and earlier return to work. No study has evaluated health care costs associated with lumbar discectomy techniques and compared cost-effectiveness.

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Discriminating spatiotemporal movement strategies during spine flexion-extension in healthy individuals

The spine is an anatomically complex system with numerous degrees of freedom. Due to this anatomical complexity, it is likely that multiple motor control options exist to complete a given task.

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Malpractice claims in spine surgery in Germany: a 5-year analysis

Retrospective analysis of anonymized malpractice claims.

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The Effect of Sprint Interval Training on Body Composition of Postmenopausal Women

Introduction Menopause is accompanied by body composition changes that include a decrease in lean mass and aerobic fitness and an increase in fat mass. Sprint interval training (SIT) may be able to reverse these changes. Purpose To examine the effect of an 8-week SIT program on body composition and aerobic fitness of overweight postmenopausal women. Methods Forty postmenopausal women were randomised into SIT (n=20) or Control (n=20) groups. The SIT group completed three SIT sessions a week for 8 weeks with each session consisting of 20 minutes of alternating 8-second sprints and 12-seconds of light pedalling. Total mass, regional lean mass, and fat mass were assessed using dual-energy x-ray absorptiometry. Maximal oxygen uptake (V[Combining Dot Above]O2max) was predicted using a submaximal test. Results Total lean mass was significantly increased from pre-test (48.1±5.81 kg) to post-test (48.8±5.96 kg) and fat mass was significantly reduced (pre: 29.5±7.29 kg; post (29.1±7.61 kg) for the SIT group. Lean mass was mostly increased in the trunk (pre: 24.4±2.79 kg; post: 24.8±2.93 kg) and legs (pre: 15.6±2.31 kg; post: 15.9 ±2.34 kg). V[Combining Dot Above]O2max was significantly increased from pre (21.7±4.89 ml⋅kg-1⋅min-1) to post-test (24.4±4.96 ml⋅kg-1⋅min-1) for the SIT group only. Conclusions The SIT intervention increased total lean mass, decreased fat mass, and increased aerobic fitness of postmenopausal women after only 8 hours of actual exercise over 8 weeks. Address correspondence to: Yati N Boutcher, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, 2052, Australia. E-mail: y.boutcher@unsw.edu.au None of the authors had a personal or financial conflict of interest. The study received no sources of funding. 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. Funding: The study received no sources of funding. Conflict of interest: The authors declare that there is no conflict of interest regarding the publication of this paper. Accepted for publication: 31 January 2019. © 2019 American College of Sports Medicine

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Aerobic Exercise Performance and Muscle Strength in Statin Users—The LIFESTAT Study

Introduction Statins are widely used in both primary and secondary prevention of cardiovascular disease. The treatment increases the risk of muscle pain (myalgia) which can affect muscle function and levels of physical activity. We investigated whether statin-associated myalgia is coupled to impaired aerobic exercise performance including fat oxidation as well as impaired muscle strength. Methods A population-based survey (6000 people) was performed to assess the prevalence of statin-associated myalgia in the Danish population. In addition, 64 statin users in primary prevention with myalgia (M; n = 25; 61 ± 1 years) or without myalgia (NM; n = 37; 63 ± 1 years) as well as a control group not taking statins (C; n = 20; 60 ± 2 years) were enrolled in a cross-sectional study where they performed aerobic exercise and muscle strength tests. Results The response rate for the survey was 51 % and data showed a prevalence of statin-associated myalgia in 19 % of responders using statins. The experimental study showed no difference between the groups in aerobic capacity (C: 29 ± 1; M: 27 ± 1; NM: 28 ± 1 ml O2·min-1·kg-1) or maximal fat oxidation (C: 247 ± 26; M: 295 ± 24; NM: 279 ± 17 mg·min-1). Measurements of strength were similar in all three groups including rate of force development (C: 795 ± 56; M: 930 ± 93; NM: 971 ± 57 Nm·s-1) and leg extension power (C: 2.6 ± 0.2; M: 2.3 ± 0.1; NM: 2.4 ± 0.1 W·kg-1). All results are mean ± SEM. Conclusion Statin users in primary prevention experiencing myalgia do not have impaired aerobic exercise performance or muscle strength compared to non-myalgic statin users or control subjects. Correspondence: Thomas Morville, Xlab, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 N, Copenhagen, Denmark. Phone: +45 29602891. thomasmor@sund.ku.dk The authors declare no conflict of interest in relation to the present scientific paper. The results of the present study do not constitute endorsement by ACSM. Authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. This study was funded by the Nordea Foundation and the University of Copenhagen 2016 Center of Excellence grant. Accepted for publication: 3 February 2019. © 2019 American College of Sports Medicine

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Monitoring Muscle Fatigue Progression during Dynamic Exercise

Purpose To develop and validate a novel model for assessment of peripheral fatigue progression during dynamic exercise. Methods Seven males and four females (24 ± 3 yrs) completed one-legged knee-extensor exercise at 40% of peak power output for 12 min (40%PPO). Additionally, an exhaustive bout lasting ~ 6 min (84 ± 2% PPO; 59 ± 10 watt) was contrasted to two bouts completed at ± 5% of the target workload. Trials were completed in randomized order. Percutaneous electrical stimulation of m. vastus lateralis during the passive knee-flexion phase allowed quantification of maximal twitch force every 30 s in parallel with rating of perceived exertion (RPE). Results Elicited twitch force remained unchanged during the 40%PPO trial. During the three exhaustive bouts, exercise differed in duration (561 ± 154 s, 366 ± 64 s, 245 ± 61 s; P

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Capsaicin supplementation increases time to exhaustion in high-intensity intermittent exercise without modifying metabolic responses in physically active men

Abstract

Purpose

The purpose of this study was to investigate the acute effect of capsaicin supplementation on performance and physiological responses during high-intensity intermittent exercise (HIIE).

Method

Thirteen physically active men (age = 24.4 ± 4.0 years; height = 176.4 ± 6.9 cm; body mass  =  78.7 ± 13.8 kg; running training per week = 3.9 ± 0.9 h) performed an incremental running test to determine peak oxygen uptake ( \(\dot {V}_}}\) ) and the speed associated with \(\dot {V}_}}\) (s \(\dot {V}_}}\) ). Thereafter, subjects completed two randomized, double-blind HIIE (15s:15 s at 120% s \(\dot {V}_}}\) ) trials 45-min after consuming capsaicin (12 mg) or an isocaloric placebo. Time to exhaustion, blood lactate concentration, oxygen consumption during and 20 min post-exercise, energy expenditure, time spent above 90% of \(\dot {V}_}}\) , and the rate of perceived exertion were evaluated.

Results

There was no difference between capsaicin and placebo for any variable except time to exhaustion [capsaicin: 1530 ± 515 s (102 efforts) vs placebo: 1342 ± 446 s (89 efforts); p < 0.001].

Conclusion

In conclusion, capsaicin supplementation increased time to exhaustion in high-intensity intermittent exercise without modifying the metabolic response of exercise or the rate of perceived exertion in physically active men. Capsaicin could be used to increase the training load during specific exercise training sessions.

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A new Cas in town

A new Cas in town

A new Cas in town, Published online: 08 February 2019; doi:10.1038/s41576-019-0101-y

A study published in Nature reports the functional and structural characterization of CasX, an RNA-guided DNA endonuclease with potential for use as a new genome editing platform.

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Induced pluripotent stem cells in disease modelling and drug discovery

Induced pluripotent stem cells in disease modelling and drug discovery

Induced pluripotent stem cells in disease modelling and drug discovery, Published online: 08 February 2019; doi:10.1038/s41576-019-0100-z

Enthusiasm for patient-specific therapies based on induced pluripotent stem cells (iPSCs) has risen in parallel with rapid advances in genome editing. This Review summarizes the progress in iPSC-based disease modelling over the past decade, with a focus on 3D organoid systems and chimeric models being exploited for new therapeutic approaches.

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Guidelines for the use of cerebral oximetry by near-infrared spectroscopy in cardiovascular anesthesia: a report by the cerebrospinal Division of the Academic Committee of the Japanese Society of Cardiovascular Anesthesiologists (JSCVA)

Abstract

Cerebral Oximetry by Near-infrared Spectroscopy (NIRS) has been used in cardiovascular anesthesia, but there was no guideline of regional cerebral oxygen saturation measured by cerebral oximetry by NIRS. This guideline provides recommendations applicable to patients at a risk of developing cerebral ischemia in cardiovascular surgery. Guidelines are intended to define practices meeting the needs of patients in most, but not all, circumstances, and should not replace clinical judgment. The Japanese Society of Cardiovascular Anesthesiologists (JSCVA) Task Force on Guidelines make an effort to ensure that the guideline writing committee contains broad views in using cerebral oximetry. Adherence to recommendations could be enhanced by shared decision making between healthcare providers and patients. This guideline was focused on cerebral oximetry of pediatric and adult cardiovascular disease. We hope this guideline would play an important role in using cerebral oximetry by measured NIRS.

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The cutaneous silent period: an underutilized tool in clinical neurophysiology

Publication date: Available online 7 February 2019

Source: Clinical Neurophysiology

Author(s): Mariano Serrao

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De novo DDX3X missense variants in males appear viable and contribute to syndromic intellectual disability

DDX3X (Xp11.4) encodes a DEAD‐box RNA helicase that escapes X chromosome inactivation. Pathogenic variants in DDX3X have been shown to cause X‐linked intellectual disability (ID) (MRX102, MIM: 300958). The phenotypes associated with DDX3X variants are heterogeneous and include brain and behavioral abnormalities, microcephaly, hypotonia, and movement disorders and/or spasticity. The majority of DDX3X variants described are de novo mutations in females with ID. In contrast, most male DDX3X variants are inherited from an unaffected mother, with one documented exception being a recently identified de novo splice site variant. It has been suggested, therefore, that DDX3X exerts its effects through haploinsufficiency in females, and that affected males carry hypomorphic alleles that retain partial function. Given the lack of male de novo DDX3X variants, loss‐of‐function variants in this gene are suspected to be male lethal. Through whole‐exome sequencing, we identified three unrelated males with hemizygous missense DDX3X variants and ID. All three variants were confirmed by Sanger sequencing, with two established as de novo. In silico analyses were supportive of pathogenicity. We report the male phenotypes and compare them to phenotypes observed in previously reported male and female patients. In conclusion, we propose that de novo DDX3X variants are not necessarily male lethal and should be considered as a cause of syndromic ID in both males and females.

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Revealing the functions of novel mutations in RAB3GAP1 in Martsolf and Warburg micro syndromes

Purpose: Martsolf (MS) and Warburg micro syndromes (WARBM) are rare autosomal recessive inherited allelic disorders, which share similar clinical features including microcephaly, intellectual disability, brain malformations, ocular abnormalities, and spasticity. Here, we revealed the functions of novel mutations in RAB3GAP1 in a Turkish female patient with MS and two siblings with WARBM. We also present a review of MS patients as well as all reported RAB3GAP1 pathogenic mutations in the literature. Methods: We present a female with MS phenotype and two siblings with WARBM having more severe phenotypes. We utilized whole‐exome sequencing to identify the molecular basis of these syndromes and confirmed suspected variants by Sanger sequencing. Quantitative (q) RT‐PCR analysis was carried out to reveal the functions of novel splice site mutation detected in MS patient. Results: We found a novel homozygous c.2607‐1G>C splice site mutation in intron 22 of RAB3GAP1 in MS patient and a novel homozygous c.2187_2188delinsCT, p.(Met729_Lys730delinsIleTer) mutation in exon 19 of RAB3GAP1 in the WARBM patients. We showed exon skipping in MS patient by Sanger sequencing and gel electrophoresis. qRT‐PCR analysis demonstrated the reduced expression of RAB3GAP1 in the patient with the c.2607‐1G>C splice site mutation compared to a healthy control individual. Conclusion: Here, we have studied two novel RAB3GAP1 mutations in two different phenotypes; a MS associated novel splice site mutation, and a WARBM1 associated novel deletion–insertion mutation. Our findings suggest that this splice site mutation is responsible for milder phenotype and the deletion–insertion mutation presented here is associated with severe phenotype.

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Fiducial placement for recurrent gastric cancer

Publication date: Available online 8 February 2019

Source: Arab Journal of Gastroenterology

Author(s): Mohamed M. Abdelfatah, Eric M. Gochanour

Abstract

A 53-year-old male was diagnosed with invasive adenocarcinoma of the pre-pyloric region. Imaging studies ruled out metastatic disease. The patient underwent neo-adjuvant chemotherapy followed by a partial gastrectomy. CT scan at 18 months' post-resection demonstrated right upper quadrant lesions suspicious for metastatic disease. EUS exam shows two round hypoechoic lesions. Fine needle aspiration with suction was performed with on-site cytology confirming malignant cells in the masses. Five gold fiducial markers were placed. Final pathology confirmed adenocarcinoma. The patient was subsequently started on stereotactic body radiation therapy (SBRT) with good results. This is the first case report EUS-guided fiducial markers for recurrent gastric cancer post-gastrectomy.

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Paraoxonase-1 and arylesterase levels in patients with ulcerative colitis

Publication date: Available online 8 February 2019

Source: Arab Journal of Gastroenterology

Author(s): Memduh Sahin, Onur Bobusoglu, Aylin Yetim, Fehmi Ates

Abstract

Background and study aims

The role of oxidative stress in inflammatory bowel disease is increasingly recognised as an important factor. It is assumed that reduced levels of paraoxonase-1 (PON-1) and arylesterase (ARE) may lead to increased inflammation due to increased oxidative stress. This study aimed to investigate the relationship between ARE and PON-1 levels in ulcerative colitis (UC) patients and the difference in these levels in UC patients in comparison to the control group.

Patients and methods

The study population consisted of 66 (73.3%) UC patients and 24 (26.7%) healthy individuals as the control group. The UC patients and the control group were compared in terms of PON-1 and ARE levels as oxidative stress markers. The UC patients were also grouped according to Mayo UC activity scores, and the differences in their PON-1 and ARE levels were assessed.

Results

The ARE values were statistically higher in the control group in comparison to the UC patients. Concentrations of PON-1 were not statistically different in the UC and control groups. The ARE value was found to be significantly lower in the UC patients with a haemoglobin level below 10 mg/dl. There was a correlation between the ARE and PON-1 values in the UC patients, but there was no difference between the ARE and PON-1 values, based on the UC patients' Mayo disease severity scores.

Conclusion

This study found that the ARE values of UC patients were lower than those of healthy subjects. The same results could not be determined for PON-1. The data suggest that the antioxidative capacity of UC patients may be reduced.

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Induced pluripotent stem cells in disease modelling and drug discovery

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A new Cas in town

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Influence of cognitive load on the dynamics of neurophysiological adjustments during fatiguing exercise

Abstract

We aimed to determine the neurophysiological mechanisms associated with reduced endurance performance during cognitive‐motor dual task at different levels of cognitive load, compared to a motor task alone. Eighteen healthy men performed isometric quadriceps contractions at 15% of maximal voluntary contraction (blocks of 170 s interspaced by neuromuscular evaluations) until exhaustion. This task was performed on three separate days: (a) in the absence of concomitant cognitive task, (b) with concomitant 1‐back task, and (c) with concomitant 2‐back task. Autonomic nervous system activity, perceived exertion, and cognitive performance were continuously monitored. Peripheral and central determinants of neuromuscular function were assessed at rest, between each block, and at task failure using femoral nerve stimulation. Endurance time was shorter during 2‐back (982 ± 545 s) and 1‐back (1,128 ± 592 s) conditions, compared with control (1,306 ± 836 s). Voluntary activation level was lower in 2‐back (87.1%; p < 0.001) and 1‐back (88.6%; p = 0.04) conditions compared to control (91.2%) at isotime (100% of the shortest test duration). Sympathetic activity showed a greater increase in 2‐back condition compared to control. Perceived muscular exertion was higher during 2‐back than during control. Cognitive performance decreased similarly with time during both cognitive‐motor dual task but was always lower during 2‐back condition. Motor performance is reduced when adding a concomitant demanding memory task to a prolonged isometric exercise. This can be explained by the interaction of various psychological and neurophysiological factors including higher perceived exertion, greater perturbations of autonomic nervous system activity, and cerebral impairments leading to earlier onset of central fatigue.

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Issue Information

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Abdominal girth has a strong correlation with ultrasound-estimated epidural depth in parturients: a prospective observational study

Abstract

Background

Preprocedural ultrasound examination of vertebral column guides to locate desired intervertebral space and provides a prevision of needle trajectory and estimated needle depth in parturients. The objective of this study was to assess the correlation between ultrasound-estimated epidural depth (ED) with abdominal girth (AG), body mass index (BMI), weight, height, and age.

Methods

In this prospective, observational study, ultrasound imaging was done at L3–4 interspace in transverse median plane (TP) and paramedian sagittal oblique plane (PSO) to obtain ultrasound estimates of skin to epidural space depth. Combined spinal epidural anesthesia was performed at L3–4 interspace. AG, BMI, age, height, and weight were recorded for every parturient.

Results

Data from 130 parturients were analyzed. Estimated ED was 56.5 ± 9.5 mm in TP, 57.5 ± 9.3 mm in PSO, and actual epidural depth was 57.9 ± 9.4 mm. Correlation coefficients between ED and AG were 0.797 in TP (95% CI 0.727–0.854, p < 0.001) and 0.803 in PSO (95% CI 0.733–0.857, p < 0.001). Correlation coefficients between ED and BMI were 0.543 in TP (95% CI 0.405–0.661, p < 0.001) and 0.566 in PSO (95% CI 0.428–0.680, p < 0.001). Correlation coefficients between ED and weight were 0.593 in TP (CI = 0.466–0.695, p < 0.001) and 0.615 in PSO (CI = 0.500–0.716, p < 0.001). Height and age had no significant correlation with ED.

Conclusions

Abdominal girth has a strong correlation with ultrasound-estimated epidural depth in parturients.

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Distinct dampening effects of progesterone on the activity of nucleus tractus solitarus neurons in rat pups

NEW FINDINGS

What is the central question of the study? Progesterone is considered as a respiratory stimulant drug, but its effect on medullary respiratory neurons are poorly documented. We investigated whether progesterone alters spontaneous activity of neurons in the nucleus of the solitary tract (NTS). What is the main finding and its importance? In NTS neurons, progesterone decreases the action potential firing frequency in response to current injections and the amplitude of excitatory postsynaptic currents (EPSC). Based on the established neuroprotective effect of progesterone against excitotoxicity resulting from insults, this inhibitory effect likely reflects inhibition of ion fluxes. These results are important as they further our understanding of the mechanisms underlying the diversity of the respiratory effects of progesterone.

Abstract

Progesterone is known to stimulate breathing, but its actions on the respiratory control system have received limited attention. We addressed this issue at the cellular level by testing the hypothesis that progesterone augments excitatory currents at the level of the NTS. Medullary slices from juvenile male rats (14–17 days of age) containing the commissural region of the NTS (NTScom) were incubated with progesterone (1 μM) or vehicle (DMSO 0.004%) for 60 min. We performed whole‐cell voltage clamp recordings of spontaneous excitatory postsynaptic currents (EPSCs) in the NTScom, and determined membrane properties by applying depolarizing current steps. By comparison with vehicle‐treated cells, progesterone exposure attenuates the firing frequency response to current injection and reduces the EPSC amplitude without modifying the EPSC frequency or the basal membrane properties. These data do not support our hypothesis as they indicate that incubation with progesterone attenuates intrinsic action potential generation and inhibits excitatory synaptic inputs in the NTS. Since these results are more in line with the protective effect of progesterone against excitotoxicity resulting from various insults, we propose that progesterone acts via inhibition of ionic flux.

This article is protected by copyright. All rights reserved

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Nerve growth factor‐dependent hyperexcitability of capsaicin‐sensitive bladder afferent neurones in mice with spinal cord injury

New Findings

What is the central question of this study?

Nerve growth factor (NGF) is reportedly a mediator inducing urinary bladder dysfunction. Is NGF directly involved in hyperexcitability of capsaicin‐sensitive C‐fibre bladder afferent pathways after spinal cord injury (SCI)?

What is the main finding and its importance?

Neutralization of NGF by anti‐NGF antibody treatment reversed the SCI‐induced increase in the number of action potentials and the reduction in spike thresholds and A‐type K⁺ current density in mouse capsaicin‐sensitive bladder afferent neurones. Thus, NGF plays an important and direct role in hyperexcitability of capsaicin‐sensitive C‐fibre bladder afferent neurones attributable to the reduction in A‐type K⁺ channel activity in SCI.

Abstract

Nerve growth factor (NGF) has been implicated as an important mediator in the induction of C‐fibre bladder afferent hyperexcitability, which contributes to the emergence of neurogenic lower urinary tract dysfunction after spinal cord injury (SCI). In this study, we determined whether NGF immunoneutralization using an anti‐NGF antibody (NGF‐Ab) normalizes the SCI‐induced changes in electrophysiological properties of capsaicin‐sensitive C‐fibre bladder afferent neurones in female C57BL/6 mice. The spinal cord was transected at the Th8/Th9 level. Two weeks later, continuous administration of NGF‐Ab (10 μg kg⁻¹ h⁻¹, s.c. for 2 weeks) was started. Bladder afferent neurones were labelled with Fast‐Blue (FB), a fluorescent retrograde tracer, injected into the bladder wall 3 weeks after SCI. Four weeks after SCI, freshly dissociated L6–S1 dorsal root ganglion neurones were prepared. Whole‐cell patch‐clamp recordings were then performed in FB‐labelled neurones. After recording action potentials or voltage‐gated K⁺ currents, the sensitivity of each neurone to capsaicin was evaluated. In capsaicin‐sensitive FB‐labelled neurones, SCI significantly reduced the spike threshold and increased the number of action potentials during membrane depolarization for 800 ms. These SCI‐induced changes were reversed by NGF‐Ab. Densities of slow‐decaying A‐type K⁺ (K_A) and sustained delayed rectifier‐type K⁺ currents were significantly reduced by SCI. The NGF‐Ab treatment reversed the SCI‐induced reduction in the K_A current density. These results indicate that NGF plays an important role in hyperexcitability of mouse capsaicin‐sensitive C‐fibre bladder afferent neurones attributable to a reduction in K_A channel activity. Thus, NGF‐targeting therapies could be effective for treatment of afferent hyperexcitability and neurogenic lower urinary tract dysfunction after SCI.

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Effects of the selective chymase inhibitor TEI‐F00806 on the intrarenal renin–angiotensin system in salt‐treated angiotensin I‐infused hypertensive mice

New Findings

What is the central question of this study?

Can chymase inhibition prevent angiotensin I‐induced hypertension through inhibiting the conversion of angiotensin I to angiotensin II in the kidney?

What is the main finding and its importance?

Treatment with TEI‐F00806 decreased angiotensin II content of the kidney, renal cortical angiotensinogen protein levels and chymase mRNA expression, and attenuated the development of hypertension.

Abstract

The effects of the selective chymase inhibitor TEI‐F00806 were examined on angiotensin I (Ang I)‐induced hypertension and intrarenal angiotensin II (Ang II) production in salt‐treated mice. Twelve‐week‐old C57BL male mice were given a high‐salt diet (4% NaCl + saline (0.9% NaCl)), and divided into three groups: (1) sham + vehicle (5% acetic acid in saline), (2) Ang I (1 μg kg⁻¹ min⁻¹, s.c.) + vehicle, and (3) Ang I + TEI‐F00806 (100 mg kg⁻¹ day⁻¹, p.o.) (n = 8–10 per group). Systolic blood pressure was measured weekly using a tail‐cuff method. Kidney Ang II content was measured by radioimmunoassay. Chronic infusion of Ang I resulted in the development of hypertension (P < 0.001), and augmented intrarenal chymase gene expression (P < 0.05), angiotensinogen protein level (P < 0.001) and Ang II content (P < 0.01) in salt‐treated mice. Treatment with TEI‐F00806 attenuated the development of hypertension (P < 0.001) and decreased Ang II content of the kidney (P < 0.05), which was associated with reductions in renal cortical angiotensinogen protein levels (P < 0.001) and chymase mRNA expression (P < 0.05). These data suggest that a chymase inhibitor decreases intrarenal renin–angiotensin activity, thereby reducing salt‐dependent hypertension.

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Genioglossus muscle activity during sniff and reverse sniff in healthy men

New Findings

What is the central question of this study?

Maximal sniff nasal inspiratory and reverse sniff nasal expiratory pressures are measured as inspiratory and expiratory muscle strength, respectively. Is the genioglossus muscle activated during short maximal inspiratory and expiratory efforts through the nose?

What is the main finding and its importance?

Genioglossus muscle activity occurred with inspiratory muscle activity during a maximal sniff and with expiratory muscle activity during a maximal reverse sniff. These results indicate that genioglossus muscle activity is closely related to the generation of maximal sniff nasal inspiratory and reverse sniff nasal expiratory pressures.

Abstract

Maximal sniff nasal inspiratory pressure (SNIP_max) is widely used to assess inspiratory muscle strength. The sniff nasal inspiratory pressure (SNIP) is lower in patients with neuromuscular disease with bulbar involvement compared with those without, possibly owing to impaired upper airway muscle function. However, the degree to which the genioglossus (GG) muscle, one of the upper airway muscles, is activated during inspiratory and expiratory efforts through the nose remains unclear. Therefore, we examined GG activity during short and sharp inspiratory and expiratory efforts through the nose, i.e. sniff and reverse sniff manoeuvres. In eight normal young subjects, we inserted fine wire electrodes into the GG muscle, parasternal intercostal and scalene (inspiratory) muscles and transversus abdominis (expiratory) muscle. We assessed EMG activity of each muscle and measured SNIP and reverse sniff nasal expiratory pressure (RSNEP) during sniffs and reverse sniffs from low to high intensities in the sitting position. The highest SNIP and RSNEP were analysed as SNIP_max and maximal RSNEP (RSNEP_max), respectively. In each subject, GG EMG activity increased linearly with increasing SNIP and RSNEP. The SNIP_max and RSNEP_max were −85.1 ± 15.9 and 83.2 ± 24.2 cmH₂O, respectively. Genioglossus EMG activity varied with EMG activity of the parasternal intercostal and scalene muscles during generation of SNIP_max and with EMG activity of the transversus abdominis muscle during RSNEP_max. Genioglossus EMG activity during generation of SNIP_max was higher than during RSNEP_max (62.9 ± 31.1% EMG of SNIP_max, P = 0.012). These results suggested that GG activity was closely related to the generation of both SNIP_max and RSNEP_max.

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Influence of food texture on energy metabolism and adiposity in male rats

New Findings

What is the central question of this manuscript?

What is the effect of food texture on fat accumulation, lipogenesis and proinflammatory factors in the adipose tissue and on energy balance in male rats?

What is the main finding and its importance?

Calorie intake and fat accumulation in rats fed soft pellets ad libitum increased, but their body weight did not. The data suggest that, even when BMI is normal, frequent consumption of soft food may contribute to the development of lifestyle‐related diseases.

Abstract

Dietary factors such as food texture are known to affect feeding behaviour and energy metabolism. We recently found that rats fed soft pellets (SPs) on a 3 h restricted feeding schedule showed glucose intolerance, insulin resistance with disruption of insulin signalling, and hyperplasia of pancreatic β‐cells, even though there were no differences in energy intake and body weight between rats fed control pellets (CPs) and rats fed SPs. We investigated the effect of food texture on fat accumulation, lipogenesis and proinflammatory factors in the mesenteric fat, as well as on energy balance in male rats fed CPs or SPs. We used 7‐week‐old Wistar rats that were randomly divided into two groups, ad libitum fed either CPs or SPs for 27 weeks. Body weight and calorie intake were monitored once a week throughout the experiment. The calorie intake, lipogenesis and fat accumulation of the rats fed SPs increased, whereas their body weight did not. Additionally, SP rats used their fat mainly as a source of energy and increased their energy expenditure. Our data suggest that the habit of frequently eating soft food causes visceral fat accumulation without an increase in body weight. Further investigations using soft‐textured foods could lead to the development of appropriate interventions for non‐overweight patients with lifestyle‐related diseases.

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Effects of intermittent hyperbaric exposure on endurance and interval exercise performance in well‐trained mice

New Findings

What is the central question of this study?

Intermittent hyperbaric exposure (1.3 atmospheres absolute with 20.9% O₂) enhances endurance capacity by facilitating oxidative and glycolytic capacities in skeletal muscle. It remains unclear whether this strategy enhances endurance performance in well‐trained individuals.

What is the main finding and its importance?

Hyperbaric exposure with endurance training enhanced oxidative and glycolytic capacities and protein levels of mitochondrial transcription factor A, dynamin‐related protein‐1 and heat shock protein 70. Hyperbaric exposure with sprint interval training increased the proportion of type I muscle fibres and promoted capillary growth and muscle fibre hypertrophy. These results may lead to a new strategy for enhancing exercise capacity in well‐trained mice.

Abstract

The study was designed to clarify the mechanisms by which hyperbaric exposure (1.3 atmospheres absolute with 20.9% O₂) improves endurance and interval exercise capacities in highly trained mice. Male mice in the training group were housed in a cage with a wheel activity device for 7 weeks from 5 weeks old. Voluntary running markedly increased maximal endurance capacity by 6.4‐fold. Trained mice were then subjected to either endurance treadmill training (20–32.5 m min⁻¹) or sprint interval training (5 s run–10 s rest, 30–42.5 m min⁻¹) with (HypET or HypSIT, respectively) and without (ET or SIT, respectively) 1 h hyperbaric exposure for 4 weeks. Maximal endurance capacity was significantly increased by HypET and HypSIT, and maximal interval capacity was significantly enhanced by HypSIT. Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha expression levels were markedly increased after HypET and HypSIT. Activity levels of 3‐hydroxyacyl‐CoA‐dehydrogenase, citrate synthase and phosphofructokinase in the red gastrocnemius muscle were increased more by HypET than by ET. Protein levels of mitochondrial transcription factor A, dynamin‐related protein‐1 and heat shock protein 70 were increased more by HypET than by ET. The proportion of type I fibres in the soleus muscle was remarkably increased by HypSIT. Capillary‐to‐fibre ratio values in the white gastrocnemius were increased more by HypSIT than by SIT. These results suggest that hyperbaric exposure has beneficial effects for endurance and interval training to improve exercise capacity in highly trained mice.

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Simultaneous monitoring of Ca2+ responses and salivary secretion in live animals reveals a threshold intracellular Ca2+ concentration for salivation

New Findings

What is the central question of this study?

The effects of Ca²⁺ responses on salivary fluid secretion have been studied indirectly by monitoring ion channel activities and other indices. Therefore, Ca²⁺ responses during salivary secretion remain poorly understood.

What is the main finding and its importance?

Herein, we developed a simultaneous monitoring system for Ca²⁺ responses and salivary secretion in live animals using a YC‐Nano50‐expressing submandibular gland and a fibre‐optic pressure sensor. This new approach revealed a clear time lag between the onset of Ca²⁺ responses and salivary secretion. We also estimated the [Ca²⁺]_i and provided direct evidence for the regulation of salivary secretion by small increases in [Ca²⁺]_i in submandibular gland acinar cells.

Abstract

We monitored changes in [Ca²⁺]_i during salivary secretion in the rat submandibular gland in live animals using a combination of intravital Ca²⁺ imaging with the ultrasensitive Ca²⁺ indicator YC‐Nano50 and a fibre‐optic pressure sensor. Intravenous infusion of ACh (10–720 nmol min⁻¹) increased [Ca²⁺]_i and salivary flow rate in a dose‐dependent manner. Repetitive stimulation with ACh induced equivalent Ca²⁺ responses and salivary secretion in the same individual animals. The accurate ACh stimulation experiments revealed a clear time lag between the onset of the increase in [Ca²⁺]_i and salivary secretion. The time lag with the lowest dose of ACh (30 nmol min⁻¹) was 106 s, which shortened to 19 s with the dose used for maximal salivary secretion (360 nmol min⁻¹). This time lag might reflect the time required for [Ca²⁺]_i to reach the level required to activate molecules for fluid secretion. The resting [Ca²⁺]_i in submandibular gland was 37 nm, and [Ca²⁺]_i at the onset of salivary secretion was 45–57 nm, irrespective of ACh dose. These results indicate that low [Ca²⁺]_i is sufficient to trigger fluid secretion in the rat submandibular gland in vivo.

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The effect of blood flow occlusion during acute low-intensity isometric elbow flexion exercise

Abstract

Purpose

Blood flow restriction (BFR) with low-intensity (< 30% of 1 repetition maximum strength) muscle contraction has been used chronically (> 4 weeks) to enhance resistance training. However, mechanisms underlying muscle adaptations following BFR are not well understood. To explore changes related to chronic BFR adaptations, the current study used blood flow occlusion (BFO) during an acute bout of low-intensity isometric fatiguing contractions to assess peripheral (muscle) factors affected.

Methods

Ten males completed separate fatiguing elbow flexor protocols to failure; one with BFO and one with un-restricted blood flow (FF). Baseline, post-task failure, and 30 min of recovery measures of voluntary and involuntary contractile properties were compared.

Results

BFO had greater impairment of intrinsic measures compared with FF, despite FF lasting 80% longer. Following task failure, maximal voluntary contraction and 50 Hz torque decreased in both protocols (~ 60% from baseline). Voluntary activation decreased ~ 11% from baseline at failure following both protocols, but recovered at a faster rate following BFO, whereas MVC recovered to ~ 90% of baseline in both protocols. The 10/50 Hz torque ratio was decreased by ~ 68% and ~ 21% from baseline, for BFO and FF, respectively (P < 0.01). 50 Hz half-relaxation-time (HRT) was significantly longer immediately following BFO (~ 107% greater than baseline), with no change following FF.

Conclusions

Thus, greater peripheral fatigue that recovers at a similar rate compared to conventional exercise is likely driving muscle adaptations observed with chronic BFR exercise. Likely BFO alters energy demand and supply of working muscle similar to chronic BFR, but is exaggerated in this paradigm.

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Ionic signalling in astroglia beyond calcium

Abstract

Astrocytes are homeostatic and protective cells of the central nervous system. Astroglial homeostatic responses are tightly coordinated with neuronal activity. Astrocytes maintain neuronal excitability through regulation of extracellular ion concentrations as well as assisting and modulating synaptic transmission by uptake and catabolism of major neurotransmitters. Moreover, they support neuronal metabolism and detoxify ammonium and reactive oxygen species. Astroglial homeostatic actions are initiated and controlled by intercellular signalling of ions, including Ca²⁺, Na⁺, Cl⁻, H⁺ and possibly K⁺. This treatise summarises current knowledge on ionic signals mediated by the major monovalent ions, which occur in microdomains, as global events or as propagating intercellular waves and thereby represent the substrate for astroglial excitability.

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Exercise initiated during pregnancy in rats born growth restricted alters placental mTOR and nutrient transporter expression

Key points

Fetal growth is dependent on effective placental nutrient transportation, which is regulated by mTORC1 modulation of nutrient transporter expression. These transporters are dysregulated in pregnancies affected by uteroplacental insufficiency and maternal obesity. Nutrient transporters and mTOR were altered in placentae of mothers born growth restricted compared to normal birth weight dams, with maternal diet‐ and fetal sex‐specific responses. Exercise initiated during pregnancy (PregEx) downregulated MTOR protein expression, despite an increase in mTOR activation in male associated placentae, and reduced nutrient transporter gene abundance, which was also dependent on maternal diet and fetal sex. Limited changes were characterised with exercise initiated before and continued throughout pregnancy (Exercise) in nutrient transporter and mTOR expression. Maternal exercise during pregnancy (PregEx) differentially regulated mTOR and nutrient transporters in a diet‐ and sex‐specific manner, which likely aims to improve late gestational placental growth and neonatal survival.

Abstract

Adequate transplacental nutrient delivery is essential for fetoplacental development. Intrauterine growth restriction and maternal obesity independently alter placental nutrient transporter expression. Although exercise is beneficial for maternal health, limited studies have characterized how the timing of exercise initiation influences placental nutrient transport. Therefore, this study investigated the impact of maternal exercise on placental mTOR and nutrient transporter expression in growth restricted mothers and if these outcomes were dependent on maternal diet or fetal sex. Uteroplacental insufficiency (Restricted) or sham (Control) surgery was induced on embryonic day (E) 18 in Wistar‐Kyoto rats. F1 offspring were fed a Chow or High‐fat diet from weaning and at 16 weeks were randomly allocated an exercise protocol; Sedentary, Exercised prior to and during pregnancy (Exercise), or Exercised during pregnancy only (PregEx). Females were mated with normal males (20 weeks) and F2 placentae collected at E20. PregEx reduced mTOR protein expression in all groups and increased mTOR activation in male associated placentae. PregEx decreased the expression of amino acid transporters in a diet and sex‐specific manner. Maternal growth restriction altered mTOR and system A amino acid transporter expression in a sex and diet specific manner. These data highlight that maternal exercise initiated during pregnancy alters placental mTOR expression, which may directly regulate amino acid transporter expression, to a greater extent than exercise initiated prior to and continued during pregnancy, in a diet and fetal sex dependent manner. These findings highlight that the timing of exercise initiation is important for optimal placental function.

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Mid‐life crisis or mid‐life gains: 2 years of high‐intensity exercise is highly beneficial for the middle‐aged heart

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Postnatal undernutrition alters adult female mouse cardiac structure and function leading to limited exercise capacity

Key Points

Impaired growth during fetal life can reprogramme heart development and increase the risk for long‐term cardiovascular dysfunction. It is uncertain if the developmental window during which the heart is vulnerable to reprogramming as a result of inadequate nutrition extends into the postnatal period. We found that adult female mice that had been undernourished only from birth to 3 wk of age had disproportionately smaller hearts compared to males with thinner ventricle walls and more mononucleated cardiomyocytes. In females, but not males, cardiac diastolic function, and heart rate responsiveness to adrenergic stimulation were limited and maximal exercise capacity was compromised. These data suggest that the developmental window during which the heart is vulnerable to reprogramming by inadequacies in nutrient intake may extend into postnatal life and such individuals could be at increased risk for a cardiac event as a result of strenuous exercise.

Abstract

Adults who experienced undernutrition during critical windows of development are at increased risk for cardiovascular disease. The contribution of cardiac function to this increased disease risk is uncertain. We evaluated the effect of a short episode of postnatal undernutrition on cardiovascular function in mice at the whole animal, organ, and cellular levels. Pups born to control mouse dams were suckled from birth to postnatal day (PN) 21 on dams fed either a control (20% protein) or a low protein (8% protein) isocaloric diet. After PN21 offspring were fed the same control diet until adulthood. At PN70 VO_2max was measured by treadmill test. At PN80 cardiac function was evaluated by echocardiography and Doppler analysis at rest and following β‐adrenergic stimulation. Isolated cardiomyocyte nucleation and Ca²⁺ transients (with and without β‐adrenergic stimulation) were measured at PN90. Female mice that were undernourished and then refed (PUN), unlike male mice, had disproportionately smaller hearts and their exercise capacity, cardiac diastolic function, and heart rate responsiveness to adrenergic stimulation were limited. A reduced left ventricular end diastolic volume, impaired early filling, and decreased stored energy at the beginning of diastole contributed to these impairments. Female PUN mice had more mononucleated cardiomyocytes; under resting conditions binucleated cells had a functional profile suggestive of increased basal adrenergic activation. Thus, a brief episode of early postnatal undernutrition in the mouse can produce persistent changes to cardiac structure and function that limit exercise/functional capacity and thereby increase the risk for the development of a wide variety of cardiovascular morbidities.

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