Comparison of accelerometer measured levels of physical activity and sedentary time between obese and non-obese children and adolescents: a systematic review

Background: Obesity has been hypothesized to be associated with reduced moderate-to-vigorous physical activity (MVPA) and increased sedentary time (ST). It is important to assess whether, and the extent to which, levels of MVPA and ST are suboptimal among children and adolescents with obesity. The primary objective of this study was to examine accelerometer-measured time spent in MVPA and ST of children and adolescents with obesity, compared with MVPA recommendations, and with non-obese peers. Methods: An extensive search was carried out in Medline, Cochrane library, EMBASE, SPORTDiscus, and CINAHL, from 2000 to 2015. Study selection and appraisal: studies with accelerometer-measured MVPA and/or ST (at least 3 days and 6 h/day) in free-living obese children and adolescents (0 to 19 years) were included. Study quality was assessed formally. Meta-analyses were planned for all outcomes but were precluded due to the high levels of heterogeneity across studies. Therefore, narrative syntheses were employed for all the outcomes. Results: Out of 1503 records, 26 studies were eligible (n = 14,739 participants; n = 3523 with obesity); 6/26 studies involved children aged 0 to 9 years and 18/26 involved adolescents aged 10.1 to19 years. In the participants with obesity, the time spent in MVPA was consistently below the recommended 60 min/day and ST was generally high regardless of the participant’s age and gender. Comparison with controls suggested that the time spent in MVPA was significantly lower in children and adolescents with obesity, though differences were relatively small. Levels of MVPA in the obese and non-obese were consistently below recommendations. There were no marked differences in ST between obese and non-obese peers. Conclusions: MVPA in children and adolescents with obesity tends to be well below international recommendations. Substantial effort is likely to be required to achieve the recommended levels of MVPA among obese individuals in obesity treatment interventions

Cardiopulmonary exercise testing in children with Cystic Fibrosis : one centre’s experience

Exercise testing is increasingly being used as a prognostic indicator in Cystic Fibrosis (CF) but it is reported to be underutilised in UK CF centres, particularly in children. Here, we evaluated the CPET results of our children with CF at the CF annual review and its possible clinical value

Two Sides of the Same Coin?—Treatment of Chronic Asthma in Children and Adults

Globally, asthma is one of the most common chronic conditions that affect individuals of all ages. When poorly controlled, it negatively impacts patient's ability to enjoy life and work. At the population level, effective use of recommended strategies in children and adults can reduce symptom burden, improve quality of life and significantly reduce the risk of exacerbation, decline of lung function and asthma-related death. Inhaled corticosteroid as the initial maintenance therapy, ideally started within 2 years of symptom onset, is highly effective in both children and adults and across various degrees of asthma severity. If asthma is not controlled, the choice of subsequent add-on therapies differs between children and adults. Evidence supporting pharmacological approach to asthma management, especially for those with more severe disease, is more robust in adults compared to children. This is, in part, due to various challenges in the diagnosis of asthma, in the recruitment into clinical trials and in the lack of objective outcomes in children, especially those in the preschool age group. Nevertheless, where evidence is emerging for younger children, it seems to mirror the observations in adults. Clinicians need to develop strategies to implement guideline-based recommendations while taking into consideration individual variations in asthma clinical phenotypes, pathophysiology and treatment responses at different ages

Comparison of accelerometer measured levels of physical activity and sedentary time between obese and non-obese children and adolescents : a systematic review

Background: Obesity has been hypothesized to be associated with reduced moderate-to-vigorous physical activity (MVPA) and increased sedentary time (ST). It is important to assess whether, and the extent to which, levels of MVPA and ST are suboptimal among children and adolescents with obesity. The primary objective of this study was to examine accelerometer-measured time spent in MVPA and ST of children and adolescents with obesity, compared with MVPA recommendations, and with non-obese peers. Method: An extensive search was carried out in Medline, Cochrane library, EMBASE, SPORTDiscus, and CINAHL, from 2000-2015. Study selection and appraisal: studies with accelerometer-measured MVPA and/or ST (at least 3 days and 6 hours/day) in free-living obese children and adolescents (0-19 years) were included. Study quality was assessed formally. Meta-analyses were planned for all outcomes but were precluded due to the high levels of heterogeneity across studies. Therefore, narrative syntheses were employed for all the outcomes. Results: Out of 1503 records, 26 studies were eligible with a total (n =14739 participants; n =3523 with obesity); 6/26 studies involved children aged 0-9 years and 18/26 involved adolescents aged 10.1-19 years. In the participants with obesity, the time spent in MVPA was consistently below the recommended 60 minutes/day and ST was generally high regardless of the participant’s age and gender. Comparison with controls suggested that the time spent in MVPA was significantly lower in children and adolescents with obesity, though differences were relatively small. Levels of MVPA in the obese and non-obese were consistently below recommendations. There were no marked differences in ST between obese and non-obese peers. Conclusions: MVPA in children and adolescents with obesity tends to be well below international recommendations. Substantial effort is likely to be required to achieve the recommended levels of MVPA among obese individuals in obesity treatment interventions

Influence of age on respiratory modulation of muscle sympathetic nerve activity, blood pressure and baroreflex function in humans

New Findings What is the central question of this study? Does ageing influence the respiratory‐related bursting of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure (Traube–Hering waves) that occur with respiration? What is the main finding and its importance? Despite the age‐related elevation in MSNA, the cyclical inhibition of MSNA during respiration is similar between young and older individuals. Furthermore, central respiratory–sympathetic coupling plays a role in the generation of Traube–Hering waves in both young and older humans. Healthy ageing and alterations in respiratory–sympathetic coupling have been independently linked with heightened sympathetic neural vasoconstrictor activity. We investigated how age influences the respiratory‐related modulation of muscle sympathetic nerve activity (MSNA) and the association between the rhythmic fluctuations in MSNA and blood pressure that occur with respiration (Traube–Hering waves; THW). Ten young (22 ± 2 years; mean ± SD) and 10 older healthy men (58 ± 6 years) were studied while resting supine and breathing spontaneously. MSNA, blood pressure and respiration were recorded simultaneously. Resting values were ascertained and respiratory cycle‐triggered averaging of MSNA and blood pressure measurements performed. The MSNA burst incidence was higher in older individuals [22.7 ± 9.2 versus 42.2 ± 13.7 bursts (100 heart beats)−1, P < 0.05], and was reduced to a similar extent in the inspiratory to postinspiratory period in young and older subjects (by ∼25% compared with mid‐ to late expiration). A similar attenuation of MSNA burst frequency (in bursts per minute), amplitude and total activity (burst frequency × mean burst amplitude) was also observed in the inspiratory to postinspiratory period in both groups. A significant positive correlation between respiratory‐related MSNA and the magnitude of Traube–Hering waves was observed in all young (100%) and most older subjects (80%). These data suggest that the strength of the cyclical inhibition of MSNA during respiration is similar between young and older individuals; thus, alterations in respiratory–sympathetic coupling appear not to contribute to the age‐related elevation in MSNA. Furthermore, central respiratory–sympathetic coupling plays a role in the generation of Traube–Hering waves in both healthy young and older humans

Validity, practical utility, and reliability of the activPAL in preschool children

&lt;p&gt;Purpose: With the increasing global prevalence of childhood obesity, it is important to have appropriate measurement tools for investigating factors (e.g. sedentary time) contributing to positive energy balance in early childhood. For pre-school children, single unit monitors such as the activPALTM are promising. However, validation is required as activity patterns differ from adults.&lt;/p&gt; &lt;p&gt;Methods: Thirty pre-school children participated in a validation study. Children were videoed for one hour undertaking usual nursery activity while wearing an activPALTM. Video (criterion method) was analyzed on a second-by-second basis to categorise posture and activity. This was compared with the corresponding activPALTM output. In a subsequent sub-study investigating practical utility and reliability, 20 children wore an activPALTM for seven consecutive 24-hour periods.&lt;/p&gt; &lt;p&gt;Results: A total of 97,750 seconds of direct observation from 30 children were categorized as sit/lie (46%), stand (35%), walk (16%); with 3% of time in nonsit/lie/upright postures (e.g. crawl/crouch/kneel-up). Sensitivity for the overall total time matched seconds detected as activPALTM ‘sit/lie’ was 86.7%, specificity 97.1%, and positive predictive value (PPV) 96.3%. For individual children, the median (interquartile range) sensitivity for activPALTM sit/lie was 92.8% (76.1-97.4), specificity 97.3% (94.9-99.2), PPV 97.0% (91.5-99.1). The activPALTM underestimated total time spent sitting (mean difference -4.4%, p&#60;0.01), and overestimated time standing (mean difference 7.1%, p&#60;0.01). There was no difference in overall % time categorised as ‘walk’ (p=0.2). The monitors were well tolerated by children during a seven day period of free-living activity. In the reliability study, at least five days of monitoring were required to obtain an intraclass correlation coefficient of ≥0.8 for time spent sit/lie according to activPALTM output.&lt;/p&gt; &lt;p&gt;Conclusion: The activPAL had acceptable validity, practical utility, and reliability for the measurement of posture and activity during freeliving activities in pre-school children.&lt;/p&gt

Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood-borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesised that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA-normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts/min) compared to NC (22 ± 9 bursts/min; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), while cardiac BRS (cBRS) was reduced in RA, RA-HTN and HTN patients (5[3-8], 4[2-7], 6[4-9] ms/mmHg) compared to NC (11[8-15] ms/mmHg; P = 0.002). HR was independently associated with hs-CRP. Increased MSNA and reduced cBRS were associated with hs-CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events. This article is protected by copyright. All rights reserved.</p

Structure-function analyses of a pertussis-like toxin from pathogenic Escherichia coli reveal a distinct mechanism of inhibition of trimeric G-proteins

Pertussis-like toxins are secreted by several bacterial pathogens during infection. They belong to the AB virulence factors, which bind to glycans on host cell membranes for internalization. Host cell recognition and internalization are mediated by toxin B subunits sharing a unique pentameric ring-like assembly. Although the role of pertussis toxin in whooping cough is well-established, pertussis-like toxins produced by other bacteria are less studied, and their mechanisms of action are unclear. Here, we report that some extra-intestinal Escherichia coli pathogens (i.e. those that reside in the gut but can spread to other bodily locations) encode a pertussis-like toxin that inhibits mammalian cell growth in vitro. We found that this protein, EcPlt, is related to toxins produced by both nontyphoidal and typhoidal Salmonella serovars. Pertussis-like toxins are secreted as disulfide-bonded heterohexamers in which the catalytic ADP-ribosyltransferase subunit is activated when exposed to the reducing environment in mammalian cells. We found here that the reduced EcPlt exhibits large structural rearrangements associated with its activation. We noted that inhibitory residues tethered within the NAD-binding site by an intramolecular disulfide in the oxidized state dissociate upon the reduction and enable loop restructuring to form the nucleotide-binding site. Surprisingly, although pertussis toxin targets a cysteine residue within the α subunit of inhibitory trimeric G-proteins, we observed that activated EcPlt toxin modifies a proximal lysine/asparagine residue instead. In conclusion, our results reveal the molecular mechanism underpinning activation of pertussis-like toxins, and we also identified differences in host target specificity

Association of Escherichia coli O157:H7 tir polymorphisms with human infection

<p>Abstract</p> <p>Background</p> <p>Emerging molecular, animal model and epidemiologic evidence suggests that Shiga-toxigenic <it>Escherichia coli </it>O157:H7 (STEC O157) isolates vary in their capacity to cause human infection and disease. The translocated intimin receptor (<it>tir</it>) and intimin (<it>eae</it>) are virulence factors and bacterial receptor-ligand proteins responsible for tight STEC O157 adherence to intestinal epithelial cells. They represent logical genomic targets to investigate the role of sequence variation in STEC O157 pathogenesis and molecular epidemiology. The purposes of this study were (1) to identify <it>tir </it>and <it>eae </it>polymorphisms in diverse STEC O157 isolates derived from clinically ill humans and healthy cattle (the dominant zoonotic reservoir) and (2) to test any observed <it>tir </it>and <it>eae </it>polymorphisms for association with human (vs bovine) isolate source.</p> <p>Results</p> <p>Five polymorphisms were identified in a 1,627-bp segment of <it>tir</it>. Alleles of two <it>tir </it>polymorphisms, <it>tir </it>255 T>A and repeat region 1-repeat unit 3 (RR1-RU3, presence or absence) had dissimilar distributions among human and bovine isolates. More than 99% of 108 human isolates possessed the <it>tir </it>255 T>A T allele and lacked RR1-RU3. In contrast, the <it>tir </it>255 T>A T allele and RR1-RU3 absence were found in 55% and 57%, respectively, of 77 bovine isolates. Both polymorphisms associated strongly with isolate source (p < 0.0001), but not by pulsed field gel electrophoresis type or by <it>stx</it>1 and <it>stx</it>2 status (as determined by PCR). Two <it>eae </it>polymorphisms were identified in a 2,755-bp segment of 44 human and bovine isolates; 42 isolates had identical <it>eae </it>sequences. The <it>eae </it>polymorphisms did not associate with isolate source.</p> <p>Conclusion</p> <p>Polymorphisms in <it>tir </it>but not <it>eae </it>predict the propensity of STEC O157 isolates to cause human clinical disease. The over-representation of the <it>tir </it>255 T>A T allele in human-derived isolates vs the <it>tir </it>255 T>A A allele suggests that these isolates have a higher propensity to cause disease. The high frequency of bovine isolates with the A allele suggests a possible bovine ecological niche for this STEC O157 subset.</p