P. S. W. Davies

Clinical longitudinal standards for height and height velocity for North American children

Longitudinally-based height and height velocity charts for North American children are presented. Centiles are given for early, middle, and late maturers. The shape of the curves is taken from a review of longitudinal studies, and the prepubertal and adult centiles for height attained are taken from National Center for Health Statistics data. The charts are suitable for following an individual childs progress during observation or treatment throughout the growth period, including puberty.

How much physical activity is enough to prevent unhealthy weight gain? Outcome of the IASO 1st Stock Conference and consensus statement

A consensus meeting was held in Bangkok, 21–23 May 2002, where experts and young scientists in the field of physical activity, energy expenditure and body‐weight regulation discussed the different aspects of physical activity in relation to the emerging problem of obesity worldwide. The following consensus statement was accepted unanimously.

Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid-β Peptides

Several epidemiological studies indicate that moderate consumption of wine is associated with a lower incidence of Alzheimers disease. Wine is enriched in antioxidant compounds with potential neuroprotective activities. However, the exact molecular mechanisms involved in the beneficial effects of wine intake on the neurodegenerative process in Alzheimers disease brain remain to be clearly defined. Here we show that resveratrol (trans-3,4′,5-trihydroxystilbene), a naturally occurring polyphenol mainly found in grapes and red wine, markedly lowers the levels of secreted and intracellular amyloid-β (Aβ) peptides produced from different cell lines. Resveratrol does not inhibit Aβ production, because it has no effect on the Aβ-producing enzymes β- and γ-secretases, but promotes instead intracellular degradation of Aβ via a mechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of Aβ could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit β5. These findings demonstrate a proteasome-dependent anti-amyloidogenic activity of resveratrol and suggest that this natural compound has a therapeutic potential in Alzheimers disease.

The validity of self-reported energy intake as determined using the doubly labelled water technique.

In the 1980s the development of the doubly labelled water (DLW) technique made it possible to determine the validity of dietary assessment methods using external, independent markers of intake in free-living populations. Since then, the accuracy of self-reported energy intake (EI) has been questioned on a number of occasions as under-reporting has been found to be prevalent in many different populations. This paper is a review of investigations using the DLW technique in conjunction with self-reported EI measures in groups including adults, children and adolescents, obese persons, athletes, military personnel and trekking explorers. In studies where a person other than the subject is responsible for recording dietary intake, such as parents of young children, EI generally corresponds to DLW determined energy expenditure. However, in instances where the subjects themselves report their intake, EI is generally under-reported when compared with energy expenditure. It was originally believed that this phenomenon of under-reporting was linked to increased adiposity and body size, however, it is now apparent that other factors, such as dietary restraint and socio-economic status, are also involved. This paper therefore aims to present a more comprehensive picture of under-reporting by tying in the findings of many DLW studies with other studies focusing particularly on the characteristics and mechanisms for under-reporting. Awareness of these characteristics and mechanisms will enable researchers to obtain more accurate self-reports of EI using all dietary recording techniques.

AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-β peptide metabolism.

Alzheimer disease is an age-related neurodegenerative disorder characterized by amyloid-β (Aβ) peptide deposition into cerebral amyloid plaques. The natural polyphenol resveratrol promotes anti-aging pathways via the activation of several metabolic sensors, including the AMP-activated protein kinase (AMPK). Resveratrol also lowers Aβ levels in cell lines; however, the underlying mechanism responsible for this effect is largely unknown. Moreover, the bioavailability of resveratrol in the brain remains uncertain. Here we show that AMPK signaling controls Aβ metabolism and mediates the anti-amyloidogenic effect of resveratrol in non-neuronal and neuronal cells, including in mouse primary neurons. Resveratrol increased cytosolic calcium levels and promoted AMPK activation by the calcium/calmodulin-dependent protein kinase kinase-β. Direct pharmacological and genetic activation of AMPK lowered extracellular Aβ accumulation, whereas AMPK inhibition reduced the effect of resveratrol on Aβ levels. Furthermore, resveratrol inhibited the AMPK target mTOR (mammalian target of rapamycin) to trigger autophagy and lysosomal degradation of Aβ. Finally, orally administered resveratrol in mice was detected in the brain where it activated AMPK and reduced cerebral Aβ levels and deposition in the cortex. These data suggest that resveratrol and pharmacological activation of AMPK have therapeutic potential against Alzheimer disease.

Remission induced by an elemental diet in small bowel Crohn's disease.

Seventeen children with active Crohns disease of the small intestine were entered into a randomised control trial comparing the efficacy of an elemental diet with that of a high dose steroid regimen. Eight children received an elemental diet (Flexical) through a nasogastric tube for six weeks, followed by reintroduction of food over six weeks during which the Flexical was stopped. Seven children were given intramuscular adrenocorticotrophic hormone followed by oral prednisolone with sulphasalazine. Two children were withdrawn from the trial. The elemental diet was equally effective in inducing an improvement in Lloyd-Still disease activity index, erythrocyte sedimentation rate, C reactive protein and albumin concentrations, and body weight as the high dose steroid regimen. Linear growth, assessed from height velocity over six months, was significantly greater in the children receiving an elemental diet.

Alzheimer Disease-specific Conformation of Hyperphosphorylated Paired Helical Filament-Tau Is Polyubiquitinated through Lys-48, Lys-11, and Lys-6 Ubiquitin Conjugation

One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of paired helical filaments (PHFs) of hyperphosphorylated microtubule-associated protein Tau. Tandem mass spectrometry was employed to examine PHF-Tau post-translational modifications, in particular protein phosphorylation and ubiquitination, to shed light on their role in the early stages of Alzheimer disease. PHF-Tau from Alzheimer disease brain was affinity-purified by MC1 monoclonal antibody to isolate a soluble fraction of PHF-Tau in a conformation unique to human AD brain. A large number of phosphorylation sites were identified by employing a data-dependent neutral loss algorithm to trigger MS3 scans of phosphopeptides. It was found that soluble PHF-Tau is ubiquitinated at its microtubule-binding domain at residues Lys-254, Lys-311, and Lys-353, suggesting that ubiquitination of PHF-Tau may be an earlier pathological event than previously thought and that ubiquitination could play a regulatory role in modulating the integrity of microtubules during the course of AD. Tandem mass spectrometry data for ubiquitin itself indicate that PHF-Tau is modified by three polyubiquitin linkages, at Lys-6, Lys-11, and Lys-48. Relative quantitative analysis indicates that Lys-48-linked polyubiquitination is the primary form of polyubiquitination with a minor portion of ubiquitin linked at Lys-6 and Lys-11. Because modification by Lys-48-linked polyubiquitin chains is known to serve as the essential means of targeting proteins for degradation by the ubiquitin-proteasome system, and it has been reported that modification at Lys-6 inhibits ubiquitin-dependent protein degradation, a failure of the ubiquitin-proteasome system could play a role in initiating the formation of degradation-resistant PHF tangles.

Habitual physical activity and physical activity intensity: their relation to body composition in 5.0-10.5-y-old children

Background: Concerns of a decrease in physical activity levels (PALs) of children and a concurrent increase in childhood obesity exist worldwide. The exact relation between these two parameters however has as yet to be fully defined in children.Objective: This study examined the relation in 47 children, aged 5–10.5 y (mean age 8.4±0.9 y) between habitual physical activity, minutes spent in moderate, vigorous and hard intensity activity and body composition parameters.Design: Total energy expenditure (TEE) was calculated using the doubly labelled water technique and basal metabolic rate (BMR) was predicted from Schofields equations. PAL was determined by PAL=TEE/BMR. Time spent in moderate, vigorous and hard intensity activity was determined by accelerometry, using the Tritrac-R3D. Body fatness and body mass index (BMI) were used as the two measures of body composition.Results: Body fat and BMI were significantly inversely correlated with PAL (r=−0.43, P=0.002 and r=−0.45, P=0.001). Times spent in vigorous activity and hard activity were significantly correlated to percentage body fat (r=−0.44, P=0.004 and r=−0.39, P=0.014), but not BMI. Children who were in the top tertiles for both vigorous activity and hard activity had significantly lower body fat percentages than those in the middle and lowest tertiles. Moderate intensity activity was not correlated with measures of body composition.Conclusions: As well as showing a significant relation between PAL and body composition, these data intimate that there may be a threshold of intensity of physical activity that is influential on body fatness. In light of world trends showing increasing childhood obesity, this study supports the need to further investigate the importance of physical activity for children.

Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking. TBNET consensus statement on the management of patients with MDR/XDR-TB has been released in the Eur Respir J http://ow.ly/uizRD

The contribution of fat and fat-free tissue to body mass index in contemporary children and the reference child

BACKGROUND: Body mass index (BMI) is widely used to assess the prevalence of childhood obesity in populations, and to infer risk of subsequent obesity-related disease. However, BMI does not measure fat directly, and its relationship with body fatness is not necessarily stable over time.OBJECTIVE: To test the hypothesis that contemporary children have different fatness for a given BMI value compared to the reference child of two decades ago.DESIGN: Comparison of children from Cambridge, UK with the reference child of Fomon and colleagues (Am J Clin Nutr 1982; 35: 1169–1175).SUBJECTS: A total of 212 children aged 1–10.99 y.MEASUREMENTS: Body composition was assessed by deuterium dilution. Fat-free mass and fat mass were both adjusted for height to give fat-free mass index and fat mass index.RESULTS: Contemporary Cambridge children have similar mean BMI values to the reference child. However, both boys and girls have significantly greater mean fatness and significantly lower mean fat-free mass than the reference child after taking height into account. Contemporary Cambridge children have greater fatness for a given BMI value than the reference child.CONCLUSION: BMI-based assessments of nutritional status may be under-estimating the increase in childrens fatness. Any change over time in the relationship between BMI and body fatness will create a mismatch between (1) current estimates of childhood obesity and (2) predicted risk of future adult illness, calculated on the basis of longitudinal cohorts recruited in childhood several decades ago. However, an alternative interpretation is that the reference data are inappropriate. Caution should therefore be used in generalizing from this study, and further investigations of the issue are required.