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Objective: To examine the reliability of a set of health-related physical fitness tests used in the European Union-funded Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study on lifestyle and nutrition among adolescents. Design: A set of physical fitness tests was performed twice in a study sample, 2 weeks apart, by the same researchers. Participants: A total of 123 adolescents (69 males and 54 females, aged 13.6 ± 0.8 years) from 10 European cities participated in the study. Measurements: Flexibility, muscular fitness, speed/agility and aerobic capacity were tested using the back-saver sit and reach, handgrip, standing broad jump, Bosco jumps (squat jump, counter movement jump and Abalakov jump), bent arm hang, 4 Â 10 m shuttle run, and 20-m shuttle run tests. Results: The ANOVA analysis showed that neither systematic bias nor sex differences were found for any of the studied tests, except for the back-saver sit and reach test, in which a borderline significant sex difference was observed (P ¼ 0.044). The Bland-Altman plots graphically showed the reliability patterns, in terms of systematic errors (bias) and random error (95% limits of agreement), of the physical fitness tests studied. The observed systematic error for all the fitness assessment tests was nearly 0. Conclusions: Neither a learning nor a fatigue effect was found for any of the physical fitness tests when repeated. The results also suggest that reliability did not differ between male and female adolescents. Collectively, it can be stated that the reliability of the set of physical fitness tests examined in this study is acceptable. The data provided contribute to a better understanding of physical fitness assessment in young people.

Chaperones (stress proteins) are essential proteins to help the formation and maintenance of the proper conformation of other proteins and to promote cell survival after a large variety of environmental stresses. Therefore, normal chaperone function is a key factor for endogenous stress adaptation of several tissues. However, altered chaperone function has been associated with the development of several diseases; therefore, modulators of chaperone activities became a new and emerging field of drug development. Inhibition of the 90 kDa heat shock protein (Hsp)90 recently emerged as a very promising tool to combat various forms of cancer. On the other hand, the induction of the 70 kDa Hsp70 has been proved to be an efficient help in the recovery from a large number of diseases, such as, for example, ischemic heart disease, diabetes and neurodegeneration. Development of membrane-interacting drugs to modify specific membrane domains, thereby modulating heat shock response, may be of considerable therapeutic benefit as well. In this review, we give an overview of the therapeutic approaches and list some of the key questions of drug development in this novel and promising therapeutic approach.

Objective: To describe the development of a European computerized 24-h dietary recall method for adolescents, and to investigate the feasibility of self-administration (self report) by comparison with administration by a dietician (interview). Methods: Two hundred and thirty-six adolescents (mean age 14.6 years (s.d. ¼ 1.7)) of eight European cities completed the 24-h recall (Young Adolescents Nutrition Assessment on Computer (YANA-C)) twice (once by self-report and once by interview). Results: A small but significant underestimate in energy (61 (s.e. ¼ 31) kcal) and fat (4.2 (s.e. ¼ 1.7) g) intake was found in the self-reports in comparison with the interviews; no significant differences were found for the intake of carbohydrates, proteins, fibre, calcium, iron and ascorbic acid. Spearman's correlations were highly significant for all nutrients and energy ranging between 0.86 and 0.91. Agreement in categorizing the respondents as consumers and non-consumers for the 29 food groups was high (kappa statistics X0.73). Percentage omissions were on average 3.7%; percentage intrusions: 2.0%. Spearman's correlations between both modes were high for all food groups, for the total sample (X0.76) as well as for the consumers only (X0.72). Analysing the consumer only, on an average 54% of the consumed amounts were exactly the same; nevertheless, only for one group 'rice and pasta' a significant difference in consumption was found. Conclusion: Adaptation, translation and standardization of YANA-C make it possible to assess the dietary intake of adolescents in a broad international context. In general, good agreement between the administration modes was found, the latter offering significant potential for large-scale surveys where the amount of resources to gather data is limited.

The Healthy Lifestyle in Europe by Nutrition in Adolescence Study aims to describe total body fat percentage and anthropometric indices of body fat distribution in European adolescents. Objective: To describe the standardization process and reliability of anthropometric and bioelectrical impedance analysis (BIA) measurements. We examined both intra-and interobserver errors for skinfolds, circumferences and BIA. Methods: For the intraobserver error assessment, first of all, 202 adolescents in the pilot study (110 boys, 92 girls, aged 13.64 ± 0.78 years) were assessed. For the second intraobserver and interobserver assessments, 10 adolescents were studied (5 boys and 5 girls). Results: The pilot study's intraobserver technical errors of measurement (TEMs) were between 0.12 and 2.9 mm for skinfold thicknesses, and between 0.13 and 1.75 cm for circumferences. Intraobserver reliability for skinfold thicknesses was greater than 69.44% and beyond 78.43% for circumferences. The final workshop's intraobserver TEMs for skinfold thicknesses and circumferences were smaller than 1; for BIA resistance TEMs were smaller than 0.1 O and for reactance they were smaller than 0.2 O. Intraobserver reliability values were greater than 95, 97, 99 and 97% for skinfold thicknesses, circumferences, BIA resistance and reactance, respectively. Interobserver TEMs for skinfold thicknesses and circumferences ranged from 1 to 2 mm; for BIA they were 1.16 and 1.26 O for resistance and reactance, respectively. Interobserver reliability for skinfold thicknesses and circumferences were greater than 90%, and for BIA resistance and reactance they were greater than 90%. Conclusions: After the results of the pilot study, it was necessary to optimize the quality of the anthropometric measurements before the final survey. Significant improvements were observed in the intraobserver reliabilities for all measurements, with interobserver reliabilities being higher than 90% for most of the measurements.

Cellular stress response is a universal mechanism of extraordinary pathophysiological and pharmacological significance [1]. Dysregulation of the stress protein expression is known to play a determining role in the pathology of different human diseases and aging [2]. Identification of the primary sensors that perceive various stress stimuli and of the transducers that carry, amplify and integrate the signals culminating in the expression of a particular heat shock protein (HSP) is therefore of key importance [3,4].HSP expression in mammalian cells is primarily regulated at the level of transcription and, although not exclusively, is mainly mediated by heat shock factors (HSF), especially HSF1 [5]. The conversion of HSFs to their active, DNA-binding form involves oligomerization to a trimeric state and reversible hyperphosphorylation at multiple sites [6]. The exact mechanism of HSF1 hyperphosphorylation is currently unknown, and the regulation of the mammalian heat shock response appears to be more complex The concentrations of two structurally distinct membrane fluidizers, the local anesthetic benzyl alcohol (BA) and heptanol (HE), were used at concentrations so that their addition to K562 cells caused identical increases in the level of plasma membrane fluidity as tested by 1,6-diphenyl-1,3,5-hexatriene (DPH) anisotropy. The level of membrane fluidization induced by the chemical agents on isolated membranes at such concentrations corresponded to the membrane fluidity increase seen during a thermal shift up to 42°C. The formation of isofluid membrane states in response to the administration of BA or HE resulted in almost identical downshifts in the temperature thresholds of the heat shock response, accompanied by increases in the expression of genes for stress proteins such as heat shock protein (HSP)-70 at the physiological temperature. Similarly to thermal stress, the exposure of the cells to these membrane fluidizers elicited nearly identical increases of cytosolic Ca 2+ concentration in both Ca 2+ -containing and Ca 2+ -free media and also closely similar extents of increase in mitochondrial hyperpolarization. We obtained no evidence that the activation of heat shock protein expression by membrane fluidizers is induced by a proteinunfolding signal. We suggest, that the increase of fluidity in specific membrane domains, together with subsequent alterations in key cellular events are converted into signal(s) leading to activation of heat shock genes.Abbreviations BA, benzyl alcohol; DPH, 1,6-diphenyl-1,3,5-hexatriene; ERK, extracellular signal-regulated kinase; HE, heptanol; HSF, heat shock factor; HSP, heat shock protein; TMA-DPH, 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene; DW m , mitochondrial membrane potential.

Targeting of the Hsp function in tumor cells is currently being assessed as potential anticancer therapy. An improved understanding of the molecular signals that trigger or attenuate the stress protein response is essential for advances to be made in this field. The present study provides evidence that the membrane fluidizer benzyl alcohol (BA), a documented nondenaturant, acts as a chaperone inducer in B16(F10) melanoma cells. It is demonstrated that this effect relies basically on heat shock transcription factor 1 (HSF1) activation. Under the conditions tested, the BA-induced Hsp response involves the up-regulation of a subset of hsp genes. It is shown that the same level of membrane fluidization (estimated in the core membrane region) attained with the closely analogous phenethyl alcohol (PhA) does not generate a stress protein signal. BA, at a concentration that activates heat shock genes, exerts a profound effect on the melting of raft-like cholesterolsphingomyelin domains in vitro, whereas PhA, at a concentration equipotent with BA in membrane fluidization, has no such effect. Furthermore, through the in vivo labeling of melanoma cells with a fluorescein labeled probe that inserts into the cholesterol-rich membrane domains [fluorescein ester of polyethylene glycol-derivatized cholesterol (fPEG-Chol)], we found that, similarly to heat stress per se, BA, but not PhA, initiates profound alterations in the plasma membrane microdomain structure. We suggest that, apart from membrane hyperfluidization in the deep hydrophobic region, a distinct reorganization of cholesterol-rich microdomains may also be required for the generation and transmission of stress signals to activate hsp genes. molecular chaperones ͉ stress signaling ͉ membrane defects ͉ rafts ͉ cancer therapy

Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks. Objective: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial). Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period. Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n 5 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P 5 .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred. Conclusion: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day. (J Allergy Clin Immunol 2020;nnn:nnn-nnn.)