Evaluation of Genetic or Cellular Impairments in Type I IFN Immunity in a Cohort of Young Adults with Critical COVID-19.

Several genetic and immunological risk factors for severe COVID-19 have been identified, with monogenic conditions relating to 13 genes of type I interferon (IFN) immunity proposed to explain 4.8% of critical cases. However, previous cohorts have been clinically heterogeneous and were not subjected to thorough genetic and immunological analyses. We therefore aimed to systematically investigate the prevalence of rare genetic variants causing inborn errors of immunity (IEI) and functionally interrogate the type I IFN pathway in young adults that suffered from critical COVID-19 yet lacked comorbidities. We selected and clinically characterized a cohort of 38 previously healthy individuals under 50 years of age who were treated in intensive care units due to critical COVID-19. Blood samples were collected after convalescence. Two patients had IFN-α autoantibodies. Genome sequencing revealed very rare variants in the type I IFN pathway in 31.6% of the patients, which was similar to controls. Analyses of cryopreserved leukocytes did not indicate any defect in plasmacytoid dendritic cell sensing of TLR7 and TLR9 agonists in patients carrying variants in these pathways. However, lymphocyte STAT phosphorylation and protein upregulation upon IFN-α stimulation revealed three possible cases of impaired type I IFN signaling in carriers of rare variants. Together, our results suggest a strategy of functional screening followed by genome analyses and biochemical validation to uncover undiagnosed causes of critical COVID-19.

Short Report: Choline plasma levels are related to Nrf2 transcriptional expression in chronic kidney disease?

BACKGROUND & AIMS: Choline is an amine osmolyte with antioxidant potential. A limited number of studies have implied that choline modulates the nuclear factor-erythroid 2-related factor 2 (Nrf 2) pathway, a major cytoprotectant system. However, there are no data regarding such an interaction in patients with chronic kidney disease (CKD). This cross-sectional pilot study therefore aimed to evaluate the possible relationship between choline plasma levels and transcriptional expression of Nrf2 in patients with CKD on hemodialysis (HD). METHODS: This study was performed in 24 HD patients [54 ± 10 years, 14 men, BMI 26.4 ± 4.5 kg/m2]. Choline plasma levels were measured by LC-MS/MS. Nrf2 mRNA expression was measured by real-time quantitative polymerase chain reaction (rt-PCR) in isolated peripheral blood mononuclear cells (PBMC). RESULTS: We used Pearson's correlation (rho) to determine the correlations with Nrf 2 expression and observed a positive correlation between choline plasma levels and Nrf2 (rho = 0.56, P = 0.004). CONCLUSIONS: This finding suggests that choline may play a role in Nrf2 expression in CKD.

Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: a Pilot Study.

Components present in the diet, L-carnitine, choline, and betaine are metabolized by gut microbiota to produce metabolites such as trimethylamine-N-oxide (TMAO) that appear to promote cardiovascular disease in chronic kidney disease (CKD) patients. The objective of this pilot study was to evaluate the effects of probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on hemodialysis (HD). A randomized, double-blind trial was performed in 21 patients [54.8 ± 10.4 years, nine men, BMI 26.1 ± 4.8 kg/m2, dialysis vintage 68.5 (34.2-120.7) months]. Ten patients were randomly allocated to the placebo group and 11 to the probiotic group [three capsules, totaling 9 × 1013 colony-forming units per day of Streptococcus thermophilus (KB19), Lactobacillus acidophilus (KB27), and Bifidobacteria longum (KB31). Plasma TMAO, choline, and betaine levels were measured by LC-MS/MS at baseline and after 3 months. While TMAO did not change after probiotic supplementation, there was a significant increase in betaine plasma levels. In contrast, the placebo group showed a significant decrease in plasma choline levels. Short-term probiotic supplementation does not appear to influence plasma TMAO levels in HD patients. Long-term studies are needed to determine whether probiotics may affect TMAO production in CKD patients.

Body condition, live weight and success in agonistic encounters in mixed parity groups of sows during gestation.

Group housing of gestating sows benefits their welfare by allowing them freedom of movement and the opportunity for social interaction. However, social life could also bring disadvantages for individuals who receive direct aggression or are displaced from the feeder. The aim of this study was to investigate associations between social behaviour, body condition and live weight. Gestating sows (n=298) were investigated on a commercial farm. Sows were housed in mixed parity groups where two single space, ad libitum trough feeders served 12 animals. Sows were weighed, body condition scored and had their back fat layer measured at mixing, 4 weeks after insemination and again before farrowing. Social status was estimated based on the numbers of won and lost agonistic interactions at mixing and at the end of gestation. In addition, tear staining was scored before the farrowing and reproductive performance data were collected. With the aid of video recordings, 100 to 150 interactions per group were observed. Winning percentage at mixing and at the end of gestation were associated (P<0.05) and appeared relatively stable within individuals. Tear staining scores and litter sizes were not associated with winning percentage at the end of gestation. However, live weight, relative weight, body condition and back fat thickness were associated with winning percentage (P<0.05), giving heavier animals an advantage. Low winning percentage related to lower live weight gain, probably due to poorer success in competition for feed. Live weight within a mixed parity group could be used as a proxy measure for social status. Sows with low body condition score and submissive sows might need special attention with regard to group dynamics and housing to alleviate the effects of competition in group housing.

Vitamin D and tuberculosis: where next?

Tuberculosis (TB) has troubled mankind for millennia, but current treatment strategies are long and complicated and the disease remains a major global health problem. The risk of Mycobacterium tuberculosis (Mtb) infection or progression of active TB disease is elevated in individuals with vitamin D deficiency. High-dose vitamin D was used to treat TB in the preantibiotic era, and in vitro experimental data show that vitamin D supports innate immune responses that restrict growth of Mtb. Several randomized controlled trials have tested whether adjunctive vitamin D supplementation enhances the clinical and microbiological response to standard antimicrobial chemotherapy for pulmonary TB. The effects have been modest at best, and attention is turning to the question of whether vitamin D supplementation might have a role in preventing acquisition or reactivation of latent Mtb infection. In this article, we describe the effects of vitamin D on host immune responses to Mtb in vitro and in vivo and review the results of clinical trials in the field. We also reflect on the findings of clinical trials of vitamin D supplementation for the prevention of acute respiratory tract infections, and discuss how these findings might influence the design of future trials to evaluate the role of vitamin D in the prevention and treatment of TB.

Daily adjunctive therapy with vitamin D3 and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia.

OBJECTIVE: Immunotherapy using vitamin D (vitD3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB). METHODS: A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention-to-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D3 concentrations. RESULTS: Most subjects had low baseline plasma 25(OH)D3 levels that increased gradually in the vitD3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L-1 ). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (-0.52, 95% CI -0.93, -0.10; P = 0.015) while the modified TB score was reduced at week 8 (-0.58, 95% CI -1.02, -0.14; P = 0.01) and 16 (-0.34, 95% CI -0.64, -0.03; P = 0.03). VitD3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD3 + PBA group (12.6%). CONCLUSION: Daily supplementation with vitD3 + PBA may ameliorate clinical TB symptoms and disease-specific complications, while the intervention had no effect on bacterial clearance in sputum.

Study protocol for a pragmatic randomised controlled trial evaluating efficacy of a smoking cessation e-'Tabac Info Service': ee-TIS trial.

INTRODUCTION: A French national smoking cessation service, Tabac Info Service, has been developed to provide an adapted quitline and a web and mobile application involving personalised contacts (eg, questionnaires, advice, activities, messages) to support smoking cessation. This paper presents the study protocol of the evaluation of the application (e-intervention Tabac Info Service (e-TIS)). The primary objective is to assess the efficacy of e-TIS. The secondary objectives are to (1) describe efficacy variations with regard to users' characteristics, (2) analyse mechanisms and contextual conditions of e-TIS efficacy. METHODS AND ANALYSES: The study design is a two-arm pragmatic randomised controlled trial including a process evaluation with at least 3000 participants randomised to the intervention or to the control arm (current practices). Inclusion criteria are: aged 18 years or over, current smoker, having completed the online consent forms, possessing a mobile phone with android or apple systems and using mobile applications, wanting to stop smoking sooner or later. The primary outcome is the point prevalence abstinence of 7 days at 6 months later. Data will be analysed in intention to treat (primary) and per protocol analyses. A logistic regression will be carried out to estimate an OR (95% CI) for efficacy. A multivariate multilevel analysis will explore the influence on results of patients' characteristics (sex, age, education and socioprofessional levels, dependency, motivation, quit experiences) and contextual factors, conditions of use, behaviour change techniques. ETHICS AND DISSEMINATION: The study protocol was reviewed by the ethical and deontological institutional review board of the French Institute for Public Health Surveillance on 18 April 2016. The findings of this study will allow us to characterise the efficacy of e-TIS and conditions of its efficacy. These findings will be disseminated through peer-reviewed articles. TRIAL REGISTRATION NUMBER: NCT02841683; Pre-results.

Drosophila as a Model for Human Diseases-Focus on Innate Immunity in Barrier Epithelia.

Epithelial immunity protects the host from harmful microbial invaders but also controls the beneficial microbiota on epithelial surfaces. When this delicate balance between pathogen and symbiont is disturbed, clinical disease often occurs, such as in inflammatory bowel disease, cystic fibrosis, or atopic dermatitis, which all can be in part linked to impairment of barrier epithelia. Many innate immune receptors, signaling pathways, and effector molecules are evolutionarily conserved between human and Drosophila. This review describes the current knowledge on Drosophila as a model for human diseases, with a special focus on innate immune-related disorders of the gut, lung, and skin. The discovery of antimicrobial peptides, the crucial role of Toll and Toll-like receptors, and the evolutionary conservation of signaling to the immune systems of both human and Drosophila are described in a historical perspective. Similarities and differences between human and Drosophila are discussed; current knowledge on receptors, signaling pathways, and effectors are reviewed, including antimicrobial peptides, reactive oxygen species, as well as autophagy. We also give examples of human diseases for which Drosophila appears to be a useful model. In addition, the limitations of the Drosophila model are mentioned. Finally, we propose areas for future research, which include using the Drosophila model for drug screening, as a validation tool for novel genetic mutations in humans and for exploratory research of microbiota-host interactions, with relevance for infection, wound healing, and cancer.

Retrospective evaluation of toceranib phosphate (Palladia®) toxicity in cats.

The purpose of this study was to describe the toxicity profile of toceranib phosphate in tumour bearing cats. Medical records were reviewed from seven institutions. Patients with incomplete medical records and those receiving concurrent chemotherapy or NSAIDs (non-steroidal anti-inflammatory) were excluded. Fifty-five cats met the inclusion criteria. Carcinoma was diagnosed in 55% of cases. Median oral toceranib dose was 2.7 mg kg-1 and was most commonly administered on Monday, Wednesday and Friday. Thrombocytopenia (16.3%) and neutropenia (9.1%) were the most common haematologic toxicities. Azotemia (14.5%) and alanine aminotransferase (ALT) elevations (7.2%) were the most frequently encountered biochemical alterations. Gastrointestinal (GI) toxicity was seen in 21.8% of cats, and was lower than previously reported in dogs. The results of this study showed that treatment of cats with toceranib is well-tolerated and toxicity is uncommon. Additional studies to define a more structured dosing schedule and to evaluate the efficacy of toceranib in the treatment of feline cancers are needed.

Genomic analysis reveals the presence of a class D beta-lactamase with broad substrate specificity in animal bite associated Capnocytophaga species.

Capnocytophga canimorsus and Capnocytophga cynodegmi can be transmitted from cats and dogs to humans, and can cause a wide range of infections including wound infections, sepsis, or endocarditis. We and others recently discovered two new Capnocytophaga species, C. canis and C. stomatis, mainly associated with wound infections. The first-line treatment of animal bite related infections is penicillin, and in case of allergy, doxycycline and trimethoprim/sulfamethoxazole. However, there is a lack of antibiotic susceptibility patterns for animal bite associated Capnocytophaga species. Thus, we set out to study the antibiotic profiles against animal bite associated Capnocytophaga species isolated from wound and blood cultures after cat and dog bites and coupled the findings to whole genome sequencing data. A total of 24 strains were included in the study. Phenotypic analysis of antibiotic resistance was performed with E-tests. The web-based tool 'Resfinder' was used to identify resistance genes in the whole genome dataset. Two strains of C. cynodegmi and two strains of the recently discovered C. stomatis were resistant to penicillin (MIC > 24 mg/L) and cephalosporins (MIC > 24 mg/L), and three out of these strains also exhibited resistance to imipenem (MIC = 32 mg/L). Genomic analysis revealed that these strains carried a class D beta-lactamase gene, which has not previously been found in Capnocytophaga spp. A class D beta lactamase with broad substrate specificity was found in animal bite associated Capnocytophaga species, which could have important implications when treating wound infections after cat and dog bites. It also suggests that pet animal bacteria can harbour resistance genes with relevance for human infections.

Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections.

A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recovery from the infection in a few days implying that APD's are promising candidates for treatment of infections.

Amyloid formation: functional friend or fearful foe?

Amyloid formation has been most studied in the context of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, as well as in amyloidosis. However, it is becoming increasingly clear that amyloid is also present in the healthy setting; for example nontoxic amyloid formation is important for melanin synthesis and in innate immunity. Furthermore, bacteria have mechanisms to produce functional amyloid structures with important roles in bacterial physiology and interaction with host cells. Here, we will discuss some novel aspects of fibril-forming proteins in humans and bacteria. First, the amyloid-forming properties of the antimicrobial peptide human defensin 6 (HD6) will be considered. Intriguingly, unlike other antimicrobial peptides, HD6 does not kill bacteria. However, recent data show that HD6 can form amyloid structures at the gut mucosa with strong affinity for bacterial surfaces. These so-called nanonets block bacterial invasion by entangling the bacteria in net-like structures. Next, the role of functional amyloid fibrils in human semen will be discussed. These fibrils were discovered through their property to enhance HIV infection but they may also have other yet unknown functions. Finally, the role of amyloid formation in bacteria will be reviewed. The recent finding that bacteria can make amyloid in a controlled fashion without toxic effects is of particular interest and may have implications for human disease. The role of amyloid in health and disease is beginning to be unravelled, and here, we will review some of the most recent findings in this exciting area.

A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden.

In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.

Vitamin D status in Well-Controlled Caucasian HIV Patients in Relation to Inflammatory and Metabolic Markers--A Cross-Sectional Cohort Study in Sweden.

To study vitamin D (25OH D3 ) in relation to (i) microbial translocation (ii) systemic inflammation and (iii) blood lipid markers, in Caucasian, well-controlled HIV patients and healthy controls, plasma and serum samples from n = 97 male, HIV patients on HAART with immeasurable viral load (<20 copies/ml) since median 6.5 years and no concurrent inflammatory or infectious disease and n = 30 healthy controls were analysed for (i) LPS; (ii) sCD14, hsCRP, IL-4, IL-6, IL-10, IL-17, MCP-1 and IFN-γ; as well as (iii) blood lipids. Vitamin D levels were similarly distributed and equally low in both HIV patients and controls. There was no association between vitamin D levels and markers of microbial translocation, systemic inflammation or dyslipidemia. LPS levels were similar in both groups but HIV patients expressed higher levels of sCD14 and hsCRP, with HIV as an independent risk factor. HIV patients had higher cholesterol and Apo B levels. Notably, more HIV patients smoked and smoking was associated with lower vitamin D levels. In conclusion; these well-treated Caucasian HIV patients had similar vitamin D levels as healthy controls. However, despite perfect virological control, they exhibited slightly increased inflammatory markers and disturbed blood lipids. However, neither of these parameters were associated with low vitamin D levels but appeared to be linked to the HIV-disease per se. Thus, the rationale for vitamin D substitution as a way to improve microbial translocation and systemic inflammation is not fully supported in this HIV population.

Identification of blood and wound isolates of C. canimorsus and C. cynodegmi using VITEK2 and MALDI-TOF.

Capnocytophaga canimorsus and C. cynodegmi are gram negative bacteria that can be transmitted to humans from dogs or cats and cause serious infections. Routine bacteriological methods, including fermentation and phenotypic tests are insufficient to correctly identify C. canimorsus or C. cynodegmi. The aim of this study was to evaluate the performance of VITEK2 and MALDI-TOF in identification of these bacteria. Twenty two isolates that were identified as C. canimorsus / C. cynodegmi by 16S rRNA sequencing were included in the study and were further investigated with VITEK2 and MALDI-TOF. A Capnocytophaga species-specific PCR was used as the reference method. Out of 22 included isolates, the species-specific PCR identified six blood isolates as C. canimorsus and 14 wound isolates as C. cynodegmi. Two isolates could not be identified with the reference method. VITEK2 identified 10/20 isolates correctly to Capnocytophaga spp. MALDI-TOF analysis correctly identified 6/6 C. canimorsus and 13/14 C. cynodegmi isolates. The mean time to identification with VITEK2 was 6 hours whereas MALDI-TOF required approximately 10 minutes per sample. Here we show that MALDI-TOF rapidly identified C. canimorsus and C. cynodegmi and thus constitutes a valuable diagnostic tool in the clinical laboratory.

Prognostic markers for canine melanocytic neoplasms: a comparative review of the literature and goals for future investigation.

Many studies have evaluated various prognostic markers for canine melanocytic neoplasms either as primary or secondary goals; however, design, methodology, and statistical validation vary widely across these studies. The goal of this article was to evaluate and compare published canine melanocytic neoplasm studies in relation to the principals established in the Recommended Guidelines for the Conduct and Evaluation of Prognostic Studies in Veterinary Oncology. Based on this evaluation, we determined which parameters currently have the most statistically supported validity for prognostic use in canine melanocytic neoplasia. This information can also be used as part of evidence-based prospective evaluations of treatment regimens. Additionally, we highlight areas in which the current data are incomplete and that warrant further evaluation. This article represents an initiative of the American College of Veterinary Pathologists' Oncology Committee and has been reviewed and endorsed by the World Small Animal Veterinary Association.

Xenogeneic murine tyrosinase DNA vaccine for malignant melanoma of the digit of dogs.

BACKGROUND: Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. Metastatic disease is a common sequela for which few effective treatment options exist. Studies show that xenogeneic tyrosinase DNA vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma. OBJECTIVES/HYPOTHESIS: Describe clinical findings and tumor characteristics of a cohort of dogs with digit malignant melanoma, and evaluate the prognostic utility of a proposed staging system. Determine if a novel xenogeneic DNA vaccine is safe and potentially effective for treatment of dogs with digit melanoma. ANIMALS: Fifty-eight dogs with digit malignant melanoma treated at the Animal Medical Center between 2004 and 2007. METHODS: Retrospective, medical records review of dogs with digit melanoma treated with xenogeneic DNA vaccine. RESULTS: Overall median survival time (MST) for dogs treated with loco-regional control and xenogeneic DNA vaccine was 476 days with a 1-year survival rate of 63%. MST for dogs presenting with metastasis was 105 days versus 533 days for dogs presenting without metastasis (P < .0001). Forty-eight percent of the dogs in the latter group were alive at 2 and 3 years. A proposed staging system proved prognostic with stages I-IV dogs surviving >952, >1,093, 321, and 76 days, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The xenogeneic murine tyrosinase DNA vaccine was safe and appears effective when used in conjunction with local and regional disease control. The proposed staging system was prognostic in this study and future studies might benefit from utilizing this staging system.

Recommended guidelines for the conduct and evaluation of prognostic studies in veterinary oncology.

There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists' Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association.

Concurrent validity of a modified version of the International Physical Activity Questionnaire (IPAQ-A) in European adolescents: The HELENA Study.

INTRODUCTION: The International Physical Activity Questionnaire (IPAQ) was developed to measure health-enhancing physical activity in adult populations. This study explores the concurrent validity of a modified version of the long IPAQ (the IPAQ-A) for the assessment of physical activity among adolescents. PARTICIPANTS AND METHODS: In total, 248 healthy adolescents, divided into one older and one younger age group (aged 15-17 years (N=188) and 12-14 years (N=60), respectively) from nine Healthy Lifestyle by Nutrition in Adolescence (HELENA) Study centres across Europe, voluntarily participated in the study. Data on total physical activity, as well as activities in different intensities derived from the IPAQ-A, were compared using Spearman's correlation coefficient and Bland-Altman analysis, with data from an accelerometer. Tertiles of total physical activity for the IPAQ-A and the accelerometer were compared using Kendall's tau-b. RESULTS: For the older age group, significant correlations between the instruments were found for time spent walking, for moderate and vigorous activities as well as for total physical activity (Rs=0.17-0.30, P<0.05). No significant correlations were found for any of the variables studied in the younger age group. Kendall's tau-b showed low but significant correlations for tertiles of total physical activity (P<0.001). CONCLUSIONS: The IPAQ-A has reasonable validity properties for assessing activities in different intensities and for total physical activity in healthy European adolescents aged 15-17 years. For adolescents aged 14 years and younger, the correlations were unsatisfactorily low and objective methodology, such as accelerometry, may be the appropriate alternative.