828 resultados para Early life stress
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Objective This study investigated environmental endotoxin exposure during early life, sensitization to aeroallergens, the production of cytokines by LPS-stimulated leukocytes, and the development of a wheezing phenotype in a prospective cohort of infants with high risk of developing allergic diseases. Materials and Methods Eighty-four infants were followed from birth until 30 months of age. We assessed endotoxin concentration in house dust of their homes during the first 6 months of life. At age 30 months they were clinically evaluated to determine the development of wheezing and other clinical events, were skin prick tested, and had blood samples collected for the evaluation of cytokine release by LPS-stimulated peripheral blood mononuclear cells (PBMC). Results The level of endotoxin exposure during early life was not associated with development of a wheezing phenotype. On the other hand a higher incidence of respiratory infections occurred among recurrent wheezing (RW) infants. PBMC from RW children exposed to higher levels of environmental endotoxin (above 50?EU/mg) released less Interleukin (IL)-12p70 and IFN-? compared to the non-RW group. TNF-a, IL-10, IL-4, IL-5, and IL17 production by LPS-stimulated PBMC from RW and non-RW children was equivalent in both groups of environmental endotoxin exposure. Conclusion In this prospective cohort of infants with high risk of developing allergic diseases we observed that RW and non-RW children were exposed to similar levels of endotoxin early in life. LPS-stimulated PBMC from RW infants exposed to higher levels of endotoxin released significantly less IL-12 and IFN-? compared to non-RW infants. Pediatr Pulmonol. 2012. 47:10541060. (C) 2012 Wiley Periodicals, Inc.
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Background: Although linear growth during childhood may be affected by early-life exposures, few studies have examined whether the effects of these exposures linger on during school age, particularly in low-and middle-income countries. Methods: We conducted a population-based longitudinal study of 256 children living in the Brazilian Amazon, aged 0.1 y to 5.5 y in 2003. Data regarding socioeconomic and maternal characteristics, infant feeding practices, morbidities, and birth weight and length were collected at baseline of the study (2003). Child body length/height was measured at baseline and at follow-up visits (in 2007 and 2009). Restricted cubic splines were used to construct average height-for-age Z score (HAZ) growth curves, yielding estimated HAZ differences among exposure categories at ages 0.5 y, 1 y, 2 y, 5 y, 7 y, and 10 y. Results: At baseline, median age was 2.6 y (interquartile range, 1.4 y-3.8 y), and mean HAZ was -0.53 (standard deviation, 1.15); 10.2% of children were stunted. In multivariable analysis, children in households above the household wealth index median were 0.30 Z taller at age 5 y (P = 0.017), and children whose families owned land were 0.34 Z taller by age 10 y (P = 0.023), when compared with poorer children. Mothers in the highest tertile for height had children whose HAZ were significantly higher compared with those of children from mothers in the lowest height tertile at all ages. Birth weight and length were positively related to linear growth throughout childhood; by age 10 y, children weighing >3500 g at birth were 0.31 Z taller than those weighing 2501 g to 3500 g (P = 0.022) at birth, and children measuring >= 51 cm at birth were 0.51 Z taller than those measuring <= 48 cm (P = 0.005). Conclusions: Results suggest socioeconomic background is a potentially modifiable predictor of linear growth during the school-aged years. Maternal height and child's anthropometric characteristics at birth are positively associated with HAZ up until child age 10 y.
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Background: Snake bite is a neglected public health problem in communities in rural areas of several countries. Bothrops jararaca causes many snake bites in Brazil and previous studies have demonstrated that the pharmacological activities displayed by its venom undergo a significant ontogenetic shift. Similarly, the venom proteome of B. jararaca exhibits a considerable variation upon neonate to adult transition, which is associated with changes in diet from ectothermic prey in early life to endothermic prey in adulthood. Moreover, it has been shown that the Brazilian commercial antibothropic antivenom, which is produced by immunization with adult venom, is less effective in neutralizing newborn venom effects. On the other hand, venom gland transcripts of newborn snakes are poorly known since all transcriptomic studies have been carried out using mRNA from adult specimens. Methods/Principal Findings: Here we analyzed venom gland cDNA libraries of newborn and adult B. jararaca in order to evaluate whether the variability demonstrated for its venom proteome and pharmacological activities was correlated with differences in the structure of toxin transcripts. The analysis revealed that the variability in B. jararaca venom gland transcriptomes is quantitative, as illustrated by the very high content of metalloproteinases in the newborn venom glands. Moreover, the variability is also characterized by the structural diversity of SVMP precursors found in newborn and adult transcriptomes. In the adult transcriptome, however, the content of metalloproteinase precursors considerably diminishes and the number of transcripts of serine proteinases, C-type lectins and bradykinin-potentiating peptides increase. Moreover, the comparison of the content of ESTs encoding toxins in adult male and female venom glands showed some genderrelated differences. Conclusions/Significance: We demonstrate a substantial shift in toxin transcripts upon snake development and a marked decrease in the metalloproteinase P-III/P-I class ratio which are correlated with changes in the venom proteome complexity and pharmacological activities.
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Glycosylation is an important post-translational modification of snake venom proteins and contributes to venom proteome complexity. Many snake venom components are known to be glycosylated, however, very little is known about the carbohydrate structures present in venom glycoproteins. Previous studies showed that the ontogenetic shift in diet, from ectothermic prey in early life to endothermic prey in adulthood, and shift in animal size are associated with changes in the venom proteome of the snake Bothrops jararaca. In this study we explored the composition of the N-glycome released from newborn and adult B. jararaca venom proteins. We used an ion trap mass spectrometer (IT-MS) to disassemble glycan structures based on the use of several pathways of MS (MSn) and demonstrate the presence of some structural isomers in both newborn and adult venom B. jararaca N-glycans. The main N-glycans identified in both venoms are of the hybrid/complex type however some mannose-rich type structures were also detected. The N-glycan composition of newborn and adult venoms did not vary indicating that differences in the utilization of the N-glycosylation motif could be the explanation for the differences in the glycosylation levels indicated by the differential electrophoretic profiles previously reported for B. jararaca newborn and adult venoms. (C) 2011 Elsevier B.V. All rights reserved.
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Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+ CD25+ Foxp3+ T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-gamma-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods.
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Abstract Background Preconception allergen immunization prevents neonatal allergen sensitization in mice by a complex interaction between regulatory cells/factors and antibodies. The present study assessed the influence of maternal immunization with ovalbumin (OVA) on the immune response of 3 day-old and 3 week-old offspring immunized or non-immunized with OVA and evaluated the effect of IgG treatment during fetal development or neonatal period. Results Maternal immunization with OVA showed increased levels of FcγRIIb expression in splenic B cells of neonates, which were maintained for up to 3 weeks and not affected by additional postnatal OVA immunization. Maternal immunization also exerted a down-modulatory effect on both IL-4 and IFN-γ-secreting T cells and IL-4 and IL-12- secreting B cells. Furthermore, immunized neonates from immunized mothers showed a marked inhibition of antigen-specifc IgE Ab production and lowered Th2/Th1 cytokine levels, whereas displaying enhanced FcγRIIb expression on B cells. These offspring also showed reduced antigen-specific proliferative response and lowered B cell responsiveness. Moreover, in vitro evaluation revealed an impairment of B cell activation upon engagement of B cell antigen receptor by IgG from OVA-immunized mice. Finally, in vivo IgG transference during pregnancy or breastfeeding revealed that maternal Ab transference was able to increase regulatory cytokines, such as IL-10, in the prenatal stage; yet only the postnatal treatment prevented neonatal sensitization. None of the IgG treatments induced immunological changes in the offspring, as it was observed for those from OVA-immunized mothers. Conclusion Maternal immunization upregulates the inhibitory FcγRIIb expression on offspring B cells, avoiding skewed Th2 response and development of allergy. These findings contribute to the advancement of prophylactic strategies to prevent allergic diseases in early life.
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This study investigated the effects of perinatal cadmium exposure on sexual behavior, organ weight, and testosterone levels in adult rats. We examined whether immediate postpartum testosterone administration is able to reverse the toxic effects of the metal. Forty pregnant Wistar rats were divided into three groups: 1) control, 2) 10 mg kg-1 cadmium chloride per day, and 3) 20 mg kg-1 cadmium chloride per day. These dams were treated on gestational days 18 and 21 and from lactation 1 to 7. Immediately after birth, half of the offspring from the experimental and control groups received 50 μl (i.p.) of 0.2% testosterone. Male sexual behavior, histological analysis and weight of organs as well as serum testosterone levels were assessed. Results showed that both cadmium doses disrupted sexual behavior in male rats, and postnatal treatment with testosterone reversed the toxic effects of 10 mg kg-1 cadmium and attenuated the effects of 20 mg kg-1 cadmium. Body weight and absolute testis, epididymis, and seminal vesicle weight were decreased by the higher cadmium dose, and testosterone supplementation did not reverse these effects. Serum testosterone levels were unaffected by both cadmium doses. No histological changes were detected in all organs analyzed. Maternal cadmium exposure effects in sexual parameters of male rat offspring were explained by the altered masculinization of the hypothalamus. We suggest that cadmium damaged cerebral sexual differentiation by its actions as an endocrine disruptor and supported by the changes discretely observed from early life during sexual development to adult life, reflected by sexual behavior. Testosterone supplementation after birth reversed some crucial parameters directly related to sexual behavior.
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Red porgy has been proposed as a candidate for diversification of marine aquaculture production (Hernández-Cruz et al., 1999). However, limited larval survival together with the elevated levels of skeletal deformities occurrence (over 50% of the population), under intensive or semi-intensive systems constitute the major bottlenecks for the production of this species at commercial scale (Roo et al., in press). Essential fatty imbalances on early life stages, may alter the osteological development of reared larvae (Cahu et al., 2003). The objective of this study was to determine the effect of rotifers enrichment, particularly on DHA, on growth, survival and occurrence of skeleton deformities in red porgy.
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Survival during the early life stages of marine species, including nearshore temperate reef fishes, is typically very low, and small changes in mortality rates, due to physiological and environmental conditions, can have marked effects on survival of a cohort and, on a larger scale, on the success of a recruitment season. Moreover, trade offs between larval growth and accumulation of energetic resources prior to settlement are likely to influence growth and survival until this critical period and afterwards. Rockfish recruitment rates are notoriously variable between years and across geographic locations. Monitoring of rates of onshore delivery of pelagic juveniles (defined here as settlement) of two species of nearshore rockfishes, Sebastes caurinus and Sebastes carnatus, was done between 2003-2009 years using artificial collectors placed at San Miguel and Santa Cruz Island, off Southern California coast. I investigated spatiotemporal variation in settlement rate, lipid content, pelagic larval duration and larval growth of the newly settled fishes; I assessed relationships between birth date, larval growth, early life-history characteristics and lipid content at settlement, considering also interspecific differences; finally, I attempt to relate interannual patterns of settlement and of early life history traits to easily accessible, local and regional indices of ocean conditions including in situ ocean temperature and regional upwelling, sea surface temperature (SST) and Chlorophyll-a (Chl-a) concentration. Spatial variations appeared to be of low relevance, while significant interannual differences were detected in settlement rate, pelagic larval duration and larval growth. The amount of lipid content of the newly settled fishes was highly variable in space and time, but did not differ between the two species and did not show any relationships with early life history traits, indicating that no trade off involved these physiological processes or they were masked by high individual variability in different periods of larval life. Significant interspecific differences were found in the timing of parturition and settlement and in larval growth rates, with S. carnatus growing faster and breeding and settling later than S. caurinus. The two species exhibited also different patterns of correlations between larval growth rates and larval duration. S. carnatus larval duration was longer when the growth in the first two weeks post-hatch was faster, while S. caurinus had a shorter larval duration when grew fast in the middle and in the end of larval life, suggesting different larval strategies. Fishes with longer larval durations were longer in size at settlement and exhibited longer planktonic phase in periods of favourable environmental conditions. Ocean conditions had a low explanatory power for interannual variation in early life history traits, but a very high explanatory power for settlement fluctuations, with regional upwelling strength being the principal indicator. Nonetheless, interannual variability in larval duration and growth were related to great phenological changes in upwelling happened during the period of this study and that caused negative consequences at all trophic levels along the California coast. Despite the low explanatory power of the environmental variables used in this study on the variation of larval biological traits, environmental processes were differently related with early life history characteristics analyzed to species, indicating possible species-specific susceptibility to ocean conditions and local environmental adaptation, which should be further investigated. These results have implications for understanding the processes influencing larval and juvenile survival, and consequently recruitment variability, which may be dependent on biological characteristics and environmental conditions.
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It is well known that the best grape quality can occur only through the achievement of optimal source/sink ratio. Vine balance is in fact a key parameter in controlling berry sugar, acidity and secondary metabolites content (Howell, 2001; Vanden Heuvel et al., 2004). Despite yield reduction and quality improvement are not always strictly related, cluster thinning is considered a technique which could lead to improvement in grape sugar and anthocyanin composition (Dokoozlian and Hirschfelt, 1995; Guidoni et al., 2002). Among several microclimatic variables which may impact grape composition, the effect of cluster light exposure and temperature, which probably act in synergistic and complex way, has been widely explored showing positive even sometimes contradictory results (Spayd et al., 2001; Tarara et al., 2008). Pre-bloom and véraison defoliation are very efficient techniques in inducing cluster microclimatic modification. Furthermore pre-bloom defoliation inducing a lower berry set percentage On these basis the aim of the first experiment of the thesis was to verify in cv Sangiovese the effects on ripening and berry composition of management techniques which may increase source/sink ratio and /or promote light incidence on berries throughout grape ripening. An integrated agronomic, biochemical and microarray approach, aims to understand which mechanisms are involved in berry composition and may be conditioned in the berries during ripening in vines submitted to three treatments. In particular the treatments compared were: a) cluster thinning (increasing in source/sink ratio) b) leaf removal at véraison (increasing cluster light exposure) c) pre-bloom defoliation (increasing source sink ratio and cluster light exposure). Vine response to leaf removal at véraison was further evaluated in the second experiment on three different varieties (Cabernet Sauvignon, Nero d’Avola, Raboso Piave) chosen for their different genetic traits in terms of anthocyanin amount and composition. The integrated agronomic, biochemical and microarray approach, employed in order to understand those mechanisms involved in berry composition of Sangiovese vines submitted to management techniques which may increase source/sink ratio and induce microclimatic changes, bring to interesting results. This research confirmed the main role of source/sink ratio in conditioning sugars metabolism and revealed also that carbohydrates availability is a crucial issue in triggering anthocyanin biosynthesis. More complex is the situation of pre-bloom defoliation, where source/sink and cluster light increase effects are associated to determine final berry composition. It results that the application of pre-bloom defoliation may be risky, as too much dependent on seasonal conditions (rain and temperature) and physiological vine response (leaf area recovery, photosynthetic compensation, laterals regrowth). Early induced stress conditions could bring cluster at véraison in disadvantage to trigger optimal berry ripening processes compared to untreated vines. This conditions could be maintained until harvest, if no previously described physiological recovery occurs. Certainly, light exposure increase linked to defoliation treatments, showed a positive and solid effect on flavonol biosynthesis, as in our conditions temperature was not so different among treatments. Except the last aspects, that could be confirmed also for véraison defoliation, microclimatic changes by themselves seemed not able to induce any modification in berry composition. Further studies are necessary to understand if the peculiar anthocyanic and flavonols composition detected in véraison defoliation could play important role in both color intensity and stability of wines.
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Während des frühen Lebens stellen epileptische Anfälle schwere neurologische Zustände dar, weil sie ein großer Risikofaktor für die Manifestation der Epilepsie sind und eine hohe pharmakologische Resistenz zeigen. In meiner Doktorarbeit konzentrierte ich mich auf die Frage, wie verschiedene Neurotransmitter-Systeme und klinisch verwendete Medikamente epileptiforme Entladungen im perinatalen Hippocampus beeinflussen. rnIm ersten Teil meines Projektes untersuchte ich die Wirkung von GABA-Antagonisten und Modulatoren, die zwischen phasischen und tonischen GABAergen Strömen differenzieren, auf Feldpotentialaktivität in Hippocampusschnitten. Diese Experimente zeigten, dass im unreifen Hippocampus synaptische GABAerge Aktivität benötigt wird, um die Erregbarkeit zu begrenzen, während tonische GABAerge Ströme die Erregbarkeit verstärken können. Dies könnte darauf hinweisen, dass Antiepileptika mit einer höheren Spezifität für synaptische GABAA-Rezeptoren wirksamer zur Behandlung von epileptischen Anfällen bei Neugeborenen sein können. rnUm den Einfluss von Dopamin auf die Erregbarkeit des unreifen Hippocampus herauszufinden, untersuchte ich im zweiten Teil meiner Arbeit die Wirkung von verschiedenen Dopaminkonzentrationen und spezifische Agonisten und Antagonisten der Dopamin-Rezeptor-Subtypen auf epileptiforme Entladungen. Diese Experimente zeigten, dass niedrige Dopamin Konzentrationen eine antikonvulsive Wirkung haben, welche vom D2-ähnliche-Rezeptor-Agonisten Quinpirol nachgeahmt werden kann, während höhere Dopamin-Konzentrationen eine prokonvulsive Wirkung über Aktivierung von D1-ähnlichen Rezeptoren hervorrufen. Obwohl unsere Untersuchungen eine mögliche Verwendung von D2-ähnlichen Rezeptor-Agonisten zur Kontrolle epileptischer Anfälle in Neugeborenen nahelegen, müssen mögliche negative Auswirkungen von DAergen Agonisten und Antagonisten auf die neuronale Entwicklung berücksichtigt werden.rnIm dritten Teil meiner Arbeit untersuchte ich welche Konzentrationen von Methylxanthinen epileptische Anfälle in Hippocampuspreparationen auslösen die synaptische Übertragungen verändern können. Diese Experimente zeigten, dass sowohl Theophyllin als auch Koffein in höheren Konzentrationen die basale synaptische Übertragungen in der CA1-Region des Hippocampus modifizieren und epileptiforme Entladungen provozieren. Die Auswirkungen auf die postsynaptischen Antworten und spontanen epileptiformen Entladungen durch Koffein waren weniger ausgeprägt, was darauf hindeutet, dass diese Substanz potentiell vorteilhafter für therapeutische Anwendungen bei Frühgeborenen sein kann. rnZusammenfassend bereichern die Ergebnisse meiner Studie erheblich unser Wissen über die zugrunde liegenden Mechanismen epileptiformer Aktivität im unreifen Hippocampus und den therapeutischen Einsatz von Methylxanthinen und Pharmaka, die auf das GABAerge und DArge System einwirken.rnrn
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Background: Several cross-sectional studies during the past 10 years have observed an increased risk of allergic outcomes for children living in damp or mouldy environments. Objective: The objective of this study was to investigate whether reported mould or dampness exposure in early life is associated with the development of allergic disorders in children from eight European birth cohorts. Methods: We analysed data from 31 742 children from eight ongoing European birth cohorts. Exposure to mould and allergic health outcomes were assessed by parental questionnaires at different time points. Meta-analyses with fixed- and random-effect models were applied. The number of the studies included in each analysis varied based on the outcome data available for each cohort. Results: Exposure to visible mould and/or dampness during first 2 years of life was associated with an increased risk of developing asthma: there was a significant association with early asthma symptoms in meta-analyses of four cohorts [0–2 years: adjusted odds ratios (aOR), 1.39 (95%CI, 1.05–1.84)] and with asthma later in childhood in six cohorts [6–8 years: aOR, 1.09(95%CI, 0.90–1.32) and 3–10 years: aOR, 1.10 (95%CI, 0.90–1.34)]. A statistically significant association was observed in six cohorts with symptoms of allergic rhinitis at school age [6–8 years: aOR, 1.12 (1.02–1.23)] and at any time point between 3 and 10 years [aOR, 1.18 (1.09–1.28)]. Conclusion: These findings suggest that a mouldy home environment in early life is associated with an increased risk of asthma particularly in young children and allergic rhinitis symptoms in school-age children.
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Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning.
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Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.