Structural Evolution of Gene Promoters Driven by Primate-Specific KRAB Zinc Finger Proteins.

Krüppel-associated box (KRAB) zinc finger proteins (KZNFs) recognize and repress transposable elements (TEs); TEs are DNA elements that are capable of replicating themselves throughout our genomes with potentially harmful consequences. However, genes from this family of transcription factors have a much wider potential for genomic regulation. KZNFs have become integrated into gene-regulatory networks through the control of TEs that function as enhancers and gene promoters; some KZNFs also bind directly to gene promoters, suggesting an additional, more direct layer of KZNF co-option into gene-regulatory networks. Binding site analysis of ZNF519, ZNF441, and ZNF468 suggests the structural evolution of KZNFs to recognize TEs can result in coincidental binding to gene promoters independent of TE sequences. We show a higher rate of sequence turnover in gene promoter KZNF binding sites than neighboring regions, implying a selective pressure is being applied by the binding of a KZNF. Through CRISPR/Cas9 mediated genetic deletion of ZNF519, ZNF441, and ZNF468, we provide further evidence for genome-wide co-option of the KZNF-mediated gene-regulatory functions; KZNF knockout leads to changes in expression of KZNF-bound genes in neuronal lineages. Finally, we show that the opposite can be established upon KZNF overexpression, further strengthening the support for the role of KZNFs as bona-fide gene regulators. With no eminent role for ZNF519 in controlling its TE target, our study may provide a snapshot into the early stages of the completed co-option of a KZNF, showing the lasting, multilayered impact that retrovirus invasions and host response mechanisms can have upon the evolution of our genomes.

A reference human induced pluripotent stem cell line for large-scale collaborative studies.

Human induced pluripotent stem cell (iPSC) lines are a powerful tool for studying development and disease, but the considerable phenotypic variation between lines makes it challenging to replicate key findings and integrate data across research groups. To address this issue, we sub-cloned candidate human iPSC lines and deeply characterized their genetic properties using whole genome sequencing, their genomic stability upon CRISPR-Cas9-based gene editing, and their phenotypic properties including differentiation to commonly used cell types. These studies identified KOLF2.1J as an all-around well-performing iPSC line. We then shared KOLF2.1J with groups around the world who tested its performance in head-to-head comparisons with their own preferred iPSC lines across a diverse range of differentiation protocols and functional assays. On the strength of these findings, we have made KOLF2.1J and its gene-edited derivative clones readily accessible to promote the standardization required for large-scale collaborative science in the stem cell field.

La incorporación de la atención telefónica a la oferta de atención primaria y sus efectos sobre la salud y la satisfacción de los pacientes: propuesta / Incorporation of telephone care into the provision of primary care and its effects on patient health and satisfaction: Proposal

Se presenta una revisión, análisis y propuesta de implantación, desarrollo y evaluación de la atención telefónica en atención primaria, enfocada como una nueva modalidad de oferta que responda a exigencias normalizadas de seguridad, efectividad, eficiencia y equilibrio, no siempre fácil de alcanzar, entre los intereses de los usuarios y los profesionales (AU)

We present a review, analysis and proposal for the implantation, development and evaluation of telephone attention in primary care, focused as a new modality of offer that responds to standardized requirements of safety, efficacy, efficiency and balance not always easy to achieve, between the interests of users and professionals (AU)

[Incorporation of telephone care into the provision of primary care and its effects on patient health and satisfaction: Proposal]. / La incorporación de la atención telefónica a la oferta de atención primaria y sus efectos sobre la salud y la satisfacción de los pacientes: propuesta.

We present a review, analysis and proposal for the implantation, development and evaluation of telephone attention in primary care, focused as a new modality of offer that responds to standardized requirements of safety, efficacy, efficiency and balance not always easy to achieve, between the interests of users and professionals.

Liver transplantation in Mexican older adults: A comparative single-center study. / Trasplante de hígado en adultos mayores mexicanos: un estudio comparativo en un solo centro.

INTRODUCTION: Liver disease is currently one of the leading causes of death in older adults and the only option deemed curative is liver transplantation. However, it is uncertain whether the successful results obtained in older adults that receive a liver transplant in developed countries can be replicated in developing countries. AIM: To determine if there are differences in the survival time between older (≥60years) and younger adults that underwent liver transplantation at a university-affiliated tertiary care center in Mexico City. MATERIALS AND METHODS: A 2-year longitudinal study was conducted. It included 244 participants that were divided into 2groups according to age at the time of transplantation: older adults (≥60years) and younger adults (18-59years). Survival time was defined as the number of days that elapsed between transplantation and death. Survival was expressed as Kaplan-Meier curves. RESULTS: Median age in the older adults (n=52) was 63.0 (IQR=60-69) and 23 participants were females (44.2%). In the younger adults (n=196) median age was 47.0 (IQR=16-59) and 104 were females (52%). The leading indication for transplant was hepatitisC virus. After the follow-up, fifteen participants died (12 younger adults and 3 older adults). No significant differences were observed between older and younger participants in postoperative complications, the number of re-admissions, or mean post-transplantation survival time. CONCLUSIONS: There were no statistically significant differences in relation to survival times between older and younger adults that received a liver transplant. Older patients in developing countries should not be excluded from the selection process due only to age.

Perceptions of aging and ageism among Mexican physicians-in-training.

INTRODUCTION: Attributing negative stereotypes to older adults (ageism) may lead to undertreatment, but little is known about the prevalence of ageism among physicians treating patients with cancer in Ibero-America. We studied stereotypes of aging among Mexican physicians-in-training. MATERIALS AND METHODS: Physicians-in-training attending an oncology meeting answered the "Negative Attributes and Positive Potential in Old Age" survey. Ten questions assessed positive characteristics of aging (PPOA; score 1-4, higher scores represent a positive perception), and four assessed negative characteristics (NAOA; score 1-4, higher score representing a negative perception). Descriptive statistics were used to analyze the questionnaires. Participants completed the "Image-of-Aging" question by writing five words describing older adults and young individuals. Each word was rated from - 5 (negative) to + 5 (positive), and presented as word clouds. RESULTS: One hundred physicians-in-training (median age 28.5) were included. For the PPOA scale, the mean score was 2.9 (SD 0.4), while for the NAOA scale it was 2.1 (SD 0.4). Perceptions of aging were better among women and trainees enrolled in geriatrics and/or oncology-related programs. In the "Image-of-Aging" questions, median rating of words describing older adults was - 2, compared to + 3 for young individuals (p < 0.001). Among words used to describe older adults, the most frequent was "frail/frailty" (n = 45), while "health" (n = 46) was the most frequent for younger individuals. CONCLUSIONS: Mexican physicians-in-training showed mostly negative perceptions of aging, exemplified by the use of negative terms to describe older adults. Creating educational initiatives aimed at decreasing ageism among oncology trainees is necessary across Ibero-America.

Frailty Is not Associated with Mistreatment.

Muscle Frailty has been previously associated with increased vulnerability for adverse health-related outcomes that could lead to social consequences such as mistreatment. The aim of this cross-sectional study is to determine the association between frailty and mistreatment in 852 community-dwelling persons aged 70 or older. Mistreatment was defined as one positive answer in the Geriatric Mistreatment Scale and frailty was used as a continuum where the greater number of positive criteria according to Fried et al. indicates a higher frailty score. Multivariate logistic regression models were run to establish this association. The mean age of participants was 77.7 years (SD=6.1). Prevalence of frailty phenotype and mistreatment were 13.9% and 20% respectively. Unadjusted analysis showed frailty score was associated with mistreatment (OR = 1.16; 95% CI 1.02 to 1.3, p=0.022). However, after adjustment, the association was no longer present. The results showed that in the presence of other geriatric syndromes such as disability or depression, frailty did not show association with mistreatment in this population.

Successful Aging, a New Challenge for Developing Countries: The Coyoacán Cohort.

OBJECTIVE: To determine the socio-demographic and health factors associated with a biomedical phenotype of successful aging (SA) among Mexican community-dwelling elderly. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 935 older adults aged 70 or older participating in the Mexican Study of Nutritional and Psychosocial Markers of Frailty. MEASUREMENTS: SA was operationalized in accordance with the phenotype proposed by Rowe and Kahn. Univariate and multivariate logistic regression analyses were carried out in order to identify the correlates of SA. RESULTS: The phenotype of SA was present in 10% of participants. Age (P < 0.001), illiteracy (P = 0.021), polypharmacy (P < 0.001), and physical pain (P < 0.001) were factors independently and inversely associated with the presence of the SA phenotype. The only variable positively associated with SA was good self-perceived health-status (P < 0.001). CONCLUSION: Although age is not modifiable, several other factors associated with SA are. If we are to promote SA, efforts should be made towards improving those modifiable factors negatively associated with its presence, such as pain or polypharmacy. Also, enhancing factors positively associated to it might play a role in improving wellbeing.

25-OH-Vitamin D Is Not Associated with Cognitive Performance among Mexican Community-Dwelling Older Persons.

BACKGROUND: Low cognitive performance has been associated with a wide array of adverse health-related outcomes in elderly populations. Recently, the effect of vitamin D on cognition has been studied; however, its benefits are still controversial. Moreover, most studies have been carried out on North-American and European populations where vitamin D deficiency could represent a greater public-health issue when compared to Latin American ones. OBJECTIVE: To investigate the association between 25-OH-vitamin D and cognitive performance in Mexican community-dwelling elderly. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study sample of 331 community-dwelling elderly aged 70 and older, participating in the Mexican Study of Nutritional and Psychosocial Markers of Frailty. MEASUREMENTS: Serum 25-OH-vitamin D, cognitive performance as per the Mini-Mental State Examination (MMSE) and the IST (Isaacs Set Test), as well as several elements from the comprehensive geriatric assessment. RESULTS: Mean age of participants was 79.3 years (SD 5.9), 54.1% were women. The mean serum 25-OH-vitamin D level was 59.0 (SD 23.3) nmol/L while mean MMSE score was 22.3 (SD 3.4) and mean IST score was 37.1 (SD 9.1). Although 25-OH-vitamin D levels were lower across all the definitions of low cognitive perfomance, the difference between groups was not statistically significant in any of them. CONCLUSION: No association between 25-OH-vitamin D level and cognitive performance was found in this population of Mexican community-dwelling elderly. Further investigation is required in order to clarify its existence and if so, to delineate its characteristics.

'Because you can't live on love': living kidney donors' perspectives on compensation and payment for organ donation.

CONTEXT AND OBJECTIVE: Living kidney donation accounts for approximately half of all kidney transplantation in many countries and is central to health policy focused on increasing organ supply. However, little examination of the economic consequences of living kidney donation has been undertaken from the perspective of donors themselves. This article documents living kidney donors' views regarding recompense and payment for organ donation, based on their experience. PARTICIPANTS: Twenty-five living kidney donors from New Zealand participated in this study. METHODS: This qualitative study, based on thematic analysis, uses semi-structured in-depth interviews to examine the experiences of living kidney donors. Themes were organized around altruism and the 'gift', perceptions of shared corporeality and identity, and donor support. RESULTS: Most participants agreed the donation process was costly in terms of time and money. Many incurred personal costs, and some experienced financial hardship. All the participants viewed financial hardship as a barrier to organ donation and favoured recompense for direct and indirect costs. Most did not support payment for organs, and none supported commercialization. DISCUSSION AND CONCLUSIONS: The findings show that framing organ donation as a 'gift' can stymie discussion about reciprocity, remuneration and exchange, making talk about financial recompense difficult. Financial well-being, nonetheless, has implications for the ability to care for self and others post-operatively. We conclude that the economic consequences for living kidney donors in jurisdictions where recompense for direct and indirect costs is insufficient are unfair. Review of financial assistance for live organ donors is therefore recommended.

Association between Self-Reported Health Status and Frailty in Community-Dwelling Elderly.

BACKGROUND: The phenotype of frailty proposed by Fried et al. has been related with increased vulnerability for the development of adverse health-related outcomes. However, this phenotype is not often used in daily clinical practice. On the other hand, poor self-reported health status (SRHS) has been associated with similar adverse health-related outcomes. OBJECTIVES: To determine the association between poor SRHS and frailty. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 927 community-dwelling elderly aged 70 and older, participating in the Mexican Study of Nutritional and Psychosocial Markers of Frailty. MEASUREMENTS: SRHS was established by the question "How do you rate your health status in general?" Frailty was defined according to the phenotype proposed by Fried et al. The association between SRHS and frailty was determined through the construction of multinomial logistic regression models. Final analyses were adjusted by socio-demographic and health covariates, including depressive symptoms. Also, agreement between SRHS and the phenotype of frailty was explored. RESULTS: Prevalence of frailty was 14.1%, and 4.4% of participants rated their health status as "poor". The unadjusted regression analyses demonstrated that fair and poor SRHS were significantly associated with prefrail and frail status. After adjustment for multiple covariates, the association remained statistically significant. However, in the final adjustment for depressive symptoms, only the association between poor SRHS and frail status continued to be statistically significant. Fair agreement between poor SRHS and frail status was also found. CONCLUSION: Poor SRHS shares common correlates as well as health-related adverse outcomes with frailty syndrome, and remains associated with it even when possible confounders are taken into account. Therefore, poor SRHS could be further explored as an option for frailty syndrome screening.

Pax2+ astrocytes in the fish optic nerve head after optic nerve crush.

The transcription factor Pax2 actively participates in the development of the vertebrate visual system. In adults, Pax2 expression persists in a subpopulation of Müller cells and/or astrocytes in the retina and optic nerve head (ONH), although its function remains elusive. In a previous work we showed that the pax2 gene expression is modified and the Pax2(+) astrocyte population in the ONH strongly reacted during the regeneration of the retina after a lesion in goldfish. In the present work we have analyzed Pax2 expression in the goldfish ONH after optic nerve (ON) crush. At one week post-injury, when the regenerating axons arrive at the ONH, the pax2 gene expression level increases as well as the number of Pax2(+) astrocytes in this region. These Pax2(+) astrocytes show a higher number of Cytokeratin (Ck)(+)/GFAP(+) processes compared with control animals. In contrast, a different S100(+) astrocyte population is not modified and persists similar to that of controls. Furthermore, we find a ring that surrounds the posterior ONH that is formed by highly reactive astrocytes, positive to Pax2, GFAP, Ck, S100, GS and ZO1. In this region we also find a source of new astrocytes Pax2(+)/PCNA(+) that is activated after the injury. We conclude that Pax2(+) astrocytes constitute a subpopulation of ONH astrocytes that strongly reacts after ON crush and supports our previous results obtained after retina regeneration. Altogether, this suggests that pax2 gene expression and Pax2(+) astrocytes are probably directly involved in the process of axonal regeneration.

The Phenotype of Frailty and Health-Related Quality of Life.

BACKGROUND: Frailty is a multidimensional problem in the elderly, but there is little information about its implications on health-related quality of life (HRQoL). OBJECTIVES: To determine the association between frailty and HRQoL as well as the association between each component of the phenotype of frailty and the physical (PCS) and mental (MCS) components summaries of QoL. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 496 community-dwelling elderly aged 70 and older, participating in the Mexican Study of Nutritional and Psychosocial Markers of Frailty. MEASUREMENTS: Frailty was defined by the presence of at least three of the following criteria: weight loss, exhaustion, low physical activity, slowness, and weakness. QoL and both of its components were assessed through the SF-36. The association of each component of frailty with the PCS and the MCS of QoL was determined through the construction of multivariate lineal regression models. Final analyses were adjusted by socio-demographic characteristics and by the remaining four components of frailty as covariates. RESULTS: Mean age of participants was 78.0 (SD ± 6.2), 49.4% were women, and 12.7% were frail. Multivariate lineal regression analysis showed that frail and prefrail participants had lower scores for the PCS (P < .001) and the MCS (P < .001) of QoL in comparison with non-frail subjects. Weight loss (P < .001) and exhaustion (P < .001) had an independent inverse association with the MCS of QoL while gait speed (P < .001) and grip strength (P < .001) were also inversely associated with the PCS score. CONCLUSION: Frailty is independently associated with lower scores in the MCS and the PCS of QoL. The finding that different components of frailty were associated with both dimensions of QoL reflects the need for individualized treatment of frail elderly.

The Phenotype of Frailty Predicts Disability and Mortality among Mexican Community-Dwelling Elderly.

BACKGROUND: Frailty represents a major public health priority in Western countries. Specific social and cultural factors may influence the prevalence and predictive value for negative health-related events of this syndrome. OBJECTIVE: To determine the prevalence and predictive value of the phenotype of frailty among community-dwelling Mexican American older persons. DESIGN, SETTING AND PARTICIPANTS: Two-year longitudinal study of 5,644 men and women aged 60 years and older participating in the Mexican Health and Aging Study. MEASUREMENTS: The Frailty index used in the present study was a modified version of the operational definition proposed in the Cardiovascular Health Study (CHS). Frailty was defined by the presence of at least three of the four following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. The main outcomes were incident disability and mortality. Chi-square, ANOVA and multiple logistic regression analyses were used to test the prognostic value of frailty for the outcomes of interest. RESULTS: The mean age of the study sample was 68.7 (SD 6.9) years. Thirty-seven percent of participants (n=2,102) met the definition of frailty. Frail subjects were significantly older, and more likely to be women than non-frail participants. They also presented lower education, more chronic diseases, lower income, and poorer self-reported health status. After adjusting for potential confounders, frailty was found to be a predictor of incident mobility disability (odds ratio [OR] 1.91, 95% confidence interval [CI] 1.37-2.66), activities of daily living (ADL) disability (OR 9.33; 95%CI 3.37-25.82), and instrumental ADL (IADL) disability (OR 1.81, 95%CI 1.23-2.68). The risk of mortality among frail participants was almost three-fold higher than in non-frail ones. CONCLUSION: The prevalence of frailty is higher in this elderly population than what previously reported in other cohorts. The phenotype of frailty was confirmed to be a predictor for adverse health-related outcomes (including mobility, ADL, and IADL disability). Further studies in Latin American countries are needed to identify frailty and develop adapted interventions for the prevention of adverse outcomes in older persons.

Characterisation of neuronal and glial populations of the visual system during zebrafish lifespan.

During visual system morphogenesis, several cell populations arise at different time points correlating with the expression of specific molecular markers We have analysed the distribution pattern of three molecular markers (zn-1, calretinin and glial fibrillary acidic protein) which are involved in the development of zebrafish retina and optic tectum. zn-1 is a neural antigen expressed in the developing zebrafish central nervous system. Calretinin is the first calcium-binding protein expressed in the central nervous system of vertebrates and it is widely distributed in different neuronal populations of vertebrate retina, being a valuable marker for its early and late development. Glial fibrillary acidic protein (GFAP), which is an astroglial marker, is a useful tool for characterising the glial environment in which the optic axons develop. We describe the expression profile changes in these three markers throughout the zebrafish lifespan with special attention to ganglion cells and their projections. zn-1 is expressed in the first postmitotic ganglion cells of the retina. Calretinin is observed in the ganglion and amacrine cells of the retina in neurons of different tectal bands and in axons of retinofugal projections. GFAP is localised in the endfeet of Müller cells and in radial processes of the optic tectum after hatching. A transient expression of GFAP in the optic nerve, coinciding with the arrival of the first calretinin-immunoreactive optic axons, is observed. As axonal growth occurs in these regions of the zebrafish visual pathway (retina and optic tectum) throughout the lifespan, a relationship between GFAP expression and the correct arrangement of the first optic axons may exist. In conclusion we provide valuable neuroanatomical data about the best characterised sensorial pathway to be used in further studies such as teratology and toxicology.

Pathophysiology of bronchial smooth muscle remodelling in asthma.

Whereas the role of bronchial smooth muscle remains controversial in healthy subjects its role is well established in asthmatics. Bronchial smooth muscle contraction induces airway narrowing. The smooth muscle also contributes to bronchial inflammation by secreting a range of inflammatory mediators, recruiting and activating inflammatory cells, such as mast cells or T-lymphocytes. In addition, bronchial smooth muscle mass is significantly increased in asthma. Such an increase has been related to a deposition of extracellular matrix proteins, and an increase in both cell size and number. However, the mechanisms of this smooth muscle remodelling are complex and not completely understood. The article will review recent data regarding the pathophysiology of bronchial smooth muscle remodelling in asthma.

Mast cell adhesion to bronchial smooth muscle in asthma specifically depends on CD51 and CD44 variant 6.

BACKGROUND: Mast cells infiltrate the bronchial smooth muscle (BSM) in asthmatic patients, but the mechanism of mast cell adhesion is still unknown. The adhesion molecules CD44 (i.e. hyaluronate receptor) and CD51 (i.e. vitronectin receptor) are widely expressed and bind to many extracellular matrix (ECM) proteins. The aims of the study are (i) to identify the role of ECM in mast cell adhesion to BSM and (ii) to examine the role of CD51 and CD44 in this adhesion. METHODS: Human lung mast cells, human mast cell line (HMC-1), and BSM cells from control donors or asthmatic patients were cultured in the presence/absence of various cytokines. Mast cell-BSM interaction was assessed using (3)H-thymidine-pulsed mast cells, confocal immunofluorescence, or electron microscopy. Adhesion molecules expression and collagen production on both cell types were evaluated by quantitative RT-PCR, western blot, and flow cytometry. RESULTS: Mast cell adhesion to BSM cells mostly involved type I collagen of the ECM. Such an adhesion was increased in normal BSM cells under inflammatory condition, whereas it was maximal in asthmatic BSM cells. Blockade of either CD51 or CD44 significantly decreased mast cell adhesion to BSM. At the molecular level, protein and the transcriptional expression of type I collagen, CD51 or CD44 remained unchanged in asthmatic BSM cells or in mast cells/BSM cells under inflammatory conditions, whereas that of CD44 variant isoform 6 (v6) was increased. CONCLUSIONS: Mast cell-BSM cell adhesion involved collagen, CD44, and CD51, particularly under inflammatory conditions. CD44v6 expression is increased in asthmatic BSM cells.

Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics.

BACKGROUND: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. OBJECTIVES: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. METHODS: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. RESULTS: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of -78% and -57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. CONCLUSIONS: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma

[Atopic dermatitis aggravates the allergic airways inflammation in acute viral bronchiolitis]. / La dermatite atopique aggrave l'inflammation allergique dans la bronchiolite aiguë virale.

INTRODUCTION: Exhaled nitric oxide (FeNO) is a putative non-invasive marker of eosinophilic airway inflammation with a good predictive value for allergic asthma in preschool children. The aim of the present study was to compare FeNO after acute viral bronchiolitis (AVB) in children aged less than 2 years without atopic dermatitis (AD) vs those with atopic dermatitis, as well as children with AD without any history of AVB. METHODS: Forty-two children (mean age +/- SD: 12.3 +/- 5.2 months; range 5.0-23.5; sex-ratio M: F=1.3: 1) were included in this prospective study, > 8 wks after an episode of AVB. The patients' atopic status was assessed both by clinical phenotype and IgE- mediated response to inhaled and/or food allergens. FeNO (ppb) was measured off-line by the chemoluminescence method on samples obtained from gas collected in a balloon during tidal breathing. RESULTS: There was a significant difference between the AVB/AD (23.4 +/- 14.3 ppb, n=15) vs the AVB without AD group (13.5 +/- 10. 1 ppb, n=13) or the AD without AVB group (11.0 +/- 8.3 ppb, n=14). Maternal feeding for more than 2 months decreased FeNO by 50%. CONCLUSION: Atopic children below 2 years with AD produce more NO after AVB than non-atopic children or atopic children without any history of AVB. Maternal feeding decreases FeNO.