Impact of Nondigestible Oligosaccharides on Gut-Associated Lymphoid Tissue and Oral Tolerance Induction

Human milk is very rich in nondigestible oligosaccharides, which support colonization of Bifidobacteria and Lactobacilli and immune maturation. Manufactured nondigestible oligosaccharides are added to infant formula in order to mimic functional aspects of human milk oligosaccharides. They support the growth of beneficial microbes and reduce gastrointestinal and respiratory infections. Furthermore they reduce the risk of developing allergic disease when provided early in life. Oral tolerance induction is key in the prevention of allergies. Environmental factors such as dietary constituents and the colonization with commensal microorganisms at the mucosal surface are crucial for the generation of mucosal tolerance. Evidence is building that nondigestible galacto- and fructo-oligosaccharides can either directly or indirectly modulate the GALT and systemic immune system in health and disease. Besides increasing IL-10 and IgA in mice and human, they were found to induce functional regulatory T-cells in spleens of mice affected with cow’s milk allergy. In addition, they induce galectin-9 capable of IgE neutralization. The immunologic basis by which nondigestible oligosaccharides may affect the mucosal and systemic immune system is discussed in this book chapter

The relationship between perceived immune functioning and autism spectrum disorder scores in healthy young adults

Introduction: Altered immune functioning has been demonstrated in individuals with autism spectrum disorder (ASD) [1,2]. Skewed cytokine profiles have been linked to ASD, because of their ability to interact with neural systems of development and maintenance [1,2]. In this context, it has been argued that high fetal levels of testosterone suppress immune functioning, and at the same time increase the risk of developing ASD [3]. The current study explores the relationship between perceived immune functioning and experiencing ASD symptoms in healthy young adults. Aim of the study: To examine the relationship between ASD and the perceived immune functioning. Methods: Students from Utrecht University were asked to complete a survey on autism and immune functioning. The 19- item Immune Function Questionnaire (IFQ) was completed [4] to assess perceived immune functioning. The overall IFQ-score ranges from 0 to 76, with higher scores implying worse immune functioning. The Dutch translation of the Autism-Spectrum Quotient (AQ) [5] was completed to examine variation in autistic traits. The total AQ score was based on the 4-point Likert scale scores (ranging from “definitely agree” to “definitely disagree”), with a higher sum score implying endorsing more autism characteristics. This questionnaire consists of 5 subscales, each assessing a different domain of ASD, covering 'social insights and behavior', 'difficulties with change', 'communication', 'phantasy and imagination', and 'detail orientation'. Correlational analyses were conducted to examine the relationship between ADS and its domains, and the IFQ immune score. Results: N= 259 participants completed the AQ questionnaire. Significant correlations were found between the IFQ immune score and the total AQ score (r = 0.169, p = 0.007), and the subscales 'difficulties with change' (r = 0.185, p = 0.003) and 'communication' (r = 0.146, p = 0.018). In women, the IFQ immune score correlated significantly with the total AQ score (r = 0.223, p = 0.010), and the subscale 'social insights and behavior' (r = 0.190, p = 0.025). In men, significant correlations were found between the IFQ immune score and the total AQ score (r = 0.196, p = 0.033), and the subscales 'difficulties with change' (r = 0.231, p = 0.011) and 'communication' (r = 0.208, p = 0.022). Conclusions: Our findings confirm the relationship between immune functioning and several aspects of autism spectrum disorder. The association between total AQ score and the level of immune functioning was significant in both men and women. Although the observed associations are modest, it should be taken into account that the current sample comprised healthy young volunteers. Interestingly, regarding specific ASD domains, although in both men and women an association was found with 'difficulties with change', associations with other ASD domains seem to be more gender specific. The latter warrants further research, preferably in patients formally diagnosed with ASD

The developmental origins of autism spectrum disorder: The 2D:4D digit ratio as biomarker

Introduction: Autism spectrum disorder (ASD) is identified as a sexually dimorphic disorder, meaning that it may be influenced by fetal levels of testosterone and estrogen [1]. As described by several studies, levels of prenatal sex hormones can be related to the digit ratio of the index (2D) and ring (4D) finger [2]. It has been known that males tend to have longer fourth digits relative to second digits than females, indicating higher levels of fetal testosterone in comparison to estrogen in males [2]. As the development of the central nervous system (CNS) is also influenced by prenatal sex hormones, it has been suggested that the 2D:4D digit ratio may be a biomarker for the risk of developing CNS diseases such as autism. One study found that N= 72 children diagnosed with autism had lower 2D:4D digit ratios when compared to age-matched healthy controls [3], and a 2012 meta-analysis confirmed that adults with autism tend to have a lower 2D:4D digit ratio [4]. However, recent studies could not replicate these findings [5]. Aim(s) of the study: To determine the usefulness of the 2D:4D digit ratio as biomarker for autism spectrum disorder. Methods: Participants were recruited among students from Utrecht University. For both hands, digit lengths of the second (2D, index finger) and fourth (4D, ring finger) finger were measured using digital Vernier calipers recording to 0.01 mm. In addition to demographics, the Autism Spectrum Quotient (AQ) questionnaire was completed. The AQ is divided into four subscales, each assessing a different aspect of ASD. The subscales comprise 'social insights and behavior', 'difficulties with change', 'communication', 'phantasy and imagination', and 'detail orientation'. Using correlational analyses, the relationship between the 2D:4D digit ratio and the overall AQ scores and those of its subscales was computed. Results of participants with dove-type personality (2D:4D >1.00) were compared to those with a hawk-type personality (2D:4

The relationship between perceived immune functioning and autism spectrum disorder scores in healthy young adults

Introduction: Altered immune functioning has been demonstrated in individuals with autism spectrum disorder (ASD) [1,2]. Skewed cytokine profiles have been linked to ASD, because of their ability to interact with neural systems of development and maintenance [1,2]. In this context, it has been argued that high fetal levels of testosterone suppress immune functioning, and at the same time increase the risk of developing ASD [3]. The current study explores the relationship between perceived immune functioning and experiencing ASD symptoms in healthy young adults. Aim of the study: To examine the relationship between ASD and the perceived immune functioning. Methods: Students from Utrecht University were asked to complete a survey on autism and immune functioning. The 19- item Immune Function Questionnaire (IFQ) was completed [4] to assess perceived immune functioning. The overall IFQ-score ranges from 0 to 76, with higher scores implying worse immune functioning. The Dutch translation of the Autism-Spectrum Quotient (AQ) [5] was completed to examine variation in autistic traits. The total AQ score was based on the 4-point Likert scale scores (ranging from “definitely agree” to “definitely disagree”), with a higher sum score implying endorsing more autism characteristics. This questionnaire consists of 5 subscales, each assessing a different domain of ASD, covering 'social insights and behavior', 'difficulties with change', 'communication', 'phantasy and imagination', and 'detail orientation'. Correlational analyses were conducted to examine the relationship between ADS and its domains, and the IFQ immune score. Results: N= 259 participants completed the AQ questionnaire. Significant correlations were found between the IFQ immune score and the total AQ score (r = 0.169, p = 0.007), and the subscales 'difficulties with change' (r = 0.185, p = 0.003) and 'communication' (r = 0.146, p = 0.018). In women, the IFQ immune score correlated significantly with the total AQ score (r = 0.223, p = 0.010), and the subscale 'social insights and behavior' (r = 0.190, p = 0.025). In men, significant correlations were found between the IFQ immune score and the total AQ score (r = 0.196, p = 0.033), and the subscales 'difficulties with change' (r = 0.231, p = 0.011) and 'communication' (r = 0.208, p = 0.022). Conclusions: Our findings confirm the relationship between immune functioning and several aspects of autism spectrum disorder. The association between total AQ score and the level of immune functioning was significant in both men and women. Although the observed associations are modest, it should be taken into account that the current sample comprised healthy young volunteers. Interestingly, regarding specific ASD domains, although in both men and women an association was found with 'difficulties with change', associations with other ASD domains seem to be more gender specific. The latter warrants further research, preferably in patients formally diagnosed with ASD

Analysing the protection from respiratory tract infections and allergic diseases early in life by human milk components: the PRIMA birth cohort

BACKGROUND: Many studies support the protective effect of breastfeeding on respiratory tract infections. Although infant formulas have been developed to provide adequate nutritional solutions, many components in human milk contributing to the protection of newborns and aiding immune development still need to be identified. In this paper we present the methodology of the "Protecting against Respiratory tract lnfections through human Milk Analysis" (PRIMA) cohort, which is an observational, prospective and multi-centre birth cohort aiming to identify novel functions of components in human milk that are protective against respiratory tract infections and allergic diseases early in life. METHODS: For the PRIMA human milk cohort we aim to recruit 1000 mother-child pairs in the first month postpartum. At one week, one, three, and six months after birth, fresh human milk samples will be collected and processed. In order to identify protective components, the level of pathogen specific antibodies, T cell composition, Human milk oligosaccharides, as well as extracellular vesicles (EVs) will be analysed, in the milk samples in relation to clinical data which are collected using two-weekly parental questionnaires. The primary outcome of this study is the number of parent-reported medically attended respiratory infections. Secondary outcomes that will be measured are physician diagnosed (respiratory) infections and allergies during the first year of life. DISCUSSION: The PRIMA human milk cohort will be a large prospective healthy birth cohort in which we will use an integrated, multidisciplinary approach to identify the longitudinal effect human milk components that play a role in preventing (respiratory) infections and allergies during the first year of life. Ultimately, we believe that this study will provide novel insights into immunomodulatory components in human milk. This may allow for optimizing formula feeding for all non-breastfed infants

The developmental origins of autism spectrum disorder: The 2D:4D digit ratio as biomarker

Introduction: Autism spectrum disorder (ASD) is identified as a sexually dimorphic disorder, meaning that it may be influenced by fetal levels of testosterone and estrogen [1]. As described by several studies, levels of prenatal sex hormones can be related to the digit ratio of the index (2D) and ring (4D) finger [2]. It has been known that males tend to have longer fourth digits relative to second digits than females, indicating higher levels of fetal testosterone in comparison to estrogen in males [2]. As the development of the central nervous system (CNS) is also influenced by prenatal sex hormones, it has been suggested that the 2D:4D digit ratio may be a biomarker for the risk of developing CNS diseases such as autism. One study found that N= 72 children diagnosed with autism had lower 2D:4D digit ratios when compared to age-matched healthy controls [3], and a 2012 meta-analysis confirmed that adults with autism tend to have a lower 2D:4D digit ratio [4]. However, recent studies could not replicate these findings [5]. Aim(s) of the study: To determine the usefulness of the 2D:4D digit ratio as biomarker for autism spectrum disorder. Methods: Participants were recruited among students from Utrecht University. For both hands, digit lengths of the second (2D, index finger) and fourth (4D, ring finger) finger were measured using digital Vernier calipers recording to 0.01 mm. In addition to demographics, the Autism Spectrum Quotient (AQ) questionnaire was completed. The AQ is divided into four subscales, each assessing a different aspect of ASD. The subscales comprise 'social insights and behavior', 'difficulties with change', 'communication', 'phantasy and imagination', and 'detail orientation'. Using correlational analyses, the relationship between the 2D:4D digit ratio and the overall AQ scores and those of its subscales was computed. Results of participants with dove-type personality (2D:4D >1.00) were compared to those with a hawk-type personality (2D:4

The association between insomnia and perceived health status

Introduction: Impaired sleep can have a significant impact on perceived health status. The aim of the current study was to examine the relationship between perceived health status and sleep quality, total sleep time, and insomnia. Materials and methods: A survey was conducted among Dutch university students. General health and perceived immune status were scored on a scale ranging from 0 (very poor) to 10 (excellent). Sleep parameters were collected with the insomnia subscale of the SLEEP-50 questionnaire. Total sleep time (TST) was recorded, and sleep quality was scored on a scale ranging from 0 (very poor) to 10 (excellent). Non-parametric correlations (Spearman)were used to examine the association between perceived heath and immune status and the sleep parameters. Results: N = 509 subjects completed the survey (N = 143 men, and N = 366 women). They were on average 20.8 (2.6) years old and reported a TST of 7.7 (0.9) hours. Mean (SD) scores were 14.6 (4.3) for insomnia, 7.3 (1.2) for sleep quality, 7.7 (1.0) for general health, and 7.8 (1.3) for perceived immune status. Perceived general health correlated significantly with scores for insomnia (r = -0.228, p = 0.0001) and sleep quality (r = 0.235, p = 0.0001), but not with TST (r = 0.058, p = 0.196). Similarly, perceived immune status correlated significantly with scores for insomnia (r = -0.193, p = 0.0001) and sleep quality (r = 0.234, p = 0.0001), but not with TST (r = 0.051, p = 0.254). A significant correlation was found between perceived health status and immune functioning (r = 0.704, p = 0.0001). Insomnia scores were highly correlated to sleep quality (r =-0.697, p = 0.0001) and to a lesser extent with TST (r = -0.218, p = 0.0001). Overall, the observed associations were stronger in men when compared with women. Conclusion: Whereas insomnia and sleep quality were significantly related to perceived general health and immune status, this relationship was not found for total sleep time

Cyclopiazonic acid attenuates the divalent cations and augments the mRNA level of iNOS in the liver and kidneys of chickens

An investigation was carried out into the occurrence of cyclopiazonic acid (CPA) producing fungi, the level of CPA contamination in chickens' diet, CPA effects on serum levels of divalent cations, on nitric oxide (NO) content and mRNA level of inducible nitric oxide synthase (iNOS) in the liver and kidney of chickens, as well as the cellular and molecular pathways of CPA toxicity. Mycological and HPLC analyses were used to determine the mycobiota and CPA level, respectively. The mycological studies revealed that 34.46 and 23.07% of the isolated fungi were Aspergillus flavus and Penicillium cyclopium, respectively. HPLC analyses showed the highest (0.95±0.35 μg/g) and lowest (0.08±0.03 μg/g) levels of CPA in maize and mix diet, respectively. For toxicological studies, male chickens (Ross 308) were assigned to the control and test groups (n=8), which received normal saline and 10, 25 and/or 50 μg/kg CPA for 28 days. The effects of CPA on NO content of the liver and kidneys were determined using the Griess reaction, and the effects on the serum level of divalent cations were established using commercially available kits. The effects of CPA on the mRNA level of iNOS were investigated using RT-PCR. CPA lowered the serum level of divalent cations, while NO contents were enhanced significantly (

The very beginning of Europe ? Cultural and Social Dimensions of Early-Medieval Migration and Colonisation (5th-8th century). Archaeology in Contemporary Europe. Conference, Brussels - may 17-19, 2011

In 2007 the Flanders Heritage Agency joined the European network ‘Archaeology in Contemporary Europe’ along with thirteen other partner institutions from all over Europe. The ACE partners aim to promote contemporary archaeology at a European level by exchanging ideas and expertise and undertaking research, data collection and related activities along four major thematic axes. Within the framework of theme I - Researching the significance of the past, the Flanders Heritage Agency organised the international symposium ‘The very beginning of Europe? Cultural and Social Dimensions of Early-Medieval Migration and Colonisation (5th-8th century)’ from 17 to 19 May 2011 in Brussels. This volume of Relicta contains the proceedings of this symposium on issues surrounding early medieval migration and colonization