Association between genome-wide association studies reported SNPs and pediatric-onset Crohn’s disease in Canadian children

A recent pediatric-focused genome-wide association study has implicated three novel susceptibility loci for Crohn’ disease (CD).We aimed to investigate whether the three recently reported and other previously reported genes/loci were also associated with CD in Canadian children. A case–control design was implemented at three pediatric gastroenterology clinics in Canada. Children <19 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in 19 reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. A total of 563 cases and 553 controls were studied. The mean (±SD) age of the cases was 12.3 (±3.2) years. Most cases were male (56.0%), had ileo-colonic disease (L3 ± L4, 48.8%) and inflammatory behavior (B1 ± p, 87.9%) at diagnosis. Allelic association analysis (two-tailed) showed that 8 of the 19 targeted SNPs were significantly associated with overall susceptibility for CD. Associations with one additional SNP was borderline non-significant. Significantly associated SNPs included SNPs rs1250550 (p = 0.026) and rs8049439 (p = 0.04), recently reported to be specifically associated with pediatric-onset CD.Based on the results, we confirmed associations between two of the three novel pediatric-CD loci and other regions reported for associations with either pediatric and/or adult-onset CD.     

Positive association between soil arsenic concentration and mortality from alzheimer’s disease in mainland China

ObjectivesThe current study was designed to investigate the relationship between the soil arsenic (As) concentration and the mortality from Alzheimer’s disease (AD) in mainland China.Study designEcological study.MethodsTwenty-two provinces and 3 municipal districts in mainland China were included in this study. The As concentrations in soil in 1990 was obtained from the China State Environmental Protection Bureau; the data on annual mortality of AD from 1991 to 2000 were obtained from the National Death Cause Surveillance Database of China. Using these data, we calculated the spearman correlation coefficient between soil As concentration and AD mortality, and the relative risk (RR) between soil As levels and AD mortality by quartile-dividing study groups.ResultsThe spearman correlation coefficient between As concentration and AD mortality was 0.552 (p = 0.004), 0.616 (p = 0.001) and 0.622 (p = 0.001) in the A soil As (eluvial horizon), the C soil As (parent material horizon), and the Total soil As (A soil As + C soil As), respectively. When the A soil As concentration was over 9.05 mg/kg, 10.40 mg/kg and 13.10 mg/kg, the relative risk was 0.835 (95 % CI: 0.832, 0.838), 1.969 (95 %CI: 1.955, 1.982), and 2.939 (95 % CI: 2.920, 2.958), respectively; when the C soil As reached 9.45 mg/kg, 11.10 mg/kg and 13.55 mg/kg, the relative risk was 4.349 (95 % CI: 4.303, 4.396), 6.108 (95 % CI: 6.044, 6.172), and 9.125 (95 %CI: 9.033, 9.219), respectively. No correlation was found between lead, cadmium, and mercury concentration in the soil and AD mortality.ConclusionThere was an apparent soil As concentration dependent increase in AD mortality. Results of this study may provide evidence for a possible causal linkage between arsenic exposure and the death risk from AD.     

The Green’s function formalism as a bridge between single- and multi-compartmental modeling

Neurons are spatially extended structures that receive and process inputs on their dendrites. It is generally accepted that neuronal computations arise from the active integration of synaptic inputs along a dendrite between the input location and the location of spike generation in the axon initial segment. However, many application such as simulations of brain networks use point-neurons—neurons without a morphological component—as computational units to keep the conceptual complexity and computational costs low. Inevitably, these applications thus omit a fundamental property of neuronal computation. In this work, we present an approach to model an artificial synapse that mimics dendritic processing without the need to explicitly simulate dendritic dynamics. The model synapse employs an analytic solution for the cable equation to compute the neuron’s membrane potential following dendritic inputs. Green’s function formalism is used to derive the closed version of the cable equation. We show that by using this synapse model, point-neurons can achieve results that were previously limited to the realms of multi-compartmental models. Moreover, a computational advantage is achieved when only a small number of simulated synapses impinge on a morphologically elaborate neuron. Opportunities and limitations are discussed.     

Modifiers of the temperature–mortality association in Shanghai, China

Various factors can modify the health effects of temperature. Prior findings about modifiers are inconsistent, and such studies have been conducted mostly in developed countries. We conducted a time-series analysis to examine the modifying effect of gender, age and education on the association between temperature and daily mortality in Shanghai, China, using 4 years (2001–2004) of daily data. A natural spline model was used to analyze the data. Elderly subjects were found to be more vulnerable to temperature health effects compared with younger people. We observed no significant modifying effect of gender or education level. These findings may provide useful information for local governments seeking to take steps to protect vulnerable sub-populations.     

Non-Linear Association between Exposure to Ambient Temperature and Children’s Hand-Foot-and-Mouth Disease in Beijing,China

BackgroundHand, foot and mouth disease (HFMD) was listed as a notifiable communicable disease in 2008 and is an emerging public health problem in China, especially for children. However, few data are available on the risk assessment of the potential reasons for HFMD in Beijing. This study examined the association of temperature with the incidence of children’s HFMD in Beijing at the daily scale for the first time.MethodsA newly developed case-crossover design with a distributed lag nonlinear model (DLNM) was used to assess the delayed and cumulative associations of daily temperature with gender- and age-specific HFMD in Beijing, China, during 2010–2012. Relative humidity, day of the week, public holiday, season and long-term trends were controlled in the model.ResultsAmong the total of 113,475 cases, the ratio between males and females was 1.52:1. HFMD was more prevalent in May-July. The temperature-HFMD relationships were non-linear in most age groups except for children aged 6–15 years, with a peak at 25.0~27.5°C. The high-temperature risks were greater, appeared earlier and lasted longer than the low-temperature risks. The relative risks for female children and those aged 6–15 years were higher than those among other groups.ConclusionRising temperatures increased the incidence of children’s HFMD, with the largest association at 25.0~27.5°C. Females and children aged 6–15 years were more vulnerable to changes in temperature with regard to the transmission of HFMD than males and other age groups, respectively. Further studies are warranted to confirm these findings in other populations.     

Catecholamine metabolism in children with Asperger’s and Kanner’s syndromes

In a stable state children with Asperger’s and Kanner’s syndromes demonstrate a similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine, and by an increase in dopamine and homovanillic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanillic acid, epinephrine and 3-methoxy-4-hydroxyphenylglycol (MHPG). In the aggravated state children with Kanner’s syndrome were characterized by increased plasma MHPG, decreased excretion of tyrosine and increased expression of normetanephrine. The observed imbalance in dopamine and epinephrine/norepinephrine systems suggests importance of combined analysis of changes in catecholamines and their metabolites as the most informative approach in the study of the effect of autistic disorders.     

The Relationship between Visuospatial Impairments and Retinal and Cortical Thickness in Parkinson’s Disease

The paper touches upon current views on the pathophysiology of visuospatial impairments in Parkinson’s disease (PD). To assess thickness of retina’s ganglionic layer, retinal nerve fiber layer, and macular map, optical coherence tomography method was used. Brain MRI was also performed followed by evaluation of the cortical thickness. Patients underwent neuropsychological tests, including those for assessment of visuospatial perception and cognitive functions. We found certain retinal regions and areas of visual cortex with significant changes in PD patients on different stages. Our findings allowed us to speculate on the role of changes in the peripheral and central structures of the visual sensory system in the pathophysiology of visuospatial impairments in PD.     

The study of the association between genotype and phenotypic manifestations of the Huntington’s chorea pathogenesis

Direct molecular-genetic analysis of the region containing CAG and CCG repeats of the IT15 gene from 37 patients with the clinical diagnosis of Huntington’s chorea was carried out. The allele with the expansion of CAG repeats in the state of heterozygosity was found in 33 patients; DNA analysis did not confirm a clinical diagnosis in four cases. Twenty probable asymptomatic carriers were examined; 11 of them inherited a mutant chromosome. A disequilibrium in the linkage between the (CGG)₁₀ allele and the alleles with the expansion of CAG repeats in the IT15 gene in a group of patients from Ukraine was found. Significant differences in character of instability of CAG repeats that depends on paternal or maternal inheritance were revealed. The genetic factors that are associated with age variability of onset of the disease were studied.     

The ontogeny and phylogeny of children’s object and fantasy play

We examine the ontogeny and phylogeny of object and fantasy play from a functional perspective. Each form of play is described from an evolutionary perspective in terms of its place in the total time and energy budgets of human and nonhuman juveniles. As part of discussion of functions of play, we examine sex differences, particularly as they relate to life in the environment of evolutionary adaptedness and economic activities of human and nonhuman primates. Object play may relate to foraging activities. Although fantasy play has been viewed as limited to humans, we speculate that certain types of fantasy play may be present in some nonhuman primates. Fantasy play may enable juveniles to see situations from different perspectives. We conclude that fantasy play may have immediate effects and object play may have deferred effects.     

The Relationship between Thermoregulation and REM Sleep Behaviour Disorder in Parkinson’s Disease

Background

This study explored the relationship between symptoms of rapid eye movement sleep behaviour disorder, thermoregulation and sleep in Parkinson’s Disease.

Methods

The study group comprised 12 patients with Parkinson’s Disease and 11 healthy age-matched controls. We investigated markers of thermoregulation (core-body temperature profile), circadian rhythm (locomotor actigraphy) and sleep (polysomnography).

Results

The mesor (the mean value around which the core temperature rhythm oscillates) of the core-body temperature in patients with Parkinson’s Disease was significantly lower than that of controls. In addition, the nocturnal fall in CBT (the difference between the mesor and the nadir temperature) was also significantly reduced in PD patients relative to controls. Furthermore, in patients the reduction in the amplitude of their core-body temperature profile was strongly correlated with the severity of self-reported rapid eye movement sleep behaviour disorder symptom, reduction in the percentage of REM sleep and prolonged sleep latency. By contrast, these disturbances of thermoregulation and sleep architecture were not found in controls and were not related to other markers of circadian rhythm or times of sleep onset and offset.

Conclusions

These findings suggest that the brainstem pathology associated with disruption of thermoregulation in Parkinson’s disease may also contribute to rapid eye movement sleep behavioural disorder. It is possible that detailed analysis of the core-body temperature profile in at risk populations such as those patients with idiopathic rapid eye movement sleep behaviour disorder might help identify those who are at high risk of transitioning to Parkinson’s Disease.     

The association between prion proteins and Aβ₁₋₄₂ oligomers in cytotoxicity and apoptosis

Microglia are cells from non-neuronal lineages that reside in the central nervous system. In zebrafish, early macrophages migrate from the yolk sac to the brain and retina at 26-30 hour post fertilization (hpf) and transform into microglia at 55-60 hpf. The migration of macrophages into the central nervous system requires signaling by macrophage colony stimulating factor-1 receptor (csf-1r), which is encoded by the gene fms. In this study, we show that the targeted knockdown of csf-1r with morpholino oligonucleotides delays migration of macrophages from the yolk sac to the retina, and this delay in macrophage migration results in microphthalmia, delay in cell cycle withdrawal among retinal progenitors and the absence of neuronal differentiation. When embryos were allowed to survive beyond the time when morpholino-dependent translation inhibition is lost, microglia re-occupy the retina and neuronal differentiation partially recovers. Our data demonstrate that microglia are required for normal retinal growth and neurogenesis. This study provides new insight into the neurogenic role of microglia during retinal development in zebrafish.     

Street working children in lima: The child's ‘Surcharge’ between survival strategies and socialisation

Child labour is usually analysed within the framework of exploitation. This essay is an attempt to analyse children's economic activities in the street using the concept ‘surcharge”, which may be defined as a child's negative experience of overload or over work. In the comparison between dissatisfactory and satisfactory working conditions, it has been argued that the first is linked not only to a lack of protection, but also to a lack of autonomy and recognition. Analyses include examinations of extreme conditions, different representations of the family, childhood and labour, as too women's roles. Such dimensions are considered essential for the comprehension of children's experience, since they are often surcharged due to the lack of economic resources, the unequal division of labour within the family and contradictory practices found in the research population. Examples of those difficulties draw on children and families' experiences of compulsory and ‘free’ education. The author concludes the need for better knowledge of socialisation processes and children's experience of work that should ideally integrate into the theoretical framework of exploitation.     

Parental nonemployment in childhood and children’s health later in life

While the effects of joblessness on the health of the non-employed are well-documented, its long-term spillover consequences on the health of their relatives, especially children, remain poorly understood. This research explores the long-term associations of parental nonemployment spells experienced during early, mid and late childhood on children’s mental and physical health. The analysis exploits data drawn from the British Household Panel Survey (BHPS) and the UK Household Longitudinal Study (UKHLS), linking detailed parental socioeconomic information with their children between the years 1993 and 2013. This paper employs a Correlated Random Effects (CRE) probit model that allows accounting for unobserved heterogeneity as well as a non-linear Generalized Estimating Equations (GEE) random effects estimator accounting in addition for the dependency structure of the data. Results indicate that experiencing parental nonemployment during early and late childhood has a negative association on the children’s likelihood of suffering from long-standing illnesses later in life, while experiencing parental nonemployment during middle childhood negatively affects the young adult’s mental health. Moreover, experiencing parental nonemployment during late childhood increases the probability of both reporting poor or fair self-assessed health and the likelihood of consuming prescribed medicines in early adulthood. However, there seems to be a considerable effect heterogeneity by family socioeconomic status, parents’ gender, and frequencies of parental nonemployment spells. Current adulthood circumstances, such as level of educational attainment, job situation and household demographics, are used to explore the potential mechanisms affecting results. These findings may help policymakers shape appropriate responses to mitigate the psychological and physical burden derived from parental nonemployment, especially among already disadvantaged households.     

TNF-α system and lung function impairment in obesity

A potential interaction between pulmonary function, abnormal adipose tissue activity, and systemic inflammation has been suggested. This study explores the relationship between circulating soluble TNF-α receptors (sTNF-R1 and sTNF-R2) and respiratory function parameters in obese subjects. Thirty-one non-diabetic morbidly obese women with a history of non-smoking and without prior cardiovascular or respiratory disease were prospectively recruited in the outpatient Obesity Unit of a referral center. Pulmonary function test included a forced spirometry, static pulmonary volume measurements, non-attended respiratory polygraphy, and arterial gas blood sampling. Circulating levels of sTNFR-R1, sTNF-R2, interleukine 6 and adiponectin were determined using ELISA. Statistical analysis included a multivariate regression analysis taking into account the potential confounders. sTNF-R1 positively correlated with BMI (r=0.571, p=0.001) and arterial carbon dioxide pressure (PaCO(2), r=0.381, p=0.038), but negatively with forced expiratory volume in 1s (FEV(1), r=-0.437, p=0.012), maximum midexpiratory flow (FEF(25-75), r=-0.370, p=0.040) and forced vital capacity (FVC, r=-0.483, p=0.005). However, no correlation between sTNF-R2 and BMI and either pulmonary function tests or arterial blood samples was observed. Multiple linear regression analysis showed that sTNF-R1 independently predicted FEV(1) (beta=-0.437, p=0.012) and FVC (beta=-0.483, p=0.005). Thus, circulating levels of sTNF-R1, but not sTNF-R2, are related to reduced lung volumes and airflow limitation in morbidly obese patients prior to the development of a clinically recognized respiratory disease. Therefore, studies addressed to evaluating the potential beneficial effect of anti-TNF-α agents on pulmonary function tests in obese subjects seem warranted.     

Further evidence for a synergistic association between APOEɛ4 and BCHE-K in confirmed Alzheimer’s disease

Recent reports on a potential association between the K-variant of the gene for butyrylcholinesterase (BCHE-K) and Alzheimer’s disease (AD) are discordant. An initial finding of association through a synergistic enhancement of risk of APOEɛ4 with late-onset AD has not been confirmed by others. We have conducted a case-control study of histopathologically confirmed AD (n=135) and non-AD (n=70) cases (age of death ≥60 years), in which we have genotyped for APOEɛ4, BCHE-K, and BCHE-A1914G, a silent polymorphism 299 bp downstream of the BCHE-K mutation. The allelic frequency of BCHE-K was 0.13 in the controls and 0.23 in the AD cases, giving a carrier odds ratio (OR_c) of 2.1 (95% C.I. 1.1–4.1) for BCHE-K in confirmed AD. The allelic frequency for the BCHE-1914G variant was 0.19 and 0.33 in controls and AD cases, respectively (OR_c=2.4; 95% C.I. 1.3–4.5). In an older sub-sample of 27/70 controls and 89/135 AD patients with ages of death ≥75 years, the OR_c was increased to 4.5 (95% C.I. 1.4–15) for BCHE-K and 2.7 (95% C.I. 1.0–7.2) for BCHE–1914G carriers. The BCHE-K association with AD became even stronger in carriers of at least one APOEɛ4 allele. Only three out of 19 controls compared with 39/81 AD cases carried BCHE-K in addition to APOEɛ4, giving an odds ratio of confirmed AD of 5.0 (95% C.I. 1.3–19) for BCHE-K carriers within APOEɛ4 carriers. Five out of 19 controls and 52/81 AD cases carried BCHE-1914G, giving the same odds ratio of confirmed AD of 5.0 (95% C.I. 1.6–16) for BCHE-1914G carriers within APOEɛ4 carriers. In addition, our results suggest strong linkage disequilibrium between BCHE-K and BCHE-1914G but no major association of the sole BCHE-1914G chromosome with AD. We conclude that BCHE through its K-variant, rather than a nearby marker, is a susceptibility factor for AD and enhances the AD risk defined by APOEɛ4 alone in an age-dependent manner. Received: 29 September 1998 / Accepted: 29 December 1998     

Is there an association between variables of postural control and strength in prepubertal children?

The risk of sustaining falls and sports-related injuries is particularly high in children. Deficits in balance and muscle strength represent 2 important intrinsic fall and injury-risk factors. Therefore, the purpose of this study was to investigate the relationship between variables of static and dynamic postural control and isometric and dynamic muscle strength and to find out whether there is an association between measures of postural control and muscle strength in prepubertal children. Thirty children participated in this study (age 6.7 ± 0.5 years; body mass index 16.0 ± 1.8 kg·m(-2)). Biomechanic tests included the measurements of maximal isometric torque and rate of force development (RFD) of the plantar flexors on an isokinetic device, jumping power and height (countermovement jump [CMJ]) on a force plate, and the assessment of static and dynamic posture during bipedal stance on a balance platform. The significance level was set at p < 0.05. No significant associations were observed between variables of static and dynamic postural control. Significant positive correlations were detected between the RFD of the plantar flexors and CMJ height (r = 0.425, p < 0.01). No statistically significant associations were found between measures of postural control and muscle strength. The nonsignificant correlations between static and dynamic postural control and muscle strength imply that primarily dynamic measures of postural control should be incorporated in fall and injury-risk assessment and that postural control and muscle strength appear to be independent of each other and may have to be trained in a complementary manner for fall and injury-preventive purposes.