Meta-Analyses of the 5-HTTLPR Polymorphisms and Post-Traumatic Stress Disorder

Objective

To conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases

Methods Data Sources

Potential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network) up until December 2011. Study Selection: Published observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review. Data Extraction: Two reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol. Statistical analysis: A biallelic and a triallelic meta-analysis, including the total S and S'' frequencies, the dominant (S+/LL and S''+/L''L'') and the recessive model (SS/L+ and S''S''/L''+), was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran''s Q-Statistic and I² index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed.

Results

13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias.

Conclusions

Current evidence does not support a direct effect of 5-HTTLPR polymorphisms on PTSD. Further analyses of gene-environment interactions, epigenetic modulation and new studies with large samples and/or meta-analyses are required.     

Calcium and Dairy Intake and Measures of Obesity in Hyper‐ and Normocholesterolemic Children

Objective: Calcium intake has been inversely associated with body weight and body fatness in adults and, to a lesser extent, in children. Dairy intake has been inversely associated with metabolic syndrome in overweight but not normal‐weight adults. We assessed whether intakes of calcium and dairy foods were associated with measures of obesity in hypercholesterolemic (HC) and normocholesterolemic (non‐HC) children at baseline and over 1 year. Research Methods and Procedures: Non‐obese 4‐ to 10‐year‐old HC and non‐HC children (342) completed three 24‐hour dietary recalls and provided measures of relative weight (BMI and BMI z scores) and adiposity (sum of skinfolds, trunk skinfolds) at baseline, 3, 6, and 12 months. Cross‐sectional and longitudinal regression analyses, stratified by cholesterol risk status (HC vs. non‐HC) and age (4 to 6 years and 7 to 10 years) and adjusted for potential confounders, were conducted. Results: After adjusting for age, sex, energy intake, and percentage energy from fat, calcium intake was inversely associated with BMI, sum of skinfolds, and trunk skinfolds at baseline and over 1 year in the 7‐ to 10‐year‐old non‐HC children. Results from the regression models also indicated an inverse relation between intake of dairy foods and measures of obesity at baseline in these children. Calcium or dairy intake was not associated with measures of obesity in HC children or in the 4‐ to 6‐year‐old non‐HC children. Discussion: These results suggest a complex relation among intake of calcium and dairy foods, measures of obesity, age, and serum cholesterol in children. Older children without risk of metabolic syndrome may benefit most from increased calcium intake.     

Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study

BackgroundDepression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear.MethodsWe evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from “InveCe.Ab”, a population-based study of 1321 subjects aged 70–74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms–a GDS score ≥5 points (GDS≥5) indicated the presence of clinically relevant symptoms–and performed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the serotonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors.ResultsTwo hundred subjects (15.76%) had a GDS≥5. The 5-HTTLPR triallelic polymorphism was significantly associated with GDS≥5. Only S′S′ carriers showed an increased risk of depressive symptoms (OR_adj = 1.81, p = .022); one extra adverse life event increased this risk by 14% (p = .061) independently of genotype. Other factors significantly related to GDS≥5 were: female gender (OR_adj = 2.49, p < .001), age (OR_adj = 1.19, p = .007), a history of depression (OR_adj = 4.73, p < .001), and comorbidity (OR_adj = 1.23, p = .001). One extra adverse life event increased the risk of depressive symptoms by 57% (p = .005) only in the L′L′ carriers, while antidepressant intake was directly related to GDS≥5 in the L′S′ carriers (OR_adj = 2.46, p = .036) and borderline significant in the S′S′ carriers (OR_adj = 2.41, p = .081).DiscussionThe S′S′ genotype and recent exposure to adverse life events were independently associated with depressive symptoms. The S′S′ genotype, compared with the environment, exerted a predominant effect on depressive symptoms, suggesting that it reduces the efficacy of antidepressant therapy. We conclude that genetics may be an important risk factor for depressive symptoms in late adulthood.     

Blood lead level and nutritional status indicators in preadolescent Polish schoolchildren

BackgroundEnvironmental pollutions with heavy metals may have toxic effects on human health and development. One of the most detrimental is lead exposure, which may disturb neurodevelopment and linear growth in children. However, data on the effect of lead exposure on nutritional and weight status in children are limited, thus this study aimed to assess the effect of blood lead (Pb) level on nutritional and weight status in preadolescent schoolchildren from the industrialized, mining region in southwestern Poland.MethodsOur study sample involved N = 709 schoolchildren (402 boys and 307 girls) in the preadolescent developmental period (7–11 years of age for boys and 7–10 years of age for girls). Anthropometric measurements were used to assess nutritional and weight status: body mass index (BMI), mid-upper arm circumference (MUAC) and skinfolds thicknesses (triceps, subscapular, abdominal and the sum of skinfolds). Blood Pb level was evaluated and divided into two groups: above (>3.7 μg/dL) and below median value (≤3.7 μg/dL).ResultsAnalysis of covariance (with children’s age controlled as a covariate) revealed that children with blood Pb level above median value had significantly lower values of BMI, MUAC and all skinfolds (at least p < 0.01). However, this effect was significant only in boys, whereas in girls differences were non-significant (p > 0.05). The highest effect size of blood Pb level was noted for skinfolds thicknesses (partial η²: 0.015 for the sum of skinfolds).ConclusionsNutritional status in children with higher blood Pb level is significantly impaired in preadolescent boys, who appear to be more sensitive to this environmental factor. Our findings indicate a particular need for nutritional and environmental interventions among preadolescent children in regions with higher lead exposure.     

Impact of the Fukushima nuclear accident on obesity of children in Japan (2008–2014)

This study used prefecture-level panel data from Japan for the period 2008–2014 to investigate the influence of the 2011 Fukushima nuclear accident on the body mass index (BMI) z-score and obesity rates of children over time. I adopted a difference-in-differences approach and found the following: (1) for the cohort aged 5–7 years in 2010, the BMI z-score and obesity rates in disaster-affected areas were higher than in other areas, although this was not observed for the other cohorts; (2) for the cohort aged 5–7 years in 2010, the influence of the accident persisted even after 3 years; and (3) the differences in the BMI z-score and obesity rate before and after the accident were greater for Fukushima Prefecture than for the other affected areas (Iwate and Miyagi prefectures). I infer that health-conscious parents, whose children had lower BMIs, may have moved from Fukushima, thereby increasing the BMI z-score of the child population living in Fukushima by around 0.05 for the cohort aged 5–7 years. The enforced reduction in physical activity increased the BMI z-score of children living in Fukushima by around 0.19 for that cohort.     

Zinc status is independently related to the bone mineral density,fracture risk assessment tool result,and bone fracture history: Results from a U.S. nationally representative survey

PurposePrevious reports have identified the important role of zinc in bone health. Although the risk of zinc deficiency is still a concern in the U.S., there has never been an in-depth study of the association between zinc status and bone health in a sample representing the country.MethodsWe included 2,895 subjects (aged ≥ 40 years) from National Health and Nutrition Examination Survey (NHANES) 2013–2014 to explore the relationship among three biomarkers of zinc (serum, food, and total intake), the bone mineral density (BMD) of the total spine and femur, the FRAX® scores, and the previous history of bone fractures.ResultsWe showed a one-unit increase in the ln-serum zinc level was associated with an increase in the total spine BMD (ß = 0.068; S.E. = 0.028; P = 0.030) and total femur BMD (ß = 0.061; S.E. = 0.017; P = 0.003), while a one-unit increase in the ln-food zinc intake amount was correlated with an increase in the total femur BMD in the participants (ß = 0.023; S.E. = 0.009; P = 0.021). The ln-total zinc intake amount was correlated with an increase in the total femur BMD in women (ß = 0.016; S.E. = 0.007; P = 0.041). We also found food zinc intake was negatively correlated with the FRAX® score, while increased levels of all three zinc biomarkers were associated with a decreased incidence of previous bone fractures.ConclusionsIn this representative survey of American adults above 40 years old, higher zinc status was associated with higher total spine and femoral BMD, lower FRAX® scores, and lower incidence of previous fractures. If this finding is causal, increased zinc intake remains an important issue for Americans.     

Association of Functional Polymorphisms from Brain-Derived Neurotrophic Factor and Serotonin-Related Genes with Depressive Symptoms after a Medical Stressor in Older Adults

Depressive symptoms are common in older adults after a disabling medical event and interfere with rehabilitation and recovery from the disability. This prospective study examined the role of genetic polymorphisms implicated in synaptic integrity and stress-associated depression as predictors of depressive symptoms after hip fracture. We recruited healthy comparisons from the community and participants with hip fracture after surgical fixation from Saint Louis, Missouri hospitals. We examined the valine (Val) to methionine (Met) polymorphism in brain-derived neurotrophic factor (BDNF), serotonin 1A receptor (5HT1a-rs6295) polymorphism, and the serotonin transporter-linked polymorphic region (5HTTLPR) interaction with the rs25531 A to G single nucleotide polymorphism (5HTTLPR-rs25531) as predictors of depressive symptoms. We also examined whether depressive symptoms mediate the influence of BDNF genotype on functional recovery. Among 429 participants with hip fracture, BDNF Met/Met carriers developed significantly more depressive symptoms than Val/Val carriers during a four-week period after the fracture (p=.012). BDNF genotype also predicted functional recovery over the ensuing year, mediated by its effects on depressive symptoms (CI: 0.07-3.37). Unlike prior studies of stressful life events, the S′ 5HTTLPR-rs25531 variant did not predict higher levels of depressive symptoms; instead, we report an exploratory finding of an epistatic effect between BDNF and 5HTTLPR-rs25531 whereby the compounded effects of two LA alleles and BDNF Met/Met genotype elevate risk of depressive symptoms after hip fracture (p=.006). No differences between 5HT1a genotypes were found. Our findings suggest plasticity-related genetic factors contribute to the neural mechanisms of mental and functional well-being after a disabling medical stressor.     

Human Triallelic Sites: Evidence for a New Mutational Mechanism?

Most SNPs in the human genome are biallelic; however, there are some sites that are triallelic. We show here that there are approximately twice as many triallelic sites as we would expect by chance. This excess does not appear to be caused by natural selection or mutational hotspots. Instead we propose that a new mutation can induce another mutation either within the same individual or subsequently during recombination. We provide evidence for this model by showing that the rarer two alleles at triallelic sites tend to cluster on phylogenetic trees of human haplotypes. However, we find no association between the density of triallelic sites and the rate of recombination, which leads us to suggest that triallelic sites might be generated by the simultaneous production of two new mutations within the same individual on the same genetic background. Under this model we estimate that simultaneous mutation contributes ∼3% of all distinct SNPs. We also show that there is a twofold excess of adjacent SNPs. Approximately half of these seem to be generated simultaneously since they have identical minor allele frequencies. We estimate that the mutation of adjacent nucleotides accounts for a little less than 1% of all SNPs.ALTHOUGH the density of biallelic SNPs in the human genome is reasonably low, there are some sites that have three (triallelic sites) or even four nucleotides segregating in the human population. We show here that there are approximately twice as many triallelic sites as we would expect by chance. There are at least three mutational mechanisms that could potentially generate such an excess of triallelic sites. First, some sites may be hypermutable, and if the mutation rate of at least two pathways (e.g., C → T and C → A) is elevated at such sites, then there will be an excess of triallelic sites. The mutation rate of a site is known to depend upon the adjacent nucleotides, the best known example being the CpG dinucleotide (Coulondre et al. 1978; Bird 1980) at which the frequency of both transition and transversion mutations is elevated. However, other adjacent nucleotides also influence the mutation rate (Blake et al. 1992; Zhao et al. 2003; Hwang and Green 2004). Furthermore, we have recently shown that there is variation in the mutation rate that does not depend upon the identity of the adjacent nucleotides or any specific context (Hodgkinson et al. 2009).Second, it is possible that two of the alleles at a triallelic site are generated simultaneously within a single individual. Point mutations are generally assumed to involve the production of a single new allele per mutation event at a rate that is governed by the effects mentioned above. However, it is not difficult to imagine mechanisms that might induce mutations on both strands of the DNA duplex; for example, the presence of a base mismatch may itself be unstable, so we might go from a G-C base pair to a G-A, which then may mutate to C-A; if DNA replication reads through this mismatch, the G allele will have mutated to both C and T. Alternatively, the mutation may occur across both strands of the duplex at the same time, possibly as a result of a chemical or radiation event. Third, in a similar manner, we might imagine a single SNP inducing subsequent mutations if base mismatches are formed during recombination in heteroduplex DNA.Here we attempt to identify the cause of the excess of triallelic sites by analyzing sequence data around triallelic sites.     

5-HTTLPR Expression Outside the Skin: An Experimental Test of the Emotional Reactivity Hypothesis in Children

Background

There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity −the intensity of an individual’s response to other’s emotions− has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors. However, the association between 5-HTTLPR and emotional reactivity in children has not yet been empirically tested. Therefore, the goal of this study was to test this association in a large-scale experiment.

Methods

Children (N = 521, 52.5% boys, Mage = 9.72 years) were genotyped and randomly assigned to happy, angry or neutral dynamic facial expressions and vocalizations. Motor and affective emotional reactivity were assessed through children’s self-reported negative and positive affect (n = 460) and facial electromyography activity (i.e., fEMG: the zygomaticus or “smile” muscle and the corrugator or “frown” muscle, n = 403). Parents reported on their negative and positive parenting behaviors.

Results

Children mimicked and experienced the emotion they were exposed to. However, neither motor reactivity nor affective reactivity to these emotions depended on children’s 5-HTTLPR genotype: SS/SL-genotypes did not manifest any stronger response to emotional stimuli than LL-genotypes. This finding remained the same when taking the broader family environment into account, controlling for kinship, age, gender and genetic ancestry, and when including a tri-allelic factor.

Conclusions

We found no evidence for an association between the 5-HTTLPR polymorphism and children’s emotional reactivity. This finding is important, in discounting one potential underlying endophenotype of G×E between the 5-HTTLPR and affective environmental stressors.     

The functional state of the serotonergic system and the 5-HTTLPR polymorphism of the serotonin transporter gene in patients with schizophrenia

Blood serotonin concentration is implicated in the regulation of behavior as well as in the development of psychopathological symptoms. Serotonin transporter regulates the serotonin level by reuptaking it from the synaptic cleft. In this study, platelet serotonin concentrations and the serotonin binding constant (V _max) were compared in patients with schizophrenia and healthy individuals with different 5-HTTLPR genotypes. The study included 60 patients and 62 controls. The above biochemical parameters were associated with the 5-HTTLPR genotype. Both in patients and controls, carriers of the LL genotype had lower blood serotonin concentrations and V _max as compared to those with genotypes containing one or two S alleles. These results suggest that the 5-HTTLPR polymorphism of the serotonin transporter gene is involved in regulating the state of the serotonergic system.     

Resistant starch does not affect zinc homeostasis in rural Malawian children

ObjectiveThis study tested the hypothesis that Malawian children at risk for zinc deficiency will have reduced endogenous fecal zinc (EFZ) and increased net absorbed zinc (NAZ) following the addition of high amylose maize resistant starch (RS) to their diet.MethodsThis was a small controlled clinical trial to determine the effects of added dietary RS on zinc homeostasis among 17 stunted children, aged 3–5 years consuming a plant-based diet and at risk for perturbed zinc homeostasis. Dual zinc stable isotope studies were performed before and after 28 d of intervention with RS, so that each child served as their own control. The RS was incorporated into fried wheat flour dough and given under direct observation twice daily for 28 d. Changes in zinc homeostatic measures were compared using paired Student's t-tests and linear regression analysis.ResultsChildren had a mean height-for-age Z-score of −3.3, and consumed animal source foods ≤twice per month. Their habitual diet contained a phytate:zinc molar ratio of 34:1. Children avidly consumed the RS without complaints. EFZ was 0.8 ± 0.4 mg/d (mean ± SD) both before and after the intervention. Fractional absorption of zinc was 0.38 ± 0.08 and 0.35 ± 0.06 before and after the RS intervention respectively. NAZ was 1.1 ± 0.5 and 0.6 ± 0.7 before and after the RS intervention. This reduction of NAZ corresponded with diminished dietary zinc intake on the study day following intervention with RS. Regression analysis indicated no change in zinc absorption relative to dietary intake as a result of the RS intervention.ConclusionConsumption of RS did not improve zinc homeostasis in rural African children without zinc deficiency. RS was well tolerated in this setting.     

Lack of Association Between PCK1 Polymorphisms and Obesity,Physical Activity,and Fitness in European Youth Heart Study (EYHS)

Phosphoenolpyruvate carboxykinase‐1 (PCK1) is the rate‐limiting enzyme in the hepatic gluconeogenic pathway. Studies have shown that overexpression of Pck1 in mice results in obesity‐related traits and higher levels of physical activity (PA). Therefore, our aims were to investigate whether common genetic variation in the PCK1 gene influences obesity‐related traits, PA, and fitness, and to examine whether PA and fitness attenuate the influence of the PCK1 polymorphisms on obesity in children. Analyses were undertaken on data from Danish and Estonian children (958 boys and 1,104 girls) from the European Youth Heart Study (EYHS), a school‐based, cross‐sectional study of children (mean ± s.d. age: 9.6 ± 0.4 years) and adolescents (15.5 ± 0.5 years). We genotyped eight polymorphisms that captured the common genetic variations in the PCK1 gene. The association between the PCK1 polymorphisms and BMI, waist circumference (WC), sum of four skinfolds, PA, and fitness was tested using an additive model adjusted for age, age‐group, gender, maturity, and country. Interactions were tested by including interaction terms in the model. None of the polymorphisms were significantly associated with BMI, WC, sum of four skinfolds, PA, and fitness, and also with the risk of being overweight or obese (P > 0.05). The interactions between the polymorphisms and age‐group, gender, PA, and fitness were not statistically significant. This is the first study to comprehensively examine the association of PCK1 polymorphisms with obesity, PA, and fitness. Despite strong evidence from animal studies, our study in the EYHS cohort failed to identify an association of PCK1 polymorphisms with obesity, PA, and fitness.     

Quality control for quantitative PCR based on amplification compatibility test

Quantitative qPCR is a routinely used method for the accurate quantification of nucleic acids. Yet it may generate erroneous results if the amplification process is obscured by inhibition or generation of aberrant side-products such as primer dimers. Several methods have been established to control for pre-processing performance that rely on the introduction of a co-amplified reference sequence, however there is currently no method to allow for reliable control of the amplification process without directly modifying the sample mix. Herein we present a statistical approach based on multivariate analysis of the amplification response data generated in real-time. The amplification trajectory in its most resolved and dynamic phase is fitted with a suitable model. Two parameters of this model, related to amplification efficiency, are then used for calculation of the Z-score statistics. Each studied sample is compared to a predefined reference set of reactions, typically calibration reactions. A probabilistic decision for each individual Z-score is then used to identify the majority of inhibited reactions in our experiments. We compare this approach to univariate methods using only the sample specific amplification efficiency as reporter of the compatibility. We demonstrate improved identification performance using the multivariate approach compared to the univariate approach. Finally we stress that the performance of the amplification compatibility test as a quality control procedure depends on the quality of the reference set.     

5-HTTLPR and Early Childhood Adversities Moderate Cognitive and Emotional Processing in Adolescence

Background

Polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) and exposure to early childhood adversities (CA) are independently associated with individual differences in cognitive and emotional processing. Whether these two factors interact to influence cognitive and emotional processing is not known.

Methodology and Principal Findings

We used a sample of 238 adolescents from a community study characterised by the presence of the short allele of 5-HTTLPR (LL, LS, SS) and the presence or absence of exposure to CA before 6 years of age. We measured cognitive and emotional processing using a set of neuropsychological tasks selected predominantly from the CANTAB® battery. We found that adolescents homozygous for the short allele (SS) of 5-HTTLPR and exposed to CA were worse at classifying negative and neutral stimuli and made more errors in response to ambiguous negative feedback. In addition, cognitive and emotional processing deficits were associated with diagnoses of anxiety and/or depressions.

Conclusion and Significance

Cognitive and emotional processing deficits may act as a transdiagnostic intermediate marker for anxiety and depressive disorders in genetically susceptible individuals exposed to CA.     

Development of subcutaneous fat in Spanish and Latin American children and adolescents: Reference values for biceps,triceps, subscapular and suprailiac skinfolds

Subcutaneous fat skinfolds represent a reliable assessment instrument of adiposity status. This study provides current percentile references for four subcutaneous skinfolds (biceps, triceps, subscapular, suprailiac) applicable to children and adolescents in Spain and in Latin American countries where data are scarce.The design consisted of a cross-sectional multicenter study performed with identical methods in 5 countries (Argentina, Cuba, Mexico, Spain and Venezuela). Total sample comprised 9163 children and youths (boys 4615 - girls 4548) aged 6–18 years, healthy and without apparent pathologies. Percentiles 3, 5, 10, 25, 50, 75, 90, 95 and 97 were calculated by the LMS method. Sexual dimorphism was assessed using the t-test and age differences with ANOVA. Normalized growth percentile references were obtained according to sex and age for each skinfold. The mean values of four skinfolds were significantly greater in girls than boys (p < 0.001) and, in both sexes, all skinfolds show statistical differences through age (p < 0.001) with different magnitudes.Except triceps in girls, peaks between 11 and 12 years of age are more noticeable in boys than in girls. Although the general model of growth is known, the skinfold measurements show variability among populations and differences of magnitude are presented according to the analyzed population. Therefore, these age and sex-specific reference percentile values for biceps, triceps, subscapular and suprailiac skinfolds, derived from a large sample of Spanish and Latin American children and adolescents, are a useful tool for adiposity diagnosis in this population for which no reference values were available.     

Differences in the Faecal Microbiome in Schistosoma haematobium Infected Children vs. Uninfected Children

BackgroundSeveral infectious diseases and therapeutic interventions cause gut microbe dysbiosis and associated pathology. We characterised the gut microbiome of children exposed to the helminth Schistosoma haematobium pre- and post-treatment with the drug praziquantel (PZQ), with the aim to compare the gut microbiome structure (abundance and diversity) in schistosome infected vs. uninfected children.MethodsStool DNA from 139 children aged six months to 13 years old; with S. haematobium infection prevalence of 27.34% was extracted at baseline. 12 weeks following antihelminthic treatment with praziqunatel, stool DNA was collected from 62 of the 139 children. The 16S rRNA genes were sequenced from the baseline and post-treatment samples and the sequence data, clustered into operational taxonomic units (OTUs). The OTU data were analysed using multivariate analyses and paired T- test.ResultsPre-treatment, the most abundant phyla were Bacteroidetes, followed by Firmicutes and Proteobacteria respectively. The relative abundance of taxa among bacterial classes showed limited variation by age group or sex and the bacterial communities had similar overall compositions. Although there were no overall differences in the microbiome structure across the whole age range, the abundance of 21 OTUs varied significantly with age (FDR<0.05). Some OTUs including Veillonella, Streptococcus, Bacteroides and Helicobacter were more abundant in children ≤ 1 year old compared to older children. Furthermore, the gut microbiome differed in schistosome infected vs. uninfected children with 27 OTU occurring in infected but not uninfected children, for 5 of these all Prevotella, the difference was statistically significant (p <0.05) with FDR <0.05. PZQ treatment did not alter the microbiome structure in infected or uninfected children from that observed at baseline.ConclusionsThere are significant differences in the gut microbiome structure of infected vs. uninfected children and the differences were refractory to PZQ treatment.     

Differences in Overweight and Obesity among Children from Migrant and Native Origin: The Role of Physical Activity,Dietary Intake,and Sleep Duration

A cross-sectional survey was performed to examine to what degree differences in overweight and obesity between native Dutch and migrant primary school children could be explained by differences in physical activity, dietary intake, and sleep duration among these children. Subjects (n=1943) were primary school children around the age of 8–9 years old and their primary caregivers: native Dutch children (n=1546), Turkish children (n=93), Moroccan children (n=66), other non-western children (n=105), and other western children (n=133). Multivariate regressions and logistic regressions were used to examine the relationship between migrant status, child’s behavior, and BMI or prevalence of overweight, including obesity (logistic). Main explanatory variables were physical activity, dietary intake, and sleep duration. We controlled for age, sex, parental educational level, and parental BMI. Although sleep duration, dietary intake of fruit, and dietary intake of energy-dense snacks were associated with BMI, ethnic differences in sleep duration and dietary intake did not have a large impact on ethnic differences in overweight and obesity among children from migrant and native origin. It is suggested that future preventive strategies to reduce overweight and obesity, in general, consider the role of sleep duration. Also, cross-cultural variation in preparation of food among specific migrant groups, focusing on fat, sugar, and salt, deserves more attention. In order to examine which other variables may clarify ethnic differences in overweight and obesity, future research is needed.     

Hair levels of heavy metals and essential elements in Chinese children with autism spectrum disorder

BackgroundDisproportional heavy metals and essential elements were reported in children with autism spectrum disorder (ASD) that is obscure in etiology. Inevitably, the association is biased by diet and environmental factors.MethodsFifty pairs, one with ASD and the other living together from the same special school with cerebral palsy (CP), were recruited in Hangzhou (China), aged from 2 to 11 years old (74.0 % male). All samples were divided into two subgroups: preschool-aged (2–5 years old) and school-aged (6–10 years old). Heavy metals (As, Hg, Pb) and essential elements (Al, Ca, Cu, Mg, Mn, Zn) in hair were quantified by inductively coupled plasma mass spectrometry analysis and flame atomic absorption spectroscopy.ResultsThe children with ASD generally had lower hair levels of Mn (ASD 0.124 μg/g, CP 0.332 μg/g, P = 0.001) compared to the children with CP. After stratification for age, there were no significant differences detected in preschool-aged group. In school-aged group, the results exhibited the children with ASD had higher hair Pb (1.485 μg/g, 0.690 μg/g, P = 0.007) and Cu/Zn ratio (0.092, 0.060, P = 0.003), while hair Hg (0.254 μg/g, 0.353 μg/g, P = 0.016)、Mn (0.089 μg/g, 0.385 μg/g, P = 0.002)、Mg (17.81 μg/g, 24.53 μg/g, P = 0.014) and Zn (100.15 μg/g, 135.83 μg/g, P = 0.007) showed an opposite pattern.ConclusionsThese results suggest an imbalance of Mn in Chinese children with ASD.     

Laboratory-based surveillance of Shigella spp. from human clinical cases in Colombia, 1997-2018

IntroductionShigellosis is endemic in low-and middle-income countries, causing approximately 125 million episodes of diarrhea and leading to approximately 160 .000 deaths annually one-third of which is associated with children.ObjectiveTo describe the characteristics and antimicrobial resistance profiles of Shigella species recovered in Colombia from 1997 to 2018.Materials and methodsWe received isolates from laboratories in 29 Colombian departments. We serotyped with specific antiserum and determined antimicrobial resistance and minimal inhibitory concentrations for ten antibiotics with Kirby-Bauer tests following the Clinical and Laboratory Standards Institute recommendations.ResultsWe analyzed 5,251 isolates of Shigella spp., most of them obtained from stools (96.4%); 2,511 (47.8%) were from children under five years of age. The two most common species were S. sonnei (55.1%) and S. flexneri (41.7%). The highest resistance rate was that of tetracycline (88.1%) followed by trimethoprim-sulfamethoxazole (79.3%) and ampicillin (65.5%); 50.8% of isolates were resistant to chloramphenicol, 43.6% to amoxicillin/clavulanic acid, and less than 1% to cefotaxime, ceftazidime, gentamicin, and ciprofloxacin. In S. sonnei, the most common resistance profile corresponded to trimethoprim-sulfamethoxazole (92%) whereas in S. flexneri the most common antibiotic profiles were multidrug resistance.ConclusionsIn Colombia, children under five years are affected by all Shigella species. These findings should guide funders and public health officials to make evidence-based decisions for protection and prevention measures. The antimicrobial resistance characteristics found in this study underline the importance of combating the dissemination of the most frequently isolated species, S. sonnei and S. flexneri.     

The intergenerational transmission of BMI in China

Based on the China Health and Nutrition Survey longitudinal data from 1989 to 2009 and using BMI z-score as the measure of adiposity, we estimate the intergenerational transmission of BMI in China. The OLS estimates suggest that a one standard deviation increase in father's or mother's BMI is associated with an increase of around 20% in child's Body Mass Index (BMI) z-score. These estimates decrease to around 14% when we control for family fixed effects. We examine the heterogeneity of this BMI intergenerational transmission process across family income, parental occupation and poverty status and also find this intergenerational correlation tends to be higher among children of higher BMI levels, though this tendency becomes weaker as children approach adulthood.