Clustering of Metabolic Risk Factors Is Associated with High-Normal Levels of Liver Enzymes Among 6- to 8-Year-Old Children: The PANIC Study

Abstract Background: We studied the associations of clustering of metabolic risk factors with plasma levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) in healthy prepubertal children. Methods: The subjects were a representative population sample of 492 children 6-8 years of age. We assessed body fat percentage (dual-energy X-ray absorptiometry), body mass index, waist circumference, systolic and diastolic blood pressure, glucose, insulin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, ALT, GGT, and high-sensitivity C-reactive protein (hsCRP) and calculated a continuous metabolic syndrome score variable. We also used factor analysis to examine whether high-normal liver enzymes are a feature of metabolic syndrome among children. Results: Children with overweight or obesity, defined by International Obesity Task Force (IOTF) criteria, had a 2.1-times higher risk of having ALT and a 4.5-times higher risk of having GGT in the highest fifth of its distribution than normal weight children. Children in the highest sex-specific third of metabolic syndrome score, body fat percentage, waist circumference, and insulin had a two to three times higher risk of being in the highest fifth of ALT and GGT. Moreover, children in the highest third of glucose and hsCRP had a 2.5-fold risk of being in the highest fifth of GGT. First-order factor analysis yielded three factors; the first included insulin, glucose, and triglycerides; the second waist circumference, insulin, GGT, and hsCRP; and the third HDL-C, triglycerides, waist circumference, and insulin. Second-order factor analysis yielded a single metabolic syndrome factor, explaining 64.1% of the variance. Conclusions: Clustering of metabolic risk factors, particularly excess body fat, is associated with high-normal levels of ALT and GGT in prepubertal children. High-normal levels of liver enzymes, especially GGT, and systemic low-grade inflammation could be considered features of metabolic syndrome among children. Subtle changes in liver function may play an important role in the pathogenesis of metabolic syndrome beginning in childhood.     

Novel retinal findings in β-thalassemia major: older age and higher ferritin level as the risk factors

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate retinal changes in β-thalassemia major patients and identify their association with systemic risk factors. In...     

Intra-word consistency and accuracy in Finnish children aged 3–6 years

This study examined intra-word consistency and accuracy in typically developing Finnish children and their relation to children’s vocabulary size and phonological skills. A total of 80 typically developing Finnish children aged 3;0 to 6;11 were asked to name 20 words three separate times during a single assessment session. Responses were classified into four categories: 1) consistently correct productions, 2) consistently incorrect productions, 3) variable productions with hits (variable productions including at least one matched adult target), and 4) variable productions with no hits. The results revealed that 5- and 6-year-old children produced significantly more often consistently correct responses than younger children. However, even for the 3- and 4-year old children the most frequent response type was consistently correct production. Between these two youngest age groups (3 and 4), the only significant difference was in consistently incorrect responses, which the 3-year-olds produced more often than the older children. There was a significant negative correlation between consistently incorrectly produced words and children’s phonological skills, but no other relationships were found. The results indicate that when assessing children with speech sound disorder (SSD), Finnish clinicians need to take into account the fact that even 3-year-old typically developing children generally produce words correctly, either consistently or inconsistently.     

Peer victimization and social phobia: a follow-up study among adolescents

Objective

This study examined longitudinal associations between direct and relational peer victimization (DV/RV) and self-reported social phobia (SP) among adolescents from 15 to 17 years of age, controlling for depression and family socioeconomic covariates.

Methods

A total of 3,278 Finnish adolescents with a mean age of 15.5 years were surveyed at baseline (T1), and followed up 2 years afterwards (T2) their mean age being 17.6 years. In all, 2,070 adolescents were reached for the follow-up. Both types of victimization were assessed with structured questions, SP with the Social Phobia Inventory, and depression with the 13-item Beck Depression Inventory. Socioeconomic covariates were assessed with items from the Life Events Checklist. Frequency of victimization and SP were assessed at T1 and T2, and incidence and persistence from T1 to T2. Longitudinal associations between victimization and SP were examined with three logistic regression analyses with depression and socioeconomic covariates controlled for, with SP, DV, and RV in turn as the dependent endpoint (T2) variables.

Results

Among boys a bidirectional association between DV and SP was found with DV both predicting SP [Odds Ratio (OR) 2.6] and being predicted by SP (OR 3.9). Among girls RV predicted SP (OR 2.8), but not vice versa, while depression in turn predicted DV (OR 4.3).

Conclusions

Direct victimization and SP have a bidirectional association among boys, while among girls RV increases the risk of subsequent SP.     

Subthalamic deep brain stimulation affects heading perception in Parkinson’s disease

Journal of Neurology - Parkinson’s disease (PD) presents with visuospatial impairment and falls. It is critical to understand how subthalamic deep brain stimulation (STN DBS) modulates...     

Controlled ovarian hyperstimulation with sequential letrozole co-treatment in normo/high responders

Objective: To investigate the effect of co-administration of letrozole in an ovarian stimulation protocol using recombinant FSH and GnRH antagonists for ICSI in normo/high responders.

Methods: Computerized data of 320 antagonist ICSI/ET cycles with or without letrozole were retrospectively analyzed. In 105 cases, letrozole (5?mg/day) was started at the second day of the cycle continued for 5 days. At the second day of letrozole, gonadotropins were added. The remaining 215 cases were stimulated with recombinant FSH only. In all cases on day 6, GnRH antagonist was started. Ovarian stimulation protocols with or without letrozole were compared for cycle outcome parameters.

Results: In cycles with letrozole, significantly lower gonadotropin consumption and lower peak estradiol levels were found. In cycles with letrozole, mean number of metaphase II and fertilized oocytes retrieved were significantly higher compared to cycles without letrozole. The pregnancy and clinical pregnancy rates were similar.

Conclusion: Should the number of oocytes retrieved being higher in letrozole group might indicate that letrozole might contribute to successful ovarian stimulation with a lower dosage of gonadotropins. Despite the lower peak estradiol levels, pregnancy rates being similar to other group also support the idea that letrozole can contribute to normal potential of implantation.     

Post-neonatal hospitalization and health care costs among IVF children: a 7-year follow-up study

BACKGROUND: The objective of this study was to evaluate whether the post-neonatal hospitalization and resulting health care costs are increased among in vitro fertilization (IVF) children up to 7 years of age. METHODS: We conducted a population-based cohort study with linkage to a national hospital discharge register including 303 IVF children, born from 1990 to 1995, and 567 control children (1:2) randomly chosen from the Finnish Medical Birth Register and matched for sex, year of birth, area of residence, parity, maternal age and socioeconomic status. The cost calculations were stratified for singleton (n = 152 vs. n = 285) and twin (n = 103 vs. n = 103) status. Main outcome measures were hospitalizations and societal health care costs. RESULTS: The full-sample and singleton analyses showed that IVF children were significantly more frequently admitted to hospital (mean 1.76 vs. 1.07, P < 0.0001; 1.61 vs. 1.07, P = 0.0004, respectively) and spent significantly more days in the hospital (mean 4.31 vs. 2.61, P < 0.0001; 3.47 vs. 2.56, P = 0.0014, respectively) than control children. No differences were detected between IVF and control twins. The costs of post-neonatal hospital care per child were 2.6-fold for IVF singletons, but 0.7-fold for IVF twins when compared with controls. Cost estimation showed 2.6-fold costs for total IVF population in comparison to general population based controls. CONCLUSIONS: The incidence of multiple births increases the utilization of post-neonatal health care services and costs among IVF children in comparison to naturally conceived children. Increased hospitalization and costs were also seen among IVF singletons.     

The human GIMAP5 gene has a common polyadenylation polymorphism increasing risk to systemic lupus erythematosus

Background

Several members of the GIMAP gene family have been suggested as being involved in different aspects of the immune system in different species. Recently, a mutation in the GIMAP5 gene was shown to cause lymphopenia in a rat model of autoimmune insulin‐dependent diabetes. Thus it was hypothesised that genetic variation in GIMAP5 may be involved in susceptibility to other autoimmune disorders where lymphopenia is a key feature, such as systemic lupus erythematosus (SLE).

Material and methods

To investigate this, seven single nucleotide polymorphisms in GIMAP5 were analysed in five independent sets of family‐based SLE collections, containing more than 2000 samples.

Result

A significant increase in SLE risk associated with the most common GIMAP5 haplotype was found (OR 1.26, 95% CI 1.02 to 1.54, p = 0.0033). In families with probands diagnosed with trombocytopenia, the risk was increased (OR 2.11, 95% CI 1.09 to 4.09, p = 0.0153). The risk haplotype bears a polymorphic polyadenylation signal which alters the 3′ part of GIMAP5 mRNA by producing an inefficient polyadenylation signal. This results in higher proportion of non‐terminated mRNA for homozygous individuals (p<0.005), a mechanism shown to be causal in thalassaemias. To further assess the functional effect of the polymorphic polyadenylation signal in the risk haplotype, monocytes were treated with several cytokines affecting apoptosis. All the apoptotic cytokines induced GIMAP5 expression in two monocyte cell lines (1.5–6 times, p<0.0001 for all tests).

Conclusion

Taken together, the data suggest the role of GIMAP5 in the pathogenesis of SLE.