Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.     

Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.     

The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes. By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells. Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia. During maturation, DCs undergo profound rearrangements of actin cytoskeleton. Immature DCs are adherent with visible actin cables, while fully mature, MARCO-expressing, splenic DCs are nonadherent, round in shape, and have an actin cytoskeleton with a punctate distribution. The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs. MARCO-transfected immature DCs acquired a typical morphology of mature DCs and did not rearrange the actin cytoskeleton following activation. Moreover, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs. MARCO expression in DCs and microglial cells was also associated with a decrease of antigen internalization capacity. Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation.     

The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.     

Detecting familial hypercholesterolemia by serum lipid profile screening in a hospital setting: Clinical,genetic and atherosclerotic burden profile

Background and aims

Familial hypercholesterolemia (FH) is underdiagnosed and public cholesterol screening may be useful to find new subjects. In this study, we aim to investigate the prevalence of FH patients in a hospital screening program and evaluate their atherosclerotic burden using intima-media thickness (IMT).

Relational Memory in the Early Stage of Psychosis: A 2-Year Follow-up Study

BackgroundRelational memory, the ability to bind information into complex memories, is moderately impaired in early psychosis and severely impaired in chronic schizophrenia, suggesting relational memory may worsen throughout the course of illness. MethodsWe examined relational memory in 66 early psychosis patients and 64 healthy control subjects, with 59 patients and 52 control subjects assessed longitudinally at baseline and 2-year follow-up. Relational memory was assessed with 2 complementary tasks, to test how individuals learn relationships between items (face-scene binding task) and make inferences about trained relationships (associative inference task).ResultsThe early psychosis group showed impaired relational memory in both tasks relative to the healthy control group. The ability to learn relationships between items remained impaired in early psychosis patients, while the ability to make inferences about trained relationships improved, although never reaching the level of healthy control performance. Early psychosis patients who did not progress to schizophrenia at follow-up had better relational memory than patients who did.ConclusionsRelational memory impairments, some of which improve and are less severe in patients who do not progress to schizophrenia, are a target for intervention in early psychosis.     

Effect of BH4 on blood phenylalanine and tyrosine variations in patients with phenylketonuria

BackgroundIn patients with phenylketonuria, stability of blood phenylalanine and tyrosine concentrations might influence brain chemistry and therefore patient outcome. This study prospectively investigated the effects of tetrahydrobiopterin (BH4), as a chaperone of phenylalanine hydroxylase on diurnal and day-to-day variations of blood phenylalanine and tyrosine concentrations.MethodsBlood phenylalanine and tyrosine were measured in dried blood spots (DBS) four times daily for 2 days (fasting, before lunch, before dinner, evening) and once daily (fasting) for 6 days in a randomized cross-over design with a period with BH4 and a period without BH4. The sequence was randomized. Eleven proven BH4 responsive PKU patients participated, 5 of them used protein substitutes during BH4 treatment. Natural protein intake and protein substitute dosing was adjusted during the period without BH4 in order to keep DBS phenylalanine levels within target range. Patients filled out a 3-day food diary during both study periods. Variations of DBS phenylalanine and Tyr were expressed in standard deviations (SD) and coefficient of variation (CV).ResultsBH4 treatment did not significantly influence day-to-day phenylalanine and tyrosine variations nor diurnal phenylalanine variations, but decreased diurnal tyrosine variations (median SD 17.6 μmol/l, median CV 21.3%, p = 0.01) compared to diet only (median SD 34.2 μmol/l, median CV 43.2%). Consequently, during BH4 treatment diurnal phenylalanine/tyrosine ratio variation was smaller, while fasting tyrosine levels tended to be higher.ConclusionBH4 did not impact phenylalanine variation but decreased diurnal tyrosine and phenylalanine/tyrosine ratio variations, possibly explained by less use of protein substitute and increased tyrosine synthesis.