Seasonal changes in gene expression represent cell-type composition in whole blood.

Seasonal patterns in behavior and biological parameters are widespread. Here, we examined seasonal changes in whole blood gene expression profiles of 233 healthy subjects. Using weighted gene co-expression network analysis, we identified three co-expression modules showing circannual patterns. Enrichment analysis suggested that this signal stems primarily from red blood cells and blood platelets. Indeed, a large clinical database with 51 142 observations of blood cell counts over 3 years confirmed a corresponding seasonal pattern of counts of red blood cells, reticulocytes and platelets. We found no direct evidence that these changes are linked to genes known to be key players in regulating immune function or circadian rhythm. It is likely, however, that these seasonal changes in cell counts and gene expression profiles in whole blood represent biological and clinical relevant phenomena. Moreover, our findings highlight possible confounding factors relevant to the study of gene expression profiles in subjects collected at geographical locations with disparaging seasonality patterns.

Fluorescence of neutrophil granulocytes as a biomarker for clozapine use.

Non-adherence to medication is a major issue in the treatment of schizophrenia in general and in particular for those treated with clozapine. A reliable tool to quantify patients long-term adherence to clozapine is currently unavailable. Enhanced FL3 neutrophil granulocyte fluorescence was serendipitously observed in a small population of schizophrenic patients treated with clozapine. The present study was aimed at assessing the association between clozapine use and FL3-fluorescence. A cross-sectional study was performed using data from the Utrecht Patient Oriented Database (UPOD). A total of 38,390 inpatients were included, of which 124 (0.33%) used clozapine. FL3-fluorescence was significantly higher (U=240,179, P<0.001) in clozapine users (mean (SD)=90.5 (11.8)) than in non-users (mean (SD)=69.8 (3.3)). Observed FL3-fluorescence was found to increase with increasing clozapine dose. The area under the receiver operating characteristic curve was 0.95. Our results confirm the association between use of clozapine and elevated FL3-fluorescence. Further research is needed to unravel the underlying mechanism and to investigate the true potential of FL3-fluorescence as a clozapine-adherence biomarker in clinical practice.

Valproic acid treatment is associated with altered leukocyte subset development.

Valproic acid (VPA) has been used for decades in the treatment of epilepsy and psychiatric disorders, and the long-term use of VPA is regularly accompanied by hematological toxicity, including neutropenia. More recently, it has been demonstrated that VPA can be used as a histone deacetylase inhibitor (HDACi) for the treatment of hematological malignancies. In order to determine the specific effects of VPA in both hematological malignancies and normal hematopoiesis, recent studies have demonstrated that VPA treatment affects the differentiation of normal myeloid progenitors in vitro. In this study, we demonstrate that in a large patient population treated for neurological or psychiatric disorders, VPA treatment affects neutrophil as well as lymphocyte subset counts.

The Mediterranean diet and fetal size parameters: the Generation R Study.

Developmental adaptations due to early nutritional exposures may have permanent health consequences. Studies of diet and fetal size have mainly focused on individual nutrients despite evidence that the pattern of food consumption may be of significance. Hence, we evaluated the associations of dietary habits in early pregnancy (gestational age < 18 weeks) with fetal size, uteroplacental vascular resistance, placental weight and birth weight in a prospective observational study of 3207 Caucasian pregnant mothers in Rotterdam, the Netherlands. Participants completed a semiquantitative FFQ during early pregnancy. Logistic regression analysis was used to predict the occurrence of intra-uterine growth retardation at birth as a function of food intake. The derived solution was considered as the dietary pattern. As it was characterised by higher intakes of fruit, vegetables, vegetable oil, fish, pasta and rice, and lower intakes of meat, potatoes and fatty sauces, it was labelled the 'Mediterranean' diet. The degree of adherence to the diet was positively associated with plasma folate and serum vitamin B12 concentrations and showed an inverse relationship with homocysteine and high-sensitivity C-reactive protein plasma concentrations (P <0·05). Important fetal size and placental parameters were associated with the degree of adherence to the diet, revealing a 72 g lower birth weight (95% CI -110·8, -33·3) and a 15 g lower placental weight (95% CI -29·8, -0·2) for women with low adherence to the diet. To conclude, low adherence to a Mediterranean diet in early pregnancy seems associated with decreased intra-uterine size with a lower placental and a lower birth weight.

Major dietary patterns and blood pressure patterns during pregnancy: the Generation R Study.

OBJECTIVE: We sought to evaluate associations between dietary patterns and systolic blood pressure (SBP) and diastolic blood pressure during pregnancy. STUDY DESIGN: This was a prospective study of 3187 pregnant women. Participants completed a food-frequency questionnaire in early pregnancy. The Mediterranean dietary pattern, comprising high intake of vegetables, vegetable oils, pasta, fish, and legumes, and the Traditional dietary pattern, comprising high intake of meat and potatoes, were identified using factor analysis. RESULTS: A higher SBP was observed among mothers with high Traditional pattern adherence. Low adherence to the Mediterranean pattern was also associated with higher SBP but only in early and mid pregnancy. A higher diastolic blood pressure throughout pregnancy was observed in mothers with high adherence to the Traditional pattern and low adherence to the Mediterranean pattern. These effect estimates were most pronounced in mid pregnancy. CONCLUSION: Low adherence to a Mediterranean and high adherence to a Traditional dietary pattern is associated with a higher blood pressure in pregnancy.

Maternal milk consumption, fetal growth, and the risks of neonatal complications: the Generation R Study.

BACKGROUND: Maternal cow-milk consumption may increase birth weight. Previous studies did not assess the association of maternal milk consumption with trimester-specific fetal growth. OBJECTIVE: The objective was to assess associations of first-trimester maternal milk consumption with fetal growth characteristics in different trimesters and the risk of neonatal complications. DESIGN: In total, 3405 mothers participating in a prospective cohort study completed a 293-item semiquantitative food-frequency questionnaire to obtain information about dairy consumption during the first trimester of pregnancy. Fetal head circumference, femur length, and weight were estimated in the second and third trimesters by ultrasonography. RESULTS: Maternal milk consumption of >3 glasses/d was associated with greater fetal weight gain in the third trimester of pregnancy, which led to an 88-g (95% CI: 39, 135 g) higher birth weight than that with milk consumption of 0 to 1 glass/d. In addition, head circumference tended to be 2.3 cm (95% CI: -0.0, 4.6 cm) larger when mothers consumed >3 glasses/d. Maternal milk consumption was not associated with length growth. Maternal protein intake (P for trend = 0.01), but not fat or carbohydrate intake, from dairy products was associated with higher birth weight. This association appeared to be limited to milk (P for trend < 0.01), whereas protein intake from nondairy food or cheese was not associated with birth weight. CONCLUSIONS: Maternal milk consumption is associated with greater fetal weight gain. The association seems to be due to milk protein, or milk components closely associated with protein, rather than to the fat or carbohydrate fraction of milk.

Discriminative value of platelet size indices for the identification of the mechanism of chemotherapy-induced thrombocytopenia.

CONTEXT: A biomarker for discriminating mechanisms of chemotherapy-induced thrombocytopenia (CIT) (i.e. increased platelet destruction and decreased platelet production) would be valuable in managing treatment. OBJECTIVE: We explored the discriminating value of platelet size indices for this purpose in a population of adult oncology patients. MATERIALS AND METHODS: Mean platelet volume (MPV) and platelet distribution width (PDW) were compared between patients with (i) thrombocytopenia possibly due to increased platelet destruction; (ii) thrombocytopenia possibly due to decreased platelet destruction; and (iii) no thrombocytopenia. RESULTS AND CONCLUSIONS: We obtained negative results, suggesting that these indices are not useful for discriminating different CIT mechanisms.