Ecological association between indoor radon concentration and childhood leukaemia incidence in France, 1990-1998.

The objective of this study was to evaluate the ecological association between indoor radon concentration and acute leukaemia incidence among children under 15 years of age in the 348 geographical units (zones d'emploi, ZE) of France between 1990 and 1998. During that period, 4015 cases were registered by the French National Registry of Childhood Leukaemia and Lymphoma. Exposure assessment was based on a campaign of 13 240 measurements covering the whole country. The arithmetic mean radon concentration was 85 Bq/m (range, 15-387 Bq/m) and the geometric mean, 59 Bq/m (range: 13-228 Bq/m). A positive ecological association, on the borderline of statistical significance (P=0.053), was observed between indoor radon concentration and childhood leukaemia incidence. The association was highly significant for acute myeloid leukaemia (AML) (P=0.004) but not for acute lymphocytic leukaemia (ALL) (P=0.49). The standardized incidence ratio (SIR) increased by 7, 3 and 24% for all acute leukaemia, ALL and AML, respectively, when radon concentration increased by 100 Bq/m. In conclusion, the present ecological study supports the hypothesis of a moderate association between indoor radon concentration and childhood acute myeloid leukaemia. It is consistent with most previous ecological studies. Since the association is moderate, this result does not appear inconsistent with the five published case-control studies, most of which found no significant association.     

Performances,feasibility and acceptability of nasopharyngeal swab,saliva and oral-self sampling swab for the detection of severe acute respiratory syndrome coronavirus 2

European Journal of Clinical Microbiology & Infectious Diseases - Molecular diagnosis on nasopharyngeal swabs (NPS) is the current standard for COVID-19 diagnosis, but saliva may be an...     

Conditional ablation of NKp46+ cells using a novel Ncr1greenCre mouse strain: NK cells are essential for protection against pulmonary B16 metastases

To study gene functions specifically in NKp46⁺ cells we developed novel Cre mice allowing for conditional gene targeting in cells expressing Ncr1 (encoding NKp46). We generated transgenic Ncr1^greenCre mice carrying an EGFPcre fusion under the control of a proximal Ncr1 promoter that faithfully directed EGFPcre expression to NKp46⁺ cells from lymphoid and nonlymphoid tissues. This approach allowed for direct detection of Cre‐expressing NKp46⁺ cells via their GFP signature by flow cytometry and histology. Cre was functional as evidenced by the NKp46⁺ cell‐specific expression of RFP in Ncr1^greenCreRosa‐dtRFP reporter mice. We generated Ncr1^greenCreIl2rg^fl/fl mice that lack NKp46⁺ cells in an otherwise intact hematopoietic environment. Il2rg encodes the common gamma chain (γ_c), which is an essential receptor subunit for cytokines (IL‐2, ‐4, ‐7, ‐9, ‐15, and ‐21) that stimulate lymphocyte development and function. In Ncr1^greenCreIl2rg^fl/fl mice, NK cells are severely reduced and the few remaining NKp46⁺ cells escaping γc deletion failed to express GFP. Using this new NK‐cell‐deficient model, we demonstrate that the homeostasis of NKp46⁺ cells from all tissues (including the recently described intraepithelial ILC1 subset) requires Il2rg. Finally, Ncr1^greenCreIl2rg^fl/fl mice are unable to reject B16 lung metastases demonstrating the essential role of NKp46⁺ cells in antimelanoma immune responses.     

Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship.

P-glycoprotein (P-gp) is involved in the ATP-dependant cellular efflux of a large number of drugs including ivermectin, a macrocyclic lactone (ML) endectocide, widely used in livestock and human antiparasitic therapy. The interactions of P-gp with ivermectin and other MLs were studied. In a first approach, the ability of ivermectin (IVM), eprinomectin (EPR), abamectin (ABA), doramectin (DOR), selamectin (SEL), or moxidectin (MOX) to inhibit the rhodamine123 efflux was measured in recombinant cells overexpressing P-gp. Then, the influence of these compounds on the P-gp ATPase activity was tested on membrane vesicles prepared from fibroblasts overexpressing P-gp. All the MLs tested increased the intracellular rhodamine123. However, the potency of MOX to inhibit P-gp function was 10 times lower than the other MLs. They all inhibited the basal and decreased the verapamil-stimulated P-gp ATPase activity. But SEL and MOX were less potent than the other MLs when competing with verapamil. According to the structural specificity of SEL and MOX, we conclude that the integrity of the sugar moiety is determinant to achieve the optimal interaction of macrocyclic lactones with P-gp. The structure-affinity relationship for interaction with P-gp is important information for improving ML bioavailability and reversal of multidrug resistance (MDR).     

Maturational changes of caffeine concentrations and disposition in infancy during maintenance therapy for apnea of prematurity: influence of gestational age, hepatic disease, and breast-feeding

Twenty-three premature infants receiving caffeine maintenance therapy were followed prospectively for several months. Three to nine determinations of caffeine half-life (peak and trough caffeine levels) were made in each baby. This first longitudinal study confirmed that the half-life of caffeine is prolonged during the neonatal period (97.6 + 32 hours and for as many as 38 weeks' gestation in several very premature babies). Contrary to previous assumptions, gestational age and postconceptional age seem to be closely related to maturation of hepatic caffeine elimination after the neonatal period, although a high variability of caffeine half-life was observed between infants. Adult values (6 hours) were obtained about 60 weeks postconceptional. Caffeine half-life was greatly increased in two infants who had cholestatic hepatitis secondary to prolonged parenteral alimentation and one infant who was breast-fed exclusively. In this last case, the role of maternal hormones in repressing the normal enzymatic maturation process is strongly suspected. Adequate blood levels of caffeine were usually obtained with a caffeine half-life greater than 30 hours up to 46 weeks postconceptional with a dose of 5 mg/kg of caffeine citrate. Caffeine predose monitoring is adequate up to 46 weeks postconceptional, and caffeine half-life determination is mandatory whenever the trough level is too high or too low, icterus is present, and from 46 to 50 weeks postconception.     

Delay in caffeine elimination in breast-fed infants

Because of a persistently elevated caffeine half-life observed in a breast-fed infant during caffeine maintenance therapy, we conducted this prospective longitudinal study in two groups of infants (five exclusively breast-fed and 12 formula-fed). After 46 weeks' postconceptional age, all five breast-fed infants had a marked delay in caffeine elimination, compared with one infant in the formula-fed group. Four breast-fed infants had measurements of significantly longer caffeine half-lives compared with 12 formula-fed infants (76 +/- 13 hours v 21 +/- 28 hours and 54 +/- 9 hours v 16 +/- 13 hours at 47 to 50 weeks and 51 to 54 weeks postconceptional age, respectively), as well as significantly higher trough blood levels (three- to five-fold) after 46 weeks' postconceptional age. The fifth breast-fed infant accumulated caffeine secondary to a steep increase in caffeine half-life from 102 hours at 44 weeks to 372 hours at 51 weeks. The elevated blood caffeine levels in breast-fed infants was not related to higher daily dosage of caffeine citrate (4.4 mg/kg compared with 8.3 mg/kg in the formula-fed group at 56 weeks' postconceptional age). Daily consumption of caffeine was low or nonexistent in four nursing mothers, and transfer of caffeine to the infant was considered to be trivial. The findings from this study suggest, as does breast milk jaundice due to inhibition of glycuronyl transferase, that some components of human milk (free fatty acid, lipase activity, or other factors) inhibit or repress the postnatal normal maturation process of caffeine metabolism by hepatic cytochrome P-450.     

Family resemblance in breakfast energy intake: the Stanislas Family Study

BACKGROUND: There seems to be a consensus that family influences on dietary habits are important. However, no data relative to breakfast have been published yet. OBJECTIVE: To investigate whether and how breakfast energy intake aggregates within French families. DESIGN: A total of 398 families of the Stanislas Family Study who filled in a 3 day food consumption diary were selected. Absolute and relative breakfast energy intakes (BEI in kcal/day and RBEI in percentage of daily intake, respectively) were both studied. RESULTS: By using a variance component analysis, no genetic influence was shown in family aggregation of both BEI and RBEI. Intra-generation common environmental contribution to total phenotypic variance of BEI and RBEI was higher than inter-generation; both were increased with frequency of sharing breakfast. Furthermore frequency of sharing breakfast contributed to increase family resemblance in breakfast energy intake, particularly in offspring for BEI and RBEI, and in spouses for RBEI. Smoking habits, alcohol consumption, BMI or physical activity were related to family resemblance, but after adjustment on each factor degrees of resemblance were almost unchanged. CONCLUSION: General findings of this study were that family aggregation in breakfast absolute and relative energy intakes was significant within Stanislas families. Family resemblance depended on inter- and intra-generation components and was modified by the number of shared breakfasts. Our study confirmed that familial habits act on family resemblance in both absolute and relative breakfast energy intakes, so that family should be a favorite unit for health and diet promotion programs. SPONSORSHIP: Kellogg's PA, France.