Epidemiology of and diagnostic strategies for toxoplasmosis

The apicomplexan parasite Toxoplasma gondii was discovered a little over 100 years ago, but knowledge of its biological life cycle and its medical importance has grown in the last 40 years. This obligate intracellular parasite was identified early as a pathogen responsible for congenital infection, but its clinical expression and the importance of reactivations of infections in immunocompromised patients were recognized later, in the era of organ transplantation and HIV infection. Recent knowledge of host cell-parasite interactions and of parasite virulence has brought new insights into the comprehension of the pathophysiology of infection. In this review, we focus on epidemiological and diagnostic aspects, putting them in perspective with current knowledge of parasite genotypes. In particular, we provide critical information on diagnostic methods according to the patient's background and discuss the implementation of screening tools for congenital toxoplasmosis according to health policies.     

A study of magnesium deficiency in human and experimental pulmonary hypertension

Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure above 25?mmHg. Pulmonary vasoconstriction, cellular proliferation, inflammation, and oxidative stress are involved in the pathophysiology of PH. Since hypomagnesemia was reported to promote endothelial cell dysfunction leading to inflammation and oxidative stress, we investigated the potential involvement of magnesium (Mg) deficiency in experimental and human PH. Our results indicate that Mg deficiency has no impact on hypoxia-induced PH development or severity, and that no reduction in Mg plasma concentration was observed in patients with severe pulmonary arterial hypertension. Thus, hypomagnesemia does not appear to play a role in the pathophysiology of experimental and human pulmonary hypertension.     

Les eaux embouteillées

Bottled waters, natural mineral water and spring water, meet the specific criteria defined by the regulation. Natural mineral water is characterized by its underground origin, the stability of its composition and its “original purity”. Water is an essential nutrient whose primary function is to hydrate. However, some natural mineral water can contribute to meet the recommended daily allowances (RDA) of minerals such as calcium and magnesium. These minerals from water are well absorbed and as consequence can contribute to meeting until 64 and 44% of daily intake in calcium and magnesium respectively. This recommendation is particularly relevant for children and adolescents, pregnant and lactating women, menopausal women and the elderly whom daily needs are increased. Concerning sulphates, the studies conducted to date do not allow establishing an upper limit of consumption via drinking water as they do not conclude on adverse effects in human being. In conclusion, as part of a balanced diet, natural mineral waters represent a natural source of minerals not negligible all the more they may have beneficial effects on health.     

Echographic measurement of skin thickness in sites suitable for intradermal vaccine injection in infants and children

Whereas the knowledge of skin thickness is essential to determine microneedle length and ensure proper administration of and better responses to intradermal vaccines, very few figures are available, especially in infants and children. Using ultrasound echography, we investigated skin thickness in 384 children aged 4-7, 12-18, and 54-66 months at potential body sites for intradermal vaccine delivery: deltoid, suprascapular, upper back, and lumbar area. The mean epidermis plus dermis thickness was significantly higher at the suprascapular than at the deltoid site (1.29 mm vs. 1.22 mm) and remained relatively unchanged whatever the BMI, age, sex, and skin phototype. In the 43 children aged 54-66 months, the mean skin thickness was significantly higher in the upper than in the lumbar area (1.39 mm vs. 1.31 mm). In this study setting, the heterogeneity in skin thickness cannot be considered sufficient to indicate various microneedle lengths for various ages or injection sites.     

Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: the effects of methamphetamine, alcohol, and polydrug exposure

Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure.     

Age-related Purkinje cell death is steroid dependent: RORα haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival

A major problem of ageing is progressive impairment of neuronal function and ultimately cell death. Since sex steroids are neuroprotective, their decrease with age may underlie age-related neuronal degeneration. To test this, we examined Purkinje cell numbers, plasma sex steroids and cerebellar neurosteroid concentrations during normal ageing (wild-type mice, WT), in our model of precocious ageing (Rora(+/sg), heterozygous staggerer mice in which expression of the neuroprotective factor RORα is disrupted) and after long-term hormone insufficiency (WT post-gonadectomy). During normal ageing (WT), circulating sex steroids declined prior to or in parallel with Purkinje cell loss, which began at 18 months of age. Although Purkinje cell death was advanced in WT long-term steroid deficiency, this premature neuronal loss did not begin until 9 months, indicating that vulnerability to sex steroid deficiency is a phenomenon of ageing Purkinje neurons. In precocious ageing (Rora(+/sg)), circulating sex steroids decreased prematurely, in conjunction with marked Purkinje cell death from 9 months. Although Rora(+/sg) Purkinje cells are vulnerable through their RORα haplo-insufficiency, it is only as they age (after 9 months) that sex steroid failure becomes critical. Finally, cerebellar neurosteroids did not decrease with age in either genotype or gender; but were profoundly reduced by 3 months in male Rora(+/sg) cerebella, which may contribute to the fragility of their Purkinje neurons. These data suggest that ageing Purkinje cells are maintained by circulating sex steroids, rather than local neurosteroids, and that in Rora(+/sg) their age-related death is advanced by premature sex steroid loss induced by RORα haplo-insufficiency.     

Frequency of CXCR4-using viruses in primary HIV-1 infections using ultra-deep pyrosequencing

We used ultra-deep pyrosequencing and the Toulouse Tropism Test phenotypic assay to determine the prevalence of CXCR4-using viruses in 21 patients with primary HIV-1 infections. We found X4-containing virus populations in 9% of patients by ultra-deep pyrosequencing using position-specific scoring matrices (PSSM(X4/R5)) or geno2pheno(5.75) and in 14% using the combined 11/25 and net charge rule. The phenotypic assay identified 9% of CXCR4-using viruses. This confirms that R5 viruses are predominant in primary HIV-1 infections.