The focal form of persistent hyperinsulinemic hypoglycemia of infancy: morphological and molecular studies show structural and functional differences with insulinoma

Paternal mutation of ATP-sensitive K(+) (K(ATP)) channel genes and loss of heterozygosity (LOH) of the 11p15 region including the maternal alleles of ABCC8, IGF2, and CDKN1C characterize the focal form of persistent hyperinsulinemic hypoglycemia of infancy (FoPHHI). We aimed to understand the actual nature of FoPHHI in comparison with insulinoma. In FoPHHI, the lesion consists in clusters of beta-cells surrounded by non-beta-cells. Compared with adjacent islets, proinsulin mRNA is similar and proinsulin production higher (P < or = 0.02), indicating regulation at a translational level, with slightly lower insulin stock and lower ABCC8 peptide labeling (P<0.05). Insulinomas, composed of beta-cell nests or cords, have similar proinsulin mRNA compared with adjacent islets, highly variable proinsulin production, lower insulin stock (P < or = 0.02), and higher ABCC8 peptide labeling (P<0.05). Proinsulin mRNA is lower than in FoPHHI (P<0.001). Islets adjacent to FoPHHI appear to be resting, in contrast to those adjacent to insulinomas, evidencing intrapancreatic regulation of islet beta-cell activity. IGF2 peptide is present inside and outside both lesions, but IGF2 mRNA is restricted to the lesions. The 11p15 LOH and absence of CDKN1C peptide staining are demonstrated in all FoPHHI but also in three of eight insulinomas. Despite some molecular similarities, FoPHHI is thus fundamentally different from insulinoma.     

Assessment of circadian rhythms by actimetry in healthy subjects and patients with advanced colorectal cancer

Circadian rhythms can be altered in severe illness such as cancer; the rest-activity circadian cycle has been used as a reference for the administration of chemotherapy at specific times in order to improve tolerability and efficacy. We assessed the feasibility of the method in our center in a sample of patients with metastatic colorectal cancer selected for chronomodulated chemotherapy. Activity of the circadian rhythms were measured non-invasively in 10 patients with metastatic colorectal cancer by wrist actimetry, and compared to healthy subjects. Patients and healthy subjects were requested to wear an actigraph, a wristwatch that records the number of accelerations per minute, for 3 days. Healthy subjects exhibited high activity levels during daytime, followed by low activity levels during the night. In patients, the contrast between daytime activity and nocturnal sleep was noticeably less marked, and a wide inter-patient variability was observed. All the patients wore the actigraph with a total compliance. Actimetry may provide a simple and innovative tool to study the circadian system and may be considered as an objective and accurate method to evaluate the individual health status ("conditions of life") in cancer patients, independently of all ("quality of life" questionnaires.     

In vitro infection of human primary adipose cells with HIV-1: a reassessment

We reassessed the infection ability of human primary preadipocytes. The use of X4, R5 or VSV-G-pseudotyped viral particles indicated that viral entry is the limiting step. However, transfection with HIV-1 receptors restored efficient infection. Analyses of CD4, CXCR4 and CCR5 expression on preadipocytes and adipocytes revealed that receptor co-expression levels did not permit HIV-1 entry into adipose cells from all biopsies tested. We concluded that adipose tissue cannot be infected with HIV-1 in vivo.     

Extracellular Matrix Produced by Osteoblasts Cultured Under Low-Magnitude, High-Frequency Stimulation is Favourable to Osteogenic Differentiation of Mesenchymal Stem Cells

The effects of low-magnitude, high-frequency (LMHF) mechanical stimulation on osteoblastic cells are poorly understood. We have developed a system that generates very small (15–40 με), high-frequency (400 Hz, sine) deformations on osteoblast cultures (MC3T3-E1). We investigated the effects of these LMHF stimulations mainly on extracellular matrix (ECM) synthesis. The functional properties of this ECM after decellularization were evaluated on C3H10T1/2 mesenchymal stem cells (MSCs). LMHF stimulations were applied 20 min once daily for 1, 3, or 7 days in MC3T3-E1 culture (1, 3, or 7 dLMHF). Cell number and viability were not affected after 3 or 7 dLMHF. Osteoblast response to LMHF was assessed by an increase in nitric oxide secretion, alteration of the cytoskeleton, and focal contacts. mRNA expression for fibronectin, osteopontin, bone sialoprotein, and type I collagen in LMHF cultures were 1.8-, 1.6-, 1.5-, and 1.7-fold higher than controls, respectively (P < 0.05). In terms of protein, osteopontin levels were increased after 3 dLMHF and ECM organization was altered as shown by fibronectin topology after 7 dLMHF. After decellularization, 7 dLMHF-ECM or control ECM was reseeded with MSCs. Seven dLMHF-ECM improved early events such as cell attachment (2 h) and focal contact adhesion (6 h) and, later (16 h), modified MSC morphological parameters. After 5 days in multipotential medium, gene-expression changes indicated that 7 dLMHF-ECM promoted the expression of osteoblast markers at the expense of adipogenic marker. LMHF stimulations of osteoblasts are therefore efficient and sufficient to generate osteogenic matrix.     

Parental use of the Internet to seek health information and primary care utilisation for their child: a cross-sectional study

Background  

Using the Internet to seek health information is becoming more common. Its consequences on health care utilisation are hardly known in the general population, in particular among children whose parents seek health information on the Internet. Our objective was to investigate the relationship between parental use of the Internet to seek health information and primary care utilisation for their child.     

Panmictic structure of the genetic diversity of apomictic Meloidogyne nematodes (Nematoda: Tylenchida)

Species delineation in parthenogenetic tropical species of Meloidogyne nematodes is particularly difficult although they are strictly apomictic. In fact, parthenogenesis in Meloidogyne nematodes is a recent phenomenon and the structure of the genetic diversity is mainly explained by crosses prior to the establishment of parthenogenesis. Under such hypothesis, increasing the size of a characterized sample by adding individuals should result in the decrease of the diversity structure. Twelve individuals from different geographical origins were added to the initial pool of 26 lines characterized in a previous study and an AFLP study was conducted on the whole set of 38 lines. As expected under the panmixy hypothesis, this resulted in a loss of genetic structure. This confirms thus that the genetic structure of tropical parthenogenetic Meloidogyne is due to crosses anterior to the establishment of apomixy.