Biomarkers of cardiometabolic health are associated with body composition characteristics but not physical activity in persons with spinal cord injury

Objective: To examine (i) the associations between physical activity dimensions, cardiorespiratory fitness and body composition and, (ii) the associations between physical activity dimensions, cardiorespiratory fitness, body composition and biomarkers of cardiometabolic health in persons with spinal cord injury (SCI).

Methods: A cross-sectional prospective cohort study with 7-day follow-up was conducted. Body composition, cardiorespiratory fitness and biomarkers of cardiometabolic health were measured in thirty-three participants with SCI (> 1 year post injury). Physical activity dimensions were objectively assessed over 7-days.

Results: Activity energy expenditure (r =.43), physical activity level (r =.39), and moderate-to-vigorous physical activity (MVPA) (r =.48) were significantly (P < 0.001) associated with absolute (L/min) peak oxygen uptake (?O₂ peak). ?O₂ peak was significantly higher in persons performing ≥150 MVPA minutes/week compared to <40 minutes/week (P?=?0.003). Individual physical activity dimensions were not significantly associated with biomarkers of cardiometabolic health. However, body composition characteristics (BMI, waist and hip circumference) showed significant (P < 0.04), moderate (r >.30) associations with parameters of metabolic regulation, lipid profiles and inflammatory biomarkers. Relative ?O₂ peak (ml/kg/min) was moderately associated with only insulin sensitivity (r?=?0.37, P?=?0.03).

Conclusions: Physical activity dimensions are associated with cardiorespiratory fitness; however, stronger and more consistent associations suggest that poor cardiometabolic health is associated with higher body fat content. Given these findings, the regulation of energy balance should be an important consideration for researchers and clinicians looking to improve cardiometabolic health in persons with SCI.     

La relation mère-fille. Une histoire sans nom de Barbey d’Aurevilly

In 1967, some hematologists who were inspired by Barbey d’Aurevilly’s novel, “A story without a name”, described the syndrome of Lasthénie de Ferjol: recurrent anemia resulting from voluntarily provoked hemorrhages. We used the same novel as a basis for studying the mother-daughter relationship. Madame de Ferjol is widowed, and lives a reclusive life with her only daughter, Lasthénie, until such time as a capuchin priest enters their life during Lent. This unexpected encounter with sexuality (Lasthénie becomes pregnant) has a marked effect upon the young woman; she withdraws into total silence, and displays self-mutilating behavior (provoked bouts of anemia) which leads to her death and to that of her unborn child. In this tale, we see a paradigm of the mother-child relationship that has already been observed in anorexia nervosa. Mother and daughter are caught up in a narcissistic dyad fom which neither is able to extricate herself. The mother remains in a pathological state of mourning, and we put forward the hypothesis that this dead mother is affected by a melancholic process in which her hatred is projected onto her daughter. Finally, we have attempted to examine the connections between hysteria and anorexia nervosa, as in this story rivalry between mother and daughter also plays a role, and in which sexuality—therefore involving a third party—is unmentionable.     

Effect of LY 83583 on relaxation induced by non-adrenergic non-cholinergic nerve stimulation and exogenous nitric oxide in the rat gastric fundus.

In the rat gastric fundus, the reported cGMP-lowering agent LY 83583 (10(-5) M) inhibited the relaxation induced by nitric oxide (NO), without altering the response to isoprenaline, vasoactive intestinal polypeptide, sodium nitroprusside or electrical field stimulation of inhibitory non-adrenergic non-cholinergic neurones, which are thought to release NO. Incubation with superoxide dismutase partially prevented the effect of LY 83583. When added during a relaxation maintained by continuous NO infusion, LY 83583 reversed the relaxation. It is concluded that LY 83583 inactivates exogenous NO through the generation of superoxide anions.     

Childhood fractures are associated with decreased bone mass gain during puberty: an early marker of persistent bone fragility?

Whether peak bone mass is low among children with fractures remains uncertain. In a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures. Among those, BMC gain at multiple sites and vertebral bone size at pubertal maturity were significantly decreased. Hence, childhood fractures may be markers of low peak bone mass acquisition and persistent skeletal fragility. INTRODUCTION: Fractures in childhood may result from a deficit in bone mass accrual during rapid longitudinal growth. Whether low bone mass persists beyond this period however remains unknown. MATERIALS AND METHODS: BMC at the spine, radius, hip, and femur diaphysis was prospectively measured over 8.5 years in 125 girls using DXA. Differences in bone mass and size between girls with and without fractures were analyzed using nonparametric tests. The contribution of genetic factors was evaluated by mother-daughter correlations and that of calcium intake by Cox proportional hazard models. RESULTS: Fifty-eight fractures occurred in 42 among 125 girls (cumulative incidence, 46.4%), one-half of all fractures affecting the forearm and wrist. Girls with and without fractures had similar age, height, weight. and calcium intake at all time-points. Before and during early puberty, BMC and width of the radius diaphysis was lower in the fracture compared with no-fracture group (p < 0.05), whereas aBMD and BMAD were similar in the two groups. At pubertal maturity (Tanner's stage 5, mean age +/- SD, 16.4 +/- 0.5 years), BMC at the ultradistal radius (UD Rad.), femur trochanter, and lumbar spine (LS), and LS projected bone area were all significantly lower in girls with fractures. Throughout puberty, BMC gain at these sites was also decreased in the fracture group (LS, -8.0%, p = 0.015; UD Rad., -12.0%, p = 0.004; trochanter, -8.4%, p = 0.05 versus no fractures). BMC was highly correlated between prepuberty and pubertal maturity (R = 0.54-0.81) and between mature daughters and their mothers (R = 0.32-0.46). Calcium intake was not related to fracture risk. CONCLUSIONS: Girls with fractures have decreased bone mass gain in the axial and appendicular skeleton and reduced vertebral bone size when reaching pubertal maturity. Taken together with the evidence of tracking and heritability for BMC, these observations indicate that childhood fractures may be markers for low peak bone mass and persistent bone fragility.     

Cyclic AMP increases the release of parathyroid hormone-related protein from a lung-cancer cell line

Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of malignant hypercalcemia by stimulating bone resorption and/or renal tubular reabsorption of calcium. In cultured cancer cells, its production can be influenced by various factors or ions, but the regulation of its production is still poorly understood. We investigated the effects of stimulators of cAMP synthesis on PTHrP release by a human lung squamous-carcinoma cell line (BEN). In supervised cells grown on microcarrier beads, PTHrP production was significantly increased after incubation with calcitonin for only 20 min. The release of immunoreactive and bioactive PTHrP was increased by incubating the cells with forskolin, 3-isobutyl-I-methylxanthine or dibutyryl cAMP even in the presence of the protein-synthesis inhibitor cycloheximide for 6 hr. The calcitonin-mediated stimulation was not accompanied by. concomitant changes in PTHrP mRNA. The microfilament-disrupter cytocha-lasin D was shown to enhance the basal and calcitonin-induced production of PTHrP. These results indicate that stimulators of cAMP synthesis enhanced PTHrP release by BEN cells.     

Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity.

We compared and contrasted the mechanism of action for the cysteine knot protein subfamily, Wise and Sost (Sclerostin). Our data suggest that functional interactions between Sost or Wise and LRP5/LRP6 have the potential to regulate bone deposition by modulating the Wnt pathway. INTRODUCTION: The human disease sclerosteosis exhibits an increase in bone mass thought to be caused by hyperactive osteoblasts. Sclerostin, SOST, the gene affected in this disease, has been postulated to exert its activity by functioning as a BMP antagonist. However, recent evidence indicates that SOST is highly related to Wise, which can also modulate the Wnt pathway by binding to LRP5 and LRP6. MATERIALS AND METHODS: For this study, we used cell culture to test the BMP and Wnt activity function of both Wise and Sost. In addition, we used Xenopus in vivo Wnt assays along with Xenopus in vitro Wnt assays to support our cell culture results. Epitope tagged cell supernatants containing either Sost or soluble mutant or wildtype LRP5/LRP6 were used for immunoprecipitation. Sost immunoprecipitation results were confirmed in vivo using cell culture. Finally, to support our in vitro data, we co-localized Sost, Wise, LRP5, and LRP6 in mouse long bone sections. Results: In this study, we report in vitro and in vivo evidence to show that Sost physically interacts with Lrp5 and Lrp6 and inhibits the canonical Wnt signaling pathway. Furthermore, using in vitro and in vivo assays, we showed that a variant of LRP5 (LRP5(G171V)) known to cause the human high bone mass (HBM) trait and a homologous change in LRP6 (LRP6(G158V)) abolished protein interactions with Sost. We used variants of Sost amino acids to further identify the contact points between Sost and LRP6. In Xenopus and mammalian cell culture assays, we showed that SOST is able to attenuate Wnt signaling and that this attenuation can be rescued by the addition of alpha-Sost antibodies or by the introduction of single amino acid substitution that alter its binding to LRP6. Sost differs from Wise in that it is unable to stimulate Wnt signaling. Using immunohistochemistry, we found that Sost and Wise are co-localized to osteoblasts, along with LRP5 and LRP6. CONCLUSIONS: Our data suggest that functional interactions between Sost or Wise and LRPs have the potential to regulate bone deposition by modulating Wnt signaling.     

France: a focus on the new reproduction

This bibliographic essay's initial focus is on publications reflecting European concern with the ethical implications of reproductive technologies. Titles by P. Verspieren, the Institut Catholique de Lyon, C. Lefèvre, E. Loumaye and J-F. Malherbe, and J-L. Baudouin and C. Labrusse-Riou are briefly discussed. Also mentioned are recently published works on biomedical technologies by B. Edelman, M-A. Hermite, Labrusse-Riou, and M. Remond-Gouilloud; on the social impact of science by G. Hottois, J. DeVooght, R. Rasmont, and P. Van Gansen; on medical ethics by C. Ambroselli, and by Malherbe; on AIDS by E. Hirsch, by E. Conan, and by Malherbe and S. Zorrilla. All cited titles are in French.     

T helper cell epitopes of the human immunodeficiency virus (HIV-1) nef protein in rats and chimpanzees.

T helper cell antigenic and immunogenic determinants of the nef protein were investigated in the rat and chimpanzee models using recombinant nef protein and five synthetic peptides selected according to their amphipathic and alpha-helicity properties. The nef protein was shown to be immunogenic with both Freund's or aluminium hydroxide adjuvants. After immunization with the nef protein the 45-69 peptide was the most antigenic in rat and monkey models. In contrast, the 98-112 peptide, that required a carrier protein to induce in vitro rat T cell recall proliferation, was able to restimulate monkey T cells in the absence of a carrier. The amino acid sequence carrying the antigenic activity of the 45-69 peptide was further investigated by synthesizing short peptides overlapping this region. The antigenic sequence was precisely located in the middle of the peptide (region 50-59). This sequence was antigenic only when N alpha-acetylated. Circular dichroism analysis of the 45-69 peptide and the in vitro activity of the N-terminus group indicate in this case the involvement of the alpha-helical propensity for antigen presentation. However, the shorter sequence 50-64, able to induce a T cell reactivity, was determined as a beta-pleated sheet structure in aqueous solution. The 45-69 peptide was not only antigenic but also immunogenic and behaved in vivo as a functional T helper cell epitope. Indeed, the priming with the peptide or the transfer of peptide specific T cells to a naive recipient, followed by immunization with the nef protein, enhanced the subsequent antibody response to the nef protein. Together, these data indicate that the 45-69 peptide appears as a candidate for the in vivo elicitation of T cell immunity to the HIV-1 nef regulatory protein.     

Medical record linkage in health information systems by approximate string matching and clustering

Background  

Multiplication of data sources within heterogeneous healthcare information systems always results in redundant information, split among multiple databases. Our objective is to detect exact and approximate duplicates within identity records, in order to attain a better quality of information and to permit cross-linkage among stand-alone and clustered databases. Furthermore, we need to assist human decision making, by computing a value reflecting identity proximity.     

Purification and partial characterization of a 32-kilodalton sialic acid-specific lectin from Aspergillus fumigatus

Adherence of the opportunistic fungus Aspergillus fumigatus to the extracellular matrix components is considered a crucial step in the establishment of the infection. Given the high carbohydrate content of these glycoproteins and the role of carbohydrate-protein interactions in numerous adherence processes, the presence of a lectin in A. fumigatus was investigated. Different fungal extracts obtained by sonication or grinding in liquid nitrogen from resting or swollen conidia, as well as from germ tubes and mycelium, were tested by hemagglutination assays using rabbit erythrocytes. A lectin activity was recovered in all the extracts tested. However, sonication of resting conidia resulted in the highest specific activity. Purification of the lectin was achieved by gel filtration followed by ion-exchange and hydrophobic-interaction chromatographies. Analysis of the purified lectin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed an apparent molecular mass of 32 kDa, which is similar to that of the alkaline protease already identified from different strains of A. fumigatus. However, as evidenced by the use of an alkaline protease-deficient mutant, the two activities were supported by distinct proteins. In addition, hemagglutination inhibition experiments using different saccharides and glycoproteins demonstrated the specificity of the lectin for sialic acid residues. Together these results suggest that this lectin may contribute to the attachment of conidia to the extracellular matrix components through the recognition of the numerous terminal sialic acid residues of their carbohydrate chains.