Examining the neural correlates of goal priming with the NeuroShop, a novel virtual reality fMRI paradigm.

OBJECTIVE: Health goal priming has been shown to stimulate healthy food choices by activating an individual's weight-control goal. The present study combined fMRI with a novel virtual reality food choice task to elucidate the underlying neural mechanisms of health goal priming. Previous research has suggested that the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) play a role in the incorporation of health considerations into the food choice process. Responses may be more representative for those found in real life when assessed in an environment similar to the actual choice environment. Therefore, the first aim of the study was to explore if a novel virtual reality food choice task is sufficiently sensitive to detect basic valuation processes in food choice. The second aim was to examine whether increased activation in the dlPFC drives the effects of health goal priming. METHODS: Fifty-six female participants performed an fMRI food choice task embedded in a virtual supermarket environment. They chose between perceived healthy and unhealthy products in a health prime, hedonic prime, and non-food control condition, while activation in brain areas involved in self-control and valuation (vmPFC, dlPFC) was assessed. RESULTS: There were no differences in relative preference for perceived healthy products over unhealthy products between the conditions. There were also no main effects of prime condition on brain activation in the vmPFC and dPFC during food choice. Across conditions, activation in the vmPFC correlated with the tastiness of the chosen product during food choice. CONCLUSIONS: Although the study does not provide support for health goal priming triggering neural self-control mechanisms, results did show that virtual reality has potential for a more realistic fMRI food choice paradigm.

New measure for fathers of children with developmental challenges.

BACKGROUND: There is a relative lack of measures tailored to the study of fathers of children with developmental challenges (DCs). The goal of the current study was to create and validate a brief measure designed to capture the perceptions and experiences of these fathers. The Fathers of Children with Developmental Challenges (FCDC) questionnaire was designed to assess fathers' perceptions of the supports for, and challenges to, their efforts to be involved in the rearing of their children. METHOD: Participants were 101 fathers of children with DCs who completed an online survey. Scale validation included tests to determine reliability, validity and factor structure. Used to establish validity were measures of parenting stress, parenting commitment, parent personality and child social-communicative skills. RESULTS: Analyses indicated that the FCDC is reliable (α = 0.89), demonstrates content validity, construct validity and acts in theoretically expected ways. Factor analysis on the 20-item measure yielded two sub-scales: (1) impact on parenting, and (2) involvement with child intervention. CONCLUSIONS: The FCDC fills a gap in the literature by offering an easy-to-administer self-report measure of fathers' perceptions of supports for, and barriers to, their involvement with their children with DCs. The FCDC could assist professionals in delivering support services specifically for fathers of children with DCs.

γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate.

BACKGROUND: γ-Glutamyl hydrolase (GGH) regulates intracellular folate and antifolates for optimal nucleotide biosynthesis and antifolate-induced cytotoxicity, respectively. The modulation of GGH may therefore affect chemosensitivity of cancer cells, and exogenous folate levels may further modify this effect. METHODS: We generated a novel model of GGH modulation in human HCT116 and MDA-MB-435 cancer cells and investigated the effect of GGH modulation on chemosensitivity to 5-fluorouracil (5FU) and methotrexate (MTX) at different folate concentrations in vitro and in vivo. RESULTS: Overexpression of GGH significantly decreased chemosensitivity of MDA-MB-435 cells to 5FU and MTX at all folate concentrations as expected. In contrast, in HCT116 cells this predicted effect was observed only at very high folate concentration, and as the folate concentration decreased this effect became null or paradoxically increased. This in vitro observation was confirmed in vivo. Inhibition of GGH significantly increased chemosensitivity of both cancer cells to 5FU at all folate concentrations. Unexpectedly, GGH inhibition significantly decreased chemosensitivity of both cancer cells to MTX at all folate concentrations. In both GGH modulation systems and cell lines, the magnitude of chemosensitivity effect incrementally increased as folate concentration increased. CONCLUSION: Modulation of GGH affects chemosensitivity of cancer cells to 5FU and MTX, and exogenous folate levels can further modify the effects.

Bayesian rank-based hypothesis testing for the rank sum test, the signed rank test, and Spearman's ρ.

Bayesian inference for rank-order problems is frustrated by the absence of an explicit likelihood function. This hurdle can be overcome by assuming a latent normal representation that is consistent with the ordinal information in the data: the observed ranks are conceptualized as an impoverished reflection of an underlying continuous scale, and inference concerns the parameters that govern the latent representation. We apply this generic data-augmentation method to obtain Bayes factors for three popular rank-based tests: the rank sum test, the signed rank test, and Spearman's ρ s .

[Two cases of Crimean-Congo haemorrhagic fever (CCHF) in two tourists in Senegal in 2004]. / Deux cas de fièvre hémorragique de Crimée-Congo (FHCC) contractée au Sénégal, en 2004, par des résidentes temporaires.

Two cases of Crimean-Congo haemorrhagic fever (CCHF) occurred in two French tourists during their visit in Senegal in November 2004. Febrile and hemorrhagic syndrome with ulorrhagia, petechiae, haematemesis, haematomas associated with biological signs of disseminated intramuscular coagulation were observed. For the first case who had a medical evacuation to France before diagnosis, Crimean-Congo virus infection was revealed by laboratory tests performed by the National Reference Center for Hemorrhagic Fevers (NRCHF, Institut Pasteur, Lyon) and secondly by the Centre de Référence OMS sur la Recherche des Arbovirus et des virus des Fièvres Hémorragiques (CRORA) in the Dakar Pasteur Institute (DPI). The second case diagnosed by the CRORA died after clinical deterioration with liver failure and severe haemorrhages. Healthcare workers and family members who had contact with tissue or blood from patients were followed up after the putative exposure either in France or in Senegal.

Kinetic behavior of the reaction between hydroxyl radical and the SV40 minichromosome.

Aqueous solutions containing the minichromosomal form of the virus SV40 and the radical scavenger DMSO were subjected to gamma-irradiation, and the resulting formation of single strand breaks (SSB) was quantified. Under the irradiation conditions, most SSBs were produced as a consequence of hydroxyl radical ((•)OH) reactions. By controlling the competition between DMSO and the viral DNA substrate for (•)OH, we are able to estimate the rate coefficient for the reaction of (•)OH with the SV40 minichromosome. The results cannot be described adequately by homogeneous competition kinetics, but it is possible to describe the rate coefficient for the reaction as a function of the scavenging capacity of the solution. The experimentally determined rate coefficient lies in the range 1×10(9) - 2×10(9) L mol(-1) s(-1) at 10(7) s(-1), and increases with increasing scavenging capacity.

Repair of oxidative DNA damage by amino acids.

Guanyl radicals, the product of the removal of a single electron from guanine, are produced in DNA by the direct effect of ionizing radiation. We have produced guanyl radicals in DNA by using the single electron oxidizing agent (SCN)2-, itself derived from the indirect effect of ionizing radiation via thiocyanate scavenging of OH. We have examined the reactivity of guanyl radicals in plasmid DNA with the six most easily oxidized amino acids cysteine, cystine, histidine, methionine, tryptophan and tyrosine and also simple ester and amide derivatives of them. Cystine and histidine derivatives are unreactive. Cysteine, methionine, tyrosine and particularly tryptophan derivatives react to repair guanyl radicals in plasmid DNA with rate constants in the region of approximately 10(5), 10(5), 10(6) and 10(7) dm3 mol(-1) s(-1), respectively. The implication is that amino acid residues in DNA binding proteins such as histones might be able to repair by an electron transfer reaction the DNA damage produced by the direct effect of ionizing radiation or by other oxidative insults.

[Nicorandil-associated anal ulceration]. / Ulcérations anales induites par le nicorandil.

BACKGROUND: Nicorandil is a potassium-channel activator used in the treatment of angina pectoris. The first cases of anal ulcerations induced by nicorandil were published in 2002. CASE REPORT: A 71-year-old man presented with a 2-year history of anal ulcerations occurring within a few months of initiation of treatment with Nicorandil. Histological tests on a biopsy sample showed granulation tissue with non-specific chronic inflammation. Nicorandil was stopped and this resulted in complete healing of the ulcers after three months. DISCUSSION: Nicorandil can induce chronic and extensive anal ulcerations. The pathogenesis is unknown. Patients are usually treated with high doses of nicorandil. Dermatologists should be aware of this rare side-effect which heals after withdrawal of the drug.

[Increased risk of type II diabetes mellitus and cardiovascular disease after gestational diabetes mellitus: a systematic review]. / Verhoogd risico op diabetes mellitus type 2 en hart- en vaatziekten na diabetes gravidarum: een systematische review.

OBJECTIVE: To determine the long-term risk of developing type II diabetes (T2D) and cardiovascular disease (CVD) for women with a history of gestational diabetes mellitus. DESIGN: Systematic review and meta-analysis. METHOD: Two search strategies were used in PubMed and Embase to determine the long-term risks of developing T2D and CVD after a pregnancy complicated by gestational diabetes mellitus. After critical appraisal of the papers found, 11 papers were included, involving a total of 328,423 patients. Absolute and relative risks (RRs) were calculated. RESULTS: Eight studies (n=276,829) reported on the long-term risk of T2D and 4 (n=141,048) on the long-term risk of CVD. Follow-up ranged from 3.5 to 11.5 years for T2D and from 1.2 to 74.0 years for CVD. Women with gestational diabetes had a risk of T2D varying between 9.5% and 37.0% and a risk of CVD of between 0.28% and 15.5%. Women with gestational diabetes were at increased risk of T2D (weighted RR: 13.2; 95% CI: 8.5-20.7) and CVD (weighted RR: 2.0; 95% CI: 1.1-3.7) compared to women without gestational diabetes. CONCLUSION: Women with prior gestational diabetes mellitus have a significantly increased risk of developing T2D and CVD. It is very important that gestational diabetes is recognised as a cardiovascular risk factor in daily practice. It would be desirable to screen this group of women for the presence of hyperglycaemia and other cardiovascular risk factors. Further research is required to be able to specify the long-term risk of T2D and CVD and to demonstrate whether such screening is cost-effective.

Plasmodium falciparum clinical malaria in Dielmo, a holoendemic area in Senegal: no influence of acquired immunity on initial symptomatology and severity of malaria attacks.

Six hundred eighty-nine Plasmodium falciparum malaria attacks were observed during a three-year period among 226 inhabitants of the village of Dielmo, Senegal, an area of high malaria transmission. Malaria attacks were defined as clinical episodes with fever (body temperature > or = 38.0 degrees C) or reporting of fever or headache or vomiting, associated with a parasite:leukocyte ratio above an age-dependent pyrogenic threshold identified in this population. The symptom frequencies were tested against age, gender, and parasite density using a random-effect logistic regression model and the study of distinguishable clinical presentations was carried out by multi-correspondence analysis. There was little difference between the severity of symptoms during the initial course of attacks in young children and adults, and this severity was not correlated with the duration of the pathologic episode. It was not possible to distinguish objectively different malaria attack types according to the severity of clinical manifestations. In contrast, the duration of fever, symptoms, and parasite clearance were significantly longer among the youngest children than among the oldest children and adults. These findings suggest that of the two components of protective immunity, anti-parasite immunity and anti-toxic immunity, only the first would play a major role as age increases. They suggest also that the initial clinical presentation of malaria attacks is not predictive of the level of protective immunity.

False synergy between vancomycin and beta-lactams against glycopeptide-intermediate Staphylococcus aureus (GISA) caused by inappropriate testing methods.

The combination of vancomycin and beta-lactams is often considered synergistic and has been recommended for the treatment of glycopeptide-intermediate Staphylococcus aureus (GISA) infections. In this study, the combination of vancomycin or teicoplanin with different beta-lactams was tested. When using NaCl 4% w/v, for better expression of heterogeneous resistance to beta-lactams, with a longer (48-h) incubation period and a higher (10(7) CFU/mL) inoculum, the association of vancomycin with beta-lactams was antagonistic. However, a synergistic effect was observed for teicoplanin under the same conditions.

Expression of insulin-like growth factor-I in rat glioma cells is associated with change in both immunogenicity and apoptosis.

Insulin-like growth factor I (IGF-I), has a role in cellular differentiation and is also expressed in neoplastic transformation of glioma cells. We recently demonstrated inhibition in expression of cellular IGF-I after transfection with vectors that incodes a segment of the human IGF-I RNA in antisense orientation. The transfected cells expressed increased levels of both MHC-I and B7 molecules. In this paper we show that IGF-I antisense transfected cells also become apoptotic. Moreover, the phenomenon of programmed cell death is related to the phenomenon that results in increased expression of MHC-I and B7 molecules. Co-transfection of rat glioma cells with the vector expressing IGF-I antisense RNA and with vectors encoding the expression of MHC-I and B7 antisense cDNA suppressed the expression of both of these molecules and was associated with a decrease in apoptosis.

Composition of plaque and saliva following use of an alpha-tricalcium-phosphate-containing chewing gum and a subsequent sucrose challenge.

Previous studies demonstrated that the chewing of a 2.5% (mass fraction) alpha-tricalcium-phosphate-fortified (alpha-TCP) experimental chewing gum released sufficient calcium and phosphate to eliminate any fall in the tooth mineral saturation of plaque fluid after a sucrose rinse (Vogel et al., 1998). In contrast, the chewing of a conventional sugar-free gum did not eliminate this decrease in saturation. The purpose of this study was to examine if the release of ions from plaque calcium-phosphate pools induced by this gum could provide protection during subsequent exposure to cariogenic conditions. Fourteen subjects accumulated plaque for 48 hrs, fasted overnight, chewed a control or experimental gum for 15 min, and subsequently rinsed 1 min with a mass fraction 10% sucrose solution. Before gum chewing, and at 7 min and 15 min afterward, whole plaque, plaque fluid, and salivary samples were obtained and analyzed by micro-analytical techniques. Additional samples were collected and analyzed at 25 min (7 min after the sucrose rinse). Although the results confirmed the deposition of large amounts of calcium and phosphates in plaque seen in the previous study, only a small increase was seen in plaque-fluid-free calcium and phosphate before sucrose administration. This suggests that few of the mineral ions were mobilized under non-cariogenic conditions. However, 7 min after the sucrose rinsing, an increase in these concentrations was seen which, based on hydroxyapatite ion activity product calculations, indicated a decrease in the driving force for demineralization compared with that seen with the control gum. These results suggest that the chewing of the experimental gum deposits a labile mineral reservoir in plaque that can resist a subsequent cariogenic challenge.

Composition of plaque and saliva following a sucrose challenge and use of an alpha-tricalcium-phosphate-containing chewing gum.

Calcium phosphate concentrations in plaque, plaque fluid, and saliva play an important role in caries prevention. In this study, we used a microanalytical technique to examine the anticaries potential of a 2.5% (mass fraction) alpha-tricalcium-phosphate-fortified experimental gum by measuring the pH, free and total calcium, and total phosphate in plaque fluid, whole plaque, and saliva, and centrifuged saliva from 14 subjects who (1) accumulated plaque for 48 hours, (2) fasted overnight, (3) rinsed for 1 min with sucrose, and (4) chewed a control or experimental gum for 15 min. From these data, the hydroxyapatite (HAp) ion activity products (IAP[HAp]) of saliva and plaque fluid were calculated as a measure of tooth mineral saturation. Results, compared with those of the control gum, show significant increases in pH and in free calcium and phosphate concentrations in plaque fluid and saliva when the experimental gum was chewed following sucrose ingestion. These increases result in a rise in fluid saturation with respect to tooth mineral that, for plaque fluid, nearly cancels the decrease seen with the control gum after the sucrose rinse. This suggests that the experimental gum may be more effective than a conventional gum in ameliorating the cariogenic effects of sucrose. Similar statistically significant increases were also seen in the total calcium content of the plaque fluid, centrifuged saliva, whole saliva, and whole plaque, and in the total phosphate of whole plaque and whole saliva. These results suggest that the deposition of a mineral reservoir in plaque and saliva by the experimental gum may help resist future cariogenic challenges.

The effect of different treatment regimens on the epidemiology of seasonally transmitted Schistosoma haematobium infections in four villages in the Senegal River Basin, Senegal.

This paper describes the present epidemiological situation of Schistosoma haematobium in 4 villages in the middle valley of the Senegal River Basin, in terms of level and intensity of infection, seasonality of transmission, and intermediate hosts, and the effect of different treatment schedules with praziquantel on the overall infection levels and re-infection rates. The longitudinal study involving 7 surveys was carried out between June 1995 and March 1997 in Diatar, Guia, Donaye and Niandane. The prevalence and intensity of infection remained low throughout the survey (< 55% and < 12 eggs/10 mL urine), and there were no systematic differences in the prevalence or intensity of infection between men and women. Before treatment, infections were highly aggregated in individuals and were concentrated in children (aged < 15 years) with 85% of the potential contamination; no individual aged > 24 years produced > 50 eggs/10 mL urine. Using WHO guidelines mass treatment was given to all Diatar and Guia villagers in December 1995, whereas in Donaye and Niandane only individuals positive for eggs were treated. Six weeks post-treatment cure rates in all villages were > 80%, with marked declines in levels of infection (< 20% and < 4.5 eggs/10 mL). By March 1997 infection levels in Donaye and Niandane had returned to pre-treatment levels, whereas in the 2 mass-treated villages (Diatar and Guia) infection levels were still markedly reduced compared to pre-treatment levels. Rates of conversion were very low between all surveys; however, there was an apparent high level of reversion (> 20%), due to the alternation of individuals apparently positive and negative between surveys. Water and infected snails were present from June to March. Therefore, owing to the high aggregation of infections in children, the low overall infection levels and the transmission period, it is suggested that in this area the best treatment schedule would be selective treatment of school-aged children in March/April, probably on an annual basis.

Efficacy of praziquantel against Schistosoma mansoni in northern Senegal.

Two treatments with praziquantel (PZQ) 40 mg/kg, 40 d apart, were given to individuals in a recently established (< 6 years) Schistosoma mansoni focus in the Senegal River Basin (SRB). Efficacy of treatment was evaluated 4 weeks after each treatment. Among 130 individuals who provided stool samples on days 0, 118 and 153 and were treated on days 85 and 125, 113 (87%) were infected with S. mansoni before treatment. The overall geometric mean faecal egg count of the infected individuals was 478 eggs/g. Four weeks after the first treatment (day 118), the overall cure rate was only 42.5% and the overall reduction in intensity of infection was 70.7%. However, 4 weeks after the second treatment (day 153), the overall cure rate rose to 76.1% and the overall reduction in intensity was 88.1%. The greatest increase in cure rate between the 2 treatments was in those individuals who were initially the most heavily infected (> 1000 eggs/g). There was no apparent difference in cure rate between younger (< 20 years) and older individuals (> 20 years). No evidence for the existence of a PZQ tolerant strain of S. mansoni was found. Two treatments of PZQ 40 mg/kg, 40 d apart, were sufficient to give an adequate cure rate and high reductions in the intensity of infection. As there was insufficient time for reinfection between treatment and follow-up to result in egg production, the low cure rate observed after one treatment was probably the result of a combination of high infection intensity and the maturation of pre-existing prepatents S. mansoni infections.

Malaria co-infection in children influences antibody response to schistosome antigens and inflammatory markers associated with morbidity.

The epidemiological coexistence of schistosomiasis and malaria is frequently observed in developing countries. Co-infection with malaria in children could influence the development of acquired immunity associated with the resistance or the pathology of schistosomiasis. In the present study, performed during May to June 1996 in Senegal, the humoral immune response to Schistosoma haematobium 28 kDa glutathione S-transferase (Sh28GST) vaccinal antigen and to soluble egg antigens (SEA) has been evaluated in individuals infected by S. haematobium. Specific immunoglobulin G3 (IgG3) and IgE responses were significantly higher in co-infected children with Plasmodium falciparum compared with children infected with S. haematobium only. In addition, circulating levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble tumor necrosis factor receptor II (sTNF-RII), 3 parameters associated with schistosomiasis morbidity, were significantly increased in co-infected children. Taken together, this study indicated that malaria co-infection can both influence the acquired specific immune response to schistosome antigens and unbalance the regulation of inflammatory factors closely involved in schistosomiasis pathology.

Alterations in tumorigenicity of embryonal carcinoma cells by IGF-I triple-helix induced changes in immunogenicity and apoptosis.

IGF-I antisense gene therapy has been applied successfully to animal models of glioma, hepatoma and teratocarcinoma. The antisense strategy has shown that tumor cells transfected with vectors encoding IGF-I antisense RNA lose tumorigenicity, become immunogenic and are associated with tumor specific immune response involving CD8+ lymphocytes. An IGF-I triple helix approach to gene therapy for glioma was recently described. The approach we have taken is to establish parameters of change using the IGF-I triple helix strategy. PCC-3 embryonal carcinoma cells derived from murine teratocarcinoma which express IGF-I were used as a model. The cells were transfected with vector which encodes an oligoribonucleotide that forms RNA-IGF-I DNA triple-helix structure. The triple-helix stops the production of IGF-I. Cells transfected in this manner underwent changes in phenotype and an increase in MHC-I and B-7 cell surface molecules. They also showed enhancement in the production of apoptotic cells (60-70%). The "triple helix" transfected cells lost the ability to induce tumor when injected subcutaneously in syngeneic 129 Sv mice. When co-transfected in vitro with expression vectors encoding both MHC-I and B-7 cDNA in antisense orientation, the "triple-helix" transfected cells were down-regulated in expression of MHC-I and B-7 and the number of apoptotic cells was significantly decreased. Injection of the doubly co-transfected cells into 129 Sv mice was associated with induction of teratocarcinoma. Comparison between antisense and triple-helix transfected cells strategies showed similar immunogenic and apoptotic changes. The findings suggest that triple-helix technology may offer a new clinical approach to treatement of tumors expressing IGF-I.