Mother’s education and offspring asthma risk in 10 European cohort studies

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3–8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother’s age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence’s of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.     

Mental distress and sexual harassment in Italian university students

Only a few studies have analyzed the association between sexual harassment (SH) and mental health controlling for other types of violence. The aim of this study was to describe SH among male and female university students and analyze the association between harassment and mental distress controlling for sexual violence. An observational survey was conducted at Trieste University (Italy). Students answered an anonymous questionnaire about harassment that included three domains—sexual harassment, gender harassment, cyber harassment—and three psychological health indicators. The global harassment index was computed, with three levels: 0, no harassment; level 1, harassment in at least one of the three domains; and level 2, harassment in two or three domains. The symptoms of mental distress were measured by the 12-item General Health Questionnaire (GHQ) for depressive symptoms; a question about panic symptoms; and a question about general health. The sample included 759 students (412 women; 18 to 29 years old). After adjustment for age, birth country, couple relationship, employment status, mother’s education, and previous sexual violence, the risk of mental distress was increased with harassment exposure. Men were affected in perceived health and depressive symptoms (GHQ score ≥ 6); women were affected in panic symptoms. Harassment has a strong negative impact on the mental health of victims; in some cases, men may be more affected than women. Clinicians should be aware of the negative impact of SH also on men.

     

Preliminary studies of new proteasome inhibitors in the tumor targeting approach: synthesis and in vitro cytotoxicity

The proteasome is a multicatalytic protease that plays a critical role in the cell. The control of proteasomes could, thus, provide a weapon for the treatment of cancer. Therefore, we have synthesized six new peptide aldehyde inhibitors of the proteasome linked to the N-(2-diethylaminoethyl)benzamide (BZA-CO) structure, in order to target the cytotoxic activity to malignant melanoma cells. Biological studies demonstrated the influence of length and composition of the amino acid chain on the cytotoxicity of our compounds. Among them, compound 19 presents the highest cytotoxicity (IC50 = 0.64 +/- 0.07 micromol): this cytotoxicity was maintained in the presence of BZA-CO but decreased 8-fold compared to the control MG132. Fluorescence activated cell sorter (FACS) and cytotoxic activity analysis demonstrated the selectivity of compound 19 for melanoma cells. Finally, western blottings of ubiquitinated proteins in IPC227F cells as well as proteasome assays confirmed that the cytotoxicity was linked to an inhibition of the proteasome activity.     

The integration of information across lexical and sublexical processes in spelling

We report on a brain-injured subject, LAT, who made phonologically plausible errors in word spelling (e.g., "bouquet" spelled as BOUKET). Although many of his errors are phonologically plausible they contained low-frequency (yet lexically correct) spellings (/ei/ spelled as ET in BOUK ET). Because these errors are phonologically plausible they do not appear to have been generated by the lexical process, yet because they contain low probability, lexically correct elements they do not appear to be have been generated by the sublexical process. We present analyses that specifically support the conclusion that many of LAT's phonologically plausible responses to word stimuli consist of the integrated output of elements generated by both the lexical and sublexical processes. This evidence constitutes strong support for the notion that lexical and sublexical processes share information during the course of spelling a familiar word.     

Effect of tomato product consumption on the plasma status of antioxidant microconstituents and on the plasma total antioxidant capacity in healthy subjects

OBJECTIVES: to identify the plasma antioxidant microconstituents mainly affected by tomato product consumption, to check whether tomato product consumption can affect antioxidant status, and to identify tomato-product antioxidant-microconstituents mainly involved in the effect of these products on oxidative stress. DESIGN: Medium-term dietary supplementation study. SETTING: Human Nutrition Laboratory, Clermont-Ferrand, France. SUBJECTS: Twenty healthy young (20 < years < 40), non obese (18 < BMI (kg/m2) < 25), females were recruited by advertisement. All of them completed the study. INTERVENTION: The usual diet of the subjects was supplemented for three weeks with 96 g/day tomato puree. The volunteers then avoided tomato-product-rich foods for a subsequent three-week period. Measures of Outcome: Fasting blood samples were collected the day before supplementation, the day after the supplementation period, and the day after the depletion period. The status of several antioxidant microconstituents (plasma microconstituent concentrations), and the antioxidant status (plasma total antioxidant capacity) were assessed. RESULTS: Supplementation with tomato puree significantly increased plasma lycopene, beta-carotene and lutein. Conversely it did not significantly affect plasma vitamin C and E, plasma antioxidant trace metals (Cu, Zn and Se), and plasma total antioxidant capacity. Avoidance of tomato-product-rich foods for three weeks significantly (p < 0.05) decreased plasma lycopene, beta-carotene, lutein and vitamin C, as well as plasma total antioxidant capacity. Plasma total antioxidant capacity, as measured by chemiluminescence, was positively related (p < 0.05) to the status of lycopene, vitamin C and beta-carotene. CONCLUSIONS: Tomato product consumption can affect not only the lycopene status, but also that of other antioxidant microconstituents (beta-carotene and lutein). Lycopene, but also beta-carotene, are apparently the main tomato microconstituents responsible for the effect of tomato products on antioxidant status.     

Evaluation of radiolabeled (hetero)aromatic analogues of N-(2-diethylaminoethyl)-4-iodobenzamide for imaging and targeted radionuclide therapy of melanoma

Targeted radionuclide therapy using radioiodinated compounds with a specific affinity for melanoma tissue is a promising treatment for disseminated melanoma, but the candidate with the ideal kinetic profile remains to be discovered. Targeted radionuclide therapy concentrates the effects on tumor cells, thereby increasing the efficacy and decreasing the morbidity of radiotherapy. In this context, analogues of N-(2-diethylaminoethyl)-4-iodobenzamide (BZA) are of interest. Various (hetero)aromatic analogues 5 of BZA were synthesized and radioiodinated with (125)I, and their biodistribution in melanoma-bearing mice was studied after i.v. administration. Most [ (125)I] 5-labeled compounds appeared to bind specifically and with moderate-to-high affinity to melanoma tumor. Two compounds, 5h and 5k, stood out with high specific and long-lasting uptake in the tumor, with a 7- and 16-fold higher value than BZA at 72 h, respectively, and kinetic profiles that makes them promising agents for internal targeted radionuclide therapy of melanoma.     

Zoledronic Acid and renal toxicity: data from French adverse effect reporting database

BACKGROUND: Zoledronic acid-associated renal impairment leading to renal failure has been recently reported in a cohort of US patients. However, the presence of such toxicity in other populations has not yet been determined. OBJECTIVE: To analyze French cases of zoledronic acid-associated nephrotoxicity. METHODS: We evaluated available cases with acute deterioration of renal function associated with zoledronic acid therapy drawn from the French Adverse Event Reporting System database until July 1, 2004. RESULTS: We identified 4 men and 3 women between the ages of 52 and 70 years, with multiple myeloma or different types of metastatic cancer, who had experienced renal impairment during zoledronic acid therapy. Four patients developed de novo acute renal failure, while the other 3 patients experienced acute deterioration of preexisting chronic renal failure. Renal failure occurred after various durations of zoledronic acid therapy (1-120 days). Three patients completely recovered and one partially recovered their previous renal function after discontinuation of zoledronic acid, but renal impairment was associated with a fatal outcome in 2 cases; the outcome of the other case was unknown. Our data confirm the previously reported risk factors for zoledronic acid-associated nephrotoxicity such as advanced cancer, multiple myeloma, preexisting renal failure, diabetes, hypertension, and concomitant use of nephrotoxic drugs. CONCLUSIONS: These cases emphasize the need for regular monitoring of renal function during zoledronic acid treatment, with particular attention to patients with preexisting impaired renal function.     

Synthesis, radiosynthesis, and biological evaluation of new proteasome inhibitors in a tumor targeting approach

Proteasome inhibition is a new strategy in cancer therapy. We synthesized three new peptide aldehyde inhibitors linked to the benzamide derivative structure to use their cytotoxic activity against malignant melanoma cells. Of these, 10 displayed the highest cytotoxicity (0.18 +/- 0.16 microM). A radiosynthesis of the iodine aldehyde was performed. Its drug biodistribution showed that some selectivity of the benzamide group toward malignant melanoma tissue was conserved.