How much and why does the mum matter? Mechanisms explaining the intergenerational transmission of smoking.

Offspring whose mother smokes during pregnancy have higher risk of smoking themselves. In this study, epigenetics, antisocial behaviours, and social learning were investigated as potential mechanisms of mother-to-child transmission of smoking among a population sample drawn from the Birth Cohort Study 1970. Findings on daughters showed that the direct epigenetic hypothesis was mediated by social learning mechanisms, suggesting that exposure to maternal smoking across childhood and adolescence strongly explained why the smoking habits of mother and daughter correlate. However, prenatal smoking effects on sons were only partially explained by observational learning of mother smoking habits. Our estimates provided evidence concerning the potential role also played by the child's persistent antisocial behaviours. These results were confirmed after controlling for early life circumstances and current socioeconomic conditions. Policy implications of the results are discussed.

Parents who exit and parents who enter. Family structure transitions, child psychological health, and early drinking.

This paper seeks to extend prior research by exploring whether family structure transition is associated with an increase in early alcohol consumption and whether this association is mediated by; children's socio-emotional problems, providing information on whether the effects of the transition; differ according to the number of changes, the family's initial status, or the time of exposure. The; data have been drawn from the UK Millennium Cohort Study to explore associations framed with; a life-course approach. Our findings suggest that types of family transitions (such as distinguishing; parental exits from and parental entrances to the family) are more important than the number of; family changes during childhood. The results show that moving from a two-parent household to a single-parent household directly increased the probability of being a frequent alcohol consumer among early adolescent boys, whereas the indirect effect on girls was found via socio-emotional difficulties. Our findings also show an increase in socio-emotional and behavioural difficulties in boys due to the entrance of a step-parent only if the transition occurred in the earliest childhood. Indeed, a sensitivity analysis of the time to which the children were exposed to the transition to a new family structure showed stronger effects for those who experienced a family structure change in the early life course, consistent with the cumulative disadvantage process.

Pre-pregnancy body mass index, gestational weight gain and adverse birth outcomes: some evidence from Italy.

BACKGROUND: Overweight and obese women present an increased risk of poor maternal and child health outcomes. The aim of this paper is to analyze the joint effects of pre-pregnancy body mass index and inadequate gestational weight gain on birth weight and gestational age in an Italian sample of pregnant women. METHODS: Data were obtained from a sample of about 2,000 pregnant women at the University Teaching Hospital of Perugia University (Italy) in 2013. We used the revised classification proposed by Institute of Medicine to identify gestational weight gains considered as appropriate. Logistic regression models were used to estimate the adjusted odds-ratios of women belonging to any BMI class different from normal (used as the reference category) and of women who increased their weight by an amount smaller or greater than normal, controlling for a large set of observable confounders. RESULTS: Higher probability of low birth weight was associated with both obesity (OR = 1.9124, s.e. = 0.526) and less than normal weight gains (OR = 2.3614, s.e. = 0.388). The probability of fetal macrosomia was found to be positively associated with more than normal weight increases (OR = 2.6232, s.e. = 0.465). Pre-term deliveries were associated with less than normal gestational weight gains (OR 1.7338, s.e. = 0.320). CONCLUSION: Overweight and obesity represent a big issue for public health. In particular, weight management during pregnancy and pre-pregnancy could determine negative health outcomes in newborns. In our study we found that inadequate weight variations during pregnancy, according to the Classification of the Institute of Medicine, negatively influence health conditions at birth. Stronger initiatives, especially in terms of midwifery, nurse training and informative policies should be adopted by policy makers.

Health and income inequalities in Europe: What is the role of circumstances?

Equality of opportunity theories distinguish between inequalities due to individual effort and those due to external circumstances. Recent research has shown that half of the variability in income of World population was determined by country of birth and income distribution. Since health and income are generally strictly related, the aim of this paper is to estimate how much variability in income and health is determined by external circumstances. We use data from the Survey of Health, Ageing and Retirement (SHARE) and the English Longitudinal Survey on Ageing (ELSA), two comparable multidisciplinary surveys that provide micro-level data on health and financial resources among the elderly for a large number of European countries. Our baseline estimation shows that about 20% of the variability in income is explained by current country-specific circumstances, while health outcomes range from 12% using BMI to 19% using self-rated health. By including early-life circumstances, the explained variability increases almost 20 percentage points for income and for self-rated health but less for other health outcomes. Finally, by controlling for endogeneity issues linked with effort, our estimates indicate that circumstances better explain variability in health outcomes. Results are robust to some tests, and the implications of these findings are discussed.

MDM4/HIPK2/p53 cytoplasmic assembly uncovers coordinated repression of molecules with anti-apoptotic activity during early DNA damage response.

The p53 inhibitor, MDM4 (MDMX) is a cytoplasmic protein with p53-activating function under DNA damage conditions. Particularly, MDM4 promotes phosphorylation of p53 at Ser46, a modification that precedes different p53 activities. We investigated the mechanism by which MDM4 promotes this p53 modification and its consequences in untransformed mammary epithelial cells and tissues. In response to severe DNA damage, MDM4 stimulates p53Ser46(P) by binding and stabilizing serine-threonine kinase HIPK2. Under these conditions, the p53-inhibitory complex, MDM4/MDM2, dissociates and this allows MDM4 to promote p53/HIPK2 functional interaction. Comparative proteomic analysis of DNA damage-treated cells versus -untreated cells evidenced a diffuse downregulation of proteins with anti-apoptotic activity, some of which were targets of p53Ser46(P)/HIPK2 repressive activity. Importantly, MDM4 depletion abolishes the downregulation of these proteins indicating the requirement of MDM4 to promote p53-mediated transcriptional repression. Consistently, MDM4-mediated HIPK2/p53 activation precedes HIPK2/p53 nuclear translocation and activity. Noteworthy, repression of these proteins was evident also in mammary glands of mice subjected to γ-irradiation and was significantly enhanced in transgenic mice overexpressing MDM4. This study evidences the flexibility of MDM2/MDM4 heterodimer, which allows the development of a positive activity of cytoplasmic MDM4 towards p53-mediated transcriptional function. Noteworthy, this activity uncovers coordinated repression of molecules with shared anti-apoptotic function which precedes active cell apoptosis and that are frequently overexpressed and/or markers of tumour phenotype in human cancer.

Antiulcerogenic Activity and Toxicity of Bauhinia holophylla Hydroalcoholic Extract.

Several species of Bauhinia are used in traditional medicine for the treatment of gastrointestinal diseases, diabetes, and inflammation, among other conditions. The aim of this study was to investigate the antiulcer effect of a hydroalcoholic extract from the leaves of B. holophylla. The chemical profile of the extract was determined by HPLC-PAD-ESI-IT-MS. A dose-effect relation was constructed using the ethanol-induced gastric ulcer model in male Wistar rats. Histological analyses and studies of antioxidant and anti-inflammatory activities were performed in stomach samples. The involvement of SH compounds, NO, K(+) ATP channels, and α 2-adrenergic receptors in the gastroprotective effect was evaluated. A toxicity study was performed with a single oral dose of 5000 mg/kg. The extract was composed mainly of cyanoglucoside and flavonol-O-glycosides derivatives of quercetin and myricetin. SH compounds, NO release, K(+) ATP channel activation, and presynaptic α 2-adrenergic receptor stimulation each proved to be involved in the antiulcer effect. The levels of GSH and activity of GR and GPx were increased, and the levels of TNF-α, IL-6 and IL-10 were modulated. There was an antidiarrheal effect and there were no signs of toxicity. B. holophylla presents antiulcer activity mainly by decreasing oxidative stress and attenuating the inflammatory response, without inducing side effects.

Food prices and overweight patterns in Italy.

In this paper, we examine the role of relative food prices in determining the recent increase in body weight in Italy. Cross-price elasticities of unhealthy and healthy foods estimated by a demand system provide a consistent framework to evaluate substitution effects, when a close association is assumed between unhealthy (healthy) foods and more (less) energy-dense foods. We used a dataset constructed from a series of cross-sections of the Italian Household Budget Survey (1997-2005) to obtain the variables of the demand system, which accounts for regional price variability. The relative increase in healthy food prices was found to produce nontrivial elasticities of substitution towards higher relative consumption of unhealthy foods, with effects on weight outcomes. In addition, these changes were unevenly distributed among individuals and were particularly significant for those who were poorer and had less education.

Accuracy of GFR predictive equations in renal transplantation: validation of a new turbidimetric cystatin C assay on Architect c8000.

OBJECTIVES: To evaluate the Sentinel-PETIA cystatin C on Architect c8000 analyzer. DESIGN AND METHODS: We assessed analytical performances and clinical relevance by comparison with a reference isotopic method in kidney transplant recipients. RESULTS: This assay exhibited reliable precision and was close to the non standardized Siemens-PENIA method. All tested equations allowed reliable assessment of GFR. CONCLUSIONS: Cystatin C improved GFR determination at the critical level of 60 mL/min/1.73 m². New formulas might be necessary after IFCC standardization.

[Consequences for clinical biochemists of the modifications of the creatinine-based evaluation of glomerular filtration rate between 2005 and 2008]. / Evolution des modalités d'évaluation de la fonction rénale basée sur la créatinine entre 2005 et 2008: conséquences pour les biologistes.

Since 2005, international guidelines propose a stadification for chronic renal failure based on the glomerular filtration rate (GFR) value. The performance of the creatinine-based equations allowing the estimation of GFR and the bias of the creatinine measurements is, more than ever, a crucial issue. The consequences for the clinical biologists are of importance. First, the Cockcroft-Gault formula must be replaced by the four variable-MDRD equation. Second, the biologists must chose from the "175" and the "186" versions of the MDRD equation. The first one fits the creatinine methods which are traceable to the reference method (liquid or gas chromatography coupled to mass spectrometry). The second equation must be used for creatinine methods, which are not traceable to the reference method. Today, only some enzymatic methods can prove that they are traceable to the reference method. For the colorimetric methods, future is inclear.

[Cystatin C: current step and future prospects]. / Cystatine C: point d'étape et perspectives.

Cystatin C is a low molecular weight-protein, which may replace creatinine for the evaluation of renal function, particularly in the clinical settings where the relationship between creatinine production and muscular mass impairs the clinical performance of creatinine. This paper intends to summarize the current knowledge about the physiology of cystatin C and about its use as a renal marker, alone or within formulas developed to estimate the glomerular filtration rate. Moreover, this paper reviews the recent data about potential other applications of cystatin C, especially in cardiology, in oncology and in clinical pharmacology.

Symmetry and binding in visuo-spatial working memory.

Three experiments study the impact of symmetry on a sequential block tapping immediate memory task in human subjects. Experiment 1 shows an advantage from vertical symmetry over non-symmetrical sequences, while finding no effect of horizontal or diagonal symmetry. Experiment 2 tests the possible role of verbal labeling by means of a secondary task that prevents this by articulatory suppression. No evidence of verbalization was observed. A third study examines the effects of a concurrent executive load, finding an overall impairment, that did not differ between symmetrical and asymmetric patterns, suggesting that the effect of symmetry reflects automatic rather than executive processes. Implications for the episodic buffer component of working memory are discussed.

Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women.

OBJECTIVE: We assessed the relationships between four circulating acute phase proteins and the circulating and adipose tissue levels of three adipocytokines. SUBJECTS: In all, 15 nondiabetic obese women with a body mass index (BMI) above 32 kg/m(2) were investigated. METHOD: Circulating concentrations of C-reactive protein (CRP), alpha 1 acid glycoprotein (AAG), fibrinogen, alpha 1 antitrypsin and both circulating and adipose tissue levels of interleukin (IL)-6, tumor necrosis factor (TNF)alpha and leptin were measured by either nephelometry or enzyme-linked immunosorbent assay. RESULTS: We found a strong positive correlation between both circulating and adipose tissue levels of IL-6, TNFalpha and leptin and serum CRP levels. All these adipose tissue adipocytokines were also positively correlated with serum AAG levels. These correlations disappeared when adjusted for fat mass, suggesting that the relationship observed was dependent on fat amount. CONCLUSION: Our results indicate a strong relationship between adipocytokines and inflammatory markers, and suggest that cytokines secreted by adipose tissue in obese subjects could play a role in increased inflammatory proteins secretion by the liver.

Interpretation of circulating C-reactive protein levels in adults: body mass index and gender are a must.

OBJECTIVE: The recently demonstrated association between C-reactive protein (CRP) level and body mass index (BMI) raised the question of the link between CRP and the degree of obesity. In the present study, we measured CRP in a healthy population with a wide range of BMI in order to appreciate the influence of overweight in the interpretation of CRP results in clinical use. METHOD: Blood donors, aged from 19 to 65 years, were included in the study. According to BMI, subjects were classified into 3 groups: A (BMI<25 kg/m(2), n=611); B (25-30, n=147); C (> 30, n=34). RESULTS: CRP values were different among women and men. CRP progressively increased with BMI in women. These results clearly showed that average level of CRP was quite different according to BMI and gender of the subjects and generated different normal ranges of CRP expressed in mg/L (median, 75(th) percentile): Group A: women: 0.44, 0.93; men: 0.40, 0.79, Group B: women: 1.28, 1.84; men: 0.84, 2.17, Group C: women: 3.61, 7.21; men: 1.16, 3.08. CONCLUSION: Our results suggest that for an inflammatory disease diagnosis, a CRP concentration of 5 mg/L is normal for obese women but is five times the 75(th) percentile for normal people.

Towards the use of baculovirus as a gene therapy vector.

The use of baculovirus vectors for gene expression in mammalian cells is in continuous expansion. These vectors do not replicate in mammalian cells, do not cause a cytopathic effect upon infection and are able to carry large DNA inserts. Baculovirus vectors have been shown to transduce various cell types in vitro and in vivo with significant efficiency leading to stable gene expression. This review focuses on recent developments with baculovirus that highlight its potential usefor new gene therapy strategies.

In vivo gene transfer in mouse skeletal muscle mediated by baculovirus vectors.

Baculovirus vectors are efficient tools for gene transfer into mammalian cells in vitro. However, in vivo gene delivery by systemic administration is hindered by the vector inactivation mediated by the complement system. To characterize further the gene transfer efficacy of baculovirus we examined the vector transduction efficiency in skeletal muscle. Vectors expressing vesicular stomatitis virus glycoprotein (VSV-G) in the viral envelope were generated by inserting the VSV-G coding sequence downstream of the polyhedrin promoter. Two viruses were constructed to carry either the Escherichia coli beta-galactosidase (beta-Gal) gene or the mouse erythropoietin (EPO) cDNA cloned downstream of the cytomegalovirus immediate-early promoter and enhancer. The greater gene transduction efficiency of the Bac-G-betaGal vector was confirmed by comparing the beta-Gal expression level in a variety of human and mouse cell lines with that obtained on infection with Bac-betaGal, a vector that lacks VSV-G. Similarly, a 5- to 10-fold increase in beta-Gal expression between Bac-G-betaGal and Bac-betaGal was observed when mouse myoblasts and myotubes were infected. The same increase in beta-Gal expression was detected on injection of the Bac-G-betaGal vector in the quadriceps of BALB/c and C57BL/6 mice. In contrast, a 2-fold difference in transduction was observed between these two vectors in DBA/2J mouse strain. Last, expression of EPO cDNA was detected for at least 178 days in DBA/2J mice on Bac-G-EPO injection into the quadriceps whereas EPO expression declined to normal values by 35 days postinfection in BALB/c and C57BL/6 mice. Thus, these results indicate that baculovirus may be considered a useful vector for gene transfer in mouse skeletal muscle and that persistence of expression may depend on the mouse strain used.

Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study.

BACKGROUND: Liver biopsy is thought mandatory for management of patients with hepatitis C virus (HCV) infection, especially for staging fibrosis. We aimed, in our prospective study, to assess the predictive value of a combination of basic serum biochemical markers for diagnosis of clinically significant fibrosis (including early stages). METHODS: We assessed liver-biopsy patients with detectable HCV by PCR, for eligibility, and took a blood sample on the day of the procedure. The analysis was done in a first-year period for 205 patients and then tested in a second period on 134 patients. We devised a fibrosis index that included the most informative markers (combined with age and sex) for the first-year group. 11 serum markers were assessed as well as fibrosis stage: F0=no fibrosis and F1=portal fibrosis; and for clinically significant fibrosis, F2=few septa, F3=many septa, and F4=cirrhosis. Statistical analysis was by logistic regression, neural connection, and receiver-operating characteristic (ROC) curves. FINDINGS: First-year and second-year patient-group characteristics and biochemical markers did not differ. The overall frequency of clinically significant fibrosis was 40% (138 patients). The most informative markers were: alpha2 macroglobulin, alpha2 globulin (or haptoglobin), gamma globulin, apolipoprotein A1, gamma glutamyltranspeptidase, and total bilirubin. The areas (SD) under the ROC curves for the first-year (0.836 [0.430]) and second-year groups (0.870 [0.340]) did not differ (p=0.44). With the best index, a high negative predictive value (100% certainty of absence of F2, F3, or F4) was obtained for scores ranging from zero to 0.10 (12% [41] of all patients), and high positive predictive value (>90% certainty of presence of F2, F3, or F4) for scores ranging from 0.60 to 1.00 (34% [115] of all patients). INTERPRETATION: A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection.

Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance.

High plasminogen activator inhibitor 1 (PAI-1) levels are associated with an increased cardiovascular risk of atherothrombosis. Furthermore, increased plasma PAI-1 levels are associated with dyslipidemia, hyperinsulinemia and hypertension. This association between PAI-1 and metabolic components of the Metabolic Syndrome could explain the predisposition of insulin resistant patients to atherothrombosis. Recent studies have suggested that visceral adipose tissue might be the link between elevated plasma PAI-1 and insulin resistance in the Metabolic Syndrome. Indeed, visceral adipose tissue was proposed as a potentially important source of PAI-1 in humans. However, in light of recent studies, visceral adipose tissue appears to be involved in the increase of plasma PAI-1 via the metabolic disorders usually associated with central obesity, rather than directly. High plasma PAI-1 levels are undoubtedly related to insulin resistance, and the mechanisms which could explain such an increase in the Metabolic Syndrome appear to be multi-factorial and remain to be elucidated. These mechanisms may involve several metabolic disorders such as hyperinsulinemia, dyslipidemia, impaired glucose tolerance and hypertension, which would favor PAI-1 synthesis and release from different cell types.

Early steps of replication of moloney murine leukemia virus in resting lymphocytes.

We explored the role of cell type in the early steps of replication of Moloney murine leukemia virus (Mo-MLV) by comparing viral entry and reverse transcription in physiologically quiescent peripheral blood B and T lymphocytes. Virus entry was identical in both cell types. In contrast to previous results, full-length viral DNA was synthesized in resting B lymphocytes, but in agreement with earlier reports, reverse transcription was abortive in resting T lymphocytes. The addition of exogenous nucleosides in the culture medium of resting T lymphocytes allowed reverse transcription to proceed in these cells, without inducing cell cycling. These data suggest that the difference in the ability of quiescent T and B lymphocytes to sustain reverse transcription of Mo-MLV can be explained by a difference in the dNTP pool sizes of these two populations of quiescent cells.