The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk

Background The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC). Methods we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk. Results and Conclusions In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.

Depression with atypical features and increase in obesity, body mass index, waist circumference, and fat mass: a prospective, population-based study.

IMPORTANCE: Depression and obesity are 2 prevalent disorders that have been repeatedly shown to be associated. However, the mechanisms and temporal sequence underlying this association are poorly understood. OBJECTIVE: To determine whether the subtypes of major depressive disorder (MDD; melancholic, atypical, combined, or unspecified) are predictive of adiposity in terms of the incidence of obesity and changes in body mass index (calculated as weight in kilograms divided by height in meters squared), waist circumference, and fat mass. DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based cohort study, CoLaus (Cohorte Lausannoise)/PsyCoLaus (Psychiatric arm of the CoLaus Study), with 5.5 years of follow-up included 3054 randomly selected residents (mean age, 49.7 years; 53.1% were women) of the city of Lausanne, Switzerland (according to the civil register), aged 35 to 66 years in 2003, who accepted the physical and psychiatric baseline and physical follow-up evaluations. EXPOSURES: Depression subtypes according to the DSM-IV. Diagnostic criteria at baseline and follow-up, as well as sociodemographic characteristics, lifestyle (alcohol and tobacco use and physical activity), and medication, were elicited using the semistructured Diagnostic Interview for Genetic Studies. MAIN OUTCOMES AND MEASURES: Changes in body mass index, waist circumference, and fat mass during the follow-up period, in percentage of the baseline value, and the incidence of obesity during the follow-up period among nonobese participants at baseline. Weight, height, waist circumference, and body fat (bioimpedance) were measured at baseline and follow-up by trained field interviewers. RESULTS: Only participants with the atypical subtype of MDD at baseline revealed a higher increase in adiposity during follow-up than participants without MDD. The associations between this MDD subtype and body mass index (β = 3.19; 95% CI, 1.50-4.88), incidence of obesity (odds ratio, 3.75; 95% CI, 1.24-11.35), waist circumference in both sexes (β = 2.44; 95% CI, 0.21-4.66), and fat mass in men (β = 16.36; 95% CI, 4.81-27.92) remained significant after adjustments for a wide range of possible cofounding. CONCLUSIONS AND RELEVANCE: The atypical subtype of MDD is a strong predictor of obesity. This emphasizes the need to identify individuals with this subtype of MDD in both clinical and research settings. Therapeutic measures to diminish the consequences of increased appetite during depressive episodes with atypical features are advocated.

Skinfold thickness and adiposity index in premature infants.

In order to assess the validity of the weight per square of length ratio as an index of adiposity during the neonatal period, 37 premature infants (gestational age, mean +/- SD, = 31.5 +/- 1.1 weeks, birthweight, mean +/- SD, = 1.448 +/- 147 g) were studied for weight, length and skinfold thickness at 5 sites (biceps, triceps, subscapular, suprailiac and quadriceps) during their stay in the Neonatal Unit of the University Hospital in Lausanne. The results show a significant correlation between the adiposity index and the sum of 5 skinfold thickness sites in premature infants. The adiposity index gives a fair estimate of the body fat mass during the postnatal growth in premature infants.

High fat diet has a prominent effect upon the course of chronic schistosomiasis mansoni in mice

This study investigated whether a long-term high-fat diet has an effect on the outcome of chronic murine schistosomiasis mansoni compared to a standard diet. Swiss Webster female mice (3 weeks old) were fed each diet for up to six months and were then infected with 50 Schistosoma mansoni cercariae. Their nutritional status was assessed by monitoring total serum cholesterol and body mass. Infected mice were examined 6-17 weeks post infection to estimate the number of eggs in faeces. Mice were euthanised the next day. Total serum cholesterol was lower in infected mice in comparison to uninfected controls (p = 0.0055). In contrast, body mass (p = 0.003), liver volume (p = 0.0405), spleen volume (p = 0.0124), lung volume (p = 0.0033) and faecal (p = 0.0064) and tissue egg density (p = 0.0002) were significantly higher for infected mice fed a high-fat diet. From these findings, it is suggested that a high-fat diet has a prominent effect on the course of chronic schistosomiasis mansoni in mice.

Frequency of Fabry disease in male and female haemodialysis patients in Spain

BACKGROUND: Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme alpha-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression. METHODS: A combined enzymatic and genetic strategy was used, measuring the activity of alpha-galactosidase A and genotyping the alpha-galactosidase A gene (GLA) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain. RESULTS: GLA alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with GLA causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients. CONCLUSIONS: Excluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy.

Does bariatric surgery improve the patient's quality of life?

Objective: The aim of this investigation was to assess the effect of malabsorptive bariatric surgery (BS) on the quality of life (QoL), applying the Nottingham Health Profile (NHP) and the bariatric analysis and reporting outcome system (BAROS). Design: A prospective cohort study was performed in 100 adult patients (> 18 years) undergoing bariatric surgery by malabsorptive technique for one year. Research methods and procedures: Patients were monitored from the beginning of the BS program until a year after the intervention, applying the NHP and the BAROS test. At baseline, the mean weight of the women was 132 ± 22 kg and the Body Mass Index (BMI) was 50.7 kg/m2. Results: The values obtained from different areas applying the NHP questionnaire showed statistical significant differences (p < 0.001) with respect to baseline values. According to the BAROS test, 48% of patients lost 25-49% of weight excess and 80.8% had resolved major comorbidities at 1 yr. According to the Moorehead-Ardelt QoL score, there were major improvements in employment and self-esteem in 89% and 87% of patients, respectively, and improvements in physical activity, sexual and social relationships. According to the total mean BAROS score, the outcome was considered “very good”. Conclusion: NHP and BAROS questionnaires appear to be useful and easily applicable tools to assess the QoL of obese patients.

Delta-9-tetrahydrocannabinol accumulation, metabolism and cell-type-specific adverse effects in aggregating brain cell cultures.

Despite the widespread use of Cannabis as recreational drug or as medicine, little is known about its toxicity. The accumulation, metabolism and toxicity of THC were analyzed 10 days after a single treatment, and after repeated exposures during 10 days. Mixed-cell aggregate cultures of fetal rat telencephalon were used as in vitro model, as well as aggregates enriched either in neurons or in glial cells. It was found that THC accumulated preferentially in neurons, and that glia-neuron interactions decreased THC accumulation. The quantification of 11-OH-THC and of THC-COOH showed that brain aggregates were capable of THC metabolism. No cell-type difference was found for the metabolite 11-OH-THC, whereas the THC-COOH content was higher in mixed-cell cultures. No cell death was found at THC concentrations of 2 microM in single treatment and of 1 microM and 2 microM in repeated treatments. Neurons, and particularly GABAergic neurons, were most sensitive to THC. Only the GABAergic marker was affected after the single treatment, whereas the GABAergic, cholinergic and astrocytic markers were decreased after the repeated treatments. JWH 015, a CB2 receptor agonist, showed effects similar to THC, whereas ACEA, a CB1 receptor agonist, had no effect. The expression of the cytokine IL-6 was upregulated 48 h after the single treatment with 5 microM of THC or JWH 015, whereas the expression of TNF-alpha remained unchanged. These results suggest that the adverse effects of THC were related either to THC accumulation or to cannabinoid receptor activation and associated with IL-6 upregulation.

Segmental body composition assessed by bioelectrical impedance analysis and DEXA in humans.

The present study assessed the relative contribution of each body segment to whole body fat-free mass (FFM) and impedance and explored the use of segmental bioelectrical impedance analysis to estimate segmental tissue composition. Multiple frequencies of whole body and segmental impedances were measured in 51 normal and overweight women. Segmental tissue composition was independently assessed by dual-energy X-ray absorptiometry. The sum of the segmental impedance values corresponded to the whole body value (100.5 +/- 1.9% at 50 kHz). The arms and legs contributed to 47.6 and 43.0%, respectively, of whole body impedance at 50 kHz, whereas they represented only 10.6 and 34.8% of total FFM, as determined by dual-energy X-ray absorptiometry. The trunk averaged 10.0% of total impedance but represented 48.2% of FFM. For each segment, there was an excellent correlation between the specific impedance index (length2/impedance) and FFM (r = 0.55, 0.62, and 0.64 for arm, trunk, and leg, respectively). The specific resistivity was in a similar range for the limbs (159 +/- 23 cm for the arm and 193 +/- 39 cm for the leg at 50 kHz) but was higher for the trunk (457 +/- 71 cm). This study shows the potential interest of segmental body composition by bioelectrical impedance analysis and provides specific segmental body composition equations for use in normal and overweight women.

Determination of chlorzoxazone and 6-hydroxychlorzoxazone in plasma by gas chromatography--mass spectrometry.

A gas chromatographic-mass spectrometric method is presented which allows the determination of chlorzoxazone and 6-hydroxychlorzoxazone after derivatization with the reagent N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamide. No interference was observed from endogenous compounds following the extraction of plasma samples from six different human subjects. The standard curves were linear over a working range of 20 to 4000 ng/ml and of 20 to 1000 ng/ml for chlorzoxazone and 6-hydroxychlorzoxazone, respectively. Recoveries ranged from 65 to 97% for the two compounds and intra- and inter-day coefficients of variation were always less than 9%. The limit of quantitation of the method was found to be 5 ng/ml for the two compounds, hence allowing its use for single low dose pharmacokinetics.

Sexueller Missbrauch bei Kindern und Jugendlichen- Aufdeckung, Untersuchung und Erstbetreuung [Sexual abuse of female children and adolescents--detection, examination and primary care].

Epidemiological studies show a prevalence of sexual abuse experience among girls from 14-33%. Although indicators of abuse are unspecific, the combination of several findings may be indicative: Somatic signs may be sexually transmitted diseases, vulvovaginal complaints. Psychosocial nonsexual indicators are abrupt behavioural changes, running away from home, eating disorders. Psychosexual signs are hypersexualisation of the language and behaviour, disturbed body image and gender identity. Indirect evidence of abuse is given not only in cases of old vaginal and anal lesions but also in situations, where deep tears of the hymen in the typical localization at the posterior part can be found. The workup and care for children in whom there is suspicion of abuse but no clear evidence asks for highly competent professionals in a multidisciplinary cooperation including pediatric gynecologists, child psychiatrists, children-protection groups and other specialists to avoid on one hand unjustified destabilisation or even destruction of familial structures but to assure on the other hand, that the child victims are treated and followed after in a short and long term comprehensive medical and psychosocial care.

A fatal overdose of cocaine associated with coingestion of marijuana, buprenorphine, and fluoxetine. Body fluid and tissue distribution of cocaine and its metabolites determined by hydrophilic interaction chromatography-mass spectrometry(HILIC-MS).

Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3-microm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below +/- 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.

Prevention of overweight and obesity: a Spanish approach

Background. Obesity is considered a major public health issue in most developed countries nowadays. This paper provides an overview of current population data available in Spain and the approach to develop preventive strategies in the country. Methods. Review of population data available is based on individually measured weight and height as well as determinants. On this basis, the approach used in the country to develop preventive strategies is discussed. Results. According to the DORICA study, the prevalence of obesity (BMI ≥30 kg m−2) is 15.5% in Spanish adults aged 25–60 years (13.2% in men and 17.5% in women). Obesity rates are higher among women aged 45 years and older, low social class, living in semi-urban places. Population estimates for the prevalence of obesity in Spanish children and young people based on the enKid study are 13.9% for the whole group. In this study, overweight and obesity is related to absence of breastfeeding, low consumption of fruit and vegetables, high consumption of cakes, buns, softdrinks and butchery products, low physical activity levels and a positive association with time spent watching TV. In 2005, the Spanish Ministry of Health jointly with the Spanish Agency for Food Safety and Nutrition launched the multifaceted NAOS strategy for nutrition, physical activity and the prevention of obesity. The important role of the family and the school setting as well as the responsibility of the Health Administration and Pediatric Care in the prevention of obesity is highlighted in the document. The need for environmental actions is recognised. The PERSEO programme, a multicomponent school-based intervention project is part of the strategy currently in place. Conclusion. Obesity is a public health issue in Spain. A national multifaceted strategy was launched to counteract the problem. Environmental and policy actions are a priority. Young children and their families are among the main target groups.

Non-invasive dry mass determination and monitoring at the single cell level with digital holographic microscopy

Digital holography microscopy (DHM) is an optical microscopy technique which allows recording non-invasively the phase shift induced by living cells with nanometric sensitivity. Here, we exploit the phase signal as an indicator of dry mass (related to the protein concentration). This parameter allows monitoring the protein production rate and its evolution during the cell cycle. ©2008 COPYRIGHT SPIE

Sulfur isotope analysis of cinnabar from Roman wall paintings by elemental analysis/isotope ratio mass spectrometry - tracking the origin of archaeological red pigments and their authenticity

The most valuable pigment of the Roman wall paintings was the red color obtained from powdered cinnabar (Minium Cinnabaris pigment), the red mercury sulfide (HgS), which was brought from mercury (Hg) deposits in the Roman Empire. To address the question of whether sulfur isotope signatures can serve as a rapid method to establish the provenance of the red pigment in Roman frescoes, we have measured the sulfur isotope composition (delta(34) S value in parts per thousand VCDT) in samples of wall painting from the Roman city Aventicum (Avenches, Vaud, Switzerland) and compared them with values from cinnabar from European mercury deposits (Almaden in Spain, Idria in Slovenia, Monte Amiata in Italy, Moschellandsberg in Germany, and Genepy in France). Our study shows that the delta(34) S values of cinnabar from the studied Roman wall paintings fall within or near to the composition of Almaden cinnabar; thus, the provenance of the raw material may be deduced. This approach may provide information on provenance and authenticity in archaeological, restoration and forensic studies of Roman and Greek frescoes. Copyright (c) 2010 John Wiley & Sons, Ltd.

Effectiveness and costs of phototest in dementia and cognitive impairment screening

BACKGROUND To assess and compare the effectiveness and costs of Phototest, Mini Mental State Examination (MMSE), and Memory Impairment Screen (MIS) to screen for dementia (DEM) and cognitive impairment (CI). METHODS A phase III study was conducted over one year in consecutive patients with suspicion of CI or DEM at four Primary Care (PC) centers. After undergoing all screening tests at the PC center, participants were extensively evaluated by researchers blinded to screening test results in a Cognitive-Behavioral Neurology Unit (CBNU). The gold standard diagnosis was established by consensus of expert neurologists. Effectiveness was assessed by the proportion of correct diagnoses (diagnostic accuracy [DA]) and by the kappa index of concordance between test results and gold standard diagnoses. Costs were based on public prices and hospital accounts. RESULTS The study included 140 subjects (48 with DEM, 37 with CI without DEM, and 55 without CI). The MIS could not be applied to 23 illiterate subjects (16.4%). For DEM, the maximum effectiveness of the MMSE was obtained with different cutoff points as a function of educational level [k = 0.31 (95% Confidence interval [95%CI], 0.19-0.43), DA = 0.60 (95%CI, 0.52-0.68)], and that of the MIS with a cutoff of 3/4 [k = 0.63 (95%CI, 0.48-0.78), DA = 0.83 (95%CI, 0.80-0.92)]. Effectiveness of the Phototest [k = 0.71 (95%CI, 0.59-0.83), DA = 0.87 (95%CI, 0.80-0.92)] was similar to that of the MIS and higher than that of the MMSE. Costs were higher with MMSE (275.9 ± 193.3€ [mean ± sd euros]) than with Phototest (208.2 ± 196.8€) or MIS (201.3 ± 193.4€), whose costs did not significantly differ. For CI, the effectiveness did not significantly differ between MIS [k = 0.59 (95%CI, 0.45-0.74), DA = 0.79 (95%CI, 0.64-0.97)] and Phototest [k = 0.58 (95%CI, 0.45-0.74), DA = 0.78 (95%CI, 0.64-0.95)] and was lowest for the MMSE [k = 0.27 (95%CI, 0.09-0.45), DA = 0.69 (95%CI, 0.56-0.84)]. Costs were higher for MMSE (393.4 ± 121.8€) than for Phototest (287.0 ± 197.4€) or MIS (300.1 ± 165.6€), whose costs did not significantly differ. CONCLUSION MMSE is not an effective instrument in our setting. For both DEM and CI, the Phototest and MIS are more effective and less costly, with no difference between them. However, MIS could not be applied to the appreciable percentage of our population who were illiterate.