Menopause and colorectal cancer

Post-menopausal women who have never used hormone replacement therapy have a higher risk of colon, but not rectal, cancer than do premenopausal women of the same age, socio-cultural class and dietary habits. Such risk increase seems to last about 10 years and to be restricted to lean women, a group who have lower levels of oestradiol after ovarian function ceases after menopause. © 2000 Cancer Research Campaig

Attitudes to antipsychotic drugs and their side effects: a comparison between general practitioners and the general population

BACKGROUND: Attitudes towards antipsychotic medication play an important part in the treatment for schizophrenia and related disorders. We aimed measuring general practitioners' attitudes to antipsychotic drugs and their adverse side effects and comparing these with the attitudes of the general population. METHODS: Analysis and comparison of two representative samples, one comprising 100 General Practitioners (GPs), the other 791 individuals randomly selected from the general population. The setting was the German speaking cantons of Switzerland. RESULTS: General practitioners have significantly more positive attitudes towards anti-psychotic drugs than the general public. They reject widespread prejudices about the use of anti-psychotic medication significantly more than the general population. In particular the risk of dependency was assessed as 'low' by GP's (80%), in contrast to only 18% of the general population sample. In no instance did a majority of the GPs advise not tolerating any of the 10 possible adverse effects presented in this study. This is in marked contrast to the general population sample, where a majority recommended discontinuation for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%). CONCLUSION: As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects

Outsmarted by nooptropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog.

2-[(Diphenylmethyl)sulfinyl]acetamide (modafinil) is commonly prescribed for the treatment of narcolepsy and increasing popularity and off-label use as a cognitive enhancer resulted in a reputation as an intelligence boosting ‘wonder drug’. Common alternatives available from online shops and other retail outlets include 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide (adrafinil), 2-{[bis(4- fluorophenyl)methyl]sulfinyl}acetamide (CRL-40,940), 2-{[bis(4- fluorophenyl)methyl]sulfinyl}-N-hydroxyacetamide (CRL-40,941) and N-methyl-4,4-difluoro-modafinil (modafiendz), respectively. Gas chromatography mass spectrometry (GC-MS) is a common tool used in forensic and clinical analysis but there is a potential for inducing analysis-related ambiguities. This study reports on the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL- 40,941 due to exposure to the heated GC injection port dissolved in a variety of solvents. Key degradation products common to modafinil, modafinic acid, adrafinil analysis included diphenylmethanol and 1,1,2,2-tetraphenylethane (TPE), the latter of which was verified by its synthesis and characterization by x-ray crystallography. The investigated compounds were also characterized by 1H and 13C NMR. Diphenylmethane and thiobenzophenone were also identified in some instances. TPE formation was suggested to involve the generation of a benzhydrylium ion and its reaction with the sulfoxide oxygen of the parent compound to give an oxysulfonium intermediate. Correspondingly, the fluorinated TPE analog was formed during heat-induced degradation of modafiendz, CRL-40,940 and CRL-40,941, respectively. When a mixture of modafinil (non-fluorinated) and modafiendz (fluorinated) were subjected to GC analysis, 4,4'-(2,2-diphenylethane-1,1-diyl)bis(fluorobenzene) was detected as a third cross reaction product in addition to the two expected TPE analogs. These observations served as a reminder that the seemingly straightforward implementation of GC-MS analysis can lead to challenges during routine analysis

Predicting effective diffusion coefficients in mudrocks using a fractal model and small-angle neutron scattering measurements

The determination of effective diffusion coefficients of gases or solutes in the water‐saturated pore space of mudrocks is time consuming and technically challenging. Yet reliable values of effective diffusion coefficients are important to predict migration of hydrocarbon gases in unconventional reservoirs, dissipation of (explosive) gases through clay barriers in radioactive waste repositories, mineral alteration of seals to geological CO2 storage reservoirs, and contaminant migration through aquitards. In this study, small‐angle and very small angle neutron scattering techniques have been utilized to determine a range of transport properties in mudrocks, including porosity, pore size distributions, and surface and volume fractal dimensions of pores and grains, from which diffusive transport parameters can be estimated. Using a fractal model derived from Archie's law, we calculate effective diffusion coefficients from these parameters and compare them to laboratory‐derived effective diffusion coefficients for CO2, H2, CH4, and HTO on either the same or related mudrock samples. The samples include Opalinus Shale from the underground laboratory in Mont Terri, Switzerland, Boom Clay from a core drilled in Mol, Belgium, and a marine claystone cored in Utah, USA. The predicted values were compared to laboratory diffusion measurements. The measured and modeled diffusion coefficients show good agreement, differing generally by less than factor 5. Neutron or X‐ray scattering analysis is therefore proposed as a novel method for fast, accurate estimation of effective diffusion coefficients in mudrocks, together with simultaneous measurement of multiple transport parameters including porosity, pore size distributions, and surface areas, important for (reactive) transport modeling

Does dietary calcium interact with dietary fiber against colorectal cancer? : a case-control study in Central Europe

BACKGROUND: An unfavorable trend of increasing rates of colorectal cancer has been observed across modern societies. In general, dietary factors are understood to be responsible for up to 70% of the disease’s incidence, though there are still many inconsistencies regarding the impact of specific dietary items. Among the dietary minerals, calcium intake may play a crucial role in the prevention. The purpose of this study was to assess the effect of intake of higher levels of dietary calcium on the risk of developing of colorectal cancer, and to evaluate dose dependent effect and to investigate possible effect modification. METHODS: A hospital based case–control study of 1556 patients (703 histologically confirmed colon and rectal incident cases and 853 hospital-based controls) was performed between 2000–2012 in Krakow, Poland. The 148-item semi-quantitative Food Frequency Questionnaire to assess dietary habits and level of nutrients intake was used. Data regarding possible covariates was also collected. RESULTS: After adjustment for age, gender, education, consumption of fruits, raw and cooked vegetables, fish, and alcohol, as well as for intake of fiber, vitamin C, dietary iron, lifetime recreational physical activity, BMI, smoking status, and taking mineral supplements, an increase in the consumption of calcium was associated with the decrease of colon cancer risk (OR = 0.93, 95% CI: 0.89-0.98 for every 100 mg Ca/day increase). Subjects consumed >1000 mg/day showed 46% decrease of colon cancer risk (OR = 0.54, 95% CI: 0.35-0.83). The effect of dietary calcium was modified by dietary fiber (p for interaction =0.015). Finally, consistent decrease of colon cancer risk was observed across increasing levels of dietary calcium and fiber intake. These relationships were not proved for rectal cancer. CONCLUSIONS: The study confirmed the effect of high doses of dietary calcium against the risk of colon cancer development. This relationship was observed across different levels of dietary fiber, and the beneficial effect of dietary calcium depended on the level of dietary fiber suggesting modification effect of calcium and fiber. Further efforts are needed to confirm this association, and also across higher levels of dietary fiber intake

Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a common psychiatric disease affecting about 1% of population. One major problem in the treatment is finding the right the drug for the right patients. However, pharmacogenetic results in psychiatry can seldom be replicated.</p> <p>Methods</p> <p>We selected three candidate genes associated with serotonergic neurotransmission for the study: serotonin 2A (<it>5-HT2A</it>) receptor gene, tryptophan hydroxylase 1 (<it>TPH1</it>) gene, and G-protein beta-3 subunit (<it>GNB3</it>) gene. We recruited 94 schizophrenia patients representing extremes in treatment response to typical neuroleptics: 43 were good responders and 51 were poor responders. The control group consisted of 392 healthy blood donors.</p> <p>Results</p> <p>We do, in part, replicate the association between <it>5-HT2A </it>T102C polymorphism and response to typical neuroleptics. In female patients, C/C genotype was significantly more common in non-responders than in responders [OR = 6.04 (95% Cl 1.67–21.93), p = 0.005] or in the control population [OR = 4.16 (95% CI 1.46–11.84), p = 0.005]. <it>TPH1 </it>A779C C/A genotype was inversely associated with good treatment response when compared with non-responders [OR = 0.59 (95% Cl 0.36–0.98), p = 0.030] or with the controls [OR = 0.44 (95% CI 0.23–0.86, p = 0.016], and <it>GNB3 </it>C825T C/T genotype showed a trend-like positive association among the male patients with a good response compared with non-responders [OR = 3.48 (95% Cl 0.92–13.25), p = 0.061], and a clearer association when compared with the controls [OR = 4.95 (95% CI 1.56–15.70), p = 0.004].</p> <p>Conclusion</p> <p>More findings on the consequences of functional polymorphisms for the role of serotonin in the development of brain and serotonergic neurotransmission are needed before more detailed hypotheses regarding susceptibility and outcome in schizophrenia can be formulated. The present results may highlight some of the biological mechanisms in different courses of schizophrenia between men and women.</p

Study protocol of the iMPaCT project : A longitudinal cohort study assessing psychological determinants, sexual behaviour and chlamydia (re)infections in heterosexual STI clinic visitors

Acknowledgements We are grateful to the staff at the STI clinics of Amsterdam, Kennemerland, Hollands Noorden, Twente, who are involved in the recruitment and data collection of participants, and Marlous Ratten and Klazien Visser from Soapoli-online, who are involved in the coordination of laboratory testing of the home-based sampling kits at six-month follow-up. We also thank the staff at the STI department at the National Institute for Public Health and the Environment, especially Birgit van Benthem. Funding This project is funded by the Strategic Programme (SPR) of the National Institute for Public Health and the Environment (RIVM) (project number S/113004/01/IP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Availability of data and materials The dataset (anonymised) generated during this study will be made available for interested parties on request.Peer reviewedPublisher PD

Environmental factors in early childhood are associated with multiple sclerosis: a case-control study

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with increasing incidence mainly in high-income countries. One explanation of this phenomenon may be a higher prevalence of allergic and autoimmune diseases in industrialized countries as a consequence of otherwise beneficial advances in sanitation (hygiene hypothesis). We investigated environmental factors in early childhood associated with MS.</p> <p>Methods</p> <p>A case-control study was performed of 245 MS patients and 296 population-based controls in Berlin. The study participants completed a standardized questionnaire on environmental factors in childhood and youth, including aspects of personal and community hygiene. Multivariable logistic regression analysis was performed to investigate factors in childhood and youth associated with the occurrence of MS.</p> <p>Results</p> <p>Mean age was 46 years (range, 20-80) in the MS group and 42 years (range 18-80) in the control group, of which 73.9% in the MS and 61.5% in the control group were female. The multivariable analysis showed that having at least two older siblings (OR 0.54; p = 0.05, for individuals with two older siblings compared to individuals without older siblings), attending a day-care center (OR 0.5; p = 0.004) and growing up in an urban center with more than 100, 000 inhabitants (OR 0.43; p = 0.009) were factors independently associated with a lower chance for MS.</p> <p>Conclusions</p> <p>The hygiene hypothesis may play a role in the occurrence of MS and could explain disease distribution and increasing incidence.</p