Whole animal experiments should be more like human randomized controlled trials

Beverly S. Muhlhausler, Frank H. Bloomfield, Matthew W. Gillma

The Association among Literacy, Numeracy, HIV Knowledge and Health-Seeking Behavior: A Population-Based Survey of Women in Rural Mozambique

BACKGROUND: Limited literacy skills are common in the United States (US) and are related to lower HIV knowledge and worse health behaviors and outcomes. The extent of these associations is unknown in countries like Mozambique, where no rigorously validated literacy and numeracy measures exist. METHODS: A validated measure of literacy and numeracy, the Wide Range Achievement Test, version 3 (WRAT-3) was translated into Portuguese, adapted for a Mozambican context, and administered to a cross-section of female heads-of-household during a provincially representative survey conducted from August 8 to September 25, 2010. Construct validity of each subscale was examined by testing associations with education, income, and possession of socioeconomic assets, stratified by Portuguese speaking ability. Multivariable regression models estimated the association among literacy/numeracy and HIV knowledge, self-reported HIV testing, and utilization of prenatal care. RESULTS: Data from 3,557 women were analyzed; 1,110 (37.9%) reported speaking Portuguese. Respondents' mean age was 31.2; 44.6% lacked formal education, and 34.3% reported no income. Illiteracy was common (50.4% of Portuguese speakers, 93.7% of non-Portuguese speakers) and the mean numeracy score (10.4) corresponded to US kindergarten-level skills. Literacy or numeracy was associated (p<0.01) with education, income, age, and other socioeconomic assets. Literacy and numeracy skills were associated with HIV knowledge in adjusted models, but not with HIV testing or receipt of clinic-based prenatal care. CONCLUSION: The adapted literacy and numeracy subscales are valid for use with rural Mozambican women. Limited literacy and numeracy skills were common and associated with lower HIV knowledge. Further study is needed to determine the extent to which addressing literacy/numeracy will lead to improved health outcomes

Prediagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors

BACKGROUND: Recent findings suggest that exposure to organochlorine (OC) compounds, chlordanes and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) in particular, may increase the risk of developing testicular germ cell tumors (TGCTs). OBJECTIVE: To further investigate this question, we conducted a nested case-control study of TGCTs within the Norwegian Janus Serum Bank cohort. METHODS: The study was conducted among individuals with serum collected between 1972 and 1978. TGCT cases diagnosed through 1999 (n = 49; 27-62 years of age at diagnosis) were identified through linkage to the Norwegian Cancer Registry. Controls (n =51) were matched to cases on region, blood draw year, and age at blood draw. Measurements of 11 OC insecticide compounds and 34 polychlorinated biphenyl (PCB) congeners were performed using gas chromatography/high-resolution mass spectrometry. Case-control comparisons of lipid-adjusted analyte concentrations were performed using the Wilcoxon signed-rank test. Odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles of analyte concentration were calculated using conditional logistic regression. RESULTS: TGCT cases had elevated concentrations of p,p′-DDE (tertile 3 vs. tertile 1 OR (ORT3) 2.2; 95% CI, 0.7-6.5; p Wilcoxon = 0.07), oxychlordane (ORT3 3.2; 95% CI, 0.6-16.8; pWilcoxon = 0.05), trans-nonachlor (ORT3 2.6; 95% CI, 0.7-8.9; pWilcoxon = 0.07), and total chlordanes (OR T3 2.0; 95% CI, 0.6-7.2; pWilcoxon = 0.048) compared with controls, although no ORs were statistically significant. Seminoma cases had significantly lower concentrations of PCB congeners 44, 49, and 52 and significantly higher concentrations of PCBs 99, 138, 153, 167, 183, and 195. CONCLUSIONS: Our study provides additional but qualified evidence supporting an association between exposures to p,p′-DDE and chlordane compounds, and possibly some PCB congeners, and TGCT risk

Increased insolation threshold for runaway greenhouse processes on Earth like planets

Because the solar luminosity increases over geological timescales, Earth climate is expected to warm, increasing water evaporation which, in turn, enhances the atmospheric greenhouse effect. Above a certain critical insolation, this destabilizing greenhouse feedback can "runaway" until all the oceans are evaporated. Through increases in stratospheric humidity, warming may also cause oceans to escape to space before the runaway greenhouse occurs. The critical insolation thresholds for these processes, however, remain uncertain because they have so far been evaluated with unidimensional models that cannot account for the dynamical and cloud feedback effects that are key stabilizing features of Earth's climate. Here we use a 3D global climate model to show that the threshold for the runaway greenhouse is about 375 W/m$^2$, significantly higher than previously thought. Our model is specifically developed to quantify the climate response of Earth-like planets to increased insolation in hot and extremely moist atmospheres. In contrast with previous studies, we find that clouds have a destabilizing feedback on the long term warming. However, subsident, unsaturated regions created by the Hadley circulation have a stabilizing effect that is strong enough to defer the runaway greenhouse limit to higher insolation than inferred from 1D models. Furthermore, because of wavelength-dependent radiative effects, the stratosphere remains cold and dry enough to hamper atmospheric water escape, even at large fluxes. This has strong implications for Venus early water history and extends the size of the habitable zone around other stars.Comment: Published in Nature. Online publication date: December 12, 2013. Accepted version before journal editing and with Supplementary Informatio

Early exposure to secondhand tobacco smoke and the development of allergic diseases in 4 year old children in Malmö, Sweden

<p>Abstract</p> <p>Background</p> <p>Earlier studies have shown an association between secondhand tobacco smoke and allergy development in children. Furthermore, there is an increased risk of developing an allergy if the parents have an allergy. However, there are only few studies investigating the potential synergistic effect of secondhand tobacco smoke and allergic heredity on the development of an allergy.</p> <p>Methods</p> <p>The study was population-based cross-sectional with retrospective information on presence of secondhand tobacco smoke during early life. The study population consisted of children who visited the Child Health Care (CHC) centres in Malmö for their 4-year health checkup during 2006-2008 and whose parents answered a self-administered questionnaire (n = 4,278 children). The questionnaire was distributed to parents of children registered with the CHC and invited for the 4-year checkup during the study period.</p> <p>Results</p> <p>There was a two to four times increased odds of the child having an allergy or having sought medical care due to allergic symptoms if at least one parent had an allergy, while there were rather small increased odds related to presence of secondhand smoke during the child's first month in life or at the age of 8 months. However, children with heredity for allergies and with presence of secondhand tobacco smoke during their first year in life had highly increased odds of developing an allergy and having sought medical care due to allergic symptoms at 4 years of age. Thus, there was a synergistic effect enhancing the independent effects of heredity and exposure to secondhand tobacco smoke on allergy development.</p> <p>Conclusions</p> <p>Children with a family history of allergies and early exposure to secondhand tobacco smoke is a risk group that prevention and intervention should pay extra attention to. The tobacco smoke effect on children is an essential and urgent question considering it not being self chosen, possibly giving life lasting negative health effects and being possible to reduce.</p

Duloxetine Inhibits Effects of MDMA (“Ecstasy") In Vitro and in Humans in a Randomized Placebo-Controlled Laboratory Study

This study assessed the effects of the serotonin (5-HT) and norepinephrine (NE) transporter inhibitor duloxetine on the effects of 3,4–methylenedioxy­methamphetamine (MDMA, ecstasy) in vitro and in 16 healthy subjects. The clinical study used a double-blind, randomized, placebo-controlled, four-session, crossover design. In vitro, duloxetine blocked the release of both 5-HT and NE by MDMA or by its metabolite 3,4-methylenedioxyamphetamine from transmitter-loaded human cells expressing the 5-HT or NE transporter. In humans, duloxetine inhibited the effects of MDMA including elevations in circulating NE, increases in blood pressure and heart rate, and the subjective drug effects. Duloxetine inhibited the pharmacodynamic response to MDMA despite an increase in duloxetine-associated elevations in plasma MDMA levels. The findings confirm the important role of MDMA-induced 5-HT and NE release in the psychotropic effects of MDMA. Duloxetine may be useful in the treatment of psychostimulant dependence

Association between long travel and venous thromboembolic disease: a systematic review and meta-analysis of case-control studies

The term “economy-class syndrome” defines an infrequent episode of venous thromboembolism (VTED) related to a long travel, namely by plane. However, this relation has not clearly been demonstrated by investigators. We carried out a systematic review and a meta-analysis of cases-control studies that had studied this topic. We realised a systematic review of the literature and selected all the case-control studies published. Two authors carried out a methodological evaluation according to the Scottish Intercollegiate Guidelines Network items (concordance was analysed by weighted kappa index), and a systematic analysis of the potential biases of each study was assessed. We carried out the meta-analysis with the data extracted from the studies. We recovered eight cases-control studies. The relation between the antecedent of a long travel and subsequent VTED varied from OR = 1.1 to OR = 4.0 and was found to be significant in four studies. The studies were highly heterogeneous in methodology and so the results obtained about the relation between the long travel and the VTED and the score at SIGN50. Two meta-analysis were carried out: only with travels by plane in which the relation was not significant (OR = 1.21; CI 95%, 0.95–1.55) and with all types of transport, with a slightly significant relation (OR = 1.46; CI95%, 1.24–1.72). We may deduce from this systematic review that there does exist a weak association between episodes of VTED and a long travel, but not by plane specifically. The heterogeneity and the methodological quality of the studies published preclude of more robust conclusions

Media response to colon cancer campaigns in Switzerland 2005-2007: regional newspapers are the most reliable among the printed media

<p>Abstract</p> <p>Background</p> <p>Health campaigns are frequently covered by printed media, but coverage is not homogeneous across different types of newspapers. Switzerland as a multilinguistic country with many newspapers offers a good field for study. A better understanding of how printed media report on national campaigns against colon cancer in the three main linguistic regions may help to improve future public health interventions. Therefore, we analyzed articles published between 2005 and 2007 during the campaigns "<it>Darmkrebs-nie</it>?" and "<it>Self-Care</it>" in the German, French and Italian regions of Switzerland.</p> <p>Findings</p> <p>Some 65% of articles reporting on colon cancer were in German, 23% and 12% were in French and Italian respectively. During the campaign, topics linked to colon cancer were increasingly covered by the media. Regional newspapers (66%) reported significantly more about colon cancer and produced the most detailed articles.</p> <p>Both gain- and loss-framed messages have been used by journalists, whereas the campaigns used merely gain-framed messages. Latin (French and Italian) newspapers mixed gain- and loss-framed messages in the same articles, while German articles mainly used a single frame throughout.</p> <p>Conclusions</p> <p>Swiss-German papers reported more about the topic and the reporting was quantitatively and qualitatively more prominent in regional papers. The press followed the campaigns closely only during the period of campaigning, with high coverage. We propose to consider the regional press as an important vehicle of health information. Moreover, slight differences in framing can be observed between German and Latin articles.</p

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion