The efficacy of periodic +Gz exposure in the prevention of bedrest induced orthostatic intolerance

What is the most efficient dosage of periodic exposure to positive 1G(z) during microgravity to maintain a functional upright position after returning to a positive 1G(z) environment? The answer has implications for the type of countermeasures astronauts will be required to perform during long term space flight. Methods: Nine males were subjected to four different positive 1G exposure protocols plus a control protocol ('zero G(z)') during four days of continuous bedrest. The four positive 1G(z) exposures consisted of periodic standing or walking, each for a total period of two or four hours. Each subject was returned for bedrest on five different occasions over a period of approximately one year to obtain data on each of the nine subjects across all four positive 1G(z) treatments and the control. A 30 min tilt test was used to measure orthostatic response during pre and post bedrest. Results: In terms of survival rate (percentage of subjects who did not faint after 30 sec of tilt), four hours of intermittent standing was the only protocol that maintained a rate comparable to pre bedrest levels (87.5 percent). Although the other three positive 1G(z) protocols performed better than the 'zero G(z) control (22.2 percent), only the four hour standing returned post bedrest survival rates to pre bedrest levels. Conclusions: The results will need to be evaluated with regards to a variety of other physiological systems which are known to decondition during microgravitry

The Toxic Effects of Cigarette Additives. Philip Morris' Project Mix Reconsidered: An Analysis of Documents Released through Litigation

Stanton Glantz and colleagues analyzed previously secret tobacco industry documents and peer-reviewed published results of Philip Morris' Project MIX about research on cigarette additives, and show that this research on the use of cigarette additives cannot be taken at face value

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations

A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing

Age-related changes to histone levels are seen in many species. However, it is unclear whether changes to histone expression could be exploited to ameliorate the effects of ageing in multicellular organisms. Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally, through eIF3-mediated translation. Elevated expression of H3/H4 in intestinal enterocytes in Drosophila alters chromatin organization, induces intestinal autophagy through transcriptional regulation, prevents age-related decline in the intestine. Importantly, it also mediates rapamycin-induced longevity and intestinal health. Histones H3/H4 regulate expression of an autophagy cargo adaptor Bchs (WDFY3 in mammals), increased expression of which in enterocytes mediates increased H3/H4-dependent healthy longevity. In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions

Ciguatera fish poisoning in the Pacific Islands (1998 - 2008)

Background: Ciguatera is a type of fish poisoning that occurs throughout the tropics, particularly in vulnerable island communities such as the developing Pacific Island Countries and Territories (PICTs). After consuming ciguatoxin-contaminated fish, people report a range of acute neurologic, gastrointestinal, and cardiac symptoms, with some experiencing chronic neurologic symptoms lasting weeks to months. Unfortunately, the true extent of illness and its impact on human communities and ecosystem health are still poorly understood

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (>= 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model facto Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates