Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.

Inhibitors against the p110δ isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumours. Here we report that p110δ inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110δ inactivation in regulatory T cells unleashes CD8(+) cytotoxic T cells and induces tumour regression. Thus, p110δ inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology

A longitudinal study of gene expression in healthy individuals

<p>Abstract</p> <p>Background</p> <p>The use of gene expression in venous blood either as a pharmacodynamic marker in clinical trials of drugs or as a diagnostic test requires knowledge of the variability in expression over time in healthy volunteers. Here we defined a normal range of gene expression over 6 months in the blood of four cohorts of healthy men and women who were stratified by age (22–55 years and > 55 years) and gender.</p> <p>Methods</p> <p>Eleven immunomodulatory genes likely to play important roles in inflammatory conditions such as rheumatoid arthritis and infection in addition to four genes typically used as reference genes were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), as well as the full genome as represented by Affymetrix HG U133 Plus 2.0 microarrays.</p> <p>Results</p> <p>Gene expression levels as assessed by qRT-PCR and microarray were relatively stable over time with ~2% of genes as measured by microarray showing intra-subject differences over time periods longer than one month. Fifteen genes varied by gender. The eleven genes examined by qRT-PCR remained within a limited dynamic range for all individuals. Specifically, for the seven most stably expressed genes (CXCL1, HMOX1, IL1RN, IL1B, IL6R, PTGS2, and TNF), 95% of all samples profiled fell within 1.5–2.5 Ct, the equivalent of a 4- to 6-fold dynamic range. Two subjects who experienced severe adverse events of cancer and anemia, had microarray gene expression profiles that were distinct from normal while subjects who experienced an infection had only slightly elevated levels of inflammatory markers.</p> <p>Conclusion</p> <p>This study defines the range and variability of gene expression in healthy men and women over a six-month period. These parameters can be used to estimate the number of subjects needed to observe significant differences from normal gene expression in clinical studies. A set of genes that varied by gender was also identified as were a set of genes with elevated expression in a subject with iron deficiency anemia and another subject being treated for lung cancer.</p

Why media representations of corporations matter for public health policy : a scoping review

BACKGROUND: Media representations play a crucial role in informing public and policy opinions about the causes of, and solutions to, ill-health. This paper reviews studies analysing media coverage of non-communicable disease (NCD) debates, focusing on how the industries marketing commodities that increase NCD risk are represented. METHODS: A scoping review identified 61 studies providing information on media representations of NCD risks, NCD policies and tobacco, alcohol, processed food and soft drinks industries. The data were narratively synthesized to describe the sample, media depictions of industries, and corporate and public health attempts to frame the media debates. RESULTS: The findings indicate that: (i) the limited research that has been undertaken is dominated by a focus on tobacco; (ii) comparative research across industries/risk-factors is particularly lacking; and (iii) coverage tends to be dominated by two contrasting frames and focuses either on individual responsibilities ('market justice' frames, often promoted by commercial stakeholders) or on the need for population-level interventions ('social justice' frames, frequently advanced by public health advocates). CONCLUSIONS: Establishing the underlying frameworks is crucial for the analysis of media representation of corporations, as they reflect the strategies that respective actors use to influence public health debates and decision making. The potential utility of media research lies in the insights that it can provide for public health policy advocates about successful framing of public health messages and strategies to counter frames that undermine public health goals. A better understanding of current media debates is of paramount importance to improving global health

Magnetic Resonance Imaging in Huntington's Disease.

Magnetic resonance imaging (MRI) is a noninvasive technique used routinely to image the body in both clinical and research settings. Through the manipulation of radio waves and static field gradients, MRI uses the principle of nuclear magnetic resonance to produce images with high spatial resolution, appropriate for the investigation of brain structure and function

Soda and Tobacco Industry Corporate Social Responsibility Campaigns: How Do They Compare?

In an article that forms part of the PLoS Medicine series on Big Food, Andrew Cheyne and colleagues compare soda companies' corporate social responsibility (CSR) campaigns - which are designed to bolster the image and popularity of their products and to prevent regulation - with the tobacco industry's CSR campaigning

The use of discrete choice experiments to inform health workforce policy: a systematic review.

BACKGROUND: Discrete choice experiments have become a popular study design to study the labour market preferences of health workers. Discrete choice experiments in health, however, have been criticised for lagging behind best practice and there are specific methodological considerations for those focused on job choices. We performed a systematic review of the application of discrete choice experiments to inform health workforce policy. METHODS: We searched for discrete choice experiments that examined the labour market preferences of health workers, including doctors, nurses, allied health professionals, mid-level and community health workers. We searched Medline, Embase, Global Health, other databases and grey literature repositories with no limits on date or language and contacted 44 experts. Features of choice task and experimental design, conduct and analysis of included studies were assessed against best practice. An assessment of validity was undertaken for all studies, with a comparison of results from those with low risk of bias and a similar objective and context. RESULTS: Twenty-seven studies were included, with over half set in low- and middle-income countries. There were more studies published in the last four years than the previous ten years. Doctors or medical students were the most studied cadre. Studies frequently pooled results from heterogeneous subgroups or extrapolated these results to the general population. Only one third of studies included an opt-out option, despite all health workers having the option to exit the labour market. Just five studies combined results with cost data to assess the cost effectiveness of various policy options. Comparison of results from similar studies broadly showed the importance of bonus payments and postgraduate training opportunities and the unpopularity of time commitments for the uptake of rural posts. CONCLUSIONS: This is the first systematic review of discrete choice experiments in human resources for health. We identified specific issues relating to this application of which practitioners should be aware to ensure robust results. In particular, there is a need for more defined target populations and increased synthesis with cost data. Research on a wider range of health workers and the generalisability of results would be welcome to better inform policy

Original Article

The pancreas taken from the frog (Rana nigromaculata) was fixed in 1% OsO_4 and sliced into ultrathin sections for electron microscopic studies. The following observations were made: 1. A great \u27number of minute granules found in the cytoplasm of a pancreatic cell were called the microsomes, which were divided into two types, the C-microsome and S-microsome. 2. Electron microsopic studies of the ergastoplasm showed that it is composed of the microsome granules and A-substance. The microsomes were seen embedded in the A-substance which was either filamentous or membranous. The membranous structure, which was called the Am-membrane, was seen to form a sac, with a cavity of varying sizes, or to form a lamella. 3. The Am-membrane has close similarity to α-cytomembrane of Sjostrand, except that the latter is rough-surfaced. It was deduced that the Am-membrane, which is smooth-surfaced, might turn into the rough-surfaced α-cytomembrane. 4. There was the Golgi apparatus in the supranuclear region of a pancreatic cell. It consisted of the Golgi membrane, Golgi vacuole and. Golgi vesicle. 5. The mitochondria of a pancreatic cell appeared like long filaments, and some of them were seen to ramify. 6. The membrane of mitochondria, i. e. the limiting membrane, consisted of the Ammembrane. The mitochondria contained a lot of A-substances, as well as the C-microsomes and S-microsomes. When the mitochondria came into being, there appeared inside them chains of granules, which appeared like strips of beads, as the outgrowths of the A-substance and the microsome granules attached to the Am-membrane. They are the so-called cristae mitochondriales. 7. The secretory granules originate in the microsomes. They came into being when the microsomes gradually thickened and grew in size as various substances became adhered to them. Some of the secretory granules were covered with a membrane and appeared like what they have called the intracisternal granule of Palade.It seemed that this was a phenomenon attendant upon the dissolution and liqutefaction of the secretory granule. 8. Comparative studies were made of the ergastoplasm of the pancreatic cells from the frogs in hibernation, the frogs artificially hungered, the frogs which were given food after a certain period of fasting, the frogs to which pilocarpine was given subcutaneously, and the very young, immature frogs. The studies revealed that the ergastoplasm of the pancreatic cells greatly varied in form with the difference in nutritive condition and with different developmental stages of the cell. The change in form and structure occured as a result of transformation of the microsomes and A-substance. The ergastoplasm, even after it has come into being, might easily be inactivated if nutrition is defective. The ergastoplasm is concerned in the secretory mechanism, which is different from the secretory phenomenon of the secretory granules. It would seem that structurally the mitochondria have no direct relation to this mechanism