Praxeon Blog

Are Middle-aged Male Mice at a Disadvantage?

Often the advice given to a woman with multiple sclerosis (MS) is not to exacerbate the condition by becoming pregnant. It appears that this advice is about to change. UCLA neurologists believe they’ve identified a basis for the controversial claim that the MS relapse rate for women during pregnancy decreases.

"Apr. 19, 2007 (KABC-TV) - Doctors diagnosed Melissa Glasser with multiple sclerosis at 15. MS is when your own immune system attacks your central nervous system….Despite this, she didn't want MS to stop her from having the family she dreamed of….For decades, scientists knew that something in pregnancy helped women with MS, but there are so many chemical changes researchers didn't know what to isolate. Now, UCLA neurologists say they think they've figured out the answer."

This report highlights estriol which is made in the placenta and has been observed to have the effect of reducing MS symptoms in women and the researchers at UCLA are planning a larger clinical trial with estriol at multiple sites.

The observation of the beneficial effects of estrogen hormones has been known for many years and it now appears that other estradiol derivatives, such as 17-beta-estradiol, also have a beneficial effect. A simple Curbside.MD search "What effect does estradiol have on the symptoms of MS?" traces what is known about the field from all the major sources of medical information available. Interestingly, there is an on-going clinical trial sponsored by the Hospices Civils de Lyon which hopes to control the symptoms in post-partum women: The POPART’MUS study is a European, multicentre, randomized, placebo-controlled and double-blind clinical trial, which aims to prevent MS relapses related to the post-partum condition, by administering high doses of progestin (nomegestrol acetate), in combination with endometrial protective doses of estradiol (see "Clinical Trials").

Unfortunately men may not be able to expect the same benefits from their hormones; research shows the same protective behavior for male mice does not hold. Middle-aged male mice are very sensitive to the symptoms of MS and are unresponsive to testosterone therapy (see “Best Hits”). In this case MS was induced by injection of homogenized brain or spinal cord with Freund’s adjuvant (experimental autoimmune encephalomyelitis).

Still, if male menopause proves to be a real condition rather than just emotional revenge, perhaps more men would consider estrogen therapy and MS might join the growing list of male conditions responsive to female hormones.

dennis.underwood@praxeon.com

Introducing Document DNA

Computer representation of language is still in its infancy but none-the-less advances have been made, especially in domains with the special qualities of being highly defined and rigorously controlled. The language of science and medicine is an example.

The languages of genetics and chemistry have their own strict syntax and well defined semantics, well captured in binary computer representations. It's remarkable how similar the representations are given the physical differences of the processes. Each genetic sequence or chemical structure is powerfully captured by a characteristic signature or 'fingerprint'. This fingerprint is a simple linear abstraction that enables powerful computer algorithms for searching by substructure matching and similarity. Scientists use signatures to rapidly search and organize millions of chemical and genetic entities. Yet people searching for medical answers among the mountains of knowledge published on the Web are limited to keyword searches returning countless unorganized pages of results, ordered by popularity rather than trustworthiness or reliability.

As we have attempted to capture the language of medicine, we have grappled with the following fundamental questions. What are the essential building blocks of meaning that can be manipulated effectively and efficiently to find, compare, categorize, and organize large collections of documents? How can we provide intuitive tools to medical professionals and experts that will transform digital information from a frustrating technical puzzle into the agile, intuitive, living resource that it was truly meant to be? If these tools can be combined with trustworthy and reliable information, we can deliver a useful tool that is valuable to the medical community. The path we followed to answer this question led
us through areas of chemical searching and fingerprinting, ontological theory and practice, full-text search, tagging, and user interface design. We injected our own twists and developed our own approaches and solutions at many points along the way, always organizing our thoughts around the ultimate end user experience. The resulting solution is built on a characteristic signature for written language that we call the Document DNA. We use the Document DNA to power many important features of Curbside.MD.

• A built-in understanding of synonyms. In genetics, several different codons often encode the same amino acid. In written language, several different synonyms often represent the same concept. Document DNA technology works with concepts (amino acids) rather than words (codons).
• The hierarchical nature of concepts is deeply embedded. Medical and scientific concepts such as
  drugs, diseases, genes, proteins, treatments, and devices are all naturally hierarchical. The Document DNA technology understands and leverages these hierarchies in many useful ways, usually without placing any demands on the user.
• Just as some codons on a DNA strand control the transcription process itself, some concepts in a document describe the document rather than being part of the written text. For example, the intended audience of a scientific paper, the phase of a clinical trial, and the methods employed in a randomized controlled trial are all 'meta' concepts. We represent these 'meta' concepts as tags, and use them in the search ranking algorithms and to organize the display.

The Document DNA is composed of the concepts extracted from a text and the tags that annotate it. Future posts will discuss how specific features of Curbside.MD use the Document DNA and how these features benefit our users.