ABCD's of Melanoma.

Malignant Melanoma is the most aggressive of malignant cutaneous tumours. Cases with lymphonode involvement, and distant metastases, carry a very poor prognosis, (50% and 20% respectively alive in 5 years), while those presenting without evident lymphonode involvement have a much better survival rate (60% alive in 5 years).

It is therefore extremely important to do early malignant melanoma diagnosis. There are several criteria that may lead to the diagnosis of a malignant melanoma. The most important one is the ABCD rule.

The ABCD diagnosis of Malignant Melanoma -
A = Asymmetry: Moles are commonly symmetrical and round. Very early melanomas, are asymmetrical assuming different forms. One half does not match the other half.
B = Border: Commonly moles, have even and smooth borders. Early melanomas, are usually uneven and notched borders. The edges are ragged, notched or blurred.
C = Color: Moles commonly are a single shade of brown, early malignant melanomas shows brown-tan or black color. Further, as melanomas progress, may see red, white, and blue color.
D = Diameter: Early malignant melanomas, differently from moles, tend to grow larger in diameter. First suspects in melanoma start from a 6 millimeters diameter on. Any sudden or continuing increase in size should be of special concern.

Synthesis: a mole with diameter of 6 millimeter, that it introduces alterations - irregular asymmetry, edges, color - must induce the patient to address early on dermatologist to careful clinical and dermatoscopic examination and consequently, if necessary, to surgical removal of the lesion, with successive hystological examination.

Melanoma Prevention
According to the risk factors for malignant melanoma, the following preventive measures are also recommended:

* UV exposure, should be reduced. Prolonged sunbathing, as well as the use of tanning lamps, is not recommended. Children, under three years of age, should be held in the shade.
* Sun protection, should be obtained through suitable clothing. Children should be peculiarly dressed when playing outside.
* Use adequate sunscreens.
* Sunburns should be avoided, particularly in children.

Therefore people with multiple and abnormal moles, or with a family history of malignant melanoma, should have their skin checked continuously by a doctor/dermatologist.

For four years after the U.S. dropped atom bombs on Hiroshima and Nagasaki to end World War II, America held a monopoly on the production of atomic weapons. During this period, debate centering on the use of nuclear bombs in future wars proliferated among government officials, scientists, religious leaders, and in the popular press. In the following article from Collier's, former Navy lieutenant commander William H. Hessler, using data from the Strategic Bombing Survey, argued that saturation bombing of urban areas during World War II, while devastating for civilians, did not achieve war aims. A future atomic war, therefore, might well destroy cities but fail to stop enemy aggression. Furthermore, with a much higher urban concentration than the Soviet Union, the U.S. had more to lose from atomic warfare. The article, while providing detailed explanations of the bomb's destructive capability, demonstrated the lack of information available regarding the long-term medical and ecological effects of radioactivity. Hessler's prose also evoked both the fascination that gadgetry of atomic warfare held for Americans of the time and the fear many felt about the risks involved in putting this technology to use. On September 24, 1949, one week after publication of this article, news that the Russians had conducted atom bomb tests shocked the nation. The following April, a National Security Council report to President Harry S. Truman advised development of a hydrogen bomb--some 1,000 times more destructive than an atom bomb--and a massive buildup of non-nuclear defenses. The subsequent outbreak of war in Korea in June 1950 justified to many a substantial increase in defense spending.

In 1981, the U.S. medical community noticed a significant number of gay men living in urban areas with rare forms of pneumonia, cancer, and lymph disorders. The cluster of ailments was initially dubbed Gay-Related Immune Disease (GRID), but when similar illnesses increased in other groups, the name changed to Acquired Immune Deficiency Syndrome (AIDS). The mid-1980s saw a number of advances toward understanding and treating the disease, but no vaccine or cure was forthcoming. Gay advocacy and community-based organizations began providing services and pressuring government to increase funding for finding a cure and helping victims. As two representatives of AIDS health services organizations stated in the following 1987 testimony to Congress, AIDS spread in disproportionately high numbers throughout U.S. minority and disadvantaged communities. They advocated increased federal funding for prevention efforts targeted at minority communities and administered by community-based organizations. Despite such efforts, the number of minority AIDS cases continued to rise sharply, and by 1996, African Americans accounted for a higher percentage of reported adult cases of AIDS (41%) than did whites.

Simulation of tumor cord growth where conversion of the tumor to glycolytic (anaerobic) metabolism takes place under hypoxia. This video shows evolution of the region where the aerobic cells suffer from hypoxia (ATP deficit) as well as the limit where the glycolytic cells start suffering too. This video reflects work in progress and may be different from the final results.

This is a simulation of tumor cord growth, where cells suffer from hypoxia (energy deficit shown with color). The tumor grows along the blood vessel (coincides with x-axis). Red line shows the position of the tumor–host interface. This particular simulation was programmed in FreeFEM++ out of curiosity. The source code for simulation may be found at http://code.google.com/p/cord. This video reflects work in progress and may be different from the final results.

Background
MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterized the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis.

Methods and Findings
By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis scores versus wild-type mice, p , 0.01) and chronic diarrhea Monitoring over 300 mice of each strain demonstrated that 25% and 40% of each strain, respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced by a luminal toxin. Enhanced local production of IL-1b, TNF-a, and IFN-c was seen in the distal colon, and intestinal permeability increased 2-fold. The number of leukocytes within mesenteric lymph nodes increased 5-fold and leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-c, TNF-a, and IL-13). This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress. In human ulcerative colitis we demonstrate similar accumulation of nonglycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in noninflamed intestinal tissue. Although our study demonstrates that mucin misfolding and ER stress initiate colitis in mice, it does not ascertain the genetic or environmental drivers of ER stress in human colitis.

Conclusions
Characterization of the mouse models we created and comparison with human disease suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of human colitis and that clinical studies combining genetics, ER stress-related pathology and relevant environmental epidemiology are warranted.

Animation of cardiovascular trauma in Spanish

CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design.

Watch Captain Chemo and his cadets as they embark on five adventures dealing with different issues concerned with cancer. The animated adventures have been created by Gameplay's specialist multimedia division - doUno.com. The animated and interactive educational site is primarily aimed at cancer patients, relatives and friends to explain the disease and its treatment. You can assist Captain Chemo and Chemo Command to answer questions about cancer and search for the answers to gain points, together with manoeuvring the chemo craft to shoot and destroy tumours.

Inspired by Mary Shelley's novel about a man-made monster who turned upon its creator, this cartoon depicted the railroad trampling the rights of the American people. Agriculture

Explores the changing roles, ethical conflicts, and public perceptions of science and scientists in American society from World War II to the present. Studies specific historical episodes focusing on debates between scientists and the contextual factors influencing their opinions and decisions. Topics include the atomic bomb project, environmental controversies, the Challenger disaster, biomedical research, genetic engineering, (mis)use of human subjects, scientific misconduct and whistleblowing.

Background
The present study was designed to test the hypothesis that inactivation of virtually any component within the pathway containing the BRCA1 and BRCA2 proteins would increase the risks for lymphomas and leukemias. In people who do not have BRCA1 or BRCA2 gene mutations, the encoded proteins prevent breast/ovarian cancer. However BRCA1 and BRCA2 proteins have multiple functions including participating in a pathway that mediates repair of DNA double strand breaks by error-free methods. Inactivation of BRCA1, BRCA2 or any other critical protein within this "BRCA pathway" due to a gene mutation should inactivate this error-free repair process. DNA fragments produced by double strand breaks are then left to non-specific processes that rejoin them without regard for preserving normal gene regulation or function, so rearrangements of DNA segments are more likely. These kinds of rearrangements are typically associated with some lymphomas and leukemias.

Methods
Literature searches produced about 2500 epidemiology and basic science articles related to the BRCA pathway. These articles were reviewed and copied to a database to facilitate access. Meta-analyses of statistical information compared risks for hematologic cancers vs. mutations for the components in a model pathway containing BRCA1/2 gene products.

Results
Deleterious mutations of genes encoding proteins virtually anywhere within the BRCA pathway increased risks up to nearly 2000 fold for certain leukemias and lymphomas. Cancers with large increases in risk included mantle cell lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, and prolymphocytic leukemia. Mantle cell lymphoma is defined by a characteristic rearrangement of DNA fragments interchanged between chromosomes 11 and 14. DNA translocations or rearrangements also occur in significant percentages of the other cancers.

Conclusion
An important function of the BRCA pathway is to prevent a subgroup of human leukemias and lymphomas that may involve non-random, characteristic gene rearrangements. Here, the genetic defect in BRCA pathway deficiencies is a chromosomal misrepair syndrome that may facilitate this subgroup of somatic cancers. Inactivation of a single gene within the pathway can increase risks for multiple cancers and inactivation of a different gene in the same pathway may have similar effects. The results presented here may have clinical implications for surveillance and therapy.

An introduction to the Ruby language for the Computer-Aided Discovery Methods course taught at Baylor College of Medicine.

An introduction to the Ruby language for the Computer-Aided Discovery Methods course taught at Baylor College of Medicine.

In this autobiographical account of the life that awaited new nursing recruits in 1893, former nurse Mary Roberts Rinehart painted a vivid portrait of the daily obstacles that stood between nurses and the professional status they hoped to attain. Rinehart described the "simple, plain hell" faced by the young nurse, a description that challenged conventional expectations about professional work.

Many difficult ethical questions have arisen from the explosive growth of biomedical research and the health-care industry since World War II. When and how should doctors be allowed to help patients end their lives? Should embryos be cloned for research and/or reproduction? Should parents be given control over the genetic make-up of their children? What sorts of living things is it appropriate to use as research subjects? How should we distribute scarce and expensive medical resources? While some of these questions are genuinely new, products of rapid changes in biomedical technology, others have been debated for centuries. Drawing on philosophy, history, and anthropology, this course will show students how problems in bioethics can be approached from a variety of perspectives, with the aim of understanding how we have gotten where we are, and how we should decide where to go next.

" This course does not seek to provide answers to ethical questions. Instead, the course hopes to teach students two things. First, how do you recognize ethical or moral problems in science and medicine? When something does not feel right (whether cloning, or failing to clone) — what exactly is the nature of the discomfort? What kind of tensions and conflicts exist within biomedicine? Second, how can you think productively about ethical and moral problems? What processes create them? Why do people disagree about them? How can an understanding of philosophy or history help resolve them? By the end of the course students will hopefully have sophisticated and nuanced ideas about problems in bioethics, even if they do not have comfortable answers."

Students use a Bioethics Organizer worksheet to consider a bioethical dilemma from the perspective of a stakeholder.

Dr. Laura Elnitski, Head of the Genomic Functional Analysis Section, Genome Technology Branch NHGRI/NIHDr. Elnitski uses experimental and Bioinformatic methods to discover non-coding functional elements in the human genome. On 7 March 2008, Dr. Elnitski came to MSU-Bozeman to participate in the Women In Bioinformatics Seminar Series.