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New findings in rodents and human brain shed light on the mechanisms of major depressive disorder (MDD), uncovering over-expression of MKP-1 (mitogen-activated protein kinase [MAPK] phosphatase-1)...and identifying a new therapeutic target. MKP-1, also known as dual-specificity phosphatase-1 (DUSP1), is a member of a family of proteins that dephosphorylate both threonine and tyrosine residues and thereby serves as a key negative regulator of the MAPK cascade4, a major signaling pathway involved in neuronal plasticity, function and survival This study identifies MKP-1 as a key factor in MDD pathophysiology, and as a new target for therapeutic interventions.f Here we use whole-genome expression profiling of postmortem tissue and show significantly increased expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1, encoded by DUSP1, but hereafter called MKP-1) in the hippocampal subfields of subjects with MDD compared to matched controls. MKP-1, also known as dual-specificity phosphatase-1 (DUSP1), is a member of a family of proteins that dephosphorylate both threonine and tyrosine residues and thereby serves as a key negative regulator of the MAPK cascade4, a major signaling pathway involved in neuronal plasticity, function and survival. We tested the role of altered MKP-1 expression in rat and mouse models of depression and found that increased hippocampal MKP-1 expression, as a result of stress or viral-mediated gene transfer, causes depressive behaviors. Conversely, chronic antidepressant treatment normalizes stress-induced MKP-1 expression and behavior, and mice lacking MKP-1 are resilient to stress. These postmortem and preclinical studies identify MKP-1 as a key factor in MDD pathophysiology and as a new target for therapeutic interventions.

"Improving Medical Information Systems Through Human Factors"

There is reasonable evidence that the use of imiquimod for small (<2 cm) superficial BCC that occur other than on the face provides outcomes only marginally less satisfactory than surgery. There would be a place for imiquimod in treating patients with frequent multiple primary lesions when access to surgery is difficult or where clinical judgment may be influenced by patient factors as reported in some of the studies, eg, where patients may have contraindications to surgery.  It was noted that if recurrences occurred in this study they mostly occurred during the first 9 months after the end of treatment. The initial response was therefore predictive of long-term outcome so these authors recommend and encourage continued monitoring of skin lesions.

The precise mechanism of the anti-tumor effect of imiquimod in BCC is not known. It has been postulated that ultraviolet radiation induces mutations in the tumor-suppressor genes and alters the immuno-surveillance, so that tumor cells escape from cytotoxic T cells and apoptosis.[1] Th-2 cytokines, that downregulate tumor surveillance, are raised in BCC.[1],[5] Imiquimod acts on toll-like receptor-7 (TLR-7) present on dendritic cells, macrophages and monocytes and induces expression of interferons, Th-1 cytokines (IL-1, IL-6, IL-10 and IL-12), tumor necrosis factor-a and G-CSF, thereby counteracting Th2 cytokines and promoting tumor surveillance.[1],[5] It also enhances the activity of natural killer cells and epidermal Langerhans' cells. The tumor regression is achieved probably by induction of Fas receptors on the tumor cells resulting in their apoptosis.[10]

The hypothesis that diets rich in total and saturated fat and poor in unsaturated fats increase the risk for cardiovascular disease is still vividly debated. The aim of this study was to examine whether total fat, saturated fat, or unsaturated fat intakes are independent risk factors for cardiovascular events in a large population-based cohort. Conclusions: In relation to risks of cardiovascular events, our results do not suggest any benefit from a limited total or saturated fat intake, nor from relatively high intake of unsaturated fat. Leosdottir, Margret; Nilsson, Peter M.; Nilsson, Jan-Åke; Berglund, Göran

Liver disease can decrease clearance of activated coagulation factors...It is often difficult to differentiate DIC from liver disease as cause of coagulation disorders...

Fewer than half of all clinical trials recently published in journals with high impact factors are adequately registered, and about a third of those that are registered properly show discrepancies between the registered primary outcome and the one that actually gets reported.

Unlike simple starvation, where body fat is lost preferentially, cancer cachexia is associated with depletion of both fat and skeletal muscle mass. Although anorexia is frequently associated with cachexia a reduction of nutrient intake alone could not explain the progressive wasting. Instead the process appears to be mediated by circulatory tumor-produced catabolic factors acting either alone or in concert with certain cytokines. A knowledge of the mechanisms involved should lead to the development of effective pharmacological intervention. Effective therapy should not only improve the quality of life of the cancer patient, but should lead to an increase in survival. Since cachexia is so common in cancer host products may be required for tumor homeostasis. Thus further knowledge in this area may lead to the development of new agents for the treatment of cancer.

Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.\nSiri--Tirino, et al.; \nAm J Clin Nutrition; 2010 Jan 13. \nPMID: 20071648\ndoi:10.3945/ajcn.2009.27725\n\nConclusions: A meta-analysis of prospective epidemiologic studies showed that there is NO significant evidence that dietary saturated fat is associated with increased risk for CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat

Journal of Skin CancerVolume 2011 (2011), Article ID 571734, 6 pagesdoi:10.1155/2011/571734 © 2011 Mary H. Lien and Vernon K. Sondak.

Endocrinological associations with prothrombotic disorders

"Hop up on the table, Honey." mThat's how an x-ray technician addressed my 89-year-old mother-in-law in 2001, when we took her for knee x-rays. Mom, who had advanced osteoporosis and arthritis as well as confusion and heart problems, had long since given up hopping. When it became obvious that she needed assistance, the technician grabbed her arm -- as if pulling on another sore appendage would magically raise the rest of her onto the table. It didn't. This incident has become our personal mantra for expressing what is wrong with America's health care system. Having helped our four parents during their final years and having both had cancer ourselves as well as other medical problems, we have had experiences with five nursing homes, two personal care facilities and a half dozen hospitals. We've lost count of the doctors, drugstores and health insurance plans. All of us have had health insurance, though some policies were better than others. Nonetheless, we have experienced incident after incident demonstrating the waste, ignorance and apathy which is rampant in the system. Unable to list them all, I have been heretofore reluctant to write about a handful of them lest the reader be persuaded that the problem is with only that hospital, only that nursing home or only that doctor. There is, however, an increasing crisis of confusion, mismanagement and ill-preparedness which is at the core of our healthcare system. We are all familiar at least with the trend line if not the specifics for healthcare costs. According to WhiteHouse.gov, "The United States spends over $2.2 trillion on health care each year-almost $8,000 per person." That's sixteen percent of the economy. Healthcare costs are projected to increase to almost twenty percent ($4 trillion a year) by 2017. Meanwhile forty-six million Americans are without health insurance (14,000 more each day), premiums and co-pays are rising and more reasons are used to refuse coverage both to those willing to pay and thos

"Hop up on the table, Honey." mThat's how an x-ray technician addressed my 89-year-old mother-in-law in 2001, when we took her for knee x-rays. Mom, who had advanced osteoporosis and arthritis as well as confusion and heart problems, had long since given up hopping. When it became obvious that she needed assistance, the technician grabbed her arm -- as if pulling on another sore appendage would magically raise the rest of her onto the table. It didn't. This incident has become our personal mantra for expressing what is wrong with America's health care system. Having helped our four parents during their final years and having both had cancer ourselves as well as other medical problems, we have had experiences with five nursing homes, two personal care facilities and a half dozen hospitals. We've lost count of the doctors, drugstores and health insurance plans. All of us have had health insurance, though some policies were better than others. Nonetheless, we have experienced incident after incident demonstrating the waste, ignorance and apathy which is rampant in the system. Unable to list them all, I have been heretofore reluctant to write about a handful of them lest the reader be persuaded that the problem is with only that hospital, only that nursing home or only that doctor. There is, however, an increasing crisis of confusion, mismanagement and ill-preparedness which is at the core of our healthcare system. We are all familiar at least with the trend line if not the specifics for healthcare costs. According to WhiteHouse.gov, "The United States spends over $2.2 trillion on health care each year-almost $8,000 per person." That's sixteen percent of the economy. Healthcare costs are projected to increase to almost twenty percent ($4 trillion a year) by 2017. Meanwhile forty-six million Americans are without health insurance (14,000 more each day), premiums and co-pays are rising and more reasons are used to refuse coverage both to those willing to pay and thos