Poor Control of Diabetes May be Linked to Low Vitamin D

Released: 6/21/2010 9:00 AM EDT
Source: Endocrine Society
Newswise — Vitamin D deficiency is highly prevalent in patients with Type 2 diabetes and may be associated with poor blood sugar control, according to a new study. The results will be presented Saturday at The Endocrine Society’s 92nd Annual Meeting in San Diego.
“This finding supports an active role of vitamin D in the development of Type 2 diabetes,” said study co-author Esther Krug, MD, an assistant professor of medicine at The Johns Hopkins University School of Medicine and an endocrinologist at Sinai Hospital, Baltimore.
Krug and her colleagues reviewed the medical charts of 124 patients with Type 2 diabetes who came to an endocrine outpatient clinic for specialty care from 2003 to 2008. Patients’ age ranged from 36 to 89 years. All patients had a single measurement of their serum 25-hydroxyvitamin D levels as part of their evaluation at the clinic. The researchers divided the patients into quartiles based on vitamin D level.
Despite receiving regular primary care visits before referral to the endocrine clinic, 91 percent of patients had either vitamin D deficiency (defined as a level below 15 nanograms per deciliter, or ng/dL) or insufficiency (15 to 31 ng/dL), the authors reported. Only about 6 percent of patients were taking vitamin D supplements at their first visit.
Additionally, the investigators found an inverse relationship between the patients’ blood levels of vitamin D and their hemoglobin A1c value, a measure of blood sugar control over the past several months. Lower vitamin D levels were discovered in patients with higher average blood sugars as measured by HbA1c, Krug said. Compared with whites, blacks had a higher average A1c and lower average vitamin D level.
“Since primary care providers diagnose and treat most patients with Type 2 diabetes, screening and vitamin D supplementation as part of routine primary care may improve health outcomes of this highly prevalent condition,” she said.

Many People with Diabetes Do Not Know or Heed Dangers of Hot Weather

Released: 6/21/2010 9:00 AM EDT
Source: Endocrine Society
Newswise — A new survey shows that diabetic individuals who live in a hot climate have important gaps in their “heat awareness,” or knowledge about proper diabetes self-care in hot weather, even though diabetes raises their risk of heat illness. The results of “Diabetes in the Desert: What Do Patients Know About the Heat?” will be presented Monday at The Endocrine Society’s 92nd Annual Meeting in San Diego.
Researchers from Mayo Clinic in Arizona, in collaboration with the National Ocean and Atmospheric Administration and the National Weather Service, surveyed patients at a Phoenix diabetes clinic and analyzed 152 surveys. Responses showed that people living with diabetes in hot climates need increased awareness of how heat affects their disease, said lead researcher Adrienne Nassar, MD, third-year medical resident at Mayo Clinic.
“People with diabetes have an impaired ability to sweat, which predisposes them to heat-related illness, as do uncontrolled, high blood sugars,” Nassar said. “Many patients surveyed had suboptimal glycemic control during the summer, possibly increasing their risk of dehydration.”
Past research shows that during hot weather people with diabetes have an increased number of emergency room visits, hospitalizations and deaths due to heat illness.
Yet one in five survey respondents said they would not take precautions until temperatures exceeded 100 degrees Fahrenheit. “Heat illness can take place at 80 to 90 degrees when you factor in the heat index,” Nassar said.
Only about half of the patients knew the definition of the heat index—the combination of air temperature and humidity. High humidity makes heat more dangerous because it slows the evaporation of perspiration, the way the body cools itself.
Heat also can harm the effectiveness of diabetes medications and supplies. “Oral medications as well as insulin have a therapeutic temperature range above which they lose efficacy,” Nassar said. The drug’s package insert includes information about proper temperatures for storage.
Although 73 percent of respondents had received information about the harmful effect of heat on insulin, fewer knew about the adverse effects of heat on their oral diabetes medications (39 percent) and on glucose meters (41 percent) and glucose test strips (38 percent).
Even when survey respondents knew that they should protect their diabetes medications and glucose-testing supplies from heat, an alarming proportion—37 percent—chose to leave them at home rather than risk heat exposure.
“If they are unable to check their blood sugars while they are away from home, that’s unsafe,” Nassar said.
“Increasingly more people with diabetes are living in places characterized by hot weather. Patient education focusing on diabetes management in hot climates is needed,” she said.




Well-Defined Quantity of Antioxidants in Diet Can Improve Insulin Resistance

Released: 6/21/2010 9:00 AM EDT
Source: Endocrine Society
Newswise — A diet rich in natural antioxidants improves insulin sensitivity in insulin-resistant obese adults and enhances the effect of the insulin-sensitizing drug metformin, a preliminary study from Italy finds. The results will be presented Monday at The Endocrine Society’s 92nd Annual Meeting in San Diego.
“The beneficial effects of antioxidants are known, but we have revealed for the first time one of their biological bases of action—improving hormonal action in obese subjects with the metabolic syndrome,” said principal author Antonio Mancini, MD, an endocrinology researcher at Catholic University of the Sacred Heart in Rome.
The metabolic syndrome is a cluster of metabolic risk factors for developing diabetes, heart disease and stroke. People with this syndrome cannot efficiently use insulin, the hormone that regulates glucose (sugar) in the blood.
Some evidence exists that oxidative stress may play a role in the metabolic syndrome, according to Mancini. Oxidative stress, a biochemical mechanism which can lead to damage to blood particles and to cells, results from an imbalance between an excessive amount of oxidants and decreased antioxidant defenses. Oxidative stress also plays a part in aging.
Antioxidants, which are found naturally in fruits, vegetables, legumes and nuts, include vitamins E and C, selenium and carotenoids, such as beta-carotene. Past research shows that antioxidants can prevent oxidative damage to cells and in some cases also help repair damage.
Mancini and his colleagues studied the effects of dietary antioxidants on insulin resistance, with partial financial support from MIUR, the Italian Department for University and Research. The study included 16 men and 13 women, ages 18 to 66 years, who were obese and insulin-resistant, but were not yet diabetic.
The researchers randomly assigned the subjects to one of four treatment groups. All groups ate a low-calorie, Mediterranean-type diet averaging 1,500 calories daily, containing only 25 percent from protein foods, with the rest made up of low-glycemic-index carbohydrates (carbs that do not raise blood sugar levels quickly or greatly, such as whole grains). Group A only ate this kind of diet, and group B ate the same diet plus took the drug metformin. For groups C and D, the researchers prescribed a diet enriched in antioxidant, with a calculated intake, 800 to 1,000 milligrams a day, coming from fruits and vegetables, but group D also took metformin.
Despite similar weight loss in all the groups, only the two groups receiving the antioxidant diet (groups C and D) had a significant decrease in insulin resistance, the authors reported. Group D had the best improvement in insulin resistance on some measures of insulin response to an oral glucose tolerance test, according to the abstract.
Subjects reported no adverse effects from the antioxidant diet, Mancini said. When asked about the risk of adding more antioxidants to a diet, he stated, “We think that a total antioxidant level of 800 to 1,000 milligrams a day is safe and probably not close to the maximum tolerable level.”


Well-Defined Quantity of Antioxidants in Diet Can Improve Insulin Resistance

Released: 6/21/2010 9:00 AM EDT
Source: Endocrine Society
Newswise — A diet rich in natural antioxidants improves insulin sensitivity in insulin-resistant obese adults and enhances the effect of the insulin-sensitizing drug metformin, a preliminary study from Italy finds. The results will be presented Monday at The Endocrine Society’s 92nd Annual Meeting in San Diego.
“The beneficial effects of antioxidants are known, but we have revealed for the first time one of their biological bases of action—improving hormonal action in obese subjects with the metabolic syndrome,” said principal author Antonio Mancini, MD, an endocrinology researcher at Catholic University of the Sacred Heart in Rome.
The metabolic syndrome is a cluster of metabolic risk factors for developing diabetes, heart disease and stroke. People with this syndrome cannot efficiently use insulin, the hormone that regulates glucose (sugar) in the blood.
Some evidence exists that oxidative stress may play a role in the metabolic syndrome, according to Mancini. Oxidative stress, a biochemical mechanism which can lead to damage to blood particles and to cells, results from an imbalance between an excessive amount of oxidants and decreased antioxidant defenses. Oxidative stress also plays a part in aging.
Antioxidants, which are found naturally in fruits, vegetables, legumes and nuts, include vitamins E and C, selenium and carotenoids, such as beta-carotene. Past research shows that antioxidants can prevent oxidative damage to cells and in some cases also help repair damage.
Mancini and his colleagues studied the effects of dietary antioxidants on insulin resistance, with partial financial support from MIUR, the Italian Department for University and Research. The study included 16 men and 13 women, ages 18 to 66 years, who were obese and insulin-resistant, but were not yet diabetic.
The researchers randomly assigned the subjects to one of four treatment groups. All groups ate a low-calorie, Mediterranean-type diet averaging 1,500 calories daily, containing only 25 percent from protein foods, with the rest made up of low-glycemic-index carbohydrates (carbs that do not raise blood sugar levels quickly or greatly, such as whole grains). Group A only ate this kind of diet, and group B ate the same diet plus took the drug metformin. For groups C and D, the researchers prescribed a diet enriched in antioxidant, with a calculated intake, 800 to 1,000 milligrams a day, coming from fruits and vegetables, but group D also took metformin.
Despite similar weight loss in all the groups, only the two groups receiving the antioxidant diet (groups C and D) had a significant decrease in insulin resistance, the authors reported. Group D had the best improvement in insulin resistance on some measures of insulin response to an oral glucose tolerance test, according to the abstract.
Subjects reported no adverse effects from the antioxidant diet, Mancini said. When asked about the risk of adding more antioxidants to a diet, he stated, “We think that a total antioxidant level of 800 to 1,000 milligrams a day is safe and probably not close to the maximum tolerable level.”



Fructose Sugar Makes Maturing Human Fat Cells Fatter, Less Insulin-Sensitive

Released: 6/20/2010 2:00 PM EDT
Source: Endocrine Society
Newswise — Fructose, the sugar widely used as high-fructose corn syrup in soft drinks and processed foods, often gets some of the blame for the widespread rise in obesity. Now a laboratory study has found that when fructose is present as children’s fat cells mature, it makes more of these cells mature into fat cells in belly fat and less able to respond to insulin in both belly fat and fat located below the skin.
The results will be presented Sunday at The Endocrine Society’s 92nd Annual Meeting in San Diego by lead author Georgina Coade, a PhD student at the University of Bristol in the U.K.
“Our results suggest that high levels of fructose, which may result from eating a diet high in fructose, throughout childhood may lead to an increase in visceral [abdominal] obesity, which is associated with increased cardiometabolic risk,” Coade said.
Defined by a large waistline, abdominal obesity raises the risk of heart disease and Type 2 diabetes. The abdominal cavity contains one of two major types of fat in the body: visceral fat. The other type, subcutaneous fat, is found below the surface of the skin.
Although researchers have shown the negative effects of fructose on the fat distribution of rodents, the effects of this sugar on human adipocytes, or fat cells, are not clear, according to Coade. Therefore, she and her fellow researchers studied biopsy specimens of both subcutaneous and visceral fat from 32 healthy-weight children who had not yet gone through puberty.
From the biopsy samples, the investigators obtained preadipocytes—the precursors to fat cells that have the potential to differentiate, or mature, into fat-containing adipocytes. They then allowed the precursor cells to mature for 14 days in culture media containing normal glucose (the main sugar found in the bloodstream and the principal source of energy in the body), high glucose or high fructose. The researchers assessed cell differentiation by measuring activity of an enzyme (GPDH) and the abundance of the adipocyte fatty acid binding protein, which are both present only in mature fat cells.
Fructose, the research team found, had different effects to that of glucose and caused the fat cells to differentiate more—that is, to form more mature fat cells—but only in visceral fat.
For both types of fat cells, maturation in fructose decreased the cells’ insulin sensitivity, which is the ability to successfully take up glucose from the bloodstream into fat and muscles. Decreased insulin sensitivity is a characteristic of Type 2 diabetes.
Although prolonged exposure to fructose had a negative effect on insulin sensitivity, when Coade and her co-workers exposed mature fat cells, rather than preadipocytes, to fructose for 48 hours, the cells’ insulin sensitivity increased. The reason why is unknown. However, she said, “Fructose alters the behavior of human fat cells if it is present as the fat cells mature. We can maybe compare this [timing] to periods in children when they are making their fat.”
The London-based organization Diabetes UK helped fund this study.


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Deadly Effect of Arsenic in Drinking Water Measured in Massive Study

Released: 6/18/2010 9:00 AM EDT
Embargo expired: 6/18/2010 6:30 PM EDT
Source: University of Chicago Medical Center
Newswise — More than 20 percent of deaths in a study of 12,000 Bangladeshis were attributable to arsenic exposure from contaminated drinking water, new research reports.
The large 10-year study is the first to prospectively measure the relationship between individual exposure to arsenic and its associated mortality risk, the authors said. The data, collected by an international team from Chicago, New York, and Bangladesh, will be published early online Saturday in The Lancet.
Since the widespread installation of hand-pumped wells to tap groundwater sources in the 1970's, as many as 77 million people - about half the population of Bangladesh - have been accidentally exposed to dangerous levels of arsenic. The World Health Organization calls the exposure "the largest mass poisoning of a population in history."
The Health Effects of Arsenic Longitudinal Study (HEALS) was led by Habibul Ahsan, MD, MMedSc, Director of the Center for Cancer Epidemiology and Prevention at the University of Chicago Medical Center. Arsenic levels from well drinking-water and repeated biennial urine samples of 12,000 subjects were associated with deaths in that population over the last decade.
For the 25 percent of people exposed to the highest levels of arsenic, mortality risk increased by nearly 70 percent, the study determined. People exposed to moderate levels of the poisonous chemical also exhibited increased deaths from chronic disease, relative to those whose exposure was within WHO recommendations of 10 parts per million.
"The results of this study have important public health implications for arsenic in drinking water," the authors write. The exposure levels studied are "similar to other populations that have low-level arsenic exposure."
Arsenic is known to be a potent carcinogen and toxic to organs such as the liver, skin, kidney and the cardiovascular system. But previous studies assessing the effects of long-term drinking-water exposure to arsenic have lacked resolution, relying upon retrospective analysis and estimations of exposure on a group, rather than individual, level.
The HEALS project sought to improve upon this body of research with a prospective study, actively monitoring exposure levels in a large set of individual Bangladeshis. Nearly 12,000 subjects were recruited and tested for baseline arsenic levels in drinking water and urine between 2000 and 2002, then underwent follow-up tests approximately every 2 years thereafter.
"We set up this study to measure health effects based on individual level data so that other factors or biases that may affect our study findings were much less likely," Ahsan said. "This allowed us to examine disease quite reasonably in a more accurate way."
The collection of so many samples was no simple task. More than 100 staff members traveled to remote Bangladesh villages by foot, car, or boat to collect samples from subjects and measure arsenic levels in the water from local wells. Millions of such wells were installed by global health organizations in the 1970's to provide a supposedly cleaner source of water than that available from dirty rivers and streams.
"In Bangladesh, waterborne illnesses have gone down in the last 2 to 3 decades," Ahsan said. "Unfortunately, there is now this new problem affecting them."
While a quarter of the study's population was within the WHO-determined safe range of 10 µg/L, the upper quartile was exposed to 27 times that amount on average. Those individuals were found to be 68 percent more likely to die from a chronic disease over the time period studied, compared to individuals with exposure less than 10 µg/L, after controlling for other factors such as sex, age, body mass, blood pressure and smoking.
Subjects with moderate arsenic exposure were at a smaller yet still elevated risk of mortality. When the entire population exposed to arsenic levels above the WHO guideline was combined, 21.4 percent of all deaths and 23.5 percent of deaths from chronic disease could be attributed to arsenic exposure, the authors wrote.
An ongoing expansion of the HEALS project to 20,000 subjects hopes to clarify the deleterious effects of the lower doses, which are similar to the levels found in the groundwater of some regions in the United States, Argentina, Mexico and other countries.
"With a larger population, we can make much more definitive conclusions on whether this low dose exposure between 10 to 150 micrograms that some US populations have been exposed to are indeed deleterious, increasing cancer or even deaths," Ahsan said.
The study found no reduction in mortality risk for subjects with high baseline arsenic levels that were subsequently lowered in follow-up measurements. That suggests that the effects of chronic exposure to high levels of arsenic are not reduced even when the individual is given access to cleaner drinking water – at least not during the time surveyed by the study.
"This says that further exposure to arsenic for those individuals already exposed needs to be reduced immediately if possible," Ahsan said. "Unfortunately in a developing country such as Bangladesh, the real solution of replacing the source of drinking water from contaminated to safe water sources for 50 million people is quite a task. What is needed is for the government and international community to deal with that challenge."
The paper, "Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study," will be published online Saturday by The Lancet. Other authors include Maria Argos, Tara Kalra, Paul J. Rathouz, and Brandon Pierce of the University of Chicago; Faruque Parvez, Vesna Slavkovich, Alexander van Geen, and Joseph Graziano of Columbia University; Yu Chen of New York University; and Tariqul Islam, Alauddin Ahmed, Muhammad Rakibuz-Zaman, Rabiul Hasan, Golam Sarwar of the University of Chicago Research Office in Bangladesh. Funding for the study was provided by the National Institutes of Health.





  • Study Examines Outcomes of Lowering Homocysteine Levels With Folic Acid and Vitamin B12

    Released: 6/18/2010 1:05 PM EDT
    Embargo expired: 6/22/2010 4:00 PM EDT
    Source: American Medical Association (AMA)
    Newswise — Patients who had experienced a heart attack and lowered their blood homocysteine levels with folic acid and vitamin B12 supplementation did not have an associated lower risk of heart attack, coronary death or stroke, according to a study in the June 23/30 issue of JAMA. However, the researchers did find that folic acid supplementation did not increase the risk of cancer, which has been speculated.
    Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal, according to background information in the article. A meta-analysis of prospective studies indicated that, after adjustment for known risk factors, a 25 percent lower than usual homocysteine concentration was associated with an 11 percent lower risk of coronary heart disease and 19 percent lower risk of stroke. “Daily supplementation with folic acid typically lowers homocysteine levels by about 25 percent, and the addition of vitamin B12 lowers it by a further 7 percent,” the authors write. Other research has suggested supplementation with folic acid may offer a protective effect against stroke.
    Jane M. Armitage, F.R.C.P., of the University of Oxford, United Kingdom, and colleagues with the Study of the Effectiveness of Additional Reductions In Cholesterol and Homocysteine (SEARCH) trial assessed the effects of lowering homocysteine levels with folic acid plus vitamin B12 in 12,064 survivors of myocardial infarction (heart attack) in secondary care hospitals in the United Kingdom between 1998 and 2008. Patients were randomized to receive either 2 mg. folic acid plus 1 mg. vitamin B12 daily or matching placebos. The primary outcomes measured included first major vascular event, defined as major coronary event (coronary death, heart attack, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization.
    Patients who received the study vitamins reduced homocysteine by an average of 3.8 µmol/L (28 percent). During 6.7 years of follow-up, major vascular events occurred in 1,537 of 6,033 participants (25.5 percent) allocated folic acid plus vitamin B12 vs. 1,493 of 6,031 participants (24.8 percent) allocated placebo. “There was no evidence of any benefit beginning to emerge with more prolonged treatment and follow-up,” the authors write.
    Receipt of study vitamins also was not associated with a significant effect on any stroke (vitamins, 4.5 percent vs. placebo, 4.4 percent); noncoronary revascularizations (vitamins, 3.0 percent vs. placebo, 2.5 percent); or major coronary events (vitamins, 20.4 percent vs. placebo, 19.6 percent). There were no apparent differences in the numbers of deaths attributed to vascular causes or nonvascular causes.
    New primary cancers (excluding non-melanoma skin cancer) were diagnosed in 11.2 percent of the participants allocated folic acid plus vitamin B12 vs. 10.6 percent allocated placebo, with this difference not being significant.
    “Taken together with the previous homocysteine-lowering trials, the results of SEARCH indicate that folic acid supplementation has no significant adverse effects on cancer or other major health outcomes, even if it also produces no beneficial effects on cardiovascular disease. In addition, these results highlight the importance of focusing on drug treatments (e.g., aspirin, statins, and antihypertensive therapy) and lifestyle changes (in particular, stopping smoking and avoiding excessive weight gain) that are of proven benefit, rather than lowering homocysteine with folic acid-based vitamin supplements, for the prevention of cardiovascular disease,” the authors conclude.
    (JAMA. 2010;303[24]:2486-2494. Available pre-embargo to the media at www.jamamedia.org)
    Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.








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Obesity, Weight Gain in Middle Age Associated With Increased Risk of Diabetes Among Older Adults

Released: 6/18/2010 1:15 PM EDT
Embargo expired: 6/22/2010 4:00 PM EDT
Source: American Medical Association (AMA)
Newswise — For individuals 65 years of age and older, obesity, excess body fat around the waist and gaining weight after the age of 50 are associated with an increased risk of diabetes, according to a study in the June 23/30 issue of JAMA.

“Incidence of diabetes in the United States has doubled in the past 15 years, and is highest among adults 65 to 79 years of age. Approximately 70 percent of U.S. men and women 60 years of age and older are overweight or obese [BMI - body mass index 25 or greater]. Adiposity [body fat] is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, however, the relationships between different measures of body composition and diabetes in older adults [65 years of age or older] are not well described,” the authors write.
Mary L. Biggs, Ph.D., of the University of Washington, Seattle, and colleagues examined the relationship between measures of overall body fat, fat distribution, changes in these measures, and diabetes risk among 4,193 men and women 65 years of age and older. Measures of adiposity were determined when participants entered the study, and repeated 3 years later. The incidence of diabetes was ascertained based on use of antidiabetic medication or a fasting blood glucose level of 126 mg/dL or greater.
Over a median (midpoint) follow-up of 12.4 years, 339 new cases of diabetes were diagnosed among the study participants. The researchers found that BMI at baseline, BMI at 50 years of age, weight, fat mass, waist circumference, waist-hip ratio, and waist-height ratio were all strongly related to the risk of diabetes. “For each measure, there was a graded increase in the risk of diabetes with increasing quintiles of adiposity. Participants in the highest category of adiposity had an approximately 2- to 6-fold increased risk of developing diabetes compared with those in the lowest category. We found no evidence of significant statistical interaction by sex or race,” the authors write.
Also, compared with participants whose weight remained stable (plus or minus 4.4 lbs.) over the time period, those who gained 20 lbs. or more between the age of 50 years and study entry had an approximately 3-fold greater risk of developing diabetes during follow-up, regardless of their BMI at 50 years of age. Participants who were obese (BMI 30 or greater) at 50 years of age and who experienced the most weight gain (more than 20 lbs.) between the age of 50 years and study entry had 5 times the risk of developing diabetes compared with weight-stable participants with normal BMI (less than 25) at 50 years of age.
The researchers also found that participants in the highest categories of both BMI and waist circumference had more than 4 times the risk of those in the lowest category of both measures. Participants with a greater than 4 inch increase in waist size from baseline to the third follow-up visit had a 70 percent higher risk of type 2 diabetes compared with those who gained or lost 0.8 inches or less.
“Results of this study affirm the importance of maintaining optimal weight during middle age for prevention of diabetes and, while requiring confirmation, suggest that weight control remains important in reducing diabetes risk among adults 65 years of age and older,” the authors conclude.
(JAMA. 2010;303[24]:2504-2512. Available pre-embargo to the media at www.jamamedia.org)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.




Investigators Perfect New Version of Blood-Regulator Thrombin

Released: 6/18/2010 11:45 AM EDT
Source: Saint Louis University Medical Center
Newswise — In research led by a Saint Louis University investigator, molecular biologists have discovered a way to harness the enzyme thrombin’s anti-blood clotting properties. The finding opens the door to new medications that will treat diseases related to thrombosis, the presence of blood clots in blood vessels, which is responsible for nearly a third of all deaths in the U.S.
“Thrombosis is one of the most prevalent causes of fatal disease,” said lead researcher Enrico Di Cera, M.D., chair of the department of biochemistry and molecular biology at Saint Louis University School of Medicine. “If we could develop an anti-thrombotic drug that didn’t carry a risk of hemorrhage, it would revolutionize the treatment of cardiovascular disease, the leading cause of death in the U.S. and Western world.
“This research carries us closer to that goal.”
Blood clotting has long ensured our survival, stopping blood loss after an injury. On the other hand, if triggered in the wrong conditions, clotting can lead to debilitating or fatal conditions like heart attack, stroke and deep vein thrombosis.
Funded by the National Institutes of Health, and published in the June 18, 2010 edition of The Journal of Biological Chemistry (Vol. 285. No. 25), researchers zeroed in on thrombin, a vitamin K-dependent enzyme key to blood coagulation.
An unusual enzyme, thrombin performs distinct and even opposing functions, acting as a pro-coagulant, pro-thrombotic but also as an anti-coagulant factor depending on which target protein – fibrinogen, PAR1 or protein C – becomes activated in the blood. Researchers studied thrombin to decipher the structure-function code that enables this protein to do so many different things.
Tackling this problem far below the level of tissue and organs, molecular biologists looked deep inside the structure, examining thrombin’s amino acids to note how they behave and interact with each other.
Using protein engineering, researchers produced mutations in the enzyme’s amino acid sequence, carefully taking out pieces and replacing them, a few at a time, to find the exact locations that influence the function of thrombin. Once they found these “hot spots,” researchers went even further – trying each of the 20 natural amino acids to see which mutation would allow them to turn on and off the pro-coagulant, pro-thrombotic and anti-coagulant functions.
“We asked the question, what if we can take this enzyme and dissociate the functions, allowing only the function we want?” said Di Cera.
In earlier research, Di Cera’s team did just that. They engineered thrombin to promote activity toward protein C – the anticoagulant target protein – and minimize activity toward fibrinogen and PAR1 – the procoagulant and prothrombotic targets.
“In 2000, we engineered a thrombin mutant with potent anticoagulant properties both in vitro and in vivo and we are moving this mutant to a phase I trial,” said Di Cera. “In this study, however, we pressed further. We wanted to optimize this mutant to completely abrogate activity toward fibrinogen and PAR1.”
“With this research we optimized the mutant so that there is no clotting at all. Furthermore, we generated a new mutant with exclusive prothrombotic activity, thereby demonstrating that the individual functions of thrombin can be dissociated by replacing a single amino acid in the protein.”
Once clinical trials are performed, researchers hope to have developed an alternative to heparin, a blood thinner that is used to prevent blood clots and is often used before surgery, but which also causes allergic reactions, dosage challenges and bleeding.
“Heparin is a brute-force remedy that shuts down all thrombin functions, including its beneficial anti-coagulant role,” said Di Cera. “Our approach is a new strategy that like a smart bomb only targets the functions we want to turn off.”
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.

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WHY AM I HERE?

I am reading a book about the miracles of synchronicity. I hesitate to give the title or its link on Amazon for fear of turning people off because the author is popular, and you may have preconceived notions about him/her.

I have believed that "coincidences" are the miracles that the Divine doesn't sign their name to for many years. I have watched these miracles come into my life and transform it. Many people say, "Everything happens for a reason." It's true. The trick is to get with the flow and direct the coincidences to be aligned with your intentions.

"Intentions create coincidences," the author writes.

The Upanishads say, "You are what your deepest desire is. As is your desire, so is your intention. As is your intention, so is your will. As is your will, so is your deed. As your deed, so is your destiny."

What intentions do I live with unconsciously, I wondered. Earlier the book (Don't worry, I'll tell you later), had an exercise that was very illuminating. You were to write, "Why am I here?" I listed 15 responses with number one, of course, being to love, with to create, find justice (?), to seek and some other sort of lame ones.

Then you were to do it again. "Why Am I Here"? This time I quickly wrote 28 reasons that were not lame. Some of them surprised me, but all were intuitively on target with my inner knowledge. The began with "to love," and went on with reasons such as: to create, to write, to listen, to understand, to have compassion, to give support, to give guidance, to show the way, to seek oneness, to be God, to gain knowledge, to learn, to gain wisdom, to find joy, to find peace, to find serenity, to radiate light, to inspire, to edify, to lift up spirits and to motivate.

You were asked to see if you saw any pattern or progression in the two responses, and, "What does this tell you about how you see your life?"

The book writes, "Every coincidence becomes an opportunity for you to become the person the universe intended you to be."

"Whatever you put your attention becomes energized. Whatever you take your attention away from dwindles."

"The more attention you put on coincidences, the more you will attract other coincidences which will help you clarify their meaning."

I decided I wanted the highest intentions I could formulate and get behind. They would attract the right coincidences. I would have a better chance of achieving my soul's purpose in life.

I went back to my second list of "Why Am I Here?" I then reworded each response to form it into an intention; e.g., "I desire to love, I want to create, I wish to write, I desire to have compassion, I plan to allow synchronicity to work in my life..."

When I was a young Flower Child in the Sixties, we noticed the incredible amount of "coincidences"--how everything was always all "synched" up. One friend named the force behind this, "Cosmo." I like that. I am going to get out of the way with my limited local mind of rationalizations and unmindful sleeping while awake and let Cosmo work her/his magic on my life.

The book suggests that you journal or keep a list of the coincidences you find. Then add to them the ones that occur that relate to them. You'll find the meaning for them. You will learn what you're supposed to learn.

Okay, cynics, the book is The Spontaneous Fulfillment of Desire by Deepak Chopra. Did you ever think that he has a large publishing and speaking presence because he has a lot to share?

Why I Am Like A Box Of Chocolates









My own dear sister  was the first to tell me that I was definitely like a box of chocolates because (imagine an evil sneer here),  "You never know what you're going to get."  She wasn't just whistling "Dixie." 

When you open up that yummy looking box of Fannie May Chocolates, you might even find an empty box devoid of all but a few crumbs.  That's how I roll.  It's the well-known label you can't trust  when come to town.  "I am large. I contain multitudes," wrote Walt Whitman.  "Hey, beatnik, me too!"

My multitudes are biochemical.  Hey, I'm bipolar.  Life is one big roller coaster ride for me.  What can you expect?   I might be sweeter than chocolate covered marshmallow fluff one day, or as innocent as plain milk chocolate, or as quirky as a piece of covered pineapple.  The girl can't help it!  It's all in the way the brain is wired.  The disorder is marked by wild, cyclical mood swings from highs or mania to deep depressions which include angry outbursts. 

The ironic part for me of being described as being like a box of chocolates  is that it is supposed to be a comfort food.  It is normally ingested to prompt feelings of coziness and security.  We eat it when we are unhappy to cheer ourselves up.  It's as though Lucy van Pelt, Linus' mean older sister, poured fire ants all over his security blanket.  Doubly cruel.

Candy lovers beware!  I may not have taken all my medications lately, in which case I can seem quite nutty or taste like the "mystery" chocolates that no one really is sure of what the contents are,  and everyone is as sorry they ate it as they would be eating a big serving of meat loaf at the Target diner.

Chocolate is unfortunately not the comfort food others think of it as, when it's my personality traits its covering.  It may look enticing, but so does the Venus flytrap to an insect.  My trap slams shut just as quickly,  if I haven't taken my mood stabilizers.   I have had two ex-husbands and some long-term partners who could have attested to that,  if several of them hadn't died from sheer exhaustion and aggravation.  Yeah, they would have told you about the "Days of Wine, Chocolates and Roses."

Look out for that nougat.  You don't know what it's capable of doing inside your mouth.   It can kick back with the recoil of a .458 Winchester Mag. (500 grain, 68.9 ft. lbs.).  It can break your teeth into splinters.   Just call it one of my black moods.

The cheaters who pick up a chocolate,  and, thinking no one is the wiser, take a tiny nibble to see what's inside and then put it back, are in for some rough trade action.  They get what they deserve from my box:  mold, decay and hunks of some unknown foreign matter that they'll regret chewing and pull right out of their mean little mouths.  The result of another roller coaster day gone South.

Myself, I naturally prefer dark chocolate.  'Nuff said.

Life is like a box of chocolates because so many suffer from near multiple personalities, as I do.

Psychosis comes in different fillings and flavors too.  I relate to having a wide selection from which to choose:  "Hmmm, let's see.  Today feels like obsessive-compulsive, no, make that paranoid, but I think I feel an attack of borderline personality creeping up. Am I going up?  Down?   Have a chocolate won't you?"

Life is like a box of pre-licked chocolates if you ask me.   Where is the uniqueness and freshness?  Why is it always the same old euphoria or gloom and doom?   Why is it never the middle ground?

Have one with a cherry in it, won't you?  So I can watch as it splashes all over your face and clothes!  Gosh, I needed that laugh.

Today is a nice day.  I am mellow.  I am a chocolate covered jelly piece.  I only get a little stuck in your teeth too because I feel so good.  I like myself today.  Hey, mister, do you like me today?  If not, who cares.  I won't give two shits tomorrow. 

I'm no Rock of Gibraltar which is how one expert with nothing better to do described the appeal of the large rectangles that come in an assorted box.   Far from it, I crumble like a used Kleenex if called upon to take responsibility or act like an adult.  That's why those chocolate covered jaw-breakers will pull your teeth out by their roots.

This same time-waster candy expert says circle shapes are for party animals:  people who don't like to be alone and feel lost without company.  I prefer conflict and chaos myself--it makes me feel at home.  So I make sure that the circles contain coconut for all the people who dislike it so.

Sometimes, due to my personality disorders, and I forgot to mention adult attention deficit disorder too.  I am a piece of a little of everything like the marzipan almonds in my box.  Yes, a marzipan center topped with a roasted almond in a dark chocolate shell--a little bit of everything all rolled into one.  Too much for some, I call it a creative offering.  If I were a candy bar, I'd be a Whatchamacallit. 

And I'm nothing if not creative. I analyze everything.   If a chocolate is not made with the right ingredients, it may not taste right, look dreadful and even lead to illness.  If it is placed in fancy wrapping though it could just as easily be hiding the fact that it is cheap, nasty and inedible.  The burden of consumption is not mine.  The confined enclosure of the box could lead these delicate little gifts  to perish if not presented in the right manner.  Then the world for them would really be a terrible place. 

In summary, to throw my crazy-cone hat into the ring with Thomas Hobbes,* "The life of man (is) solitary, poor, nasty, brutish and short."  That's why my life and I are like a box of chocolates.  Now you know.  "Want a Prozac, partner?"

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*"Thomas Hobbes (5 April 1588- 4 December 1679, English Philosopher,  remembered for his work on political philosophy.  His account of human nature as self-interested cooperation has proved to be an enduring theory in the field of philsophical anthropology." -- Wikipedia



MS. REFUSENIK TELLS IT ALL: "OH, IT COULD HAVE HAPPENED TO ANYONE.''

MS. REFUSENIK TELLS IT ALL: "OH, IT COULD HAVE HAPPENED TO ANYONE.''

"OH, IT COULD HAVE HAPPENED TO ANYONE.''




I don't think I should be blamed for the little faux pas that occurred on the night of my almost first date with the cat of the walk from work. 

I was trying to get ready for my much anticipated first date with a luscious specimen from work that all the women called "The Prince."  He was the sole embodiment of everything that all the other male worker losers didn't have:  he was intelligent, great looking, and had interests other than bean counting. He had been seen reading Salon.com  at his desk while Forbes were stacked up in the wastebasket.  He drove a hot car.  Okay, call me superficial, but it's been a long dry spell since I've been out on a date.

Oprah wouldn't blame me for what happened, and I don't even think Dr. Phil would.  I have a serious case of adult A.D.D.  And if you do watch Oprah at all, then you know that hoarders have a disease beyond their control.  They deserve understanding and not criticism.

I blame my friends too.  They refused to support me in getting a pet.  They insist that even a medium-sized dog or cat would get lost in my squalor,  and never again see the light of day. I do have a pet, a very good pet, and I hide him if one of them comes over.

Aiden rang the buzzer just as I was wrestling a red leather sandal free from a clump of computer cables, mystery and extension cords and a few belts that got into the mix for some reason.   I got to him on his fourth buzz.  I like impatience in a suitor, don't you?

He looked as if he always wore that impeccable suit coat and lovely silk tie. I tried to imagine him in beat up looking jeans and a torn tee, and I couldn't. He was too perfect, while I was wracking my brain trying to remember if I had removed all of the paper towel I'd stuck in my dripping armpits while putting on my makeup.

I tried not to look at him as he took stock of his surroundings.  The look revulsion which always came over the countenances of all my new guests was just too much for me at the moment.  I had manners though, and  asked if he would care for a cool drink.  He said water would be "grand."  I liked that, "grand."  He spoke the King's English, alrighty rooh.

Of course there wasn't a single clean glass in the house.  I found one less filthy than the others, rinsed it out and filled it with cold tap water.  Then I set it down the only place where there was room:  on the floor.  It was a wide-mouthed empty jar but it would do.  

I ran to the bathroom to check for stray paper towel bits and to wipe the sweat off my face.  Then I returned to get the glass which was now a bit opaque thanks to the three pieces of ice I had pried up off the bottom of the freezer.   I handed it to Adien with all the grace I could muster as I climbed over a very tall stack of yellowed newspapers to reach him, nearly tearing the hem out of my skirt with my high heel.  

And then the man proved that he could pass an audition as a screamer in a slasher flick.  I swear the effeminate, high-pitched wail he let out had to wake not just the dead, but my zombie neighbors who were usually transfixed in front of the tube hypnotized by game shows, sit coms and fried pigs feet or some other disgusting slop.  I saw him throw the offending glass on my pile of last spring's vacation laundry, where it ricocheted off unharmed.

I was confused at first.  I thought he was some princess and the pea type who had spotted my spit-and-a-promise washing job on the pickle jar. I waited to take my scolding, as he continued to cough up sputum from the bottom of his lungs and spit the crud on my floor.  Uncalled for I say.  I don't care what kind of dive you live in.  You can't just go around spitting on people's floors!

"Did you put that creature in my glass on purpose?" he managed.  "Is that your idea of a practical joke, because, listen you bitch,  there's nothing funny about passing on germs, disease and God only knows what kind of infections."

I walked over to the glass, curious,  picked it up and yelled to my little reptile buddy, "Timmy, how did you get in there?  Did I forget to change your island home again?  I am so mean.  You just needed some clean water to get you going again."


Sure enough the high-strung little Map turtle, needed water to duck into because he felt afraid because we had a guest.  Map turtles became especially aquatic when they felt nervous or fearful.  I had neglected to provide enough water for him to cover himself.   Thank goodness he was an independent kind of guy who could look out for himself.  But being thrown across the room couldn't have soothed his nerves any.

Aiden found his way to the bathroom.  I heard him gargling with my Listerine like a row boat with a tug boat engine.   I owed Timmy some peat moss, wet sand and a little ivy plant for saving me from an evening with this hysterical neurotic.   I had a new mystery I wanted to read anyhow. So much for dating.  I think it's overrated.  Too much trouble and too many changes to go through, if you ask me. 

A TOTAL OF FOUR ROADS, TWO TAKEN, TWO NOT, by R. Frost and Me

 The Road Not Taken


Two roads diverged in a yellow wood,
And sorry I could not travel both
And be one traveler, long I stood
And looked down one as far as I could
To where it bent in the undergrowth;

Then took the other, as just as fair
And having perhaps the better claim,
Because it was grassy and wanted wear;
Though as for that, the passing there
Had worn them really about the same,

And both that morning equally lay
In leaves no step had trodden black
Oh, I kept the first for another day!
Yet knowing how way leads on to way,
I doubted if I should ever come back.

I shall be telling this with a sigh
Somewhere ages and ages hence:
two roads diverged in a wood, and I --
I took the one less traveled by,
And that has made all the difference.

Copyright © 1962, 1967, 1970
by Leslie Frost Ballantine.



 
The Street Not Taken, by MsRefusenik (with apologies to R. Frost)

Two streets forked in a bad slum.
I didn't want to go down either one.
I stood there trying not to look too dumb.
As far as I could see all was scum.
If only I had carried a big gun.

I chose the one without the dead rat,
Too late, I saw it had all the crack dealers.
When they spoke to me I sure didn't chat.
Could the other have been where it was at?
Next time, I vowed, I'll first put out some feelers.

I had a choice and I chose Crack Lane.
No wonder I didn't see many people walking here.
If I ever make this trip again I'll take a plane.
Or maybe I could hire me an Andy Frain.
I won't come back because I feel too much fear.

I'll be home soon and here I come.
The guys in the bar will buy me a drink.
Two streets forked in a bad slum,
And I ran before I knew what from
It very nearly sent me over the brink

(fish surrendering) haiku

fish surrendering
their flesh to man's foul contempt
an ocean of shame

I TOUGHT I LOST MY BLOG TONIGHT

You know my Mac is hacked.  I say that because it is true without a doubt.  The a-hole took over my little 17-inch iMac 5,2 and turned it into a Leopard server.  I read that Tiger 10.4 Macs made very good servers.  I won't go into all the torment, persecution, money and jobs lost, sanity threatened, well-being undermined, etc.  You can guess if you have half an imagination.

I got desperate to get rid of this guy the other day, not that I'm not always desperate, but now he's used up all but a whif of memory and the poor thing is dying.  I went to the Ethical Hackers Network forum and posted my problem looking for advice.  What I really wanted was for some good soul, some once black hat and now white hat hacker to come forward and tell me he'd hack my Mac back.  But instead I got two replies telling me to pack it up and move on.  The one reply suggested that I might try not broadcasting on the Internet or something like that.  I didn't know what he was talking about until I saw the link there.  I clicked on it and was staring at MsRefusenik's 400 Google mentions, many of them taken from private sources.  I flame across the Internet and I guess now I am paying the price.

I checked my Gmail account today and happened to notice a lot of drafts--over 220.  That didn't look right to me.  I started opening up the ones that said "no subject."  They were all scripts--probably Trojans he put there.  I began to delete and there were so many I just got overwhelmed and gave up.  I had to get out of there.

Then tonight I went back to pull the plug on Buzz.   I had just read the above article, "Top 10 Privacy Tweaks You Should Know About," by Kevin Purdy,  originally published in Lifehacker.  It's a really good article and one you should pick up just for the links on how to do a background check on yourself if nothing else.

I had just been wondering last night what this Buzz was that has appeared on my Gmail page.  I read somewhere on Google that you would get more traffic for your blog by linking to it, so I did.  Kevin says no, no, no.  It's the last thing you want to do.  Buzz exposes parts of your e-mail; namely your contacts and a profile page, and I'm not sure what else.

So I'm there to try to get Google to limit my public exposure, and lo and behold, I see above all my mail a huge banner with a picture of me, parts of profile taken from my blogs, and a bunch of personal info.  They wanted me to give out my e-mail address too.  All of this was going into Google pages I read.

I could not believe it.  Without reading the whole thing, I just checked where it said "delete."  The last line I saw vanishing said that my blog was attached.  I was outraged.  How could Blogger do this to me?  I have about 50 posts in this thing, and there's some sentimental value as an online journal.

My heart was beating fast as I jumped all over the help pages looking for how to undelete it.  I searched the topic in the help forum and was relieved to learn that some people actually got there's back.  I followed one suggestion and went back to my dashboard and just kept clicking on the "Save All" or whatever it says on the bottom of the page to bring up the extra blog there's not room for which is always the only one I still use.  I kept pushing that sucker and suddenly as if  by magic my sweet blog reappeared.

I still am angry at Google and Blogger.  Don't they know that we don't live in a world where we can afford to advertise ourselves anymore?  I'm re-thinking Facebook even though two good friends just re-entered my life after about a thousand years of being gone.

I have been a bit publicity hungry because I like traffic.  I like to have readers write to me, and I write back.  I think I've learned my lesson.  When will Google?

Anyhow I get to Gmail tonight

I OUGHT TO BE IN PICTURES


I was whining about my hacked computer over at Ethical Hacking Network Forum, and looking for some advice and help tonight. Now he has locked me out of the computer which sits on my desk. I have been through so much with this hacker that I believe I have to write a book to adequately outline all of my unbelievable adventures as a hackee.

Anyhow, I only got two replies from my plea. One man strongly suggested that I might want to change my screen name, you know, MsRefusenik. He included a link. I clicked on the link and came to Google's lengthy spread of MsRefusenik's embarrassments, exploits, writings and misadventures. There are something like 437 of them. So I guess it's safe to say that I haven't been a real private person--at least MsRefusenik hasn't been.

But I found the coolest thing while I was scanning what all is there. There are pictures of Refuseniks from all over the world. I was beginning to feel like the only one. No, there must be hundreds. I saved the best ones I saw, and I didn't even even go through them all.

So if you've ever wondered why she (me) calls herself "Refusenik," know now that she is in good company with courageous people.

Here now is a gallery of some of my fellow Refuseniks:

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Mafia Refusenik

I HAVE A BOOK OUT! (Oh, I am so grandiose. I contributed an essay to an anthology.)




Of course, the theme of these non-fiction, true essays is that when a door is shut, a window is often miraculously opened for us and we continue on--even if perhaps we find ourselves on a whole new path.

My essay is "The Transformation." It's on page 130. Here is the blog page the editor keeps us about the book's progress:


ANNOUNCEMENT to Family, Blog Readers, and Friends:

Friday, March 12, 2010

The book is here!
When One Door Closes
Reflections from Women on Life’s Turning Points


On behalf of all of the authors in this book, I am happy to announce the publication of this fascinating collection of diverse stories by 53 remarkable women from the U.S, Canada and The Netherlands!

Every book purchased will help women and girls facing difficult transitions in their lives. Sugati Publications is donating 35% of all profits to five non-profit organizations that assist women. For more information about the designated non-profit recipients, go to the Reflections From Women website.

When One Door Closes brings forth genuine and heartfelt accounts that offer readers an opportunity to make a connection, to engage in reflection, to find encouragement on their own journeys, and to discover that even in the most difficult of circumstances, compassion, hope, forgiveness, and peace can be found.

To see previews of each of the stories or to provide comments on any of the essays/poems, visit the blog at: ] Consider leaving a comment if an essay or poem calls out to you. The authors will appreciate your feedback.

Thank you for your interest in this book and your support of the 53 authors. May you find peace on your own journey and at every turning point.

Terri Spahr Nelson, Editor

Check out this review!
I found "When One Door Closes" powerful. I think it should be required reading for all men. The complexity and depth of the experiences, emotions and wisdom captured in these essays is amazing. --Greg Flannery, Editor, Street Vibes

So dear MsRefusenik Readers, if there are any (blog stats say there aren't), if you do get a chance to pick up the book, I hope that you will find as I did that it empowers your feminine spirit that knows it can overcome any hardship and achieve a life of greatness and giving. If you benefit from what you read, please be so kind as to take a few minutes and write a review:

In the meantime, I must get started on revising my novel that I wrote in 90 days for

I Wrote A Novel

I did it. I wrote a Novel in 30 days with support and encouragement from people at NaNovWriMo. I have my certificate to prove that I am a winner. I have wanted to write a novel since I was first old enough to read one. It has been on my goals list for the past umpteen years. And I finally did it. I'm not saying it's a brilliant novel. I'm not saying that it will be published and become a bestseller. It may sit forever in my desk drawer, but I'll know that I wrote a novel. I am very proud of myself. I can't wait to get started on the next one. But that will have to wait until I finish revising this one and sending it off to get printed as a book. I have a lot of editing to do. I learned how to write a novel as I felt my way along the process. I made tons of mistakes. I figured if I waited to write one until I knew exactly how to do it perfectly, I might never write one. NaNovWriMo seemed a great opportunity to just go for it, dive in and get the deed done. I'm so glad I did it. I even sort of kept up with my freelancing work. I was late on a couple of deadlines, but I still got perfect evaluations from project directors. My apartment was a disaster and I did no laundry or dishes, but that's nothing new. Neither was the mountain of unopened mail left for me to sort or the pounds of magazines and newspapers to sort and recycle. It was all well worth it.

Walt Whitman's quote from the preface of "Leaves Of Grass:" A Call To Free, Passionate People

"This is what you shall do: Love the earth and sun and the animals, despise riches, give alms to every one that asks, stand up for the stupid and crazy, devote your income and labor to others, hate tyrants, argue not concerning God, have patience and indulgence toward the people, take off your hat to nothing known or unknown or to any man or number of men, go freely with powerful uneducated persons and with the young and with the mothers of families, read these leaves in the open air every season of every year of your life, re-examine all you have been told at school or church or in any book, dismiss whatever insults your own soul; and your very flesh shall be a great poem and have the richest fluency not only in its words but in the silent lines of its lips and face and between the lashes of your eyes and in every motion and joint of your body." - Preface to the 1855 edition of Walt Whitman's Leaves of Grass I have loved Walt Whitman since I first was introduced to him in high school. His poetry is full, authentic, passionate, dangerous and courageous. He is never afraid to be himself and to say exactly what he feels and thinks. Yes, "stand up for stupid and crazy," I'm sure there wasn't a large following behind that exhortation, and yet it is so disarmingly candid and innocent. "Take off your hat to nothing known or unknown to any man or number of men." Stand tall and proud and be counted as an authentic, noble and proud person who knows who he or she is and need not bow to anyone. I love it that he asks the readers to "re-examine all you have been told at school or church or in any book." Learn to be an original thinker. Trust your own judgment. Don't believe everything you have been spoonfed. Don't take second-hand information to heart as truth until you have sieved it through your mind for its purity of truth. "Dismiss whatever insults your soul." It would be fair to guess that some of what insulted Whitman's soul might have been narrow mindedness, judgmentalism, puritanicalness, false morality, hypocrisy, phoniness, bad poetry, hurting the environment, looking down on the common man and the like. This is only a small part of the long preface. In it he writes about his love for the United States of America and his love for poetry that sings. He says about poetry: "The poems distilled from other poems will probably pass away. The coward will surely pass away." How accurate his views. Whitman's poetry is still powerful because he had the courage to show his whole authentic self in his poems. His poems were as unique and as original as he was. The imitators' poetry we do not still study in high school and college classrooms. To me this quote is electric in its vibrancy and power. It rings with the truth of a man's heart and soul. It is a prayer for every man, woman and child. It is a spiritual meditation on originality, art, nature, simplicity, simple people, the poor, God, the uneducated, mothers with families, and for our human frailties and strengths. Author Notes Walter Whitman (May 31, 1819 - March 26, 1892) was an American poet, essayist, journalist, and humanist. Proclaimed the "greatest of all American poets" by many foreign observers a mere four years after his death, he is viewed as the first urban poet. He was a part of the transition between Transcendentalism and Realism, incorporating both views in his works. His works have been translated into more than twenty-five languages. Whitman is among the most influential and controversial poets in the American canon. His work has been described as a "rude shock" and "the most audacious and debatable contribution yet made to American literature."

HE WAS JUST A POOR MIXED UP MISUNDERSTOOD KID

Why are they selling Michael Jackson's 911 tapes? And crowding at the hospital where he died? It's another media circus run by apes. For voyeurs who have absolutely no sense of pride. He was society's monster who never got to grow up. Dragged too soon, too fast into the sickly green of the limelight. Too much fame, way too much wealth, power not meant for a pup. He was seen in every kind of pose, lit from above, and in backlight. An aging child with no one to play with that was like himself. He got in trouble for trying to spend time with his real peers. He didn't mean anyone any harm. He was just a little elf. It was hard to know that he had grown up over the years.

101 BEST WEBSITES FOR WRITERS IS OUT

The 11th annual 101 Best Websites for Writers is out courtesy of Writers Digest. Hooray for them. This year they say they went through 2,700 nominations and got the best of the bunch for the listing. This year's list features more blogs and free market listings than in previous years. There are eight sections: Creativity and Challenges, General Resources, Agent Blogs, Publishing Resources, Jobs and Markets, Writing Communities, Genres/Niches and Fun for Writers. It's easier than ever to scan for what you're looking for--blogs, chatting, critiques, classes/workshops, contests, forums, jobs, markets, e-newsletters, podcasts and content for young writers.