Morphine is currently the gold standard of analgesics used to relieve severe pain and suffering. Angiogenesis, or new blood vessel growth, is critical for tumor progression from dormant to malignant. Morphine is commonly used to treat cancer pain, but the effects of morphine use on new blood vessel and tumor growth remain controversial.

Using a clinically relevant morphine dose in a mouse model of Lewis lung carcinoma, researchers led by Dr. Sabita Roy of the University of Minnesota Medical School in Minneapolis, MN examined the effect of morphine use on new blood vessel growth in tumors. They found that chronic morphine use decreased levels of tumor angiogenesis in a manner dependent on the opioid receptor. This effect was mediated by suppression of signaling induced by low oxygen concentrations, leading to a reduction in the levels of pro-angiogenic factors. Therefore, morphine may not only serve as an analgesic for cancer patients, but may also inhibit tumor angiogenesis and growth.

Koodie et al conclude that "morphine is a potential inhibitor of tumor growth, through the suppression of tumor cell-induced angiogenesis and hypoxia-induced p38 MAPK activation of HIF-1. In addition to its analgesic potential, morphine can be exploited for its anti-angiogenic potential in cancer pain management; these findings support the use of morphine for cancer pain management."

This work was supported by the National Institutes of Health (NIDA/NIH, F31-DA021005-01 to LK; CA114340 to SR; and NIDA/NIH grants RO1 DA 12104; RO1 DA 022935; KO2 DA 015349; P50 DA 011806 to SR).

The device, built by a research team, led by biomedical engineer Jiping He, Ph.D., and his colleagues at Arizona State University and Kinetic Muscles, Inc., a start up biotech company, can also assess the effectiveness of the physical therapy so adjustments can be made to the regimen if necessary. He will present a paper on the robotic arm this summer at the 9th International Conference on Rehabilitation Robotics in Chicago.

Recent research suggests that stroke survivors can recover significant use of their arms by performing repetitive motor function exercises over a period of time. This labor intensive physical therapy is expensive, however, claiming up to 4 percent of the national health budget, according to the National Institutes of Health. Moreover, health insurers may limit or deny coverage before stroke survivors achieve best results, He said.

"This device is intended to provide cost-effective therapy to a wider population for a longer period of time for maximum recovery of motor function," He said of the device, dubbed RUPERT I, for Robotic Upper Extremity Repetitive Therapy.

RUPERT I is powered by four pneumatic muscles and is movable at the shoulder, elbow and wrist. The design was based on a kinematics model of the arm, which showed where to locate the pneumatic muscles and how much force was needed for normal reaching and feeding movements. The mechanical arm is adjustable to accommodate different arm lengths and body sizes.

The first prototype was fitted and tested on able-bodied individuals and stroke survivors at Banner Good Samaritan Regional Medical Center in Phoenix. Eight able-bodied individuals tried on RUPERT I to see how well it could be adjusted to fit each in each case. The testers ranged from 5-foot females to over-6-foot males. In addition, two stroke survivors completed a three-week course of therapy using the device.

RUPERT II, a second generation prototype, is under development using results of the fitting evaluations and therapy testing at the medical center.

Researchers have long observed significant differences in normal people’s sleep. Some are light sleepers, whereas others sleep deeply. Some fall asleep right away, while others take their time.

Such sleeping pattern variability has long been attributed solely to differences in circumstances, habits, and other non-biological factors. But now a study led by Hans Van Dongen, associate research professor and assistant director of the Sleep and Performance Research Center at Washington State University Spokane, has shown that these individual differences constitute traits—that is, they are in large part biologically determined and may even prove to be genetic in origin.

“This is the first study to reveal that substantial differences in sleep patterns exist even among healthy adults who are good sleepers,” said Van Dongen, who emphasized that normal sleep covers a wide terrain and that many different sleep patterns qualify as good sleep. “How much sleep people need and what the structure of their sleep looks like depends in large measure on their biology.”

The results of the NIH-funded research study were published in the June 2007 issue of the Journal of Sleep Research, with WSU graduate student Adrienne Tucker as the lead author. The study, which was conducted in large part at the University of Pennsylvania and was recently continued at Washington State University, assessed the presence and magnitude of biologically determined individual differences in the structure of sleep for a group of 21 carefully screened healthy young adults, and compared these individual differences to the effect of prior sleep deprivation on the structure of their sleep.

Over 11 consecutive days and nights, study participants were monitored continuously in a strictly controlled laboratory environment. They spent eight nights sleeping for up to 12 hours. These nights were interspersed with three 36-hour sleep deprivation periods—that is, three nights without any sleep. During the eight nights when sleep was allowed, polysomnographic recordings—which show brain waves, eye movements, and muscle tone—were done.

The researchers assessed 18 standard sleep parameters, including sleep duration, time to fall asleep, and the amount of time in each sleep stage (stages 1 through 4 and REM sleep). They found large individual differences in these sleep parameters, which showed up consistently across the eight nights with sleep—regardless of whether or not there had been sleep deprivation in the night before. This meant that the individual differences were not driven by circumstance, but were at least partially biologically determined. For deep sleep (stages 3 and 4) in particular, the individual differences were overwhelmingly biological in nature.

“In this group of healthy young adults, the wide variation in the duration and structure of their sleep was, to a large extent, biological in nature. The next logical step is to look for genes that may be responsible for these large individual differences,” Van Dongen said.

The physiological or functional significance of these sleep traits remains a mystery. The fact that all subjects were healthy, young adults and good sleepers seems to rule out any immediate clinical relevance of the differences among them. However, Van Dongen thinks that the sleep differences may be predictive of future clinical conditions.

“Recognition of trait individual differences in sleep may help to understand the increasing evidence for a functional link between sleep and health,” he said.

The brain is composed of billions of neurons that must connect their axons with an appropriate set of targets to form the neuronal circuits that underlie its function. Developing axons are guided to their targets by attractive and repulsive guidance molecules. Inappropriate wiring or damage of these neuronal connections leads to severe abnormalities of the nervous system.

Three years ago, while he was a postdoctoral fellow in the laboratory of Dr. Marc Tessier-Lavigne, Dr. Charron discovered that Sonic Hedgehog (Shh) is an axonal attractant for brain and spinal cord neurons. However, the mechanism by which Shh elicited this effect remained unknown. The recent work of Dr. Charron, performed in close collaboration with Dr. Ami Okada and the teams of Drs. Sue McConnell and Marc Tessier-Lavigne, at Stanford University and Genentech, respectively, showed that Shh exerts its attractive effect through a novel receptor named Boc. Remarkably, this novel Shh receptor is absolutely required for the axon guidance role of Shh and the role of Shh in brain neural circuit formation.

"The findings of Dr. Charron and his team are of great relevance in developmental neurobiology and our understanding of normal brain development. This research could eventually have an impact on our understanding of neurodevelopmental disorders," says Dr. Rémi Quirion based in Montréal and Scientific Director of the Canadian Institutes of Health Research Institute of Neurosciences, Mental Health and Addiction. "No matter how specialized research findings may be, the knowledge we gain from them, holds the key to improved health and quality of life for Canadians and people throughout the world afflicted by neurodevelopmental disorders," adds Dr. Quirion.

In addition to helping us understand the immense complexity underlying the wiring of the nervous system, the Dr. Charron’s research will also help to identify novel strategies to promote the proper guidance and wiring into neural circuits of axons damaged by neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, or by brain and spinal cord injuries.

This work will be published only a year after Dr. Charron established his laboratory at the Institut de recherches cliniques de Montréal (IRCM).

"Dr. Charron is one of the country’s leading newly arrived neuroscientists. This research has important long-term implications for the repair of spinal cord injury: if we knew all of the molecules required to guide axons correctly during spinal cord healing, we’d know how to heal spinal cord injuries " says Dr. Rod McInnes, Scientific Director of the Canadian Institutes of Health Research Institute of Genetics. "This is beautiful research that adds another major brick to our building a complete understanding of how the spinal cord is made, and how injury of it can be treated."

As people age, their bones lose calcium and they are more at risk of fractures and osteoporosis — this is especially the case for women. As well as causing individual suffering, fractures are a huge drain on health services.

With aging populations, this burden will increase in the coming years and therefore preventing them is a major public health issue, say the authors, led by Dr Eva Warensjö from Uppsala University in Sweden.

The importance of increasing calcium intake to compensate for the loss of calcium has been debated for a long time and there is still no clear advice. This is reflected by the wide range of daily calcium recommendations for the over fifties — in the UK it is currently 700 mg; it is 800 mg in Scandinavia and 1,200 mg in the US.

In order to investigate the links between long-term dietary calcium intake and the risk of fractures, the authors reviewed data from a large population study of Swedish women carried out in 1987.

Over 61,433 women (born between 1914 and 1948) took part in the Swedish Mammography Study and of these 5,022 participated in a smaller sub-research group. All participants were followed up for 19 years.

During the follow-up, 14,738 (24%) women had a first fracture and, of these, 3,871 (6%) had a first hip fracture. Twenty percent of the sub-group had osteoporosis.

The researchers used a series of questionnaires to gain in-depth knowledge of the participants’ changing diet and in particular their calcium intake and use of supplements and multivitamins.

The women also provided information about their menopausal status, whether or not they used post-menopausal oestrogen therapy, their weight, height, smoking habits, how much physical activity they did and their educational attainment.

The results show that women had the lowest risk of having a fracture when they consumed around 750 mg a day of calcium. However, the fracture risk in women who started to increase their calcium intake over time did not decrease.

There is some evidence that high intake of calcium may actually increase the rate of hip fractures, though the authors stress that this result needs to be interpreted with caution.

The authors conclude that while low levels of calcium intake (less than 700 mg per day) increase the risk of fractures and osteoporosis, there is no need to start increasing calcium intake above the amount. Increases did not further reduce the fracture and osteoporosis risk.

Dr. Karin Olson, a U of A professor from the Faculty of Nursing, argues that there are differences between tiredness, fatigue and exhaustion and that recognizing those distinctions will help health-care workers create better treatment plans for their patients. Her findings are published in the current issue of "Oncology Nursing Forum."

Olson has studied fatigue in six ill and non-ill populations: shift workers, recreational long distance runners, individuals with cancer in active treatment or palliative settings, and individuals diagnosed with depression or chronic fatigue syndrome. Having worked with cancer patients for many years, she saw how serious fatigue was and the impact it had on the patients’ quality of life. Some patients even withdrew for a potentially curative treatment saying they were "too tired."

"The kind of fatigue experienced by individuals with cancer is different from the feeling that you or I have at the end of a busy week," said Olson. "Interestingly, when you start looking at other populations, such as people with chronic illnesses or shift workers and take a broad view, the descriptions of fatigue are the same. Thus, while the reasons for fatigue may vary, the kinds of adaptations required may not."

Olson, who is currently an Alberta Heritage Foundation for Medical Research (AHFMR) Health Scholar, has created new definitions for tiredness, fatigue and exhaustion and argues that they represent various points on an energy continuum. The amount of energy a person has influences how easily he can adapt to stress that comes his way. Individuals who are tired still have a fair bit of energy, so although they may feel forgetful, and impatient, and experience gradual heaviness or weakness in muscles following work, this is often alleviated by rest. Fatigue, on the other hand, is characterized by difficulty concentrating, anxiety, a gradual decrease in stamina, difficulty sleeping, increased sensitivity to light and the limiting of social activities once viewed as important. Individuals with exhaustion report frank confusion that resembles delirium, emotional numbness, sudden loss of energy, difficulty both in staying awake and in sleeping and complete social withdrawal.

"It is important to recognize the difference between tiredness and fatigue, because fatigue is a marker that the body is not able to keep up," says Olson. "The onset of the manifestations of fatigue, particularly if these are not normal states for you, should be taken seriously."

Failing to understand the distinctions between tiredness, fatigue and exhaustion could result in the use of inappropriate interventions that inadvertently promote fatigue and exhaustion. Olson has some evidence that while exercise appears to help those who are tired, it may decrease the ability to adapt in individuals experiencing fatigue and exhaustion. Long-term use of caffeine and other stimulants should also be avoided by people experiencing fatigue and exhaustion, as these substances "fool" the body into thinking it has more energy available than it really does.

"The important thing is to try to prevent or at least delay the progression from tiredness to fatigue and then from fatigue to exhaustion," said Olson. "We are starting to work on some interventions that we think may be helpful. In the meantime, families and friends can help by recognizing changes consistent with fatigue and exhaustion and look for ways to help minimize stress."

This work may also have applications to other population, such as students or individuals with chronic illnesses, who have not been studied to date. "Students tend to stay up late at night, studying hard," said Olson. "Some studies show that changes in sleep patterns are may compromise one’s ability to remember things and to integrate new information.

"We’re a long way from having all the answers but this study was a start. It has provided us with a great foundation for future research among individuals with cancer and other groups ranging from ‘burned out’ workers to recreational athletes and people with chronic diseases."

"The results indicate that gay men encounter significant barriers in the hiring process because, at the initial point of contact, employers more readily disqualify openly gay applicants than equally qualified heterosexual applicants," writes the study’s author, András Tilcsik of Harvard University.

The research will be published October 4 in the American Journal of Sociology.

For the study, Tilcsik sent two fictitious but realistic resumes to more than 1,700 entry-level, white collar job openings — positions such as managers, business and financial analysts, sales representatives, customer service representatives, and administrative assistants. The two resumes were very similar in terms of the applicant’s qualifications, but one resume for each opening mentioned that the applicant had been part of a gay organization in college.

"I chose an experience in a gay community organization that could not be easily dismissed as irrelevant to a job application," Tilcsik writes. "Thus, instead of being just a member of a gay or lesbian campus organization, the applicant served as the elected treasurer for several semesters, managing the organization’s financial operations."

The second resume Tilcsik sent listed experience in the "Progressive and Socialist Alliance" in place of the gay organization. Since employers are likely to associate both groups with left-leaning political views, Tilcsik could separate any "gay penalty" from the effects of political discrimination.

The results showed that applicants without the gay signal had an 11.5 percent chance of being called for an interview. However, gay applicants had only a 7.2 percent chance. That difference amounts to a 40 percent higher chance of the heterosexual applicant getting a call.

The callback gap varied widely according to the location of the job, Tilcsik found. In fact, most of the overall gap detected in the study was driven by the Southern and Midwestern states in the sample — Texas, Florida, and Ohio. The Western and Northeastern states in the sample (California, Nevada, Pennsylvania, and New York) had only small and statistically insignificant callback gaps.

"This doesn’t necessarily mean that there is no discrimination in those states, just that the callback gaps were small in the case of the jobs to which I sent applications," Tilcsik explained. "I think it’s very plausible that, even in those states, there might be a large callback gap in some other jobs, industries, or counties. What this does show is that discrimination in white-collar employment is substantially stronger for the Southern and Midwestern states in the sample."

The research also found that employers seeking stereotypically heterosexual male traits were more likely to discriminate gay men. Gay applicants had lower callback rates when the employer described the ideal candidate for the job as "assertive," "aggressive," or "decisive.

"It seems, therefore, that the discrimination documented in this study is partly rooted in specific stereotypes and cannot be completely reduced to a general antipathy against gay employees," Tilcsik writes.

The technique Tilcsik used, known as audit study, has been used in the past to expose hiring prejudice based on race and on sex. This is the first major audit study to test the receptiveness of employers to gay male job applicants.

Understanding the ways in which these biases might operate at the interview stage of the employment process, or how they might apply to lesbian job seekers in the U.S., requires additional research, Tilcsik says.

The protein, called the calcium-sensing receptor, sits on the surface of lung cancer cells that make up tumors known as squamous-cell carcinomas, according to new research.

As these tumors grow, the receptor releases a hormone that sets off a biological cycle that leads to the erosion of bone throughout the body. When the bone breaks down, calcium is released. The excess calcium that can’t be filtered by kidneys cycles back to the receptors, which release more of the damaging hormone. That same hormone promotes the growth and spread of cancer.

The result is a syndrome called hypercalcemia, a debilitating disorder that signals lung cancer patients will survive only about three more months and eventually leads to acute multi-organ system failure.

Knowing the receptor’s role in squamous-cell lung cancers will help guide future research on new treatment options for both the cancer and hypercalcemia, said Gwendolen Lorch, assistant professor of veterinary clinical sciences at Ohio State University and lead author of the study.

"The calcium-sensing receptor clearly has a huge role in hypercalcemia. Though it’s too soon to say it could be a target for treatment, we won’t ever be able to find the right target if we don’t know how hypercalcemia develops in the first place," Lorch said.

The researchers also found that lung cancer patients who have a specific type of inherited genetic mutation are at risk of developing hypercalcemia earlier than others. This finding is likely to have clinical implications in the future, as sequencing of the human genome becomes more affordable and available as part of standard medical care, Lorch said.

The research is published in a recent issue of the journal Neoplasia.

Before this study, previous research had established that the calcium-sensing receptor is important to lung development because mice lacking the receptor showed stunted lung growth. But its presence had never been documented in adult human lungs.

Researchers also knew that hypercalcemia was associated with unregulated release of a specific hormone, and that it developed in patients with cancers based in the epithelia, or tissue that makes up the lining of organs, blood vessels and body cavities. Squamous-cell carcinoma of the lung is one of these types of cancers.

Despite all that was known, however, the connection between the receptor and hypercalcemia had never been established in lung cancer. Studies suggest that anywhere from a fourth to two-thirds of lung cancer patients will develop the deadly syndrome.

Hypercalcemia symptoms include nausea and vomiting, loss of appetite, heart arrhythmia, high blood pressure and acute kidney failure. Most patients suffer dementia, become irritable and have sleep problems, and eventually have seizures, slip into a coma and die.

Some of the few treatment options available include two types of drugs that inhibit the bone loss. Fluid therapy also helps wash away the calcium. But Lorch said drugs that target the culprit hormone itself — known as PTHrP, or parathyroid hormone-related protein — are not available for human use.

"What we really need is something that works at the level of the tumor cell," Lorch said. "We don’t have anything that can reduce the tumor burden and therefore reduce the production of PTHrP."

In the study, Lorch and colleagues obtained squamous-cell lung cancer cell lines from three human patients. The researchers first showed with genetic data that all of these cells had produced proteins that indicated that the cells contained calcium-sensing receptors — a new finding in itself.

They then tested the cell lines to see how much calcium it would take for the receptors on those cells to produce the maximum amount of the PTHrP hormone. All three lines produced the highest hormone levels when the calcium concentration reached the equivalent of 12 milligrams per deciliter of calcium in blood in humans — the level at which hypercalcemia is diagnosed. Normal values range from 8.5 to 10.2 milligrams per deciliter.

"This told us that when people are hypercalcemic, they are producing the maximum level of PTHrP," Lorch said.

An experiment in mice confirmed the calcium-sensing receptor’s role. Mice were injected with either regular tumor cells or cells from which the calcium-sensing receptor had been stripped away. Mice that received cells without the receptor developed hypercalcemia in 49 days, compared to 29 days for mice that received typical tumor cells, which do have the receptor.

"That’s a very big difference in time in mice," Lorch said. "This suggests that the calcium-sensing receptor was necessary for the rapid development of hypercalcemia."

The receptors on those cells also behaved as expected in additional cell line experiments exploring their behavior after the PTHrP hormone was released. All three lines led to the release of what is known as intercellular calcium, but at different levels and rates. One line in particular stood out. This line, called HARA, had previously produced the most PTHrP when stimulated with calcium, and then released much more excess calcium than the other two cell lines.

These findings in the tissue studies led the scientists to sequence the calcium-sensing receptors in the three cell lines to look for genetic variants. The HARA line contained a mutation known as a single nucleotide polymorphism, or SNP (pronounced snip), that influenced how much of the PTHrP protein the receptors produced and how much calcium it took to stimulate that action.

What this means is that lung cancer patients who have two copies of this mutation — one from each parent — are more likely to develop hypercalcemia even before their blood work shows elevated levels of calcium.

"The significance of this is if you have two copies of the mutation, it would be ideal for a clinician to know that you have this mutation and start pre-emptive fluid therapy or other preventive treatment. Even in the normal calcium range, this mutation is going to set a person up for hypercalcemia much earlier than other patients," Lorch said.

Calcium-sensing receptors are present in other areas of the body, which complicates their status as a potential drug target specifically for hypercalcemia in lung cancer, Lorch noted. She is continuing to study this receptor and others in a family of proteins known as G-protein-coupled receptors, which are important to tumor initiation, promotion and development.

This work was supported by grants from the National Institutes of Health.

Co-authors include Serge Viatchenko-Karpinski, Hsiang-Ting Ho and Sandor Györke of the Davis Heart and Lung Research Institute; Wessel Dirksen and Thomas Rosol of the Department of Veterinary Biosciences; and Ramiro Toribio of the Department of Veterinary Clinical Sciences, all at Ohio State; and John Foley of Indiana University.

Suzanna M. Zick, N.D., M.P.H., a research assistant professor at the University of Michigan Medical School, and colleagues enrolled 30 patients and randomly assigned them to two grams of ginger root supplements per day or placebo for 28 days.

After 28 days, the researchers measured standard levels of colon inflammation and found statistically significant reductions in most of these markers, and trends toward significant reductions in others.

Inflammation has been implicated in prior studies as a precursor to colon cancer, but another trial would be needed to see how ginger root affects that risk, Zick said.

"We need to apply the same rigor to the sorts of questions about the effect of ginger root that we apply to other clinical trial research," she said. "Interest in this is only going to increase as people look for ways to prevent cancer that are nontoxic, and improve their quality of life in a cost-effective way."

Zick is a naturopathic doctor (N.D.), which is a four-year degree that supplements a traditional medical education with instruction on the proper use of natural therapies, diet, nutrition and other alternative treatments. Her program is one of eight in the country, compared with about 135 traditional medical schools.

The study was funded by a National Cancer Institute grant.

“In fact, the appearance of insulin-producing cells occurs in both type 1 (juvenile) and type 2 (adult-onset) diabetic mice,” said Dr. Lawrence Chan, chief of the BCM endocrinology section and professor in the department of medicine and molecular and cellular biology.

“The common denominator in all the animals is high blood sugar, not insulin-deficiency,” he said. “High blood sugar causes these cells to produce insulin.”

The numbers of cells and the amount of insulin produced are both very small and do not seem to ameliorate the animals’ disease, said Chan.

He found that the source of the insulin-producing cells is the bone marrow, which had been identified as the origin of many different kinds of tissues in recent years. He and his colleagues were surprised that only a brief three-day period of high blood glucose was sufficient to nudge the cells outside the pancreas to produce insulin.

If this inherent property of cells can be harnessed and augmented, Chan speculates, scientists could it to generate insulin-producing cells from other tissues for the treatment of diabetes. If the production of insulin by cells outside the pancreas affects the immune system, which goes awry in people predisposed to type 1 diabetes, it could affect the course of the disease.