Speak, Memory: Research Challenges Theory Of Memory Storage

Daily events are minted into memories in the hippocampus, one of the oldest parts of the brain. For long-term storage, scientists believe that memories move to the neocortex, or “new bark,” the gray matter covering the hippocampus. This transfer process occurs during sleep, especially during deep, dreamless sleep.

Many neuroscientists have embraced and built upon this theory of memory storage, or consolidation, for a generation. But the theory is difficult to test. New research led by Brown University neuroscientist Mayank Mehta, conducted with Nobel Prize-winning physiologist Bert Sakmann, shows the best evidence yet of the sleep dialogue between the old brain and the new.

Their work, published in Nature Neuroscience, also shows that this interaction occurs in a startling way. Instead of the hippocampus uploading information to the neocortex in a burst of brain cell communication, Mehta found the opposite: the neocortex seems to drive the dialogue with the hippocampus.

The findings may give scientists a new understanding of how the brain manages memories in health and during dementia, offering up a fresh look at the causes of diseases such as Alzheimer’s, as well as potential treatments.

“Long-term memory making may be a very different process than we previously thought,” said Mehta, an assistant professor in the Department of Neuroscience at Brown. “Either this reversed dialogue is, somehow, a part of memory storage or this transfer of information from the old to the new brain may not occur during sleep. Either way, the results call into question commonly held theories about the role of cortico-hippocampal dialogue in sleep.”

Edvard Moser, a professor at the Norwegian University of Science and Technology and director of the Centre for the Biology of Memory, is a leading expert on memory processes in the hippocampus. Moser said of the new research, “This technically sophisticated study may significantly influence our view of hippocampal-neocortical interactions during sleep-related memory consolidation processes.”

To study this dialogue, Mehta recorded electrical activity in rat brains. To mimic the deepest sleep states, the rats were anesthetized then fitted with two electrodes. One electrode measured the electrical activity of thousands of cells in the neocortex. These cells were excitatory, meaning that they spark communication between nerve cells. The other electrode recorded the activity of a single inhibitory cell in the hippocampus. These inhibitory cells shut down dialogue between nerve cells.

Using this groundbreaking single-cell recording technique, honed in Sakmann’s laboratory at the Max Planck Institute for Medical Research, researchers made an important finding: During deepest sleep, in both the hippocampus and neocortex, the patterns of neural activity are both regular and highly related. The cells in the old and new brains fired nearly in synch, evidenced by similar peaks and troughs shown on electroencephalographs.

This is surprising; Previous studies showed that during deep sleep, when the excitatory cells in the neocortex showed rhythmic activity, excitatory neurons in the hippocampus showed erratic activity. This stumped Mehta and his colleagues: If these two parts of the brain talk during deep sleep, why didn’t they appear to be speaking the same language? They are, Mehta and his team discovered, if you listen to inhibitory, not excitatory, cells in the hippocampus. Mehta and his team also showed that the activity of the cells is related. The timing of activity, or talk, was the same in both brain regions, with a small delay in the hippocampus – as if those cells were echoing the speech in the neocortex.

This discovery of synchronized communication between the old and the new brain – a phenomenon known as “phase-locking” – has two key implications. It suggests that the neocortex, not the hippocampus, drives the discussion between these brain systems during deep sleep. It also suggests that the inhibitory neurons control the conversation.

Mehta says the findings may change the way neuroscientists look at past experimental data and the way they conduct future research.

“We now have a way, experimentally and theoretically, to see how the two parts of the brain talk to each other,” he said. “This will help us better understand the mechanisms behind learning and memory. But what is really exciting is that this method – simultaneously studying two different cell types in two different brain areas – could be used to study other aspects of brain function, such as perception, emotion, movement. It could open important new avenues for basic and applied research.”

Along with Mehta and Sakmann, Thomas Hahn, a graduate student in the Department of Cell Physiology at the Max Planck Institute for Medical Research, helped conduct the research and also served as lead author of the journal article.

The Max Planck Institute for Medical Research, the National Science Foundation, the National Institutes of Health, NARSAD: The Mental Health Research Association, the Rhode Island Foundation and the Salomon Family Foundation supported the work.

Contact: Wendy Lawton

Brown University

Washington Post Profiles Helene Gayle, President, CEO Of CARE USA

The Washington Post on Wednesday profiled Helene Gayle, president and CEO of CARE USA, an Atlanta-based international humanitarian group (Boustany, Washington Post, 5/17). Gayle, former director of the Bill & Melinda Gates Foundation’s HIV, Tuberculosis and Reproductive Health program, was named as CARE USA’s new president and CEO in December 2005 after serving five years with the foundation. Gayle, who also serves as president of the International AIDS Society, has 20 years of experience with HIV/AIDS, including previously directing CDC’s National Center for HIV, STD and TB Prevention (Kaiser Daily HIV/AIDS Report, 12/5/05). Donna Shalala, president of the University of Miami and former HHS secretary, said that Gayle “really represents a new generation of health diplomats,” adding that she is “experienced at negotiating at the highest levels of government or with a sex worker in Calcutta.” Gayle said she wants to have a broad impact on population health. “When you talk to people working on the front lines of survival, I feel there is nothing better I can do with my life than enable them to do what they do,” Gayle said (Washington Post, 5/17).

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Conventional MRI And Computer Analysis Could Be Used To Detect Alzheimer’s

Researchers using conventional, as opposed to high powered MRI equipment, and computer-
based methods to analyze the scans, are breaking new ground in the diagnosis of the telltale signs of
Alzheimer’s Disease, increasing the likelihood that there will be reliable ways of diagnosing the disease
non-invasively and before it is too late to do something about it.

Three studies, one on successful use of conventional MRI to image brain plaques in animals, and two
on using computers to analyze MRI images, are being presented at the Alzheimer’s Association’s
2008 International Conference on Alzheimer’s Disease (ICAD 2008), which is taking place in Chicago
from 26th to 31st July.

Autopsy exams that find amyloid plaques (abnormal protein deposits around brain cells) and other
characteristic lesions in the brain (such as neurofibrillary tangles, where unwanted strands of tau
protein collect inside brain cells) are currently the only definitive diagnosis of Alzheimer’s, so any
approaches that help to spot these signs non-invasively, while the patient is alive, and early in the
disease, is a huge step forward.

High powered MRI scanners have already been used to show images of amyloid plaques in animals,
as have PET scans combined with chemical markers, but until these studies, being able to image the
plaques using conventional, clinical strength MRI scanners, was not possible.

Conventional MRI scanners are more common and less expensive than other imaging machines, and
they don’t expose people to radiation compared to high energy technologies.

Vice president of Medical and Scientific Relations at the Alzheimer’s Association, Dr William Thies,
said:

“As we get closer to the development of therapies that can slow or even stop the progression of
Alzheimer’s, earlier detection of the disease becomes crucial for early intervention.”

“Early evaluation and diagnosis is also important because some Alzheimer’s-like symptoms can be
reversed if they are caused by treatable conditions, such as depression, drug interaction, or thyroid
problems,” he added.

Early diagnosis also opens a host of other possibilities, such as access to the right medical skills,
medications, support programs, and so on. “Plus, there is the opportunity to participate in studies of
experimental drugs or other disease modifying treatments,” said Thies.

Thies said we may soon be able to use the approaches described in the studies to find out who is at
greater risk of Alzheimer’s.

Study Number 1: Amyloid Plaques in Rabbits

Researchers at Robarts Research Institute and University of Western Ontario, London, Ontario,
Canada fed laboratory rabbits a high cholesterol diet for more than 2 years so their brains formed
amyloid plaques. They then used clinical strength MRI scanners to take brain images from the
animals. These showed “signal voids”, or “black spots”, in several parts of the brain, including the
hippocampus, which is very important for memory. Autopsies showed that these areas had small
clusters of amyloid plaques together with high levels of iron, which the researchers suggest caused the
signal voids in the MRI images. Animals fed on a normal diet did not show these signal
voids.

One of the researchers, John Ronald, who is doing a PhD in Medical Biophysics at Robarts,
said:

“Although some of the technology used to generate these images was designed specifically for rabbits,
this preliminary discovery hints at the promise of using clinical MRI scanners to visualize plaques in
people with Alzheimer’s.”

“Extension of these technologies to living animals is practical, and should allow us to study the course
of Alzheimer’s in animals over time,” he added, explaining that they customized the MRI equipment in
some very important ways, such as adding hardware that sees things smaller than 50 microns across
(0.05 mm), and is able to detect iron more sensitively.

Study Number 2: Developing an Alzheimer’s Disease Severity “Score” Based on Computer
Analysis of MRI Images of Tangles

As well as amyloid plaques, neurofibrillary tangles of tau protein that collect inside brain cells are
another telltale sign of Alzheimer’s, and there is a way of measuring these as an index of disease severity (post mortem)
using a “gold standard” called Braak staging.

Researchers at the Mayo Clinic, Rochester, Minnesota, developed a computer algorithm that takes
characteristic information from a person’s three-dimensional MRI scan and compares it to a standard
score called STAND (STructural Abnormality iNDex, a measure of tangle severity), which was
calibrated from comparing people’s MRI scans before death with their Braak stage after death.

The person is given a STAND score based on the degree of atrophy in their brain compared to atrophy
patterns from a library of MRI scans of 160 Alzheimer’s and 160 patients who did not have the disease
(cognitively normal). A positive STAND score means more Alzheimer’s-like, and a negative score
means more normal-like. STAND scores are adjusted for demographcs, and have a 90 per cent
accuracy, said the researchers, who validated the adjusted STAND scores against Braak staging
using 101 patients who had MRI scans within 4 years of their death and who underwent post mortem
Braak staging.

One of the researchers, Dr Prashanthi Vemuri, said:

“This study shows that information extracted from MRI scans can accurately capture the severity of
Alzheimer’s tangle pathology.”

“While this work needs to be replicated and confirmed, because there is evidence indicating that
structural changes in the brain precede cognitive symptoms, STAND scores may also prove to be
useful for early identification of Alzheimer’s,” added Vemuri.

Study Number 3: Measuring Alzheimer’s-like Brain Abnormality in Normal Elderly

In a previously unreported study, researchers at the University of Pennsylvania, Philadelphia, and
National Institute on Aging, Bethesda, Maryland, analyzed computer-based images (using a new
approach called advanced high-dimensional pattern classification) of MRI scans of participants in the
Alzheimer’s Disease Neuroimaging Initiative (ADNI) and developed an index of Alzheimer-like brain
abnormality.

Then, in a new study presented at the conference, for 9 years they studied 109 elderly participants who were
cognitively normal and a small group who had mild cognitive impairment (MCI), from the
Baltimore Longitudinal Study of Aging (BLSA). They found that Alzheimer’s-like patterns of brain
atrophy were more common in participants who were over 80 years old. The rate of progression,
based on their new index, was also higher among the older participants.

They found that healthy elderly participants, and those with MCI, where both had the Alzheimer’s-like
brain atrophy patterns, performed worse in memory tests, compared to people who did not have the
abnormal brain patterns and had lower Alzheimer’s-like index values.

One of the researchers, Dr Christos Davatzikos, of the Department of Radiology at the University of
Pennsylvania, said:

“Although the clinical significance of these Alzheimer’s-like patterns of brain atrophy must be further
evaluated, we are very hopeful that these pattern analysis tools will provide early indicators of brain
changes that resemble those seen in people with Alzheimer’s, years before memory problems are
recognized clinically.”

“Direct visualization of [beta]-amyloid plaques in hypercholesterolemic rabbits using clinical
field-strength MRI.”
John Ronald
ICAD 2008

“Antemortem MRI based structural abnormality index (STAND)-scores correlate with
postmortem Alzheimer disease Braak stages.”
Prashanthi Vemuri
ICAD 2008

“Longitudinal progression of Alzheimer’ disease-like patterns of brain atrophy in normal elderly
MCI diagnosis.”
Christos Davatzikos and Susan Resnick.
ICAD 2008

Click here for ICAD
2008 website.

Source: Alzheimer’s Association.

: , PhD

Moderate Alzheimer’s disease, Atorvastatin shows promise in small trial

Atorvastatin, a cholesterol-lowering drug, had some positive effects on clinical measures of cognitive and psychiatric
symptoms in patients with Alzheimer’s disease in a small trial, according to a study in the May issue of Archives of
Neurology, one of the JAMA/Archives journals.

A link between the pathology of Alzheimer’s disease (AD) and cholesterol metabolism has been suggested by a number of human
and animal studies, according to background information in the article. In addition, some epidemiological studies have shown
that prior use of statins (cholesterol-lowering drugs) for the treatment of risk of coronary artery disease may also reduce
the risk of Alzheimer’s disease later in life. The current study is a small-scale trial of the cholesterol-lowering
medication atorvastatin calcium for positive effects on cognitive and behavioral deterioration in mild to moderate
Alzheimer’s disease.

D. Larry Sparks, Ph.D., of the Sun Health Research Institute, Sun City, Arizona, and colleagues enrolled individuals with
mild to moderate Alzheimer’s disease in a double-blind, placebo-controlled, randomized one year trial of treatment with
atorvastatin. Patients were evaluated at baseline, three, six, nine and twelve months to determine the effect of atorvastatin
on cognitive and/or behavioral decline, using standard measures of cognitive function, psychiatric symptoms, activities of
daily living and cholesterol levels. Sixty-seven individuals were randomized to receive either atorvastatin calcium or
placebo; 63 patients were evaluated at the three month visit; 56 patients completed the 6-month visit; 48 patients completed
the 9-month visit; and 46 completed the one-year study, 25 receiving atorvastatin and 21 receiving placebo.

“We have found that daily administration of 80 mg of atorvastatin calcium significantly reduces circulating cholesterol
levels and may have a positive effect on the progressive deterioration of cognitive function and behavior anticipated in mild
to moderate AD,” the authors write. “As a pilot proof-of-concept study, significant differences were not expected, but
benefits identified tend to support the trial’s rationale based on the hypothesis that excess brain cholesterol-promoting
amyloid beta production [excess amyloid beta protein deposits are a hallmark of AD] and subsequently the symptoms of AD come
from the blood because of increased circulating levels.”

“Finally, although the results clearly hold promise, this was a pilot proof-of-concept trial with a small number of
participants,” the authors conclude. “We believe that we provide evidence for proof of concept, and establishment of similar
benefit of atorvastatin in a multicenter trial investigating the effect in a much larger population may provide proof of
therapy. Two such studies are ongoing.”

(Arch Neurol. 2005; 62:753-757. Available post-embargo at archneurol.)

Editor’s Note: This study was supported by the Institute for the Study of Aging, the Estee Lauder Charitable Trust, and
Pfizer Inc., New York.

For more information, contact JAMA/Archives Media Relations at 312-464-JAMA (5262) or email mediarelationsjama-archives.

Contact: Linda Tyler
623-815-7604
JAMA and Archives Journals
jamamedia

Child Mortality Closely Linked To Women’s Education Levels

Over half of the reduction in the global mortality of children under 5 years of age is linked to increased education among females of reproductive age, says a reports from the Institute for Health Metrics and Evaluation, University of Washington, published in the medical journal The Lancet. Sixteen million children under the age of five died in 1970, compared to 7.8 million in 2009, the report informs – 4.2 million fewer children died in 2009 thanks in large part to better and more widely accessible schooling for women.

The authors write that education is growing in every part of the world. The report states that:

Average years of schooling for women of reproductive age (ages 15 to 44) in developing countries have grown from 2.2 years to 7.2 years.

In some countries, however, women still receive no more than one year of schooling. Those countries include, Burkina Faso, Yemen, Niger, Chad, Mali and Afghanistan.

Dr. Emmanuela Gakidou, lead author, Associate Professor of Global Health at the Institute for Health Metrics and Evaluation (IHME), said:

We know that direct health interventions, such as immunizations, preventive care, and hygiene classes, are crucial to improving health worldwide. What this study shows is that by focusing on education as well, we can increase the impact that we are having on health.

In 87 countries in 2009, women had greater levels of education than men. In 40 nations, however, the gender gap grew during the period 1970 to 2009.

Dr. Emmanuela Gakidou and team collected data from 915 censuses and national surveys globally to create a time series of education levels for 175 nations.

They found that:

31 nations had improved average years of schooling of women of reproductive age by over three years between 1990 and 2009. Saudi Arabia, the Lebanon and the United Arab Emirates were among these countries.
Out of the ten countries with the highest populations in the world, women of reproductive age had complete at least primary school in seven of them.
Most of the countries that are on track to achieving the Millennium Development Goal 4 – reducing the child mortality rate by 66% between 1990 and 2015 – have achieved a faster improvement for average rate of schooling for women of reproductive age than the global 1.9 years over the last two decades.
According to their findings, economic growth accounted for just 7.2% of the reduction in child mortality during the 1970-2009 period.

Dr. Christopher Murray, IHME Director and one of the paper’s co-authors, said:

More education helps mothers make better choices in a range of areas – personal hygiene, nutrition, parenting approaches. It also helps them take better care of their own health when pregnant, and, after the child is born, they are able to navigate the expanding array of health services being offered to their families.

The authors believe that mothers with more education will drive advances in global health, embracing immunization programs, for example.

Dr. Rafael Lozano, Professor of Global Health at IHME:

The next phase could include building new secondary schools and hiring teachers. But before that work begins, it would be wise to weigh the potential benefits and costs of this approach against building clinics and hiring health workers.

Source: The Institute for Health Metrics and Evaluation

Increased educational attainment and its effect on child mortality in 175 countries between 1970 and 2009: a systematic analysis
Dr Emmanuela Gakidou PhD, Krycia Cowling BS, Prof Rafael Lozano MD, Prof Christopher JL Murray MD
The Lancet, Volume 376, Issue 9745, Pages 959 – 974, 18 September 2010
doi:10.1016/S0140-6736(10)61257-3

Skin Disorders Found Among Katrina And Rita Construction Workers

Construction workers who helped repair damaged structures after hurricanes Katrina and Rita were found to have four distinct skin disorders, according to an article published today in Archives of Dermatology (JAMA/Archives).

The authors explain that skin diseases/disorders are commonly found among people after floods and hurricanes. However, not much research has been carried out after outbreaks occur. The researchers write “Hurricane Katrina made landfall on Aug. 29, 2005, and Hurricane Rita on Sept. 24, 2005. Syndromic surveillance in New Orleans, Louisiana, following these hurricanes indicated that 22 percent of diseases treated were dermatologic conditions (i.e., skin or wound infections and rashes).”

Rebecca Noe, M.P.H., CDC (Centers for Disease Control and Prevention), Atlanta, and team looked at survey results, skin biopsy samples and the environmental exposures of 136 construction workers – all of them civilians who worked and lived at a New Orleans military base during August 2005 – October 2005. The majority of these workers had limited sanitation facilities and lived in tents and wooden huts.

Of 136 workers

– 58 reported rash, an attack rate of 42.6 percent

– 41 (70.7 percent) of those who reported a rash were examined for diagnosis

– 27 (65.9 percent) had papular urticaria, a sensitivity reaction to insect bites resulting in solid raised bumps on the skin

– 8 (19.5 percent) had bacterial folliculitis, an infection causing inflammation around the hair follicles

– 6 (14.6 percent) had fiberglass dermatitis, an irritation and inflammation of the skin from contact with fiberglass

– 2 (4.9 percent) had brachioradial photodermatitis, an abnormal skin reaction to sunlight causing irritation and burning in the arms.

Native American workers who were roofers or slept in huts that had been flooded during Katrina were more likely to develop papular urticaria than the other workers, the researchers observed. The Native American workers had a higher incidence of fiberglass dermatitis, compared to workers of other races.

The researchers concluded “A suspected mite infestation of flooded housing units is the most plausible hypothesis, although we were unable to identify the arthropod (insects, spiders and scorpions) source. People working and living in post-hurricane environments where flooding has occurred may be at an increased risk of exposure to arthropods. To reduce dermatologic morbidity, we suggest avoiding flooded areas, fumigating with an acaricide (pesticide), wearing protective clothing and using arthropod repellant.”

Arch Dermatol
2007;143(11):1393-1398

Survival Benefit Demonstrated In Placebo-Controlled Trial In Patients With Refractory Non-Small Cell Lung Cancer

Agennix Incorporated today announced
results from a fourth positive Phase II trial with its lead molecule
talactoferrin alfa, an immunomodulatory protein with a novel mechanism of
action. This trial, which compared oral talactoferrin monotherapy to
placebo in patients with refractory non-small cell lung cancer (NSCLC), met
its primary endpoint of a statistically significant improvement in overall
survival. Secondary efficacy endpoints also showed improvement consistent
with the primary endpoint results. Oral talactoferrin was well tolerated in
this patient population with fewer adverse events observed in the
talactoferrin arm. These data were presented Saturday, June 2, at the 2007
American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Oral talactoferrin significantly improved overall survival in this
study. In the 100-patient intent-to-treat (ITT) population, median overall
survival was 62% higher in the talactoferrin group than in the placebo
group – 6.0 months versus 3.7 months, respectively (hazard ratio=0.69;
p=0.0476). In the 81-patient prospectively-defined evaluable population,
the median overall survival was 73% higher in the talactoferrin group than
in the placebo group – 7.6 months versus 4.4 months, respectively (hazard
ratio=0.60; p=0.0213). The six-month survival rate in the ITT population
was also significantly better in the talactoferrin group (49%) than the
placebo group (28%), p=0.0276. In addition, overall survival improvement
trends were consistent across subsets of patients grouped by prognostic
factors, including disease stage, performance status, and line of therapy.

In addition to improving overall survival, oral talactoferrin was well
tolerated by refractory NSCLC patients. Adverse events (AEs) were generally
mild, and no drug-related serious AEs were reported. In addition, there
were 28% fewer AEs and 51% fewer Grade 3/4/5 AEs in the talactoferrin group
relative to the placebo group (p=0.0015 and p=0.0005, respectively).

This was the second successful placebo-controlled trial with oral
talactoferrin in NSCLC. The first was in combination with first-line
chemotherapy. Preparations for Phase III trials with talactoferrin are
underway in both NSCLC indications: (i) first-line in combination with
chemotherapy, and (ii) single-agent treatment of patients with refractory
disease.

About the Study

In this Phase II single-agent study, 100 patients with stage IIIB/IV
NSCLC, whose cancer had progressed after first- or second-line
chemotherapy, were enrolled at 10 leading oncology centers in India and
randomized to receive standard supportive care plus either placebo (n=53)
or talactoferrin 1.5 g orally twice a day (n=47). Patients did not receive
any other anti- cancer therapy while on the trial. Treatment was
administered in 14-week cycles (12 weeks on, two weeks off) for up to three
cycles or until disease progression. The primary endpoint was overall
survival. All 100 patients were included in the ITT population. The 81
patients who had at least one CT scan after initiating treatment were
prospectively defined as the evaluable population.

About Talactoferrin Alfa

Talactoferrin alfa is a unique recombinant form of human lactoferrin,
an immunomodulatory protein. Talactoferrin acts by binding to specific
receptors found on target cells and inducing the production of key
immunomodulatory cytokines and chemokines. Orally administered
talactoferrin binds to enterocytes lining the upper gastrointestinal tract,
initiating an immunostimulatory cascade in the gut associated lymphoid
tissue. This results in the activation of both innate and adaptive
immunity, including recruitment and activation of dendritic cells, NK-T
cells and CD8+ lymphocytes. This is followed by systemic immunostimulation,
the activation of tumor-draining lymph nodes, and infiltration of distant
tumors by immune cells, which results in killing of the cancer cells.
Topically administered talactoferrin binds to keratinocytes and fibroblasts
and increases the local production of cytokines and chemokines critical to
wound healing.

Both oral and topical formulations of talactoferrin appear to be well
tolerated. Over 600 patients have been dosed with talactoferrin, including
patients who had exposure to talactoferrin lasting over two years, without
any drug-related serious AEs.

About NSCLC

In the United States, lung cancer is the second most frequent cancer in
both men (next to prostate cancer) and women (next to breast cancer). It
remains the major cause of cancer death, killing more people than breast
cancer, prostate cancer and colorectal cancer combined, and accounting for
almost 30% of all cancer-related deaths.

NSCLC accounts for approximately 80% of all new lung cancer cases, with
approximately 150,000 patients in the United States and 300,000 patients in
Europe diagnosed each year. Most patients diagnosed with NSCLC have late-
stage disease (Stage IIIB or IV), which is not surgically resectable. The
current U.S. standard of care for these patients is systemic chemotherapy.
Even with the available therapy, the five-year survival rate for these
patients is less than 3%.

About Agennix

Agennix is a private biotechnology company developing a first-in-class
molecule for the treatment of cancer and for wound healing. This molecule,
talactoferrin, is an immunomodulatory recombinant protein with a novel
mechanism of action. The Company is developing an oral liquid formulation
of talactoferrin for cancer indications, and a topical gel formulation for
the treatment of diabetic foot ulcers. Agennix has 95 issued patents and 47
pending patents broadly protecting talactoferrin composition of matter,
use, and manufacturing methods.

Agennix Incorporated
agennix

Racial Biases Can Skew Perceptions Of How Much Help Victims Need

When assessing the amount of help someone needs, people’s perceptions can be skewed by their racial biases, according to a Kansas State University study.

Donald Saucier, K-State associate professor of psychology, and psychology graduate students Sara Smith, Topeka, and Jessica McManus, Maineville, Ohio, surveyed undergraduate students a year after Hurricane Katrina to examine their perceptions of the hurricane victims and the helping response.

The researchers created a questionnaire that evaluated the participants’ perceptions of Hurricane Katrina victims. The questionnaire evaluated whom the participants perceived to be the victims based on measures like gender, race and socioeconomic status. The results showed that participants generally thought people impacted by Hurricane Katrina were black and lower class.

“What we wanted to do was see how perceptions of victims of Hurricane Katrina would interact with things like racism,” Saucier said. “We wanted to look at how much the participants felt that the victims may have been to blame for their own situation in Katrina.”

The researchers measured differences in the participants, including their levels of conservatism, empathy and racism. The findings showed that when recalling victims of Hurricane Katrina, participants who were less racist thought the victims did not receive adequate help from the government. Participants who were more racist thought the victims received adequate government assistance and were at fault for their situation. The survey also asked questions that measured whether the participants thought the victims had enough time to evacuate and whether they had enough resources to get out before the hurricane hit.

“We asked the participants to make personality attributions about individuals, such as whether they thought the victims were lazy, stupid, sinful or unlucky,” Saucier said. “If they said they were lazy, stupid or sinful, they were putting more blame on the victims for the situation. If they said they were unlucky, they took away the blame.”

The results suggest that perceptions of the victims and the Hurricane Katrina situation depended on the participants’ individual differences, including their levels of racism. Negative perceptions and placing blame on the victims were generally associated with the participants’ perceptions that the situation was less of an emergency and that the victims needed less help.

Saucier said although the findings can’t fix what happened to the victims, the study helps show how people interpret the situation. He said when something negative happens, people often evaluate the situation and see whether they can fix it, and sometimes they avoid the situation by blaming the victim.

The researchers study the effects of group membership, and groups can be categorized in various ways, including by gender, race and socioeconomic status. Studies show there are specific factors that cause someone to help a member of their own group more than others. In helping situations, discrimination is often expressed by not giving help to those of a different group than the helper, Saucier said.

“Rather than doing something bad, the person who chooses not to help the out-group member fails to do something good,” Saucier said. “I think this illustrates the complexity of how prejudice is expressed in contemporary society despite the social norms that usually serve to suppress the expression of prejudice.”

Saucier said discrimination is often expressed only when other factors are present that would justify the action and rationalize it as something other than an expression of prejudice. Factors that contribute to the justification of not helping someone include the time it would take to help; the risk, effort, difficulty and financial cost involved; the distance between the potential helper and the person needing help; the level of emergency and the ambiguity of the helping situation.

The researchers said the Hurricane Katrina situation had several elements that studies show trigger acts of discrimination, such as a high cost of help, a high level of emergency and a large amount of time and effort required to help. The researchers are exploring other helping situations and how other group memberships affect the helping response.

“We want to examine how the perception of someone that you’re going to be helping is going to affect your perception of how much help they need and how much help you’ll want to give,” Saucier said.

Though it’s unlikely that researchers can fix the beliefs and attitudes that lead to discrimination, studies are being done to try to change the behavior that is expressed when related to discrimination, Saucier said.

The researchers’ findings on Hurricane Katrina victims are included in a chapter about discrimination against out-group members in helping situations in “The Psychology of Prosocial Behavior: Group processes, intergroup relations and helping,” published in September 2009.

Source:
Donald Saucier

Kansas State University

In Alzheimer’s Disease, Harmful Amyloid Interferes With Trash Pickup For Cells

Chemists at the University of California, San Diego, have identified how a protein that accumulates in the brains of people with Alzheimer’s disease interferes with the ability of cells to get rid of debris. They also found a natural mechanism by which this protein, amyloid beta, itself may be discarded.

Plaques of amyloid are a hallmark of the ailment, but no one is sure exactly how they contribute to catastrophic loss of memory and cognition.

Scientists have begun to suspect that amyloid disables a structure called a proteasome, which chops up proteins that cells no longer need into pieces that can be reused or discarded. Proteins that have been tagged for destruction pile up in the brains of Alzheimer’s patients.

“Basically the trash is put out to the curb, but no one is picking it up,” said Jerry Yang, an associate professor of chemistry and biochemistry who led the research effort.

Yang and postdoc Xiaobei Zhao showed that amyloid actually doesn’t harm the proteasome. Instead it interferes with the processing of other proteins by competing for access, they report in a forthcoming issue of the journal ACS Chemical Neuroscience.

They found that the proteasome breaks long chains of toxic amyloid into smaller, harmless pieces. And because the proteasome has a greater affinity for amyloid, other proteins build up undigested.

“The fact that the proteasome can hack up amyloid fairly efficiently gives us some insight as to how normal clearance mechanisms actually work,” Yang said. “We all have amyloid peptides, and we all get rid of them as well. The proteasome is in every cell.”

Scientists believe amyloid plays a central role in the development of Alzheimer’s disease and that an imbalance between production and clearance of amyloid leads to build up and the formation of plaques. But they aren’t certain how amyloid is normally broken down and removed from the brain.

“Relatively little attention has been paid to how you get rid of it,” Yang said. “Minimally, this finding reveals a little bit more about what the amyloid is doing within the cell – how it’s altering the function of this very important piece of machinery. If proteasomal dysfunction turns out to be a primary factor in Alzheimer’s disease then this will be a key finding.”

The Alzheimer’s Association and the Alzheimer’s Disease Research Center funded this work.

Source:
Jerry Yang

University of California – San Diego

Smoking Linked To Severity Of Osteoarthritis In Men

Men who smoke and have osteoarthritis in the knees tend to lose more
cartilage and suffer more severe knee pain than non-smoking men. This was
the conclusion of a study headed by Dr Shreyasee Amin of the Mayo Clinic
College of Medicine in the US.

The results of the study were published this month in the Annals of the
Rheumatic Diseases.

The 30-month study investigated 159 men, of which 19 were smokers. The
smokers tended to be younger and leaner (of lower body mass index, BMI)
than the men who did not smoke. However, once the results were adjusted
for BMI and age, they revealed an increased risk of cartilage loss and
significantly elevated pain scores in the smokers compared to the non-
smokers.

The researchers used MRI scans at the start, middle and end of the 30-month period to detect cartilage wear, and the men assessed their pain
intensity on a Visual Analogue Scale (VAS) using a scale of 0 to 100.

Osteoarthritis (OA), sometimes known as “degenaritive joint disease” is
the most common type of arthritis and tends to occur in older people.
Cartilage is a resilient but slippery tissue that stops bones in joints
like the knees from rubbing against each other and therefore wearing each
other down.

In OA the cartilage becomes thin and the bones rub against
each other and cause inflammation, pain and loss of mobility. In time, the
joint can become swollen and misshapen, bits of cartilage break off, and also spurs of bone
tissue grow across the joint.

“Cigarette smoking and the risk for cartilage loss and knee pain in men with knee osteoarthritis”
Shreyasee Amin, Jingbo Niu, Ali Guermazi, Mikayel Grigoryan, David J
Hunter, Margaret Clancy, Michael P LaValley, Harry K Genant, and David T
Felson
Ann Rheum Dis, Dec 2006; doi:10.1136/ard.2006.056697
Click here to see the Abstract of the study.

Information on Osteoarthritis from National Institutes of Health (US).

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