Defective cilia cause a range of diseases including Bardet-Biedl syndrome (BBS), a rare, multi-tissue disorder linked to mutations in 12 different proteins. Seven of these form a complex called the BBSome, but the function of this protein assembly in cilia and flagella is unclear. In worms, the complex glues together the intraflagellar transport (IFT) machinery that assembles and maintains cilia by hauling cargo back and forth along the organelle’s microtubules. But most mammalian cell types can still form cilia in the absence of BBS proteins, suggesting that the BBSome isn’t essential for IFT.

Lechtreck et al. turned to the green alga Chlamydomonas, and found that BBS proteins were only present on a subset of IFT particles in each of the alga’s two flagella. Strains lacking components of the BBSome showed normal rates of IFT and proper flagellar structure, but couldn’t steer away from bright light like wild-type cells could. Mutant flagella accumulated several signaling-related proteins, which the researchers think may disrupt the alga’s response to light.

The researchers speculate that a similar buildup of disruptive proteins causes cilia dysfunction in BBS patients; the BBSome may remove excess signaling proteins from flagella by linking them to a subset of IFT particles undergoing retrograde transport out of the cilia. Author Karl Lechtreck says that the next step is to fluorescently tag the signaling proteins and compare their movements to BBS and IFT proteins.

One new study from the National Institute on Aging (NIA) and Dr. Roy Verdery at
the Arizona Center on Aging shows that a 30 percent reduction in calories in a
monkey's diet leads to elevation in good cholesterol (HDL2B) levels with a
subsequent reduction in risk for cardiovascular disease. A second recent study
from the NIA has shown that caloric restriction slows the age-related decrease
in amounts of a naturally occurring steroid hormone, DHEA. Using natural DHEA
levels as a biomarker of aging may assist scientists in their search for a way
to slow down the aging process.

Previous research in shorter-lived species such as fruit flies and rats has
demonstrated that a 30 percent caloric restriction can lead to 30 percent longer
life in addition to enhanced markers of good health.

The first of the two studies (American Journal of Physiology, October,
1997, Vol. 36, No. 4) demonstrates that, over a ten year period, a 30 percent
reduction in caloric intake in rhesus monkeys leads to up to a 25 point
elevation in HDL2B levels as well as a 20 point decrease in triglyceride levels
(as measured in milligrams per deciliter). Increases in HDL2B and decreases in
triglycerides of this magnitude in humans would be a great health benefit to
many, especially for those at risk for stroke or heart attack.

Principal investigator, George Roth, Ph.D., Acting Chief of NIA's Laboratory of
Cellular and Molecular Biology, says, "In addition to enhanced HDL2B and lower
triglyceride levels, we also see a small drop in blood pressure. These HDL2B
results, combined with previous findings from our lab showing better glucose
tolerance and insulin sensitivity (which should predict lower incidence of
diabetes), lower body temperature, and other such biomarkers suggesting that
caloric restriction may exert beneficial effects in primates similar
to those previously observed in rodents. These results may someday serve as a
model for human studies."

One interesting aspect of this particular study is that neither the control
monkeys nor the calorically restricted monkeys eat much fat or cholesterol as
part of their diets. Thus the study demonstrates that even in non-obese
monkeys, a reduction in calorie intake can benefit cholesterol, triglycerides
and blood pressure. This research presents an important contrast to studies
that usually look at obesity and how weight loss from that level can benefit
health.

It is demonstrated here for the first time that caloric restriction can
lead to changes in HDLs and other lipid profiles that may be associated with
health benefits for both those animals that are lean as well as those that are
heavier.

Recent research under the direction of Mark Lane, Ph.D., Senior Staff Fellow at
the NIH's Animal Center, has turned up an interesting added benefit to caloric
restriction. In addition to boosting good cholesterol and reducing
triglycerides, monkeys on caloric restricted diets experience a favorable
redistribution of fat away from their central regions thus reinforcing the
current finding about reduction in cardiovascular risk with caloric restriction.

The second study from Drs. Roth, Lane, and Donald Ingram at NIA and Dr. Sheldon
Ball at the University of San Francisco-Fresno, appeared in the July 1997 issue
of the Journal of Clinical Endocrinology and Metabolism (Vol. 82,
No. 7, pp. 2093-2096). In this study, monkeys whose calorie intake was
restricted by 30 percent showed a slower decline in DHEAS
(dehydroepi-androsterone sulfate) and DHEA (the unsulfated form) levels than
those observed in control monkeys.

Dr. Lane, principal investigator of this study, says, "DHEA levels are of great
interest to us, not because we believe that DHEA is the fountain of youth, but
rather because it gives us a very good marker to measure the rates of aging in
control versus calorically restricted monkeys. It is important to distinguish
between levels of DHEA that occur naturally in the body and decline with age and
levels that are seen in people who pop DHEA pills to pharmacologically raise
their natural levels in hope of extending their lives. These artificially
higher levels may or may not give them any benefit. Controlled clinical trials
are needed before this question can be answered." Dr. Ingram adds, "It is
important to develop markers such as DHEAS which can be used to determine the
effects of various interventions, such as diet and exercise, on aging."

According to Dr. Roth, "this study shows that monkeys eating a calorically
restricted diet which contains little fat maintain higher DHEA levels in their
bodies. In this setting, DHEA is a marker of aging. We do not yet know if DHEA
plays a role in slowing the aging process."

Until NIA initiated studies in rhesus monkeys in 1987, the phenomena of longer
life and better health and vigor through caloric restriction had never been
investigated in longer-lived primate species. These studies will continue for
many more years with the goal of eventually giving a more precise understanding
of the mechanisms of how caloric restriction extends life.

The National Institute on Aging, one of the 18 Institutes which make up the
National Institutes of Health, leads the Federal effort supporting basic,
clinical, epidemiological and social research on aging and the special needs of
older people. A brochure, "Pills, Patches and Shots: Can Hormones Prevent
Aging?" is available from the NIA by calling 1-800-222-2225 or by visiting the
NIA's website at nih/nia

Coaches also should allow enough recovery between practices and gradually introduce parts of the uniform, experts say.

Most
high school and younger players are already fighting a losing battle
when they show up to practice, says Dr. Michael F. Bergeron, panel
co-chair and assistant professor of physical therapy at the Medical
College of Georgia. The panel’s full statement and recommendations are
published in the August issue of Medicine & Science in Sports &
Exercise.

“What we’ve found is that most players typically begin
practice dehydrated – pretty significantly dehydrated,” Dr. Bergeron
says. “Young players generally just don’t drink enough, especially
following extensive exercise or training in the heat.”

Surprisingly,
though, hydration isn’t the most important aspect of preventing
heat-related injuries. Players are often simply not acclimated to the
environment, the intensity of practice and the uniform, he says.

“What
coaches and staff need to recognize and appreciate is that the athletes
are not coming into the preseason as well-conditioned as they might
hope,” Dr. Bergeron says. “High school kids are going to be less fit
and not only are they not accustomed to the physical exertion that
workouts require, they’re not really acclimatized to the heat and
working out in that environment, especially while wearing a uniform and
protective gear.”

To help protect ill-prepared players, coaches
should introduce a training schedule that progresses slowly – waiting
until week two to introduce twice-daily conditioning and training
sessions, experts say. They also should realize that adding a heavy
uniform adds to the heat and strain players are already experiencing
when weather conditions are unbearable. That can significantly add to
the risk of heat injury.

“Most heat-related injuries and deaths
occur within the first four days of practice, particularly on days one
and two,” Dr. Bergeron says. “The primary factors for driving body
temperature during practice and clinical risk related to overheating
are the environment and the intensity/duration of the workouts and the
uniform.”

During the first week of practice, protective equipment
should be introduced in stages, starting with the helmet, progressing
to shoulder pads and helmet and, finally, to the full uniform, the
authors write.

Other suggestions include requiring a preseason
exam to determine what medications and dietary supplements athletes are
using and to rule out undiagnosed heart problems and other genetic risk
factors. Also, twice-daily practice sessions, once introduced, should
be staggered throughout the week to allow for at least a one-day break
between multiple-session days.

And even if the temperature outside hasn’t reached the boiling point, players and coaches should still take precautions.

“What
we are beginning to appreciate more and more is that it doesn’t have to
be unbearably hot to have problems,” Dr. Bergeron says. “The focus of
this is prevention.”

However, the Virahep-C Study Group, at Saint Louis University, has now developed an approach that predicted the outcome of therapy, raising the possibility of a test to predict treatment response and reduce treatment failures, something that could save a great deal of pain and expense for HCV-infected patients.

The research team, led by John Tavis and Rajeev Aurora, used a method known as covariation analysis to analyze variation in the genome-wide amino-acid sequence of viruses isolated from HCV-infected patients before they underwent treatment.

Using this approach, networks of covariation were found to associate with specific responses of the patients to treatment.

The authors suggest that the data has implications for the development of a test to predict how an individual infected with HCV will respond to treatment and might help identify targets for new antiviral drugs.

In an accompanying commentary, Thomas Oh and Charles Rice, at Rockefeller University, New York, discuss further the therapeutic implications of these data.

"For many patients—even the very fit ones, such as an aerobics instructor—the upper to mid-line back where the rolls and bulges form was very frustrating," said senior author Joseph Hunstad, MD and ASPS Member Surgeon. "This redundancy of skin occurs generally from aging and cannot be exercised away. For those who desire to wear form-fitting outfits, this procedure eliminates the problem."

The study reviewed seven female patients who had the bra-line back lift between 2001 and 2007 with an average follow-up of 22 months. Pre-operative marks were placed to outline the patient’s brassiere, as well as delineate the excess back tissue to be removed. The procedure removed the redundant skin, sometimes up to 8 or 10 inches wide, and connected the remaining tissue together. According to the study, the procedure takes about an hour from start to finish. The authors have completed the bra-line back lift on 20 patients to date.

The study found minimal complications and about two weeks after surgery, patients were allowed to increase their activity levels based on their discomfort. Feedback from all seven patients was uniformly positive, according to the study.

The study concluded that the procedure is a safe and powerful method to contour the middle and upper back – literally removing all of the back rolls and folds. By placing the scar within the patient’s bra-line, it is easily concealed even by a two-piece bathing suit, according to the study.

"This is an exciting new procedure that gives patients concerned about this area of their body a possible new option to discuss with their plastic surgeon," said James Wells, Chair of the ASPS Public Education Committee. "As with all new procedures that are not yet widely practiced, patients need to choose an ASPS Member Surgeon who has a comprehensive understanding of how bodies change over time, the impact of environment and lifestyle and the know-how to develop the best treatment plan for the best result."

According to the ASPS, more than 19,500 lower back lifts were performed in 2007. Currently, statistics for upper back lifts are not available.

Proteinuria, its presence and degree, is currently an essential criterion in diagnosing pre-eclampsia and is widely considered to predict adverse outcomes for mother and fetus. In a systematic, quantitative review of 16 primary research articles including 6749 women, the authors found that proteinuria was a poor predictor of maternal and fetal complications. Outcomes tested for included eclampsia, abruption, HELLP syndrome, stillbirth, neonatal death, perinatal death, small for gestational age and NICU admission.

Shakila Thangaratinam of Birmingham Women’s Hospital and her colleagues used four databases (MEDLINE, EMBASE, MEDION and the Cochrane Library) to select the studies for systematic review. By calculating likelihood ratios for positive and negative test results for each individual test threshold and each outcome of interest, they demonstrated the clinical relevance of assessing proteinuria levels in pre-eclampsia for each outcome. The LRs were not significant for any adverse maternal outcome. At cut-off level of proteinuria of 5g in 24hours, they found a slight association with stillbirths for positive test results. However, with no significant positive and negative LRs, proteinuria estimates were found to be poor predictors of neonatal and perinatal deaths.

According to Thangaratinam, ‘Our systematic review has shown proteinuria levels in pre eclampsia to be poor predictors of adverse maternal and fetal outcomes. We need large well-conducted studies to estimate the risk of complications especially in the subgroup of women who have pre eclampsia before 34 weeks when the management decision is often critical to mother and baby.’

"Processing of many edible plants through heating, grinding, mixing or drying dramatically increases their nutrition value, including their cancer prevention potential. It appears that the greatest protective effect from tomatoes comes by rehydrating tomato powder into tomato paste," said Valeri V. Mossine, Ph.D., research assistant professor of biochemistry at the University of Missouri.

The protective effect of tomato products against prostate cancer has been suggested in many studies, but researchers remain uncertain about the exact mechanisms. Mossine and colleagues demonstrated that FruHis, an organic carbohydrate present in dehydrated tomato products, exerts a strong protective effect.

Researchers divided rats into groups of 20 and fed them a control diet or a diet that included tomato paste, tomato powder or tomato paste plus additional FruHis. All animals were then injected with prostate cancer-causing chemicals.

Animals fed the tomato paste plus FruHis diet had the longest survival from cancer at 51 weeks compared with 50 weeks in the tomato powder group, 45 weeks in the tomato paste alone group and 40 weeks in the control group.

On post-mortem exam, prostate tumors were found in 10 percent of the rats that had been given a combination of tomato paste and FruHis, compared with 30 percent of animals in the tomato powder group, 25 percent in the tomato paste alone group and 60 percent in the control group.

Mossine said the protective effect of tomato-based products was restricted to prostate tumors, which is consistent with other research on tomatoes and cancer. Incidence of other tumors was too small to examine.

In vitro, Mossine and colleagues evaluated the anti-cancer properties of FruHis and 14 other D-fructose amino acids and found that FruHis in a concentrated form protected against DNA damage known to lead to prostate cancer. When combined with lycopene, FruHis stopped cancerous cell growth more than 98 percent of the time.

"Before this study, researchers attributed the protective effect of tomatoes to ascorbic acid, carotenoids, or phenolic compounds," Mossine said. "FruHis may represent a novel type of potential dietary antioxidant. Experiments like these suggest that a combination of FruHis and lycopene should be investigated as a potential therapeutic anti-tumor agent, not just a prevention strategy."

Although Mossine cautioned against drawing broad conclusions from this animal study, he said, "the result may introduce an additional intrigue into an ongoing dispute over the beneficial effects of dietary lycopene and tomato products in lowering the risk of prostate cancer. Human trials are certainly warranted."

The data from the early trial of 30 Fragile X patients, found the drug, called AFQ056, made by Novartis Pharmaceuticals, helped improve symptoms in some patients. Patients who had the best response have a kind of "fingerprint" in their DNA that could act as a marker to determine who should get treatment.

"This is an exciting development. It is the first time we have a treatment targeted to the underlying disorder, as opposed to supportive treatment of the behavioral symptoms, in a developmental brain disorder causing intellectual disability. This drug could be a model for treatment of other disorders such as autism," said pediatric neurologist Dr. Elizabeth Berry-Kravis, a study author and director of the Fragile X Clinic and Research Program and the Fragile X-Associated Disorders Program at Rush.

The drug is designed to block the activity of mGluR5, a receptor protein on brain cells that is involved in most aspects of normal brain function, including regulation of the strength of brain connections, a key process required for learning and memory. Fragile X patients have a mutation in a single gene, known as Fragile X Mental Retardation-1 or FMR1. The mutation prevents FMR1 from making its protein, called FMRP, such that FMRP is missing in the brain. FMRP normally acts as a blocker or "brake" for brain cell pathways activated by mGluR5. When FMRP is missing, mGluR5 pathways are overactive resulting in abnormal connections in the brain and the behavioral and cognitive impairments associated with Fragile X.

The research team, led by Sebastien Jacquemont of Vaudois University in Switzerland in collaboration with Baltazar Gomez-Mancilla of Novartis, found no significant effects of treatment when the entire group of 30 patients was analyzed. However, in a subsequent analysis, seven patients who had a fully methylated gene, a gene that was fully shut down, presumably resulting in no FMR protein in the blood or brain, showed significant improvement in behavior, hyperactivity and inappropriate speech with the treatment compared to placebo.

"The treatment period in this pilot study was very short and longer treatment might have been needed to see improvement in the whole group of patients. Importantly, the drug was well-tolerated and there were no safety problems," said Berry-Kravis.

A larger study of the drug is now underway that will recruit 160 patients worldwide and test the effects of a longer period of treatment. Rush University Medical Center is one of the participating sites.

Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and ethnic groups. It is the most common known single gene cause of autism or "autistic-like" behaviors. Symptoms also can include characteristic physical and behavioral features and delays in speech and language development. The impairment can range from learning disabilities to more severe cognitive and intellectual disabilities.

A related University of Iowa-led study, published in the May 2007 issue of the Journal of General Internal Medicine, found a similar, although smaller, gap between physicians’ attitudes and actual actions in the disclosing of medical errors to patients.

Information from the two studies, which were based on surveys of doctors in teaching hospitals, shows an apparent disconnect between error disclosure to patients and error reporting to hospitals and points to the need for a more integrated view of medical error communication, said Lauris Kaldjian, M.D., Ph.D., associate professor of internal medicine at the University of Iowa Carver College of Medicine.

As an example, 41 percent of physicians in the earlier study said they actually had disclosed a minor error to a patient but only 18 percent of physicians in the current study said they had reported a minor error to their hospital.

"Taken together, the findings indicate that physicians have more experience talking to patients about medical errors than reporting them to hospitals," said Kaldjian, who also is director of the college’s Program in Biomedical Ethics and Medical Humanities.

"It may be that physicians find it more important or meaningful to talk to patients about mistakes and may not see as much value in communicating the same mistakes to a reporting system," he added.

Kaldjian points out that disclosing errors to patients relates directly to real-time patient care, while reporting errors to institutions is directed toward improving the care of future patients. "It is important that we try to find a way to accomplish both kinds of error communication," he said.

Kaldjian and co-investigators received survey responses from 338 physician participants from different regions in the United States. Among them, 73 percent said they would report to their institution a hypothetical error resulting in minor harm, and 92 percent said they would report a hypothetical error resulting in major harm. However, in actuality few physicians have reported a minor error — 18 percent — or a major error — 4 percent — to their hospital. In addition, 17 percent acknowledged not reporting an actual minor error and 4 percent acknowledged not reporting an actual major error.

The discrepancy between attitude and action is particularly notable, Kaldjian said, given that the survey showed that 84 percent of physicians believe error reporting can improve the quality of care.

The answer to the gap may lie partly in other findings from the survey, he noted: Only 55 percent of the respondents knew how to report errors, and only 39 percent knew what kinds of errors to report.

"The fact that nearly every physician is likely to make a minor error at some point in his or her career, taken together with the lack of understanding on how and what to report, indicates we need to clarify what errors should be reported and how to report them," he said.

Half the respondents said they would report errors if they knew they would receive feedback, and individuals who had been involved in malpractice cases were not less likely to report hypothetical errors.

"While it is encouraging that even doctors who have been sued are still inclined to report errors, there still is widespread concern that any disclosure might put a doctor at risk of malpractice litigation," Kaldjian said.

In addition, the study results indicated that a doctor’s prior experience with reporting medical errors to his or her hospital seemed to reinforce reporting behavior. Respondents who had actually reported a minor medical error in the past were more likely to indicate that they would report hypothetical errors.

Kaldjian said that while the study results may not generalize to non-teaching hospitals, the patient safety movement that came into full force around 2000 clearly depends on how medical errors or mistakes are handled.

"We can fix a system only if we know what is wrong," he said. "We’re gathering information about errors in order to improve systems and reduce errors. If a doctor does not report an error, then we miss an opportunity to gather potentially important information about health care delivery, and the ability to improve is compromised.

"We should also recognize that a physician’s willingness to be straightforward about errors depends on their beliefs about errors and the value of error communication, so we should think creatively about ways to encourage clinicians to draw upon the personal and professional commitments that can motivate error reporting in the midst of countervailing pressures," he added.

The study was funded by the Robert Wood Johnson Foundation’s Generalist Physician Faculty Scholars Program through a grant to Kaldjian.

In addition, the study involved investigators with the Center for Research in the Implementation of Innovative Strategies in Practice at the Department of Veterans Affairs Iowa City Health Care System; Hospital of St. Raphael in New Haven, Conn.; Yale University School of Medicine; and Penn State College of Medicine and Hershey Medical Center.

Multiple sclerosis (MS) and Guillain-Barré syndrome (GBS) — the two autoimmune diseases covered by the thesis — can follow vastly different courses, with symptoms ranging from insignificant to life-threatening, the reason for which has been largely unknown. In the thesis the researchers have now found a factor in the immune defence that can explain this mechanism.

The immune system’s white blood cells play an important role in the fight against invading micro-organisms. They contain an enzyme called NADPH oxidase, which converts oxygen into reactive oxygen radicals. It has long been known that these oxygen radicals stop infections by breaking down micro-organisms. New studies using animal models have shown that inadequate production of oxygen radicals can lead to the development of autoimmune diseases, where a patient’s immune system attacks the body’s own tissues. This would indicate that oxygen radicals are important for preventing the occurrence of autoimmune diseases.

"We wanted to look at this in humans, and examined the NADPH oxidase in the white blood cells of patients with MS, GBS and recurring GBS (RGBS)," says Natalia Mossberg, doctoral student at the Institute of Neuroscience and Physiology at the Sahlgrenska Academy. "The results show that patients with more severe forms of the illness have lower levels of oxygen radical production in their white blood cells as a result of deficient NADPH oxidase function."

The researchers discovered that the body’s ability to produce reactive oxygen radicals at an early stage in the immune defence against infections has a major impact on how these illnesses develop. "We’ve shown that a strong but controlled production of oxygen radicals by the immune system is important for subduing illnesses such as MS and GBS," says Mossberg.

The researchers think that this method of measuring oxygen radical production in white blood cells can be used for investigating other autoimmune diseases and for diagnosing the severity of these illnesses. The discovery could also lead to a new approach to the treatment of MS in its early stages with medicines that trigger the production of NADPH oxidase or a vaccination for people at risk of developing this type of illness.