CAN SLEEP LOSS AFFECT YOUR BRAIN SIZE

Sleep difficulties may be linked to faster rates of decline in brain volume, according to a study published in the September 3, 2014, online issue of Neurology, the medical journal of the American Academy of Neurology

Sleep has been proposed to be "the brain's housekeeper," serving to repair and restore the brain.

The study included 147 adults 20 and 84 years old. Researchers examined the link between sleep difficulties, such as having trouble falling asleep or staying asleep at night, and brain volume.

All participants underwent two MRI brain scans, an average of 3.5 years apart, before completing a questionnaire about their sleep habits.

A total of 35 percent of the participants met the criteria for poor sleep quality, scoring an average of 8.5 out of 21 points on the sleep assessment. The assessment looked at how long people slept, how long it took them to fall asleep at night, use of sleeping medications, and other factors.

The study found that sleep difficulties were linked with a more rapid decline in brain volume over the course of the study in widespread brain regions, including within frontal, temporal and parietal areas.

The results were more pronounced in people over 60 years old.

"It is not yet known whether poor sleep quality is a cause or consequence of changes in brain structure," said study author Claire E. Sexton, DPhil, with the University of Oxford in the United Kingdom. "There are effective treatments for sleep problems, so future research needs to test whether improving people's quality of sleep could slow the rate of brain volume loss. If that is the case, improving people's sleep habits could be an important way to improve brain health."

OPTIMAL PARTICLE SIZE FOR ANTICANCER NANOMEDICINES DISCOVERED

Nanomedicines consisting of nanoparticles for targeted drug delivery to specific tissues and cells offer new solutions for cancer diagnosis and therapy. Understanding the interdependency of physiochemical properties of nanomedicines, in correlation to their biological responses and functions, is crucial for their further development of as cancer-fighters.

"To develop next generation nanomedicines with superior anti-cancer attributes, we must understand the correlation between their physicochemical properties -- specifically, particle size -- and their interactions with biological systems," explains Jianjun Cheng, an associate professor of materials science and engineering at the University of Illinois at Urbana-Champaign. In a recent study, published in theProceedings of the National Academy of Sciences, Cheng and his collaborators systematically evaluated the size-dependent biological profiles of three monodisperse drug-silica nanoconjugates at 20, 50 and 200 nm.

"There has been a major push recently in the field to miniaturize nanoparticle size using novel chemistry and engineering design," Cheng added. "While most current approved anti-cancer nanomedicines' sizes range from 100-200 nm, recent studies showed that anti-cancer nanomedicines with smaller sizes -- specifically of 50 nm or smaller -- exhibited enhanced performance in vivo, such as greater tissue penetration and enhanced tumor inhibition."

"Over the last 2-3 decades, consensus has been reached that particle size plays a pivotal role in determining their biodistribution, tumor penetration, cellular internalization, clearance from blood plasma and tissues, as well as excretion from the body -- all of which impact the overall therapeutic efficacy against cancers," stated Li Tang, first author of this PNAS article. "Our studies show clear evidence that there is an optimal particle size for anti-cancer nanomedicines, resulting in the highest tumor retention.

Among the three nanoconjugates investigated, the 50 nm particle size provided the optimal combination of deep tumor tissue penetration, efficient cancer cell internalization, as well as slow tumor clearance, exhibits the highest efficacy against both primary and metastatic tumors in vivo.

To further develop insight into the size dependency of nanomedicines in tumor accumulation and retention, the researchers developed a mathematical model of the spatio-temporal distribution of nanoparticles within a spherically symmetric tumor. The results are extremely important to guide the future research in designing new nanomedicines for cancer treatment, Cheng noted. In addition, a new nanomedicine developed by the Illinois researchers -- with precisely engineered size at the optimal size range -- effectively inhibited a human breast cancer and prevented metastasis in animals, showing promise for the treatment of a variety of cancers in humans.

Cheng, a Willett Faculty Scholar at Illinois, is affiliated with the departments of Bioengineering and of Chemistry, the Beckman Institute for Advanced Science and Technology, the Micro and Nanotechnology Laboratory, the Institute of Genomic Biology, the Frederick Seitz Materials Research Laboratory, and University of Illinois Cancer Center.

Tang, who obtained his PhD degree from the University of Illinois with Jianjun Cheng, is currently a CRI Irvington postdoctoral fellow at the Massachusetts Institute of Technology. Collaborators and co-corresponding authors of the paper at Illinois include Timothy Fan, associate professor, veterinary clinical medicine; Andrew Ferguson, assistant professor, materials science and engineering; and William Helferich, professor, food science and human nutrition.

SIZE AT BIRTH AFFECTS MENTAL DISORDER RISK

New research from the Copenhagen Centre for Social Evolution and Yale University offers compelling support for the general evolutionary theory that birth weight and -length can partially predict the likelihood of being diagnosed with mental health disorders such as autism and schizophrenia later in life. The study analyzed medical records of 1.75 million Danish births, and subsequent hospital diagnoses for up to 30 years, and adjusted for almost all other known risk factors. The study is published in theProceedings of the Royal Society, London B.

The number of people diagnosed with mental health disorders is on the rise in most affluent countries, but we do not yet have a comprehensive understanding of the factors that make people vulnerable to these disorders.

A new analysis of the extensive Danish public health database suggests that part of the answer may reside in genetic imprints established at conception that influence both size at birth and mental health during childhood and early adolescence.

The study tests predictions of the evolutionary theory of genomic imprinting -- the idea that during fetal development some genes inherited from the mother are expressed differently to those inherited from the father. The potential consequence of this asymmetry is that maternal and paternal genes in a fetus will not cooperate fully during this period, even though they subsequently have shared interests due to their lifetime commitment to the same body.

Opposite forces balance each other

The reason for the conflict is that some of the genes known to be expressed in the placenta and the brain carry imprints that affect resource provisioning of the unborn child. When such genes come from the father, they favor investment of more of the mother's resources in the developing fetus, whereas the maternally-imprinted genes will normally compensate for such paternally-influenced manipulative effects to lessen the drain on maternal resources. These opposite forces balance each other in most pregnancies, with the result that most children are born with close to average length and weight and with a high likelihood of balanced mental health development.

Small deviations may well be favorable in human populations, when somewhat heavier babies are more likely to develop abstract talents and somewhat lighter babies above average social talents, for instance. However, this incurs the risk of increasing the frequency of autistic- and schizophrenic-spectrum disorders in the rare cases where imprinting imbalances are larger. The theory may explain why natural selection has not removed this portion of the burden of mental disease from our ancestors.

The new study tests these predictions^, and its results are remarkably consistent. They show that the change to the risk of developing mental disorders when born smaller or larger than average are relatively small, but very consistent, clearly diametrical, and part of the single continuum that the theory predicts.

"When we started this large scale analysis four years ago, we hoped to find evidence that genetic imprinting happens, but we did not expect that the results would match the predictions as consistently as we found," explains Professor Jacobus Boomsma, Director of the Centre for Social Evolution, University of Copenhagen, who coordinated the work.

Boomsma adds: "Our study confirms that larger babies have a higher risk for incurring autism-spectrum diagnoses later in life and lower risk for schizophrenia-spectrum disorders. For example, Danish newborns are on average 52 cm long and being born at 54 cm increases the autism risk by 20%. However, these are relative risks and these disorders remain rare: in this example the absolute risk increases from 0.65% to 0.78%. Risk patterns are opposite in smaller newborns, who have higher risks for schizophrenia and lower risks for autism. Only for the smallest, prematurely-born babies does this diametric pattern disappear, because they have elevated risks for almost all disease categories."

Evolutionary conflicts

Boomsma also underlines that focused genomic studies will be needed to find out which genes are involved and how they affect brain function: "Our Centre's main objective is to develop and test evolutionary theory about the ways in which gene-level conflicts can corrupt even the most sophisticated forms of naturally evolved cooperation. It is no surprise that humans are vulnerable to such deep evolutionary conflicts, as are other mammals, and it is both useful and interesting to be aware of this part of our biological heritage," says Professor Boomsma.