POOR SPERM QUALITY LINKED TO HYPERTENSION OTHER HEALTH PROBLEMS

A study of men who were evaluated for the cause of their infertility finds previously unknown relationships between deficiencies in their semen and other, seemingly unrelated health problems.

A study of more than 9,000 men with fertility problems has revealed a correlation between the number of different defects in a man's semen and the likelihood that the man has other health problems.

The study, conducted by investigators at the Stanford University School of Medicine, also links poor semen quality to a higher chance of having various specific health conditions, such as hypertension, and more generally to skin and endocrine disorders.

The findings, published online Dec. 10 in Fertility and Sterility, may spur more-comprehensive approaches to treating male infertility. They also point to the wisdom of performing complete physical examinations of men experiencing reproductive difficulties.

"About 15 percent of all couples have fertility issues, and in half of those cases the male partner has semen deficiencies," said the study's lead author, Michael Eisenberg, MD, assistant professor of urology and director of male reproductive medicine and surgery at Stanford. "We should be paying more attention to these millions of men. Infertility is a warning: Problems with reproduction may mean problems with overall health."

A study Eisenberg co-authored a few years ago showed that infertile men had higher rates of overall mortality, as well as mortality linked to heart problems, in the years following an infertility evaluation. "But here, we're already spotting signs of trouble in young men in their 30s," he said.

Analyzing medical records

In the new study, Eisenberg and his colleagues analyzed the medical records of 9,387 men, mostly between 30 and 50 years old, who had been evaluated at Stanford Hospital & Clinics (now Stanford Health Care) between 1994 and 2011 to determine the cause of their infertility. The men had routinely provided semen samples, which the researchers assessed for characteristics including volume, concentration and motility. In about half of all the male infertility cases, the problem was abnormal semen; in the rest, the fault lay elsewhere. So, using the database, the investigators were able to compare the overall health status of men who had semen defects to that of the men who didn't.

With a median age of 38, this was a fairly young group of men. However, 44 percent of all the men had some additional health problem besides the fertility problem that brought them to the clinic. In particular, the investigators found a substantial link between poor semen quality and specific diseases of the circulatory system, notably hypertension, vascular disease and heart disease. "To the best of my knowledge, there's never been a study showing this association before," said Eisenberg. "There are a lot of men who have hypertension, so understanding that correlation is of huge interest to us."

In addition, as the number of different kinds of defects in a man's semen rose, so did his likelihood of having a skin disease or endocrine disorder. When looking at the severity of all health problems, the scientists observed a statistically significant connection between the number of different ways in which a man's semen was deficient and the likelihood of his having a substantial health problem.

Health, semen quality 'strongly correlated'

The study wasn't designed to determine precisely how connections between semen deficiencies and seemingly unrelated disorders, such as cardiovascular or endocrine disease, come about. But, Eisenberg noted, some 15 percent of all genes in the human genome are connected fairly directly to reproduction, and most of these genes also have diverse functions in other bodily systems. He also noted that it may not be a disease itself, but the treatment for the disease, that's actually responsible for reproductive malfunction. He said he is exploring this possibility now.

As we treat men's infertility, we should also assess their overall health.

"A man's health is strongly correlated with his semen quality," he said. "Given the high incidence of infertility, we need to take a broader view. As we treat men's infertility, we should also assess their overall health. That visit to a fertility clinic represents a big opportunity to improve their treatment for other conditions, which we now suspect could actually help resolve the infertility they came in for in the first place."

The senior author of the study is Mark Cullen, MD, professor of medicine at Stanford. Other Stanford co-authors are professor of reproductive endocrinology and fertility Barry Behr, PhD; former professor of obstetrics and gynecology Renee Reijo Pera, PhD; and statistical programmer Shufeng Li.

SENSE OF PURPOSE IN LIFE LINKED TO LOWER MORTALITY AND CARDIOVASCULAR RISK

People who have a higher sense of purpose in life are at lower risk of death and cardiovascular disease, reports a pooled data analysis inPsychosomatic Medicine: Journal of Biobehavioral Medicine, the official journal of the American Psychosomatic Society

"Possessing a high sense of purpose in life is associated with a reduced risk for mortality and cardiovascular events," according to the study by Drs. Randy Cohen and Alan Rozanski and colleagues at Mt. Sinai St. Luke's-Roosevelt Hospital, New York. While the mechanisms behind the association remain unclear, the findings suggest that approaches to strengthening a sense of purpose might lead to improved health outcomes.

How Does Purpose in Life Affect Health and Mortality Risks?

Using a technique called meta-analysis, the researchers pooled data from previous studies evaluating the relationship between purpose in life and the risk of death or cardiovascular disease. The analysis included data on more than 136,000 participants from ten studies -- mainly from the United States or Japan. The US studies evaluated a sense of purpose or meaning in life, or "usefulness to others." The Japanese studies assessed the concept of ikigai, translated as "a life worth living."

The study participants, average age 67 years, were followed up for an average of seven years. During this time, more than 14,500 participants died from any cause while more than 4,000 suffered cardiovascular events (heart attack, stroke, etc).

The analysis showed a lower risk of death for participants with a high sense of purpose in life. After adjusting for other factors, mortality was about one-fifth lower for participants reporting a strong sense of purpose, or ikigai.

A high sense of purpose in life was also related to a lower risk of cardiovascular events. Both associations remained significant on analysis of various subgroups, including country, how purpose in life was measured, and whether the studies included participants with pre-existing cardiovascular disease..

There is a well-documented link between "negative psychosocial risk factors" and adverse health outcomes, including heart attack, stroke, and overall mortality. "Conversely, more recent study provides evidence that positive psychosocial factors can promote healthy physiological functioning and greater longevity," according to the authors.

The new analysis assembles high-quality data from studies assessing the relationship between purpose life and various measures of health and adverse clinical outcomes. The researchers write, "Together, these findings indicate a robust relationship between purpose in life and mortality and/or adverse cardiovascular outcomes."

While further studies are needed to determine how purpose in life might promote health and deter disease, preliminary data suggest a few basic mechanisms. The association might be explained physiologically, such as by buffering of bodily responses to stress; or behaviorally, such as by a healthier lifestyle.

"Of note, having a strong sense of life purpose has long been postulated to be an important dimension of life, providing people with a sense of vitality motivation and resilience," Dr. Rozanski comments. "Nevertheless, the medical implications of living with a high or low sense of life purpose have only recently caught the attention of investigators. The current findings are important because they may open up new potential interventions for helping people to promote their health and sense of well-being."

KIDS DNA TEST FOR DISEASES LINKED TO BLINDNESS

Researchers in the United Kingdom have demonstrated that advanced DNA testing for congenital cataracts can quickly and accurately diagnose a number of rare diseases marked by childhood blindness, according to a study published online in Ophthalmology, the journal of the American Academy of Ophthalmology. Using a single test, doctors were able to tailor care specifically to a child's condition based on their mutations, reducing the time and money spent on diagnosis and enabling earlier treatment and genetic counseling

Each year, between 20,000 and 40,000 children worldwide are born with congenital cataracts, a disease that clouds the lens of the eye and often requires surgery and treatment to prevent blindness.[i] The disease can arise following a maternal infection or be inherited as an isolated abnormality. Congenital cataracts can also appear as a symptom of more than 100 rare diseases, making mutations in the 115 genes associated with congenital cataracts useful as diagnostic markers for the illnesses.

Diagnosing these rare diseases previously proved a lengthy, costly and inconclusive process involving numerous clinical assessments and taking a detailed family history. DNA testing, one gene at a time, would have taken years to complete. Employing new DNA sequencing technology, called targeted next-generation sequencing, researchers at the University of Manchester sped up diagnosis to a matter of weeks by testing for mutations in all 115 known congenital cataracts genes at one time.

In 75 percent of the 36 cases tested, the DNA test determined the exact genetic cause of congenital cataracts. In one case, the DNA test helped diagnose a patient with Warburg Micro syndrome, an extremely rare disease that is marked by an abnormally small head and the development of severe epilepsy, among other medical issues. Having a clear diagnosis allowed for genetic counseling and appropriate care to be delivered quicker than previously possible without the test.

"There are many diseases that involve congenital cataracts but finding the exact reason was always difficult," said Graeme Black, DPhil., professor of genetics and ophthalmology at the University of Manchester and strategic director of the Manchester Centre for Genomic Medicine. "Even with a family history, diagnosing these rare diseases was always a bit of a shot in the dark."

In the course of their work, done in collaboration with Manchester Royal Eye Hospital, researchers also found previously undescribed mutations linked to cataract formation. "There is hope that our work may one day provide more insight into the development and treatment of age-related cataracts, a leading cause of blindness worldwide," said Rachel Gillespie, MSc, lead author of the study who designed and developed the test.

The test was made available to U.K. patients through the country's National Health Service in December 2013. Infants and children who have congenital cataracts can be tested as well as prospective parents with a history of the condition who wish to evaluate the risk to their child. Results generally take about two months. While only available in the U.K., the congenital cataract DNA test can be requested by registered medical facilities through international referral.

As with all genetic testing, the American Academy of Ophthalmology encourages clinicians and patients to consider the benefits as well as the risks. Ophthalmologists who order genetic tests either should provide genetic counseling to their patients themselves, if qualified to do so, or should ensure that counseling is provided by a trained individual, such as a board-certified medical geneticist or genetic counselor. For more information, please see the Academy's recommendations on genetic testing for inherited eye diseases.

COMMON ANTIBIOTICS LINKED WITH HEART DEATH

The antibiotic clarithromycin -- widely used for treating common bacterial infections -- is associated with an increased risk of heart deaths, finds a study published on thebmj.com today.

The authors say their findings require urgent confirmation, given that many millions of people are prescribed the drug each year. But they stress that the absolute risk is small and that prescribing practice should not be changed until results have been confirmed in an independent study.

Clarithromycin belongs to a group of antibiotics known as macrolides. Macrolide antibiotics prolong the duration of electrical activity of the heart muscle (known as the QT interval) and are therefore thought to increase the risk of potentially fatal heart rhythm problems.

Given this background, the cardiac safety profiles of individual macrolides need to be studied in greater detail to help guide clinical treatment decisions.

So a team of Danish researchers decided to assess the risk of cardiac death associated with clarithromycin and another macrolide called roxithromycin, compared with penicillin V, an antibiotic with no known cardiac risk.

Using national databases, they identified over 5 million treatment courses among Danish adults aged 40-74 years from 1997 to 2011 (160,297 with clarithromycin, 588,988 with roxithromycin and 4,355,309 with penicillin V).

Individuals with serious disease, who may be at high baseline risk of death, were excluded from the analysis.

A total of 285 cardiac deaths were observed during ongoing use with the study drugs, 18 of which occurred during use of clarithromycin and 32 during use of roxithromycin.

After adjusting for factors such as age, sex, baseline cardiac risk and use of other medication, ongoing use of clarithromycin was associated with a 76% higher risk of cardiac death compared with use of penicillin V. There was no increased risk of cardiac death with clarithromycin after treatment had ended.

The absolute risk difference was 37 cardiac deaths per 1 million courses with clarithromycin. No increased risk of cardiac death was found with ongoing or past use of roxithromycin.

"Our study expands on the available knowledge of the cardiac safety of macrolides, being the first large scale population based observational study to show significantly increased cardiac risk with clarithromycin and the relative cardiac safety of roxithromycin," write the authors.

The authors emphasise that the absolute increase in risk is small and should have limited, if any, effect on the prescribing practice in individual patients. However, they note, "clarithromycin is one of the more commonly used antibiotics in many countries and many millions of people are prescribed this drug each year; thus, the total number of excess (potentially avoidable) cardiac deaths may not be negligible."

Before these results are used to guide clinical decision making, "confirmation in independent populations is an urgent priority given the widespread use of macrolide antibiotics," they conclude.

Sleep Apnea And Neuropathy Linked

Today's post from jfponline.com (see link below) looks at the relationship between neuropathy and OSN (obstructive sleep apnoea). There have long been suggestions that the two conditions are linked but this article looks at some evidence via case studies. It certainly seems that many people with neuropathy also have sleep apnoea (where you actually stop breathing a number of times during sleep - mostly harmless but can be serious) the moderator of this blog among them. The question is, does either condition cause the other, or play a part in causing it? Interesting read.

Peripheral neuropathy linked to obstructive sleep apnoea? J Fam Pract. 2013 October;62(10):577-578.

OSA may not be the first thing that comes to mind when examining a patient with peripheral neuropathy, but treating the sleep disorder can produce surprising benefits.

Siegfried Schmidt, MD, PhD; Anthony Rodrigues, MD; Maria Elisa Lupi, MD; Fong Wong, DDS, MS

Department of Community Health and Family Medicine, College of Medicine (Drs. Schmidt and Lupi), Department of Restorative Dental Sciences, College of Dentistry (Dr. Wong), University of Florida, Gainesville; Department of Child Neurology, Floating Hospital for Children at Tufts Medical Center and Tufts University School of Medicine, Boston, Mass (Dr. Rodrigues)

Fwong@dental.ufl.edu

The authors reported no potential conflict of interest relevant to this article.

CASE A 57-year-old white woman presented with symptoms of bilateral “stocking-like numbness” and the sensation of “wearing socks for a few weeks” but denied any injury, previous chemotherapy, or diabetes. Her medical history was positive for untreated obstructive sleep apnea (OSA), obesity (body mass index, 36 kg/m2), osteoarthritis in various joints, impaired fasting glucose with normal glycosylated hemoglobin (HbA1c), hypertension, gastroesophageal reflux disease, hypothyroidism, hypercholesterolemia, and osteoporosis.

Our initial examination revealed decreased sensation to light palpation and pin prick over the distal portion of her lower extremities in a stocking-like fashion. Proprioception was decreased at the distal joint of the big toe. Her deep tendon reflex pattern was symmetric with 2+ at the knees, ankles, and toes. The rest of her lower extremity exam was within normal limits and there were no obvious vascular abnormalities.

Given the suspicion of peripheral neuropathy, the patient underwent laboratory tests and a nerve conduction study. Vitamin B12, vitamin B1, methylmalonic acid (MMA), thyroid function, thyroid peroxidase (TPO), serum protein electrophoresis (SPEP), rapid plasma reagin (RPR), sedimentation rate, vitamin D, complete blood count, and chemistry profile 24 were all negative. The antinuclear antibody test revealed a homogenous 1:80 titer with a negative nuclear deoxyribonucleic acid. Her fasting glucose had been elevated between 107 to 117 mg/dL in the last 5 years but HbA1c was normal (5.8%). The patient had not been diagnosed with diabetes and her latest glucose values had been stable.

However, electromyography and a nerve conduction study were abnormal, with electrophysiological evidence of mild axonal polyneuropathy. During the month prior to her presentation, she had developed burning pain in addition to the numbness/stocking sensation. Pregabalin, gabapentin, duloxetine, celecoxib, hydrocodone, methadone, and other medications were ineffective. Eventually the foot pain became so severe—she described it as “walking on tacks”—that she was unable to walk.

Our team decided to do a nerve block to relieve the pain. Initially she underwent right and later left peroneal and posterior tibial nerve blocks, which gave her immediate relief that lasted about 2 months.

Relief from the pain, but what about the OSA symptoms?

In the meantime, our patient developed increasing OSA symptoms, including snoring, nonrestorative sleep, daytime somnolence, and fatigue. (To learn more about OSA, see “Obstructive sleep apnea: A diagnostic and treatment guide” on page 565.)

Her history of mild-to-moderate OSA dated back 2 years, and included an apnea-hypopnea index (AHI) of 20 events per hour and 133 episodes of oxygen desaturation with a low O2 desaturation of 83%. The patient had never been treated, however, because she felt that she couldn’t tolerate the continuous positive airway pressure (CPAP) mask.

The patient finally agreed to a CPAP titration study. Her AHI improved from 20 to less than 2 events per hour; the oxygen desaturation dropped from 133 to 104 episodes; and the lowest O2 desaturation went from 83% to 85%.

When we initially started CPAP, our patient did not tolerate it very well. However, after consulting with our sleep clinic, she was placed on bilevel positive airway pressure, which she did tolerate. Surprisingly, she also noticed immediate improvement of the neuropathic foot pain; after a few weeks it resolved completely.

Still no foot pain…We continue to follow the patient’s progress and, after 3 years, she remains free of foot pain. Her initial numbness remains, however. She has not After starting CPAP, the patient noticed immediate improvement of the neuropathic foot pain; after a few weeks, it resolved completely. developed diabetes, with similar fasting sugar levels and an HbA1c of 5.4%. She is not taking any medication for neuropathic pain, but remains on methadone for unrelated severe intractable osteoarthritic pain of the lumbar spine, bilateral knee joints, and left hip.

The link between sleep apnea and neuropathy

Our case report suggests that clinicians should consider OSA as a cause of neuropathic pain. A recent review of the literature supports the relationship between the 2 conditions.

The prevalence of neuropathy in the general population is 2.4%, rising to 8% with advancing age.1 Many different types of peripheral neuropathy have been described; they have different symptoms and characteristics, depending on the specific part of the nervous system that is affected.2

The literature reveals a strong association between OSA and peripheral neuropathy and sight-threatening retinopathy.3 One study found that nearly 60% of patients with diabetes and OSA also have peripheral neuropathy.4 Another report found that OSA is an independent risk factor for axonal damage of peripheral nerves.5 Furthermore, a case-control study revealed that the impaired neural function is at least partly reversible with treatment for sleep apnea.4 Finally, Tahrani et al6 have found that “neuropathy prevalence was higher in patients with OSA than those without” (60% vs 27%; P is less than .001), which supports our case finding.

The specific mechanism linking OSA and neuropathy remains elusive, but the evidence suggests that peripheral nervous tissue is affected by chronic endoneural hypoxia in this patient population.7 In patients with OSA, 2 types of nerve dysfunction are apparent: ischemia-related axonal degeneration and resistance to ischemic nerve failure.8

An approach worth considering. While nerve blocks did provide some relief for our patient, they are not a long-term solution. To our knowledge, this case report is the first one published in the United States describing resolution of neuropathic pain by treatment of OSA. This approach is certainly worth considering in patients who have not responded to more traditional therapy.

Correspondence

Fong Wong, DDS, MS, Associate Professor, Department of Restorative Dental Sciences, College of Dentistry, University of Florida, 1395 Center Drive, PO Box 100435, Gainesville, FL 32610; Fwong@dental.ufl.edu

 http://www.jfponline.com/topics/neurologic/article/peripheral-neuropathy-linked-to-obstructive-sleep-apnea.html

BABIES INTEREST IN FACES LINKED TO CALLOUS EMOTIONAL TRAITS

Scientists at King's College London, the University of Manchester, and the University of Liverpool have found that an infant's preference for a person's face, rather than an object, is associated with lower levels of callous and unemotional behaviors in toddlerhood.

The study, published in Biological Psychiatry, assessed if 213 five-week-old infants spent longer tracking a person's face compared to an inanimate object -- in this case a red ball. The researchers showed that greater tracking of the face relative to the ball was linked to lower callous unemotional behaviors measured using questionnaires when children were two and a half years old. The study also showed that if a mother responds more sensitively to their baby during playtime, then the child is less likely to display callous unemotional behavior as a toddler.

Callous and unemotional behaviors include a lack of guilt and empathy, reduced concern for other's distress and difficulties with understanding emotions. In older children and adults, callous unemotional traits have been associated with reduced attention to important social features such as other people's faces and eyes. This study is the first to examine whether such a relationship is present from the first few weeks of life.

This is the latest finding from the Medical Research Council (MRC) funded Wirral Child Health and Development Study, an ongoing interdisciplinary investigation into the interplay of social and biological factors in the emotional and cognitive development of children. The children are currently being followed to test whether face preference in infancy can predict callous unemotional behavior through to middle childhood.

Dr Rachael Bedford, a Sir Henry Wellcome Postdoctoral Fellow at the Biostatistics Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, says: "Callous and unemotional behaviors in children are known to be associated with an increased emotional burden on families as well as later criminality and antisocial behavior. This study takes us a step further in understanding the earliest origins of callous and unemotional behaviors. An important next step will be to seek replication of the findings before working towards developing early interventions."

Dr Jonathan Hill, University of Manchester, says: "While our findings are interesting, we don't yet know how stable callous unemotional behaviors are. Our follow-up work will assess how these early indicators affect children in later life."

PRENATAL EXPOSURE TO COMMON HOUSEHOLD CHEMICALS LINKED WITH SUBSTANTIAL DROP IN CHILD IQ

Children exposed during pregnancy to elevated levels of two common chemicals found in the home--di-n-butyl phthalate (DnBP) and di-isobutyl phthalate (DiBP)--had an IQ score, on average, more than six points lower than children exposed at lower levels, according to researchers at Columbia University's Mailman School of Public Health.

The study is the first to report a link between prenatal exposure to phthalates and IQ in school-age children. Results appear online in the journal PLOS ONE.

DnBP and DiBP are found in a wide variety of consumer products, from dryer sheets to vinyl fabrics to personal care products like lipstick, hairspray, and nail polish, even some soaps. Since 2009, several phthalates have been banned from children's toys and other childcare articles in the United States. However, no steps have been taken to protect the developing fetus by alerting pregnant women to potential exposures. In the U.S., phthalates are rarely listed as ingredients on products in which they are used.

Researchers followed 328 New York City women and their children from low-income communities. They assessed the women's exposure to four phthalates--DnBP, DiBP, di-2-ethylhexyl phthalate, and diethyl phthalate--in the third trimester of pregnancy by measuring levels of the chemicals' metabolites in urine. Children were given IQ tests at age 7.

Children of mothers exposed during pregnancy to the highest 25 percent of concentrations of DnBP and DiBP had IQs 6.6 and 7.6 points lower, respectively, than children of mothers exposed to the lowest 25 percent of concentrations after controlling for factors like maternal IQ, maternal education, and quality of the home environment that are known to influence child IQ scores. The association was also seen for specific aspects of IQ, such as perceptual reasoning, working memory, and processing speed. The researchers found no associations between the other two phthalates and child IQ.

The range of phthalate metabolite exposures measured in the mothers was not unusual: it was within what the Centers for Disease Control and Prevention observed in a national sample.

"Pregnant women across the United States are exposed to phthalates almost daily, many at levels similar to those that we found were associated with substantial reductions in the IQ of children," says lead author Pam Factor-Litvak, PhD, associate professor of Epidemiology at the Mailman School.

"The magnitude of these IQ differences is troubling," says senior author Robin Whyatt, DrPH, Professor of Environmental Health Sciences and deputy director of the Columbia Center for Children's Environmental Health at the Mailman School. "A six- or seven-point decline in IQ may have substantial consequences for academic achievement and occupational potential."

"While there has been some regulation to ban phthalates from toys of young children," adds Dr. Factor-Litvak, "there is no legislation governing exposure during pregnancy, which is likely the most sensitive period for brain development. Indeed, phthalates are not required to be on product labeling."

While avoiding all phthalates in the United States is for now impossible, the researchers recommend that pregnant women take steps to limit exposure by not microwaving food in plastics, avoiding scented products as much as possible, including air fresheners, and dryer sheets, and not using recyclable plastics labeled as 3, 6, or 7.

The findings build on earlier, similar observations by the researchers of associations between prenatal exposure to DnBP and DiBP and children's cognitive and motor development and behavior at age 3. This September, they reported a link between prenatal exposure to phthalates and risk for childhood asthma.

It's not known how phthalates affect child health. However, numerous studies show that they disrupt the actions of hormones, including testosterone and thyroid hormone. Inflammation and oxidative stress may also play a role.

GENE LINKED TO INCREASED DENTRITIC SPINES AUTISM FINDINGS

Scientists at the UNC School of Medicine have discovered that knocking out the gene NrCAM leads to an increase of dendritic spines on excitatory pyramidal cells in the brains of mammals. Other studies have confirmed that the overabundance of dendritic spines on this type of brain cell allows for too many synaptic connections to form between neurons – a phenomenon strongly linked to autism.

The finding, published in The Journal of Neuroscience, adds evidence that NrCAM is a major player in neurological disorders. Previous UNC studies showed that knocking out the NrCAM gene caused mice to exhibit the same sorts of social behaviors associated with autism in humans.

“There are many genes involved in autism, but we’re now finding out exactly which ones and how they’re involved,” said Patricia Maness, PhD, professor of biochemistry and biophysics and senior author of the Journal of Neuroscience paper. “Knowing that NrCAM has this effect on dendrites allows us to test potential drugs, not only to observe a change in behaviors linked to autism but to see if we can improve dendritic spine abnormalities, which may underlie autism.

Maness’s finding comes on the heels of a report from Columbia University researchers who found an overabundance of the protein MTOR in mice bred to develop a rare form of autism. By using a drug to limit MTOR in mice, the Columbia researchers were able to decrease the number of dendritic spines and thus prune the overabundance of synaptic connections during adolescence. As a result, the social behaviors associated with autism were decreased. However, the drug used to limit MTOR can cause serious side effects, and it is located inside cells, making it a potentially difficult protein to target.

It is too early to tell if NrCAM and MTOR are linked, but Maness is now studying if the decreased amount of the NrCAM protein could trigger activation of MTOR. If so, then NrCAM, which is an accessible membrane-bound protein, might be a preferred therapeutic target for certain autism-related conditions.

In their study, Maness and her colleagues found that the NrCAM protein forms a complex with two other molecules to create a receptor on the membrane of excitatory pyramidal neurons. Maness’s team found that this receptor allows dendritic spines to retract, allowing for proper neuron pruning during maturation of the cortex. As a result, excitatory and inhibitory synapses between neurons develop in a balanced ratio necessary for brain circuits to function properly.

Maness, a member of the UNC Neuroscience Center and the Carolina Institute for Developmental Disabilities, also said that there are likely many other proteins downstream of NrCAM that depend on the protein to maintain the proper amount of dendritic spines. Decreasing NrCAM could allow for an increase in the levels of some of these proteins, thus kick starting the creation of dendritic spines.

“Basic science in autism is converging in really exciting ways,” Maness said. “Too many spines and too many excitatory connections that are not pruned between early childhood and adolescence could be one of the chief problems underlying autism. Our goal is to understand the molecular mechanisms involved in pruning and find promising targets for therapeutic agents.”

PARTICULAR BRAIN CONNECTIONS LINKED TO POSITIVE HUMAN TRAITS

There is a strong correspondence between a particular set of connections in the brain and positive lifestyle and behaviour traits, according to a new study by Oxford University researchers.

A team of scientists led by the University's Centre for Functional MRI of the Brain has investigated the connections in the brains of 461 people and compared them with 280 different behavioural and demographic measures that were recorded for the same participants. They found that variation in brain connectivity and an individual's traits lay on a single axis -- where those with classically positive lifestyles and behaviours had different connections to those with classically negative ones. The findings are published in Nature Neuroscience.

The team used data from the Human Connectome Project (HCP), a $30m NIH-funded brain imaging study led by Washington, Minnesota and Oxford Universities. The HCP is pairing up functional MRI scans of 1,200 healthy participants with in-depth data gained from tests and questionnaires. "The quality of the imaging data is really unprecedented," explains Professor Stephen Smith, who was the lead author of the paper. "Not only is the number of subjects we get to study large, but the spatial and temporal resolution of the fMRI data is way ahead of previous large datasets." So far, data for 500 subjects have been released to researchers for analysis.

The Oxford team took the data from 461 of the scans and used it to create an averaged map of the brain's processes across the participants. "You can think of it as a population-average map of 200 regions across the brain that are functionally distinct from each other," explains Professor Smith. "Then, we looked at how much all of those regions communicated with each other, in every participant."

The result is a connectome for every subject: a detailed description of how much those 200 separate brain regions communicate with each other, which can be thought of as a map of the brain's strongest connections. The team then added the 280 different behavioural and demographic measures for each subject and performed a 'canonical correlation analysis' between the two data sets -- a mathematical process that can unearth relationships between the two large sets of complex variables.

They found one strong correlation that relates specific variations in a subject's connectome with their behavioural and demographic measures. Interestingly, the correlation shows that those with a connectome at one end of scale score highly on measures typically deemed to be positive, such as vocabulary, memory, life satisfaction, income and years of education. Meanwhile, those at the other end of the scale were found to exhibit high scores for traits typically considered negative, such as anger, rule-breaking, substance use and poor sleep quality.

The researchers point out that their results resemble what psychologists refer to as the 'general intelligence g-factor': a variable first proposed in 1904 that's sometimes used to summarize a person's abilities at different cognitive tasks. While the new results include many real-life measures not included in the g-factor -- such as income and life satisfaction, for instance -- those such as memory, pattern recognition and reading ability are strongly mirrored.

Proponents of the g-factor point out that many intelligence-related measures are inter-related -- suggesting that if you're good at one thing, you're likely to be good at the others, too. However, in the past, the g-factor has also received some criticism, partly because it is not necessarily clear if these correlations between different cognitive abilities are truly reflecting correlations between distinct underlying brain circuits. The new results, however, may provide an opportunity to understand if that's correct, or if the processes in the brain tell a more complex story.

"It may be that with hundreds of different brain circuits, the tests that are used to measure cognitive ability actually make use of different sets of overlapping circuits," explains Professor Smith. "We hope that by looking at brain imaging data we'll be able to relate connections in the brain to the specific measures, and work out what these kinds of test actually require the brain to do."

The team will continue to pursue this investigation as the set of Human Connectome Project data sets made available to researchers increases.

CARBONATED DRINKS LINKED WITH OUT OF HOSPITAL CARDIAC ARREST OF CARDIAC ORIGIN

Carbonated beverages are associated with out-of-hospital cardiac arrests of cardiac origin, according to results from the All-Japan Utstein Registry presented for the first time today at ESC Congress. The study in nearly 800,000 patients suggests that limiting consumption of carbonated beverages may be beneficial for health.

"Some epidemiologic studies have shown a positive correlation between the consumption of soft drinks and the incidence of cardiovascular disease (CVD) and stroke, while other reports have demonstrated that the intake of green tea and coffee reduced the risk and mortality of CVD," said principal investigator Professor Keijiro Saku, Dean and professor of cardiology at Fukuoka University in Japan. "Carbonated beverages, or sodas, have frequently been demonstrated to increase the risk of metabolic syndrome and CVD, such as subclinical cardiac remodeling and stroke. However, until now the association between drinking large amounts of carbonated beverages and fatal CVD, or out-of-hospital cardiac arrests (OHCA) of cardiac origin, was unclear."

The study compared the age-adjusted incidence of OHCAs to the consumption of various beverages per person between 2005 and 2011 in the 47 prefectures of Japan. It included 797 422 patients who had OHCAs of cardiac and non-cardiac origin from the All-Japan Utstein Registry of the Fire and Disaster Management Agency. Data on the consumption of the various beverages per person was obtained from the Ministry of Health, Labour and Welfare of Japan, using expenditure on beverages as a proxy measure.

The analysis focused on the 785 591 OHCA cases that received resuscitation, of which 435 064 (55.4%) were of cardiac origin and 350 527 (44.6%) were of non-cardiac origin. Those of non-cardiac origin included cerebrovascular disease, respiratory disease, malignant tumour, and exogenous disease (4.8%, 6.1%, 3.5%, and 18.9%, respectively).

The researchers found that expenditures on carbonated beverages were significantly associated with OHCAs of cardiac (r=0.30, p=0.04), but not non-cardiac origin (r=-0.03, p=0.8).

Expenditures on other beverages, including green tea, black tea, coffee, cocoa, fruit or vegetable juice, fermented milk beverage, milk and mineral water were not significantly associated with OHCAs of cardiac origin.

"Carbonated beverage consumption was significantly and positively associated with OHCAs of cardiac origin in Japan, indicating that beverage habits may have an impact on fatal CVD," said Professor Saku. "The acid in carbonated beverages might play an important role in this association."

Professor Saku concluded: "Our data on carbonated beverage consumption is based on expenditure and the association with OHCA is not causal. But the findings do indicate that limiting consumption of carbonated beverages could be beneficial for health."