If you look old, your heart may feel old, according to research presented at the American Heart Association’s Scientific Sessions 2012.

In a new study, those who had three to four ageing signs — receding hairline at the temples, baldness at the head’s crown, earlobe crease, or yellow fatty deposits around the eyelid (xanthelasmata) — had a 57 percent increased risk for heart attack and a 39 percent increased risk for heart disease .

‘The visible signs of ageing reflect physiologic or biological age, not chronological age, and are independent of chronological age,’ said Anne Tybjaerg-Hansen, M.D., the study’s senior author and professor of clinical biochemistry at the University of Copenhagen in Denmark.

Researchers analysed 10,885 participants 40 years and older (45 percent women) in the Copenhagen Heart Study. Of these, 7,537 had frontoparietal baldness (receding hairline at the temples), 3,938 had crown top baldness, 3,405 had earlobe crease, and 678 had fatty deposits around the eye.

In 35 years of follow-up, 3,401 participants developed heart disease and 1,708 had a heart attack.

Individually and combined, these signs predicted heart attack and heart disease independent of traditional risk factors. Fatty deposits around the eye were the strongest individual predictor of both heart attack and heart disease.

Heart attack and heart disease risk increased with each additional sign of ageing in all age groups and among men and women. The highest risk was for those in their 70s and those with multiple signs of ageing.

In the study, nurses and laboratory technicians noted the quantity of gray hair, prominence of wrinkles, the type and extent of baldness, the presence of earlobe crease and eyelid deposits.

‘Checking these visible ageing signs should be a routine part of every doctor’s physical examination,’ Tybjaerg-Hansen said. American Heart Association

International researchers, including a team at McGill University, have discovered a new cause for thyroid hormone deficiency, or hypothyroidism. This common endocrine disorder is typically caused by problems of the thyroid gland, and more rarely, by defects in the brain or the pituitary gland (hypophysis). However, a new cause of the disease has been discovered from an unsuspected source. The scientists, led by McGill Professor Daniel Bernard, Department of Pharmacology and Therapeutics in the Faculty of Medicine, identified a new hereditary form of hypothyroidism that is more prevalent in males than in females. This sex bias shone a light on where to look for the underlying cause.
‘Our collaborators in the Netherlands had been following a family in which two cousins had an unusual syndrome of hypothyroidisim and enlarged testicles,’ said Prof. Bernard. ‘Using state-of-the-art DNA sequencing technologies, we identified a mutation in a gene called immunoglobulin superfamily, member 1 (IGSF1), in both boys and their maternal grandfather. As one of few labs in the world studying this gene, we initiated a collaboration to determine whether the observed mutation might cause the disorder. At the time, the IGSF1 gene was known to be active in the pituitary gland, but its function was a mystery’.
‘Shortly after, we were contacted independently by a second group of researchers, studying a second family, in which two young brothers suffered from hypothyroidism and also harboured a mutation in the IGSF1 gene, though it was a different mutation than that observed in the Dutch family,’ said Prof. Bernard, ‘The fact that there were two unrelated families with the same male-biased clinical syndrome and mutations in the same gene strongly suggested that the mutations played a causal role in hypothyroidism’.

The groups reached out to researchers in the Netherlands, the UK, Italy and Australia who were following similar families and found that affected males all had mutations in their IGSF1 gene. Overall, the team identified 11 families with 10 different mutations in IGSF1.

‘We went on to show that mutations in IGSF1 block the protein it encodes from moving to the cell surface, where it normally functions’, explained Beata Bak, McGill Ph.D. student and the paper’s co-first author. ‘We also observed that the pituitary glands of mice lacking IGSF1 had reduced levels of the receptor for a brain-derived hormone known as thyrotropin-releasing hormone (TRH). If we think of TRH as a key, then its receptor is the lock into which the key fits to produce its effects. Our results suggest that in the absence of IGSF1, the pituitary gland becomes less sensitive to the brain’s instructions to secrete thyroid-stimulating hormone (TSH). As a result, the thyroid gland receives a reduced impetus to produce thyroid hormones’.

The group’s findings are significant as IGSF1 mutations cause a variable, though principally mild, form of hypothyroidism that would likely escape detection by most perinatal thyroid function screening methodologies. In addition, since the IGSF1 gene is highly polymorphic, there may be many individuals (boys and men, in particular) in the general population with presently undetected, but clinically significant hypothyroidism.

Symptoms of the disease include fatigue, weight gain, cold sensitivity, and muscle weakness. If left untreated, hypothyroidism increases the risk of developing heart disease. In infants, hypothyroidism can cause neurodevelopmental delay and, in extreme circumstances, cretinism.

‘A simple test could identify carriers of IGSF1 gene mutations or variants who might benefit from thyroid hormone replacement therapy. Our results highlight a fundamental role for this protein in how the brain and pituitary gland control thyroid function and therefore the whole body metabolism. We hope our work will inspire new research on IGSF1’s function in the pituitary gland under various physiological and pathophysiological conditions’, said Prof. Bernard. McGill University

Perhaps variety is the very spice of life, but as a matter of producing human life, it could be the bane of existence. That’s the indication of a new study that found men with wider variation in sperm length, particularly in the flagellum, had lower concentrations of sperm that could swim well. Those with more consistently made sperm seemed to have more capable ones.
‘Our study reveals that men who produce higher concentrations of competent swimming sperm also demonstrate less variation in the size and shape of those sperm,’ said Jim Mossman, a postdoctoral scholar at Brown University and lead author of the paper. ‘It suggests that in some cases, testes are working more optimally to produce high numbers of consistently manufactured sperm, and vice versa.’
At the University of Sheffield, where Mossman did his doctoral studies, he and his co-authors measured the heads, midpieces, and flagella of 30 sperm per man, from 103 men randomly selected from a pool of about 500 who were recruited for a larger fertility study. They also measured other characteristics of each man’s semen, such as sperm concentration and motility, that the World Health Organisation recognises as important markers of fertility.
‘The WHO suggests that measurements should be made on multiple components of sperm, but generally it’s only the sperm head that is considered,’ Mossman said. ‘No one’s ever looked at this before across sperm components. What we show is that measurements on other sperm parts, such as the flagellum that propels the sperm, can provide additional information about the quality and consistency of sperm manufacture.’
The result of the novel analysis yielded two overall findings. One was that men who had higher mean flagellum length, total sperm length, and flagellum-to-head length ratios had higher concentrations of motile sperm. But perhaps the more interesting finding was that the greater the inconsistency of length in the sperm a man manufactures, particularly with regard to the flagellum, the lower his concentration of sperm that could swim well.
‘The finding could give clinicians new insight into the diagnosis and treatment of male fertility problems, which accounts for up to 50 percent of the cases where couples struggle to conceive,’ Mossman said. The research suggests that at least in some men, measurable inconsistency in sperm length may be a sign of trouble with his process of making sperm, a process known as spermatogenesis. That trouble, akin to a manufacturing line with poor quality control, could result in a lower concentration of good swimmers. Brown University

Neuroscientists studying the link between poor sleep and schizophrenia have found that irregular sleep patterns and desynchronised brain activity during sleep could trigger some of the disease’s symptoms. The findings suggest that these prolonged disturbances might be a cause and not just a consequence of the disorder’s debilitating effects.
The possible link between poor sleep and schizophrenia prompted the research team, led by scientists from the University of Bristol, the Lilly Centre for Cognitive Neuroscience and funded by the Medical Research Council (MRC), to explore the impact of irregular sleep patterns on the brain by recording electrical brain activity in multiple brain regions during sleep.
For many people, sleep deprivation can affect mood, concentration and stress levels. In extreme cases, prolonged sleep deprivation can induce hallucinations, memory loss and confusion all of which are also symptoms associated with schizophrenia.
Dr Ullrich Bartsch, one of the study’s researchers, said: ‘Sleep disturbances are well-documented in the disease, though often regarded as side effects and poorly understood in terms of their potential to actually trigger its symptoms.’
Using a rat model of the disease, the team’s recordings showed de-synchronisation of the waves of activity which normally travel from the front to the back of the brain during deep sleep. In particular the information flow between the hippocampus — involved in memory formation, and the frontal cortex — involved in decision-making, appeared to be disrupted. The team’s findings reported distinct irregular sleep patterns very similar to those observed in schizophrenia patients.
Dr Matt Jones, the lead researcher from the University’s School of Physiology and Pharmacology, added: ‘Decoupling of brain regions involved in memory formation and decision-making during wakefulness are already implicated in schizophrenia, but de-coupling during sleep provides a new mechanistic explanation for the cognitive deficits observed in both the animal model and patients: sleep disturbances might be a cause, not just a consequence of schizophrenia. In fact, abnormal sleep patterns may trigger abnormal brain activity in a range of conditions.’
Cognitive deficits — reduced short term memory and attention span, are typically resistant to medication in patients. The findings from this study provide new angles for neurocognitive therapy in schizophrenia and related psychiatric diseases. Bristol University

Many patients who have genetic testing for Lynch syndrome, a hereditary predisposition to colon cancer, receive the inconclusive result ‘variants of uncertain clinical significance.’ This can be a problem, as people with Lynch syndrome have a much higher probability to develop colon cancer, and often develop colon cancer at an earlier age than is common among the general population; consequently, they need to begin screening at a much younger age.
Now, between two-thirds and three-fourths of these genetic variants can be classified into categories that indicate the most appropriate screening and treatment guidelines, according to two complementary papers recently published. The two papers, both co-authored by Sean Tavtigian, Ph.D., a Huntsman Cancer Institute (HCI) investigator and associate professor in the Department of Oncological Sciences at the University of Utah, provide a model that could help physicians as they assess their patient’s risk to develop cancer.
According to the American Cancer Society, about 143,460 new cases of colon cancer will be diagnosed in the United States this year. The National Cancer Institute estimates that two to four percent of all colon cancer is attributable to Lynch syndrome.
Mutations in mismatch repair genes, which proof-read DNA to correct genetic typos that occur during the replication process, are known to be the cause of the syndrome. ‘Some people in families with Lynch syndrome have already known mutations, and a small number of missense substitutions have also been classified as pathogenic,’ said Tavtigian. ‘But a fair number have other missense substitutions for which the clinical significance could not be determined, creating uncertainty concerning proper screening and treatment for patients and physicians alike.’
The first of the two studies reported on standardising several already available computer programs that grade the severity of missense substitutions (at the genomic level, these mutations affect only a single structural unit of DNA rather than an entire gene; at the protein level, they affect only a single amino acid rather than the entire protein). The second describes how clinical data concerning the tumours, family history, and other factors were combined with that initial information about severity. Taken together, the procedures described in the two papers allow previously unclassified genetic variations to be assessed for the level of risk they pose in colon cancer development.
‘Using these tools, we can evaluate any particular missense substitution and come up with a percentage indicating the probability that it is pathogenic,’ said Tavtigian. ‘I’m very careful to avoid saying pathogenic or neutral as an either-or statement. With missense substitutions, I don’t believe in a binary classification.’ A scale developed by his team in 2008 indicates the appropriate level of clinical action for a given percentage of risk, he adds. Huntsman Cancer Institute