Science Weekly: Cern, space and sniffing

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The woman behind Cern’s Atlas experiment; the Rosetta mission’s stunning pictures of asteroid Lutetia; and communicating by sniffing

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Doctors Defy Death: Transplant Advance in Windpipe Cancer

This past July, windpipes were successfully transplanted into two cancer patients in an innovative procedure that uses stem cells to allow a donated trachea to 1) ___ tissue and create an organ biologically close to the original. The 31-year-old Czech and 19-year-old British patients are in good condition and have been released from the hospital just weeks after the surgery. The British woman was 2) ___ after only three or four days.

Surgeons have been making advances in the 3) ___ of windpipes, but previous cases have mostly focused on patients whose windpipes have been physically damaged due to trauma. While trachea 4) ___ is rare, it is very difficult to treat because it is resistant to chemotherapy and radiation and transplants of mechanical devices to replace the windpipe have not been effective. The new technique is extraordinary, said Alessandro Nanni Costa, the director of Italy’s National Transplant Center. “What is new about this procedure is combining a surgical technique with biotechnology, through the use of 5) ___ cells.”

The surgical team was headed by Dr. Paolo Macchiarini, who participated in a windpipe transplant in Spain nearly two years ago. In that case, doctors gave a Colombian woman a new windpipe with 6) ___ grown from her own stem cells, eliminating the need for anti-rejection drugs. A similar procedure was followed in this case. The donor windpipe was stripped of all cells until it was just a tube with no organic material. Just before being transplanted, Dr. Macchiarini injected the donor trachea with the stem cells. In the Spanish case, the stem cells were grown on the 7) ___ before the transplant. It takes two to three months for the stem cells to completely cover the trachea, creating a new organ, Giovannini said.

In the meantime, the windpipe is functional without the cells – acting as a sort of mechanical device before the stem cells transform it into an organ. Because the new trachea contains no organic substance foreign to the patient, no anti-rejection 8) ___ are needed. Macchiarini told a press conference in Florence the procedure could in the future be applied to other organs. “I’m thinking about the larynx or surgeries involving lungs,” Macchiarini said.

ANSWERS: 1) regenerate; 2) speaking; 3) transplant; 4) cancer; 5) stem; 6) tissue; 7) trachea; 8) drugs

Brainstem, Spinal Cord Images Hidden in Michelangelo’s Sistine Chapel Fresco

Michelangelo, the 16th century master painter and accomplished anatomist, appears to have hidden an image of the brainstem and spinal cord in a depiction of God in the Sistine Chapel’s ceiling. These findings by a neurosurgeon and a medical illustrator, published in the May Neurosurgery, may explain long controversial and unusual features of one of the frescoes’ figures.

Michelangelo is known to have dissected numerous cadavers starting in his teenage years, these anatomic studies aiding him in creating extremely accurate depictions of the human figure in his sculptures and paintings, notably the statue of David in Florence and paintings of God and other figures from the Book of Genesis in the Vatican’s Sistine Chapel in Rome. Although the vast majority of subjects in this painting are considered anatomically correct, art historians and scholars have long debated the meaning of some anatomical peculiarities seen on God’s neck in the part of the painting known as Separation of Light From Darkness. In this image, the neck appears lumpy, and God’s beard awkwardly curls upward around his jaw.

“Michelangelo definitely knew how to depict necks – he knew anatomy so well,” says Rafael Tamargo, M.D., a professor in the Department of Neurosurgery at the Johns Hopkins University School of Medicine. “That is why it was such a mystery why this particular neck looked so odd.”

To investigate, Tamargo enlisted the help of his Hopkins colleague Ian Suk, a medical illustrator and associate professor in the Department of Neurosurgery. Together, the researchers realized that the unusual features in the neck strongly resemble a brainstem, the portion of tissue at the base of the brain that connects to the spinal cord. “It’s an unusual view of the brainstem, from the bottom up. Most people wouldn’t recognize it unless they had extensively studied neuroanatomy,” says Suk.

Suk adds that the strategically placed brainstem might also explain another unusual feature of the painting. In this same image, God is depicted in a red robe with an odd tubular structure depicted in the chest. Although God wears the same red robe in other images in the fresco, this tubular structure is absent elsewhere. The structure has the right placement, shape, and size to be a spinal cord, say the researchers, suggesting another piece of hidden anatomy in the artwork. Tamargo and Suk explain that, if their proposition is correct, it wouldn’t be the first time that such concealed anatomical depictions have been proposed to exist in the Sistine Chapel’s ceiling. In 1990, Frank Lynn Meshberger, an obstetrician based in Indiana, published a paper suggesting that the shroud surrounding the image known as the Creation of Adam strongly resembles an anatomically correct brain. “It looks like the central nervous system may have been too good a motif to use only once,” Tamargo says. Story Source: Johns Hopkins School of Medicine; Journal Reference: Ian Suk, Rafael J. Tamargo. Concealed Neuroanatomy in Michelangelo’s Separation of Light From Darkness in the Sistine Chapel. Neurosurgery, 2010; 66 (5): 851 DOI: 10.1227/01.NEU.0000368101.34523.E1

New Compound Improves Obesity-Related Health Complications

Obesity and its metabolic consequences are a major public health concern worldwide. Obesity is associated with overactivity of the endocannabinoid system, which is involved in the regulation of appetite, lipogenesis, and insulin resistance. Cannabinoid-1 receptor (CB1R) antagonists reduce body weight and improve cardiometabolic abnormalities in experimental and human obesity. However, the clinical advancement of such compounds has been stymied by behavioral side effects associated with their use, such as anxiety, depression and suicidal thoughts.

According to a study published online in the Journal of Clinical Investigation (26 July 2010), it was demonstrated that a CB1R neutral antagonist, largely restricted to the periphery, does not affect behavioral responses mediated by CB1R in the brains of mice with genetic or diet-induced obesity. However, it does cause weight-independent improvements in glucose homeostasis, fatty liver, and plasma lipid profile. The authors reasoned that a compound that is unable to penetrate into the brain would selectively block the activity of endocannabinoid receptors in peripheral tissues, and therefore might alleviate metabolic and hormonal problems related to obesity, all the while avoiding the behavioral problems that result from blocking endocannabinoid receptors in the brain.

According to the authors, these results suggest that targeting peripheral CB1R has therapeutic potential for alleviating cardiometabolic risk in obese patients.

A School-Based Intervention for Diabetes Risk Reduction

According to an article published in the New England Journal of Medicine (2010; 363:443-453), a study was performed to examine the effects of a multicomponent, school-based program addressing risk factors for diabetes among children whose race or ethnic group and socioeconomic status placed them at high risk for obesity and type 2 diabetes.

Using a cluster design, the study randomly assigned 42 schools to either a multicomponent school-based intervention (21 schools) or assessment only (control, 21 schools). A total of 4,603 students participated (11.3 years of age; 54.2% Hispanic and 18.0% black; 52.7% girls). At the beginning of 6th grade and the end of 8th grade, students underwent measurements of body-mass index (BMI), waist circumference, and fasting glucose and insulin levels.

Results showed that there was a decrease in the primary outcome – the combined prevalence of overweight and obesity – in both the intervention and control schools. However, the intervention schools had greater reductions in the secondary outcomes of BMI score, percentage of students with waist circumference at or above the 90th percentile, fasting insulin levels (P=0.04 for all comparisons), and prevalence of obesity (P=0.05). Similar findings were observed among students who were at or above the 85th percentile for BMI at baseline. Less than 3% of the students who were screened had an adverse event; the proportions were nearly equivalent in the intervention and control schools.

While the comprehensive school-based program did not result in greater decreases in the combined prevalence of overweight and obesity than those that occurred in control schools, the intervention did result in significantly greater reductions in various indexes of adiposity. These changes may reduce the risk of childhood-onset type 2 diabetes.

Social Relationships and Mortality Risk: A Meta-analytic Review

According to an article published in PLoS Medicine (July 2010), a meta-analytic review was conducted to determine the extent to which social relationships influence risk for mortality, which aspects of social relationships are most highly predictive, and which factors may moderate the risk.

For the study, data were extracted on several participant characteristics, including cause of mortality, initial health status, and pre-existing health conditions, as well as on study characteristics, including length of follow-up and type of assessment of social relationships.

Across 148 studies (308,849 participants), the random effects weighted average effect size was 1.50, indicating a 50% increased likelihood of survival for participants with stronger social relationships. This finding remained consistent across age, gender, initial health status, cause of death, and follow-up period. Significant differences were found across the type of social measurement evaluated (p<0.001). The association was strongest for complex measures of social integration (OR = 1.91) and lowest for binary indicators of residential status (living alone versus with others) (OR = 1.19).

According to the authors, the quality and quantity of an individual’s social relationships is linked not only to mental health but also to both morbidity and mortality.

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FDA Approves Drug for Chronic Drooling in Children

Drooling is normal in infants. But a significant proportion of the developmentally disabled population experiences drooling caused primarily by neuromuscular dysfunction that makes it hard to swallow. Cuvposa reduces drooling by lowering the volume of saliva produced.

The FDA has approved Cuvposa (glycopyrrolate) Oral Solution (Shionogi Pharma Inc. of Osaka, Japan) to treat chronic severe drooling caused by neurologic disorders in children ages 3 years to 16 years. Glycopyrrolate was approved decades ago to treat peptic ulcers and reduce salivation in patients under anesthesia. Until now, glycopyrrolate has been used on an off-label basis to treat drooling in the developmentally disabled population, but in a different dosage form than the approved product. A drug is said to be used off-label when a physician prescribes its use in a different way than described in the FDA-approved drug label.

In 2001, the FDA held an advisory committee meeting to discuss how best to develop products for drooling with ethically and scientifically sound trials in children who have neurological disorders. Utilizing the advice provided, the FDA has been able to move forward in addressing the needs of this population.

The FDA drug approval process provides a review of product-specific information that is critical to ensuring the safety and efficacy of a finished drug product. For instance, the applicant must demonstrate that its manufacturing processes can reliably produce drug products of expected identity, strength, quality, and purity. FDA’s review of the applicant’s labeling ensures that health care professionals and patients have the information necessary to understand a drug product’s risks and its safe and effective use.

When used off label, oral tablets of glycopyrrolate had to be crushed to treat drooling in children with neurological disorders. Cuvposa is a flavored oral solution that is easier to administer and provides the optimal dose for each patient.

In clinical trials of Cuvposa glycopyrrolate oral solution, 78% of the children on the drug reached clinical improvement in drooling compared with 19% of those given an inactive substance (placebo). Common adverse reactions reported with glycopyrrolate are dry mouth, constipation, flushing, and urinary retention.

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