The critical early cellular and molecular events that give rise to a type of esophageal cancer has been identified by scientists. The findings challenge conventional wisdom regarding the origin and development of this deadly cancer and its precursor lesion, Barrett's esophagus, and highlight possible targets for new clinical therapies.

Lacking a good animal model of esophageal adenocarcinoma (EAC), researchers have been hard pressed to explain exactly where and how this cancer arises. What is known is that EAC is usually triggered by gastro-esophageal reflux disease (GERD), in which bile acid and other stomach contents leak backwards from the stomach to the esophagus, the muscular tube that moves food from the mouth to the stomach.

Over time, acid reflux can irritate and inflame the esophagus, leading to Barrett's esophagus, an asymptomatic precancerous condition in which the tissue lining the esophagus is replaced by tissue similar to the lining of the intestine. A small number of people with Barrett's esophagus eventually go on to develop EAC.

Using a new genetically engineered mouse model of esophagitis, the CUMC researchers have clarified critical cellular and molecular changes that occur during the development of Barrett's esophagus and EAC. In human patients, acid reflux often leads to over expression of a molecule called interleukin-1 beta, an important mediator of the inflammatory response. A transgenic mouse was created in which interleukin-1 beta was over expressed in the esophagus.

Over expression of interleukin-1 beta in the mouse esophagus resulted in chronic esophageal inflammation (esophagitis) and expansion of progenitor cells that were sustained by the notch signaling pathway.

Notch is a fundamental signaling system used by neighboring cells to communicate with each other in order to assume their proper developmental role. "When we inhibited notch signaling, that blocked proliferation and survival of the pre-malignant cells, so that's a new possible clinical strategy to use in Barrett's patients at high risk for cancer development," noted Dr. Wang.

For decades, investigators thought that the physiological changes associated with Barrett's esophagus originate in the lower esophagus. "However, our study shows that Barrett's esophagus actually arises in the gastric cardia, a small region between the lower part of the esophagus and the upper, acid-secreting portion of the stomach," said the concerned doctor. "What happens is that the bile acid and inflammatory cytokines activate stem cells at this transition zone, and they begin migrating up toward the esophagus, where they take on this intestinal-like appearance."

The researchers also demonstrated that these changes occur primarily in columnar-like epithelial cells, rather than in goblet cells, as was previously thought.

"All told, the findings present a new model for the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma," said the concerned doctor.

Barrett's esophagus affects about 1 percent of adults in the United States. Men are affected by Barrett's esophagus twice as frequently as women, and Caucasian men are affected more frequently than men of other races. The average age at diagnosis is 50. At present, there is no way to determine which patients with the condition will develop EAC. EAC is increasing in incidence about 7 to 8 percent a year, making it the most rapidly rising solid tumor in the U.S.

Treatment with acid-reducing drugs can lessen symptoms of GERD and lower the chances of developing Barrett's esophagus and EAC. Low-grade EAC is highly treatable with endoscopic radiofrequency ablation, photodynamic therapy, or surgical resection. Patients with severe disease may require open surgery, in which most of the esophagus is removed. The overall five-year survival rate with advanced disease is about 25 percent.

Candy, soda, chips, and other junk food available at schools doesn't cause weight gain among children-at least for middle school students, a new study has suggested.

The study relies on data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998-1999, which follows a nationally representative sample of students from the fall of kindergarten through the spring of eighth grade (the 1998-1999 through 2006-2007 schools years).

"We were really surprised by that result and, in fact, we held back from publishing our study for roughly two years because we kept looking for a connection that just wasn't there," said Jennifer Van Hook, a Professor of Sociology and Demography at Pennsylvania State University and lead author of the study.

Van Hook and her co-author Claire E. Altman, a sociology and demography doctoral student at Pennsylvania State University, used a sub-sample of 19,450 children who attended school in the same county in both fifth and eighth grades (the 2003-2004 and the 2006-2007 school years).

They found that 59.2 per cent of fifth graders and 86.3 per cent of eighth graders in their study attended schools that sold junk food.

But, while there was a significant increase in the percentage of students who attended schools that sold junk food between fifth and eighth grades, there was no rise in the percentage of students who were overweight or obese.

In fact, despite the increased availability of junk food, the percentage of students who were overweight or obese actually decreased from fifth grade to eighth grade, from 39.1 per cent to 35.4 per cent.

"There has been a great deal of focus in the media on how schools make a lot of money from the sale of junk food to students, and on how schools have the ability to help reduce childhood obesity," Van Hook said.

"In that light, we expected to find a definitive connection between the sale of junk food in middle schools and weight gain among children between fifth and eighth grades. But, our study suggests that-when it comes to weight issues-we need to be looking far beyond schools and, more specifically, junk food sales in schools, to make a difference," she said.

According to Van Hook, policies that aim to reduce childhood obesity and prevent unhealthy weight gain need to concentrate more on the home and family environments as well as the broader environments outside of school.

Serious injuries involving pedestrians wearing headphones have more than tripled since 2004, a US study showed.

Researchers from the University of Maryland found that people often were hit by vehicles because their music blocked out horns or sirens alerting them to danger.

In 70 percent of cases, the headphone wearing pedestrians died as a result of the injuries they sustained from being hit by traffic.

The researchers studied the data of 116 accidents involving pedestrians wearing headphones between 2004 and 2011. The number of incidents rose from 16 in 2004 to 47 in 2011.

"Everybody is aware of the risk of cell phones and texting in automobiles, but I see more and more teens distracted with the latest devices and headphones in their ears," lead author Dr. Richard Lichenstein said. "Unfortunately, as we make more and more enticing devices, the risk of injury from distraction and blocking out other sounds increases."

For the first time, India has gone a full year without a new polio case, the World Health Organization announced last week.
The last case, the only one in 2011, was of an 18-month-old girl in West Bengal State whose sudden paralysis was confirmed as polio on Jan. 13. There were 42 known cases in 2010.

Polio eradication officials described a year without new cases as a "game-changer" and a "milestone" because India was for decades one of the biggest centers of the disease.

But the country won't be certified as polio-free until it has gone three years without a new case, and there have been new cases recently in three nearby countries: Pakistan, Afghanistan and China. For every case of paralysis, there are an estimated 200 asymptomatic carriers, any of whom can spread the disease.

There have also been recent cases in several countries in Africa; in 2009, an Indian polio strain turned up in Angola, so the virus could theoretically travel in the opposite direction, to India from Africa.

India, which has spent more than $2 billion fighting polio, must keep vaccinating to suppress any possibility of an imported case's taking hold, and in rare cases the weakened live strain used as a vaccine can mutate back into a form that can paralyze and spread. The country's vaccine drives have tried to reach 175 million children twice a year.

India's health minister described his country as "excited and hopeful" but also "vigilant and alert."

A new study has refuted any link between smoking during pregnancy and autism spectrum disorders (ASD) in children.

Researchers have considered a variety of chemical exposures in the environment during pregnancy and early life as possible contributing factors in the development of autism spectrum disorders.

Many have considered prenatal exposure to tobacco smoke a possible cause due to known associations with behavioral disorders and obstetric complications.

Past studies of maternal smoking and autism have had mixed results.

"We found no evidence that maternal smoking during pregnancy increases the risk of autism spectrum disorders," Dr. Brian Lee, an epidemiologist at Drexel's School of Public Health, who led the research in collaboration with researchers from Sweden's Karolinska Institute and the University of Bristol (Bristol, UK) said.

In the new study, Lee and colleagues analyzed data from Swedish national and regional registries for a set of 3,958 children with autism spectrum disorders, along with a control set of 38,983 children born during the same period who did not receive an ASD diagnosis.

Overall, 19.8 per cent of the ASD cases were exposed to maternal smoking during pregnancy, compared to 18.4 per cent of control cases.

These rates showed an association between maternal smoking and the odds of an autism spectrum disorder, in unadjusted analyses.

The report helps to reassure mothers who smoked during pregnancy that their behavior was not likely responsible for their child's autism,

Lee said, and "crosses off another suspect on the list of possible environmental risk factors for ASD."

However, he cautioned that smoking during pregnancy is still unhealthy for mothers and has other known risks for their children.
The study will appear in a forthcoming issue of the Journal of Autism and Developmental Disorders .