HOUSTON — (May 24, 2009) — Using a specially adapted tool called P[acman], a collaboration of researchers led by Baylor College of Medicine has established a library of clones that cover most of the genome of Drosophila melanogaster (fruit fly) and should speed the pace of genetic research.

In a report in the current online issue of the journal Nature Methods, Dr. Hugo Bellen (http://flypush.imgen.bcm.tmc.edu/lab/), a professor of molecular and human genetics at BCM and a Howard Hughes Medical Institute investigator, and his colleagues describe the new libraries.

P[acman]– developed by Dr. Koen Venken (http://flypush.imgen.bcm.tmc.edu/lab/koenv/index.html) in Bellen’s laboratory– allows scientists to study large chunks of DNA in living flies. The vector – officially P/phiC31 artificial chromosome for manipulation – combines different technologies: a specially designed bacterial artificial chromosome (BAC) that allows maintenance of large pieces of DNA in bacteria, recombineering that allows the manipulation of large pieces of DNA in bacteria, and the ability to insert the genomic DNA into the genome of the fly at a specific site using phiC31-mediated transgenesis.

Venken adapted the P[acman] vector to create genomic libraries, so that a researcher can choose a gene and find the corresponding clones in the library that cover that gene. Their collaborators at Lawrence Berkeley National Laboratory, Drs. Roger Hoskins and Joseph Carlson, played a key role in the design, construction, and annotation of the libraries.

“You can insert a single copy of a gene and rescue a mutation, or do a structure/function analysis of the gene,” Bellen said. “If you don’t know where the gene is expressed, you can tag it, put it back and locate where it is expressed.”

The library is available at http://pacmanfly.org/.

Source: Baylor College of Medicine

As the swine flu continues its global spread, researchers from the Children’s Hospital of Philadelphia, Pennsylvania, have discovered important clues about why influenza is more severe in some people than it is in others. In their research study published online in the Journal of Leukocyte Biology (http://www.jleukbio.org), the scientists show that the influenza virus can actually paralyze the immune systems of otherwise healthy individuals, leading to severe secondary bacterial infections, such as pneumonia. Furthermore, this immunological paralysis can be long-lived, which is important to know when developing treatment strategies to combat the virus.

According to Kathleen Sullivan, M.D., Ph.D., the senior researcher involved in the study and Chief of the Division of Allergy and Immunology at the Children’s Hospital of Philadelphia, “We have a very limited understanding of why some people who get influenza simply have a bad cold and other people become very sick and even die. The results of this study give us a much better sense of the mechanisms underlying bacterial infections arising on top of the viral infection.”

Sullivan and colleagues recruited pediatric patients with severe influenza and examined the level of cytokines, which serve as the first line initiators of immune response, in the blood plasma. Although they found elevated levels of cytokines, they also found a decreased response of toll-like receptors, which activate immune cell responses as a result of invading microbes. This suggests that the diminished response of these receptors may be responsible for the paralysis of the immune system, leading to secondary bacterial infections. The influenza patients were compared with patients with moderate influenza, respiratory syncytial virus, and a control group of healthy individuals. The immune paralysis appeared to be specifically a result of influenza infection and was not seen in patients with respiratory syncytial virus. This process might explain why one quarter of children who die from influenza, die from a bacterial infection occurring on top of the virus.

“Despite major medical advances since the devastating flu outbreak of 1918 and 1919, influenza virus infection remains a very serious threat,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, “and the current swine flu outbreak is a grim reminder of this fact. The work by Dr. Sullivan and colleagues brings us a step closer to understanding exactly what goes wrong in some people who get the flu, so, ultimately, physicians can develop more effective treatment strategies.”

Source: Federation of American Societies for Experimental Biology

A possible flu outbreak in the U.S. and Mexico has health officials across the globe keeping an eye on developments.

It’s the perfect time to remind everyone that the biggest weapon we all have is simply washing our hands as often as possible.

Margaret Chan, the director-general of the World Health Organzation, said on Saturday that the outbreaks have the potential to cause a global pandemic and urged health authorities everywhere to be on alert for cases in their areas.

The situation is worst south of the border, where more then 1,000 have been diagnosed with a new strain of swine flu that is blamed for nearly 70 deaths in Mexico. The new H1N1 flu strain is a mixture of swine, human and avian flu viruses.

In the U.S., so far all the cases have been limited to California and Texas, where one family was under quarantine after a teenager tested positive for swine flu.

What’s of greatest concern is that the flu appears to be a new mutation of the swine flu that killed millions all over the world back in 1918.

The Centers for Disease Control has set up a page on its website that tallies the number of cases so far in the outbreak investigation. Click here to learn more.

It has many people asking, what is swine flu, and how does someone get it?

The CDC also has answers to these questions and more on its website. Some of them are listed below.

What is swine flu?
Swine Influenza is a respiratory disease in pigs caused by type A influenza viruses.

Is this swine flu virus contagious?
CDC has determined that this virus is contagious and is spreading from human to human.

What are the signs and symptoms of swine flu in people?
The symptoms are similar to regular human flu and include fever, cough, sore throat, body aches, headache, chills and fatigue. Some people have reported diarrhea and vomiting associated with swine flu. In the past, severe illness (pneumonia and respiratory failure) and deaths have been reported with swine flu infection in people.

How do you catch swine flu?
Spread of swine flu can occur in two ways:  Through contact with infected pigs or environments contaminated with swine flu viruses.  Through contact with a person with swine flu.

Are there medicines to treat swine flu?
Yes. CDC recommends the use of oseltamivir or zanamivir for the treatment and/or prevention of infection with these swine influenza viruses. Antiviral drugs are prescription medicines (pills, liquid or an inhaler) that fight against the flu by keeping flu viruses from reproducing in your body.

What can I do to protect myself from getting sick?
Since there is no vaccine available right now, common sense steps can best protect your health, such as: Cover your nose and mouth with a tissue when you cough or sneeze, then throw it away, wash your hands with soap and water, especially after you cough or sneeze. (Use of alcohol-based hand cleaners is also effective), try to avoid close contact with sick people. If you get sick with influenza, it is recommended that you stay home from work or school and limit contact with others to keep from infecting them. Avoid touching your eyes, nose or mouth. Germs spread this way.

How many swine flu viruses are there?
Like all influenza viruses, swine flu viruses change constantly. Pigs can be infected by avian influenza and human influenza viruses as well as swine influenza viruses. When influenza viruses from different species infect pigs, the viruses can reassort (i.e. swap genes) and new viruses that are a mix of swine, human and/or avian influenza viruses can emerge. Over the years, different variations of swine flu viruses have emerged. At this time, there are four main influenza type A virus subtypes that have been isolated in pigs: H1N1, H1N2, H3N2, and H3N1. However, most of the recently isolated influenza viruses from pigs have been H1N1 viruses.

Can I get swine influenza from eating or preparing pork?
No. Swine influenza viruses are not food-borne illnesses and are not spread by eating pork products.

A test developed by physician-scientists at Washington University School of Medicine in St. Louis may help assess more quickly the ability of Alzheimer’s drugs to affect one of the possible underlying causes of Alzheimer’s disease in humans, accelerating the development of new treatments.

Scientists used the test to show that an Alzheimer’s drug given to healthy volunteers reduced production of a substance known as amyloid beta (A-beta), a normal byproduct of human metabolism that builds to unhealthy levels forming brain plaques in Alzheimer’s patients. The drug candidate, LY450139, which is also known as semagacestat, is being studied in clinical trials by Eli Lilly and Company.

Ongoing clinical trials are studying the effect that semagacestat may have on cognitive function and biochemical and brain imaging biomarkers in patients with Alzheimer’s disease. Washington University researchers wanted to see whether the new measurement technique, stable isotope-linked kinetics (SILK), could detect the study drug’s impact on A-beta synthesis in healthy volunteers.

“Bringing an Alzheimer’s disease drug into clinical trials from tests in animal models has always been challenging,” says study director Randall Bateman, M.D., a Washington University neurologist who treats patients at Barnes-Jewish Hospital. “We haven’t had a way to quickly and accurately assess a drug’s effects, and that meant there always had to be some degree of educated guesswork when it came to setting the optimal dosage for humans. SILK may help to eliminate much of that guesswork.”

The results appear online in Annals of Neurology on April 10.

Scientists are unsure whether increased A-beta production, reduced clearance or a combination of the two lead to the A-beta buildup in the brain, a process that many believe triggers Alzheimer’s disease. Bateman and his colleagues are currently using SILK to try to answer this question.

Until SILK, there has not been a way to directly measure the production or clearance of A-beta. The efficacy of potential new Alzheimer’s drug candidates has been assessed by monitoring the cognitive functions of patients with the disease for extended periods of time, which require large, lengthy and expensive studies.

In their double-blind study, scientists gave 20 healthy volunteers varying doses of either a study drug or a placebo. At the start of the SILK test, volunteers were connected to an intravenous drip that gave them a slightly altered form of the amino acid leucine, which is a component of A-beta.

Over the course of several hours, cells in the brain picked up the labeled leucine and incorporated it into the new copies made of A-beta and other proteins. The scientists took periodic samples of the subjects’ cerebrospinal fluid to determine how much of the A-beta included altered leucine.

Tracking the rise of the percentage of labeled A-beta over time reveals the A-beta production rate. Scientists then stop the leucine labeling but continue analyzing spinal fluid samples. As the body removed old A-beta and made new A-beta, the percentage of A-beta containing altered leucine dropped, revealing the A-beta clearance rate.

The results suggest a dose-dependent drop in A-beta production, with an 84 percent reduction in A-beta production being measured with the highest study drug dose.

The SILK procedure takes 36 hours, but provides scientists a more detailed assessment of amyloid beta production and clearance levels than they can obtain through conventional methods.

“You could use a spinal tap to look directly at the amount of A-beta present in the cerebrospinal fluid, but we’ve shown that natural processes cause A-beta levels to change dynamically,” says Bateman. “Such changes make it more difficult to assess the effects of a drug in that fashion.”

Source: Washington University in St. Louis

They do not go to parks over the weekend or to the beach in summer. They do not receive gifts under the Christmas tree. They only see the sun behind the bars. Until before 2006 (the year the parliament granted a major pardon which decreased the number of prisoners), children up to three years of age living with their mothers in prison were around one hundred. Italian law states that, in order to avoid the trauma of mother-child separation, mothers sentenced to prison or awaiting trial can bring with them their children in specific nest areas of the jail.

Of course little ones living in such an inconvenient situation still face many problems. For the first time in Italy, physicians of the Institute of Paediatric Clinic of the Catholic University of Rome – Policlinico Agostino Gemelli entered in the Casa di reclusione di Roma Rebibbia, the main prison of Rome, where the majority of these unfortunate children live, to assess their health conditions. The paper has been published on the last issue of the Scandinavian Journal of Public Health.

“When we first began this study”, explains Pietro Ferrara, researcher of the Institute of Paediatric Clinic of the Catholic University of Rome, and one of the authors of the article, “thanks to the collaboration of the managers of the prison, we had access to all the clinical diaries of the children who had lived in the prison within one and a half year, beginning from January 2003 to mid-2005″.

The total number of children amounted to 150. For comparison, researchers also used the data of around 150 children of the same age who had visited the paediatric surgeries of the Gemelli Hospital and those of around a hundred children of immigrant parents living in Italy.

The first data measured was the gestational age, which is the length of the pregnancy. A good 20% of the children who had lived in a jail had had a gestational age lower than 37 weeks (the average length of a pregnancy). As a comparison, 9% of the children of immigrants were born before time, whereas only 5% of the Italian children are premature. Why do we see this difference?

“Of course”, answers Ferrara, “environmental risk factors play an important role. Often women who end up in prison are subjected to infections, have wrong habits, like smoking or the intaking of narcotics, and frequently pregnancy is not properly taken care of”.

Another important factor is the breast-feeding. Around 70% of the mothers of all three groups decide to nurse their babies. This is not surprising: all mothers want to care for their children. But the time of weaning in jail comes earlier. Both Italian mothers and foreign mothers by and large cease breast-feeding after 5 months. In jail, on the other hand, the weaning takes place before. “An early weaning – reminds Ferrara – can predispose to the risk of hypertension and obesity. Early interruption of the contact with mother’s milk can also lead to sensitization towards food antigens, predisposing to allergies, and increasing the risk of intoxication of substances like preservatives or food colouring agents. In newborns, as a matter of fact, the detoxification processes are still not well developed”.

Yet what mostly differentiates the health of children in or outside a prison is certainly the immunization status. “When we realized this, we were really shocked”, tells Ferrara. “In Italian children the rate of vaccinal coverage is about 100%, which means that nearly all of them are correctly vaccinated. Immigrants’ children, who live through greater logistical and cultural hitches, still reach more than 80%. On the other hand, not more than 14% of the children in jail have been correctly vaccinated. Of course, we are talking about few children over all, but let’s not forget that these small ones are taking a very dangerous risk”.

Even so, Pietro Ferrara and his colleagues paediatricians are very optimist. “First of all, because we have verified that today even inside a prison there is a good level of health assistance”, comments Ferrara. “Also, doctors make a very good work of prevention. Mothers explained how to wean, children are correctly vaccinated and the percentage of vaccinated babies has doubled. Of course, there’s room for improvement, but let’s not forget that children remain in a prison for a variable amount of time, and it’s hard to keep track of them once they are out. The idea is to extend to mothers in prison the health care education programs we routinely perform to evaluate with a paediatrician the health of the child, to talk about prevention and to give suggestions to the parents”.

Up to some time ago, this was a taboo topic, insomuch that this is the first time a study like this is performed in Italy. “Many colleagues from other countries have written to us saying that they were happy that finally some data about Italy was made available”, says Ferrara. “We found a situation which of course still could be enhanced. For example, it would be useful to computerize the clinical diaries, so that we could save us from sifting through the pages, or to transform the meetings with the mothers into regular ones. Yet we can state that preventive and therapeutic assistance in jail is of a good level: a level that many of these children would never have had access to. If I did not fear to be misunderstood, I could nearly say that it was good for these children to have spent some time in prison”, concludes the paediatrician.

Source: Catholic University of Rome

Measuring kidney function by assessing two different factors—glomerular filtration rate (GFR) and urinary albumin levels—helps determine which patients with chronic kidney disease (CKD) will develop end-stage renal disease (ESRD), according to a study appearing in the May 2009 issue of the Journal of the American Society Nephrology (JASN). This combination test could help physicians identify patients at high risk of serious kidney trouble and allow them to intervene at an early stage.

While there is a high prevalence of CKD worldwide, relatively few individuals with the disease develop ESRD, expected to affect 785,000 people in the U.S. by 2020 (current annual cost: $32 billion). Physicians and researchers have looked for ways to identify which patients will progress to ESRD in order to target patients most in need of extensive treatment, and help establish clinical guidelines and public health plans for treating patients with CKD.

Stein Hallan, MD, PhD (St. Olav University Hospital, Norway), and his colleagues recently conducted a study to see if combining two tests commonly used to measure kidney function might help predict ESRD. One test measures an individual’s estimated glomerular filtration rate (eGFR—a measure of the volume of fluid filtered by the kidneys), while the other measures the amount of albumin (the predominant protein in the blood) that is excreted in urine. A high urinary albumin level indicates a rapid rate of kidney disease progression, and a low eGFR indicates an advanced stage of disease.

The researchers analyzed data from 65,589 adults who participated in the population-based Nord-Trøndelag Health (HUNT 2) Study and found 124 individuals who developed ESRD after more than 10 years of follow-up. Combining urinary albumin and eGFRs results identified more than 65% of patients who would develop this condition. Other factors such as hypertension, diabetes, smoking, obesity, and cardiovascular disease did not provide any additional information that could be used to predict who would develop ESRD.

“We provide clear evidence… that reduced eGFR should always be complemented by information on urine-albumin to yield optimal prediction of the risk of progression to ESRD,” said Dr. Hallan. He added that combining these measurements might also help reduce the number of patients referred to specialists without losing the ability to detect future ESRD cases.

“Future risk scores and classification systems based on these two variables will be a simple and powerful tool for improving our ability to efficiently handle the large group of patients with CKD,” the authors wrote.

Source: American Society of Nephrology

COLUMBUS, Ohio – New research suggests that a widely used treatment for persistent acid reflux among asthmatics doesn’t actually improve their quality of life. The finding that as many as one-third of those studied showed no improvement makes a strong case arguing that physicians should change how they currently treat these patients.

John Mastronarde, a clinical associate professor of medicine, along with scientists nationally, sought to determine if acid reflux disease, commonly known as gastroesophageal reflux disease, or GERD, worsens asthma symptoms. Mastronarde is also a pulmonologist and critical care specialist at Ohio State’s Medical Center and director of its asthma center.

Also, the researchers wanted to determine if the use of a class of drugs called proton pump inhibitors in poorly-controlled asthmatic patients without GERD symptoms would significantly improve asthma control. Up to 20 percent of asthma patients with reflux do not have heartburn symptoms.

The results appear in tomorrow’s (4/9) issue of the New England Journal of Medicine.

“We found that ’silent’ GERD is likely not the cause of poorly controlled asthma, and treatment with proton pump inhibitors does not improve control or provide any benefit to the patients,” says Mastronarde, who is also lead investigator of the multicenter study.

“This research is especially important because, by determining which patients do not need the additional medication, we are saving them unnecessary costs, potential side effects and the risk of interactions with other drugs,” adds Mastronarde.

Researchers from 20 universities examined 402 adults with asthma for 24 weeks to determine if using a proton pump inhibiting drug would alleviate their asthma symptoms by preventing the release of stomach and intestinal acid.

The study participants were randomized to receive either 40 milligrams of the drug esomeprazole or a placebo, and were monitored to see if asthma symptoms improved. Esomeprazole is a key ingredient in the popular drugs Prilosec and Nexium, among others. Researchers tracked patients’ lung function and measured esophageal acid, collected questionnaire responses related to asthma symptoms and control, and reviewed quality-of- life issues documented in diaries. Reports showed no benefits to participants receiving esomeprazole.

Approximately 20 million Americans have asthma, exhibiting symptoms such as coughing, wheezing, tightness in the chest and shortness of breath. Treatment options involve a combination of quick-relief medicines to expand constricted airways and long-term medications to reduce inflammation or relax muscles. Although asthma can be controlled, the disease is still responsible for between 4,000 and 5,000 deaths in the United States each year.

Symptoms of asthma and GERD often overlap, making it difficult for physicians to distinguish between the two conditions, and about half of asthma patients who have reflux also have no symptoms. Acid reflux causes the airways in the lungs to constrict and asthmatic narrowing of the airways can induce acid reflux.

Source: Ohio State University

Soy aglycons of isoflavone (SAI), a group of soybean constituent chemicals, have been shown to promote health in a rat model of the menopause. The research, described in BioMed Central’s open access journal Nutrition & Metabolism, shows how dietary supplementation with SAI lowers cholesterol, increases the anti-oxidative properties of the liver and prevents degeneration of the vaginal lining.

Robin Chiou led a team of researchers from National Chiayi University, Taiwan, who studied the effects of the dietary supplement on a group of female rats that had undergone ovary removal. He said, “These ovariectomized animals are a good model for study of the menopause as the loss of oestrogen from the ovaries mimics the natural reduction in oestrogen seen in menopausal women. SAI itself has weak oestrogenic properties and we’ve shown here that menopause-related syndromes can be prevented or improved by dietary supplementation with the compounds it contains”.

In comparison to control animals, the authors found that the ovariectomized rats fed a diet enriched with SAI showed increased liver antioxidative activities and improved lipid profiles. Levels of harmful LDL cholesterol were reduced, while beneficial HDL cholesterol was increased. According to Chiou, “It is generally agreed that the higher HDL and the lower LDL concentrations are of benefit in chemoprevention of cardiovascular diseases. Our findings support the indication that soybean consumption may prevent coronary heart disease”.

The authors hope that dietary soy supplementation may provide an alternative to hormone replacement therapy (HRT), which has been linked to the development of uterus and breast cancers.

Source: BioMed Central

Patient-to-patient transmission of hepatitis B virus (HBV) can occur as the result of routine clinical practices incorrectly thought to be risk-free. A review of 33 HBV outbreaks, published in the open access journal BMC Medicine, has shown that the most frequent HBV transmission routes are administration of drugs using multi-vial compounds and capillary blood sampling (e.g. for glucose monitoring) using non-disposable devices.

Simone Lanini led a team of researchers from the Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, Rome, who performed a systematic review of HBV outbreaks published between 1992 and 2007 within the European Union and the United States. Lanini said, “HBV remains an important cause of liver disease in developed countries. Moreover, the virus has long been recognized as one of the most insidious viral agents within healthcare settings, and in fact a number of HBV outbreaks in healthcare are reported yearly in the USA and the European Union”.

The authors included 30 papers in their review, featuring information on 33 HBV outbreaks, involving 471 patients and 16 fatal cases. Sixteen out of the 33 outbreaks were from EU countries; the remaining 17 outbreaks were from the USA. There were no significant differences in the main epidemiological parameters between the two areas. The majority of the outbreaks originated among patients already affected by one or more underlying conditions causing some degree of immunodepression. According to Lanini, “Our review highlights several topical factors. Firstly, we found that dialysis units accounted for the highest number of outbreaks (10 out of 33), and that such outbreaks were the ones with the shortest duration and the fewest number of cases. These data might be explained by the fact that, both in USA and in most of EU countries, dialysis units have widely improved and mandatory protocols for serological surveillance of blood-borne infections. The consciousness of the risk of HBV transmission might also explain the higher frequency of reporting in dialysis units than in other settings. We also found that the highest number of such outbreaks were associated with the use of multi-vials, which is not unexpected”.

The authors conclude, “We have found that several breaches in infection control measures, related to some routine clinical practices thought to be risk-free (e.g. point of care blood glucose monitoring or preparation and administration of common parenteral drugs with multi-vial compounds) could result in patient-to-patient transmission of HBV”.

Source: BioMed Central

As more and more Americans eat meals outside the home, the country also faces an epidemic of obesity. An association between eating out and weight-related diseases has led to demands for nutritional labeling of restaurant foods. A new study in the Journal of Consumer Research examines the potential benefits of such labeling.

“Using only the sense of taste, smell, and sight to accurately estimate the levels of calories, saturated fat, trans fat, and sodium found in a typical restaurant food serving is extremely difficult, if not impossible, for most consumers,” write authors Elizabeth Howlett (University of Arkansas), Scot Burton (Sam M. Walton College of Business), Kenneth Bates (University of San Diego), and Kyle Huggins (James Madison University).

The authors set out to examine how providing calorie and nutrient information on restaurant menus and menu boards influences consumers’ food-related evaluations and choices. They looked at how participants’ prior expectations came into play and whether providing calorie and nutrient information after the consumptive experience changed their subsequent food choices.

The researchers found that providing nutritional information can influence subsequent food consumption, especially when consumers’ expectations are not fulfilled when they examine the information. “When a ‘great taste’ claim was used to describe a restaurant menu item, the provision of calorie information did not affect consumers’ perceptions, presumably because foods that claim great taste are typically expected to be relatively high in calories,” the authors explain. “On the other hand, when a ‘low calorie’ claim was presented but the menu item was higher in calories than expected, the provision of nutritional information increased the perceived likelihood of 1) gaining weight and 2) developing heart disease.”

The study shows that nutritional information can help consumers moderate their eating over time. In one study, participants ate a sandwich that they later found was unexpectedly high in calories. After this discovery, the participants consumed fewer snacks throughout the rest of the day.

Source: University of Chicago Press Journals