Synthon Biopharmaceuticals Reports Positive Early Results With Its Second Generation HER2-Antibody-Drug Conjugate

Best-in-Class potential with improved therapeutic index compared to other armed antibodies

Synthon Biopharmaceuticals, a subsidiary of specialty pharma company Synthon, has reported promising results with its lead program of antibody-drug conjugates (ADCs). In pre-clinical xenograft studies using patient-derived breast cancer and non-small-cell lung cancer material, Synthon has reported complete tumor remission. Toxicity experiments conducted to-date have revealed Best-in-Class potential with a greatly improved therapeutic index compared to other armed antibodies, due to an impressive safety profile. The company has also opened a state-of-the-art GMP facility in Nijmegen for the production of ADCs up to phase III clinical trials and early launches.

ADCs are a new type of targeted therapy that combines a specific anti-cancer antibody or antibody fragment linked to a potent anti-cancer therapeutic. The aim for this class of therapy is to combine better tumor penetration and killing properties with lower side effects for cancer patients. 

Dr. Marco Timmers, chief scientific officer at Synthon Biopharmaceuticals said: "Synthon's first ADC program incorporates the HER2-binding antibody trastuzumab. The primary objective is to develop a broad therapeutic spectrum by targeting tumors that over-express HER2, such as metastatic breast cancer and non-small-cell lung cancer.  As a result of our unique linker-drug technology, this ADC program is delivering on its promise and giving us exciting preclinical results with the opportunity to become a Best-in-Class therapy."

In several xenograft models, including primary human breast cancer and non-small-cell lung cancer xenografts, Synthon's HER2-ADC dosed alone induced complete tumor remission, whereas with the antibody alone there was no effect. Toxicity studies conducted to-date have revealed that clinically effective doses are not likely to show serious side-effects since the difference between effective and toxic doses, the so-called therapeutic index, has been improved with at least one order of magnitude compared to competitor ADC technologies.

Synthon's proprietary ADC linker-drug technology is based on duocarmycin analogs. The differentiating design of Synthon's linker connecting the antibody to the duocarmycin drug, leads to high stability in circulation and also induces efficient release of the cytotoxin in the tumor cell. A key feature of Synthon's duocarmycin technology involves disruption of the DNA of (solid) tumor cells at any phase of the cellular cycle unlike many other ADCs which only attack tumor cells in a mitotic state. Another feature of duocarmycins is that these cytotoxins can also be effective against tumor cells that are multi-drug resistant. 

With the newly opened GMP facility available, Synthon will enter its drug candidate into clinical trials in 2014. Dr. Timmers added: "We strongly believe that advancing this second generation ADC technology will lead to a new class of effective, targeted medicines in oncology. Our GMP plant will also accelerate future patient access to oncology products based on this pioneering technology."

In addition to its ADC directed against HER2, Synthon is currently developing two other ADC programs for multiple indications in oncology. Depending on the indication, projects will be progressed independently until registration or will be co-developed/licensed out at an appropriate (pre-)clinical stage. Synthon also offers its linker-drug technology and manufacturing capabilities to external partners for conjugation to their own proprietary monoclonal antibodies.

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Drinking Age Laws Allowing Lower Drinking Ages Can Have An Impact On Later Drinking Patterns

Lower minimum legal drinking age (MLDA) laws have been associated with short-term effects such as a greater number of traffic fatalities and teen suicides. A new study has investigated the long-term and persistent linkages between permissive MLDA laws and specific drinking behaviors such as average alcohol consumption, frequency of drinking, patterns of binge drinking, and moderate drinking. Findings support an association with problematic drinking behaviors that persist into later adulthood, such as more frequent binge episodes.

Results will be published in the March 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Drinking age laws have been very effective in reducing alcohol related problems," said Andrew D. Plunk, post-doctoral research fellow at Washington University School of Medicine in St. Louis as well as corresponding author for the study. "Many researchers have studied the laws and there is quite a bit of evidence supporting their positive impact, especially for reducing alcohol consumption and traffic fatalities for those under the age of 21."

"Alcohol is the leading substance of abuse among youth in the United States," added Ralph Hingson, director of the Division of Epidemiology and Prevention Research at NIAAA. "Underage persons frequently binge drink, averaging six drinks per occasion five times per month."

Hingson said that persons under 21 who binge frequently are more likely to engage in a variety of behaviors that place themselves and others at risk: driving after drinking, riding with drinking drivers, never wearing safety belts, carrying weapons, having unplanned and unprotected sex, and illicit drug use. "Frequent bingers are also more likely to be injured in physical fights and suicide attempts," he said. "Furthermore, human brain development continues into the third decade of life, raising concern that heavy adolescent alcohol misuse may produce cognitive deficits and impairment in memory and attention. Finally, numerous studies have linked binge drinking to poorer academic performance."

Hingson explained that, in 1984, when less than half the states had a minimum legal drinking age of 21, the U.S. Congress passed legislation to withhold highway construction funds from states that did not raise the legal drinking age to 21. By 1988, it became illegal to sell alcohol to persons under age 21 in all states. "A review of 49 studies published in peer-reviewed scientific journals found that, when the legal drinking age was lowered in many states during the 1970s and early 1980s, there was a 10 percent increase in average alcohol-related traffic crashes in the states that lowered the age, whereas in states that raised the drinking age, there was a 16 percent decline in alcohol-related traffic crashes," he said. "Much less is known about the effects of raising the legal drinking age on persons older than 21."

"Our research is different for a few reasons," said Plunk. "First, most studies have focused on the immediate or short-term impact of MLDA laws on drinking, whether the outcome is drinking behavior or traffic fatalities. Second, while there has been some prior research on the long-term impact of MLDA laws on binge drinking, to my knowledge we are the first to look at the impact on both binge drinking and non-heavy drinking, that is, more moderate drinking that didn't cross the binge threshold. Third, we were specifically interested in looking at how the effects of these laws might have been different based on whether or not an individual attended college, which previous research on the long-term impact of the laws didn't do."

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The Effects Of Binge Drinking On The Liver

Alcoholic liver disease (ALD) is characterized by a fatty liver, hepatitis, fibrosis, and cirrhosis. Binge drinking is on the rise worldwide, and is particularly common in the U.S. A review of studies addressing the effects of binge drinking on the liver underscores the complex interactions among various immune, signaling pathways, epigenetic, and metabolic responses of the liver to binge drinking.

Results will be published in the April 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"The liver is the main metabolic site in the body," said Shivendra D. Shukla, Margaret Proctor Mulligan Professor at the University of Missouri, School of Medicine as well as corresponding author for the study. "It is involved in nutrient and drug metabolism and disposition, and in the production of a myriad of agents needed for the physiological functions of organs such as the heart, kidney, blood vessels, and brain. ALD-affected liver chemicals can also influence immunity, cardiovascular health, and coagulation. Thus, ALD can have a 'domino effect' on many organs."

"The liver is also the major organ for alcohol metabolism, and as such, is the first line of defense against excessive alcohol consumption," added Samir Zakhari, senior vice president in the Office of Science at Distilled Spirits Council of the United States. "The effects of binge drinking on the liver depend on whether binge drinking is superimposed on chronic heavy drinking, or is done on an empty stomach especially after a period of fasting or starvation."

"Binge abuse is on the rise globally," said Shukla. "For example, about 43 percent of college students have reported at least one binge episode during the previous months. It is therefore necessary to fully understand its consequences at molecular levels. This is the first review that highlights the molecular pharmacology of binge drinking and how this may offer insight into binge-induced injury and its wider implications."

Some of the review's key themes are:

• Binge consumption of alcohol is implicated in the pathophysiology of ALD. New studies from both experimental animals and humans indicate that binge drinking has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute levels of alcohol.
• "Chronic alcohol consumption renders the liver highly susceptible to binge-induced liver damage," said Shukla. "Binge-induced liver injury impacts other organs as well, a view rather poorly appreciated by the public."
• Binge drinking alters the levels of several cellular components and dramatically amplifies liver injury in the chronically alcohol-exposed liver.

"This review, the first of its kind, emphasizes the importance of molecular and epigenetic mechanisms in binge-induced liver injury," said Shukla. "This review also sets the stage for additional investigations in this field. The cross-organ implications of binge-induced liver damage must be explored."

"Binge drinking influences all the mechanisms mentioned above, but can also cause mitochondrial damage, which may result in cell death and disturbances in bioenergetics," added Zakhari. "Therefore, people should not binge drink, especially on an empty stomach, and if they are chronic heavy drinkers, binge drinking will exacerbate liver injury, especially if comorbid conditions such as obesity, Hepatitis C, or HIV infection exist."

The authors stress the importance of additional molecular investigations into the binge effects of alcohol for a better understanding of ALD. They also suggest that future research address the development of therapeutic strategies to control binge drinking.

"Our review highlights the effects of ALD on multiple molecules that in turn have effects on various organs," said Shukla. "We hope this will encourage research and development of newer approaches and tools to control and ameliorate binge-induced health effects."

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Alcohol's Effects On Normal Sleep Reviewed

Sleep is supported by natural cycles of activity in the brain and consists of two basic states: rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Typically, people begin the sleep cycle with NREM sleep followed by a very short period of REM sleep, then continue with more NREM sleep and more REM sleep, this 90 minute cycle continuing through the night. A review of all known scientific studies on the impact of drinking on nocturnal sleep has clarified that alcohol shortens the time it takes to fall asleep, increases deep sleep, and reduces REM sleep.

Results will be published in the April 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"This review has for the first time consolidated all the available literature on the immediate effects of alcohol on the sleep of healthy individuals," said Irshaad Ebrahim, medical director at The London Sleep Centre as well as corresponding author for the study.

"Certainly a mythology seems to have developed around the impact of alcohol on sleep," added Chris Idzikowski, director of the Edinburgh Sleep Centre. "It is a good time to review the research as the mythology seems to be flourishing more rapidly than the research itself. Also, our understanding of sleep has accelerated in the past 30 years, which has meant that some of the initial interpretations need to be revisited."

Some of the review's key themes are:

• At all dosages, alcohol causes a reduction in sleep onset latency, a more consolidated first half sleep, and an increase in sleep disruption in the second half of sleep.
  "This review confirms that the immediate and short-term impact of alcohol is to reduce the time it takes to fall asleep," said Ebrahim. "In addition, the higher the dose, the greater the impact on increasing deep sleep. This effect on the first half of sleep may be partly the reason some people with insomnia use alcohol as a sleep aid. However, the effect of consolidating sleep in the first half of the night is offset by having more disrupted sleep in the second half of the night."
• The majority of studies, across alcohol dose, age, and gender, confirm an increase in slow-wave sleep (SWS) in the first half of the night. SWS, often referred to as deep sleep, consists of stages 3 and 4 of NREM. During SWS, the body repairs and regenerates tissues, builds bone and muscle, and appears to strengthen the immune system. Alcohol's impact on SWS in the first half of the night appears to be more robust than its effect on REM sleep.
  "SWS or deep sleep generally promotes rest and restoration," said Ebrahim. "However, when alcohol increases SWS, this may also increase vulnerability to certain sleep problems such as sleepwalking or sleep apnoea in those who are predisposed."
• Alcohol's effects on REM sleep in the first half of sleep appear to be dose related. Low and moderate doses show no clear effects on REM sleep in the first half of the night, whereas at high doses, REM sleep reduction in the first part of sleep is significant. Total night REM sleep percent is decreased in the majority of studies at moderate and high doses.
  "Dreams generally occur in the REM stage of sleep," said Ebrahim. "During REM sleep the brain is more active, and may be regarded as 'defragmenting the drive.' REM sleep is also important because it can influence memory and serve restorative functions. Conversely, lack of REM sleep can have a detrimental effect on concentration, motor skills, and memory. REM sleep typically accounts for 20 to 25 percent of the sleep period."
• The onset of the first REM sleep period is significantly delayed at all doses and appears to be the most recognizable effect of alcohol on REM sleep, followed by a reduction in total night REM sleep.

"One consequence of a delayed onset of the first REM sleep would be less restful sleep," said Idzikowski. "The first REM episode is often delayed in stressful environments. There is also a linkage with depression."

Ebrahim agreed. "One hypothesis is that alcohol acts like medications that are used for depression and anxiety," he added. "Studies on patients with depression have identified that untreated patients had excessive REM sleep, particularly in the early part of the night, and that antidepressant medication suppressed REM sleep. Alcohol acts like antidepressants, reducing REM sleep particularly in the first part of the night. This impact of alcohol on REM sleep may explain the mood elevation and anxiety reduction associated with alcohol use."

"This review really helps to clarify findings to date as they apply to normal individuals," said Idzikowski. "The high attrition rate from 153 to 20 published studies that were examined enables us to know the real state of play regarding the impact of alcohol on normal volunteers. Whilst some of the studies were rejected on methodological grounds, many were rejected because they were on physically or mentally disordered individuals."

Both Ebrahim and Idzikowski hope this review will help readers understand that short-term alcohol use only gives the impression of improving sleep, and it should not be used as a sleep aid.

"In sum," said Idzikowski, "alcohol on the whole is not useful for improving a whole night's sleep. Sleep may be deeper to start with, but then becomes disrupted. Additionally, that deeper sleep will probably promote snoring and poorer breathing. So, one shouldn't expect better sleep with alcohol."

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Teenagers Avoid Early Alcohol Misuse Through Personality Management

Personality-targeted interventions delivered by trained teachers and school staff decrease alcohol misuse in at-risk teens and delay their classmates' alcohol uptake.

In a study published in the very first issue of the new journal JAMA Psychiatry, researchers from Sainte-Justine University Hospital Center, University of Montreal and King's College London have shown that personality-targeted school interventions delivered to high risk adolescents manage to reduce and postpone problem drinking, which is responsible for 9% of the deaths in young people between the ages of 15 and 29 in developed countries. Furthermore, by delaying alcohol uptake in at-risk youth, low-risk youth apparently gain group immunity due to reduced drinking within their social network.

"Two factors determine problem drinking: personality and peer pressure," explains Dr. Patricia Conrod, the study's first author, who supports the assumption that approaching at-risk youth from the angle of mental health rather than information on the dangers of alcohol is more effective at preventing early-onset alcohol misuse. "Teaching young people how to better manage their personality traits or vulnerabilities helps them make the right decisions in given situations," she explained, "whether it is a matter of overcoming their fears, managing thoughts that make them very emotional, controlling their compulsions, analyzing objectively the intentions of others or improving their self-perception."

The researcher conducted a two-year study called Adventure in which high-school school staff in London, England, were trained to intervene with their ninth grade students (median age of 13.7 years) in order to determine whether their intervention could reduce or postpone the participants' misuse of alcohol in the long term. The development of consumption patterns was measured by observing the drinking rates, problem drinking rates, binge drinking rates, and growth in binge-drinking rates. In addition, the study also attempted to examine a possible group ("herd") immunity effect associated with these interventions.

Participating schools were divided into two groups (control and intervention). The "intervention" school group conducted the intervention at the beginning of the study, whereas the "control" school group benefited from the program and training later on. Out of the total sample, 1,210 students were identified as being more at risk of developing future alcohol dependence after having filled out a personality questionnaire. They presented at least one of the following personality profiles: "anxiety-sensitivity," "hopelessness," "impulsivity" or "sensation-seeking." Trained school facilitators met these students during two brief personalized group sessions and asked them, based on their personality profile, to describe their reactions to various real-life scenarios and try to react to them in a different way.

"The advantage of this approach is that it is easy to implement as opposed to community-based approaches. Teachers can be trained to implement the program and closely adhere to its objectives very effectively, especially since only two interventions are required," explained Dr. Conrod.

A similar study is now under way in 32 high schools in Montreal, Canada. The study is also adding a component that analyses youth styles of thinking. Schools interested in taking part in the program can visit the project's website here.

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Five-Minute' Blood Cancer Injection Cuts Treatment Time By Two Hours

A new injection for blood cancer patients trialled at Southampton's teaching hospitals can deliver a two-hour dose of drugs in around five minutes.

Patients diagnosed with follicular non-Hodgkin lymphoma (NHL), a disease that attacks one specific type of infection-fighting cell, previously had rituximab administered via an intravenous drip.

Around 4,000 people, mainly in their 60s, are diagnosed with the condition in the UK every year and the majority of them will receive the drug, which targets and destroys specific proteins on the surface of cancerous cells, alongside chemotherapy to help eliminate all signs of the lymphoma and induce remission.

At the moment, most sufferers receive both treatments via a drip in a four-hour session once every three weeks. When the six-month course of chemotherapy ends, patients often require a further two years of rituximab given over two hours once every eight weeks.

Results of the multi-centre international study, presented at the annual meeting of the American Society of Hematology in Atlanta, showed that giving the drug by a quick injection under the skin was as safe and effective as the conventional intravenous treatment.

Dr Andrew Davies, a consultant in medical oncology at Southampton General Hospital and study lead, said: "This is a new formulation of a drug we are very familiar with and have been using for many years and the study demonstrates injection is equivalent to the intravenous drip method.

"In the near future, patients will be able to benefit from shorter, more convenient and potentially less complicated hospital visits, which will greatly reduce administration time for NHL patients and ease the capacity burden in busy chemotherapy day units."

Dr Davies, who is also a Cancer Research UK senior lecturer at the University of Southampton, added: "There is a high degree of patient preference and satisfaction with this new formulation of rituximab in Southampton and we hope to see it rolled out nationwide very soon."

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Effect Of Taking Smaller Bites Outweighs Tendency To Eat More When Distracted

Smaller bites reduce food intake even during distracted eating

Eating while distracted generally makes people eat more without being aware of it, but reducing bite sizes may be able to counter this effect, according to new research published January 23 in the open access journal PLOS ONE by Dieuwerke Bolhuis and colleagues from Wageningen University, Netherlands.

Previous studies have shown that taking smaller bites helps people eat less. Other research has also shown that people tend to eat larger meals if eating while distracted. In this new study, the authors assessed whether taking smaller bites or sips of food affected meal size if eaters were distracted during their meal. Participants in the study were given a meal of soup as they watched a 15 minute animation film. Two groups ate in pre-measured volumes of either 'small' or 'large' sips, and the rest were allowed to take sips of whatever size they liked. All participants could eat as much as they wanted, and were later asked to estimate how much they had eaten.

The authors found that people who ate pre-specified 'small' bites of food consumed about 30% less soup for their meal than those in the other two groups. The latter two groups also under-estimated how much they had eaten. Across all three groups, distractions during the meal led to a general increase in food intake, but even when distracted, people who ate pre-specified small sips of soup consumed less food than the others. According to the researchers, their results suggest that reducing sip or bite sizes during a meal may help those trying to lower their food intake, even if they are eating while distracted. 

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Sugar And Calories Cut In Soft Drinks, UK

Leading soft drinks brands Lucozade and Ribena will reduce the amount of sugar and calories in their products by up to 10 per cent as part of the Government's drive to curb obesity levels, Public Health Minister Anna Soubry announced this week.

Speaking at the Food and Drink Federation's 'Delivering Healthy Growth' stakeholder event, the minister unveiled the latest brands to sign up to the Responsibility Deal's calorie reduction pledge. Ribena ready to drink and Lucozade Energy will reduce the amount of sugar and calories by up to 10 per cent; AG Barr, who produce IrnBru, will reduce the calorific content across their portfolio of drinks by five per cent; and J2O will launch two flavours in a new slim-line can which will represent a 10 per cent calorie reduction compared with their standard 275mL bottle.

The Public Health Responsibility Deal aims to tap into the potential for businesses and other influential organisations to make a significant contribution to improving public health by helping us to create this environment.

England has some of the highest obesity rates in the developed world with 60  per cent of adults and one third of 10 and 11 year olds being overweight or obese. The Government's Obesity Call to Action outlined that consuming too many calories is at the heart of the problem and through initiatives like the Responsibility Deal Calorie Reduction pledge concerted action is needed.

Other pledges announced include:

Co-operative Food will look at controlling calories through a variety of measures, including establishing calorie guidelines and target levels in popular product lines; and

Burtons Biscuits Company will offer more portion control packs and will be reviewing its recipes to reduce calories where possible within its portfolio.

Public Health Minister Anna Soubry said:

"Being overweight and not eating well is bad for our health. To reverse the rising tide of obesity we have challenged the nation to reduce our calorie intake by five billion calories a day. On average that's just 100 calories less a day per person.

"Today's announcement will cut the calories and sugar by up to 10 per cent in leading brands like Lucozade and Ribena. Through the Responsibility Deal we are already achieving real progress in helping people reduce the calories and salt in their diet. Overall, more than 480 companies including many leading high street brands have signed up to the Responsibility Deal.

"All of the major supermarkets have now committed to removing artificial trans fats, and over 70 per cent of fast food and takeaway meals sold on the high street have calories clearly labelled, but more needs to be done.

"We are encouraged by the extra businesses which have signed up today but I want to see even more progress.  All in the food industry have a part to play and I now expect companies which are not yet taking action to come forward and make pledges."


Chair of the Responsibility Deal Food Network Dr Susan Jebb said:

"I'm pleased to see the soft drinks manufacturers, like GSK, AG Barr and Britvic join Coca-Cola and PepsiCo to make some very real commitments to help consumers  cut down on their calories as they take control of their weight."

"I hope we will now see others, including the out of home sector, taking a careful look at how they can build on this and come to the table with new commitments to encourage their customers choose smaller portions and swap to lower calorie options."

Director General of the Food and Drink Federation Melanie Leech said:

"We commend these businesses for joining existing pledge signatories in a shared commitment to support the calorie reduction challenge issued to the nation by ministers last year. Of the 31 pledge signatories, 15 are manufacturers, demonstrating our sector's willingness to engage and deliver improved public health outcomes under the Deal.

"On calorie reduction, and the other pledges already issued by the Food Network, we urge the Department of Health to continue its efforts to broaden engagement and bring in new companies to work with those of our members, and others, who have already made substantial commitments through the Responsibility Deal."  

The eight new drink and food manufacturers, supermarket and catering companies which have signed up today include GlaxoSmithKline, Co-Operative Food, Burtons Biscuits, AG Barr, Britvic, Dairy Crest Lexington Catering and CH&Co. They join the 23 companies including Mars and Tesco which have already pledged.

Further highlights from the commitments being made by companies:

GlaxoSmithKline: Targets set (including by end 2013) for the reduction of calorie and sugars content across GSK's drinks Lucozade Energy and Ribena ready to drink.

Co-operative Food: They will look at controlling calories through a variety of measures, including establishing calorie guidelines and target levels in popular product lines.

Burtons Biscuits: They will offer more portion control packs and will be reviewing its recipes to reduce calories where possible within its portfolio.

AG Barr: They will reduce the average calorific content per 100ml of their drinks' portfolio by 5% by 2016.

Britvic: They will develop a formal health and wellbeing strategy and increase their packaging mix to include smaller pack sizes. This year they will launch J2O in a new 250 ml slim-line can.

Dairy Crest: They will develop new products and broaden their range of exisiting products, to include lower calorie options and a range of portion sizes to suit customers. This includes developing cheese and spread products which contain less fat and fewer calories; and introduce single serve varities of products, where the size of the serving is fixed and the calorie content per serving controlled.

Lexington Catering (a small contract catering company)

They will reduce the number of calories by providing new menu choices, portion control, and education information at Point of Sale, on labels and menus, as well as through informative and trained staff.

CH & Co (contract catering company consisting of eight subsidiary companies, turnover £73m)

They will be working with suppliers to source low calorie new products and will reduce portion sizes (i.e. working with existing juice supplier to offer a smaller unit of sale, particularly for smoothies, reducing calorie content by 40%). 

In March 2012 we announced the first signatories to the calorie reduction pledge - in response to the Call to Action on Obesity published in October 2011. The pledge, developed through intensive work with business in the following months, focuses on reducing calories in products as well as encouraging and making it easier for people to make healthier choices.

Companies such as Asda, Coca-Cola GB, Mars, Tesco and Subway have already signed up.

About the Responsibility Deal:

The Public Health Responsibility Deal aims to tap into the potential for businesses and other influential organisations to make a significant contribution to improving public health by helping us to create this environment.

Since launching in 2011, the Responsibility Deal has worked with industry to achieve the following:

• over 70 per cent of the fast food and takeaway meals sold will have calories clearly labelled - almost 9,000 high street outlets by this year - with more companies signing up;
• all of the major supermarkets and 69 per cent of the retail market have committed to removing artificial trans fats - some 97 companies in all;
• over 70 per cent of the retail market and over half of the major high street and contract caterers are committed to further reductions in salt in over 80 categories of foods - such as bread, soups, cereals and pasta sauces;
• over 80 per cent of all alcoholic drinks on shelf will have clear labelling on units, NHS guidelines and pregnancy messages by the end of next year - with 92 companies signed up. [Early indications are that over 60 per cent of labels already carry this information].
• 23 leading food and drink companies, including Coca-cola, Mondelez International (formerly Kraft Foods UK), Nestle, Subway and the major retailers had already signed up to the calorie reduction pledge - making some strong commitments to cut and cap calories, as well as through promotional activity encouraging people to eat healthier foods.  The additional signatories bring the total to 31.
• 34 major alcohol companies have committed to removing a billion units from sale. The initiative, which includes major brands like Echo Falls, First Cape and Heineken will see a greater choice of lower strength alcohol products and smaller measures by 2015.

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HIV Patients May Benefit From Probiotics

Antiretroviral (ARV) drugs are the first line therapy for patients with HIV; however, ARV-treated, HIV-infected individuals still have a higher mortality rate than uninfected individuals. During the course of infection, HIV patients develop inflammation that damages the walls of the intestines, known as the gut mucosa, allowing intestinal microbes to escape and enter the blood stream to cause a life-threatening systemic infection. The health of the gut mucosa is significantly influenced by the complement of bacteria in the gut and there is mounting evidence that probiotic supplements benefit patients intestinal disorders, such as irritable bowel syndrome, C. difficile infection, and inflammatory bowel disease.

In this issue of the Journal of Clinical Investigation, researchers led by Jason Brenchley at the National Institute of Allergy and Infectious Disease, demonstrated that probiotic supplementation may also be beneficial for ARV-treated HIV patients. Brenchley and colleagues treated SIV-infected macaques (a model of human HIV-infection) with either ARV alone or ARV in combination with a mixture of probiotics. Macaques treated with probiotics had enhanced gastrointestinal immune function and decreased inflammation compared to macaques treated with ARV alone. In a companion article, Judith Aberg and colleagues at New York University School of Medicine discuss how these findings could benefit HIV patients.

TITLE: Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques

View this article at: http://www.jci.org/articles/view/66227?key=1cff041937d9040dfed7

ACCOMPANYING THE ATTENDING PHYSICIAN TITLE: Clash of the microbes: let's bring back the good guys

View this article at: http://www.jci.org/articles/view/66736?key=64b158b04e2a168811a3

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Simple Blood Test Reveals DNA Marker That Predicts Breast Cancer Recurrence

Medical researchers at the University of Alberta tested the DNA of more than 300 women in Alberta and discovered a 'genetic marker' method to help accurately profile which women were more apt to have their breast cancer return years later.

Sambasivarao Damaraju, a professor with the Faculty of Medicine & Dentistry, and at the Cross Cancer Institute just published his team's findings in the peer-reviewed journal, PLoS One. Using a simple blood test, Damaraju and his team, which included his PhD student Yadav Sapkota, scanned the entire human genome of 369 women who had been diagnosed with breast cancer. Of those, 155 had their cancer come back and 214 did not.

"If we can accurately predict which women are at high risk of breast cancer recurrence, it gives the physicians and oncologists treating those women time to design a more aggressive therapy in hopes of preventing the cancer from coming back," says Damaraju, who works in the Department of Laboratory Medicine & Pathology. "Treatment strategies could be tailor made for these women based on their genetic make-up and how susceptible it makes them to breast cancer recurrence."

Damaraju and his team focused their research on good prognosis breast cancer - cancer that has a high success rate in terms of initial recovery and treatment. About 70% of all breast cancers fall into this category. Yet despite the high success rate with initial treatment for this type of breast cancer, the overall numbers of those who died or had their cancer spread in this 'good prognosis' group are substantial. The numbers are high simply because so many people have this common 'good prognosis' cancer.

Currently, treatment options for breast cancer patients are based on what doctors know about the tumour itself - its size, grade and the absence or presence of certain markers within the tumour. Damaraju noted there are patients who are given an excellent prognosis based on what doctors see within the tumour, yet the cancer comes back. And other women remain cancer free even though their doctors said they had a poor prognosis based on information gleaned from the tumour. Damaraju thinks the accuracy of prognosis could be improved by complementing tumor based markers with the DNA marker that can be found through a simple blood test.

Damaraju and his team are continuing their research in this area and would like to reconfirm their findings in a larger study, pending further funding. The results from that study could be published in about three years, and he suspects about two years after that, the DNA predictor test could be tested in prospective clinical studies prior to making them widely available for women.

The research was funded by the Canadian Breast Cancer Foundation - Prairies/NWT region, and the Alberta Cancer Foundation.

"The impact of Dr. Damaraju's significant discovery on personalized treatment for breast cancer patients is substantial," says Canadian Breast Cancer Foundation - Prairies/NWT Region CEO Trish Bronsch. "Knowing individual risks of breast cancer and reccurrence provides doctors and oncologists with a better picture in which they can create a treatment plan to fit personal needs. We are very excited to have been able to help fund Dr. Damaraju and his team to this discovery."

"We are pleased to see donor dollars having a direct impact on outcomes that are important to Albertans--in this case earlier detection and improved treatment options for breast cancer recurrence," says Myka Osinchuk, CEO of the Alberta Cancer Foundation. "We are excited to follow Dr. Damaraju and his team to ensure those women successfully treated for breast cancer continue to live cancer-free lives.

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Body Language Conveys Intense Emotions Better Than The Face

Be it triumph or crushing defeat, exhilaration or agony, body language more accurately conveys intense emotions, according to recent research that challenges the predominance of facial expressions as an indicator of how a person feels.

Princeton University researchers report in the journal Science that facial expressions can be ambiguous and subjective when viewed independently. The researchers asked study participants to determine from photographs if people were experiencing feelings such as loss, victory or pain from facial expressions or body language alone, or from both. In some cases, a facial expression associated with one emotion was paired with a body experiencing the opposite emotion.

In four separate experiments, participants more accurately guessed the pictured emotion based on body language - alone or combined with facial expressions - than on facial context alone. Senior researcher and Princeton Professor of Psychology Alexander Todorov said that these results challenge the clinical - and conventional - presumption that the face best communicates feeling. Indeed, despite the findings, a majority of the study's participants sided with the face when asked how they gauge feelings, a misconception the researchers referred to as "illusory facial affect."

"We find that extremely positive and extremely negative emotions are maximally indistinctive," said Todorov, who worked with first author Hillel Aviezer, a psychology professor at Hebrew University of Jerusalem who conducted the work as a postdoctoral researcher under Todorov, and Yaacov Trope, a psychology professor at New York University.

"People can't tell the difference, although they think they can," Todorov said. "Subjectively people think they can tell the difference, but objectively they are totally at [random] chance of determining correctly. The message of this research is that there is a lot of information in body language people aren't necessarily aware of."

The paper in Science counters popular theories holding that facial expressions are universally consistent indicators of emotion. The most prominent, Todorov said, have been developed by psychologist and University of California-San Francisco professor emeritus Paul Ekman, whose work was fictionalized in the television series "Lie to Me."

Instead, facial movements may be "much blurrier" than those theories account for, Todorov said. In particular, he and his colleagues suggest that when emotions reach a certain intensity, the intricacies of facial expressions become lost, similar to "increasing the volume on stereo speakers to the point that it becomes completely distorted," he said.

"There's much more ambiguity in the face than we assume there is," Todorov said. "We assume that the face conveys whatever is in the person's mind, that we can recognize their emotions. But that's not necessarily true. If we remove all the other contextual clues, we might not be so good at picking out emotional cues."

Jamin Halberstadt, a psychology professor at the University of Otago in New Zealand, said that the work demonstrates in a new way that the physical cues of emotion are more varied and dependent on the emotion felt than predominating theories suggest. Halberstadt is familiar with the Princeton research but had no role it.

Based on theories of facial expression, one would intuit that intense emotions would be even easier to interpret from the face than subtle emotions, said Halberstadt, who studies cognitive-emotion interactions. Yet the research by Todorov, Aviezer and Trope demonstrates that facial movements at some point become secondary to the body.

"Before I read this paper, I would have thought that the body only provides contextual clues," Halberstadt said. "This is not saying that bodily context helps interpret an expression of emotion - it is saying that bodily context is the expression of emotion. And the face reveals a general intensity of feeling but doesn't communicate what the person is feeling exactly. The body is where the valid information comes from during intense feelings."

The Princeton research introduces an additional element to interpreting emotions that scientists "have to account for," Halberstadt said. In particular, interrogation and security-screening techniques - such as the U.S. Transportation Security Administration's Screening of Passengers by Observation Techniques (SPOT) program - have been developed based on facial expression research. The work by Todorov and his colleagues, however, suggests that a crucial bodily element may have been overlooked.

"This study really questions the primacy of the face in emotion," Halberstadt said. "Real emotional expressions are much more ambiguous, subtle and malleable than you would think from the research. Any application of emotion theory that relies on or assumes that emotional expressions reside primarily in the face should be under reconsideration from this kind of study."

For their study, the Princeton researchers used stock photos of people at six emotional "peaks": pain, pleasure, victory, defeat, grief and joy. In the first experiment, three groups of 15 people were shown only the facial expression, the body position or the face and body together, respectively. Participants who saw the face only had a 50-50 chance of being correct, whereas those who only saw a body or the face and body together were far more accurate.

Yet, these respondents also exhibited a high degree of illusory facial affect: 53 percent of people who saw the body-and-face photos said they relied on the face. Of a group for whom the pictures were described but not shown, 80 percent said they would rely solely on the face when determining the emotion pictured, while 20 percent they would look to the face and the body together. No one indicated they would judge by body language alone.

In the second experiment, photos were manipulated so that faces from one emotional peak such as victory were spliced onto a body from an opposing peak such as defeat. In those cases, participants more often determined the emotion to be that associated with the body.

For the third experiment, participants rated a variety of faces that fell with in the six emotional categories with ambiguous results. In fact, the authors report, respondents interpreted the positive faces as negative more than they did the negative faces. Those faces were then randomly put upon bodies in a situation of victory or pain, and victory or defeat. Again, study participants typically guessed the situation in accordance with what they gleaned from the body rather than the face.

The final experiment asked participants to mimic the facial expressions in the photos for victory and defeat. Those images were put onto corresponding or opposing body images of victory or defeat. A separate group of people then had to determine the feeling being shown in each image. As in the previous experiments, the body language more often influenced respondents, who labeled a feeling negative when a winning face was on a body of defeat, and vice versa.

If anything, Todorov said, the findings promote a more holistic view of understanding how people physically communicate feelings.

"This research involved very clear cases of positive and negative experiences, and yet people cannot tell them apart from the face," Todorov said.

"There are lots of cues that help us in the social environment, but we often think the face has this special status, that we can tell so much from it," he said. "In reality it tells us much less than we think."

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Emotional Memories Can Be Erased From Our Brains

Emotional memories that are recently formed can be erased from the human brain.

A new study by Thomas Agren, a doctoral candidate at the Department of Psychology, under the observation of Professors Mats Fredrikson and Tomas Furmark, has indicated that it is possible to erase newly formed emotional memories from the brain. This finding, published in Science, brings scientists a huge step forward in future research on memory and fear.

The results coincide previous research which suggested that memories of fear can be substantially modified into benign memories when they are ripe for change, and can be kept that way.

An enduring long-term memory is formed when individuals take in new information by using the process of consolidation, which is based on the formation of proteins. When we recall an event, a place, or anything from our past, the memory becomes unstable for a while. Another consolidation process begins, and the memory is restabilized.

This is because we are not remembering what originally happened, but instead, recalling what we remembered the previous time we thought about what happened, the authors explained.

Memory content can be impacted by interrupting the reconsolidation process that occurs after remembrance.

The participants in the study were shown a neutral picture, while given an electric shock at the same time. This was done so that the picture came to elicit fear, meaning a the subjects formed a fear memory. The picture was then displayed without any shock in order to activate the fear memory.

The reconsolidation process was disrupted in one experimental group by repeatedly showing presentations of the image. A control group was also observed, where the reconsolidation process was finished before the volunteers were shown the same repeated presentations of the picture.

In turn, the experimental group was not able to reconsolidate the fear memory, the fear they had previously connected with the picture dissipated.

The findings suggest that by disrupting the reconsolidation process, the memory was made neutral and no longer associated with fear. The scientists used a MR-scanner, which proved that the traces of that memory was no longer in the part of the brain that usually stores fearful memories, the nuclear group of amygdala in the temporal lobe.

Thomas Ågren concluded:

"These findings may be a breakthrough in research on memory and fear. Ultimately the new findings may lead to improved treatment methods for the millions of people in the world who suffer from anxiety issues like phobias, post-traumatic stress, and panic attacks."

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Genetic Clue Discovered For Why Women Outlive Men

A new study of mitochondrial DNA in fruit flies offers a number of clues that might explain why females tend to outlive males across much of the animal kingdom, including humans.

Researchers from Monash University in Australia and Lancaster University in the UK, write about their work in the 2 August online issue of Current Biology.

They found male fruit flies appear to have mutations in their mitochondrial DNA that affect how fast they age and how long they live.

Scientists use fruit flies as models for studies in genes and aging because their biological processes are remarkably similar to that of other animals, such as humans, and with a lifespan of about a month, it doesn't take too long to investigate generational effects.

Senior author Damian Dowling, a research fellow in the Monash School of Biological Sciences, told the press:

"All animals possess mitochondria, and the tendency for females to outlive males is common to many different species. Our results therefore suggest that the mitochondrial mutations we have uncovered will generally cause faster male aging across the animal kingdom."

"Intriguingly, these same mutations have no effects on patterns of aging in females. They only affect males," he added.

Mitochondria are special subunits of cells, about the same size as bacteria, that provide the energy for life. They combine sugar and oxygen into adenosine triphosphate or ATP, molecular packets of energy that are usable by cells.

Mitochondria have their own DNA that is quite separate from the cellular DNA in the nucleus of the cell.

And, unlike cellular DNA, which is inherited from the sperm and egg that fuse to make the new individual, mitochondrial DNA comes only from the egg.

Thus, as mitochondrial DNA is passed down from generation to generation, the process of natural selection has no opportunity to "screen out" mutations in mitochondrial DNA that might be harmful to males. The researchers refer to this as a "sex-specific selective sieve".

For their study, Dowling and colleagues looked at differences in longevity and biological aging in male and female fruit flies whose mitochondria came from different origins.

They found genetic variations in both male and female mitochondrial DNA, but only the male ones could be linked to life expectancy. There weren't just a few mutations in one place, there were several, spread all over the mitochondrial genome:

"... our results indicate that the mitochondrial mutation loads affecting male aging generally comprise numerous mutations over multiple sites," they write.

The researchers suggest the mutations are entirely due to the way mitochondrial DNA is passed down through the female line.

"If a mitochondrial mutation occurs that harms fathers, but has no effect on mothers, this mutation will slip through the gaze of natural selection, unnoticed. Over thousands of generations, many such mutations have accumulated that harm only males, while leaving females unscathed," Dowling explained.

In an earlier study that looked at the effect of mitochondria being passed down the female line, the team had also discovered a link with male infertility.

Dowling said combining this latest study with their earlier work suggests mitochondria are "hotspots" for mutations that influece male health.

"What we seek to do now is investigate the genetic mechanisms that males might arm themselves with to nullify the effects of these harmful mutations and remain healthy," said Dowling.

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Our Brains Make Men And Women See Things Differently

According to a new study, published in BioMed Central's open access journal Biology of Sex Differences, men and women have different ways of using the visual centers of their brains. Experts suggest that while females are better at distinguishing colors, males are more sensitive to fine detail and rapidly moving stimuli.

There are high concentrations of the male sex hormone (androgen) receptors throughout the cerebral cortex in the brain, particularly in the visual cortex, which is in charge of processing images.

Guys have 25% more neurons in the visual cortex than females because, during embryogenesis, androgens are responsible for controlling the development of those neurons.

The vision of men and women was compared by a team of researchers from Brooklyn and Hunter Colleges of the City University of New York. The experts observed people over the age of 16 from both college and high school, including students and faculty. Both sexes needed to have normal color vision and 20/20 sight (with glasses or contacts was considered fine), in order to participate.

Scientists learned that the color vision of men was shifted, after they asked the volunteers to describe colors shown to them across the visual spectrum. It also became clear that male subjects needed a slightly longer wavelength to experience the same hue as the female subjects.

It was not as easy for men to discriminate between colors as it was for women, meaning that the males had a broader ranger in the center of the spectrum.

In order to measure contrast-sensitivity functions (CSF) of vision, the researchers used an image of light and dark bars that were either horizontal or vertical, asking the participants to decide which one they saw. When the light and dark bars were alternated in each image, the image appeared to flicker.

The investigators found, by varying how quickly the bars alternated or how close together they were, that at moderate rates of image change, volunteers lost sensitivity for bars that were close together, and gained sensitivity when the bars were farther apart.

Both males and females had a harder time resolving the images over all bar widths when the image change was faster. However, men had an easier time resolving more rapidly changing images that were closer together than the women.

Professor Israel Abramov, lead author, explained:

"As with other senses, such as hearing and the olfactory system, there are marked sex differences in vision between men and women. The elements of vision we measured are determined by inputs from specific sets of thalamic neurons into the primary visual cortex.

We suggest that, since these neurons are guided by the cortex during embryogenesis, that testosterone plays a major role, somehow leading to different connectivity between males and females. The evolutionary driving force between these differences is less clear."

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Electronic Cigarettes Harm The Lungs

Electronic cigarettes, seen by many as a healthy alternative to tobacco smoking, do cause damage to the lungs, scientists from the University of Athens, Greece, explained at the European Respiratory Society's Annual Congress 2012, Vienna, on Sunday. Electronic cigarettes, also called e-cigarettes have also been marketed as effective smoking cessation devices.

Professor Christina Gratziou and team set out to determine what the short-term effects of smoking with e-cigarettes might be on different individuals, including those with no known health problems, as well as existing smokers with and without lung conditions.

They carried out experiments on 32 volunteers; of whom 8 were lifetime non-smokers and 24 were current regular smokers. Some of them had healthy lungs, while others lived with asthma or COPD (chronic obstructive pulmonary disease).
br> They were asked to use an electronic cigarette for 10 minutes, inhaling the vapors into their lungs. A spirometry test, as well as some others diagnostic procedures were used to measure their airway resistance. Airway resistance is used in respiratory physiology to measure the resistance of the respiratory tract to airflow coming in during inspiration (inhalation) and going out during expiration (exhalation).

They found that using an e-cigarette caused an instant increase in airway resistance that lasted for 10 minutes in the majority of the participants. Below are some of their findings:

• Non-smokers - even among lifetimes non-smokers, using an e-cigarette for ten minutes raised their airway resistance to 206% from 182% (mean average); the researchers described this as a "significant increase".


• Current regular smokers - among existing regular smokers, the spirometry tests revealed a significant rise in airway resistance to 220%, from 176% after using one e-cigarette for ten minutes.


• COPD and Asthma patients experienced no significant increase in airway resistance from using one e-cigarette for ten minutes.

Professor Christina Gratziou, who is Chair of the European Respiratory Society Tobacco Control Committee, said:

"We do not yet know whether unapproved nicotine delivery products, such as e-cigarettes, are safer than normal cigarettes, despite marketing claims that they are less harmful. This research helps us to understand how these products could be potentially harmful.

"We found an immediate rise in airway resistance in our group of participants, which suggests e-cigarettes can cause immediate harm after smoking the device. More research is needed to understand whether this harm also has lasting effects in the long-term. "The ERS recommends following effective smoking cessation treatment guidelines based on clinical evidence which do not advocate the use of such products."

What are electronic cigarettes (e-cigarettes)?

Electronic cigarettes, also known as vaporizer cigarettes and e-cigarettes, are devices that people use, often instead of tobacco cigarettes, that release doses of water vapor that may or may not include nicotine. E-cigarettes are powered by a small battery.

Manufacturers, distributors and marketers of electronic cigarettes say that they are an effective and healthier alternative to tobacco smoking, because the user does not inhale harmful tobacco smoke, which contains over 4,000 toxic chemicals.

Regular e-cigarette users say that the device offers them a similar sensation to tobacco-cigarette smoking. However, as there is no combustion involved - there is no smoke.

Electronic cigarettes are long tube-like devices that either look like tobacco cigarettes or biros (ballpoint pens). Most of them have replaceable cartridges; some are throwaway ones.

The user places the device between his lips and sucks in, this action activates a heating element that immediately vaporizes a liquid solution. The vapor is inhaled. Learning how to use an e-cigarettes, especially for a regular tobacco-smoker, is straightforward because the action is virtually identical to what is done when you smoke a tobacco cigarette.

A typical electronic cigarette has the following components:

• The mouthpiece - the replaceable cartridge is placed here. The user sucks or inhales from the mouthpiece.


• The atomizer - a heating element which vaporizes the liquid solution. The vapors are inhaled. In most devices, the atomizer needs to be replaced every three to six months.


• The battery - this is usually a rechargeable lithium-ion rechargeable battery. The battery is the power-source for the heating element. There is also some electronic circuitry in the device, such as the airflow sensor, a timed cutoff switch to prevent overheating, and a colored LED (light emitting diode) to indicate the device has been activated.

Electronic cigarettes are becoming increasingly popular, especially in Western Europe. It is estimated that many tens of millions of people worldwide are regular users.

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What Is Inflammation? What Causes Inflammation?

Inflammation is the body's attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens - and begin the healing process.

When something harmful or irritating affects a part of our body, there is a biological response to try to remove it, the signs and symptoms of inflammation, specifically acute inflammation, show that the body is trying to heal itself. Inflammation does not mean infection, even when an infection causes inflammation. Infection is caused by a bacterium, virus or fungus, while inflammation is the body's response to it.

The word inflammation comes from the Latin "inflammo", meaning "I set alight, I ignite".

Inflammation is part of the body's immune response. Initially, it is beneficial when, for example, your knee sustains a blow and tissues need care and protection. However, sometimes inflammation can cause further inflammation; it can become self-perpetuating. More inflammation is created in response to the existing inflammation.

According to Medilexicon's medical dictionary, Inflammation is:

"A fundamental pathologic process consisting of a dynamic complex of histologically apparent cytologic changes, cellular infiltration, and mediator release that occurs in the affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by a physical, chemical, or biologic agent, including the local reactions and resulting morphologic changes; the destruction or removal of the injurious material; and the responses that lead to repair and healing.

The so-called cardinal signs of inflammation are rubor, redness; calor, heat (or warmth); tumor, swelling; and dolor, pain; a fifth sign, functio laesa, inhibited or lost function, is sometimes added. All these signs may be observed in certain instances, but none is necessarily always present."

Plaque in coronary artery disease linked to inflammation - scientists from Stanford University, California, linked 25 new genetic regions to coronary artery disease. They found that people with coronary artery disease, the leading cause of death globally, are most likely predisposed to the disease because they have gene variants linked to inflammation.

Inflammation helps wounds heal

Our immediate reaction to a swelling is to try to bring it down. Bearing in mind that inflammation is an essential part of the body's attempt to heal itself, patients and doctors need to be sure that the treatments to reduce swelling are absolutely necessary and to not undermine or slow down the healing process.

The first stage of inflammation is often called irritation, which then becomes inflammation - the immediate healing process. Inflammation is followed by suppuration (discharging of pus). Then there is the granulation stage, the formation in wounds of tiny, rounded masses of tissue during healing. Inflammation is part of a complex biological response to harmful stimuli. Without inflammation, infections and wounds would never heal.

Neuroscientists at the Lerner Research Institute at the Cleveland Clinic in Ohio found that inflammation actually helps to heal damaged muscle tissue. Their findings clash with how sportspeople with inflammation are treated - health professionals always try to control the inflammation to encourage healing. The researchers say their findings may lead to new therapies for acute muscle injuries caused by freeze damage, medications, chemicals and trauma.

Lan Zhou, M.D., Ph.D., said that patients should be very closely monitored when therapies to combat inflammation are used to make sure that the benefits of inflammation are not completely eliminated.

Inflammation is part of our innate immunity

Our innate immunity is what is naturally present in our bodies when we are born, and not the adaptive immunity we get after an infection or vaccination. Innate immunity is generally non-specific, while adaptive immunity is specific to one pathogen:

Whooping cough vaccine - example of immunity being specific to one pathogen

After being vaccinated for whooping cough (pertussis), we develop immunity to Bordetella pertussis or Bordetella parapertussis, types of bacteria that cause pertussis. This is an example of adaptive immunity - the immunity was not there before receiving the vaccine.

Inflammation is seen as a mechanism of innate immunity.

What is the difference between chronic inflammation and acute inflammation?

Acute inflammation - starts rapidly (rapid onset) and quickly becomes severe. Signs and symptoms are only present for a few days, but in some cases may persist for a few weeks.

Examples of diseases, conditions, and situations which can result in acute inflammation include: acute bronchitis, infected ingrown toenail, sore throat from a cold or flu, a scratch/cut on the skin, exercise (especially intense training), acute appendicitis, acute dermatitis, acute tonsillitis, acute infective meningitis, acute sinusitis, or a blow.

Chronic inflammation - this means long-term inflammation, which can last for several months and even years. It can result from:

• Failure to eliminate whatever was causing an acute inflammation
• An autoimmune response to a self antigen - the immune system attacks healthy tissue, mistaking it (them) for harmful pathogens.
• A chronic irritant of low intensity that persists

Examples of diseases and conditions with chronic inflammation include: asthma, chronic peptic ulcer, tuberculosis, rheumatoid arthritis, chronic periodontitis, ulcerative colitis and Crohn's disease, chronic sinusitis, and chronic active hepatitis (there are many more).

Our infections, wounds and any damage to tissue would never health without inflammation - tissue would become more and more damaged and the body, or any organism, would eventually perish.

However, chronic inflammation can eventually cause several diseases and conditions, including some cancers, rheumatoid arthritis, atherosclerosis, periodontitis, and hay fever. Inflammation needs to be well regulated.

What happens during acute inflammation?

Within a few seconds or minutes after tissue is injured, acute inflammation starts to occur. The damage may be a physical one, or might be caused by an immune response.

Three main processes occur before and during acute inflammation:

• Arterioles, small branches of arteries that lead to capillaries that supply blood to the damaged region dilate, resulting in increased blood flow


• The capillaries become more permeable, so fluid and blood proteins can move into interstitial spaces (spaces between tissues).


• Neutrophils, and possibly some macrophages migrate out of the capillaries and venules (small veins that go from a capillary to a vein) and move into interstitial spaces. A neutrophil is a type of granulocyte (white blood cell), it is filled with tiny sacs which contain enzymes that digest microorganisms. Macrophages are also a type of white blood cells that ingests foreign material.
  
  Klaus Ley, M.D., a scientist at the La Jolla Institute for Allergy & Immunology, reported in a study published in Nature that neutrophils are the human body's first line of defense; they are the main cells that protect us from bacterial infections. Their protective function is a positive one, however, they also have inflammatory properties that may eventually lead to heart disease and several autoimmune diseases, such as lupus. Effectively manipulating neutrophils is vital in disrupting inflammatory diseases.

When our skin is scratched (and the skin is not broken), one may see a pale red line. Soon the area around that scratch goes red, this is because the arterioles have dilated and the capillaries have filled up with blood and become more permeable, allowing fluid and blood proteins to move into the space between tissues.

Edema - the area then swells as further fluid builds up in the interstitial spaces.

The five cardinal signs of acute inflammation - "PRISH"

An ingrown toenail with the five PRISH signs; pain, redness, immobility, swelling and heat



• Pain - the inflamed area is likely to be painful, especially when touched. Chemicals that stimulate nerve endings are released, making the area much more sensitive.
• Redness - this is because the capillaries are filled up with more blood than usual
• Immobility - there may be some loss of function
• Swelling - caused by an accumulation of fluid
• Heat - as with the reason for the redness, more blood in the affected area makes it feel hot to the touch

The five classical signs of inflammation

Although Latin terms are still used widely in Western medicine, local language terms, such as English, are taking over. PRISH is a more modern acronym which refers to the signs of inflammation. The traditional Latin based terms have been around for two thousand years:

• Dolor - Latin term for "pain"
• Calor - Latin term for "heat"
• Rubor - which in Latin means "redness"
• Tumor - a Latin term for "swelling"
• Functio laesa - which in Latin means "injured function", which can also mean loss of function

Dolor, Calor, Rubor, and Tumor were first described and documented by Aulus Cornelius Celsus (ca 25 BC-ca 50), a Roman encyclopaedist. Celcius is famous for creating De Medicina, which is thought to be the only surviving section of a vast encyclopedia. De Medicina was the main source of medical reference in the Roman world for pharmacy, surgery, diet and some other medical fields.

Functio laesa - it is not clear who first described and documented the fifth sign. The majority of attributions have gone to Thomas Sydenham (1624-1689) an English physician and Rudolph Carl Virchow (1821-1902), a German doctor, biologist, politician and pathologist. Virchow is seen as one of the founders of social medicine.

These five acute inflammation signs are only relevant when the affected area is on or very close to the skin. When inflammation occurs deep inside the body, such as an internal organ, only some of the signs may be detectable. Some internal organs may not have sensory nerve endings nearby, so there is be no pain, as is the case with some types of pneumonia (acute inflammation of the lung). If the inflammation from pneumonia pushes against the parietal pleura (inner lining of the surface of the chest wall), then there is pain.

Acute and chronic inflammation compared

The lists below show the difference between chronic and acute inflammation regarding the causative agents, which major cells are involved, features regarding onset, duration, and outcomes:

Acute Inflammation

• Causative agents - harmful bacteria or injury to tissue
• Major cells involved - mainly neutrophils, basophils (in the inflammatory response), and eosinophils (response to parasites and worms), and mononuclear cells (macrophages, monocytes)
• Primary mediators - eicosanoids, vasoactive amines
• Onset (when does the inflammation start) - straight away
• Duration - short-lived, only a few days
• Outcomes - the inflammation either gets better (resolution), develops into an abscess, or becomes a chronic inflammation

Chronic inflammation

• Causative agent - non-degradable pathogens that cause persistent inflammation, infection with some types of viruses, persistent foreign bodies, overactive immune system reactions
• Major cells involved - Macrophages, lymphocytes, plasma cells (these three are mononuclear cells), and fibroblasts
• Primary mediators - reactive oxygen species, hydrolytic enzymes, IFN-γ and other cytokines, growth factors
• Duration - from several months to years
• Outcomes - the destruction of tissue, thickening and scarring of connective tissue (fibrosis), death of cells or tissues (necrosis)

Sleep quality and duration impacts on inflammation risk

Scientists at Emory University School of Medicine in Atlanta, Georgia, found in a study that sleep deprivation or poor sleep quality raise inflammation, which in turn increase the risk of developing heart disease and stroke.

The team gathered data on 525 middle-aged volunteers who had completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire, which asked detailed questions about sleep quality and duration.

They tested the participants' levels of various inflammatory markers, and then tried to see whether they could link them to quality and duration of sleep. The authors concluded:

"The researchers concluded that: "Poor sleep quality, and short sleep durations are associated with higher levels of inflammation."

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Boys Starting Puberty Earlier, Like Girls

Boys in the United States are reaching puberty some 6 months to 2 years earlier than a few decades ago, reflecting the trend in girls, according to a new study by the American Academy of Pediatrics (AAP) published online before print on Saturday. The study authors suggest more research should now be done to find out why this is happening.

Lots of published evidence shows girls are reaching puberty earlier, and this is now generally accepted, but until now, there hasn't been as much research on whether today's boys are also showing a similar tendency.

AAP researchers designed and carried out the study through hundreds of pediatricians all over the US who belong to the AAP Pediatric Research in Office Settings (PROS) network and contribute data for research on children's health.

Data from this same PROS network was used in a large study that in 1997 showed US girls were reaching puberty earlier.

Parents and Doctors Need to Know

The data for this latest study covers more than 4,100 boys, and was recorded by 212 pediatricians carrying out well-child care in 144 practices in 41 states.

American boys appear to be reaching puberty at a younger age, with African-American boys entering puberty earlier than white or Hispanic boys.

Co-author Richard C. Wasserman, director of PROS, says:

"All parents need to know whether their sons are maturing within the contemporary age range, but, until now, this has not been known for US boys."

To assess puberty in boys, pediatricians measured two features: genital and pubic hair, and testicular enlargement, both standard indicators of start of puberty.

The results showed that puberty onset was happening some 6 months to two years earlier than it was several decades ago, according to records from that time.

Ethnic Differences

Overall, African-American boys are more likely to enter puberty earlier than white or Hispanic boys.

Across three ethnic groups, pediatricians recorded the earliest stage of puberty as 10.14 years in non-Hispanic white boys, 9.14 years in non-Hispanic African American boys and 10.4 years in Hispanic boys.

The authors write:

"The causes and public health implications of this apparent shift in US boys to a lower age of onset for the development of secondary sexual characteristics in US boys needs further exploration."

21st Century Standards

In a press statement, lead author Marcia E. Herman-Giddens thanks the doctors and boys who provided much needed data for "this exciting study":

"Contemporary data on the ages of pubertal characteristics in US boys from onset to maturity, lacking until now, are needed by pediatricians, public health scientists, and parents," she explains.

Wasserman says the landmark PROS study that was done in the 1990s provided up to date information on puberty in girls: it was logical there should be a similar one for boys:

"The PROS study provides 21st century standards," says Wasserman.

"Our pediatric endocrinologist colleagues now use the PROS puberty assessment training materials in their own studies and fellowship training," he adds.

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Indoor Laundry Drying Could Be Bad For Your Health

A combination of prolonged wet weather and reducing use of tumble dryers as a way to cut fuel bills, may encourage people to dry more clothes indoors, for instance on drying frames or by draping on radiators. But according to researchers in Scotland, this could pose health risks by increasing moisture that encourages moulds and dust mites, which is bad for people prone to asthma.

Also, while the intention may be to save energy and cost, that is not necessarily the result, say the researchers, from the Mackintosh Environmental Architecture Research Unit (MEARU) at The Glasgow School of Art, working with Strathclyde and Caledonian universities, because in order to dry off the 2 litres that the average load of washing releases into the air, people often turn up the heating.

The three-year research project, titled "Environmental Assessment of Domestic laundering", was funded by the Engineering and Physical Sciences Research Council (EPSRC). A report and press statement were released on 2 November.

Report co-author, Colin Porteous, a professor at MEARU, says:

"Because of increased awareness of the energy consumption of tumble dryers many people are choosing to dry clothes passively within their home."

"This results not only in a severe energy penalty, because of increased heating demand, but also a potential health risk due to higher moisture levels," he adds.

Researchers suggest a strong correlation between drying laundry indoors and increased spore growth, which can exacerbate symptoms for sufferers of asthma, hay fever and other allergies.

The researchers examined the laundry habits of residents in a wide demographic mix living in social housing in the West of Scotland, and also carried out a detailed analysis of air quality and energy consumption.

They concluded indoor drying of laundry poses environmental, economic and health problems, and the tendency in the UK toward building smaller, more airtight homes, only serves to make things worse.

In ill-ventilated rooms, putting clothes on radiators to dry can account for up to a third of the moisture in the air, and creates ideal conditions for mould spores to grow and dust mites to thrive. Both these conditions are known triggers of asthma.

The researchers also point out that indoor drying of clothes that contain fabric conditioner is likely to increase the amount of cancer-causing chemicals in the air.

Indoor laundry drying also leads to increased use of energy, as radiators are often turned up to help the drying process, and/or windows are opened. This just worsens fuel poverty, already a major issue in the West of Scotland, say the researchers.

The team recommends people dry their laundry outdoors whenever possible, or use energy-efficient, condensing tumble dryers. If you have to dry your clothes indoors, then place them by a south facing window (the message is for people in the UK), using natural light and heat. An even better method is to place the clothes on a south-facing balcony, if you have one.

They also suggest, when creating new housing stock, planners and builders should make sure the designs cater for ways of drying laundry that do not contribute to poor air quality. The researchers have published a design guide with suggestions like: upgrading balconies and sunspaces, ensuring new homes have a drying space with its own heating and ventilation, communal laundry and drying facilities, and installing energy-efficient appliances.

The team is now discussing its findings with social housing authorities, with a view to their proposals being adopted as Housing Associations upgrade existing stock and build new homes.

However they argue more sweeping changes are necessary, including updating the Building Regulations so they apply to all new housing. Such a move would have many benefits, says Porteous:

"Our research gives strong justification for the changes both in terms of health and wellbeing, and associated economic impacts. It is our hope that current statutory and advisory standards will be modified to take them on board ensuring a healthy and economically sustainable living environment."

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How Cat Litter Parasite Toxoplasma Gondii Influences The Brain

New research led by a team at the Karolinska Institutet in Sweden reveals for the first time what the common "cat litter parasite" Toxoplasma gondii does once it gets into the brain. The study is important in the light of recent observations linking the parasite to risk-taking and other human behaviours, and associations with mental illness.

The researchers write about their findings in a paper published online on 6 December in the journal PLoS Pathogens.

Toxoplasma Infection

Infection by Toxoplasma gondii or Toxoplasma is called Toxoplasmosis. Estimates suggest between 30 and 50% of the global human population is infected. In Sweden the figure is nearer 20%. In the US, the Centers for Disease Control and Prevention (CDC), puts the number of infected men, women and children at 60 million. Animals can also become infected, especially domestic cats.

People usually contract the parasite by eating poorly cooked meat: according to the CDC, toxoplasmosis is the leading cause of death from foodborne illness in the US. Another way people become infected is by touching cat feces, hence the expression "cat litter parasite" because one way of touching cat feces is handling the cat litter tray.

The vast majority of people infected have few symptoms because their immune system usually stops the parasite from causing illness. In newly infected adults the parasite can cause mild flu-like symptoms, and then it usually enters a chronic dormant phase which was thought to be symptom free.

However, when the parasite enters the brain of fetuses, and people with weak immune systems, it can be fatal. Because of this risk, uninfected pregnant women should not touch cat litter trays.

Links to Mental Illness, Risk-Taking Behavior

There is an emerging view that the toxoplasmosis parasite is active to some extent during what was previously regarded as a purely "dormant phase".

For example, rats infected with the parasite lose their fear of cats, and are even attracted by their scent, making them easy prey. Scientists have suggested this is how the parasite assures its own survival and propagation: the cats eat the infected rats, shed more parasite through their feces, and that in turn helps to infect more rats.

Other studies have found schizophrenia, depression, anxiety, and other mental diseases are more common in people with toxoplasmosis, and there is also evidence to suggest infection by the parasite is linked to more extroverted, aggressive and risk-taking behavior.

In a study published in the July 2012 issue of the Archives of Psychiatry, researchers from Denmark's Statens Serum Institut and the University of Maryland in the US, found that women carrying IgG antibodies to Toxoplasma gondii when giving birth have a higher risk of self-harm or suicide later on.

While such a description sounds alarming, study senior author Antonio Barragan, researcher at the Center for Infectious Medicine at Karolinska Institutet and the Swedish Institute for Communicable Disease Control, says:

"At the same time, it's important to emphasize that humans have lived with this parasite for many millennia, so today's carriers of Toxoplasma need not be particularly worried."

Once in the Brain, Toxoplasma Spurs GABA Secretion

The researchers didn't examine how the toxoplasmosis parasite changes host behavior, they were more interested in what it does in the brain.

They found that it takes over one of the brain's neurotransmitters: the chemical messengers that carry signals between various parts of the brain.

In one test tube experiment, they infected human dendritic cells with the parasite. Dendritic cells form the frontline of the immune system, and play a key role in triggering and adapting immune responses. Once infected, the dendritic cells started secreting GABA, a chemical messenger.

In another experiment with live mice, the researchers tracked infected dendritic cells from their initial point of infection to other parts of the brain where they continued to affect the GABA system.

In their author summary, the researchers note:

"Dendritic cells are considered the gatekeepers of the immune system but can, paradoxically, also mediate dissemination of the parasite."

"This study establishes that GABAergic signaling modulates the migratory properties of dendritic cells and that the intracellular pathogen Toxoplasma gondii sequesters the GABAergic signaling of dendritic cells to assure propagation," they add.

GABA does a number of things, but one of them is to inhibit the sensations of fear and anxiety. People with mental illnesses such as schizophrenia, bipolar diseases, anxiety syndrome and depression show disturbances in GABA systems.

Barragan describes the parasite's ability to make the immune cells secrete GABA as "very clever" and says the finding was "as surprising as it was unexpected".

The researchers call for further studies.

"It would now be worth studying the links that exist between toxoplasmosis, the GABA systems and major public health threats," Barragan suggests.

A grant from the Swedish Research Council helped fund the study.

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Gargling Sugar Water Can Boost Your Self-Control

In order to have better self-control, all you have to do is gargle sugar water.

The finding came from a study at the University of Georgia, led by professor of psychology Leonard Martin and Matthew Sanders, a doctoral candidate also in the UGA Franklin College of Arts and Sciences, and was published in Psychological Science.

Fifty-one students were involved in the study and were asked to perform two assignments so that the team could test self-control.

In the first assignment, the subjects were asked to cross out the Es on a page from a statistics book, which has been known to diminish self-control.

In the second task, they were asked to identify the color of different words, which actually spell out the names of other colors, that were flashed on a monitor. This is called the Stroop test, in which the aim is to turn off a person's inclination to read the word instead of see the color.

The participants were divided into two groups - half rinsed their mouths with lemonade sweetened with sugar while they completed the Stroop test and the other group with Splenda-sweetened lemonade.

According to the results, students who rinsed with sugar responded to the color rather than the word significantly faster than those in the artificial sweetener group.

Martin explained:

"Researchers used to think you had to drink the glucose and get it into your body to give you the energy to (have) self control. After this trial, it seems that glucose stimulates the simple carbohydrate sensors on the tongue. This, in turn, signals the motivational centers of the brain where our self-related goals are represented. These signals tell your body to pay attention."

The Stroop test was completed in about three to five minutes. A measure of self-control was seen in the results, Martin said, but a glucose mouthwash might not be sufficient to fix certain self-control hurdles such as quitting smoking or losing weight.

"The research is not clear yet on the effects of swishing with glucose on long-term self-control," Martin said. "So, if you are trying to quit smoking, a swish of lemonade may not be the total cure, but it certainly could help you in the short run."

The ambition is seen in the form of self-values, or emotive investment, the authors revealed.

"It is the self-investment," Martin said. "It doesn't just crank up your energy, but it cranks up your personal investment in what you are doing. Clicking into the things that are important to you makes those self-related goals salient." According to the scientists, emotive enhancement is what results from the glucose, which causes people to be more aware of their desires and try harder at evoking the non-dominant response.

"The glucose seems to be good at getting you to stop an automatic response such as reading the words in the Stroop task and to substitute the second harder one in its place such as saying the color the word is printed in," he said. "It can enhance emotive investment and self-relevant goals."

Prior research on self-control demonstrated a considerable decrease in performance for the Stroop test. Studies have suggested, Martin said, that this is because the first task is too difficult that you just don't have the energy to complete the second assignment.

Martin continued:

We are saying when people engage in self-control, they ignore important aspects of their goals and feelings. If you have to stay late at work, for example, but you really want to be going home, you have to ignore your desire to go home. Doing so will help you stay late at work, but it may also put you out of touch with what you personally want and feel on later tasks. Swishing glucose can focus you back on those goals and feelings and this, in turn, can help you perform better on the second task. In short, we believe self-control goes away because people send away, not because they don't have energy. People turn it off on purpose."

The study's main goal was to identify the impact of swishing glucose on a psychological level. "We think it makes your self-related goals come to mind," Martin said.

The team is conducting more research to examine how people evoke emotive responses and how they interpret them.

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Promising Saliva Gland Test For Detecting Parkinson's

Testing a part of a person's saliva gland may be a way to diagnose Parkinson's disease, according to new research by the Mayo Clinic that will be presented at the American Academy of Neurology's annual meeting in March.

Parkinson's disease is a difficult disease to diagnose. Currently the only way to pinpoint the disease is to do a clinical exam to analyze a person's symptoms. To achieve a definitive answer, an autopsy is performed on the brain after a person has passed away.

Charles Adler, M.D., Ph.D., and main researcher of the study said:

"We have previously shown in autopsies of Parkinson's patients that the abnormal proteins associated with Parkinson's are consistently found in the submandibular saliva glands, found under the lower jaw. This is the first study demonstrating the value of testing a portion of the saliva gland to diagnose a living person with Parkinson's disease. Making a diagnosis in living patients is a big step forward in our effort to understand and better treat patients."

The study consisted of 15 people with a mean age of 68 who had Parkinson's disease for an average of 12 years. The participants chosen had also responded well to Parkinson's medication and did not have any previous saliva gland issues.

Diagram of the saliva glands.
1) Parotid Gland. 2) Submandibular Gland. 3) Sublingual Gland.

Two different saliva glands were biopsied: the minor saliva glands in the lower lip and the submandibular gland. The extracted tissues were then analyzed for evidence of the irregular Parkinson's protein.

Researchers suggest that one of the most important potential advantages this test could have is creating more accurate clinical trials. Parkinson's clinical trial participants currently do not always have Parkinson's disease, making it harder to test new therapies.

In nine of the eleven patients who had an adequate amount of tissue to examine, the irregular Parkinson's protein was found. The rate of positive outcomes in the biopsies of the lower lip glands seemed much lower than for the lower jaw gland.

Dr. Alder explained:

"This study provides the first direct evidence for the use of submandibular gland biopsies as a diagnostic test for living patients with Parkinson's disease. This finding may be of great use when needing definitive proof of Parkinson's disease, especially when considering performing invasive procedures such as deep brain stimulation surgery or gene therapy."

Parkinson's, A Progressive Disease

Parkinson's disease is an accelerating disease of the nervous system that affects movement. It starts slowly, sometimes with an unnoticeable hand tremor. Tremors are the hallmark symptoms of Parkinson's - the disease also comes with stiffness and slowing of motor skills.

Diagnosis is based on medical history, an assessment of symptoms and signs, a physical and neurological analysis, and eliminating possibilities of other disorders. Close to 30 percent of patients may be misdiagnosed early on in the disease.

Even though Parkinson's cannot be cured, medications can greatly reduce symptoms.

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