The new study, in the latest issue of the journal Obesity conducted by the University of Sydney's Charles Perkins Centre (CPC), was based on a national nutrition and physical activity survey undertaken by the Australian Bureau of Statistics (ABS), and further backs the 'Protein Leverage Hypothesis'.

First put forward in 2005 by professors Raubenheimer and Stephen Simpson, the Protein Leverage Hypothesis argues that people overeat fats and carbohydrates because of the body's strong appetite for protein, which the body actively favours over everything else. Because so much of modern diets consist of highly processed and refined foods -- which are low in protein -- people are driven to consume more energy-dense foods until they satisfy their protein demand.

Processed foods lack protein and drive craving

"As people consume more junk foods or highly processed and refined foods, they dilute their dietary protein and increase their risk of being overweight and obese, which we know increases the risk of chronic disease," said lead author Dr Amanda Grech, a Postdoctoral Research Fellow at the CPC and the university's School of Life and Environmental Sciences.

"It's increasingly clear that our bodies eat to satisfy a protein target," added Professor David Raubenheimer, the Leonard Ullmann Chair in Nutritional Ecology at the School of Life and Environmental Sciences. "But the problem is that the food in Western diets has increasingly less protein. So, you have to consume more of it to reach your protein target, which effectively elevates your daily energy intake.

"Humans, like many other species, have a stronger appetite for protein than for the main energy-providing nutrients of fats and carbohydrates. That means that if the protein in our diet is diluted with fats and carbohydrates, we will eat more energy to get the protein that our bodies crave."

Protein essential to good health

Proteins are the building blocks of life: every cell in the body contains them, and they are used to repair cells or make new ones; and it's estimated that over a million forms of protein are needed to allow a human body to function. Protein sources include meats, milk, fish, eggs, soy, legumes, beans, and some grains such as wheat germ and quinoa.

The University of Sydney scientists analysed data from a cross-sectional survey of nutrition and physical activity in 9,341 adults, known as the National Nutrition and Physical Activity Survey which was conducted from May 2011 to June 2012, with a mean age of 46.3 years. They found the population's mean energy intake was 8,671 kilojoules (kJ), with the mean percentage of energy from protein being just 18.4 percent, compared with 43.5 percent from carbohydrates and from 30.9 percent from fat, and just 2.2 percent from fibre and 4.3 percent from alcohol.

They then plotted energy intake versus the time of consumption and found that the pattern matched that predicted by the Protein Leverage Hypothesis. Those who consumed lower amounts of protein in their first meal of the day went on to increase their overall food intake in subsequent meals, whereas those who received the recommended amount of protein did not -- and, in fact, declined their food intake throughout the day.

'Protein hunger' found to drive overeating

They also found a statistically significant difference between groups by the third meal of the day: those with a higher proportion of energy from protein at the start of the day had much lower total energy intake for the day. Meanwhile, those who consumed foods low in protein at the start of the day proceeded to increase consumption, indicating they were seeking to compensate with a higher consumption of overall energy. This is despite the fact the first meal was the smallest for both groups, with the least amount of energy and food consumed, whereas the last meal was the largest.

Participants with a lower proportion of protein than recommended at the first meal consumed more discretionary foods -- energy-dense foods high in saturated fats, sugars, salt, or alcohol -- throughout the day, and less of the recommended five food groups (grains; vegetables/legumes; fruit; dairy and meats). Consequently, they had an overall poorer diet at each mealtime, with their percentage of protein energy decreasing even as their discretionary food intake rose -- an effect the scientists call 'protein dilution'.

Effect seen in other studies

Professor Raubenheimer and colleagues have seen this effect before in other studies for more than a decade, including randomised control trials.

"The problem with randomised controlled trials is that it treats diet as a disease, when it's not," said Dr Grech. "Laboratory studies may not be indicative of what people are actually eating and doing at a population level. So this study is important as it builds on work, showing that people do seek out protein. And it confirms that, at a population level, as the proportion of energy from protein increases in the diet, people eat less fats and carbohydrates."

While many factors contribute to excess weight gain -- including eating patterns, physical activity levels, and sleep routines -- the University of Sydney scientists argue the body's powerful demand for protein, and its lack in highly processed and refined foods, is a key driver of energy overconsumption and obesity in the Western world.

Explanation for obesity

"The results support an integrated ecological and mechanistic explanation for obesity, in which low-protein, highly processed foods lead to higher energy intake in response to a nutrient imbalance driven by a dominant appetite for protein," said Professor Raubenheimer. "It supports a central role for protein in the obesity epidemic, with significant implications for global health."

Seeking to understand how protein drives human nutrition has also sought taken Professor Raubenheimer to study the diets of people in some of the most remote places, from the Congo to the Himalayas. "The protein mechanism in appetite is a revolutionary insight," he said. "Obesity, diabetes, cardiovascular disease -- they're all driven by diet, and we have to use what we're learning to bring them under control."

Story Source:Materials provided by University of Sydney. Note: Content may be edited for style and length.

Professor Ben Marsland from the Central Clinical School's Department of Immunology, together with Swiss colleagues at the University Hospital of Lausanne (CHUV), showed that the fermentation of fibre in the gut by bacteria and subsequent production of short-chain fatty acids (SCFAs), in particular butyrate, protected against atopic dermatitis in mice.

The research was published today in Mucosal Immunology.

While it is well established that the gut microbiome shapes the immune system, the influence it has on the skin is less explored.

"Previous work from our group, and others, has focused on the local health benefits of SCFAs in the gut as well as at distal sites such as the lung and cardiovascular system," Professor Marsland said. "We wondered if this might also extend to the skin, which is an area that has not really been investigated.

"People speculate that diet can influence skin health, but there is not a great deal of science behind this."

The researchers fed mice a diet high in fermentable fibre or gave them purified SCFAs. "This treatment was profoundly protective against allergic skin inflammation," Professor Marsland said.

They labelled the butyrate with isotopes and tracked it in the body -- it took only minutes to reach the skin where it enhanced the metabolism of keratinocytes, priming them to mature and produce the key structural components required for a healthy skin barrier.

"The upshot of this was that the skin barrier was fortified against allergens -- we were using house dust mite allergens -- that would normally penetrate the skin barrier, activate the immune system and start an allergic reaction in these models," he said.

"It turns out the immune system was secondary to this skin barrier function."

Actively improving the skin barrier could have protective effects against environmental exposures that cause allergies and perhaps even other skin diseases which are underpinned by a damaged or weak skin barrier. SCFAs could be administered orally or directly on the skin as a cream, bypassing the gut, he said.

"The fact that short-chain fatty acids can be given topically and are well-tolerated opens up possibilities for the development of preventative strategies or disease-modifying interventions -- that represents the most significant translational potential of our research."

One possibility to explore is whether this could help children who are at risk of developing skin allergies that cascade towards food allergies and asthma, the so-called 'Atopic March'.

Professor Marsland and members of his Melbourne-based team conducted the project over five or six years together with scientists at the University Hospital of Lausanne where he previously worked before being recruited to Monash. The lead author was Swiss-based Aurélien Trompette.Story Source:Materials provided by Monash University. Note: Content may be edited for style and length.

At least 20 million people worldwide suffer from tuberculosis, according to World Health Organization (WHO), with 10 million new cases every year and about 1.5 million deaths annually. The disease is caused by mycobacteria, which predominantly affect the lungs, but can also infect any other organ. Tuberculosis is particularly common in low income countries. Here, the WHO recommends that newborns be immunized against it as soon as possible.

First used 100 years ago, the BCG vaccine against the disease contains attenuated pathogens of cattle tuberculosis. "We know that BCG can prevent so-called tuberculous meningitis and miliary tuberculosis in infants with a 75 to 86 percent effectiveness rate. But this is not the case for the most common form of the disease, pulmonary tuberculosis, in all age groups. Here, BCG is only insufficiently effective," explains Kaufmann, Emeritus Director at the Max Planck Institute for Multidisciplinary Sciences in Göttingen and the Max Planck Institute for Infection Biology in Berlin.

Since the 1990s, the infection biologist and his team have been working on an improved next-generation vaccine, called VPM1002. To achieve this, the researchers genetically modified the attenuated BCG vaccine strain so that immune cells can better recognize the pathogens. "We developed VPM1002 in no small part to combine increased safety with improved efficacy for immunocompromised children," the Max Planck researcher reports.

Vaccine candidate VPM1002 is safe

The group of immunocompromised children includes, for example, HIV-exposed infants born to HIV-positive mothers. In a clinical trial in South Africa, an international research consortium including Kaufmann has now compared VPM1002 with BCG in HIV-exposed and non-HIV-exposed newborns. The study examined both the safety and the immune response induced -- called immunogenicity -- associated with the formation of immune cells and immunostimulatory proteins. The conclusion of the study: VPM1002 is safe in both HIV-exposed and non-HIV-exposed newborns, has fewer side effects than BCG, and elicits a similar immune response.

In the randomized phase II double-blind study in South Africa, 416 eligible newborns were randomly selected and vaccinated before day 12 of life. 312 of them received VPM1002, and 104 received the BCG vaccine. As the study showed, VPM1002 triggered fewer vaccine-related adverse reactions than BCG. This was true for reactions occurring at the injection site, such as scarring and abscess formation, as well as enlargement of lymph nodes. This finding is important because local and regional reactions after vaccination are among the limitations of the BCG vaccine, Kaufmann points out.

Newborns with or without HIV exposure showed similar immunogenicity with both vaccines. However, starting at six weeks of age, the BCG-triggered immune response was greater than in even younger infants.

Phase III study investigates protection

"Studies such as those described here examine a vaccine's immunogenicity, but not its protection. For the latter, we have already developed a larger phase III clinical trial and have successfully enrolled mothers with their newborns to participate. Now the clock is ticking," Kaufmann said. The infectious biologist expects initial results showing whether VPM1002 can provide comparable or better protection than existing BCG vaccines in about three years. In addition, the VPM1002 vaccine is currently evaluated in adults in two other phase III clinical trials in India for protection against tuberculosis. These trials are expected to be completed in 2023 and 2024, respectively.

The Max Planck Society licensed the VPM1002 vaccine to the company Vakzine Projekt Management (VPM) in 2004. Starting in 2012, the company continued to develop the vaccine in collaboration with the Serum Institute of India, one of the world's largest vaccine manufacturers. "Serum Institute of India is giving access to a unique solution for tuberculosis elimination by detect-treat-prevent strategy. VPM1002 is a unique component of this strategy, and it will help in preventing infection and disease. The ongoing phase III trial is one of the key trials in order to strengthen our scientific rationale. Pleased to see that we have completed recruitment of all infants in such an important trial," said Umesh Shaligram, Executive Director R&D of Serum Institute of India.

Story Source:Materials provided by Max-Planck-Gesellschaft. Note: Content may be edited for style and length.

Led by University of Melbourne researchers, Mr Jiacheng Liu and Dr Dinh Bui, the study also shows that children's risk of asthma is even higher if their father was exposed to second-hand smoke and went on to become a smoker.

The researchers say their findings highlight how smoking can damage health not only for smokers and their children, but also their grandchildren.

The study was based on data from the Tasmanian Longitudinal Health Study (TAHS), led by University of Melbourne Professor Shyamali Dharmage.

TAHS began in 1968 and is one of the world's largest and longest ongoing respiratory studies.

For this study, researchers looked at 1689 children who grew up in Tasmania, their fathers and their paternal grandparents.

They compared data on whether the children had developed asthma by the age of seven years with data on whether the fathers grew up with parents who smoked when they were under the age of 15. They also included data on whether the fathers were current or former smokers.

Mr Liu said: "We found that the risk of non-allergic asthma in children increases by 59 per cent if their fathers were exposed to second-hand smoke in childhood, compared to children whose fathers were not exposed.

"The risk was even higher, at 72 per cent, if the fathers were exposed to second-hand smoke and went on to smoke themselves."

Dr Bui said the findings show how the damage caused by smoking can have an impact not only on smokers, but also their children and grandchildren.

"For men who were exposed to second-hand smoke as children, our study suggests that they can still lower the risk they pass on to their own children, if they avoid smoking," Dr Bui said.

Although researchers can't be certain of how this damage is passed on through generations, Professor Dharmage said they think it may be to do with epigenetic changes.

"This is where factors in our environment, such as tobacco smoke, interact with our genes to modify their expression. These changes can be inherited but may be partially reversible for each generation," he said.

"It's possible that tobacco smoke is creating epigenetic changes in the cells that will go on to produce sperm when boys grow up. These changes can then be passed on to their children."

The researchers will now investigate if the increased risk of asthma persists into adult life and whether fathers who were exposed to second-hand smoke as children pass on any increase in allergies or other lung diseases to their children.

Story Source:Materials provided by University of Melbourne. Note: Content may be edited for style and length.

Now, new research from the University of South Australia gives strong evidence that vitamin D deficiency is associated with premature death, prompting calls for people to follow healthy vitamin D level guidelines.

Published in Annals of Internal Medicine, the study found that the more severe the vitamin D deficiency, the greater the risk of mortality.

Vitamin D is an important nutrient that helps maintain good health and keep our bones and muscles strong and healthy.

First author and UniSA PhD candidate, Josh Sutherland, says while vitamin D has been connected with mortality, it has been challenging to establish causal effects.

"While severe vitamin D deficiency is rarer in Australia than elsewhere in the world, it can still affect those who have health vulnerabilities, the elderly, and those who do not acquire enough vitamin D from healthy sun exposure and dietary sources," Sutherland says.

"Our study provides strong evidence for the connection between low levels of vitamin D and mortality, and this is the first study of its kind to also include respiratory disease related mortality as an outcome.

"We used a new genetic method to explore and affirm the non-linear relationships that we've seen in observational settings, and through this we've been able give strong evidence for the connection between low vitamin D status and premature death.

"Vitamin D deficiency has been connected with mortality, but as clinical trials have often failed to recruit people with low vitamin D levels -- or have been prohibited from including vitamin deficient participants -- it's been challenging to establish causal relationships."

The Mendelian randomization study evaluated 307,601 records from the UK Biobank. Low levels of vitamin D were noted as less than <25 nmol/L with the average concentration found to be 45.2 nmol/L. Over a 14-year follow up period, researchers found that the risk for death significantly decreased with increased vitamin D concentrations, with the strongest effects seen among those with severe deficiencies.

Senior investigator and Director of UniSA's Australian Centre for Precision Health, Professor Elina Hyppönen, says more research is now needed to establish effective public health strategies that can help achieve national guidelines and reduce the risk of premature death associated with low vitamin D levels.

"The take-home message here is simple -- the key is in the prevention. It is not good enough to think about vitamin D deficiency when already facing life-challenging situations, when early action could make all the difference," Prof Hyppönen says.

"It is very important to continue public health efforts to ensure the vulnerable and elderly maintain sufficient vitamin D levels throughout the year."

A 16-week course of dupilumab, a medication that targets a key immune pathway in allergies, resulted in more than half the children having at least a 75% reduction in signs of eczema and highly significant reductions in itch with improved sleep.

This is the first large-scale, randomized, placebo-controlled trial of a monoclonal antibody in any skin disease, including eczema, in children as young as 6 months. The study, which included 31 sites in Europe and North America, will be published Sept. 15 in The Lancet.

"Preschoolers who are constantly scratching, awake multiple times a night with their parents, irritable and markedly curtailed in their ability to do what other children their ages can do improved to the extent that they sleep through the night, change their personalities and have a normal life -- as babies and children should," said lead study author Dr. Amy Paller, chair of dermatology at Northwestern University Feinberg School of Medicine and an attending physician at Ann & Robert H. Lurie Children's Hospital of Chicago.

Eczema, also known as atopic dermatitis, is a chronic inflammatory skin disorder characterized by red, dry, often oozing skin and itch that can profoundly affect the lives of affected patients and their families.

An estimated 19% or more of all children under 6 years of age have eczema and 85 to 90% of individuals affected overall with eczema have the onset of disease during the first five years of life.

The children's debilitating itch leads to sleep disturbance, poor neurocognitive development and, on average, a full night of sleep lost per week.

"The ability to take this drug will significantly improve the quality of life for infants and young children who suffer tremendously with this disease," Paller said. "Atopic dermatitis or eczema is so much more than just itchy skin. It is a devastating disease. The quality of life of severe eczema -- not only for the child but also parents -- is equivalent to many life-threatening diseases."

As a result of this study, this medication is now available to infants and preschoolers as young as 6 months of age. It has "an outstanding safety profile" and does not even require any laboratory tests before starting the medication, Paller said.

Although one-half to two-thirds of young children with eczema have mild symptoms, which can be handled with steroid ointment and moisturizers, the other one-third or more have moderate-to-severe disease and require more aggressive management.

"Up to now, all we have had to treat more severe eczema is immune-suppressing medications, such as oral steroids, which we try to avoid in children, because they are associated with so many side effects and thus are not a preferred treatment for a chronic skin disease," Paller said. "The potential long-term impact on the development of the immune system in young children is also of concern with these immunosuppressants."

During the past few years, a new medication has become available called dupilumab, which is the first "biologic" drug to treat eczema in a targeted manner, meaning a narrow attack on just what scientists have found is causing the manifestations of the disease in skin. This medication was found to be effective and safe in studies with adults, then adolescents, then other school-aged children.

"But the group in whom we worry the most about safety -- those under 5 -- had not been tested and were unable to get this medication," Paller said.

The parent or a health care provider gives the child a monthly shot to administer the medication.

"The effect for most of these younger children is dramatic and at least as good as we've seen with the risky immunosuppressant medications," Paller said.

Potential added benefit by treating associated allergies

This medication has also been shown to be effective for treating asthma, gastrointestinal manifestations of allergy and other allergy-mediated problems but is not yet approved for these indications in infants and young children.

In fact, 66% of children in this trial had developed their eczema during the first six months of life and, by the time of initiating the dupilumab, more than 80% had already developed at least one allergic disorder, such as asthma or food allergy.

"By treating more aggressively to calm the immune system activation in these young children with early, severe eczema, we may also reduce the risk of their developing a range of allergic problems, changing their life beyond improving eczema," Paller said. "These associated allergic issues most often begin after the eczema starts."

Children were randomized to receive either a placebo injection or the dupilumab (weight-based dosing) every four weeks for 16 weeks. Only children who were not responding adequately to topical medications were allowed to enroll, and they had to be of a high severity, even with the topical medications.

As a result of the study, Paller said, scientists and physicians can start to better understand the relationships between eczema and a variety of allergic disorders and can consider the possibility of using this medication for other disorders that affect these very young children.

The trial was sponsored by Regeneron Pharmaceuticals, Inc. and Sanofi, who jointly developed dupilumab.

While a remedy for this severe disease has remained elusive, a recent study in the New England Journal of Medicine (Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease/Kanter et. al.), if proven applicable, may be a possible cure.

In an editorial in this week's New England Journal of Medicine, Martin Steinberg, MD, professor of medicine at Boston University School of Medicine, comments on the results of the study which was the first successful gene therapy for sickle cell disease that adds a gene to patient blood stem cells that prevents complications of sickle cell disease. "Gene therapy with autologous stem cells extends the possibility of a cure to all patients without the need for immunosuppression," explains Steinberg who also is hematologist at Boston Medical Center.

While patients in the study no longer had symptoms of sickle cell disease, Steinberg points out that most continued to have a shorter than normal lifespan of their red blood cells which he thinks could be associated with some complications in the longer-term.

Steinberg believes that for patients to accept this difficult and very expensive treatment it must be curative or nearly curative and last a lifetime. "At this point we do not yet know the sustainability of the results but based on this study the prospects seem good," he says.

Steinberg acknowledges that any highly effective gene therapy will not improve the health of most people with sickle cell disease throughout the world. "Most patients with this disease live in Africa and India where access to highly technological health care is limited. What is needed are more drugs that can be taken orally and increase fetal hemoglobin levels. This will have a higher likelihood of benefiting populations suffering the most from this disease."

The researchers, led by Krista Varady, UIC professor of nutrition, followed a group of pre- and post-menopausal obese women for a period of eight weeks on the "warrior diet" method of intermittent fasting.

The warrior diet prescribes a time-restricted feeding window of four hours per day, during which dieters can eat without counting calories before resuming a water fast until the next day.

They measured the differences in hormone levels, obtained by analyzing blood sample data, in groups of dieters who stuck to four- and six-hour feeding windows against a control group that followed no diet restrictions.

Varady and her team found that levels of sex-binding globulin hormone, a protein that carries reproductive hormones throughout the body, was unchanged in the dieters after eight weeks. The same held true for both testosterone and androstenedione, a steroid hormone that the body uses to produce both testosterone and estrogen.

However, dehydroepiandrosterone or DHEA, a hormone that fertility clinics prescribe to improve ovarian function and egg quality, was significantly lower in both pre-menopausal and post-menopausal women at the end of the trial, dropping by about 14%.

While the drop in DHEA levels was the most significant finding of the study, in both pre- and post-menopausal women, DHEA levels remained within the normal range by the end of the eight-week period.

"This suggests that in pre-menopausal women, the minor drop in DHEA levels has to be weighed against the proven fertility benefits of lower body mass," Varady said. "The drop in DHEA levels in post-menopausal women could be concerning because menopause already causes a dramatic drop in estrogen, and DHEA is a primary component of estrogen. However, a survey of the participants reported no negative side effects associated with low estrogen post-menopause, such as sexual dysfunction or skin changes."

As an added benefit, since high DHEA has been linked to breast cancer risk, Varady said a moderate drop in levels might be helpful in reducing that risk for both pre- and post-menopausal women.

The study measured levels of estradiol, estrone and progesterone -- all hormones vital to pregnancy -- as well, but only in post-menopausal women, due to the changing levels of these hormones throughout pre-menopausal women's menstrual cycles. Among post-menopausal women, there was no change in these hormones at the end of eight weeks.

Women in both the four-hour and six-hour dieting groups experienced weight loss of 3% to 4% of their baseline weight throughout the course of the study, compared with the control group, which had almost no weight loss. The dieters also saw a drop in insulin resistance and in biomarkers of oxidative stress.

Perimenopausal women, who are typically in their 40s, were excluded from the study.

Still, Varady said, "I think this is a great first step. We've observed thousands of pre- and post-menopausal women through different alternate-day fasting and time-restricted eating strategies. All it's doing is making people eat less. By shortening that eating window, you're just naturally cutting calories. Much of the negative information on intermittent fasting reported has come from studies on mice or rats. We need more studies to look at the effects of intermittent fasting on humans."