Culture

Dieting and weight worries on rise in teens

Significantly higher numbers of Generation Z boys and girls in the UK are dieting to lose weight, and are likely to overestimate their own weight, finds a new UCL-led study.

The research, published in JAMA Pediatrics, found that girls who are trying to lose weight are also more likely to experience depressive symptoms than in previous years.

In 2015, 42% of 14-year-old girls and boys said they currently were trying to lose weight, compared to 30% in 2005.

Lead author Dr Francesca Solmi (UCL Psychiatry) said: "Our findings show how the way we talk about weight, health and appearance can have profound impacts on young people's mental health, and efforts to tackle rising obesity rates may have unintended consequences.

"An increase in dieting among young people is concerning because experimental studies have found that dieting is generally ineffective in the long term at reducing body weight in adolescents, but can instead have greater impacts on mental health. We know, for instance, that dieting is a strong risk factor in the development of eating disorders."

The research team reviewed data from 22,503 adolescents in the UK, in three different decades, who are part of different cohort studies: the British Cohort Study (of people born in 1970; data was collected in 1986), the Children of the 90s study (born 1991-92, data collected in 2005), and Millennium Cohort Study (born 2000-02, data collected in 2015).

The adolescents were all asked questions about whether they were, or had been, trying to lose weight, whether they had dieted or exercised to lose weight, whether they perceived themselves to be underweight, about the right weight or overweight (which was compared to their actual height and weight measurements), and they filled out questionnaires that gauged depressive symptoms.
The researchers found that in 2015, 44% and 60% of all participants had dieted or exercised to lose weight, respectively, compared to 38% and 7% in 1986.

The researchers say other evidence suggests that engagement in vigorous physical activity has remained relatively stable among adolescents over the past few decades.

Senior author Dr Praveetha Patalay (Centre for Longitudinal Studies and MRC Unit for Lifelong Health & Ageing, UCL) said: "It seems that young people are exercising for different reasons than they did before - more adolescents seem to be thinking of exercise predominantly as a means to lose weight rather than exercising for fun, socialising and feeling healthy. We suspect that recent controversial calls to add 'exercise-equivalent' labels on food packaging may exacerbate this."

While girls have consistently been more likely to diet to lose weight, the researchers found a greater increase over the years among boys, who were also becoming more likely to be trying to gain weight.

Dr Patalay said: "Societal pressures for girls to be thin have been around for decades, but body image pressures on boys may be a more recent trend. Our findings underscore the impact that societal pressures and public health messaging around weight can have on children's health behaviours, body image and mental health."

Both girls and boys also became more likely to over-estimate their weight from 1986 to 2005, and even more so by 2015, which the researchers say adds to their concerns that increased efforts to lose weight are not necessarily due to increased obesity rates.

The reported weight-related behaviours and weight misperception were associated with depressive symptoms, and among girls, this relationship was becoming even stronger over the three decades examined in this study. The findings could possibly be part of the explanation for increases in adolescent depressive symptoms that have been observed in recent decades.

Dr Solmi said: "Media portrayals of thinness, the rise of the fitness industry and the advent of social media may all partly explain our results, and public health messaging around calorie restriction and exercise might also be causing unintended harm.

"Public health campaigns around obesity should consider adverse mental health effects, and ensure they avoid weight stigma. By promoting health and wellbeing, as opposed to focusing on 'healthy weight', they could have positive effects on both mental and physical health."

Credit: 
University College London

Researchers discover how to boost vaccine designed to prevent melanoma recurrence

New York, NY (Nov. 16, 2020)--A vaccine created to prevent the recurrence of the deadly skin cancer melanoma is about twice as effective when patients also receive two components that boost the number and effectiveness of immune system cells called dendritic cells, according to phase 2 clinical trial results published in Nature Cancer in November.

These results are important because most cancer vaccine trials have failed to show clinical efficacy. These results show that adding two immune-boosting components can boost the immune response for not only melanoma patients but possibly also others whose cancers express a protein called the vaccine antigen, which is common in some cancers.

Researchers at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, working with colleagues at the National Cancer Institute-funded Cancer Immunotherapy Trials Network (CITN) based at the Fred Hutchinson Cancer Research Center, found that adding the small molecule Flt3L, which increases the number of dendritic cells, boosted the vaccine's effectiveness at producing antibodies and T cells that can later fight melanoma. Adding a second component, called poly-ICLC, also strengthened the dendritic cells' ability to promote antibodies as well as helper and killer T cells.

Sixty patients who had stage 2 or 3 melanoma, and whose cancer was successfully removed via surgery, received the vaccine. Half of the patients received the vaccine alone while the other half received the vaccine with Flt3L and poly-ICLC.

The vaccine is designed to target dendritic cells and is composed of an antigen found in melanoma bound to an antibody to increase the chances of binding with dendritic cells.

The cocktail of the vaccine, Flt3L, and poly-ICLC nearly doubled the vaccine's efficacy, according to analysis of the T cells detected in patients' blood samples after they received four doses over four months. That immune response was seen significantly earlier in the patients who received the cocktail and at much higher levels in many more patients compared to those who received only the vaccine. Researchers found antibodies were still present in blood samples tested 12 weeks after the last dose.

"This is the first randomized clinical trial to show that an immune response to a cancer vaccine can be potentiated by the addition of Flt3L," says Nina Bhardwaj, MD, PhD, Director of the Immunotherapy Program at The Tisch Cancer Institute, and first author and a corresponding author on the study. "The response was achieved because Flt3L mobilized dendritic cells, which are the gold standard in promoting cancer immunity, and improved the overall immunogenicity of the vaccine. This may change the approach of increasing efficacy in other cancer vaccines in the future."

"These positive results are significant not only for improving cancer vaccines, but also potentially for application to other vaccine platforms," reported the study's co-corresponding and senior author Steven Fling, PhD, Director of the CITN Laboratory and Senior Staff Scientist in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center, "and we are extremely grateful and indebted to the patients whose unwavering participation made this demanding clinical protocol a success."

These findings also provide a basis for adding immunotherapies called checkpoint inhibitors, which have been successful in treating metastatic melanoma, to vaccines in order to further increase the success in fending off melanoma recurrence. Researchers also plan to follow trial participants over time and measure how many have cancer recurrence to further study the vaccine's efficacy in each group.

"Immunotherapy has already shown great promise for patients with metastatic melanoma who would normally have a difficult, sometimes grave, prognosis," said Philip Friedlander, MD, PhD, Director of the Melanoma Medical Oncology Program at The Tisch Cancer Institute at Mount Sinai and site investigator of the trial. "It's important to work toward developing effective cancer vaccines that can prevent cancer on their own or in addition to the drugs already available."

Credit: 
The Mount Sinai Hospital / Mount Sinai School of Medicine

Could robots for sex, friendship improve our aging society?

image: Nancy Jecker, Ph.D., is a professor of Bioethics and Humanities at the University of Washington School of Medicine in Seattle.

Image: 
Courtesy of Nancy Jecker

The current U.S. marketplace for sex robots is geared to fulfilling the needs of young, white, able-bodied, heterosexual males - a population perhaps least in need of such assistance - and simultaneously overlooks a vast demographic of potential customers: senior citizens.

A paper published today in the Journal of Medical Ethics calls out the opportunity among socially isolated, lonely people age 65 and over in aging societies, especially America. Many of them would value a robot's companionship and, yes, even its ability to provide sexual gratification, wrote the author, Nancy Jecker. She is a professor of bioethics and humanities at the University of Washington School of Medicine in Seattle.

"We apply ageist attitudes and negative stereotypes to older adults. We assume they're too old to indulge in sex and think that older adults having interest in sex is weird or dirty," Jecker said. "We have similar attitudes toward people with disabilities, where most research has focused on protecting them from able-bodied sexual predators instead of considering their sexual needs and desires as human beings."

For decades Jecker has studied the aging of individuals and populations, as well as justice and other human traits and ideas. Robotics entered the picture, she said, when she recognized the declining ranks of workers to help care-dependent older adults, many of whom are physically disabled.

"Designing and marketing sex robots for older, disabled people would represent a sea change from current practice. The reason to do it is to support human dignity and to take seriously the claims of those whose sexuality is diminished by disability or isolation. Society needs to make reasonable efforts to help them," Jecker said.

Western cultures tend to see sex narrowly as an expression of lust, and assume that people over 65, who suffer more chronic disease and disability, lose desire for physical affection, she said. This is evident in the scads of inventions aimed at seniors, which focus on monitoring health and easing physical burdens while ignoring social and emotional fulfillment.

Sexual function, Jecker's paper argues, is an essential human value - linked to capacities for bodily integrity, affiliation, and emotions. A sexual identity can provide a basis for self-respect, not merely physical satisfaction.

But it's not all about sex, either.

"There's a whole spectrum of human desires. It's limiting to think only of sex bots or only of friend bots. Some older people want a companion that can provide both social interaction and physical affection," Jecker said.

Among people 60 and older in the United States, 43% report feeling lonely - largely a function of social isolation, according to research published in February 2020 by the National Academies of Sciences, Engineering, and Medicine. Published in book form, the paper described how people 50 and older increasingly live alone, in many wealthy, developed societies. It summarized evidence of the detrimental health effects of loneliness and called on healthcare professionals to try to alleviate the situation.

U.S. and other Western roboticists could take a cue from counterparts in Japan, Jecker said. There, Shinto beliefs hold that spirits (kami) embody both animate and inanimate things, allowing more receptiveness to the idea of robot companions.

"They are much more open to the possibility of pet robots and friend robots. They've been at the forefront of not just the technology but the humanities questions of 'How should we design these robots? What sort of social relationships would you want to have with them?' They don't share the Western roboticists' worry that robots are mechanical empty things that we can't relate to."

Jecker challenges robot designers to "think in terms of robots' capability rather than their utility - not focusing only on the sexual pleasure that a robot gives to an older, disabled adult, but focusing on what the robot enables the person to do and be."

Credit: 
University of Washington School of Medicine/UW Medicine

Minorities benefit less from regionalizing heart attack care

California's Black and Hispanic communities may be falling further behind whites in the quality of care they receive for heart attacks, despite recent medical efforts aimed at improving the standards of care for these populations, according to a new study led by researchers at UC San Francisco.

In response to ongoing health disparities, emergency management services nationwide have implemented protocols to better coordinate care and get patients directly to hospitals that are equipped and staffed to quickly unblock coronary arteries and restore blood circulation to the heart.

Under the new guidelines, which were encouraged by the American Heart Association, California now is organized to deliver treatment to severe heart attack patients through 33 regional emergency response systems for the state's 58 counties. However, the study has found that patients living in minority communities received less benefit from these protocols than patients in non-minority communities.

"Regionalization was an attempt to equalize access to the gold standard of care for severe heart attack patients, but our research shows that inequalities have been exacerbated, not alleviated," said Renee Hsia, MD, MSc, professor in the Department of Emergency Medicine at UCSF and lead author of the study, which was published November 16, 2020, in JAMA Network Open.

The standard of care for a heart attack with complete coronary artery blockage is angioplasty, or "percutaneous coronary intervention" (PCI). A long thin tube called a catheter is threaded through an artery leading from the groin toward the heart, guiding instrumentation used to re-open the artery.

Studies have shown that faster reopening of the artery, especially if it occurs within 90 minutes of seeking care for a heart attack, offers better survival odds, but not every hospital is equipped with a cardiac catheterization lab and staffed at all hours with interventional cardiologists and other trained personnel.

Aside from the established link between speed and survival, previous studies of the regionalized system have failed to detect a mortality benefit at the population level, Hsia said. By further breaking down their analysis by minority and non-minority zip codes and using California vital statistics data, Hsia and colleagues found that one group did have greater survival after regionalization -- whites living in non-minority communities. There were no mortality benefits for whites living in minority communities, or for Blacks or Hispanics in either non-minority or minority communities.

With regionalization, access to PCI-capable hospitals improved 6.3 percent for all patients in non-minority communities, but only 4.5 percent for patients in minority communities, the study found. Same-day PCI increased by 5.1 percent for patients in non-minority communities, but only by 1.7 percent for individuals in minority communities; receipt of PCI any time during hospitalization increased by 5.0 percent for patients in non-minority communities, but only by 0.7 percent for those in minority communities.

The JAMA Network Open study compared changes over time in outcomes during the study period beginning in 2006, when only eight California counties were regionalized for heart attack care, to 2015, when all counties were participating. The researchers analyzed data from139,494 patients who suffered the most severe type of heart attack, as determined by a distinctive electrocardiogram signal. Minority communities were defined as the top third of ZIP codes with the highest percentages of Black and Hispanic residents.

Previous studies have shown that advances in heart attack care have improved care between white and minority patients receiving care within a single hospital, according to Hsia. However, the new study findings, focused on communities rather than on individual hospitals, raise the question as to whether Blacks and Hispanics, depending on their neighborhoods, are more likely to be directed to hospitals where patients do not receive optimal care, even with the new guidelines.

"Given that both emergency care in general and PCI specifically are less available in underserved communities, PCI hospitals in minority communities could already be burdened by a high volume of patients as the result of regionalization, and less able to provide guideline-directed care," according to the study.

In addition, other studies have shown that minority populations use ambulances less often due to concerns about costs and insurance, and individuals who are not taken to hospital by ambulance may not benefit from the newer guidelines as much, Hsia said. The study was not designed to measure ambulance use over time.

"Medical advances do not necessarily benefit all groups equally, and the structure of our health care system may affect how benefits accrue," Hsia said.

Credit: 
University of California - San Francisco

National supplies of protein, carbs and fats can predict your lifespan

image: Dr Alistair Senior, University of Sydney

Image: 
University of Sydney

A new global study from the University of Sydney has looked at how macronutrient supplies (proteins, carbohydrates and fats) of different countries are associated with the risk of death at different ages. It is the most extensive analysis to date of corresponding national macronutrient supplies, survival statistics and economic data.

The research led by Dr Alistair Senior, a researcher in the Charles Perkins Centre and Faculty of Science at the University of Sydney, found evidence for undernutrition is prevalent in the global data even as recently as 2016; particularly in terms of protein supplies and that the "optimal" supply changes with age.

"We found that the risk of death in early life is minimised where the supply is relatively high in fats and proteins (around 40 and 16 percent of energy, respectively)," Dr Senior said. "However, in later life reducing the supply of energy from fats and substituting it for carbohydrates has the lowest mortality."

The study is published today in the high-impact Proceedings of the National Academy of Sciences.

"It is a fascinating story, which reflects at the level of national food supplies the fact that macronutrient requirements change with age. It is also likely to be of interest when considering the food security of nations, and how changes in supply might translate to patterns of mortality," Dr Senior said.

Co-author Professor Stephen Simpson, the director of the Charles Perkins Centre and co-author of the recent book Eat Like The Animals added: "The study is fascinating. It was intriguing to see that the pattern of reduced rates of mortality in mid- to later-life with an increase in the ratio of carbohydrate-to-protein in the diet reflected studies in the laboratory on the biology of ageing."

Team member Professor David Raubenheimer, who co-authored Eat Like the Animals with Simpson and is the Nutrition Theme Leader at the Charles Perkins Centre, noted: "While food supply data are not a direct indicator of diets, they provide a good measure of differences in national food environments. It is incredible that we are seeing at that level effects also seen in detailed studies of individual diets. This attests to the power of food environments to influence diets and health, a topic that is a central theme of our new book"

Nutrition is a guiding research theme at the Charles Perkins Centre. This theme unites researchers across disciplines in unexpected collaborations, providing unique insights into nutritional ecology.

Why macronutrients matter

Macronutrients are the primary source of energy in the foods we eat, and are categorised into three major groups: proteins, fats and carbohydrates.

The study found the total calorie supply per person associated with minimal mortality is relatively stable (around 3500kcal/cap/day) with age, but the composition of calorie intake in terms of dietary proteins, fats and carbohydrates is not.

Before the age of 50, 40 to 45 percent of energy from each of fat and carbohydrates and 16 percent from protein minimises mortality. However, for later life lower fat and protein supplies at 22 percent and 11 percent, respectively, and replacing these with carbohydrates is associated with the lowest rate of mortality.

"What was really neat was that we saw a clear shift in the supply that minimised mortality at above age 50, where it looked like a high carbohydrate supply becomes important," said Dr Senior. "I think it's important to note though that this is not a guide to what an individual should be eating - we looked at the supply that a country is providing at a per capita level. This theoretically sets the upper limit to what people are eating, but there are a whole range of factors that translate a country's food supply into what ends up actually being consumed; this is something that we are really interested in looking at going forward."

Method

From a methodological perspective the paper is also interesting. Using global supply data and 1,879 lifetables from 103 countries, the researchers tested energy intake (number of calories) and the balance of macronutrients at a macro-level: between the nutrient supplies of nations and their patterns of age-specific mortality. They found that macronutrient supplies are strong predictors of age-specific mortality even after correction for time and economic factors.

"The same statistical approach that we have applied here can be reapplied to look at patterns of the risk of death and all kinds of dietary aspects including different food types (e.g. plant vs animal proteins), or broader dietary patterns (e.g. 'a Mediterranean diet')," said Dr Senior, who is also affiliated with the School of Life and Environmental Sciences and the School of Mathematics and Statistics.

The study found, globally, under-nutrition is evident, even as recently as 2016. However, in wealthy countries the effects of over-nutrition are prominent, where high supplies particularly from fats and carbohydrates are predicted to lead to high levels of mortality.

Credit: 
University of Sydney

Measles outbreaks likely in wake of COVID-19 pandemic

Major measles outbreaks will likely occur during 2021 as an unexpected consequence of the COVID-19 pandemic, according to a new academic article.

The Lancet article has called for urgent international action to prevent potentially devastating measles epidemics in the coming years.

Lead author Professor Kim Mulholland, from the Murdoch Children's Research Institute and Chair of the World Health Organization's SAGE Working Group on measles and rubella vaccines, said that many children have missed out on measles vaccination this year, making future measles outbreaks inevitable.

Professor Mulholland said while 2020 had been a quiet year for measles, in part due to travel reductions and national COVID-19 control measures, the economic impacts would lead to many cases of childhood malnutrition.

Malnutrition worsens the severity of measles, leading to poorer outcomes and more deaths, especially in low- and middle-income countries.

"Children who die from measles are often malnourished, but acute measles pushes many surviving children into malnutrition," he said. "Malnutrition, along with measles-associated immune suppression, leads to delayed mortality, while co-existing vitamin A deficiency can also lead to measles-associated blindness.

"The coming months are likely to see increasing numbers of unimmunised children who are susceptible to measles. Many live in poor, remote communities where health systems are less resilient, and malnutrition and vitamin A deficiency are already increasing."

Professor Mulholland said the COVID-19 pandemic had also had a profound effect on the control of vaccine preventable diseases, with vaccination campaigns paused in the early months of 2020 and routine immunisation services greatly disrupted in many countries.

The WHO estimates that by the end of October, 2020, delayed vaccination campaigns in 26 countries have led to 94 million children missing scheduled measles vaccine doses.

"All these factors create the environment for severe measles outbreaks in 2021, accompanied by increased death rates and the serious consequences of measles that were common decades ago," Professor Mulholland said.

"This is despite the fact that we have a highly cost effective way to prevent this disease through measles vaccination."

In 2019, before the pandemic started, the world experienced a dramatic return of measles, more than at any time in the past 20 years. WHO data indicates that there were 9.8 million measles cases and 207,000 deaths in 2019, 50 per cent more than in 2016.

Most measles deaths in 2019 have been in Africa, many associated with major outbreaks in Madagascar and the Democratic Republic of the Congo. Measles also re-emerged in South America, especially among Indigenous communities.

"The inadequate vaccination that led to the 2019 measles outbreaks has still not been adequately addressed, and the situation is now exacerbated by service disruptions during the COVID-19 pandemic so that high-risk, unimmunised children are clustered together in unreached communities," Professor Mulholland said.

The article has identified three pillars for immediate action:

Help countries reach unimmunised children through catch-up immunisation and campaigns

Better prepare countries for expected outbreaks. WHO and partners have developed a Strategic Response Plan to assist with measles outbreak prevention, preparedness and response

Maintain measles and rubella elimination targets. WHO's new Measles Rubella Strategic Framework 2021?2030, aligned with the Immunization Agenda 2030 provides a plan for strengthening routine immunisation and surveillance.

Professor Mulholland said the solutions would help end the cycle of inadequate immunisation and outbreaks of the past decade.

"Without concerted efforts now, it is likely that the coming years will see an increase in measles and its severe, frequently fatal, complications," he said.

Credit: 
Murdoch Childrens Research Institute

New drug can improve fertility in women with reproductive health problems

A drug that acts via the natural 'kisspeptin' hormone system in the body has the potential to treat reproductive health problems in women, according to a new study.

Twenty-four women were injected with a drug called MVT-602 which targets the kisspeptin system to stimulate reproductive hormones that affect fertility, sexual development and menstruation.

The naturally occurring form of kisspeptin called kisspeptin-54 (KP54) has been researched for a number of years to treat reproductive disorders, but in the new study, MVT-602 induced more potent signalling of the kisspeptin system over a longer period of time than KP54.

The researchers behind the study suggest that MVT-602 may be used to effectively treat a range of reproductive conditions that affect fertility such as polycystic ovary syndrome (PCOS) - a common condition that affects how a woman's ovaries work and hypothalamic amenorrhea (HA) - a condition where a woman's periods stop.

The researchers suggest that because of MVT-602's much longer duration of action, it can be given less frequently than the naturally occurring form of kisspeptin, whilst still being able to maintain the degree of stimulation of reproductive hormone levels required to restore reproductive health.

The study, published in the Journal of Clinical Investigation, is led by researchers at Imperial College London and clinicians at Imperial College Healthcare NHS Trust.

Professor Waljit Dhillo, lead author, NIHR Research Professor in Endocrinology and Metabolism at Imperial College London and Consultant in Endocrinology at Imperial College Healthcare NHS Trust said:

"Reproductive health issues are common for women around the world. Infertility as a result of these conditions can cause a lot of distress. Although we have made great strides in developing treatments for infertility and other reproductive disorders there is a need to find more effective treatments. Our previous work showed that kisspeptin can be used to stimulate ovulation in women undergoing in vitro fertilisation (IVF) treatment, but there are some limitations on using the naturally occurring kisspeptin hormone as its effectiveness wares off after a few hours. This study suggests that MVT-602 can stimulate kisspeptin over a longer period of time with no side effects, which means we could potentially use it to treat a wider range of reproductive disorders. This is an early stage study and more research needs to be carried out to fully determine the effects of MVT-602 on more patients."

Dr Ali Abbara, NIHR Clinician Scientist at Imperial College London and Consultant in Endocrinology at Imperial College Healthcare NHS Trust, who co-led the work added: "This is the first study to show that a single dose of MVT-602 can induce a longer duration of hormonal stimulation in women than naturally occurring kisspeptin. Therefore, it reveals exciting potential to treat a range of reproductive health conditions using MVT-602 and offer women improved treatment options. However, further research is needed to fully characterise its effects in specific disorders that affect reproductive health."

One in ten women in the UK are diagnosed with PCOS or HA. Current treatments for these conditions include dietary changes, medicines that treat infertility by restoring ovulation, and IVF treatment for those who still are unable to conceive. However, women with PCOS who undergo IVF treatment are at increased risk of 'ovarian hyperstimulation syndrome' (OHSS) - a potentially life-threatening side-effect of IVF treatment.

Kisspeptin is a naturally occurring hormone that controls the levels of other reproductive hormones in the body and plays an important role in fertility, reproductive health and the regulation of normal menstrual cycles. Previous studies have shown that kisspeptin can be used to safely stimulate reproductive hormones in women undergoing IVF treatment without causing OHSS. The research team wanted to see whether MVT-602 could target the kisspeptin pathway and produce a longer hormonal release than the naturally occurring form of kisspeptin - which is important for using kisspeptin to treat reproductive disorders.

Researchers carried out a trial at Hammersmith Hospital, part of Imperial College Healthcare NHS Trust, on 24 women aged 18-35 from 2017-2019. Twelve of the women were healthy volunteers and 12 of the women had either PCOS or HA. All of the women were given MVT-602. In addition, all of the healthy volunteers were given an injection of the naturally occurring kisspeptin (KP54) and saline placebo for comparison. The researchers then compared the women's reproductive hormone levels after receiving MVT-602 to naturally occurring kisspeptin (KP54). They also compared the reproductive hormone levels after MVT-602 between healthy women, women with HA and those with PCOS.

They found that all of the women given MVT-602 had a longer duration of raised reproductive hormones, specifically luteinising hormone (LH) and follicle stimulating hormone (FSH) levels, than when they received native kisspeptin (KP54). LH levels peaked at 21-22 hours after MVT-602 and remained elevated for 48 hours. This is in comparison to natural kisspeptin (KP54) whereby LH levels peaked at 4.7 hours after administration and remained elevated for 12-14 hours. Therefore, the duration of LH rise was extended by approximately four times using MVT-602.
LH increases following MVT-602 were similar in PCOS and healthy women, but rose more quickly in women in HA. Theoretically, this could be because women with HA have more kisspeptin receptors in the hypothalamus of the brain where kisspeptin acts as a result of their condition.

The researchers will now aim to carry out further studies on the effects of MVT-602 on women with reproductive disorders.

Credit: 
Imperial College London

Cellular powerplant recycles waste gases

image: CODH/ACS crystals obtained without oxygen. The brown color is coming from the natural metals harboured by the proteins (depicted as orange and green balls in the Figure 2).

Image: 
Max Planck Institute for Marine Microbiology/T. Wagner

Waste gases of many branches of industry contain mainly carbon monoxide and carbon dioxide. Nowadays, these gases are simply blown into our atmosphere, but this may soon change. The idea is to use the power of bacteria to turn toxic waste gases into valuable compounds such as acetate or ethanol. These can be used afterwards as biofuels or basic compounds for synthetic materials. The first real-size test plants are already under evaluation, using this conversion at an industrial scale, and the stars of these process are bacteria that devour carbon monoxide, carbon dioxide and dihydrogen, among which Clostridium autoethanogenum is by far the favorite.

"In this microbe, the main lines of the metabolism used to operate the gas conversion have been characterized," says Tristan Wagner, leader of the group Microbial Metabolism at the Max Planck Institute for Marine Microbiology. "But there are still a lot of question marks at the molecular level". The one in focus of the scientists from Bremen: How is the toxic carbon monoxide processed by enzymes at such stunning efficiency?

Big surprise in a crystal

The molecular-level knowledge of the carbon monoxide conversion is derived from studies performed in the species Moorella thermoacetica. This is a convenient and well-studied marine model organism but exhibits a poor ability to detoxify waste gases, unlike Clostridium autoethanogenum. Both bacteria use the same enzyme to convert carbon monoxide: the CO-dehydrogenase/Acetyl-CoA synthase, shortened as CODH/ACS. It is a very common enzyme which existed already in primeval times of the earth. "Since both species use the same enzyme to convert carbon monoxide, we were expecting to see exactly the same structure with eventually minor differences," says Wagner.

For their research, Wagner and his colleague Olivier N. Lemaire are studying the bacterium Clostridium autoethanogenum to understand how it can thrive at the thermodynamics of Life, using a metabolism similar to that of the first living forms. Olivier N. Lemaire grew the bacteria and purified its CODH/ACS in absence of oxygen, which is detrimental to the enzyme. The two scientists used the crystallization method to obtain crystals of the enzyme CODH/ACS and determine the protein 3D-structure by X-ray crystallography. "When we saw the results, we couldn't believe our eyes," says Wagner. "The CODH-ACS interface from Clostridium autoethanogenum drastically differs from the model of Moorella thermoacetica, even though it was the same enzyme and similar bacteria".

Same ingredients, different architecture

Afterwards, the two researchers carried out further experiments to prove that the first structure was not an artifact but the biological reality. Following experiments confirmed the initial model. Thus, the discovery clearly proves wrong the previous assumption that the enzyme CODH/ACS always has the same overall structure. "The enzyme of Moorella thermoacetica has a linear shape," explains Olivier N. Lemaire, first author of the study, which was recently published in the scientific journal BBA Bioenergetics. "In Moorella thermoacetica, the enzyme produces carbon monoxide in the CODH and uses in the ACS. Between them, it is trapped and funneled through a sealed gas-channel. ACS will ultimately synthesize acetyl-CoA, a building block further processed into acetate and ethanol. The rest of the cell do not see any carbon monoxide".

But Clostridium autoethanogenum absorbs carbon monoxide directly. "In Clostridium autoethanogenum the enzyme CODH/ACS has not only one opening, but several. In this way it can collect as much carbon monoxide as possible and conduct it into a whole system of tunnels, operating in both directions", says Lemaire. "These results show a reshuffling of internal gas-tunnels during evolution of these bacteria, putatively leading to a bidirectional complex that ensures a high flux of carbon monoxide conversion toward energy conservation and assimilation of carbon monoxide, acting as the main cellular powerplant". At the end of the process also acetate and ethanol are generated, which can be used to produce fuels.

"We now have a picture of what this very efficient and robust enzyme looks like", says Tristan Wagner. "But our discovery is only one step further. Among other things, it is still an open question how the bacterium can survive and use carbon monoxide to feed their whole cellular energy needs. We have some hypotheses, but we are still at the beginning. To understand the whole chemical process of converting carbon monoxide to acetate and ethanol, further proteins need to be studied".

Credit: 
Max Planck Institute for Marine Microbiology

Liver condition identified in patients using urine samples: new research

Fifty protein fragments known as peptides associated with liver fibrosis were found in the urine of patients, according to collaborative study between University of Warwick, Mosaiques Diagnostics, Hannover Medical School and University Hospitals Coventry and Warwickshire

The identified peptides could be potentially used in a test to spot people with the condition if further validated

Liver fibrosis is often symptomless in early stages and can progress to cirrhosis and liver cancer

Fifty fragments of proteins, termed peptides, have been identified in the urine of liver fibrosis patients in a new study that could pave the way for a potential diagnostic urine test for the condition if further validated.

The research was led by scientists from the University of Warwick, University Hospitals Coventry and Warwickshire (UHCW), Mosaiques Diagnostics and Hannover Medical School, who have published their analysis in the journal EBioMedicine.

Liver fibrosis can be a 'silent killer' as sufferers usually do not experience any symptoms until very late stage, when they start to lose the liver function. Patients then typically experience jaundice, ascites (build-up of fluid in the abdomen), variceal gastrointestinal bleeding, and in some cases can result in cancerous formation in the liver.

Previous research on biopsies from fibrotic livers has shown evidence of changes of proteins in liver tissue cells. As part of his PhD at the University of Warwick, Dr Ayman Bannaga, a clinical research fellow at UHCW, investigated whether these protein changes could also be present in a patient's urine, and whether they could act as a biomarker of the condition.

The research team used a total of 393 urine samples divided into discovery and test sets, representing individuals with various liver diseases and those with no disease present. These were investigated using an advanced technology known as capillary electrophoresis mass spectrometry, that separated out protein components in the urine at a molecular level. Following a two-step validation analysis, the researchers found fifty peptides associated with liver fibrosis in patients, mainly fragments of a protein called collagen.

When they tested a new set of patients for these fifty peptides, they correctly identified liver fibrosis patients in 84.2% of cases (sensitivity), and correctly identified those without it in 82.4% of cases (specificity).

While the results require further validation by other research teams, the researchers hope that their findings could form the basis of a simple and cost effective urine test that could spot those who have liver fibrosis before it progresses, although it may be many years before this is seen in clinical practice.

Dr Ayman Bannaga, a PhD student at Warwick Medical School, said: "A urine test is an attractive tool because it is easy to collect from patients, and so this approach can be easily applied in hospitals and GP practices. The ideal potential vision for this test would be to check the condition in people who do not have symptoms to tackle it early, through education, monitoring and medications if needed.

"There are a number of causes of liver fibrosis including viruses such as hepatitis B and C, excessive alcohol consumption, a build-up of fat in the liver, and some auto-immune diseases."

When the liver becomes fibrotic, proteins called collagens shrink the liver, causing the liver to become smaller and stiffer and affecting its function. Fragments of these proteins, which scientists term peptides, find their way into the blood, where they will be filtrated into the kidneys and leave the body via the urine. Currently detecting these protein changes would have to be done using a biopsy, but a urine test would be much easier and less invasive for patients.

Dr Bannaga adds: "Liver fibrosis affects people who are productive, those who drink lots of alcohol, people with sedentary lifestyles. A recent UK study done by a Bristol group showed that 1 in 40 people around the age of 24 years have fibrosis."

Professor Ramesh Arasaradnam OBE, Consultant Gastroenterologist and Dr Bannaga's PhD supervisor at Warwick Medical School, said: "Analysing urine for the purposes of diagnostics is a promising research area, and this new study builds on existing work in my research group looking at urine peptides in colon cancer. While we are unlikely to see this in clinical practice for some time, it provides an avenue for further investigation that could help in the prevention of this terrible condition."

Credit: 
University of Warwick

Tiny cave snail with muffin-top waistline rolls out of the dark in Laos

image: The new transparent "muffin-topped" snail, Laoennea renouardi.

Image: 
Estée Bochud

A new species of tiny cave snail that glistens in the light and has a muffin-top-like bulge, was discovered by Marina Ferrand of the French Club Etude et Exploration des Gouffres et Carrie?res (EEGC), during the Phouhin Namno caving expedition in Tham Houey Yè cave in Laos in March 2019. The new species, Laoennea renouardi, is 1.80 mm tall and is named after the French caver, Louis Renouard, who explored and mapped the only two caves in Laos known to harbor this group of tiny snails. Only two species of Laoennea snail are known so far, L. carychioides and now, L. renouardi.

Caver and scientist, Dr. Adrienne Jochum, affiliated with the Natural History Museum Bernand University of Bern (Switzerland), as well as the Senckenberg Research Institute and Natural History Museum (Frankfurt, Germany) described the new species and its cave habitat together with co-authors: Estée Bochud, Natural History Museum Bern; Quentin Wackenheim, Laboratoire de Géographie Physique (Meudon, France) and Laboratoire Trajectoires (Nanterre, France); Marina Ferrand, EEGC; and Dr. Adrien Favre, Senckenberg Research Institute and Natural History Museum, in the open-access, peer-reviewed journal Subterranean Biology.

"The discovery and description of biodiversity before it disappears is a major priority for biologists worldwide. The caves in Laos are still largely underexplored and the snails known from them remain few in number," points out Dr. Jochum.

The fact that two species of tiny cave snails of the same group were found in two caves located in two independent karstic networks 3.4 km apart, caused the authors to question evolutionary processes in these underground hotspots of biodiversity. The authors hypothesise that the two caves might have been connected during the Quaternary, around 100-200 thousand years ago. In time, the river Yè might have formed a barrier, thus disconnecting the cave systems and separating the populations. As a result, the snails evolved into two different species.

Credit: 
Pensoft Publishers

Scientists discover a new mineral

image: Petrovit

Image: 
SPbU

For more than 40 years, Stanislav Filatov, Professor at St Petersburg University, together with colleagues from other research institutions in Russia, has been studying the mineralogy of scoria cones and lava flows of fumaroles in Kamchatka. They were formed after two major eruptions of Tolbachik Volcano - in 1975-1976 and 2012-2013. This territory is unique in its mineralogical diversity. In recent years, researchers have discovered dozens of new minerals here, many of which are one-of-a-kind in the world.

The recent find by the scientists from St Petersburg University, petrovite, Na10CaCu2(SO4)8, occurs as blue globular aggregates of tabular crystals with gaseous inclusions. 'The copper atom in the crystal structure of petrovite has an unusual and very rare coordination of seven oxygen atoms. Such coordination is characteristic of only a couple of compounds, as well as of saranchinaite, which was discovered by our colleagues from St Petersburg University - the research team of Professor Oleg Siidra,' said the project manager, Professor Stanislav Filatov.

The mineral consists of oxygen atoms, sodium sulphur and copper, which form a porous framework. The voids are connected to each other by channels through which relatively small sodium atoms can move. The scientists have therefore established that the structural type of petrovite is promising for ionic conductivity and can be used as a cathode material for sodium ion batteries.

'At present, the biggest problem for this use is the small amount of a transition metal - copper - in the crystal structure of the mineral. It might be solved by synthesising a compound with the same structure as petrovite in the laboratory,' said Stanislav Filatov.

Credit: 
St. Petersburg State University

Scientists discover new mechanism controlling brain size

image: The research team used stem cells and zebrafish to investigate the role of RRP7A in brain development. The picture shows the brain of a normal zebrafish larvae (left) and a larvae with microcephaly (right).

Image: 
Assist. Prof. Canan Doganli, University of Copenhagen

Under the leadership of Professor Lars Allan Larsen and Professor Søren Tvorup Christensen at University of Copenhagen (UCPH), Denmark, an international research team has taken an important step forward in understanding the complex mechanisms that control development of the so-called cerebral cortex, which is the part of the brain that play a key role in attention, perception, awareness, thought, memory, language, and consciousness. The results have just been published in the internationally recognized journal Nature Communications.

The scientists started with genetic analyses of a large family in which children were born with primary microcephaly; a rare congenital brain disorder characterized by a reduction in the size of the cerebral cortex and varying degree of cognitive dysfunction. The scientists found that the children were carriers of a mutation in both copies of the gene, RRP7A, and by the use of stem cell cultures as well as zebrafish as model organism, RRP7A was shown to play a critical role for brain stem cells to proliferate and form new neurons. This process is extremely complex and slight disturbances may have serious consequences, which may explain why the mutation affects the brain and no other tissues and organs.

- "Our discovery is surprising, because it reveals hitherto unknown mechanisms involved in the development of the brain. In addition, it highlights the value of research in rare disorders, which is important both for the patients and family affected by the disease but also beneficial for society in the form of new knowledge about human biology", states Lars Allan Larsen, Department of Cellular and Molecular Medicine.

The researchers further discovered that the mutation in RRP7A affects the function of the so-called primary cilia, which project in a single copy as antenna-like structures on the surface of cells to register environmental cues and control the formation of new neurons in the developing brain.

- "Our results open a new avenue for understanding how primary cilia control developmental processes, and how certain mutations at these antenna-like structures compromise the formation of tissues and organs during development. To this end, we have already initiated a series of investigations to understand the mechanisms by which RRP7A regulates ciliary signaling to control formation and organization of neurons in the brain, and how defects in this signaling may lead to brain malformation and cognitive disorders, says Søren Tvorup Christensen at Department of Biology.

Credit: 
University of Copenhagen - Faculty of Science

Pesticides commonly used as flea treatments for pets are contaminating English rivers

Researchers at the University of Sussex have found widespread contamination of English rivers with two neurotoxic pesticides commonly used in veterinary flea products: fipronil and the neonicotinoid imidacloprid. The concentrations found often far exceeded accepted safe limits.

These chemicals are banned for agricultural use due to the adverse environmental effects, but there is minimal environmental risk assessment for pesticides used on domestic cats and dogs. This is due to the assumption that there are likely to be fewer environmental impacts due to the amount of product used.

But there is growing concern that this assumption may be incorrect. To investigate this, Professor Dave Goulson and Rosemary Perkins from the University of Sussex analysed data gathered by the Environment Agency in English waterways between 2016-18. They found that fipronil was detected in 98% of freshwater samples, and imidacloprid in 66%.

Rosemary Perkins, a PhD student at Sussex and a qualified vet, said: "The use of pet parasite products has increased over the years, with millions of dogs and cats now being routinely treated multiple times per year".

"Fipronil is one of the most commonly used flea products, and recent studies have shown that it degrades to compounds that are more persistent in the environment, and more toxic to most insects, than fipronil itself. Our results, showing that fipronil and its toxic breakdown products are present in nearly all of the freshwater samples tested, are extremely concerning."

According to the Veterinary Medicines Directorate (VMD), who funded the research, there are 66 licensed veterinary products containing fipronil in the UK, and 21 containing imidacloprid, either alone or in combination with other parasiticides. These include spot-on solutions, topical sprays and collars impregnated with the active ingredient.

While some of these products can be purchased only with a veterinary prescription, others can be bought without a prescription from pet shops, supermarkets, pharmacies and online. Many pet owners receive year-round preventative flea and/or tick treatment from their vet practice via healthcare plans.

Fipronil has a history of very limited agricultural use prior to its ban in 2017. It is also licensed for use in ant and cockroach baits, however only one product is licensed for use by non pest-control professionals. Use on pets seems to be the most plausible source of the widespread contamination of rivers.

The paper, co-authored with Martin Whitehead from the Chipping Norton Veterinary Hospital and Wayne Civil at the Environment Agency, examines the occurrence of fipronil and imidacloprid in English rivers as indicators of the potential contamination of waterways from the use of pet flea treatments.

They found that the average fipronil concentration across the rivers sampled by the Environment Agency exceeded chronic safety thresholds five-fold. The overall pollution levels in English rivers indicate that fipronil and its toxic breakdown products pose a high risk to aquatic ecosystems.

While, in most rivers, imidacloprid was found to pose a moderate risk, in seven out of the 20 rivers sampled there was a high environmental risk.

Co-author Professor Dave Goulson said "Fipronil and imidacloprid are both highly toxic to all insects and other aquatic invertebrates. Studies have shown both pesticides to be associated with declines in the abundance of aquatic invertebrate communities. The finding that our rivers are routinely and chronically contaminated with both of these chemicals and mixtures of their toxic breakdown products is deeply troubling."

The paper, published in Science of the Total Environment, notes that the highest levels of pollution were found immediately downstream of wastewater treatment works, supporting the hypothesis that significant quantities of pesticide may be passing from treated pets to the environment via household drains.

Bathing of pets treated with spot-on fipronil flea products has been confirmed as a potentially important route to waterways for fipronil via sewers, and the washing of hands, pet bedding or other surfaces that have come into contact with treated pets are potential additional pathways for entry to sewers. Other pathways for contamination of waterways includes swimming and rainfall wash-off from treated pets. The strong correlation between fipronil and imidacloprid levels across the river sites tested suggest that they may be coming from a common source.

Rosemary Perkins added: "We've identified a number of steps that can be taken to minimise or avoid environmental harm from pet flea and/or tick treatments. These range from introducing stricter prescription-only regulations, to considering a more judicious and risk-based approach to the control of parasites in pets, for example by moving away from blanket year-round prophylactic use.

"We'd recommend a re-evaluation of the environmental risks posed by pet parasite products, and a reappraisal of the risk assessments that these products undergo prior to regulatory approval."

Credit: 
University of Sussex

Parasite infection discovery could assist mental health treatments

image: T.gondii parasites

Image: 
plos.org

New research into how a common parasite infection alters human behaviour could help development of treatments for schizophrenia and other neurological disorders.

Scientists say behaviour changes in those infected with T. gondii, which currently infects 2.5 billion people worldwide and causes the disease Toxoplasmosis, could be linked to lowered amounts of norepinephrine, a chemical released in the brain as part of the stress response. Norephinephrine also controls neuroinflammation, the activation of the brain's immune system against infection.

Norepinephrine and neuroinflammation are associated with neuropsychological disorders such as schizophrenia, Alzheimer's disease, and ADHD.

Although usually considered asymptomatic in humans, T. gondii infection can cause headache, confusion and seizures in others as well as an increased susceptibility to schizophrenia - and can be fatal to immunocompromised patients.

T. gondii can only sexually reproduce in cats. It forms cysts which are shed in the cat's faeces. It makes its way into new hosts through ingestion of anything contaminated by these cysts, such as water, soil or vegetables; through blood transfusions, from unpasteurised goat's milk; eating raw or undercooked meat, or from mother to foetus.

After a few weeks, the infection enters a dormant phase, whereupon cysts form in the brain. They can remain there for many years, possibly for life. It is during this stage that infection decreases the regulator of the brain's immune response norepinephrine.

The mechanisms by which the parasite affects brain function have been poorly understood. But research led by the University of Leeds and Université de Toulouse now suggests that the parasite's ability to reduce norepinephrine interrupts control of immune system activation, enabling an overactive immune response which may alter the host's cognitive states.

The findings - Noradrenergic Signaling and Neuroinflammation Crosstalk Regulates Toxoplasma gondii-Induced Behavioral Changes - have been published in Trends in Immunology.

Glenn McConkey, Associate Professor of Heredity, Disease, and Development at Leeds' School of Biology, who published the research, said: "Our insight connects the two opposing theories for how Toxoplasma alters host behaviour and this may apply to other infections of the nervous system. One school believes that behaviour changes are invoked by the immune response to infection and the other that changes are due to altered neurotransmitters."

"This research will contribute to the great need in understanding how brain inflammation is connected to cognition, which is essential for the future development of antipsychotic treatments."

Credit: 
University of Leeds

Obese people found to be at increased risk of COVID-19

A new study led by researchers at Queen Mary University of London uses a novel approach to investigate the effects of cardiovascular risk factors on the risk of COVID-19 infection.

Several observational studies have reported the link between cardiovascular risk factors (such as obesity, high blood pressure, diabetes and high cholesterol) and COVID-19 severity. However, these studies could not ascertain the cause and effect relationship due to the observational design.

The new study, published in the science journal Frontiers in Genetics, used a novel approach called 'Mendelian Randomisation', which leveraged on the individual genetic information, to investigate the effects of cardiovascular risk factors on the risk of COVID-19 infection.

Lead author Dr Nay Aung from Queen Mary University of London said: "Our results show that individuals with high body mass index (BMI), a marker of obesity, and high low-density lipoprotein (LDL) cholesterol (also known as 'bad' cholesterol) are at an increased risk of getting COVID-19. Other cardiovascular risk factors (high blood pressure and diabetes) do not appear to elevate the COVID-19 risk.

"Our findings support the use of BMI and LDL cholesterol as important metrics alongside other known characteristics (such as age and ethnicity) in the risk assessment of vulnerability to COVID-19 infection."

The findings may have an impact on public health policy, whereby those who fall in the at risk obese category or those with extreme hyperlipidemia in the general population may require more rigorous social distancing or shielding.

Furthermore, studies assessing the role for cholesterol modification therapy during illness or hospital admission could be undertaken to assess potential impact on outcomes.

Credit: 
Queen Mary University of London