Culture

Bottom Line: Most transgender and gender-nonbinary teens in China who participated in a national survey study reported abuse, neglect or bullying at home and in school, which the researchers suggest may be due in part to the socially conservative values prevalent in the country.  The study included 385 adolescents (average age nearly 17) who responded to an online survey. Among the 319 teens who reported their parents knew their gender identity, 92% reported experiencing parental abuse or neglect and, among all the teens, 76.6% reported abuse or bullying at school from classmates or teachers. Limitations of the study include that survey questionnaires were only accessible to teens with internet access and all the study measures were self-reported and done over the internet.

Authors: Runsen Chen, M.Sc., M.B.M.S., of the National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders and Advanced Innovation Center for Human Brain Protection, Beijing Anding Hospital, Capital Medical University in Beijing, and coauthors

(doi:10.1001/jamanetworkopen.2019.11058)

Editor's Note: The article contains conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

September 6, 2019--BRONX, NY--A new study of New York City firefighters has found that exposure to 9/11 World Trade Center (WTC) dust is associated with a significantly increased long-term risk of cardiovascular disease (CVD). The study, conducted by researchers at Albert Einstein College of Medicine, Montefiore Health System, and the Fire Department of the City of New York (FDNY), found that those who arrived first at the WTC site--when the air-borne dust was thickest--have a 44% increased risk of CVD compared to those who arrived later in the day. The study was published online today in JAMA Network Open.

"The increase in risk was significant, even taking into account known CVD risk factors such as age, hypertension, elevated cholesterol, diabetes, and smoking," said study leader David J. Prezant, M.D., a professor of medicine at Einstein, a pulmonary disease specialist at Montefiore, and chief medical officer of the FDNY.

This study's finding of an increased risk of CVD with WTC exposure--as well as the researchers' earlier studies identifying an increased risk for autoimmune rheumatologic diseases and for a blood cancer precursor that can lead to the cancer multiple myeloma--"highlights the need to add these health conditions to the list of WTC-related diseases that are coverable under the James L. Zadroga 9/11 Health and Compensation Act," Dr. Prezant added.

Studies have repeatedly shown that WTC exposure is associated with immediate and long-term risk of adverse health effects, including respiratory problems, post-traumatic stress disorder (PTSD), and several types of cancer. A few studies have examined the association between WTC exposure and CVD. However, the results were inconsistent for a variety of reasons, primarily because they relied on first responders' self-reported health measures.

Assessing Cardiovascular Disease Risk

The current study involved 9,796 firefighters who worked at the WTC site. Most were never smokers (74%) and non-Hispanic white (94%), with an average age of 40 on September 11, 2001. All were men, since there were too few female firefighters at the WTC site to obtain meaningful data.

For this study, the firefighters were divided into four groups: (1) those who first arrived at the WTC site during the morning of 9/11 (who were believed to receive the highest dust exposure); (2) those who first arrived that afternoon; (3) those who first arrived on September 12; and (4) those who first arrived between days 3 and 14.

The researchers reviewed 16 years of medical records, physician examinations, and questionnaires to assess the participants for primary and secondary CVD events. (Primary CVD events were defined as myocardial infarction, stroke, unstable angina, coronary artery surgery or angioplasty, or CVD death; secondary events included transient ischemic attack, angina defined as either angina medication or cardiac catheterization without intervention, cardiomyopathy, and "other CVD": aortic aneurysm, peripheral arterial vascular intervention, and carotid artery surgery.)

Firefighters who arrived during and immediately after the WTC collapse (group 1) had a 44% higher risk of experiencing primary and secondary CVD events compared with those who arrived on September 12 or later (groups 3 and 4 combined). Similarly, those who worked at the WTC site for six months or more were 30% more likely to have experienced a primary or secondary CVD event compared with those who worked less time at the site. These associations were statistically significant after taking into account age, race/ethnicity, and baseline assessments of body mass index, hypertension, elevated cholesterol, diabetes, smoking, and probable PTSD.

"An important message is that new chest pain in this group should not automatically be attributed to well-known WTC-related illnesses, such as acid reflux or obstructive airway disease. It might very well be associated with CVD," said Dr. Prezant.

Monitoring Symptoms and Health

"Our results emphasize why it is crucial to monitor the long-term health of anyone exposed to massive environmental disasters, even many years after the event," said co-lead author Rachel Zeig-Owens, Dr.P.H., a research assistant professor of epidemiology & population health at Einstein and an epidemiologist at Montefiore and FDNY. "By screening for and treating the other CVD risk factors--such as elevated cholesterol, hypertension, obesity, and smoking--we are able to lower the overall risk of CVD in those most exposed to the World Trade Center disaster."

Many other studies have linked both acute and prolonged exposure to air pollution to CVD. The researchers noted that exposure to dust and products of combustion could have triggered persistent disease processes involving chronic inflammation that increased the risk for CVD years later.

Parents should help their children with better sleep patterns, along with any problem behavioural issues, because this can lead to severe insomnia in middle age, a groundbreaking new study shows.

Published in JAMA Network Open journal today, Australian researchers have used data from a long-running UK population study to find links between moderate to severe childhood behavioural problems and insomnia in adults by the age of 42 years old.

Insomnia is the most common sleep disorder in adults, estimated to affect almost one in three people. Chronic insomnia is associated with an increased risk of mental health and other health, wellbeing and economic consequences including working capacity.

"This study shows a consistent association of behavioural problems during childhood, particularly at ages 5 and 10 years, with insomnia symptoms in adulthood," says senior author Flinders University's Robert Adams, Professor of Respiratory and Sleep Medicine at the Adelaide Institute for Sleep Health (AISH) - a leading Australian research centre.

"The findings suggest that early intervention to manage children's externalised behaviours, such as bullying, irritability or constant restlessness, may reduce the risk of adult insomnia.

"As well as identifying sleep problems early in life, we should also identify children with moderate to severe behavioural problems that persist through childhood as potential beneficiaries of early intervention with a sleep health focus," Professor Adams says.

"This study is the first to our knowledge to suggest an unfavourable association between early-life behavioural problems in children and addressing insomnia, from a life-long perspective," says Flinders University lead author, Dr Yohannes Adama Melaku.

"Given the cost of sleep disorders, including insomnia, to every economy and society in the world, it's another important step towards managing this endemic problem in the community," he says.

"This first study is important because we don't know exactly the childhood or early-life factors that potentially influence this outcome of insomnia and finding these connections could reduce sleep disorders in the future."

The United Kingdom 1970 Birth Cohort Study is a large-scale study of more than 16,000 babies born in a single week. The current study includes people from the cohort aged 5 (8550 participants), 10 (9090 people) and 16 years (7653) followed up to age 42 years (2012). Statistical analysis was performed from February 1 to July 15, 2019.

The Flinders University study focused on externalised behavioural problems reported by parents, including cases of restlessness, disobedience, fighting, bullying, property damage and theft and irritability.

The research team's next paper will focus on the effect of maternal smoking during pregnancy and childhood and any impact on insomnia and related sleep issues in adults.

Cells are the basic building blocks of life - and, as such, they have been the object of intense study since the invention of the optical microscope in the 17th century. The development of mass spectrometry (MS) methods - those which define the chemical composition of cells - represented a further milestone for research in the field of cell biology. In the latest issue of the journal Nature Methods, the working group headed by Prof. Klaus Dreisewerd and Dr. Jens Soltwisch from the Institute of Hygiene at the University of Münster present a method which has improved the spatial resolution of MALDI mass spectrometry by around one-thousandth of a millimetre.

MALDI stands for matrix-assisted laser desorption/ionisation. What's so special about the technology which the researchers have named t-MALDI-2 (with 't' standing for transmission mode) is the use of two specially adapted lasers: one of them generates a particularly small focus on the material removed, while the other produces the necessary signal enhancement for many biomolecules by up to several magnitudes - for example, for fat-soluble vitamins such as vitamin D, cholesterol or administered medication. Information on their precise distribution in cells and tissues can, among other things, help to produce a better understanding of disease and inflammation processes and show new strategies for treating them.

MALDI MS methods define the nature and the composition of molecules on the basis of their characteristic mass, i.e. of their "molecular weight". This makes it possible to take a sample irradiated by the laser - for example, a thin section of tissue obtained from a biopsy - and simultaneously define often dozens, even hundreds, of different biomolecules in one single measurement. However, up to now the resolution provided by mass spectrometry imaging was well below that of classic optical microscopy. As a result of the introduction of the new t-MALDI-2 technology, it has been possible to noticeably reduce this gap

"The decisive improvement which our method offers, in comparison with established MALDI imaging methods, is based on the combination and extension of two technical methods previously in use," explains Dr. Marcel Niehaus, one of the two lead authors of the study. "For one thing, in the transmission geometry we irradiate our samples on the reverse side. This enables us to place high-quality microscope lenses very close to the sample, thus reducing the size of the laser dot. This is different from what is possible, for geometrical reasons, in standard methods - where the samples are irradiated from the direction of the mass analyzer." However, in the minute areas of the sample which are removed by the laser, there is only an extremely small amount of material available for the subsequent MS measurement. The second decisive step was therefore the use of a method (called MALDI-2) which the researchers had already introduced to the scientific world in 2015 in the Science journal. The effect is that the so-called post-ionization laser produces an increased transfer of the initially uncharged molecules to an ionic form. Only if the molecules have a positive or negative charge are they visible for the mass analyzer.

In their study, the researchers demonstrate the possibilities offered by their technology, taking the fine structures in the cerebellum of a mouse and using kidney cell cultures. "Our method could improve the future understanding of many processes in the body at molecular level," says Prof. Dreisewerd. "Also, established methods from optical microscopy - for example, fluorescence microscopy - could be merged with mass spectrometry imaging in a 'multi-modal' instrument," he adds, with a view to the future.

5000 years before the modern rise of millet as a popular grain, this Chinese crop was spread far and wide by ancient food aficionados, not for their plates but instead for their animals, suggests new research from an international collaboration led by Kiel University (Germany) and Washington University in St. Louis (USA).

At the newly discovered Dali settlement, ancient DNA from the skeletal remains of sheep and goats show that animals first domesticated in the Near East had reached eastern Kazakhstan by 2700 BC. Stable isotope analysis illustrates that these animals were fed millet spreading westward from its center of domestication in China to help them survive the punishingly cold winters of Inner Asia.

"A thriving pastoralist economy using Chinese millets at 2700 BC is a massive leap forward in understand the earliest food globalization processes in Eurasia," said Taylor Hermes, lead author of the study in Proceedings of the Royal Society B, who is a post-doctoral researcher at Kiel University.

"This is quite an early date for domesticated animals to be present in Inner Asia, and it is also the earliest dated evidence so far of millets spreading out of China. This raises the intriguing possibility that sheep and goat, originally domesticated in the Near East 10,000 years ago, helped move crops of both East Asian and, possibly, Near Eastern origins across the steppe."

The spread of domesticated plants and animals through the vast steppe grasslands of Inner Asia during the Bronze Age marked the beginning of the ancient trade routes that later formed Asia's Silk Roads. However, the exact timing of moving crops through this continental crossroads and the case for farming has remained elusive.

"Our previous research showed archaeobotanical remains of both wheat and millet in human burials around 2300 BC in the highlands of Kazakhstan at the Begash site, but there was not concrete evidence to show whether these were trade items or farmed locally," said Michael Frachetti of Washington University Arts & Sciences, who is a co-author and co-director of the underlying archaeological fieldwork.

The study draws upon excavations and museum collections as part of a longstanding scientific partnership between Washington University, led by Frachetti, and the Margulan Institute of Archaeology in Almaty, Kazakhstan. "Until the discovery of the Dali settlement and this research, we were left to speculate about the integration of intensive farming among Early Bronze Age herders in the region, and whether these grains made it into their diet," he said.

Millet has a distinct carbon isotopic 'signature' that distinguishes it from other crops such as wheat and barley. Consequently, evidence of millet consumption can be traced in the isotope ratios of human bones, but such skeletal remains dating to the third millennium BC are exceedingly rare.

"One way around this problem is to examine the stable isotopes of livestock, which offers a direct window into what and when people fed their animals in the past," says Cheryl Makarewicz, who leads the Archaeological Stable Isotope Laboratory at Kiel University and is senior author of the study.

"Modern pastoralists living in harsh environments such as those where Dali and Begash are located typically give their animals fodder in order to ensure their survival through the winter. The leaves and straw of crops are a great fodder source, and the isotopic composition of ancient sheep and cattle at these sites show the scale of millet cultivation was large enough to provide for animals throughout the winter months," Makarewicz said.

"We also see a wide range of variation in the intensity of this millet foddering strategy, showing a large degree of flexibility in food production," Hermes said. "People who lived at Dali and Begash were shifting their herding and farming strategies year-to-year depending on environment or social circumstances, which gave them critical advantages in ensuring their food security."

This study clearly links the westward dispersal of millets -- a key indigenous crop of Chinese civilization -- to livestock herding by pastoralists who used farming to enhance their animal-focused worlds.

"Millet was a prized crop for keeping healthy herds and, in essence, for being a better pastoralist," Hermes said.

Resilience--understood as the set of personal resources that help individuals deal effectively with adversity, protecting them from the negative health effects of stress--is receiving increasing attention from researchers. However, it remains under-studied in such a sensitive time of life as pregnancy.

Previous studies have found that pregnancy is a crucial period during which exposure to stress can negatively affect the health of both mother and baby. Stress has been linked to a range of adverse consequences, including premature birth or post-partum depression.

Researchers from the University of Granada (UGR)--from the Mind, Brain and Behaviour Research Centre (CIMCYC) and the Faculty of Psychology--have analysed for the first time the protective role of resilience during pregnancy. They studied the psychological state of the mother and measured the levels of cortisol in her hair--a novel approach that enables objective analysis of the amount of cortisol, the stress hormone, secreted by the woman in recent months.

A study among 151 pregnant women

In this study, 151 pregnant women were assessed, both in the third trimester and following childbirth, on the basis of psychological variables related to pregnancy stress and also hair cortisol concentrations.

When comparing pregnant women with a high level of resilience to those with a low level of resilience, the researchers found that the more resilient participants perceived themselves to be less stressed, had fewer pregnancy-related concerns, and experienced greater general psychological wellbeing overall. After childbirth, they also presented fewer symptoms of postpartum depression. The cortisol hormone tests demonstrated that the more resilient pregnant women also had lower levels of the stress hormone.

Based on these results, the researchers concluded that resilience exerts a clear protective role against the negative effects of stress, both psychological and biological--an effect that can occur during pregnancy and also after the birth.

Significantly, as these are the first-ever data on the protective role of resilience in pregnancy, the results raise questions about its potential protective role in the health of the baby. This calls for further research on this phenomenon. Studies on the effectiveness of training programmes designed to provide pregnant women with stress-management skills are also needed, to help improve the health of both the pregnant woman and her baby.

A study conducted by researchers from the University of Granada (UGR) recommends spending more time standing to increase energy expenditure and combat the negative health effects of a sedentary lifestyle. The research has also quantified exactly how many extra calories we burn when we remain standing: 45 kilocalories more, per six-hour period, than when lying or sitting.

One of the applications of the study, published in the journal PLOS ONE, could be the use of adjustable-height tables that enable people to work standing up--already a very common practice in the Nordic countries--and thus combat the negative effects of a sedentary working environment. These tables can be fully adjusted to suit the height of the user, depending on whether they want to sit or stand while working.

Francisco J. Amaro- Gahete, PhD Biomedicine student at the UGR's International School for Postgraduate Studies and member of the Department of Physiology, is the main author of the article. He notes: "We Spaniards spend between 8 and 10 hours sitting or lying down each day, not counting the hours we are asleep. Therefore, if we take steps to combat a sedentary lifestyle by making small lifestyle changes, such as spending more time standing, this could reduce the risk of developing diseases such as obesity or Type 2 diabetes."

In the published article, researchers describe how one effective way to address the effects of a sedentary lifestyle is to reduce the amount of time we spend sitting or lying down, and encourage us to stand more often. The article also presents the findings of the study regarding the energy expenditure for each of these three positions.

Two kinds of people: Energy savers and energy spenders

The scientists used a sample comprising 53 young adults, who were classified into two types, "savers" and "spenders" of energy, depending on the amount of energy expenditure they consumed when switching from sitting or lying to standing.

"Savers consume very little energy in their activities and, therefore, the difference between sitting/lying or standing is practically nil for them. But energy spenders burn approximately 10% more energy when they switch from sitting or lying to standing," explains Amaro.

So what makes a person spend more or less energy? This is a question that researchers are still trying to answer, as it is related, for example, to the issue of why some people lose weight so easily and others find it so difficult.

The factor that appears to have the greatest effect is muscle mass. "People with more muscle mass expend more energy than people with less muscle mass," observes the UGR researcher.

In light of the results, the authors recommend spending more time standing in the office as a good strategy to use up more energy and thus avoid storing it as fat.

"It is really important to change your position," comments Jonatan Ruiz, another of the authors of the article. "If a person were to get up, take 10 steps, and sit down again, it appears that the effects of a sedentary lifestyle would be greatly reduced. Therefore, we must educate our school-age children and young people, as well as teachers, about the importance of avoiding spending long periods of time sitting down to considerably reduce the negative consequences of a sedentary lifestyle such as excess weight and obesity, or the risk of developing cardiovascular disease."

The vast majority (97.4%) of players with the Spanish League are unfamiliar with the list of substances banned by the World Anti-Doping Agency (WADA). Furthermore, 95% do not even know what this agency is for.

These are among the findings of a study carried out by Jaime Morente, Thomas Zandonai, and Mikel Zabala, researchers from the Faculty of Sport Sciences of the University of Granada (UGR). A paper on the study was recently published in the prestigious international Journal of Science and Medicine in Sport.

The researchers studied and compared the attitudes, beliefs, and knowledge of footballers with the Spanish League regarding the use of banned drugs--doping--in the sport. They analysed a sample comprising 1,324 football players from 88 different teams, including 304 participants from the Professional Football League.

"If we look at the specialized scientific literature, although there are studies dealing with other sports, this is an unprecedented piece of research at a national and international level, due to the difficulty of accessing this type of sample and, of course, the taboo nature of the soccer-doping binary," explain the UGR researchers.

The "false consensus" effect

Some 5% of the footballers who participated in the study acknowledged having used banned substances at some time during their sports career, while 23.7% of the participants knew their peers were resorting to this type of substance. This phenomenon is known in the scientific literature as the false-consensus effect: the participant claims not to be a consumer of the substance, but curiously does know consumers in their environment.

The researchers conclude that "there is a significant lack of knowledge regarding doping among the players we evaluated." Doping is a complex phenomenon involving medical, ethical, pharmacological, and educational factors, among others, which therefore must be tackled by means of a multidisciplinary strategy. In short, although anti-doping controls are necessary, the researchers propose a prevention-based approach, in which educational programs are delivered even at an early age, as a way to eradicate this scourge.

In a group of internationally adopted children with cleft lip and/or palate, speech at age five is impaired compared to a corresponding group of children born in Sweden, a study shows. The adopted children also need more extensive surgery, which may be due to their surgical interventions taking place later in life.

"The study shows they undergo more operations, have more complications, and have more speech difficulties at age five," says Johnna Scholin, PhD Student in plastic surgery and first author of the study, published in Journal of Plastic Surgery and Hand Surgery.

"However, one must bear in mind that this is not an end result for the children, and as we see it, following them over time is extremely important," she emphasizes.

The study comprises 50 children, born 1994-2005. Half were born in Sweden and half adopted to Sweden from other countries, especially China. The children were born with cleft lip and/or palate (CL/P). The two groups were matched in terms of age, sex, and cleft type.

Cleft palate, which means that the face and palate have not fused early in fetal life, is a birth defect affecting around two in every thousand babies born in Sweden. When a cleft it is detected in a routine ultrasound, the parents-to-be are referred to a specialist cleft team for a consultation. This is the first meeting of many.

In the group of Swedish-born children in the study, their lip and palate surgery had been initiated when they were six months old, as usual in Sweden. In the adopted children, whose average age at arrival was two and a half years, the important palate surgery was delayed by an average of 21 months, the results show.

"Their palate function and speech were significantly impaired at age five compared to the Swedish-born children's. In some cases, it was only the parents were able to who understand their children. Both speech-enhancing surgery and speech therapy are part of further treatment options, but there's a high risk of the adopted children having to undergo several operations," Scholin says.

The adopted children had more palatal fistulas (holes between the mouth and nasal cavities) as a complication after surgery, possibly caused by poor nutritional status prior to adoption and thus impaired healing. Other conceivable explanations are multi-resistant bacteria and diseases that the children are not known to have at the time of adoption. In our experience, the medical records that follow the children from their home countries, are often both invalid and missing regarding data, hence not helpful.

Children with cleft palate generally have more ear infections, which can affect hearing. In the study, 21 of the 50 had hearing loss. Most (12) of these children were in the international adoptees' group, which entailed a further strain on their language switch.

Scholin is driven by a strong desire to help the children, both in her research at Sahlgrenska Academy, University of Gothenburg, and as a CL/P surgeon and senior consultant at the care unit for children and adolescents at Sahlgrenska University Hospital.

She emphasizes the importance of the cleft team's efforts, in which plastic surgeons, speech language pathologists, ENT doctors, dentists, a psychologists, a CL/P nurses, and clinical coordinators work together to improve the adopted children's treatment outcomes and situation.

"The good thing is that the children are coming to a well-functioning cleft team, and receive the best treatment possible. We follow the children closely until they're at least 19, and we don't stop until everything's as good as it could possibly be," she concludes.

A rare deer species that lived in central Thailand might have come back from the dead -- without the help from sci-fi-like genetic engineering.

Schomburgk's deer (Rucervus schomburgki) was added to the extinction list in 1938. But new evidence, gleaned from antlers obtained in late 1990 or early 1991, shows that it survived for at least an additional half century and might still be around today.

The research was published last week (Aug. 30) in the Journal of the Bombay Natural History Society. Gary Galbreath, professor of biological sciences at Northwestern University's Weinberg College of Arts and Sciences, was involved in the work.

After the wild population died out from overhunting in 1932, the last known Schomburgk's deer died in captivity six years later. Or so we thought. A trucker in Laos found a set of antlers, seemingly in fresh condition, in the early 1990s. He then gave the antlers to a shop in the northern Laos province of Phongsali.

In February 1991, United Nations agronomist Laurent Chazée photographed the antlers. Galbreath and his collaborator G.B. Schroering recently analyzed the antlers' physical condition in those photos. Based on the widely spreading, basket-shaped, hyper-branched structure of the antlers, the team determined the antlers belonged to a Schomburgk's deer. (Other Asian deer's antlers do not have the same signature basket shape.)

Galbreath also confirmed that the antlers were fresh when photographed in 1991. The antlers -- spotted with dark red to reddish-brown dried blood -- had been excised from the deer's head. The color of the blood and condition of the exposed bone marrow offered clues into the antlers' age.

"The relative antiquity of the antler specimens can be assessed by the materials, such as dried marrow, still adhering to them," said Galbreath, an expert in Asian wildlife. "Even the blood was still reddish; it would become black with increased age. In the tropics, the antlers would not continue to look this way even within a matter of months."

Before they were listed as "extinct," the deer were well documented in Thailand. Galbreath believes a small population probably also lived in a remote area in central Laos, where they just might still be living today.

Scientists have revealed how the typhoid toxin works to hijack DNA repair machines and accelerate the aging of cells, a breakthrough that could pave the way for new strategies to combat the killer disease.

As part of the study, experts from the Department of Biomedical Science with support from the new Healthy Lifespan Institute at the University of Sheffield, infected human cells in a lab with the bacterial pathogen for typhoid - Salmonella typhi.

Using fluorescent microscopes to study how the toxin damaged the DNA at the molecular level, they discovered it induces a peculiar form of DNA damage; the toxin takes over DNA repair machines and accelerates cellular ageing, rendering them more susceptible to infection. In time, secretions from the infected cells can also cause aging in neighbouring cells, leading to faster aging at a cellular level.

Typhoid fever is a major killer in low- and middle-income countries, affecting 21 million people annually and causing 168,000 deaths. The infectious disease is a particular problem in South Asia where it is compounded by antimicrobial resistance and a lack of effective vaccines and diagnostics.

To cause typhoid, the bacterial pathogen Salmonella typhi releases the typhoid toxin, which damages cellular DNA. Our DNA is constantly under threat by environmental factors such as smoking and UV light, but cells usually have robust DNA repair machines to combat these threats. In the case of the typhoid toxin attacking our cells, it is this repair machine function that gets hijacked. Dr Angela Ibler who made the discovery dubbed the DNA damage response RING - Response induced by a Genotoxin - in reference to the single-strand breaks in the double helix of human cell DNA that accumulate in a signature ring-like pattern.

The findings, published in Nature Communications today (6 September 2019) could potentially enable the toxin-associated cellular aging to be used as a biomarker to help with earlier diagnosis and faster treatment for typhoid sufferers.

Dr Daniel Humphreys, who led the study from the Department of Biomedical Sciences, said: "Our findings have shown that pathogenic bacteria can speed up cellular aging through a toxin and take advantage of this to establish infections. This makes sense as infections are often harder to combat and recover from as we get old, which is partly due to cellular ageing, but the fact that bacterial pathogens target this phenomenon is unexpected.

Professor Sherif El-Khamisy, Deputy Director of the University of Sheffield Healthy Lifespan Institute from the Department of Molecular Biology and Biotechnology, who co-led the work said: "Until now, how the typhoid toxin of Salmonella typhi contributed to infection had been a mystery. If we are to combat typhoid, understanding how the toxin causes breaks in the DNA of human cells and promotes infection is key and we hope this find will be the first step in developing new strategies to control typhoid, which affects some of the world's most vulnerable communities."

Currently, no routine diagnostics exist for typhoid, which is often confused in the clinic with deadly fevers such as Malaria and Dengue. As a consequence, patients receive delayed antibiotic therapy, which causes clinical complications. Better diagnostics will improve clinical diagnoses and enable faster treatment, while also helping researchers quantify the extent of typhoid in endemic settings, which is needed to convince governments to implement public health/vaccine programmes.

The work marks the first study involving the Healthy Lifespan Institute at the University of Sheffield. The Institute brings together 120 world-class researchers from a wide range of disciplines with the aim of slowing down the aging process and tackling the global epidemic of multimorbidity - the presence of two or more chronic conditions - in a bid to help everyone live healthier, independent lives for longer and reduce the cost of care.

The researchers now hope to further investigate how this discovery can be exploited to help us diagnose and treat typhoid as well as determine whether the RING phenotype is a signature of other diseases associated with DNA damage such as cancer.

ANN ARBOR--When fruit flies are exposed to a high sugar diet, key metabolites associated with brain health become depleted, according to a University of Michigan study.

This finding could tell researchers why behaviors that change with the internal energy state, such as food intake, learning and memory, and sleep, change on high-nutrient diets.

When our bodies metabolize food, that food is broken down into metabolites--small molecules that perform many functions in the body, including providing fuel to cells and activating or inhibiting enzyme production. The study, published in Nature Communications, examines how metabolites in the brains and bodies of fruit flies change as the flies transition between hunger and satiety.

Through the study, the researchers found that the flies' metabolic profiles change rapidly during the quick transition from hunger to satiety, with the flies' brains showing a larger change than their bodies. In particular, the high sugar diet lowered the levels the brain metabolites N-acetyl aspartate, or NAA, and kynurenine.

The alteration of metabolites could impact how quickly the fly senses satiety, causing it to eat more. In fact, U-M researchers previously found that an increase in a specific metabolite with a high sugar diet caused overeating and weight gain.

Although scientists aren't clear on the role of NAA in the brain, it appears to provide fuel for brain cells and balances osmolarity--or regulates cell volume--in the brain. Lower levels of another metabolite, kynurenine, which is produced in high levels during exercise, is associated with depression.

"What we found was a metabolic remodeling," said senior author Monica Dus, U-M assistant professor of molecular, cellular and developmental biology. "It wasn't just a gradual accumulation from an early to longer exposure, but by the seventh day on a high sugar diet, these fruit flies had a completely different metabolic profile."

Cancer cells also undergo this type of metabolic remodeling in order to fuel their growth, which is why diet may play a role in cancer treatment and a reason the Dus lab wanted to examine the shift of metabolites in the brain.

To examine how a high sugar diet affects the brains and bodies of fruit flies, the research team compared a group of fasting flies to a group of fed flies. In the fed flies, the researchers skipped giving them dinner, then fed them a breakfast of moderately sweet glucose jelly the next day.

The researchers mix the sugar jelly with blue or green dye, and after an hour, check the belly of the fly to make sure it's eaten. To make sure the animals have eaten their fill, the researchers put the flies on a lickometer covered with the glucose jelly. A lickometer is exactly what it sounds like: A meter that counts the number of times it has been licked.

Then, inside separate tubes, researchers freeze the sated flies as well as the group of fasting flies. This stops the metabolic process, so that researchers can look at what's going on in the flies' brains at the moment of satiety. The researchers shake the tubes, which shatters the fly. A sieve separates the fly's head, thorax, abdomen and legs. These parts were then sent to a company that uses mass spectrometry to measure the metabolites within the fly.

To help refine the list of metabolites in the flies, Alla Karnovsky, a research associate professor of computational medicine and bioinformatics at Michigan Medicine, created a tool called FlyScape. She based it on a previous tool she created for the analysis of human metabolomics data called MetScape. Like Metscape, Flyscape is open access: any researcher studying metabolites in fruit flies can use the software.

These tools help researchers look for patterns in metabolomics data. A researcher like Daniel Wilinski, a postdoctoral fellow in the Dus lab and first author of the manuscript, can input a list of metabolites found in her fruit fly subjects, as well as a list of genes from fruit flies, into Flyscape. The tool will produce visualizations of the metabolic networks of fruit flies.

"You can view the metabolites and genes that are changing between different conditions," Karnovsky said. "This helps us understand what biological processes are happening."

Co-author Peter Freddolino, assistant professor of biological chemistry and computational medicine and bioinformatics at Michigan Medicine, has worked with Dus on previous papers to study how a high sugar diet dulls the sense of taste in fruit flies.

"We examined what the changes in metabolites are that could be fundamentally perturbing the way that these cells were working," Freddolino said. "What this study tells us is what metabolomic pathways might be involved."

Ultimately, the study found that 20 metabolites, in addition to NAA and kynurenine, were impacted by sugar consumption. Next, says Dus, the research team plans to dial down into how changes in these metabolites impact the brain, altering food intake and affecting other conditions such as sleep, learning and memory.

Our sound environment is extremely dense, which is why the brain has to adapt and implement filtering mechanisms that allow it to hold its attention on the most important elements and save energy. When two identical sounds are repeated quickly, one of these filters - called auditory sensory gating - drastically reduces the attention that the brain directs to the second sound it hears. In people with schizophrenia, this ability to reduce the brain's response to identical sounds does not function properly. The brain, it seems, is constantly assailed by a multitude of auditory stimuli, which disrupt its attentional capacity. But the question is: Why? Neuroscientists from the University of Geneva (UNIGE), Switzerland, have been investigating the mechanism that lies behind this auditory sensory gating, which was previously unknown. Their results, published in the journal eNeuro, show that the filtering begins at the very beginning of the auditory stimuli processing, i. e. in the brainstem. This finding runs counter to earlier hypotheses, which held that it was a function of the frontal cortex control, which is heavily impacted in schizophrenics.

One of the main characteristics of schizophrenia, which affects 0.5% of the population, is a difficulty in prioritising and ranking surrounding sounds, which then assail the individual. This is why schizophrenia is diagnosed using a simple test: the P50. "The aim is to have the patient hear two identical sounds spaced 500 milliseconds apart. We then measure the brain activity in response to these two sounds using an external encephalogram," explains Charles Quairiaux, a researcher in the Department of Basic Neurosciences in UNIGE's Faculty of Medicine. "If brain activity decreases drastically when listening to the second sound, everything is okay. But if it's almost identical, then that's one of the best-known symptoms of schizophrenia."

Although widely used to perform such diagnostics, the functioning of this filtering mechanism - called auditory sensory gating - is still a mystery. Most hypotheses held that this brain property is provided by a frontal cortex control, located at the front of the brain. "This area of control is badly affected in people suffering from schizophrenia, and it's situated at the end of the brain's sound processing pathway," explains Dr Quairiaux.

The failure is situated at the base of sound processing

In order to test this hypothesis, the Geneva-based neuroscientists placed external electroencephalographic electrodes on mice, which were then subjected to the P50 test, varying the intervals between the two sounds from 125 milliseconds to 2 seconds. The results proved to be exactly the same as those observed in humans: there was a clear decrease in brain activity when listening to the second sound.

The scientists then placed internal electrodes in the cortical and subcortical auditory regions of the brain, from the brainstem to the frontal cortex - the pathway for processing sounds. The mice were given the P50 test a second time and, contrary to the initial hypothesis formulated by the scientists, the researchers observed that the drop in attention given to the second sound occurred already at the brainstem and not only at the cortical level, with a 60% decrease in brain activity. "This discovery means we're going to have to reconsider our understanding of the mechanism, because it demonstrates that the filter effect begins at the very moment when the brain perceives the sound!" points out Dr Quairiaux. And where does this leave people suffering from schizophrenia?

"We're currently carrying out the same study on mice with 22q11 deletion syndrome, a mutation that often leads to schizophrenia in humans, so we can see if the lack of a filter is situated in the brainstem, taking account of the new results we obtained," continues the researcher. And that does indeed seem to be the case! The first tests on "schizophrenic" mice revealed the total absence of a filter for the second sound at the brain stem. The source of one of the most common symptoms of schizophrenia is about to be discovered.

Women face discrimination and occupy fewer places in the higher reaches of the veterinary profession, even as they begin to outnumber men in the field.

Research conducted by Lancaster University Management School and Open University Business School, published in Veterinary Record, shows that sexism continues to be a big issue with clients, while managers fail to recognise or understand gender issues.

Women are increasingly dominating the profession, with 76% of vet school graduates female - but disproportionately few reach the higher echelons of practice, with their employment much more likely to be as an assistant than as a director or partner.

The researchers carried out 75 interviews with both male and female vets from across the UK, speaking to practitioners in junior and senior roles, aged between 25 and 63.

While the questions did not focus on gender-related issues, interviewees frequently raised the subject both directly and indirectly, with the prevailing perception of female vets synonymous with limited intellectual and physical strength and seen as subordinate to males in the profession. Clients are often explicitly sexist, insisting male vets treat their animals.

The team also found a widely held belief that women would not seek promotions as they only wanted to work part-time, a statement repeated both by those in power and also the victims of such a perception.

Co-author Professor David Knights, Distinguished Scholar in the Department of Organisation, Work and Technology at Lancaster University, said: "On the surface, it could appear that the trend for fewer women climbing the hierarchy is because they sacrifice career for family. But it is much more complicated than this stereotypical view implies.

"Many of the women we spoke to, especially those in their early career, reported experiences of clients - or even their own practices - treating them as having limited competence and credibility, thus threatening their professional identities. They were also automatically presumed to be potential mothers, and this was treated as problematic for long-term careers."

While many women with families opt for a partial exit from the veterinary profession through part-time work, the researchers found this only reinforced the established hierarchy of young women dominating the lower ranks and old men the senior ranks of the profession.

Those women who have children and/or go part-time are seen to have chosen family over careers and are often not taken seriously at the practice any more, no longer being considered for promotions

"Part of this must be due to the limited gender awareness of those men occupying the senior positions in practices," said report co-author Dr Caroline Clarke, of the Open University Business School. "As a result, women - or at least their career ambitions - become sacrificial lambs."

Among the interviewees, the team heard from one female farm vet whose client demanded a man come out to see her because she was not happy with the treatment she had delivered - even though the male vet then did the same thing. Another spoke of the need to prove herself to clients and starting at a disadvantage as a result.

"Such blatant sexism is rarely challenged by senior vets," added Professor Knights. "This is partly because they are oblivious to the problems, but also - even when they are aware - they fail to intervene for fear of upsetting clients who perpetuate the sexism. This lack of support can create a downward spiral, where women vets begin to doubt themselves, threatening their confidence early in their careers.

"Even when we came across example of senior vets who appeared to be sensitive to gender issues, there was often a reproduction of the chauvinistic attitudes being criticised, with one speaking of the need for female vets to use their charm to make up for a lack of physical strength.

"Veterinary medicine is still entrenched in a masculine culture. Both sexes subscribe to a narrative of females having to choose between a career or a family, a situation exacerbated by the culture of long working hours which militates against women who subscribe to the culture of caring, with these constraints giving the impression of a lower commitment to the organisation."

Despite their grievances, women are not challenging or disrupting the limitations in place or the masculine culture entrenched in veterinary practice. Instead, they tend to leave the profession or go part-time. The issues highlighted by the research are likely to come back to haunt senior vets and corporate managers since recruitment and retention is increasingly a serious problem that is exacerbated by the failure of the profession to see these gender issues as in need of attention.

The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 5th Vaccine Conference will hear that the risks of failing to vaccinate children may extend far beyond one specific vaccine, although currently the most urgent problem to address is the resurgence of measles.

Measles, a highly contagious infectious disease, is serious, causing fever, rash and other symptoms in most children and complications including pneumonia and brain inflammation. In 2018, across the globe measles killed approximately 1 in every 75 children infected with the virus, leading to over 100,000 deaths.

Furthermore, research by Assistant Professor Michael Mina, MD of Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health and Harvard Medical School, Boston, MA, USA and colleagues from his own and other groups suggests that infection with measles in unvaccinated children increases their risk of other, subsequent severe, non-measles infectious diseases in the 2-3 years following infection. Thus, after surviving measles, children may fall ill or die from other infections which they previously developed immunity to, but this immunity was erased by the measles virus.

This observation, backed by numerous studies (with the mechanism still being investigated) shows that when measles virus infects a person, it primarily infects a large proportion of the memory cells of the immune system. This results in so called immune-amnesia, whereby the immune system cannot remember some of the diseases it has fought in the past, thus exposing children to re-infection with these other diseases.

These findings would help explain the mysterious large drops in mortality of up to 50% following the introduction of measles vaccinations, even though prior to vaccines measles was usually associated with much less than 50% of childhood deaths. This has gone unnoticed in previous years because clinicians would not, for example, link a death from another infectious disease back to a measles infection that that child may have had two years earlier and that wiped away the child's immune memory for the other infecting pathogen.

"Prior to vaccination, measles infected nearly everyone. Because we now think that measles infections may erase pre-existing immune memory, by preventing measles infection through vaccination, we prevent future infection with other infectious diseases allowed back into the body by the damage done by measles," explains Dr. Mina. "The epidemiological data from the UK, USA and Denmark shows that measles causes children to be at a heightened risk of infectious disease mortality from other non-measles infections for approximately 2-3 years."

He continues: "Prior to vaccination, the incidence of measles from year to year could explain almost all of the variation in non-measles infectious disease deaths that occurred over multiple decades. Altogether, this suggests that measles may have been associated with as much as half of all childhood deaths due to infectious diseases prior to vaccination, and thus explaining the mysterious large drops in mortality seen following introduction of the vaccine."

He adds: "It may be that the only way for a child to recover from this immune-amnesia is if their memory cells 'relearn' how to recognise and defend against diseases they had known before, and they can do this through re-exposure to the pathogen or by re-vaccination against that particular infection."

However, it is this re-exposure to the other pathogens that pose the long-term risks following a measles infection. A recent epidemiological study led by Dr Mina's colleague, Dr Rik de Swart of the Department of Virosciences at Erasmus Medical Center in Rotterdam, Netherlands looked at the clinical outcomes of over 2,000 children infected with measles in the UK (see link below). In that study, they found that children were significantly more likely to require physician visits and had higher rates of antibiotic prescriptions for 2-5 years following measles. To mitigate these long-term effects, Dr Mina suggests "It might be reasonable to consider re-vaccination with other childhood vaccines following measles infection." However, he adds that "because many children who are infected with measles generally have not been vaccinated, whether because of [parental] refusal or are in settings that do not have access to vaccinations in the first place, this may not always be a viable option."

Thus - probably the most important conclusion of these fascinating studies is that prevention of measles by vaccination is crucial and high vaccination coverage is a fundamental step nowadays. However, in this symposium, Helen Johnson, Expert in Mathematical Modelling at the European Centre for Disease Prevention and Control (ECDC) Solna, Sweden and Dr Takis Panagiotopoulos of the National School of Public Health, Athens, Greece, will highlight that even when contemporary vaccination coverage is high, risk of infection may be concentrated in certain groups. Analysing data from Greece, they say that this heightened risk can be associated with age (low vaccine coverage from previous years) or social aspects (for example, barriers to access for the Roma population, and vaccine hesitancy for healthcare workers or other opinion groups).

The dangers of healthcare workers not being vaccinated are clearly highlighted by these data. "The risk of being infected, and of onwards transmission, is associated with the way people come into contact," explains Johnson. "Although only approximately 4% of cases were in healthcare workers, an individual case in this group was far more likely than any other to cause five or more secondary cases. In contrast, approximately 30% of cases were in Roma children aged 4 years and under, but each of these children caused, on average, only around one secondary infection."

Even if vaccination rates nationwide approach 95%, pockets of susceptible unvaccinated people, such as the Roma population or healthcare workers, may make outbreaks not only more likely but also considerably larger than would be expected from assessments of vaccination coverage alone. "The results highlight the imperative of maintaining high vaccination coverage at all subnational levels and in all population groups," explains Johnson.

Data from ECDC show that a large epidemic of measles has affected the EU/EEA in the past three years, with 47,690 cases reported between 1 January 2016 and 30 June 2019. Only eight countries -- Romania (14,712 cases), Italy (10,439), France (5,812), Greece (3,288 c), United Kingdom (2,412), Germany (2,240), Poland (1,874) and Bulgaria (1,295) -- were responsible for 88% of the cases in this period, but multiple cases occurred in each of the 30 countries that report data to ECDC.

The burden of measles in the EU/EEA is particularly high among infants and adults, the groups at the greatest risk of complications following infection. Notification rates are much higher in infants and children under 5 years than older age groups, however, a large proportion (39%) of cases during this period occurred in adults aged 20 years and above, reflecting immunity gaps due to historic failures to vaccinate in many countries. "Low uptake of vaccine in certain groups means that, even in countries with very high rates of vaccination coverage, re-establishment of measles is a concerning reality. It is tragic and unacceptable that children and adults continue to die from complications of measles, when safe and effective vaccines are readily available," concludes Johnson.

This ESCMID 5th Vaccines Congress, which will cover multiple vaccine-preventable diseases is taking place just one week after WHO announced that four European countries: the UK, Albania, Czech Republic and Greece: had all lost their previous 'measles-free' status due to confirmed endemic transmission in all four.

"Incidence of measles in the European Region increased in 2018 compared to previous years, and continues to escalate in 2019," says Dr Patrick O'Connor, Team Lead, Accelerated Disease Control Vaccine Preventable Diseases and Immunization for the WHO-EURO region, who is also speaking at this symposium.

He concludes: "Elimination of both measles and rubella is a priority goal that all countries of the WHO European Region have firmly committed to achieve. WHO urges health authorities to use every opportunity to reach children with routine vaccination, as well as to identify and close immunity gaps in adolescent and adult populations."

Professor Ron Dagan, Ben-Gurion University of the Negev, Beer-Sheva, Israel, the Chair of the Organising and Scientific Committee of the ESCMID 5th Vaccines Congress adds: "Measles is definitively an imminent danger worldwide that can be solved by aggressive vaccination policies."