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Breakthrough in designing a better Salmonella vaccine

image: UC Davis researchers have made a breakthrough in understanding which cells afford optimal protection against Salmonella infection -- a critical step in developing a more effective and safe vaccine against a bacterium that annually kills an estimated one million people worldwide. This image shows Salmonella (in red) invading human cells.

Image: 
Rocky Mountain Laboratories, NIAID, NIH

UC Davis researchers announce in the Proceedings of the National Academy of Sciences this week a breakthrough in understanding which cells afford optimal protection against Salmonella infection--a critical step in developing a more effective and safe vaccine against a bacterium that annually kills an estimated one million people worldwide.

Professor Stephen McSorley, interim director of the Center for Comparative Medicine, led a collaborative group of scientists from the University of Melbourne, Australia, the University of Connecticut and UC Davis. They evaluated the difference between circulating and non-circulating memory T cells in providing immunity to Salmonella infection in mice models.

"What everyone has been focused on in immunology, not just in addressing Salmonella, but all infectious diseases for the past 50 years or so, has been antibody and T cell responses," McSorley said. "What hasn't been realized until very recently is there are actually two different categories of T cells--those that circulate through tissues in the body and those that never move and are known as tissue resident or non-circulating memory cells."

Since non-circulating memory T cells were discovered, McSorley said there's been a rush in different disease models to understand whether they are important or not--in cancer and infectious diseases. It seems in some models they are very important; in others, they are less so.

"It's a new cell population we haven't looked at before and they're very effective so we need to learn more about them," McSorley said. "They may be part of the answer to developing vaccines against a variety of pathogens."

The team focused on these non-circulating memory T cells to better understand how well they protected against reinfection from Salmonella Typhi, a strain that causes life-threatening enteric fever commonly in Africa and parts of Asia. Other strains of Salmonella are capable of causing gastroenetritis or invasive non-typhoidal Salmonellosis (NTS), an emerging disease in sub-Saharan Africa. Enteric fever and NTS can be fatal in 20-25 percent of infected individuals without access to medical care.

The researchers transferred circulating and non-circulating memory T cells from mice previously vaccinated into naïve mice. Thanks to fluorescent markers, they were then able to track which of the T cells offered protection against Salmonella infection. They showed that vaccine-mediated protection requires a non-circulating population of liver memory cells that does not circulate through the rest of the body. The unexpected requirement for these liver memory T cells means that generating these cells will form the basis of future vaccines for typhoid and NTS.

Current Salmonella vaccines limited

NTS has really emerged in Africa in the last 10 years, McSorley said, mainly in young children, the elderly and HIV positive individuals--basically people with compromised immune systems. They get a strain that would normally cause gastroenteritis, but in these individuals, it causes systemic infection and can kill them.

"These forms of disease are really impactful for resource-poor communities in Asia and Africa where the vaccines are either nonexistent or terrible," McSorley said. "They are diseases of poverty."

Although there are two vaccines currently available for Salmonella, neither are practical for use in these countries and they only protect about 50 percent of people immunized.

"The goal of our lab is to understand the mechanisms of protective immunity in mice to learn tricks of the immune system and then develop a vaccine that could replicate that to use for kids and people who live in these areas," he said. "We found that you absolutely need these non-circulating T cells to protect against Salmonella. That's an important milestone because if you're going to make a vaccine, you have to know what you're trying to induce with that vaccine. Now that we know these forms of T cells exist and protect against Salmonella, the next goal is to try to develop synthetic ways to induce them to make a vaccine."

McSorley said they have some ideas about how to do that and that's where the next phase of their research is going--to try and take vaccine components in a mouse model to specifically focus on these non-circulating cells and see if they can induce them.

"If we can learn how to better induce them and if we can apply that to a new Salmonella vaccine, it should be more efficient at providing immunity than previous vaccines."

Credit: 
University of California - Davis

Some female termites can reproduce without males

Populations of the termite species Glyptotermes nakajimai can form successful, reproducing colonies in absence of males, according to a study published in the open access journal BMC Biology.

The findings by researchers at the University of Sydney, Australia and Kyoto University, Japan suggest that males are unnecessary for the maintenance of some advanced animal societies in which they previously played an active social role.

Toshihisa Yashiro, corresponding author of the said: "The complete loss of males from social insects has been previously reported only in ants and honey bees. Termite colonies were always found to have equal numbers of males and females, and to undergo sexual reproduction. Our paper is the first demonstration that termites can do away with males completely, and get along fine just with females."

The authors discovered populations of G. nakajimai with no evidence of any males in remote coastal areas of Japan. They compared the morphology of individuals from 37 colonies in these areas with those from 37 mixed-sex colonies found elsewhere in Japan. Queens in all-female colonies had empty spermathecae (an insect organ where sperm is stored after mating), whereas the queens in the mixed-sex populations had plenty of stored sperm. The eggs in the all-female colonies were all unfertilized.

Toshihisa Yashiro said: "Interestingly, we observed the occasional development of unfertilized eggs in the mixed-sex populations too. This suggests the ability to produce offspring from unfertilized eggs may have originated in mixed-sex ancestors and provided a potential pathway to the evolution of all-female colonies. We also found that all-female colonies had a soldier caste with a more uniform head size than their mixed-sex counterparts and fewer soldiers overall. This suggests that uniform female soldiers are more efficient at defense which may have contributed to the persistence and spread of the all-female colonies."

Further studies are required to find out if all-female colonies also occur in other termite species.

Credit: 
BMC (BioMed Central)

Violence in pre-Columbian Panama exaggerated, new study shows

image: One of two cases of healed blows to the cranium from the Playa Venado excavations. Most of the evidence of violence was interpreted by Harvard archaeologist, Samuel Lothrop based on body positioning in graves at the site. Smithsonian post-doctoral fellow, Nicole Smith-Guzmán, found no examples of trauma that occurred near the time of death among the skeletons in the collection.

Image: 
Nicole Smith-Guzmán, STRI

Buried alive. Butchered. Decapitated. Hacked. Mutilated. Killed. Archaeologist Samuel K. Lothrop did not obfuscate when describing what he thought had happened to the 220 bodies his expedition excavated from Panama's Playa Venado site in 1951. The only problem is that Lothrop likely got it wrong. A new evaluation of the site's remains by Smithsonian archaeologists revealed no signs of trauma at or near time of death. The burial site likely tells a more culturally nuanced story.

The "long-overdue" reexamination of the Playa Venado site, which dates to 500-900 A.D. and is located near the Pacific entrance to the Panama Canal, revealed no evidence of ritual killing, said Nicole E. Smith-Guzmán, post-doctoral fellow at the Smithsonian Tropical Research Institute (STRI). Lothrop's misinterpretations are likely due to the era of "Romantic archaeology," underdeveloped methods for mortuary studies and literal readings of Spanish accounts of indigenous peoples after European contact.

"We now realize that many of these Spanish chroniclers were motivated to show the indigenous populations they encountered as 'uncivilized' and in need of conquering," said Smith-Guzmán, adding that many accounts of sacrifice and cannibalism have not been confirmed by the archaeological record. "Rather than an example of violent death and careless deposition, Playa Venado presents an example of how pre-Columbian societies in the Isthmo-Colombian area showed respect and care for their kin after death."

The article, co-authored by STRI staff archaeologist Richard Cooke, was published in Latin American Antiquity.
But Lothrop's 1954 paper, "Suicide, sacrifice and mutilations in burials at Venado Beach, Panama," left its mark on the annals of Panamanian archaeology. It has been cited more than 35 times as evidence of violence, cannibalism or trophy decapitation. Some authors have used the paper to suggest Playa Venado is a mass burial site or a manifestation of conflict.

In defense of Lothrop, who was an archaeologist with Harvard University's Peabody Museum of Archaeology and Enthnology, bioarchaeology (the study of human remains from archaeological contexts) did not exist as a sub-discipline until two decades after his work concluded at Playa Venado. Today's practitioners also benefit from methods developed in the 1980s and 1990s.

Lothrop's careful documentation and preservation of remains made reevaluation possible. Remains from more than 70 individuals from Playa Venado are at the Smithsonian's National Museum of Natural History, sent there by Lothrop for osteological evaluation.

Upon examination, Smith-Guzmán found only wounds that showed signs of healing well before the individuals died, including blows to the head and a dislocated thumb. Various broken bones and disarticulated remains discovered by Lothrop more likely explained by normal processes of decomposition and secondary burial of remains, which is believed to have a common ancestor-veneration practice in pre-Colombian Panama.

Evidence suggests certain people's remains were preserved for long periods of time before being buried in ritual contexts. "At Playa Venado, we see a lot of evidence of adults being buried next to urns containing children, multiple burials including one primary and one secondary burial, and disturbance of previously laid graves in order to inter another individual in association," said Smith-Guzmán.

"The uniform burial positioning and the absence of perimortem (around the time of death) trauma stands in contradiction to Lothrop's interpretation of violent death at the site," said Smith-Guzmán, who also used evidence from other archaeological sites around Panama about burial rites as part of the investigation. "There are low rates of trauma in general, and the open mouths of skeletons Lothrop noted are more easily explained by normal muscle relaxation after death and decay."

Smith-Guzmán and Cooke's reassessment of the Playa Venado burials suggests that ideas about widespread violence in pre-Columbian Panama need to be reconsidered. The research is part of a larger, interdisciplinary site reanalysis that will be published by the Dumbarton Oaks Museum in Washington, D.C..

Smith-Guzmán's previous discovery of the first case of bone cancer in Latin America is featured on this month's Smithsonian Sidedoor podcast.

The Smithsonian Tropical Research Institute, headquartered in Panama City, Panama, is a part of the Smithsonian Institution. The Institute furthers the understanding of tropical nature and its importance to human welfare, trains students to conduct research in the tropics and promotes conservation by increasing public awareness of the beauty and importance of tropical ecosystems. STRI website. Promotional video.

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Reference: Smith-Guzmán, N.E., Cooke, R.G. 2018. Interpersonal Violence at Playa Venado (Venado Beach), Panama: A re-evaluation of the evidence. Latin American Antiquity

Credit: 
Smithsonian Tropical Research Institute

High-carbohydrates diet lead to weight loss, according to new study

Diets high in carbohydrates reduce body weight and body fat and improve insulin function in overweight individuals, according to a new study published in Nutrients.

In the 16-week randomized clinical trial, researchers with the Physicians Committee for Responsible Medicine placed participants in either a plant-based, high-carbohydrate, low-fat diet group or asked them to maintain their current diet. The plant-based diet group avoided all animal products and added oils and limited fat intake to 20-30 grams per day. There were no limits on calories or carbohydrate intake. The control group maintained their current diets, which included meat and dairy products. Neither group altered their exercise routines.

Total carbohydrate intake did not change in the control group, but increased significantly in the plant-based diet group, both as absolute intake and as a percentage of total calories. Participants focused on whole, complex carbohydrates from fruits, vegetables, whole grains, and legumes.

At the end of the trial, body mass index, body weight, fat mass, visceral fat volume, and insulin resistance decreased significantly in the plant-based diet group. There were no significant changes in the control group.

"Fad diets often lead people to fear carbohydrates. But the research continues to show that healthy carbohydrates--from fruits, vegetables, beans, and whole grains--are the healthiest fuel for our bodies," says lead study author Hana Kahleova, M.D., Ph.D., director of clinical research for the Physicians Committee for Responsible Medicine.

The study's results support previous research finding that a plant-based, high-carbohydrate diet can help with weight regulation and body composition and reduce the risk for type 2 diabetes. Another recent study published in The Lancet found that people who consume animal-based, low-carbohydrate diets have a shorter life expectancy, compared with those who consume more carbohydrates and/or more plant-based sources of protein or fat.

Complex carbohydrates are naturally rich in fiber--a nutrient found in plant foods that adds bulk to the diet without adding extra calories. Previous studies have shown that high-fiber diets are effective for weight loss and can help reduce the risk for type 2 diabetes, heart disease, and certain types of cancer.

The study has important implications, because more than 7 in 10 U.S. adults are considered overweight or obese. Approximately 30 million Americans have diabetes, while prediabetes affects 84 million more.

Credit: 
Physicians Committee for Responsible Medicine

One proposal for how to improve cancer research and care

The European Academy of Cancer Sciences (EACS), an independent advisory body of medical specialists and researchers, has issued a position paper encouraging the European Union and its member states to formally launch a mission to boost and streamline cancer research. Published in Molecular Oncology, a journal of the Federation of European Biochemical Societies, the goal is to increase the societal impact of research by decreasing cancer incidence, increasing cure rate, improving health-related quality of life, and developing cost-effective cancer prevention and therapeutic strategies.

Cancer is a group of complex diseases that places an increasingly heavy burden on society and healthcare systems. To address this challenge, the EU commission, national governments, research institutes, and hospitals must ensure that they coordinate their efforts. Significant advances can be made through an interactive continuum of cancer research, from innovative basic research to implementation and long-term follow-up of state-of-the-art evidence-based cancer care and prevention. This will require careful coordination between cancer research and healthcare across Europe through Comprehensive Cancer Centres. The position paper highlights specific areas where initiatives should be taken. The EACS emphasises the following 11 issues that will require further attention:

Support for high-quality basic and preclinical cancer research,

Creation of collaborative networks focussed on primary prevention,

Support for research in the area of early detection,

Support for translational research aimed at identifying new innovative therapeutic interventions,

Quality assurance of research environments and development of strategies to improve the infrastructures,

Establishment of collaborative networks with aligned diagnostic and treatment services,

Support for research that can assess the effectiveness of prevention, early detection, and clinical interventions,

Development of Open Science, Open Innovation, and Open to the World

Adoption of innovations by Healthcare Organisations,

Support for high-quality Big Data collections and intelligent use of these data,

Development of initiatives in the area of digital health.

To help address these issues, the EACS will prioritise areas of policy action, taking into consideration the urgent need to link research with healthcare systems as well as the opportunities that a cancer mission will bring to ensure that innovations will ultimately reach patients.

"Coordination of research, link to healthcare systems, and provision of evidence-based advice to inform policy will be crucial for boosting the societal impact of cancer research," said senior author Ulrik Ringborg, MD, PhD, of the Karolinska Institutet, in Stockholm, Sweden.

Credit: 
Wiley

NASA sees areas of strength in Tropical Storm Trami

image: At 8:45 a.m. EDT (1245 UTC) on Sept. 21, 2018, the MODIS instrument aboard NASA's Terra satellite looked at Tropical Storm Trami (28W) in infrared light. MODIS found coldest cloud top temperatures in two large areas, as cold as or colder than minus 80 degrees (yellow) Fahrenheit (minus 112 degrees Celsius). Surrounding them were powerful storms with cloud tops as cold as or colder than minus 70 degrees (red) Fahrenheit (minus 56.6 degrees Celsius).

Image: 
NASA/NRL

NASA's Terra satellite provided an infrared look at Tropical Storm Trami, located just over 100 miles from Guam on Sept. 21. Infrared data provides temperature information that showed two areas of the highest, coldest cloud tops and most powerful storms within the tropical storm.

NOAA's National Weather Service (NWS) in Tiyan, Guam said that a flash flood watch is in effect for all of Guam and the northern Marianas. A small craft advisory remains in effect until 6 a.m. CHST local time on Sunday, Sept. 23.

However, the Tropical Storm Watch for Rota, Tinian and Saipan has been canceled.  Because Tropical Storm Trami (28W) continues to move away from the Marianas the threat of damaging winds has ended.

At 2:20 a.m. EDT (0230 UTC) on Sept. 13, Moderate Resolution Imaging Spectroradiometer or MODIS instrument aboard NASA's Aqua satellite analyzed Hurricane Florence in infrared light. MODIS found coldest cloud top temperatures in two large areas. One was around the center of circulation and the other was in a thick band of thunderstorms wrapping into the low-level center. Those temperatures were as cold as or colder than minus 80 degrees Fahrenheit (minus 112 degrees Celsius). Surrounding them were powerful storms with cloud tops as cold as or colder than minus 70 degrees Fahrenheit (minus 56.6 degrees Celsius).

NASA research has found that cloud top temperatures as cold as or colder than the 70F/56.6C threshold have the capability to generate heavy rainfall.

On Sept. 21, Trami was located near latitude 15.3 degrees north and longitude 142.9 degrees east. That's about 175 miles west-northwest of Rota and about 180 miles northwest of Guam. Trami is moving northwest at 12 mph. It is expected to make a slight turn toward the west-northwest with little change in forward speed over the next 24 hours. Maximum sustained winds have increased to 40 mph. 28W is forecast to intensify through Saturday. Tropical storm force winds extend outward from the center up to 120 miles.

NWS issued a special weather statement for Micronesia that said areas of heavy showers and thunderstorms can be found near Trami and in the monsoon flow southwest of the storm. The westerly monsoonal flow across Yap State and the Republic of Palau will increase during the next few days. Showery weather and locally gusty winds are likely for Yap and Koror through this weekend. Sea and surf conditions may become hazardous at times.

Credit: 
NASA/Goddard Space Flight Center

TINY cancer detection device proves effective in Uganda testing

Ithaca, NY - Its name is an acronym used to convey its size, but researchers at Cornell Engineering and Weill Cornell Medicine are hoping their hand-held cancer detection device's impact in the developing world is anything but small.

About half the size of a lunch box, the Tiny Isothermal Nucleic acid quantification sYstem (or TINY) has shown promise as a point-of-care detector of Kaposi sarcoma-associated herpesvirus (KSHV) in resource-limited settings such as sub-Saharan Africa. Early testing has resulted in about 94 percent agreement with traditional methods, with results being generated in a matter of hours instead of weeks.

Developed by a team led by David Erickson, the Sibley College Professor of Mechanical Engineering, and Ethel Cesarman, M.D., professor of pathology and laboratory medicine at Weill Cornell Medicine, TINY met its goals in the first round of funding from the National Institutes of Health. The team is planning expanded testing over the next several years.

Results of the team's field testing of the device in 2017 in Uganda are detailed in the paper, "A Portable Device for Nucleic Acid Quantification Powered by Sunlight, a Flame or Electricity," published Sept. 11 in Nature Biomedical Engineering. Ryan Snodgrass, doctoral student in the Erickson lab, and Andrea Gardner, researcher technician at Weill Cornell Medicine, are first and second authors.

Kaposi sarcoma (KS) is a cancer that develops in lymph or blood vessels, and usually appears as lesions on the skin, inside of the mouth or internally. There are four types of the disease; epidemic, or AIDS-associated, KS is the most common in sub-Saharan Africa and is AIDS-defining. That means when someone with the HIV virus is diagnosed with KS, they officially have AIDS.

Early detection leads to better outcomes, but that's not always possible in the developing world, where pathological testing can take one to two weeks. "There's a problem with being able to diagnose it there," Erickson said. "A number of things look like KS ... and the time it takes for a traditional diagnosis, one to two weeks, makes it tough."

TINY has shown the ability to generate results in approximately 2½ hours.

Now in its third generation, TINY performs loop-mediated isothermal amplification (LAMP) for nucleic acid quantification. That requires heating the sample to 154 degrees, which necessitates a power source.

One of the main benefits of TINY: It can collect and store heat generated from electricity, the sun or even a Bunsen burner, and will function even during temporary power disruption, of which three occurred during testing in Uganda. TINY's power flexibility is important because in many sub-Saharan African countries healthcare facilities lack access to reliable electricity.

For the study, Erickson's team collected biopsy samples from 71 patients in Uganda suspected of having KS and tested the samples with TINY as well as via quantitative polymerase chain reaction (qPCR), the current standard for nucleic acid quantification. Agreement between TINY and qPCR was 94 percent (67 of 71), and the team showed that all disagreement stemmed from assay limitations and not TINY capability.

Not only can TINY be carried to remote locations for point-of-care use, it could also be valuable in clinics and hospitals where electric power can be unreliable. "Both applications can enable nucleic acid diagnostics to reach more of the population in [low- and middle-income countries]," the group concluded in its report.

"As a pathologist who knows how difficult it can sometimes be to diagnose KS," Cesarman said, "it is very exciting to collaborate with engineers that invented a brilliant new device that makes it so easy to support or discard a diagnosis of KS in less than three hours from the time a biopsy is taken."

Future work on TINY will include expanding testing to more locations in Africa, South America and the U.S., and developing a commercialization plan. The group has applied for patent protection through Cornell's Center for Technology Licensing.

Erickson and Cesarman began work on this device approximately five years ago. "Where we are now," Erickson said, "is beyond the best-case scenario I could have envisioned when I wrote the proposal."

And Snodgrass, who's been to Uganda twice testing TINY, said it's "very rewarding to build a device, take it there and see it used on real patients."

Credit: 
Cornell University

Most nations falling short of UN targets to cut premature deaths from chronic diseases

image: This is the probability of dying from NCD4 between 30 and 70 years of age.

Image: 
NCD Countdown 2030

People in the UK, US and China have a higher risk of dying early from conditions like cancer, heart disease and stroke than people in Italy, France, South Korea and Australia.

These are the findings of the most detailed global analysis of deaths from so-called non-communicable disease (NCDs) - chronic conditions including cancer, cardiovascular disease, chronic respiratory disease, and diabetes.

The research, led by Imperial College London, World Health Organization and NCD Alliance, reveals that a 30-year-old woman in the UK has a 9 per cent chance of dying from four key NCDs - cancer, cardiovascular disease (which includes heart disease and stroke), chronic respiratory disease and diabetes - before her 70th birthday, compared to a 12 per cent chance for a woman living in the US, and 6 per cent for a woman living in Japan. Meanwhile a 30-year-old man living in the UK has a 13 per cent chance of dying from an NCD before age 70, compared to 11 per cent for a man living in Switzerland, and 18 per cent for a man living in the US.

The analysis, published today in The Lancet, also revealed the majority of the world's nations - including the UK, US and China - look likely to fall short of the United Nations (UN) target for reducing the number of premature deaths from NCDs.

Professor Majid Ezzati, from Imperial's School of Public Health, who led the study, said: "Non-communicable diseases are the main cause of premature death for most countries. Poverty, uncontrolled marketing of alcohol and tobacco by multinational industries, and weak health care systems are making chronic diseases a larger danger to human health than traditional foes such as bacteria and viruses."

Too many people dying too soon

Non-communicable diseases kill nearly 41 million people a year, making up seven out of ten deaths globally, 17 million of these deaths are classed as premature (i.e. before the age of 70).

The new research is published ahead of a key UN meeting on NCDs next week. In 2015, the UN set the goal of a one-third reduction in premature deaths (between the ages of 30 and 70 years) from four key NCDs - cancer, cardiovascular disease, chronic respiratory disease, and diabetes - by the year 2030.

The group behind this research, who are collectively known as NCD Countdown 2030, warn that their findings suggest the UN target will be missed in all but 35 nations for women and 30 nations for men.

The study also reveals men and women in most countries around the world have a higher risk of dying prematurely from NCDs than from infectious diseases such as malaria or HIV.

US, UK and China falling short

The researchers analysed data on deaths from NCDs for more than 180 nations. Their findings revealed the lowest risks of dying early from NCDs were seen in high income countries, especially in South Korea, Japan, Switzerland and Australia.

But other high-income countries are lagging behind the leaders, including the UK (which ranks 17th for men, 27th for women), the US (53rd for men, 44th for women) and China (80th for men, 76th for women).

Overall, women in South Korea, Japan, Spain and Switzerland were least likely to die prematurely from the four key NCDs. The countries with the lowest risk for men were Iceland, Switzerland, Sweden and Norway.

In contrast, men in central Asia (Mongolia, Kazakhstan) and eastern Europe (Russia, Belarus) were among the most likely to die from the four key NCDs before the age of 70. For women, parts of sub-Saharan Africa (Sierra Leone, Côte d'Ivoire), Guyana, Afghanistan, Yemen and Papua New Guinea were among those with the greatest risk of premature death from the four key NCDs.

The study reveals that only 35 countries are on track to meet the UN target for women and only 30 countries for men.

Some of those countries on track to meet the UN target for both men and women include Denmark, New Zealand, Norway and South Korea, as well as Brazil, Iran and some of the high-risk eastern European countries. By comparison, the UK, Australia, France, Germany, India and China will fail to hit the target for both sexes.

The authors say if NCD deaths decline slightly faster in a further 50 countries (for women) and 35 countries (for men), they too would achieve the target.

According to the analysis, the situation is deteriorating or stagnating in 15 countries for women, including the US, and 24 for men.

Katie Dain, from the NCD Alliance, said: "We are sleepwalking into a sick future because of severely inadequate progress on non-communicable diseases. Post the UN High Level Meeting, NCD Countdown 2030 will assist in holding governments and donors accountable and help to ensure that the opportunity before us next week to renew, reinforce, and enhance commitments to reducing the burden of NCDs, translates the rhetoric into reality."

Solutions to help countries reduce deaths

Professor Ezzati explained: "While much of the world is falling short of the UN target to alleviate the burden of chronic diseases, dozens of countries could meet this goal with modest acceleration of already-favourable trends. This requires national governments and international donors to invest in the right set of policies."

Professor Ezzati added: "Treatment of hypertension and controlling tobacco and alcohol use alone can prevent millions of deaths from cancer, heart disease, stroke and other NCDs. But there is also a need for affordable high-quality care to diagnose and treat chronic diseases as early as possible."

The team points out the findings are limited by the available data, citing major gaps in the completeness and accuracy of data in some countries. They explain that improving death registration in countries could improve accuracy.

James Bennett, the lead author of the study from the School of Public Health, said: "It's important that international aid agencies and governments are held to account for their commitments to global targets for health. Improving the quality of health data from countries will help us identify which countries are performing best in reducing deaths from chronic diseases, as well as those that need additional help."

Regional summaries (data from 2016)

World

For women, the highest levels of premature mortality from four key NCDs - cancer, cardiovascular disease, respiratory disease and diabetes - were seen in some African countries such as Sierra Leone and Cote d'Ivoire. In these countries, 30-year-old women had a one in three chance of dying from these diseases before their 70th birthday.

The lowest risks of premature death in women were in South Korea and Japan, at 5 to 6 per cent chance.

For men, the highest levels of premature death from the four key NCDs were seen in central Asia, Eastern Europe and some Pacific Islands, for example in Mongolia, Kazakhstan, Russia, and Fiji. In these countries, 30-year-old men had a more than a one in three chance of dying from these four diseases before their 70th birthday.
The lowest levels were in Iceland, Switzerland, Sweden and Norway, where men had a 10 to 11 per cent chance.

The UK

30-year-old women in the UK had a 9 per cent chance of dying from four key NCDs before their 70th birthday, placing them at 27th lowest risk in the world and 19th lowest among 40 countries in Europe.

30-year-old men in the UK had a 13 per cent chance of dying from four key NCDs before their 70th birthday, placing them at 17th lowest risk in the world and 9th lowest in Europe.

The chance of dying from the four key NCDs declined in the UK at the 74th fastest rate in the world for women, and the 27th fastest in Europe (relative to the starting level in 2015).

For men, the rate of decline in the UK was 45th in the world and 25th in Europe.

Europe

For European women, the highest levels of premature mortality from four key NCDs were seen in Moldova and Ukraine (17 per cent and 16 per cent). The lowest levels were in Spain and Switzerland, with risk of 6 per cent and 7 per cent.

For European men, the highest levels of premature mortality from four key NCDs were seen in Russia and Belarus (37 per cent and 35 per cent). The lowest levels were in Iceland and Switzerland, with risk of 10 per cent and 11 per cent.

The US

30-year-old women in the US had a 12 per cent chance of dying from four key NCDs before their 70th birthday, placing them at 44th lowest risk in the world but the highest among all high-income nations, and worse than Vietnam, Turkey and Panama. There has been a small increase in risk of death from these diseases among American women since 2010.

30-year-old men in the US had a 18 per cent chance of dying from four key NCDs before their 70th birthday, placing them at 53rd lowest risk in the world but the highest among all high-income nation, and worse than Liberia, Mexico and Angola. There has been virtually no change in the risk of death from these diseases among American men.

Credit: 
Imperial College London

Mediterranean-style diet may lower women's stroke risk

Following a Mediterranean-style diet may reduce stroke risk in women over 40 but not in men - according to new research led by the University of East Anglia.

A new report, published today in the American Heart Association's journal Stroke, reveals that a diet high in fish, fruit, vegetables, nuts and beans, and lower in meat and dairy, reduces stroke risk among white adults who are at high risk of cardiovascular disease.

The study is one of the largest and longest-running efforts to evaluate the potential benefits of the Mediterranean-style diet in lowering the risk of stroke.

It shows that the diet may be especially protective in women over 40 regardless of menopausal status or hormone replacement therapy.

Researchers from UEA, the University of Aberdeen and the University of Cambridge collaborated to study the intake of key components of a traditional Mediterranean-style diet including high intakes of fish, fruits and nuts, vegetables, cereal foods and potatoes and lower meat and dairy consumption.

Over a 17-year period, researchers examined the diets of more than 23,000 participants and compared stroke risk among four groups ranked highest to lowest by how closely they adhered to a Mediterranean style diet.

Study participants (23,232 white adults, aged between 40 and 77) were from the EPIC-Norfolk study, the UK Norfolk arm of the multi-centre European Prospective Investigation into Cancer study.

In participants who most closely followed a Mediterranean-style diet, the reduced onset of stroke was:

17 per cent in all adults;

22 per cent in women; and

6 per cent in men (which researchers said could have been due to chance).

Lead researcher Prof Ailsa Welch, from UEA's Norwich Medical School, said: "This research shows us that following a Mediterranean-style diet rich in fish, fruits and nuts, vegetables and beans, and lower in meat and dairy, may reduce stroke risk for women over 40.

"But a healthy, balanced diet is important for everyone both young and old," she added.

"It is unclear why we found differences between women and men, but it could be that components of the diet may influence men differently than women.

"We are also aware that different sub-types of stroke may differ between genders. Our study was too small to test for this, but both possibilities deserve further study in the future."

There was also a 13 per cent overall reduced risk of stroke in participants already at high risk of cardiovascular disease across all four groups of the Mediterranean-diet scores. However, this was driven mainly by the associations in women who showed a 20 per cent reduced stroke risk. This benefit appeared to be extended to people in low risk group although the possibility of chance finding cannot be ruled out completely.

"Our findings provide clinicians and the public with information regarding the potential benefit of eating a Mediterranean-style diet for stroke prevention, regardless of cardiovascular risk," said study co-author Prof Phyo Myint, from the University of Aberdeen.

Researchers used seven-day diet diaries, which had not been done before in such a large population. Seven-day diaries are more precise than food-frequency questionnaires and participants write down everything they eat and drink over the period of a week.

Eduardo Sanchez, chief medical officer for prevention at the American Heart Association, who was not part of this study, said: "The American Heart Association recommends a heart-healthy and brain-healthy dietary pattern that includes a variety of fruits and vegetables, whole grains, low-fat dairy products, fish, poultry, beans, non-tropical vegetable oils and nuts and limits saturated fat, trans fat, sodium, red meat, sweets and sugar-sweetened beverages; this dietary pattern reduces risk factors and risk for heart disease and stroke.

"This study provides more evidence that supports AHA's recommendation."

Credit: 
University of East Anglia

Genomic dark matter activity connects Parkinson's and psychiatric diseases

image: Illustration depicting transcribed noncoding elements (TNE or enhancer RNAs) in the brain

Image: 
Clemens Scherzer, Brigham and Women's Hospital

Dopamine neurons are located in the midbrain, but their tendril-like axons can branch far into the higher cortical areas, influencing how we move and how we feel. New genetic evidence has revealed that these specialized cells may also have far-reaching effects, implicating them in conditions that range from Parkinson's disease to schizophrenia. Using a new technique known as laser-capture RNA seq, that involves cutting out dopamine neurons from a human brain section with a laser, investigators from Brigham and Women's Hospital and Harvard Medical School have cataloged more than 70,000 novel elements active in these brain cells. Their results are published this week in Nature Neuroscience.

"We found that a whopping 64 percent of the human genome - the vast majority of which is 'dark matter' DNA that does not code proteins - is expressed in dopamine neurons in the human brain," said Clemens Scherzer, MD, a neurologist and genomicist who directs the APDA Center for Advanced Parkinson's Disease Research and leads the Precision Neurology Program at BWH. "These are critical and specialized cells in the human brain, which are working sluggishly in Parkinson's disease, but might be overactive in schizophrenia."

Scherzer's team developed laser-capture RNAseq to precisely dissect out dopamine neurons from the brain and perform ultradeep RNA sequencing on human brain cells. From 86 post-mortem brains, the team was able to extract more than 40,000 dopamine neurons. While other groups have focused on protein-producing messenger RNA, Scherzer and colleagues wanted to catalog the cells' entire RNA content, which required taking a much deeper dive.

In total, they found 71,022 transcribed noncoding elements (so called TNEs). Many of these TNEs (pronounced "teenies") are active enhancers - sites that act as regulatory "switches" for turning on specialized functions for billions of neurons in the brain. Many of the TNEs the team unearthed are novel and had never before been described in the brain. Working with collaborators in England, Scherzer and colleagues tested several of the TNEs in preclinical models, including zebrafish, finding evidence that many were active in brain development.

Scherzer and first-author Xianjun Dong, PhD, who are also Principal Investigators at the Ann Romney Center at BWH, originally set out to study dopamine neurons to gain insights into Parkinson's but found that many of the genetic variants associated with schizophrenia, addiction and other neuropsychiatric diseases were also enriched in these elements.

"This work suggests that noncoding RNAs active in dopamine neurons are a surprising link between genetic risk, Parkinson's and psychiatric disease," said Scherzer. "Based on this connection we hypothesize that the risk variants might fiddle with the gene switches of dopamine-producing brain cells."

The team has also made an encyclopedia of RNA content for dopamine neurons publicly available so that other investigators can look up any protein-coding or noncoding target for biomarkers and therapeutics for Parkinson's and psychiatric diseases through the webportal http://www.humanbraincode.org.

Credit: 
Brigham and Women's Hospital

High gluten diet in pregnancy linked to increased risk of diabetes in children

A high gluten intake by mothers during pregnancy is associated with an increased risk of their child developing type 1 diabetes, suggests a study published by The BMJ today.

However, the researchers say that further studies are needed to confirm or rule out these findings before any changes to dietary recommendations could be justified.

Gluten is a general name for the proteins found in wheat, rye, and barley and is suggested to affect the development of type 1 diabetes. In animal studies, a gluten free diet during pregnancy almost completely prevented type 1 diabetes in offspring, but no intervention study has been undertaken in pregnant women.

To better understand the nature of this association, researchers led by Julie Antvorskov at the Bartholin Institute in Denmark in collaboration with researchers at Denmark's Statens Serum Institut, set out to examine whether gluten intake during pregnancy is associated with subsequent risk of type 1 diabetes in children.

They analysed data for 63,529 pregnant women enrolled into the Danish National Birth Cohort between January 1996 and October 2002.

Women reported their diet using a food frequency questionnaire at week 25 of pregnancy and information on type 1 diabetes in their children was obtained through the Danish Registry of Childhood and Adolescent Diabetes.

Average gluten intake was 13 g/day, ranging from less than 7 g/day to more than 20 g/day, and the researchers identified 247 cases of type 1 diabetes (a rate of 0.37%) among the participants' children.

After taking account of potentially influential factors, such as mother's age, weight (BMI), total energy intake, and smoking during pregnancy,they found that the child's risk of type 1 diabetes increased proportionally with the mother's gluten intake during pregnancy (per 10 g/day increase).

For example, children of women with the highest gluten intake (20 g/day or more) versus those with the lowest gluten intake (less than 7 g/day) had double the risk of developing type 1 diabetes over a mean follow-up period of 15.6 years.

This is an observational study, so no firm conclusions can be drawn about cause and effect. However, the researchers say this was a high quality study with a large sample size, and they were able to adjust for a number of factors that could have affected the results.

The mechanisms that might explain this association are not known, but could include increased inflammation or increased gut permeability (so-called leakiness of the gut), they write. However, more evidence is needed before changes to dietary recommendations could be justified, they conclude.

In a linked editorial, researchers at the National Institute for Health and Welfare in Finland, say further studies are needed "to identify whether the proposed association really is driven by gluten, or by something else in the grains or the diet."

The authors agree that it is too early to change dietary recommendations on gluten intake in pregnancy, but say doctors, researchers, and the public "should be aware of the possibility that consuming large amounts of gluten might be associated with an increased risk for the child to develop type 1 diabetes, and that further studies are needed to confirm or rule out these findings, and to explore possible underlying mechanisms."

Credit: 
BMJ Group

Study examines how heartfelt guilt affects individuals

For thousands of years, people have closely associated moral cleanliness with acts of physical cleanliness. A recent study published in the Australian Journal of Psychology explored this association by eliciting guilt, a threat to one's moral purity.

In the study, guilt was elicited by asking participants to remember personal actions that resulted in harm to others and that had yet to be repaired. Participants were then shown threat words intermixed with negative, positive, and neutral words followed by a surprise recall test. Participants were also asked to select a parting gift from several products or rate the desirability of such products. These included cleansing items (hand sanitizer and mouthwash) and merchandise neutral to the concept of cleansing (pencil and notepad).

Heartfelt guilt led to elevated arousal, enhanced memory of threat words, and biased preferences towards cleansing products.

"Guilt is a complex experience involving at least two chronologically ordered components: the experience of a threat to moral purity, which is likely to make people think of dangers, and one's defensive response to the threat, which is likely to activate the desire to cleanse," said co-author Dr. Maura A. E. Pilotti, of Prince Mohammad Bin Fahd University, in Saudi Arabia.

Credit: 
Wiley

Cardiovascular-related deaths higher for US Hispanics who live in counties with higher Hispanic populations

DALLAS, September 19, 2018 -- Hispanics living in the U.S. face more cardiovascular-related death in counties heavily populated by Hispanics than those living in more diverse areas, according to new research in Journal of the American Heart Association, the Open Access Journal of the American Heart Association/American Stroke Association.

A decade of national data showed that Hispanic ethnic density or communities with high proportions of Hispanics, was strongly associated with death from cardiovascular disease, such as heart attack or stroke, a finding that remained after adjusting for sociodemographic and healthcare factors and may be due to other unmeasured neighborhood or individual-level characteristics.

Looking at the bigger picture, Hispanics actually had lower cardiovascular death rates when compared with non-Hispanic whites (244.8 vs. 189.0 per 100,000). However, when evaluating varying densities of Hispanic populations at the county level, higher Hispanic population was associated with greater mortality from cardiovascular disease for both Hispanics and non-Hispanic whites, according to the researchers.

Hispanics are one of the largest and fastest-growing ethnic groups in the United States, currently accounting for an estimated 17 percent of the population, a number that is expected to reach 30 percent by 2050. They also experience a disproportionate burden of cardiovascular disease risk factors, including obesity, high blood pressure and type 2 diabetes.

To better understand the relationship between Hispanic population density and cardiovascular disease mortality, researchers analyzed data from 715 counties across the United States and looked at records for a total of 4,769,040 deaths, including 382,416 Hispanics and 4,386,624 non-Hispanic whites.

Overall, counties with higher Hispanic populations faced more economic disadvantages, a lack of access to quality health care, and language barriers. Among the researchers' findings:

Compared with counties that had the lowest Hispanic populations, those with the highest had 60 percent more Hispanic deaths from cardiovascular disease (215.3 vs. 134.2 per 100,000).

Counties with higher Hispanic populations were more likely to be lower-income with more families lacking education and living below the poverty line.

Counties with higher Hispanic populations had increased rates of uninsured individuals, fewer primary care physicians, and more residents with limited English proficiency.

Counties with higher Hispanic populations were more likely to be rural.

Counties with higher Hispanic populations were mostly located in the Southwestern United States, South Florida, and in a few regions in the Northeast.

The study is among one of the first to use recent national data to evaluate the impact of Hispanic population density at the county level on cardiovascular disease deaths.

"The finding that Hispanic population density is associated with increased cardiovascular mortality is noteworthy and challenges existing notions about the protective effect of cultural enclaves among Hispanics, or what's known as the 'Hispanic paradox,'" said lead study author Fatima Rodriguez, M.D., M.P.H., a cardiologist at Stanford University in Stanford, California. "Clinical and public health efforts should target cardiovascular disease prevention in counties where Hispanics live, design interventions outside of health care settings, and focus on improving neighborhood access to healthy food sources and physical activity."

Rodriguez said future studies should examine whether these findings are consistent across different Hispanic subgroups, and "need to further disentangle what neighborhood and individual-factors in areas where Hispanics live can be improved to reduce cardiovascular risk factors and mortality."

"This important study reaffirms that zip code matters. When one considers that Latinos in those higher-concentration counties were also more likely to be lower income, have lower education levels, have lower rates of insurance, and fewer available primary care doctors, the results are not so surprising." said Eduardo Sanchez, M.D., the American Heart Association's chief medical officer for prevention and chief of the Association's Centers for Health Metrics and Evaluation, who was not a part of this study. "Improving cardiovascular health and reducing cardiovascular disease mortality will take clinical approaches that increase health insurance rates and access to quality primary care as well as non-clinical, societal approaches to increase education levels and income, as well as approaches to reduce residential segregation."

Credit: 
American Heart Association

Cash, carbon, crude: How to make oil fields bury emissions

In February 2018, Donald Trump signed into law new tax credits that reward oil companies for capturing carbon dioxide and preventing it from entering the atmosphere - either by burying the gas underground or by pumping it into wells to boost production. These tax credits, which have bipartisan support, are encouraging for those who believe that trapping CO2 from the fossil fuel industry - though no substitute for deploying cleaner energy sources - could help combat runaway climate change while society remains reliant on oil, gas and coal.

Now, a Stanford University analysis published Aug. 15 in the journal Joule suggests another way the government could encourage the oil and gas industry to capture and store carbon. The article proposes a model for how relatively small government payments could pave the way for oil reservoirs to stash away more CO2 than their burned contents unleash.

"If you look at air transport, shipping, heavy-duty land-based transportation, these are uses of fossil fuels that are definitely expected to grow," said lead author Sally Benson, a professor of energy resources engineering at the School of Earth, Energy & Environmental Sciences (Stanford Earth). "As an insurance policy, getting everybody to contribute to solving this problem is really important, including the oil and gas industry."

Carbon in, oil out

When injected into reservoirs, carbon dioxide can help drive oil and profits from aging wells. The technique, known as carbon dioxide-enhanced oil recovery, has been in use since the 1970s. Oil companies using it today pump in about two-and-a-half tons of carbon for every barrel of oil produced. "When you do that, the emissions from burning the oil are almost identical to the CO2 you're putting in the reservoir," said Benson, who co-directs Stanford's Precourt Institute for Energy.

The problem is that most of the 65 million metric tons of CO2 used in these oil recovery projects each year comes from natural reservoirs - not refineries, power plants or other sources contributing to climate change.

In their analysis, Benson and co-author John Deutch, a professor emeritus at MIT, propose a cost-effective way of encouraging oil and gas companies to double the amount of carbon injected for every barrel of oil and to draw their CO2 from human-related sources. They say a 10-fold increase in the amount drawn from these sources could shrink the nation's climate emissions by as much as 9.5 percent - even when accounting for the additional oil extraction made possible by injecting all that carbon.

All of this could be done at surprisingly low cost, the researchers claim, if companies start out trapping CO2 from relatively pure streams, like those vented from ethanol and fertilizer plants. According to Benson, experience gained on these projects could then help to drive down the cost of capturing and treating CO2 from mixed emission sources, such as cement and power plants.

Lighting a fire

Benson and Deutch, who is a former head of the Central Intelligence Agency and deputy defense secretary, argue that government should encourage industry to prepare for a future with an economy-wide price on carbon emissions - in part by developing better carbon storage technology.

Doubling the amount of CO2 per barrel of oil compared to the standard practice today, as Benson and Deutch envision, would almost certainly be more expensive for operators. The new analysis suggests it would add at least $22 per ton of injected carbon in a hypothetical scenario where oil costs $100 a barrel.

"That's a lot of cost for an oil company," Benson said. "If one company does it and they don't all do it, then your products are just more expensive than the competition. People just buy the cheapest crude oil they can."

To overcome those costs and spur development of technology for carbon-negative oil recovery, the researchers suggest the government pilot test something called a reverse Dutch auction. Owners of new oil recovery projects would submit bids to the government specifying how much money they would want as a reward for carbon injection and how much CO2 they expect the project to ultimately sequester.

With this system, Benson and Deutch estimate it would cost the government about $25 per ton of carbon dioxide captured. If 30 projects earned that amount for a decade apiece, the program would trap 264 million tons of CO2, and government spending on the experiment would total $6.6 billion.

For comparison, the newly expanded tax credits offer $35 per ton of CO2 captured and put to use, or $50 per ton if the carbon is simply buried. According to Benson, her proposed pilot program could cost less and provide incentives for a wider variety of companies that may not benefit from a tax credit.

Credit: 
Stanford's School of Earth, Energy & Environmental Sciences

Tweaking cells' gatekeepers could lead to new way to fight cancer

image: Cells with the Tpr protein (top row) have fewer nuclear pores than cells without the protein (bottom row). The right column shows a close-up of the pore density, with many more pores appearing in the absence of Tpr (bottom left).

Image: 
Salk Institute

LA JOLLA--(September 18, 2018) If the cell nucleus is like a bank for DNA, nuclear pores are the security doors around its perimeter. Yet more security doors aren't necessarily better: some cancer cells contain a dramatic excess of nuclear pores.

Salk Institute researchers reported on September 18, 2018, in the journal Genes & Development that they have devised a way to manipulate numbers of individual nuclear pores--a breakthrough that may one day stop cancerous cells from proliferating out of control.

"Previously, we didn't have the tools to artificially increase nuclear pores," says lead author Martin Hetzer, who is also Salk's vice president and chief science officer. "Our study provides an experimental avenue to ask critical questions: What are the consequences of boosting the number of nuclear pores in a healthy cell to mimic those found in a cancer cell? Does this affect gene activity? Why do cancer cells increase the number of nuclear pores?"

Nuclear pores are essential elements of all cells that provide controlled ways to move cellular material in and out of a nucleus. In organisms ranging from fungi to mammals, individual cells possess these transport channels that mediate a thousand events per second. Individual nuclear pores are fashioned from multiple copies of 30 proteins known as nucleoporins. Hetzer and colleagues looked at the nucleoporin Tpr, which has been implicated in certain cancers.

The team showed, for the first time, that each of the transport channels within a cell is unique, and each cell nucleus possesses a specific number of nuclear pores. Next, the team used molecular methods to remove Tpr to see its effect on the number of nuclear pores, with a surprising result.

"Typically, when you 'knock down' or remove some of the proteins that make up the nuclear pore complex, the total number of nuclear pores goes down," says Asako McCloskey, first author of the paper and a Salk research associate. "Our surprising finding was that when we get rid of the nucleoporin Tpr, nuclear pore numbers went up dramatically."

"This is the first time that modifying a component within the transport channel has been shown to increase the number of nuclear pores," adds Hetzer.

This indicates that Tpr plays a role not in transport itself, but in regulating the assembly of nuclear pores. The knowledge could be crucial for future attempts to manipulate numbers of nuclear pores to treat disease. For example, cells with higher metabolic activity--such as stimulated thyroid follicular cells or aggressive tumors--have more nuclear pores per nucleus. Other research has shown that stopping cancer-related "cargo" proteins from being transported through the nuclear pores can lead to dramatic effects in cancer treatment. Targeting nuclear pores could also negate aggressive cancer's resistance to multiple drugs, as higher numbers of nuclear pores in tumor cells allow them to export chemotherapy out of the nuclei.

Next, the lab will use the new technique to pinpoint the effects of tweaking nuclear pore numbers in a variety of cell types.

Credit: 
Salk Institute