Culture

BOSTON - An analysis of three previous studies of children and young adults with attention-deficit hyperactivity disorder (ADHD) quantifies for the first time the extent to which stimulant treatment reduces the development of mood disorders, school problems, conduct disorders, substance use disorders and other problems. The study led by Massachusetts General Hospital investigators is being published online in the Journal of Adolescent Health.

"Our study documents that early treatment with stimulant medication has very strong protective effects against the development of serious, ADHD-associated functional complications like mood and anxiety disorders, conduct and oppositional defiant disorder, addictions, driving impairments and academic failure," says Joseph Biederman, MD, chief of the Pediatric Psychopharmacology and Adult ADHD Program at MGH and MassGeneral Hospital for Children. "In quantifying the improvement seen with stimulant treatment, it measures its potency in mitigating specific functional outcomes."

Previous studies of stimulant treatment for ADHD have had limitations, such as only investigating outcomes in boys or not calculating the magnitude of the protective effects of treatment. The current study determined the number needed to treat (NNT) statistic, often used to show the effectiveness of an intervention. As the title indicates, NNT reflects the number of individuals receiving a medication or other treatment needed to prevent a specific unwanted outcome - the lower the NNT, the more effective the treatment.

The investigators analyzed data from three separate studies they had previously published to calculate the NNT needed to prevent specific outcomes. Two of these were long-term, prospective studies of children with and without ADHD - one of boys, one of girls - some of those diagnosed with ADHD were treated with stimulants, some were not. The third study was a randomized, double blind study of young adults with ADHD that compared their performance on a driving simulation upon entering the study with their performance after six weeks of treatment with either a stimulant medication or a placebo. Participants in the long-term studies averaged age 11 upon study entry and 20 at follow-up, and the current investigation focused only on those with ADHD. Participants in the driving study were ages 18 to 26.

The NNTs for the outcomes of interest were found to be quite low:

three participants with ADHD needed to be treated to prevent one from repeating a grade or developing conduct disorder, anxiety disorders or oppositional-defiant disorder.

four participants with ADHD needed to be treated to prevent one from developing major depression or experiencing an accident during the driving simulation.

five participants with ADHD needed to be treated to prevent one from developing bipolar disorder, six to prevent one from smoking cigarettes, and ten to prevent one from developing a substance use disorder.

Adjustments for the sex of participants and several other factors did not change the impact of treatment on those outcomes, except that the protection against substance use disorders was stronger in younger participants.

"Now we have the evidence allowing us to say that stimulant treatment of ADHD prevents the development of several very serious functional outcomes," says Biederman, a professor of Psychiatry at Harvard Medical School. "However, the impact on other serious outcomes - such as post-traumatic stress disorder, traumatic brain injury, suicide risk and employment success - still needs to be investigated." (is your team planning any such studies?)

Knowing which direction to go in order to reach a food location or home is important for many animal species, including humans. For human foragers who travel long distances every day hunting and gathering, orientation skills are essential. Haneul Jang and her colleagues from the Max Planck Institute for Evolutionary Anthropology set out to study how the Mbendjele BaYaka people in Republic of Congo orient themselves in the dense rainforest. To this aim, the researchers conducted more than 600 pointing tests with 54 Mbendjele BaYaka men, women and children aged between 6 and 76 years, in which the participants were asked to point an out-of-sight target in more than 60 different rainforest locations (including the camp).

Jang and her colleagues found that the Mbendjele BaYaka are highly accurate at pointing to distant and out-of-sight target locations. The researchers found pointing accuracy was equally good in men and women. "Gender equality in the Mbendjele BaYaka population may result in Mbendjele women's long-distance foraging for fishing and hunting as do men. This might allow women and men to develop similar orientation abilities. Our results are consistent with previous studies that found no sex differences in orientation abilities in hunter-gatherer societies where both sexes actively travel away from home. Studies from various cultures suggest that sex differences in orientation abilities may indeed result from sex-specific mobility, and our results add to this growing body of evidence", says Jang, lead author of the study.

"In contrast to men and women in our society, where women may still be more likely to work at home or closer to home compared to men, we observed that Mbendjele men and women travel equally far from home, and it is therefore perhaps not surprising that they score equally well in orientation tasks. The results of our study confirm how important experience is for our cognitive development", says Karline Janmaat, main supervisor of the study.

Interestingly, Jang and her colleagues found that at around age six, Mbendjele BaYaka children already performed as accurately as adults in the pointing tests when the tests were conducted close to the camp. Moreover, the researchers found that when the sun was visible in the sky, children's pointing accuracy increased substantially, especially in more distant and less familiar areas. Adults, on the other hand, performed accurately throughout their range also on cloudy days. "Unlike the adults, who have a very good sense of direction in distant areas even if they cannot see the sun's position, the children make large pointing errors in less familiar areas when they cannot see the sun. However, if they can see the sun, children's performances improve considerably", says Jang. "The Mbendjele BaYaka people live in flat lowland rainforests where orienting oneself is challenging due to heavy vegetation and the absence of distant landmarks like mountain peaks. People who live in such an environment may need to start learning how to use the position of the sun to ascertain a direction from a very early age."

According to the authors, this study provides the first behavioural evidence for sun compass use in humans. "We know that bees can use the sun to navigate, but surprisingly there has been no scientific evidence yet that humans may have this skill, too, and that children may develop this skill by age six", says Janmaat. "Our study shows that there is still so much to discover and with a high level of urgency. All forests inhabited by human rainforest foragers in Congo have been sold to foreign companies, causing these people to lose not only their foraging grounds, but their intriguing navigation skills as well."

Previous studies showed that chimpanzees have excellent long-term memory abilities. However, little is known so far about their working memory abilities. To shed light on these abilities researchers presented chimpanzees with a task, in which they could search for food in a number of small, opaque boxes. The chimpanzees first watched how pieces of food were hidden in these boxes. Then the apes could start to search for the food items by pointing at these boxes one by one. If a chosen box contained food, the chimpanzees received this food reward. After each choice, the boxes were covered for 15 seconds.

To retrieve all of the food items chimpanzees needed to keep in mind, which boxes they had already searched for food. The researchers increased the difficulty of the task depending on the ability of each chimpanzee by increasing the number of boxes and by shuffling the boxes between each search. The study revealed key similarities between chimpanzee and human working memory: the best-performing chimpanzees remembered at least four items, one young chimpanzee more than seven items. They used both the appearance of the boxes as well as their position to remember their previous choices.

Humans typically perform worse in working memory tests if they need to do something in parallel. Likewise, if the chimpanzees had to perform a second, similar task in parallel, their performance declined. Differences in working memory ability between chimpanzees were stable over months. The most obvious difference between chimpanzees and humans was not the working memory capacity but the search strategies that humans typically employ to facilitate this task: chimpanzees did not come up with the idea to search the boxes in line from one side to the other.

This study demonstrates that chimpanzees, like humans, possess working memory abilities that allow them to keep track of a series of previous events or actions. Contrary to previous claims, chimpanzees' working memory capacity does not appear to be fundamentally different from the human capacity. "Our findings suggest that chimpanzees perform similar to seven-year-old children in an intuitive working memory task that does not rely on extensive training", says Christoph Voelter from the Max Planck Institute for Evolutionary Anthropology and the University of Veterinary Medicine Vienna.

EAST LANSING, Mich -- Scientists think that green algae are plants water-living ancestors, but we are not sure how the transition to land plants happened.

New research from Michigan State University, and published in the journal eLife, presents evidence that algae could have piggybacked on fungi to leave the water and to colonize the land, over 500 million years ago.

"Fungi are found all over the planet. They create symbiotic relationships with most land plants. That is one reason we think they were essential for evolution of life on land. But until now, we have not seen evidence of fungi internalizing living algae," said Zhi-Yan Du, study co-author and member of the labs of Christoph Benning, and Gregory Bonito.

Researchers selected a strain of soil fungus and marine alga from old lineages, respectively Mortierella elongata and Nannochloropsis oceanica.

When grown together, both organisms form a strong relationship.

"Microscopy images show the algal cells aggregating around and attaching to fungal cells," Du said. "The algal wall is slightly broken down, and its fibrous extensions appear to grab the surface of the fungus."

Surprisingly, when they are grown together for a long time - around a month - some algal cells enter the fungal cells. Both organisms remain active and healthy in this relationship.

This is the first time scientists have seen fungi internalize a eukaryotic, photosynthetic organism. They call it a photosynthetic mycelium.

"This is a win-win situation. Both organisms get additional benefits from being together," Du said. "They exchange nutrients, with a likely net flow of carbon from alga to fungus, and a net flow of nitrogen in the other direction. Interestingly, the fungus needs physical contact with living algal cells to get nutrients. Algal cells don't need physical contact or living fungus to benefit from the interaction. Fungal cells, dead or alive, release nutrients in their surroundings."

"Even better, when nutrients are scarce, algal and fungal cells grown together fend off starvation by feeding each other. They do better than when they are grown separately," explained Du.

Perhaps this increased hardiness explains how algae survived the trek onto land.

"In nature, similar symbiotic events might be going on, more than we realize," Du said. "We now have a system to study how a photosynthetic organism can live inside a non-photosynthetic one and how this symbiosis evolves and functions."

Both organisms are biotech related strains because they produce high amounts of oil. Du is testing them as a platform to produce high-value compounds, such as biofuels or Omega 3 fatty acids.

"Because the two organisms are more resilient together, they might better survive the stresses of bioproduction," Du said. "We could also lower the cost of harvesting algae, which is a large reason biofuel costs are still prohibitive."

Researchers at Tel Aviv University, led by Prof. Carmit Levy and Dr. Tamar Golan of the Department of Human Genetics and Biochemistry at TAU's Sackler School of Medicine, have discovered that fat cells are involved in the transformation that melanoma cells undergo from cancer cells of limited growth in the epidermis to lethal metastatic cells attacking patients' vital organs.

"We have answered a major question that has preoccupied scientists for years," explains Prof. Levy. "What makes melanoma change form, turning aggressive and violent? Locked in the skin's outer layer, the epidermis, melanoma is very treatable; it is still Stage 1, it has not penetrated the dermis to spread through blood vessels to other parts of the body and it can simply be removed without further damage.

"Melanoma turns fatal when it 'wakes up,' sending cancer cells to the dermis layer of skin, below the epidermis, and metastasizing in vital organs. Blocking the transformation of melanoma is one of the primary targets of cancer research today, and we now know fat cells are involved in this change."

The research was conducted in collaboration with several senior pathologists: Dr. Hanan Vaknin of Wolfson Medical Center, and Dr. Dov Hershkowitz and Dr. Valentina Zemer of Tel Aviv Medical Center.

The study was on published July 23 in Science Signaling and is featured on the journal's cover.

In the study, the researchers examined dozens of biopsy samples taken from melanoma patients at Wolfson Medical Center and Tel Aviv Medical Center, and observed a suspicious phenomenon: fat cells near the tumor sites.

"We asked ourselves what fat cells were doing there and began to investigate," adds Prof. Levy. "We placed the fat cells on a petri dish near melanoma cells and followed the interactions between them."

The researchers observed fat cells transferring proteins called cytokines, which affect gene expression, to the melanoma cells.

"Our experiments have shown that the main effect of cytokines is to reduce the expression of a gene called miRNA211, which inhibits the expression of a melanoma receptor of TGF beta, a protein that is always present in the skin," says Prof. Levy. "The tumor absorbs a high concentration of TGF beta, which stimulates melanoma cells and renders them aggressive."

Critically, the researchers have also found a way to block this transformation.

"It is important to note that we found the process reversible in the laboratory: When we removed the fat cells from the melanoma, the cancer cells calmed down and stopped migrating," adds Prof. Levy.

A trial of mouse models of melanoma yielded similar results: When miRNA211 was repressed, metastases were found in other organs, while re-expressing the gene blocked metastases formation.

In the search for a potential drug based on the new discovery, the researchers experimented with therapies that are known to inhibit cytokines and TGF beta, but which have never before been used to treat melanoma.

"We are talking about substances that are currently being studied as possible treatments for pancreatic cancer, and are also in clinical trials for prostate, breast, ovarian and bladder cancers," Dr. Golan said. "We saw that they restrained the metastatic process, and that the melanoma returned to its relatively 'calm' and dormant state."

"Our findings can serve as a basis for the development of new drugs to halt the spread of melanoma -- therapies that already exist, but were never used for this purpose," concludes Prof. Levy. "In the future, we are seeking to collaborate with drug companies to enhance the development of the metastatic melanoma prevention approach."

In an open-label study of women in southern and eastern Africa, a vaginal ring that is inserted once a month and slowly releases an antiviral drug was estimated to reduce the risk of HIV by 39%, according to statistical modeling. In addition, the study found that participants appeared to use the ring more in the open-label study than in a previous clinical trial. These and other results of the HIV Open Label Extension (HOPE) study were presented today at the 10th IAS Conference on HIV Science (IAS 2019) in Mexico City.

In 2017 alone, nearly 870,000 women and girls acquired HIV, according to UNAIDS. Currently available forms of HIV prevention for women are limited, and many women are unable to negotiate condom use with male sexual partners. The vaginal ring tested in the HOPE study, which continuously releases the anti-HIV drug dapivirine, was designed to be a discreet, long-acting HIV prevention option for women. The wearer replaces the product herself once every four weeks. The dapivirine vaginal ring is currently under regulatory review with the European Medicines Agency.

"Women need choices of HIV prevention tools that fit their needs and that they can initiate," said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health and the primary funder of the HOPE study. "With the invaluable contributions of thousands of study participants, the HOPE study has estimated the effectiveness of the dapivirine ring and examined its appeal to users. Additional efforts to develop HIV prevention options continue in the hope that one day, women will have a range of HIV prevention products from which to make an informed choice."

The Phase 3b HOPE study was a follow-on to the NIH-funded ASPIRE clinical trial. ASPIRE and a sister trial called The Ring Study demonstrated in 2016 that the dapivirine ring reduced the risk of HIV infection by roughly 30% in women ages 18 to 45 years and was well-tolerated. The goals of the HOPE study were to gather additional data on the safety of the dapivirine ring and new data on whether and how women used it knowing that the earlier trials had shown it was modestly effective.

The HOPE study began in 2016 and enrolled 1,456 former ASPIRE study participants at 14 sites in Malawi, South Africa, Uganda and Zimbabwe. The women were sexually active, HIV-negative and aged 20 to 49 years.

While the ASPIRE study participants did not know until the end of the trial whether they had received the dapivirine ring or a placebo ring, all women who enrolled in the HOPE study were offered the dapivirine ring. During their first three months in the HOPE study, participants attended monthly study visits where they could receive one new ring. Thereafter, they attended quarterly visits where they could receive three new rings, a schedule that more closely resembled how the ring might be distributed in a real-world setting.

Women could remain in the study regardless of whether they chose to accept the ring. Some 92% of participants accepted the ring at enrollment, and 90% accepted it at their first study visit. The proportion of participants who accepted the ring declined at each subsequent visit, falling to 79% at the 9-month study visit.

Although it was not possible to precisely quantify how much of the time participants wore the dapivirine ring in either the HOPE study or the ASPIRE trial, adherence appeared to be higher in HOPE than in ASPIRE. Adherence was assessed by measuring how much dapivirine was left in returned rings, since the dapivirine level declines when the ring is worn. The amount of dapivirine left in 90% of the rings returned by HOPE study participants indicated that those rings had been used for at least some of the prior month. In contrast, the amount of dapivirine left in 77% of the rings returned by ASPIRE study participants indicated that those rings had been used for at least some of the prior month. The ring is designed to be worn continuously throughout the month to provide effective protection.

The HOPE study participants became infected with HIV at a rate of 2.7% over the year of follow-up. Because the study lacked a concurrent control group receiving a placebo ring, investigators used a mathematical approach based on the ASPIRE placebo group to estimate what the HIV incidence in HOPE would have been had the women lacked access to the dapivirine ring. In this modeling exercise, the average HIV incidence was 4.4% over the year of follow-up. Based on these incidence rates, investigators estimate that the ring reduced the risk of acquiring HIV by 39% in the HOPE study. The study was not designed to determine the effectiveness of the ring.

Comparing the HOPE study population to the ASPIRE placebo group has important limitations. These include the fact that all participants in the HOPE study had previously completed the ASPIRE trial without acquiring HIV. This suggests that an aspect of their behavior other than use of the dapivirine ring, or characteristics of their sexual networks, may have contributed to protection from the virus.

Also known as MTN-025, the HOPE study was implemented by the NIH-funded Microbicide Trials Network (MTN). The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, both part of NIH, co-fund the MTN with NIAID.

The HOPE study was sponsored by the nonprofit International Partnership for Microbicides (IPM), which developed the dapivirine ring and provided it for the study. IPM conducted its own open-label study of the dapivirine ring called DREAM, which reported final results on June 13 at the South African AIDS Conference in Durban.

The HOPE study was led by Jared Baeten, M.D., Ph.D., a professor of global health, medicine and epidemiology at the University of Washington in Seattle; Thesla Palanee-Phillips, Ph.D., M.Sc., director of network trials and research center programs at the Wits Reproductive Health and HIV Institute in Johannesburg, South Africa; and Nyaradzo M. Mgodi, M.B.Ch.B., M.Med., a clinical pathologist and clinical research site leader at the University of Zimbabwe College of Health Sciences Clinical Trials Research Program in Harare.

"Women urgently need more options for HIV prevention that fit into their lives," said Dr. Baeten. "The results reported today show that some women may desire to use the monthly dapivirine vaginal ring, if available, to help protect themselves from HIV."

Pre-exposure prophylaxis, or PrEP, provides high levels of protection from HIV in women and men. PrEP involves taking daily oral tablets of the medication Truvada, which reduces the risk of HIV by more than 95 percent in people at high risk when taken as prescribed. However, taking a daily pill can present challenges for some populations.

In addition to the vaginal ring, NIH is investigating several other long-acting forms of HIV prevention that may prove to be safe and effective options for both women and men.

Among the confounding challenges of diagnosing and treating Alzheimer's disease (AD) is the fact that patients with asymptomatic and symptomatic versions of the degenerative condition may share similar neuropathological burdens but experience significantly different rates of cognitive decline.

In a new study, published July 23, 2019 in Cell Reports, a team led by researchers at University of California San Diego School of Medicine used the transcriptome -- the sum of all messenger RNA (mRNA) molecules expressed from genes -- to compare 414 study participants with clinically diagnosed and neuropathologically confirmed AD with an age-matched, non-demented control group from a community-based neuropathological study.

Their findings suggest that integrating protein interactions with gene perturbations can generate a comprehensive framework for characterizing alterations in the molecular network related to AD.

While familial AD has a strong genetic factor, the causes of sporadic AD (the most common form) are multiple and not completely known. Primary risk factors include age, gender and family history, but also include a variety of biological, psychological and social factors.

Much research has focused upon two key elements of AD pathology -- the accumulation of amyloid protein plaques and abnormal neurofibrillary tau protein tangles in the brain, which are thought to cause dysfunction and death of neurons. But scientists increasingly recognize the relevance and importance of other factors, such as inflammation, blood circulation problems and brain atrophy -- all of which "correlate with clinical symptoms of cognitive decline and have led to changes in diagnostic criteria during the last decade," wrote the authors.

The new study combined analyses of gene perturbations and protein interactions, said senior author Robert Rissman, PhD, professor of neurosciences at UC San Diego School of Medicine, director of the Biomarker Core for the Alzheimer's Disease Cooperative Study (ADCS) and director of the Neuropathology/Brain Bank and Biomarker Cores for the UC San Diego Shiley-Marcos Alzheimer's Disease Research Center, which ultimately identified functionally distinct composite clusters of genes revealing extensive changes in expression levels in AD. These clusters broadly corresponded to synaptic transmission, metabolism, cell cycle, cell survival and immune response -- all critical aspects involved in AD pathology.

"One of the big problems in AD research is identifying patients at risk at the right time," said Rissman. "Understanding the gene networks that may change in specific patient groups can help streamline clinical trials recruitment efforts and reduce costs and time to enroll trials. With the field shifting more and more toward pre-symptomatic disease, we need to expand our understanding of the molecular mechanisms that underlie the entire disease spectrum."

From searching for extraterrestrial life to tracking rainfall, non-experts are increasingly helping to gather information to answer scientific questions.
One of the most established hands-on, outdoor citizen science projects is the University of Washington-based Coastal Observation and Seabird Survey Team, COASST, which trains beachgoers along the West Coast, from California to Alaska, to monitor their local beach for dead birds.

With about 4,500 participants in its 21-year history and roughly 800 active participants today, COASST's long-term success is now the subject of scientific study in its own right. What makes people join citizen science projects, and what motivates people to stick with them over years?

A UW-led paper published in the July issue of Ecology and Society explores the interests and identities of participants who join and remain active in citizen science. Results could help other science projects aiming to harness the power of large teams.

Previous research led by the UW has shown that people who join online-based citizen science projects generally try it just once, and fewer than 1 in 10 remain active past one year. The rates for hands-on, in-person efforts are much higher: COASST, for example, has 54% of participants still active one year after joining.

But what separates those who stay from those who go? Years of responses to surveys from the COASST team's recruitment and engagement efforts provide a unique window on citizen science.

"I came to the UW to analyze a gold mine of social science datasets accumulated by COASST," said social scientist and lead author Yurong He, a postdoctoral researcher in the UW School of Aquatic and Fishery Sciences. "Over a four year period, hundreds of participants responded to survey questions about why they were joining - or continuing - with the program. This represents an unparalleled opportunity."

She analyzed answers to two freeform questions posed to project participants: "Why did you join COASST?" and "Why do you continue to be involved in COASST?" Some 310 new participants chose to answer the questions during their initial training. Another 623 seasoned participants, who had been involved for more than one year, completed a mail-in survey.

"People's memory can be a bit tricky," He said. "You may think that two or five years ago you had a particular motivation, but is that really so? With this study we can definitively answer the motivation question at two different times: at the moment of joining the program, just after they finish being trained, and once they have spent at least a year on the beach collecting monthly data."

The analysis shows that new participants wanted to be outdoors on the beach, learning about birds. Many listed their scientific degrees, previous occupations and birding expertise. But responses from longer-term contributors displayed a slightly different pattern: Although birds and beach remained dominant interests, seasoned volunteers were more likely to mention interests such as the desire to monitor and observe their beach, help in making scientific discoveries, and the importance of project data and results for environmental conservation. Moreover, their "science identity" became focused on their data-collection team and the project collective, rather than on their personal traits.

One important finding, He said, was the value of place. Volunteers often mentioned the importance of continuing to visit their beach even if they hadn't found any birds washed ashore after several months.

"We thought they would talk a lot about birds, and they did, but they actually talked more about the coastal environment, the beach and the ocean," He said. "Place was either equally important or even more important to them than birds."

Another surprising finding is the degree to which participants consider citizen science to be a social activity. Of the five tasks volunteers listed as most important in defining their work for COASST, two - "communicating project results" and "recruiting others to participate" - were social. The other three tasks were "collect data," "make measurements" and "enter data."

"Activities that help connect family members and friends, and provide opportunities to meet new people who share similar interests, can also be scientific in nature," He said. "COASST fulfills both science and social interests for coastal residents."

The study's conclusions based on the surveys included some take-home messages for organizers of hands-on citizen science efforts:

Long-term participants tend to be motivated by a project's mission and goals, and successful programs communicate scientific findings back to participants so that they can see their individual contribution as part of the big picture of project results.

Experienced participants focus on where they conduct their project activities, indicating that sense of place is important to volunteers.

Both new and long-term participants focused on their social interactions as a central part of project activities, suggesting that successful hands-on, citizen science combines high-quality scientific activity with building and maintaining social relationships.

It's long been known that people who suffer a major concussion can lose their sense of smell temporarily and also develop affective problems, such as anxiety and depression. Now scientists have found that's true even for people who get a minor concussion.

Falling off a bike with a helmet on, having a fender-bender in one's car, taking a tumble on the ski slopes, slipping on ice and hitting one's head - these kinds of minor accidents can provoke the same kinds of olfactory and anxiety problems, the researchers found.

In a study published in Brain Injury, an international team led by Université de Montréal neuropsychologists compared 20 hospital patients who had mild concussions to 22 who'd broken limbs but had no concussion. Within 24 hours of their accident, just over half of those with mild concussions had a reduced sense of smell, versus only 5 per of the patients with broken bones. A year later, although their sense of smell was back to normal, the first group of patients had significantly more anxiety than the control group.

"A lot of people will suffer a mild concussion at some point in their life, so realizing they have trouble smelling is the first step to telling their doctor about it," said lead author Fanny Lecuyer Giguère, who did the research as part of her doctoral thesis in neuropsychology supervised by UdeM associate professor of psychology Johannes Frasnelli. "It's important that patients report any loss of smell, because it's not something their general practitioner or emergency-room physician normally asks about."

Identifying the problem is a short step to getting personalized treatment, she added, with closer follow-up to see if the loss of smell and anxiety persist, indicating the severity of the injury. Physicians should also educate their patients so that they check whether symptoms crop up in the weeks following their accident, she said. "It's a question of raising awareness: the more people are told to watch for signs of olfactory loss and anxiety, the easier it will be for doctors to respond."

To test their capacity to identify smells, Lecuyer Giguère visited hospital patients in the alpine ski resort of Visp, Switzerland between December 2016 and February 2017. Almost all those with mild concussions had had a skiing accident. They were all seen within the first 24 hours following their accident, as were those with fractures but no concussion. With scented "Sniffin' Sticks' (felt-tip pens) to smell, they were asked to identify synthetic odours of roses, garlic, cloves and solvent, and more.

A year later, the patients were sent a follow-up questionnaire and a set of scratch-and-sniff booklets. By comparing the two groups of patients' results in the day following their injury and 12 months later, the researchers were able to determine that most who'd lost their sense of smell gained it back within six months of their accident.

What did not significantly diminish, however, were their symptoms of anxiety: thoughts that made them worry, difficulties to relax, and sudden feelings of panic. About 65 per cent of the concussed patients reported such symptoms.

Future studies should look at a larger sample of patients to better examine the association between anxiety and olfaction, the authors concluded.

A recent study of over 1,000 healthy women with no symptoms of urinary tract infections showed nearly 9 percent carried multi-drug resistant Escherichia coli strains in their guts.

This is of clinical concern because disease-causing E. coli bacteria can transfer from the digestive tract to the female urinary tract via the urethra, the urine duct, which is shorter and positioned differently in females than in males. The bacteria can then make their way into the bladder and other parts of the urinary tract.

More than a third of urine samples provided by those who had fluoroquinolone (Cipro) resistant gut E. coli tested positive for E. coli growth. Of those, nearly 77 percent were Cipro-resistant, and the clonal type of the bacteria matched the fecal sample.

Most of the pathogenic E. coli found belonged to the pandemic, multi-drug resistant ST131-H30R or ST1193 clonal groups that currently cause the majority of drug-resistant urinary tract and bloodstream infections. They were detected twice as frequently in the urine of people who had these specific strains in their gut, compared to other strains of E. coli in general.

In addition, the presence of ST ST131-H30R in the gut in this study was associated with older age.

The researchers also checked to see which participants might have had an antibiotic prescription during the study for any type of infection, including respiratory.

Three months after that earlier urine collection, urinary tract infections were diagnosed in nearly 7 percent of the 45 previously asymptomatic carries who consented to follow-up electronic medical record examination. The study participants were from the Puget Sound area.

"The two pandemic fluoroquinolone-resistant urinary tract pathogenic strains of E. coli found in the clinical specimens are superior gut colonizers and tend to persist there," noted the researchers. "They can also show up, at an unusually high rate, in the urine of healthy women who did not have a documented urinary tract infection diagnosis at the time of sample testing. Both phenomena appear to be interconnected."

The researchers pointed out that it has long been known that a patient's gut microbial flora often harbors urinary tract infection-causing strains. It was not certain whether pandemic, drug-resistant strains have distinct moorage patterns in the gut or lower urinary tract of healthy people.

The study was published in the Oxford University Press journal, Clinical Infectious Diseases.

The findings could have several clinical care and infection control implications, according to Evgeni V. Sokurenko, professor of microbiology at the University of Washington School of Medicine. He was the senior researcher on the study. Several other UW microbiology faculty and Kaiser Permanent Research Institute investigators in Seattle collaborated on the work. The lead researcher was Veronika L. Tchesnokova, of the UW medical school's Department of Microbiology.

The results suggest the specific multi-drug resistant E. coli strains detected in this study take up a much more prolonged residence in the gut than do some other resistant strains, and also can become present in the urine of healthy women without causing burning, urgency, blood in the urine or other warning signs of bacterial infection.

Sokurenko explained that knowing whether or not multiple drug resistant strains are present in a woman's gut could help predict the resistance profile of a subsequent clinical infection. Efforts to get rid of the pandemic E. coli strains in the carriers gut could reduce their rate of multiple drug resistant infections, and perhaps protect their household or other contacts as well.

Sokurenko also said medicine might need to revisit the clinical significance of finding bacteria in the urine, even without symptoms, during this pandemic of multiple antibiotic resistant strains of E. coli, because those strains could put the carriers at risk for a difficult-to-treat bacterial illness.

Fluoroquinolones are the most often prescribed drugs for urinary tract infections. Despite efforts to limit its use, strains resistant to this category of antibiotic are flourishing and spreading globally, according to the researchers.

The superior ability of the two pandemic strains, ST131-H30R and ST119, to take up long-term residence in people's guts may have contributed to their rapid global spread, the researcher surmised. They can be sustained and passed among healthy individuals even in the absence of antibiotic use, which can upset the microbial makeup of gut flora.

This study, the researchers concluded, highlights the likely physiological reasons behind the pandemic of these resistant E. coli strains. It also points out the value of determining female patients' carrier-status to predict future resistant infections, and the need to re-think the clinical significance of bacteria present in the urine without symptoms, especially as these pandemic strains can be superbugs: highly pathogenic to the urinary system and treatment resistant.

Sokurenko has patent applications for detecting E. coli strains and is a major shareholder in ID Genomics

RMIT University researchers have used data from mobile phone accelerometers - the tiny sensors tracking phone movement for step-counting and other apps - to predict people's personalities.

RMIT University computer scientist Associate Professor Flora Salim said previous studies had predicted personality types using phone call and messaging activity logs, but this study showed adding accelerometer data improved accuracy.

"Activity like how quickly or how far we walk, or when we pick up our phones up during the night, often follows patterns and these patterns say a lot about our personality type," said Salim, a leading expert in human mobility data.

Physical activity is proven to have a strong correlation with human personality. Therefore, researchers analysed physical activity features from different dimensions like dispersion, diversity, and regularity.

Key findings from the study:

People with consistent movements on weekday evenings were generally more introverted, while extroverts displayed more random patterns, perhaps meeting up with different people and taking up unplanned options.

Agreeable people had more random activity patterns and were busier on weekends and weekday evenings than others.

Friendly and compassionate females made more outgoing calls than anyone else.

Conscientious, organized people didn't tend to contact the same person often in a short space of time.

Sensitive or neurotic females often checked their phones or moved with their phones regularly well into the night, past midnight. Sensitive or neurotic males did the opposite.

More inventive and curious people tended to make and receive fewer phone calls compared to others.

Study lead author and RMIT University PhD student, Nan Gao, said the potential applications from this research were exciting.

"There are applications for this technology in social media with friend recommendations, online dating matches and targeted advertising, but I think the most exciting part is what we can learn about ourselves," said Gao.

"Many of our habits and behaviours are unconscious but, when analysed, they tell us a lot about who we really are so we can understand ourselves better, resist social pressure to conform and to empathize with others. Most importantly, being who we truly are can make our experience of life richer, more exciting and more meaningful."

"In Ancient Greece there is a saying about knowing yourself as the beginning of wisdom, applications like this can really help to reveal who we are to ourselves."

The results were analysed in accordance with the Big Five personality traits, which are:

Extraversion: how energetic, sociable and talkative you are.

Openness: how curious and inventive you are.

Agreeableness: how friendly and compassionate, rather than suspicious and hostile, you are to others.

Conscientiousness: how organized, efficient and careful you are.

Neuroticism: how nervous and sensitive, rather than confident and secure, you are.

Bottom Line: The U.S. Preventive Services Task Force (USPSTF) recommends screening for hepatitis B virus (HBV) infection in pregnant women at their first prenatal visit. The USPSTF routinely makes recommendations about the effectiveness of preventive care services and this statement is a reaffirmation of its 2009 recommendation. Screening for HBV infection during pregnancy identifies infants who are at risk of acquiring this infection from their mothers before or after birth. Children infected with HBV during infancy or childhood are more likely to develop chronic infection.

(doi:10.1001/jama.2019.9365)

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

Note: More information about the U.S. Preventive Services Task Force, its process, and its recommendations can be found on the newsroom page of its website.

PHILADELPHIA - Brain imaging of 40 U.S. government personnel who experienced a host of neurological symptoms after possible exposure of an unknown source while serving in Cuba revealed significant differences in brain tissue and connectivity when compared to healthy individuals, according to a new report from researchers at the University of Pennsylvania's Perelman School of Medicine. The findings are published today in JAMA.

"The areas implicated in the patients' brains, namely the cerebellum as well as the visuospatial and auditory networks, align with the neurological symptoms that were observed in the patients," said lead author Ragini Verma, PhD, a professor of Radiology and head of the DiCIPHR (Diffusion and Connectomics in Precision Healthcare Research) imaging lab at Penn. "These differences persisted even when people with some history of brain injury were excluded from the analysis."

In 2016, U.S. government personnel serving in Havana, Cuba, and their family members began to report a variety of neurological symptoms, including difficulty with concentration and memory, dizziness, visual issues, and balance problems. The symptoms were linked to sudden, intensely loud noises heard in their homes and hotel rooms, which State Department officials later referred to as a "sonic attack" or "directional phenomena," though the specifics of the alleged event remain unsolved. After initial examinations, the patients were sent to Penn's Center for Brain Injury and Repair for evaluation, treatment, and rehabilitation in the summer of 2017, under the direction of center director and study co-author Douglas H. Smith, MD, the Robert A. Groff Professor of Teaching and Research in Neurosurgery.

A 2018 JAMA report published by Penn researchers documented the neurological symptoms that 21 patients who had reported exposure to the mysterious phenomena in Cuba experienced. Summing up these findings, Smith said that the symptoms were, "similar to those found in persistent concussion syndrome, yet there was no evidence of blunt head trauma."

As part of the investigation into their signs and symptoms, the patients also underwent advanced neuroimaging with multimodal magnetic resonance imaging (MRI) at Penn, prior to receiving any comprehensive rehabilitation treatment. This retrospective analysis compared the brain images of 40 potentially-exposed personnel to 48 healthy individuals who were not exposed and did not demonstrate these signs and symptoms.

The group-based analysis, published in the new 2019 JAMA study, used various computational tools to examine structural, diffusion, and functional MRI images, finding statistically significant differences in brain volume, tissue properties, and connectivity between the patients and healthy control group. There was reduced white matter volume in the affected patients, along with a pattern of differences in measures of water diffusion in the tissue. The imaging also revealed lower functional connectivity in the visuospatial and auditory subnetworks. Notably, differences in tissue volume, water diffusion, and connectivity were found in the cerebellum, the part of the brain responsible for performing voluntary tasks, such as walking and writing.

"The cerebellar findings in this neuroimaging study are notable, given that a number of the patients evaluated exhibited abnormalities in balance and the coordinated movement of the eyes, both of which are associated with cerebellar dysfunction in the brain," said study co-author Randel Swanson, DO, PhD, an assistant professor of Physical Medicine and Rehabilitation at Penn.

According to Verma, the pattern of differences found in this study do not resemble imaging-based investigations of any other pathology, like concussion and traumatic brain injury.

"These findings may represent something not seen before," Smith said.

Verma likened the brain to a highway system, comprising roads (white matter) and traffic. Structural MRI provides information about the size of the roads, while diffusion imaging gives insight into the road conditions and how they are connected. An injury to the brain could contribute to a deterioration in the condition of the roads (reflected in white matter differences), leading to an alternate traffic pattern (altered functional connectivity). Therefore, Verma said, a multimodal investigation is essential to see a more complete picture of the injury. As the brain recovers, while the traffic pattern may go back to normal, the overuse of some roads may lead to wear and tear, or compensatory changes in the brain.

"It's hard to tell where the problem started; the brain differences observed could be an immediate effect of the brain injury, or it could a compensatory effect of the recovery process," Verma said. "It's very difficult to say, especially with a retrospective, heterogeneous study, where people were included at various times after potential exposure. The important thing is that we did see differences at the group level."

A Mediterranean-style diet in pregnancy does not reduce the risk of overall adverse maternal and offspring complications, but may reduce weight gain during pregnancy and the risk of gestational diabetes, according to a new study published this week in PLOS Medicine by Shakila Thangaratinam of Queen Mary University of London, UK, and colleagues.

A Mediterranean-style diet is defined by high intake of nuts, extra virgin olive oil, fruits, vegetables, non-refined grains and legumes; moderate intake of fish; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat. In the new ESTEEM study, researchers randomized 1252 pregnant women with metabolic risk factors from five inner city UK hospitals. 627 were assigned to a Mediterranean-style diet, and were given mixed nuts and olive oil, and participated in three face-to-face sessions as well as follow up phone calls to reinforce dietary goals. 625 women were assigned to a control group and received dietary advice per UK national guidelines.

Women in the intervention group consumed significantly more nuts (adjusted OR 6.8, 95% CI 4.3-10.6), more extra virgin olive oil (aOR 32.2, 95% CI 16.0-64.6), increased their consumption of fish, white meat and pulses, and decreased their consumption of red meat, butter, margarine and cream. There was no significant reduction in the odds of overall maternal or offspring outcomes with the Mediterranean-style diet. However, there was a reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47-0.91), and this benefit was consistently observed when ESTEEM data were combined with those of similar trials (OR 0.67, 95% CI 0.53-0.84). Women in the ESTEEM intervention group gained, on average, 6.8 kilograms in weight compared to 8.3 kilograms gained in the control group.

"Future studies should assess the effect of in utero exposure to Mediterranean-style diet, particularly to nuts and olive oil, on childhood obesity, allergy and asthma, and on mother's future risk of type 2 diabetes," the authors say.

Current concentrations of fine particulate matter pollution, which mostly meet the national ambient air quality standard, are still associated with mortality and loss of life expectancy in the US, with larger impacts in poorer counties, according to a study published July 23 in the open-access journal PLOS Medicine by an international team of researchers from the Center for Air, Climate, and Energy Solutions led by Majid Ezzati of Imperial College London, UK.

Exposure to fine particulate matter pollution (PM2.5) is hazardous to health, and reducing PM2.5 is likely to lower mortality, especially from cardiorespiratory diseases. Yet there is not only resistance to more stringent control of PM2.5, but also attempts to roll back current standards. In the new study, Ezzati and colleagues set out to directly estimate the health and longevity impacts of current PM2.5 concentrations, and the benefits of reductions from 1999 to 2015, nationally and at county level, for the entire contemporary population of the contiguous United States. To do so, they used vital registration and population data with information on sex, age, cause of death and county of residence, as well as statistical models to directly estimate mortality and life expectancy loss.

Even though reductions in PM2.5 since 1999 have lowered mortality in the great majority of counties, PM2.5 pollution in excess of the lowest observed concentration (2.8 μg/m3) was responsible for an estimated 15,612 deaths (95% credible interval 13,248-17,945) in females and for 14,757 deaths (95% credible interval 12,617-16,919) in males. These deaths would lower national life expectancy by an estimated 0.15 years (95% credible interval 0.13-0.17) for women and 0.13 years (95% credible interval 0.11-0.15) for men. The life expectancy loss due to PM2.5 was largest around Los Angeles and in some southern states, such as Arkansas, Oklahoma and Alabama. At any PM2.5 concentration, life expectancy loss was, on average, larger in counties with lower income than in wealthier counties. According to the authors, further lowering PM2.5 pollution is likely to benefit the health of the entire US population, and lower health inequalities.