Culture

Advances in genetic testing offer new insights to parents who have a child with a rare but serious form of epilepsy, epileptic encephalopathy (EE), found in one of about every 2,000 births and characterized by developmental disabilities as well as horrible seizures.

New ways of sequencing the human genome mean geneticists and genetic counselors have much more to say to parents who wonder if future children might carry the disease, says Dr. Heather Mefford, associate professor of pediatrics (genetic medicine) at University of Washington School of Medicine and Deputy Scientific Director of the Brotman Baty Institute for Precision Medicine, co-senior author of findings published this week in the New England Journal of Medicine.

These advances offer insights for all of us because they are part of the growing study of mosaicism - the fact that many of us do not in fact have just one genome in us. We are what scientists call mosaics - bunches of cells that may have different genotypes buried deep within us.

"A mosaic mutation happens some time after fertilization when cells are dividing, which requires copying all of the DNA. If one of those cells makes a copying error, that introduces a mutation. All the cells that come from that cell will carry the same mutation. So you end up with a mosaic pattern where some cells have the mutation and some cells don't. That's the mosaic," Mefford said.

The fact that, say, 10 percent of your cells scattered throughout your body might be different than other cells may be completely unimportant. But if 10 percent of your sperm or oocytes have the mutation, that could be a big problem if that mutation affects the brain development of the child.

A big question from any parent of a child with EE is, What are the odds that our other children might have this condition? For decades, parents whose child had epilepsy were told there's a 1 to 5 percent chance that other children might inherit the mutation. This was based on clinical evidence - the numbers of reoccurrences physicians saw in the clinic.

But armed with more precise testing, the geneticists found parental mosaicism that wasn't easily detected before in about 10 percent of families, putting these families at higher risk of passing the mutation to another child. What this means in practical terms is that this small group probably accounts for most of the reoccurrences. For some parents, there's good news: if this parental mosaicism was not detected, your odds of having another such child with epilepsy could be much less than 1 percent.

"We have the technology to pick out mosaic cells in a sea of otherwise normal cells. The percentage of families where we can identify mosaicism in the parent is higher than most of us thought it would be. While the overall recurrence risk (across all families) is about 1 percent, for those families where we can find the mosaic mutation in the parents, it's not a 1 percent risk. It's much higher than that. And we now have the tools to help give them that information, and help them with better family planning and decision-making down the road," Mefford said.

"Our study focused on patients with severe epilepsy. But the finding that 10 percent of the parents have mosaicism may actually apply to a broad range of other disorders, including autism and intellectual disability," Mefford added.

Use of certain anticholinergic drugs - that help to control involuntary muscle movements for conditions such as Parkinson's disease - is associated with an increased risk of dementia, finds a UK study published by The BMJ today.

The study is the largest of its kind to date and the findings prompt the researchers to say that clinicians should avoid long term prescribing of some anticholinergics to patients aged 45 and over.

Anticholinergic drugs block chemical signals to the brain that control muscle movements. They are often used for conditions linked to involuntary muscle movements, such as urinary incontinence and Parkinson's disease, as well as for depression, chronic lung disease (COPD) and asthma.

Several studies have reported associations between use of anticholinergics and future cognitive decline and dementia, but it is not clear whether this is due to the drugs themselves or the underlying conditions for which they were prescribed.

So a research team led by George Savva at the University of East Anglia, set out to estimate the association between duration and level of exposure to different classes of anticholinergic drugs and subsequent dementia.

They analysed data from the UK's Clinical Practice Research Database for 40,770 patients aged 65 to 99 years who were diagnosed with dementia between April 2006 and July 2015. Each case patient was matched to up to seven control patients of similar age and sex, but without dementia.

Drugs were scored according to their anticholinergic activity using the Anticholinergic Cognitive Burden (ACB) scale. An ACB score of 1 was classed as possibly anticholinergic, while a score of 2 or 3 was definitely anticholinergic.

Daily doses of each drug were then compared for both cases and controls over an exposure period of 4 to 20 years before a diagnosis of dementia.

A total of 14,453 (35%) cases and 86,403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 during this period.

After taking account of potentially influential factors, the researchers found that definite anticholinergic antidepressants, antiparkinson drugs, and drugs to treat urinary incontinence (ABC score of 3) were linked to increased dementia risk up to 20 years after exposure.

However, no increased risk was found for drugs with possible anticholinergic activity (ACB score of 1) - and for anticholinergic gastrointestinal or respiratory drugs (ACB score of 3).

Other antidepressants (mainly selective serotonin reuptake inhibitors) with an ACB score of 1 were linked to dementia, but only close to the time of prescription, which the researchers say is unlikely to represent a direct (causal) link.

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the authors outline some limitations, such as possible misclassification of dementia cases and a lack of information on depression severity. Nevertheless, the study was large and was able to account for several potentially influential factors.

They suggest that the association "could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia" and they call for further research into the effects of specific drug classes.

In the meantime, they say clinicians "should continue to be vigilant with respect to the use of anticholinergic drugs, and should consider the risk of long term cognitive effects, as well as short term effects, associated with specific drug classes when performing their risk-benefit analysis."

In a linked editorial, Professor Shelly Gray at the University of Washington and Professor Joseph Hanlon at the University of Pittsburgh, say this research "raises important issues about the best way to summarise anticholinergic burden for future research."

In the meantime, they agree that anticholinergics in general should be avoided in older adults. "Specifically, for most highly anticholinergic drugs, non-pharmacological and pharmacological alternatives are available and should be considered," they conclude.

A University of Cincinnati geology student is helping NASA determine whether life existed on other planets.

Doctoral candidate Andrew Gangidine is working with UC geology professor Andrew Czaja to develop a marker for ancient bacterial life on Mars. The research could help scientists put to rest one of our most fundamental mysteries.

"We're trying to answer the question: How rare is life in the universe?" Gangidine said.

Czaja, an assistant professor in UC's McMicken College of Arts and Sciences, serves on a NASA advisory committee that will decide where on Mars to send the next remote-controlled rover. Among other objectives, the rover will look for evidence that life once existed on the red planet. The advisory committee has narrowed the list of landing-site candidates to three and will recommend a finalist later this year.

Meanwhile, Gangidine is studying microbial life in silica hot springs to come up with a useful indicator of life on Mars. For the past two years, he has conducted fieldwork in the geyser basins of Wyoming's Yellowstone National Park to examine what elements are associated with bacteria that live in these geothermal pools.

"We want to remain objective. Some people think there has to be life on Mars," Gangidine said. "Others think there certainly isn't life on Mars. And either side has a good chance of being correct. Both have valid arguments. Which is why if we go there and don't see anything, it won't be 'mission fail.'"

Gangidine presented his research April 25 at the Second International Mars Sample Return conference in Berlin, Germany.

Today, we know that life cannot exist on Mars, at least not on its dry surface. Solar radiation split most of its surface water into its elemental parts nearly 3 billion years ago when the red planet lost its protective magnetic field.

But scientists are debating whether life might exist somewhere deep underground, among pockets of water trapped around geothermal areas similar to Yellowstone's geysers.

Finding evidence of life on Mars is surprisingly complicated.

If Mars ever sustained life, it's possible that it was wiped out when most of its atmosphere vanished in the solar wind, Czaja said.

So NASA scientists must be prepared to look for fossil evidence of bacterial life dating back that far. Gangidine said the good news is that similar fossils of early bacterial life more than 3.5 billion years ago have been found on Earth. This makes him optimistic that if similar life ever existed on Mars, NASA has a chance of finding a fossil record of it.

"We can look at life being preserved in these silica deposits today. We have evidence of this happening throughout geologic time," Gangidine said. "What we're trying to do is catch fossilization as it happens. What happens to the microbes themselves? And what happens to the trace elements we think are associated with them while they're alive?"

To unearth clues about ancient life on Mars, geologists look to hot springs such as those found in America's first national park.

Gangidine and his colleagues need permits to collect samples in the park's backcountry. But exploring the geyser basins can be tricky and dangerous. A tourist died in 2017 after falling into one of the basin's boiling pools while hiking off-trail.

"These things really can strip the flesh off your bones," Gangidine said. "At the bottom of hot springs we study you see skulls of bison and other animals that were unfortunate enough to wander too close."

Gangidine's team includes an experienced backcountry field researcher, UC postdoctoral fellow Jeff Havig who is now with the University of Minnesota. They pick their way carefully across the caldera. Sometimes, they can see where a bison's hoof has broken through the thin crust to reveal steaming mud.

The geology work takes them across "quaking bogs," a thin layer of peat and grass covering deep shifting mud. Gangidine was walking alongside a colleague on one such hike when he sank above his knees in the treacherous mire.

"Luckily, that place wasn't super hot. But I was walking just a foot away from someone else. The ground can really change quickly," he said. "When we go into these settings, we have to be very careful."

Boiling acid and lava-like mud aren't the only hazards for researchers in the geyser basins. They also have to be careful not to spend too long around the steam vents, which contain a mix of gases such as carbon dioxide, hydrogen sulfide and methane that can asphyxiate a person under the right conditions.

The U.S. Geological Survey documented this phenomenon in 1888 in part of the park nicknamed "Death Gulch," a natural depression between two steep hills where toxic gases bubble up from Cache Creek. Harvard University geologist T.A. Jaggar Jr. returned to the area in 1899 and found six bears, an elk and various small animals that died apparently after succumbing to the toxic fumes.

But even in the fresh air, the gas rising from the ground can have a cumulative effect, Gangidine said.

"These hot springs emit a lot of gases you don't want to breathe in. They bind to the hemoglobin that carries oxygen through your body. Breathing that in, you get very fatigued," Gangidine said.

"That's why we try to schedule a day out of the field for every three days we work in the field. If you're there for four days, you can really feel like a zombie. It's really hard to think, hard to move."

As a biology undergraduate at UC, Gangidine worked with UC biology professor Dennis Grogan to examine microbial life called extremophiles that live in hostile places such as Yellowstone's acidic or alkaline hot springs. Now as a geologist, Gangidine is studying the fossils these hardy single-celled creatures leave behind.

"Hot springs make silica deposits that preserve life really well," Gangidine said. "When left exposed on a planet's surface, it doesn't crystallize and doesn't metamorphose. So these samples should be relatively well preserved if we find them."

In UC professor Czaja's geology lab, Gangidine peers through a microscope at slides he prepared from chunks of Yellowstone silica he took from a mountainous steam cone geyser.

The bacterial filaments from samples taken at the top of the geyser are full of color. But the older samples, some perhaps thousands of years old, are colorless, even if they hold their shape. So for more clues about this basic form of life, Gangidine subjects the bacterial samples to elemental analysis using a secondary ion mass spectrometer. The analysis renders the elements in vivid color: deep yellows, reds and greens representing chromium or gallium perhaps associated with the bacterial life.

If Gangidine finds a correlation between the concentrations and spatial distributions of particular elements and the bacteria, it might serve as a biosignature that scientists can use to identify past life on Mars.

"The reason we chose gallium is it's not known to be associated with life. But when we look at the fossilized bacterial samples, we find it, so there must be something going on," Gangidine said. "Do the bacteria store certain elements preferentially as opposed to what you would find elsewhere in these rocks?"

Gangidine is working with researchers in Australia, home to some of the world's oldest fossils, some dating back 3.5 billion years.

"If I want to create a biosignature, I have to prove that it persists throughout time," Gangidine said. "It exists in these relatively younger samples. But does it exist in these ancient samples, too? That will be crucial to figure out."

Gangidine also plans to build an artificial hot spring in a lab aquarium using similar elements found in geysers. By introducing a super-saturation to the water, the excess silica will precipitate much the same way it does in nature. Then he can add trace chemicals associated with life and study what happens in a miniature world absent of life.

"To prove we found a biosignature, we have to prove the signature doesn't occur without life," he said.

"Gallium is the one we were surprised by," Czaja said. "It is associated with silica near the bacteria but isn't in the bacteria."

Like Gangidine, Czaja got his start in the sciences by studying biology before pursuing a career in paleontology.

Czaja's NASA advisory committee will meet in October to decide where on Mars they would like to send the rover among the three preferred destinations. The rover is tentatively slated for launch in July or August of 2020, arriving on Mars about seven months later.

"NASA tends to like to go new places to push the frontier. Geologists like to go back to the same places over and over to ask new questions," Czaja said.

The rover will collect samples in sealed containers for shipping back to Earth in a later mission. So it could be many years before geologists such as Czaja and Gangidine know whether their hunches about where best to look for life on Mars were correct.

Helping to frame a question that you may never live to see answered is one of science's most selfless pursuits, Czaja said.

"One thing I like about these NASA missions is the long-term thinking and planning," he said. "People working on these projects now may never see the results. But they're still willing to put in the work because it's such a fascinating question."

The Mars 2020 mission will not be a failure if scientists find no evidence of life. Quite the contrary, Gangidine said.

"If we find it, we can say maybe life is not that rare among planets," Gangidine said. "But if we don't find life in places that would be the most ideal and best preserved candidates, then maybe life is pretty rare."

But if NASA does find evidence of life on Mars, that might suggest that sparking life from a primordial soup isn't so extraordinary after all. And the first question will be how life on Mars compares to life on Earth, Czaja said. Was there a common ancestor?

"Maybe we're all Martians," Czaja said.

Any claim about the existence or absence of life on Mars will be subjected to worldwide scrutiny and skepticism. Czaja said researchers must be prepared to provide a wealth of evidence to fortify their findings.

"It's not nearly enough to find something that looks like a bacterial cell," Czaja said. "There are nonbiological things that could look like that. But if you have a cascade of traits -- this and this and this added together -- it's hard to explain it any other way except for life."

INDIANAPOLIS - The largest and most detailed study of the long-term impact of anticholinergic drugs, a class of drugs commonly prescribed in the United States and United Kingdom as antidepressants and incontinence medications, has found that their use is associated with increased risk of dementia, even when taken 20 years before diagnosis of cognitive impairment.

An international research team from the US, UK and Ireland analyzed more than 27 million prescriptions as recorded in the medical records of 40,770 patients over age 65 diagnosed with dementia compared to the records of 283,933 older adults without dementia.

The researchers found greater incidence of dementia among patients prescribed anticholinergic antidepressants, anticholinergic bladder medications and anticholinergic Parkinson's disease medications than among older adults who were not prescribed these drugs.

Dementia increased with greater exposure to anticholinergic medications.

"Anticholinergic Medication and Risk of Dementia: Case-control Study" is published in BMJ (formerly the British Medical Journal) an international peer-reviewed medical journal.

"Anticholinergics, medications that block acetylcholine, a nervous system neurotransmitter, have previously been implicated as a potential cause of cognitive impairment," said Regenstrief Institute and Indiana University Center for Aging Research investigator Noll Campbell, PharmD, MS, a co-author of the new BMJ study. "This study is large enough to evaluate the long-term effect and determine that harm may be experienced years before a diagnosis of dementia is made." Dr. Campbell is also an assistant professor of pharmacy practice at Purdue University College of Pharmacy.

"These findings make it clear that clinicians need to carefully consider the anticholinergic burden of their patients and weigh other options," said study co-author Malaz Boustani, M.D., MPH, a Regenstrief Institute and IU Center for Aging Research investigator. Dr. Boustani is the founder of the Indiana Clinical and Translational Science Institute's IU Center for Health Innovation and Implementation Science and the Richard M. Fairbanks Professor of Aging Research at IU School of Medicine.

"Physicians should review all the anticholinergic medications - including over-the-counter drugs - that patients of all ages are taking and determine safe ways to take individuals off anticholinergic medications in the interest of preserving brain health," Dr. Boustani said.

The study, which was led by the University of East Anglia and funded by the Alzheimer's Society, both in the UK, utilized data from the Clinical Practice Research Datalink which includes anonymized diagnosis, referral and prescription records for more than 11 million patients from 674 primary care practices across the UK. The data is broadly representative of the UK population in terms of age, sex and ethnicity.

"This research is really important because there are an estimated 350 million people affected globally by depression. Bladder conditions requiring treatment are estimated to affect over 13 percent of men and 30 percent of women in the UK and US," said study lead researcher George Savva, PhD, visiting researcher at University of East Anglia's School of Health Sciences.

"We don't know exactly how anticholinergics might cause dementia," said study co-author Chris Fox, MD, professor of clinical psychiatry at UEA's Norwich Medical School and a consultant psychiatrist. "Further research is needed to understand possible reasons for this link. In the meantime, I strongly advise patients with any concerns to continue taking their medicines until they have consulted their doctor or pharmacist."

Study co-author Ian Maidment, PhD, senior lecturer in clinical pharmacy at Aston University in the UK, said: "With many medicines having some anticholinergic activity, one key focus should be de-prescribing. Clinical staff, patients and carers need to work together collaboratively to limit the potential harm associated with anticholinergics."

Patients undergoing emergency surgery who are treated by older surgeons (aged 60 or over) have slightly lower death rates in the first few weeks after their operation than patients treated by younger surgeons (aged less than 40) within the same hospital, finds US study published by The BMJ today.

There was no evidence that death rates differ between male and female surgeons.

If the results are causal, the researchers say that for every 333 of these patients who undergo surgery in the US, one fewer death would occur if quality of care was the same between younger and older surgeons.

Despite strong interest in improving the quality of surgical care, the relationship between surgical characteristics - especially age and sex of surgeons - and patient outcomes is not well understood.

So a research team led by Yusuke Tsugawa at UCLA in California, set out to investigate whether patient mortality differs based on age and sex of surgeons.

They analysed the operative mortality rate (defined as death while in hospital or within 30 days of surgery) of Medicare patients aged 65-99 years who underwent one of 20 major emergency surgical procedures at US acute care hospitals between 2011 and 2014.

After adjusting for a range of patient, surgeon and hospital characteristics that could have affected the results, they compared operative mortality according to surgeon age and sex.

A total of 892,187 patients were treated by 45,826 surgeons with an overall operative mortality rate of 6.4% (56,803).

The researchers found that patient mortality was slightly lower for older surgeons than for younger surgeons within the same hospital (6.6% for surgeons aged less than 40, 6.5% for surgeons aged 40-49, 6.4% for surgeons aged 50-59, and 6.3% for surgeons aged 60 or over), but did not differ meaningfully between male and female surgeons.

When they analysed the data by both surgeon age and sex, patient mortality declined with surgeon age for both male and female surgeons, with female surgeons in their 50s showing the lowest operative mortality across all groups.

Operative mortality did not differ between male and female surgeons by patient illness severity or for individual procedures. And there was no evidence that mortality differed by surgeon age or sex for non-emergency (elective) procedures.

Previously, the researchers found worse outcomes among patients treated by older hospital physicians, which they attributed to practice changes since training, and possibly poor adherence to guidelines. In contrast, these new findings suggest improved surgical skills with extra years in practice.

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the findings may not be generalisable to other outcomes, such as patient experience or complication rates, they explain. Nevertheless, the study was large, and was able to account for a wide range of potentially influential factors.

As such, they conclude: "Our finding that younger surgeons have higher mortality suggests that more oversight and supervision early in a surgeon's career may be useful and at least warrants further investigation. Equivalent outcomes between male and female surgeons suggest that patients undergoing surgery receive high-quality care irrespective of surgeon sex."

In a linked editorial, Natalie Coburn and colleagues based in Toronto say the researchers "demonstrate clear variation in patient outcomes, identifying opportunities to improve care."

However, they warn that even objective measures are insufficient to address systemic bias. "We must learn to recognise and reduce the implicit biases that each of us inherently holds," they write. "Surgical care will improve faster when we embrace and foster teamwork, communication and diversity within our field."

A new systematic review of available evidence appearing in Nutrition Reviews indicates that consuming protein supplements with meals may be more effective at promoting weight control than consuming supplements between meals in adults following a resistance training regimen.

It is well established that consuming dietary protein proximate to resistance-type exercise sessions promotes a positive net protein balance during post-exercise recovery. Protein supplements are available in ready-to-drink, powdered, and solid form and are marketed for different outcomes such as weight gain, weight loss, and weight management. However, for each outcome, the promoted timing of protein intake varies. Protein supplements designed to augment weight gain or support weight stability are promoted for consumption between meals. Protein supplements either with meals or as meal replacements are often recommended for ingestion to promote weight loss.

Consuming protein supplements between meals may decrease compensatory eating behaviors, thereby increasing energy intakes and body weight. Conversely, adults undergoing a resistance training program and consuming protein supplements twice daily with meals may compensate for the protein supplement by decreasing their self-chosen diet. Consequently, the timing of protein supplementation may be of particular importance, depending on the desired body weight and body composition outcome.

The impact of timing the consumption of protein supplements relative to meals has not previously been evaluated systematically. In the newly published review of the literature, the researchers investigated whether the existing research studies support consuming protein supplements between meals, vs. with meals, to differentially change body composition in adults who initiate resistance training regimens.

Researchers here assessed 34 randomized controlled trials with 59 intervention groups. Of the intervention groups designated as consuming protein supplements with meals vs. between meals, 56% vs. 72% increased their body mass, 94% vs. 90% increased their lean mass, 87% vs. 59% reduced their fat mass, and 100% vs. 84% increased the ratio of lean to fat mass over time, respectively.

With-meal ingestion of protein was defined as consumption of a dietary protein-rich supplement immediately after a meal, with a meal, or as a high-protein meal replacement. Between-meal ingestion of protein was defined as consumption of a dietary protein supplement predominantly either very near a workout or during another non mealtime.

The results from this systematic review provide novel information for people who choose to consume protein supplements as part of their dietary pattern to promote body mass gain or improve body composition through fat mass reduction. However, consuming protein supplements with meals, rather than between meals, may be a more effective dietary strategy to improve resistance training-induced changes in body composition by reducing fat mass, which may be relevant for adults looking to improve their health status. Consuming protein supplements between meals may be more effective at increasing overall body mass.

AUGUSTA, Ga. (April 25, 2018) - A daily dose of baking soda may help reduce the destructive inflammation of autoimmune diseases like rheumatoid arthritis, scientists say.

They have some of the first evidence of how the cheap, over-the-counter antacid can encourage our spleen to promote instead an anti-inflammatory environment that could be therapeutic in the face of inflammatory disease, Medical College of Georgia scientists report in the Journal of Immunology.

They have shown that when rats or healthy people drink a solution of baking soda, or sodium bicarbonate, it becomes a trigger for the stomach to make more acid to digest the next meal and for little-studied mesothelial cells sitting on the spleen to tell the fist-sized organ that there's no need to mount a protective immune response.

"It's most likely a hamburger not a bacterial infection," is basically the message, says Dr. Paul O'Connor, renal physiologist in the MCG Department of Physiology at Augusta University and the study's corresponding author.

Mesothelial cells line body cavities, like the one that contains our digestive tract, and they also cover the exterior of our organs to quite literally keep them from rubbing together. About a decade ago, it was found that these cells also provide another level of protection. They have little fingers, called microvilli, that sense the environment, and warn the organs they cover that there is an invader and an immune response is needed.

Drinking baking soda, the MCG scientists think, tells the spleen - which is part of the immune system, acts like a big blood filter and is where some white blood cells, like macrophages, are stored - to go easy on the immune response. "Certainly drinking bicarbonate affects the spleen and we think it's through the mesothelial cells," O'Connor says.

The conversation, which occurs with the help of the chemical messenger acetylcholine, appears to promote a landscape that shifts against inflammation, they report.

In the spleen, as well as the blood and kidneys, they found after drinking water with baking soda for two weeks, the population of immune cells called macrophages, shifted from primarily those that promote inflammation, called M1, to those that reduce it, called M2. Macrophages, perhaps best known for their ability to consume garbage in the body like debris from injured or dead cells, are early arrivers to a call for an immune response.

In the case of the lab animals, the problems were hypertension and chronic kidney disease, problems which got O'Connor's lab thinking about baking soda.

One of the many functions of the kidneys is balancing important compounds like acid, potassium and sodium. With kidney disease, there is impaired kidney function and one of the resulting problems can be that the blood becomes too acidic, O'Connor says. Significant consequences can include increased risk of cardiovascular disease and osteoporosis.

"It sets the whole system up to fail basically," O'Connor says. Clinical trials have shown that a daily dose of baking soda can not only reduce acidity but actually slow progression of the kidney disease, and it's now a therapy offered to patients.

"We started thinking, how does baking soda slow progression of kidney disease?" O'Connor says.

That's when the anti-inflammatory impact began to unfold as they saw reduced numbers of M1s and increased M2s in their kidney disease model after consuming the common compound.

When they looked at a rat model without actual kidney damage, they saw the same response. So the basic scientists worked with the investigators at MCG's Georgia Prevention Institute to bring in healthy medical students who drank baking soda in a bottle of water and also had a similar response.

"The shift from inflammatory to an anti-inflammatory profile is happening everywhere," O'Connor says. "We saw it in the kidneys, we saw it in the spleen, now we see it in the peripheral blood."

The shifting landscape, he says, is likely due to increased conversion of some of the proinflammatory cells to anti-inflammatory ones coupled with actual production of more anti-inflammatory macrophages. The scientists also saw a shift in other immune cell types, like more regulatory T cells, which generally drive down the immune response and help keep the immune system from attacking our own tissues. That anti-inflammatory shift was sustained for at least four hours in humans and three days in rats.

The shift ties back to the mesothelial cells and their conversations with our spleen with the help of acetylcholine. Part of the new information about mesothelial cells is that they are neuron-like, but not neurons O'Connor is quick to clarify.

"We think the cholinergic (acetylcholine) signals that we know mediate this anti-inflammatory response aren't coming directly from the vagal nerve innervating the spleen, but from the mesothelial cells that form these connections to the spleen," O'Connor says.

In fact, when they cut the vagal nerve, a big cranial nerve that starts in the brain and reaches into the heart, lungs and gut to help control things like a constant heart rate and food digestion, it did not impact the mesothelial cells' neuron-like behavior.

The affect, it appears, was more local because just touching the spleen did have an effect.

When they removed or even just moved the spleen, it broke the fragile mesothelial connections and the anti-inflammatory response was lost, O'Connor says. In fact, when they only slightly moved the spleen as might occur in surgery, the previously smooth covering of mesothelial cells became lumpier and changed colors.

"We think this helps explain the cholinergic (acetylcholine) anti-inflammatory response that people have been studying for a long time," O'Connor says.

Studies are currently underway at other institutions that, much like vagal nerve stimulation for seizures, electrically stimulate the vagal nerve to tamp down the immune response in people with rheumatoid arthritis. While there is no known direct connection between the vagal nerve and the spleen - and O'Connor and his team looked again for one - the treatment also attenuates inflammation and disease severity in rheumatoid arthritis, researchers at the Feinstein Institute for Medical Research reported in 2016 in the journal Proceedings of the National Academy of Sciences.

O'Connor hopes drinking baking soda can one day produce similar results for people with autoimmune disease.

"You are not really turning anything off or on, you are just pushing it toward one side by giving an anti-inflammatory stimulus," he says, in this case, away from harmful inflammation. "It's potentially a really safe way to treat inflammatory disease."

The spleen also got bigger with consuming baking soda, the scientists think because of the anti-inflammatory stimulus it produces. Infection also can increase spleen size and physicians often palpate the spleen when concerned about a big infection.

Other cells besides neurons are known to use the chemical communicator acetylcholine. Baking soda also interact with acidic ingredients like buttermilk and cocoa in cakes and other baked goods to help the batter expand and, along with heat from the oven, to rise. It can also help raise the pH in pools, is found in antacids and can help clean your teeth and tub.

San Diego (April 25, 2018)--A new study in medical students finds that summer, not winter, is the season when people are most likely to have higher levels of circulating stress hormones. These non-intuitive findings contradict traditional concepts of the taxing physical toll of winter and the relaxed ease of summer. Researchers will present their findings today at the American Physiological Society (APS) annual meeting at Experimental Biology 2018 in San Diego.

Cortisol--often referred to as the "stress hormone" because it is released into the bloodstream during stressful situations--helps regulate the body's levels of sugar, salt and fluids. The hormone helps reduce inflammation and is essential for maintaining overall health. Cortisol levels are typically highest in the morning and gradually drop throughout the day. Levels are lower in the evening to maintain healthy sleeping patterns. Illness, lack of sleep and certain medications can affect cortisol levels more than normal daily fluctuations. Researchers from Poznan University of Medical Sciences in Poland have now discovered seasonal patterns in the cortisol levels of medical students.

The research team studied a group of female medical students on two separate days in the winter and for two days again in the summer. The researchers took saliva samples every two hours during each testing period--a full 24-hour cycle--to measure levels of cortisol and markers of inflammation. The volunteers completed a lifestyle questionnaire during each testing session about their sleep schedule, type of diet they followed and physical activity levels.

Previous studies on the seasonal variability of cortisol have shown inconsistent findings--possibly because participants were tested in their own homes and not in a uniform setting. In the current study, however, the research team found cortisol levels to be higher on the summer testing dates. Inflammation levels did not change significantly between seasons.

Dominika Kanikowska, of Poznan University of Medical Sciences, will present the poster "Daily and seasonal rhythms of interleukin 6 and cortisol levels in saliva and some lifestyle habits of medical students in Poland" on Wednesday, April 25, in the Sails Pavilion of the San Diego Convention Center.

By tracing the use of the word and hashtag 'shithole' on Twitter, researchers have examined who is engaged in the stigmatizing discourse of denigration, the types of place that are stigmatized, and the responses to stigmatized places.

In a Transactions of the Institute of British Geographers study, the majority of tweets were aimed at places where the tweeter was not from, a form of othering consistent with how territories are stigmatized by those in positions of power such as policymakers, politicians, and journalists. Also, an important and gendered minority of tweets were characterized by a 'cry for help' and powerlessness, where the stigma was aimed at their own places.

"As well as showing what people think about other places, our research showed how people talk about the places where they live and how a significant proportion--38% of the tweets we studied--maligned the place where they live," said lead author Alice Butler, of the University of Leeds, in the UK. "There was a significant gender difference in the way that men and women experience living in a place, and we also noted a tendency to try and separate place from self-identity."

Drinking kefir may have a positive effect on blood pressure by promoting communication between the gut and brain. Kefir is a fermented probiotic milk beverage known to help maintain the balance of beneficial bacteria in the digestive system. Researchers will present their findings today at the American Physiological Society (APS) annual meeting at Experimental Biology 2018 in San Diego.

Previous research has shown that an imbalance in the gut's colony of bacteria (microbiota) may cause high blood pressure in some people. Similarly, probiotics--live bacteria supplements that are beneficial to the digestive system--have been found to lower blood pressure, but the mechanisms by which this occurs are unclear.

A research team from Auburn University in Alabama, in collaboration with the University of Vila Velha in Brazil, studied three groups of rats to determine how kefir reduces high blood pressure (hypertension):

One group had hypertension and was treated with kefir ("treated").

One group had hypertension and was not treated ("untreated").

One group had normal blood pressure and was not treated ("control").

After nine weeks of kefir supplementation, the treated rats had lower levels of endotoxins (toxic substances associated with disruption in the cells), lower blood pressure and improved intestinal permeability when compared with the untreated group. Healthy intestines allow some substances to pass through, but generally act as a barrier to keep out harmful bacteria and other potentially dangerous substances. In addition, kefir supplementation restored the natural balance of four different bacteria in the gut and of an enzyme in the brain essential for normal nervous system function, suggesting that the nervous and digestive systems work together to reduce hypertension.

"Our data suggests that kefir antihypertensive-associated mechanisms involve gut microbiota-brain axis communication during hypertension," the researchers wrote.

Mirian Silva-Cutini, of Auburn University, will present "Probiotic kefir antihypertensive effects in spontaneously hypertensive rats involve central and peripheral mechanisms" on Wednesday, April 25, in the Sails Pavilion of the San Diego Convention Center.

PITTSBURGH--Searches involving multiple websites can quickly get confusing, particularly when performed on a mobile device with a small screen. A new web browser developed at Carnegie Mellon University now brings order to complex searches in a way not possible with conventional tabbed browsing.

The Bento browser, inspired by compartmentalized bento lunch boxes popular in Japan, stores each search session as a project workspace that keeps track of the most interesting or relevant parts of visited web pages. It's not necessary for a user to keep every site open to avoid losing information.

"With Bento, we're structuring the entire experience through these projects," said Aniket Kittur, associate professor in the Human-Computer Interaction Institute (HCII). The projects are stored for later use, can be handed off to others, or can be moved to different devices. "This is a new way to browse that eliminates the tab overload that limits the usefulness of conventional browsers."

Someone planning a trip to Alaska with a conventional browser, for instance, might create multiple tabs for each location or point of interest, as well as additional tabs for hotels, restaurants and activities. With Bento, users can identify pages they found useful, trash unhelpful pages and keep track of what they have read on each page. Bento also bundles the search result pages into task cards, such as accommodations, day trips, transportation, etc. The project could be shared with other people planning their own trips.

Kittur's research team will present a report on their mobile web browser at CHI 2018, the Conference on Human Factors in Computing Systems, April 21-26 in Montreal, Canada. A research version of the Bento Browser for iPhones is available for download from the App Store.

Mobile devices now initiate more web searches than do desktop computers. Yet the limitations of conventional browsers become more acute on mobile devices. Not only is screen size limited, but mobile users are more often interrupted and distracted and have more difficulty saving and organizing information, said Nathan Hahn, a Ph.D. student in HCII.

In user studies that compared Bento with the Safari browser, users said they preferred Bento in cases where they wanted to continue a search later and wanted to pick up where they left off. They also said Bento kept their searches better organized. Though most participants found it easier to learn how to use Safari, they found Bento more useful for finding pages and believed that Bento made their mobile searches more effective.

One goal was to design Bento to work in a way that complements the way the mind works.

"If we get a lot of people using it, Bento could serve as a microscope to study how people make sense of information," Kittur said, noting people who use the research version are asked to consent to their searches becoming part of the research data. "This might lead to a new type of artificial intelligence," he added.

Bento Browser is now a search app for iPhones, but its capabilities for organizing searches and helping people resume searches also could benefit people using desktop computers. To accommodate those users, Kittur's team is now preparing a Bento plug-in for the Chrome browser.

Joseph Chee Chang, a Ph.D. student in CMU's Language Technologies Institute, also is part of the Bento team and a co-author of the CHI paper. More information is available at https://bentobrowser.com/.

Many people of African heritage are protected against malaria by inheriting a particular version of a gene, a large-scale study has shown.

Another variation of the same gene can have the opposite effect of raising susceptibility to malaria - but it reduces the risk of other common childhood diseases, the study found.

The findings give new insights to explain why some children, but not all, develop severe malaria. The condition, which is spread by mosquito bites, kills half a million African children each year before they have had time to acquire immunity to the disease.

Scientists also revealed that the impact of both gene variations is linked to whether or not individuals carry a third genetic mutation. Their research, which highlights the complex links that can exist between genes in our DNA, helps explain inconsistencies in previous research.

In a study of more than 5,000 Kenyan children, researchers from the University of Edinburgh with colleagues from Oxford, Kenya and Mali examined two variations, or mutations - known as Sl2 and McCb - in a gene called CR1. These gene variations, common in African populations, were believed to have evolved in response to malaria, but previous studies have been unable to confirm this.

By studying the complex relationships between the gene variants, researchers found that the Sl2 mutation in the CR1 gene protects against cerebral malaria and death - but only if children did not carry a third gene mutation, known as alpha-thalassaemia. A separate study showed that the Sl2 variant helped prevent clumps of cells called rosettes, found in severe malaria.

The other mutation in CR1, known as McCb, was found to be linked to increased risk of cerebral malaria and death, but to lower the risk of childhood diseases such as respiratory and gastrointestinal infections. The study, supported by Wellcome, was published in eLife.

Professor Alexandra Rowe, of the University of Edinburgh's School of Biological Sciences, who supervised the study, said: "Genes have complex effects on one another and on the chances of disease. These findings point towards avenues for further research in understanding factors that influence life-threatening illness in African children."

Dr Olivia Swann, of the School of Biological Sciences, who jointly led the study, said: "This study is a missing piece in the puzzle of how genes protect people against malaria. It also reminds us how complex this protection is and how hard it can be to untangle the influence of one gene from another."

WACO, Texas (April 24, 2018) - Do you consider yourself more ethical than your coworker?

Caution! Your feelings of ethical superiority can cause a chain reaction that is detrimental to you, your coworker and your organization, according to Baylor University management research.

A new study published in the Journal of Business Ethics suggests that your feelings of ethical superiority can lead you to have negative emotions toward a "less ethical" coworker. Those negative emotions can be amplified if you also believe you do not perform as well as that coworker. And, furthermore, those negative emotions can lead to your mistreatment and/or ostracism (social exclusion) of that less ethical, higher-performing coworker.

"One way to think of this is that it is - and should be - concerning to us to believe that we are more ethical than our coworkers, especially if we do not perform as well as they do," said lead author Matthew Quade, Ph.D., assistant professor of management in Baylor University's Hankamer School of Business and an expert on workplace ethics and ostracism.

The research, Quade said, can help managers create better atmospheres and improve the bottom line.

"The managerial implication is that we need to create environments where ethics and performance are both rewarded," he said.

A total of 741 people, among them 310 employees ("focal employees") and an equal number of their coworkers ("comparison coworkers"), were surveyed for the study. Focal employees compared themselves with their coworkers based on two areas: perceived ethics and performance. Then they rated their levels of negative emotions (i.e., feelings of contempt, tension or disgust) toward those same comparison coworkers.

Results show that employees who believe they are more ethical than similar coworkers (i.e., those that hold similar positions, have similar education background and similar tenure in the organization) feel negative emotions (i.e., contempt, disgust, stress, repulsion) when thinking about those coworkers. These negative emotions about the coworker are amplified when the employees also believe they do not perform as well as those same coworkers.

In turn, the comparison coworkers rated how often they experienced social undermining (i.e., insults, spreading of rumors, belittling of ideas) and ostracism (i.e., ignored, avoided, shut out of conversations) from the focal employee.

Results also show that the negative emotions that the "more ethical, lower performing" employees experience may result in them behaving in unethical ways directed at their coworkers. Specifically, they become more likely to socially undermine and ostracize those "less ethical, higher performing" coworkers. All the study's results exist regardless of gender and any positive emotion the employees may experience as a result of believing they are more ethical.

Ultimately, such workplace scenarios pose a conundrum for managers, Quade said. On one hand, there is the ethical worker who doesn't perform as well. On the other hand, there's the less ethical worker who hits all the goals.

Who gets rewarded?

"If high performance is the result of questionable or unethical behavior, that combination should not be celebrated," the researchers wrote. "Instead, organizations should be cautious when rewarding and promoting performance within organizations, ensuring that they also consider the way the job is done from an ethical standpoint."

The ideal situation, the study reveals, is when high ethics and high performance are the norm - and employees are rewarded.

"Enhancing the ethical behavior of all employees should be an emphasis to attempt to remove some of the disparity that tends to exist between employees when it comes to their moral behavior at work," the researchers wrote.

INDIANAPOLIS -- New research shows that patients in the hospital are eager to collaborate with clinicians to track their health data. Traditionally, clinicians have been the only ones who collect, track and reflect on that data.

The findings uncover new directions for researchers in the field of human-computer interaction, said Andrew Miller, one of the researchers and an assistant professor in the Department of Human-Centered Computing in the School of Informatics and Computing at IUPUI.

The researchers reported their findings in a paper, ?"Supporting Collaborative Health Tracking in the Hospital: Patients' Perspectives," that was published by the 2018 ACM CHI Conference on Human Factors in Computing Systems, the premier international conference of human-computer interaction.

Previous studies have shown that patients have a better care experience -- and a better health outcome -- when they are engaged in their care, compared to disengaged patients.

But tracking health data in the hospital isn't easy for patients. One of the challenges is that much of a patient's health information is presented verbally. Access to information depends on their alertness and their ability to recall what was said.

"The big idea for this paper was to consider bringing into the hospital the models, approaches and mechanisms that human-computer interaction research has generated for people outside of the hospital to track their physical activity, with devices like Fitbits, and help them manage chronic health conditions like diabetes with glucose monitors," Miller said.

The question, Miller said, was whether those types of devices would help people make sense of their health data when they were in the hospital.

The researchers first questioned patients and their caregivers about what kind of information they would want to track, Miller said.

"We then looked at these models from outside of the hospital to see where there is a match and where we could bring some of the insights from outside of the hospital into the hospital," Miller said. "We think there is substantial evidence in this study to show there is a real opportunity here, and it's something patients are interested in doing."

In fact, he said, researchers were surprised by the degree of interest among patients in tracking their health data. "There was a palpable sense in patients that this is actually something they could use right now."

At the same time, however, patients don't want to track the data by themselves, Miller said: "They're interested in partnering with their care team to get better and doing what they can to help."

Imagining that a future event will go well may lead you to remember it more positively after it's over, according to findings from research published in Psychological Science, a journal of the Association for Psychological Science.

"Our results suggest that imagining an upcoming event can essentially 'color' your memory for that event once it comes to pass," says psychological scientist Aleea Devitt of Harvard University, first author on the study.

"Research has shown that healthy adults tend to have an unrealistically favorable outlook, and our studies suggest that one potential benefit of this optimism might be that we remember events in a more positive way, which could contribute to general well-being," she explains.

Daydreaming about the future is a common experience and many of the events we muse about eventually come to pass. Devitt and study coauthor Daniel L. Schacter, also of Harvard University, hypothesized that simulating a future event may produce a mental representation that ultimately competes with and alters memory for the event after it has happened.

In one experiment, the researchers presented 27 participants with a series of 12 randomly-selected scenarios. For each scenario, participants imagined the event going well (or going poorly) and described it aloud for 3 minutes.

After a 15-minute break, the researchers told the participants to imagine that it was a year later and that they were going to learn how the events turned out. The participants then read brief narratives of the events, each of which contained some positive, negative, and neutral details.

On a subsequent recognition test 48 hours later, they saw 12 details (some positive and some negative) for each narrative, and indicated whether those details had appeared in the narrative.

Emotional content mattered: Participants incorrectly identified more positive details as "true" than they did negative details.

Importantly, how they imagined the event influenced what they remembered from the narrative later. Participants were more likely to mistakenly identify positive details as "true" if they had previously imagined the event going well. Imagining a negative outcome before learning how an event turned out did not seem to influence participants' memory for the event details.

A second experiment produced similar results, showing that imagining a positive event, either in the future or the past, biased participants' subsequent recall toward positive details. Participants who imagined scenarios in a positive light also rated the actual event more positively when they took the recognition test.

"These results suggest that adopting an optimistic outlook can actually transfer to a rosier reflection once those upcoming experiences become part of the personal past," says Devitt.

Devitt and Schacter are now investigating whether a similar phenomenon occurs among healthy old adults, as research has shown that older adults tend to imagine events with less detail but also show an overall positive bias in attention and memory.