How To Avoid Fighting In the Car on 4th of July

Happy Fourth of July! Doing anything fun for the weekend? Like, for instance, getting into a car with your significant other tonight to drive somewhere with a beach or some beautiful nature…just like everybody else? And then you’re idling on I-95 for hours, you’re out of podcasts, and one of you is quietly seething that if you’d just taken 78 West you could have avoided most of this traffic, even though it looked longer on the map, and you always ruin things you never listen to me I hate you.

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We’ve all been there, and while getting into fights is something that happens to all couples, they’re particularly annoying if you are stuck in a metal box in the middle of the highway with no bathrooms in sight. Traffic can’t be avoided, but with some planning and emotional honesty, maybe your fight can be.

Samantha Burns, a relationship counselor and dating coach, says it’s no surprise fights happen in the car. “Traffic can be a stressful and anxiety-inducing situation, especially if you’re the driver and splitting your mental attention between the road and your partner,” she told ELLE.com. Stress makes your brain go into fight-or-flight mode, and instead of being able to take a walk or do something else to calm yourself down, when you’re stuck in a car “you’re left with engaging in the argument or ignoring your partner, which can be just as damaging.”

The thing is, long car rides can also be wonderful times to reconnect, whether it’s with deep conversations or listening to albums or podcasts you both enjoy. And ultimately, we never stop being children who need games and toys and songs to distract us from how little control we have over the world around us. Pick out books on tape to listen to in advance, bring a crossword puzzle and call out the questions, or play the same games you played as a kid. “It sounds silly, but can be a good distraction from the mundane scenery or tense conversations, and will get you into a playful state of mind,” says Burns. “It’s also important to pack plenty of snacks and water since hunger can get the best of you, and it’s never fun to deal with a hangry partner.”

“It’s also important to pack plenty of snacks and water since hunger can get the best of you, and it’s never fun to deal with a hangry partner.”

Unfortunately, the best-laid plans, etc., etc. You may yet run out of snacks, or reach the end of your playlist, or entered a slightly wrong address into your phone only to discover you’ve been driving for an hour in the wrong direction. At home you can yell, go to a different room and take a breather, and then revisit the conversation with clearer heads. But you don’t have the luxury of a door here, so you need to be proactive if you feel you’re about to snap.

As always, safety first. Fighting and driving is a recipe for disaster, so pull over if you need to. But no matter what, “take a mental pause and rate your current frustration on a scale from 1 to 10. If you’re over a 5, you could be approaching an explosion or shutting down and ignoring your partner,” Burns says.

If that’s the case, say so. “It’s essential to communicate that you’re feeling overwhelmed and need a few moments to calm down so that you can really listen and respond without the conversation escalating.” Don’t just shut down and pretend everything is fine until you’re both so stressed from the tension that the fight is 10 times worse than it should have been. What? Who does that? Not me, never.

Once you’ve communicated that you’re overwhelmed, cool off by listening to some music (Burns suggests a comedy album or podcast to shift the mood), or talking about experiences you’ve shared that make you feel connected, like “the first time you slept together, your wedding day, or the epic vacations you’ve taken together.”

A lot of the frustrations that lead us to snap at each other during long car rides are out of our control. We can’t make the traffic move faster. We can’t catch the ferry we missed. We can’t suddenly be somewhere else where there are no outside stressors. Admit you’re frustrated and that things aren’t perfect, and see what you can do to make things better for the moment. And honestly, just buy that extra pack of string cheese before you leave. It’ll be worth it.

Does the United States Really Take All Kinds?

I used to be sad

about not having an identity

then I thought it was liberating

not to have roots

now I am envious of you

with your nation in your voice

and I am angry

at Bangladesh, at Nigeria

for rejecting me

at America for taking all kinds

In 1961, my father came to America from what was then East Pakistan. He was 27, and had won a visiting Fulbright Scholarship at Johns Hopkins University. He landed in New York City, and then flew to Bloomington, Indiana, where a host family was to help him acclimate to America for a few days.

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My father was primed for America well before he would become a citizen. He had spent the four years before his Fulbright scholarship working for an American oil company in Karachi. He liked the forthright manner of the Americans he had met, and was secretly relieved not to be continuing the colonial tradition of going to Britain for further studies or work. But on his first visit to America in 1961, he arrived fevered and ill and spent his first two days in bed. He only vaguely registered his surroundings, a bed at the top of a long set of stairs, two stories high, in a building within a sprawling estate. He was brought sandwiches and water, and on the third day, when he was well enough, he was invited to dinner.

Coming down the stairs, he found himself in a stable, with two magnificent horses. The host family’s son was an avid equestrian, and disappointed to learn my father didn’t know how to ride. They crossed the lawn and entered the main house. He remembers the enormous dining table covered with silverware (“more forks than food!”) and the black servants waiting on them as they ate.

It was only later that he realized that his hosts had not deemed him worthy of a bedroom in the main house, that they thought it was okay to put a foreign scholar in the stables. He told this story to someone at Johns Hopkins, where he later received his Masters, and they were shocked and horrified. But he replied, “I was not humiliated. Rather, I felt that I now understood a little of how terrible it was for the blacks.” He said, “I’ve read your country’s history, how you treated your blacks, your American Indians. It cannot go away so easily.”

“I’ve read your country’s history, how you treated your blacks, your American Indians. It cannot go away so easily.”

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After Johns Hopkins, my father went on to complete his Ph.D. at the University of Pittsburgh. By 1966, he was a professor, off to teach geology in Iraq, then Libya, and finally Nigeria. The year before he left, the US passed the 1965 Immigration and Nationality Act, ending a long era of exclusion, discrimination, and violence, including anti-Asian riots, lynchings, indentured servitude, internment camps, and severe quotas that had basically banned non-European immigration since the Chinese Exclusion Act of 1882. This new legislation set off a wave of immigration, which would eventually bring my father back to the States, this time with a wife and three children.

It’s conventional wisdom that history is a series of progressive steps, each one bringing us closer to wiser. This isn’t true, and moreover, it’s a dangerous perspective. It ignores the essential revolutionary work of activists, allows for apathetic citizens (because things will get better no matter what, right?), and might even blindside you with a 2017 Muslim Ban.

In 1986, my family left Nigeria where I was born and had lived for thirteen years. The government of Nigeria had just been overthrown by its military, and its once thriving economy was plummeting. Food staples were increasingly difficult to find and university strikes had become common. My younger sister, brother, and I were presented with four options, places my father had gotten job offers: Oman, Papua New Guinea, Tampa, and Pittsburgh.

We chose Pittsburgh for a reason any immigrant will understand: we had friends there. As a doctoral student at Pitt, my father had met a friendly Bangladeshi couple who used to have him over for dinner. In the late 1980s, there were fewer than five Bangladeshi families living in Pittsburgh (there are almost one hundred now, and my parents know every single one).

The city was struggling to recover from the death of the steel industry, and its spectacular hilly and riverine landscape was dotted with rusted metal towers, slanted chutes, smoke stacks, some still flaming into the grey sky. Some neighborhoods smelled so bad that we would hold our noses driving through them. My parents enrolled my siblings and me in public school in the outer suburbs, one so deep in the boondocks even Pittsburghers don’t recognize its name.

Researchers found an RNA species identifying critically short telomeres; publication in Cell — ScienceDaily

Researchers at the Institute of Molecular Biology (IMB) and Johannes Gutenberg University Mainz (JGU) have further uncovered the secrets of telomeres, the caps that protect the ends of our chromosomes. They discovered that an RNA molecule called TERRA helps to ensure that very short (or broken) telomeres get fixed again. The work, which was recently published in the journal Cell, provides new insights into cellular processes that regulate cell senescence and survival in ageing and cancer.

Telomeres protect the ends of our chromosomes, much like the plastic cap at the end of a shoelace that prevents the lace from unravelling. Over a cell’s lifetime, telomeres get gradually shorter with each cell division and therefore the protective cap becomes less and less effective. If they get too short, it is a signal for the cell that its genetic material is compromised and the cell stops dividing. Telomere shortening and reduced cell division are considered a hallmark of ageing and likely contribute to the ageing process. However, telomere shortening is also a defense mechanism against cancer because highly proliferative cells can only divide when their telomeres do not shorten. Therefore, telomere shortening is a double-edged sword and has to be carefully regulated to strike a balance between ageing and cancer prevention. When a telomere accidentally gets cut short early in a cell’s lifetime, it needs to be fixed so that the cell doesn’t become senescent too early.

“In the life of a cell, you have to find some sort of balance between cancer prevention and ageing. Telomeres are at the nexus between the two, so understanding how they are maintained is really important,” said Brian Luke, Professor at the JGU Institute for Developmental Biology and Neurobiology and Adjunct Director at IMB.

Luke and his lab were interested in understanding how the cell recognizes these shortened and damaged telomeres that have lost their caps. Furthermore, they wanted to determine which factors were important for promoting the repair of short telomeres. This information could help in understanding why cells either commit to senescence or continue to grow.

In their recent paper, published in the journal Cell, Luke and his group have shown that one of the keys to understanding this problem is TERRA. TERRA is an RNA species that accumulates specifically at the ends of critically short telomeres by binding directly to the DNA and signals to the cell that these telomeres should be repaired, allowing the cell to carry on dividing.

“We already knew that short telomeres play a key role in determining the onset of cellular senescence, but we didn’t really understand which features of short telomeres were important. What we have found with TERRA is an intricate regulatory system that explains how short telomeres are identified by the cell,” said Luke.

The paper is actually the result of two different research projects on telomeres in the Luke lab. Diego Bonetti was looking into the regulation of TERRA in the cell cycle and found that TERRA levels were different at different stages of the cell cycle. Meanwhile, Arianna Lockhart and Marco Graf were investigating the accumulation of TERRA at short telomeres. When they discovered that the pattern of cyclic TERRA accumulation was different between short and long telomeres, they knew they were on to something and joined forces for this project.

Their joint work led them to realize that TERRA actually accumulates at all telomeres, but at long telomeres it is rapidly removed with the help of proteins Rat1 and RNase H2. These proteins bind preferentially to the long telomeres and ensure that TERRA is removed, but they are not present at the critically short telomeres, which means that TERRA remains for a longer time. This mechanism ensures the subsequent repair of the short telomere, which is crucial for the cell to survive and keep dividing.

Luke’s work was carried out in yeast; however, telomeres and TERRA are found across all organisms with linear chromosomes. The researchers expect their work to be applicable to humans as well. Their next step will be to look into these processes in human cells and interrogate their implications for ageing and cancer.

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Picture overload hinders children’s word learning from storybooks — ScienceDaily

Less is more when it comes to helping children learn new vocabulary from picture books, according to a new study.

While publishers look to produce ever more colourful and exciting texts to entice buyers, University of Sussex psychologists have shown that having more than one illustration per page results in poorer word learning among pre-schoolers.

The findings, published in Infant and Child Development, present a simple solution to parents and nursery teachers for some of the challenges of pre-school education and could help in the development of learning materials for young children.

Doctoral researcher and co-author Zoe Flack said: “Luckily, children like hearing stories, and adults like reading them to children. But children who are too young to read themselves don’t know where to look because they are not following the text. This has a dramatic impact on how well they learn new words from stories.”

The researchers read storybooks to three-year-olds with one illustration at a time (the right-hand page was illustrated, the left-hand page was blank) or with two illustrations at a time (both pages had illustrations), with illustrations introducing the child to new objects that were named on the page.

They found that children who were read stories with only one illustration at a time learned twice as many words as children who were read stories with two or more illustrations.

In a follow-up experiment, researchers added a simple hand swipe gesture to guide the children to look at the correct illustration before the page was read to them. They found this gesture was effective in helping children to learn words when they saw two illustrations across the page.

Zoe, who has written a blog post about the research, said: “This suggests that simply guiding children’s attention to the correct page helps them focus on the right illustrations, and this in turn might help them concentrate on the new words.

“Our findings fit well with Cognitive Load Theory, which suggests that learning rates are affected by how complicated a task is. In this case, by giving children less information at once, or guiding them to the correct information, we can help children learn more words.”

Co-author Dr Jessica Horst, said: “Other studies have shown that adding ‘bells and whistles’ to storybooks like flaps to lift and anthropomorphic animals decreases learning. But this is the first study to examine how decreasing the number of illustrations increases children’s word learning from storybooks.”

She added: “This study also has important implications for the e-Book industry. Studies on the usefulness of teaching vocabulary from e-Books are mixed, but our study suggests one explanation is that many studies with e-Books are only presenting one illustration at a time.”

The study is one of many being carried out at Sussex in The WORD Lab, a research group that focuses on how children learn and acquire language. Previous research has shown children learn more words from hearing the same stories repeated and from hearing stories at nap time.

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Zoning in on specifics of Mediterranean diet for colorectal health — ScienceDaily

The benefits of a “Mediterranean diet” (MD) are well-known when it comes to colorectal protection, but it’s hard to know specifically what elements of the diet are the healthiest.

Now a new study, presented today at the ESMO 19th World Congress on Gastrointestinal Cancer suggests loading up on fish and fruit, and cutting back on soft drinks are the three most important things.

“We found that each one of these three choices was associated with a little more than 30% reduced odds of a person having an advanced, pre-cancerous colorectal lesion, compared to people who did not eat any of the MD components. Among people who made all three healthy choices the benefit was compounded to almost 86% reduced odds,” said Naomi Fliss Isakov, PhD fromTel-Aviv Medical Center, in Tel Aviv, Israel.

Colorectal cancer (CRC) develops from intestinal polyps and has been linked to a low-fibre diet heavy on red meat, alcohol and high-calorie foods, said Fliss Isakov.

And while the Mediterranean diet has been associated with lower rates of colorectal cancer, the definition of what elements in the diet are the most beneficial, has not always been clear.

Using dietary questionnaires from 808 people who were undergoing screening or diagnostic colonoscopies, the research team was able to dig down to look at the fine details of their daily meals.

All subjects were between 40 and 70 years old, without high risk of CRC, and answered a food frequency questionnaire.

Adherence to the MD components was defined as consumption levels above the group median for fruits, vegetables and legumes, nuts and seeds, whole grains, fish and poultry and a high ratio of monounsaturated to saturated fatty acids, as well consumption below the median of red meat, alcohol, and soft drinks.

The investigators found that compared to subjects with clear colonoscopies, those who had advanced polyps reported fewer components of the Mediterranean diet (a mean of 1.9 versus 4.5 components). Yet even consumption of two to three components of the diet, compared to none, was associated with half the odds of advanced polyps.

Odds were reduced in a dose response manner with additional MD components — meaning that the more MD components people adhered, the lower their odds of having advanced colorectal polyps.

After adjusting to account for other CRC risk factors, including other dietary components, the researchers narrowed in on high fish and fruit and low soft drinks as the best combo for reduced odds of advanced colorectal polyps.

The next step will be to see whether the MD is linked to lower risk of CRC in higher risk groups, she concluded.

Commenting on the study, ESMO spokesperson Dirk Arnold, MD, PhD, from Instituto CUF de Oncologia in Lisbon, Portugal, said “this large population-based cohort-control study impressively confirms the hypothesis of an association of colorectal polyps with diets and other life-style factors. This stands in line with other very recent findings on nutritive effects, such as the potential protective effects of nut consumption and Vitamin D supplementation which have been shown earlier this year. However, it remains to be seen whether these results are associated with reduced mortality, and it is also unclear if, and when a dietary change would be beneficial. Despite this lack of information, it makes sense to consider this diet for other health-related reasons also.”

Doctors divided about tutoring future colleagues — ScienceDaily

Professionally active doctors increasingly hesitate to take on the task of tutoring students from undergraduate medical education. Stress and pressure from higher up, and sometimes also from colleagues, contributes to this ambivalence, according to a thesis at Sahlgrenska Academy.

“If you don’t have clear support from management, a mistrust of the tutors can arise; you’re viewed as someone who doesn’t take care of patients and is just a burden. Tutoring should provide academic merits and a useful qualification in the same way as when somebody conducts research on the side,” says Bernhard von Below, MD/PhD, Researcher at the Institute of Medicine with a base in primary health care as a specialist in general medicine at the Närhälsan health care center in Floda.

As the educational director for the Early Professional Contact course, he has monitored developments concerning medical students’ in-service training during undergraduate studies for several years. Periods of in-service training at health care centers and hospitals are held throughout the medical program’s 11 semesters. In the first two years, it involves three to four days a semester, and they increase considerably later in the program.

“Learning the profession at the workplace is an incredibly important part of their education. They have to have well-educated tutors, otherwise it hurts the medical student’s training and, in the long term, the medical profession itself,” says Bernhard von Below.

A stimulating task

The thesis shows that clinical tutorship is appreciated by the tutoring physicians and gives them joy and stimulation. The tutors are motivated and driven by a desire to give the students their best, better than what they themselves received once upon a time. Another driving force is the loyalty to their own professional specialty.

However, junior doctors more often seem to consider whether the conditions are reasonable before they take on the task. These are the findings of a study that Bernhard von Below did with doctors training for to become clinical tutors.

“Today’s healthcare system is being pressured from many directions, with high demands on production and detailed management that mean that tutoring is at risk of becoming the exception rather than the rule. Doctors are loyal to their patients and if they feel that they don’t have the support of managers and colleagues, they often choose to leave the tutoring role and not take it on the next time,” he says.

“This is a trend that has been happening for eight to ten years and is associated with increasing pressure in the healthcare system and physicians’ difficulties deciding over their own workdays,” continues Bernhard von Below.

Conflicts on the factory floor

Important factors that make it easier for the doctors to be tutors are clear support from management and time allocated for the task. They also need support from the others at the workplace and understanding for there being fewer patient contacts. Training and feedback on how the tutoring was carried out are also important.

According to Bernhard von Below, the structures are often in place. How a health care center or clinic should accept students is decided and set, but in reality things can nonetheless slip.

“There’s a positive development in terms of agreements. What’s hard is securing the time for tutoring. In theory, it’s going in one direction, in practice it’s going in another. There can be an agreement in principle, but on the factory floor conflicts still arise,” he notes.

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Subtle molecular changes along the upper digestive tract could guide cancer therapy — ScienceDaily

Based on a new molecular study of tissues biopsied from various parts of the upper digestive tract, researchers at Georgetown Lombardi Comprehensive Cancer Center have identified significant, if subtle, differences in gene mutations and other factors that could help in developing more tailored treatment options for cancer patients. This finding is notable because as the digestive tract winds its way down from the mouth to the rectum, a continuum of cancers can arise, each of which may be amenable to precision treatment.

In this study, the researchers focused primarily on small bowel adenocarcinomas (SBAs) and compared them with parts of the upper digestive tract that precede it and follow it — the gastroesophageal area and right-sided colon cancers, respectively. Each section of the gastrointestinal, or GI, tract plays a role in digestion of food and hence has distinct structural as well as molecular differences. The finding will be presented June 30, 2017, at the European Society for Medical Oncology gastrointestinal meeting in Barcelona, Spain.

“Our study was undertaken primarily because SBAs are greatly understudied, as well as increasing in incidence nationwide, and we wanted to determine what may make them unique,” says Mohamed E. Salem, MD, assistant professor of medicine at Georgetown Lombardi, and principal investigator for the study. “We really didn’t have good data on SBAs so we’ve been treating the tumors as if they were colon cancers and we really need to start treating them based on their unique properties.”

The investigators looked at 4,278 tumor samples from a tissue repository of patients with GI tract cancers. The researchers were able to clearly identify 531 SBAs; 2,674 gastroesophageal cancers; and 1,073 ride-sided colon cancers. Using a variety of genetic sequencing techniques, they ascertained how well the genes were expressed, or “turned on” to make proteins. They also calculated what is called the tumor mutational load, or TML, which can be a marker for how responsive a tumor is to immunotherapy — which, paradoxically, could indicate that immunotherapy more effective when a higher TML is found.

The researchers found a set of frequently mutated genes in SBAs that could be helpful to clinicians when they are looking to use targeted therapies that work best in cancers with specifics mutations. In this case, KRAS, BRAF, BRCA2 and a few other genes were identified in SBAs. Mutations to these genes can affect the choice of therapy as well as how to better target the mutations.

Next, the investigators compared the SBA mutations with mutations in the two other parts of the GI tract and found higher and lower mutation frequencies across a wide array of genes. They were able to discern that SBAs were more like colon than gastric cancers.

More importantly, though, they found about a two-fold higher PD-L1 expression level for gastroesophageal cancers compared to right-side colon cancers but did not find such a marked difference between those tumors and SBAs. PD-L1 is often used as a marker to indicate if a cancer might be responsive to immunotherapy, and usually the higher the PD-L1 level, the more responsive a cancer would be to certain immunotherapies.

“With this study we now have what I think is one of the biggest datasets on SBAs,” says Salem. “Previously, investigators studying the colon found very unique differences between the left and ride sides, and our study therefore took advantage of those findings by exploring the differences between ride-sided colon cancers and SBAs. We now see a continuum of molecular changes that occur as these regions of the digestive tract transition from one area to the other.”

The next step, says Salem, will be to try to correlate these findings with patient treatment outcomes, initially as a retrospective, or backward looking study, and then hopefully design a forward looking clinical trial to determine which treatments may be best for patients with SBAs.

Overactive scavenger cells may cause neurodegeneration in Alzheimer’s — ScienceDaily

For the first time, researchers have demonstrated a surprising effect of microglia, the scavenger cells of the brain: If these cells lack the TDP-43 protein, they not only remove Alzheimer’s plaques, but also synapses. This removal of synapses by these cells presumably lead to neurodegeneration observed in Alzheimer’s and other neurodegenerative diseases.

Similar to other neurodegenerative disorders, Alzheimer’s is a disease in which the cognitive abilities of afflicted persons continuously worsen. The reason is the increasing loss of synapses, the contact points of the neurons, in the brain. In the case of Alzheimer’s, certain protein fragments, the β-amyloid peptides, are suspected of causing the death of neurons. These protein fragments clump together and form the disease’s characteristic plaques.

Voracious microglia cells destroy brain synapses

Together with researchers from Great Britain and the United States, the group of Lawrence Rajendran from the Institute for Regenerative Medicine of the University of Zurich now shows that dysfunctional microglia cells contribute to the loss of synapses in Alzheimer’s and other neurodegenerative diseases. These scavenger cells usually monitor the function of neurons in the brain by removing excess synapses during development or toxic protein aggregates. Until now, their role in neurodegenerative disorders remains controversial.

In an initial step, the researchers looked at the effect that certain risk genes for Alzheimer’s have on the production of the β-amyloid peptide. They found no effect in neurons. This led the researchers then to examine the function of these risk genes in microglia cells — and made a discovery: If they turned off the gene for the TDP-43 protein in these scavenger cells, these cells remove β-amyloid very efficiently. This is due to the fact that the lack of TDP-43 protein in microglia led to an increased scavenging activity, called phagocytosis.

The TDP-43 protein regulates the activity of scavenger cells

In the next step, researchers used mice, which acted as a disease model for Alzheimer’s. In this case, as well, they switched off TDP-43 in microglia and observed once more that the cells efficiently eliminated the β-amyloid. Surprisingly, the increased scavenging activity of microglia in mice led also to a significant loss of synapses at the same time. This synapse loss occurred even in mice that do not produce human amyloid. This finding that increased phagocytosis of microglia can induce synapse loss led researchers to hypothesize that perhaps, during aging, dysfunctional microglia could display aberrant phagocytic activity. “Nutrient deprivation or starvation-like mechanism during aging could enhance phagocytic mechanism in microglia and this could lead to synaptic loss” Lawrence Rajendran assumes.

Direct role in neurodegeneration

The results show that the role of microglia cells in neurodegenerative diseases like Alzheimer’s has been underestimated. It is not limited to influencing the course of the disease through inflammatory reactions and the release of neurotoxic molecules as previously assumed. Instead, this study shows that they can actively induce neurodegeneration. “Dysfunction of the microglia cells may be an important reason why many Alzheimer’s medications reduce the amyloid plaques in clinical testing, but the cognitive functions in patients do not lead to improvement,” Rajendran says.

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Popular class of drugs reverse potentially harmful genetic changes from heart disease — ScienceDaily

Beta blockers are commonly used world-wide to treat a variety of cardiovascular conditions, such as arrhythmias and heart failure. Scientists have known for decades that the medications work by slowing the heart rate and reducing the force of contraction — lessening the burden of work carried out by the heart. However, new research out of York University has now shown that these drugs also reverse a number of potentially detrimental genetic changes associated with heart disease.

Using an experimental model of heart failure and next generation sequencing to get a snapshot of all of the RNA in the heart cells, the researchers identified the global gene expression changes that occur in heart failure. Then they explored what happened to this pattern of gene expression when beta blocker treatment was implemented, and what they found not only surprised them, but could have important ramifications for future treatments of heart disease.

“We discovered that beta blockers largely reverse the pathological pattern of gene expression observed in heart failure,” said Faculty of Science Professor John McDermott, who led the research, along with York U collaborators Professor Gary Sweeney and Professor Jorg Grigull. “This could mean that the reversal or suppression of pathological gene expression by beta blockers is somehow protective against heart failure, but it’s something we would need to look into further to understand how individual genes function in the heart.”

Interestingly, the study also found that some genes associated with the immune system were dysregulated in heart failure, supporting recent research that has suggested the immune system and inflammation are involved in heart disease.

About 600,000 Canadians are living with heart failure, and the disease is expected to rise as more people survive heart attacks and other heart conditions and continue to live longer.

McDermott and his team have identified genes that will be further explored for their potential use in diagnosis and treatment in heart failure.

The study, “Heart Failure and MEF2 Transcriptome Dynamics in Response to B-Blockers,” was published today in Nature Scientific Reports.

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A perturbed skin microbiome can be ‘contagious’ and promote inflammation — ScienceDaily

Even in healthy individuals, the skin plays host to a menagerie of bacteria, fungi and viruses. Growing scientific evidence suggests that this lively community, collectively known as the skin microbiome, serves an important role in healing, allergies, inflammatory responses and protection from infection.

In a new study, researchers at the University of Pennsylvania have shown for the first time that, not only can infection with the Leishmania parasite alter the skin microbiome of affected mice, but this altered microbial community can be passed to uninfected mice that share a cage with the infected animals.

Mice with the perturbed microbiome, or dysbiosis, had heightened inflammatory responses and more severe disease when they were subsequently infected with Leishmania. The findings are published in the journal Cell Host & Microbe.

“To my knowledge, this is the first case where anyone has shown that a pre-existing skin microbiome can influence the outcome of an infection or a disease,” said Elizabeth Grice, co-senior author and assistant professor in the departments of Dermatology and Microbiology in Penn’s Perelman School of Medicine. “This opens the door to many other avenues of research.”

In addition, when the researchers examined samples from human Leishmania patients, they found similar patterns of dysbiosis as in the infected mice, a hint that the findings may extend to people.

“The transmission of dysbiosis in the skin from one animal to another is a key finding,” said Phillip Scott, professor of immunology in the Department of Pathobiology in Penn’s School of Veterinary Medicine and co-senior author on the study. “And the fact that we saw similar patterns of dysbiosis in humans suggests there could be some very practical implications of our work when it comes to treating people with leishmaniasis.”

Grice and Scott collaborated with researchers from Penn Medicine and Penn Vet, including lead author Ciara Gimblet, a Ph.D. student in Scott’s lab, and colleagues from Brazil’s Oswaldo Cruz Foundation.

Cutaneous leishmaniasis is a tropical disease caused by a parasite and transmitted by the bite of a sand fly. The disease results in sores on the skin, which can sometimes become severe and disfiguring. There is no vaccine for the disease and the limited drugs available often fail to provide a complete cure.

Curious about the influence of the skin microbiome on the disease, the Penn-led team swabbed the skin of 44 Leishmania patients, analyzing the microbiota not only of their lesions but also the area around them and a portion of skin on the opposite side of the bodies as the lesion. They noticed that the lesion samples contained less bacterial diversity than the samples of other skin sites. But not all of them were the same; they found three distinct community types: one dominated by Staphylococcus, one by Streptococcus and one that was mixed.

To get a clearer picture of how these microbiome shifts were connected to the disease, the researchers turned to a mouse model of Leishmania infection. Mirroring the findings in humans, the team found that infection with the Leishmania parasite induced a change in the skin microbiota in mice. They also found an association between the microbiota community type and disease severity. In mice that eventually resolved their infections, Staphylococcus dominated in the lesions, while Streptococcus was the dominant species in lesions on mice with a persistent, severe form of the disease.

A major discovery was that these shifts in microbiota were transmissible not only to other parts of the same mouse but to cage mates. When they kept mice infected with Leishmania in the same cage as uninfected mice for six weeks, the uninfected mice acquired a perturbed skin microbiome “profile” that resembled the infected mice.

The researchers hope to see whether the sharing of perturbed microbiota happens not just in mouse cages but also in households.

“I think an important next step will be to see if this sharing of microbiota occurs in people, and whether that could be a factor in affecting the severity of infections in humans,” Grice said.

A final question was to determine whether this naturally transmitted dysbiosis would predispose the uninfected animals’ response to an enhanced inflammatory response. And indeed, when infected with Leishmania, these mice had more severe inflammation and skin ulcers than mice with unperturbed skin microbiota. In a more general assay, the researchers used a contact hypersensitivity assay, which uses a skin irritant to elicit an immune response, on the mice that had been housed with Leishmania-infected mice. These dysbiotic mice, too, had a heightened inflammatory response.

To follow up on their findings, the researchers hope to examine whether sharing of a dysbiosis occurs in other infections and whether the resulting alteration in skin microbiota affect processes such as wound healing.

In addition, the Penn researchers will be working with their colleagues in Brazil to further examine the connections between the microbiome and leishmaniasis. Specifically, they hope to determine whether there is a connection between the type of skin microbiome present in Leishmania lesions and the severity of disease, or the responsiveness to treatment.

If true, “this may make us rethink the role of antibiotics in treating leishmaniasis,” Scott said.

Though previous studies are mixed about the effectiveness of antibiotics in alleviating the disease, additional information about the microbes that exacerbate inflammation could lead to more tailored therapies to tame skin lesions.