Body

DALLAS, July 31, 2019 -- People enrolled in a large clinical hypertension management trial were half as likely to control their blood pressure if they received care at clinics and primary care practices in low-income areas, according to new research in Journal of the American Heart Association, the Open Access Journal of the American Heart Association/American Stroke Association.

Participants in a low-income area had a 25% higher chance of dying from any cause and a 25% higher likelihood of hospitalization and death related to heart failure over the course of the study period, than those receiving care in higher income areas.

In addition, participants at low-income sites also had an 86% higher likelihood of developing end stage kidney disease and were 30% less likely to receive a procedure performed to open the blood vessels to the heart for patients experiencing chest pain or heart attack.

The findings are based on data obtained from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the largest randomized clinical trial of high blood pressure treatment in North America, which compared the effectiveness of three blood pressure lowering drugs. The study used 140/90 mm Hg as the threshold for high blood pressure, while the American Heart Association recognizes high blood pressure as 130/80 mm Hg.

Researchers know that living in low-income areas is associated with higher rates of high blood pressure, heart failure and stroke. The new study explored whether cardiovascular outcomes vary by socioeconomic factors in a randomized clinical trial in which participants are treated equally.

"Typically in a randomized controlled trial where we try to equalize care across treatment arms and across clinical sites, we aim to isolate the effect of a medication to understand its efficacy," said senior study author Erica Spatz, M.D., an associate professor of medicine at Yale School of Medicine. "While medications are the mainstay of hypertension control, there are other factors that we need to pay attention to that are impacting blood pressure control, and the ultimate outcomes we care about - heart disease, stroke, hospitalization and longevity."

ALLHAT enrolled men and women aged 55 years and older with untreated or treated hypertension in the United States, Canada, Puerto Rico and the Virgin Islands from 1994 to 2002. Because of differences in comparing socioeconomic status across geographic regions, the new study was restricted to the roughly 13,000 participants in the continental United States. Of these, 7.8% received care in the lowest income sites and 37.6% received care in the highest income sites.

Participants in the low-income areas were more likely to be female, black, Hispanic, have fewer years of education and live in the South. Participants in low-income areas also surprisingly had fewer cardiovascular risk factors such as history of heart attack or stroke, Type 2 diabetes and cigarette smoking. Also, participants in the low-income areas visited their doctors less compared to higher income areas, potentially due to transportation access, social support and health behaviors which may have indirectly impacted some outcomes. The findings suggest that clinical trial design should consider the socioeconomic context of the treatment site and participants' neighborhoods.

Baltimore, MD--A newly developed technique that shows artery clogging fat-and-protein complexes in live fish gave investigators from Carnegie, Johns Hopkins University, and the Mayo Clinic a glimpse of how to study heart disease in action. Their research, which is currently being used to find new drugs to fight cardiovascular disease, is now published in Nature Communications.

Fat molecules, also called lipids, such as cholesterol and triglycerides are shuttled around the circulatory system by a protein called Apolipoprotein-B, or ApoB for short. These complexes of lipid and protein are called lipoproteins but may be more commonly known as "bad cholesterol."

Sometimes this fat-and-cholesterol ferrying apparatus stops in its tracks and embeds itself in the sides of blood vessels, forming a dangerous buildup. Called plaque, these deposits stiffen the wall of an artery and makes it more difficult for the heart to pump blood, which can eventually lead to a heart attack.

"These ApoB-containing lipoproteins are directly responsible for creating plaques in blood vessels, so learning more about them is essential to fighting the global epidemic of cardiovascular disease," explained lead author James Thierer a graduate student at Johns Hopkins who does research at Carnegie's Department of Embryology.

Identifying ways to lower levels of plaque-forming lipoproteins in the bloodstream would save lives. But ApoB is a very large protein complex, making it difficult to study using traditional molecular biology research techniques.

So, Thierer and Carnegie's Steven Farber, together with a colleague from the Mayo Clinic, developed the LipoGlo system, which used state-of-the-art genome engineering to tag ApoB with a glowing enzyme that's similar to the one that lights up fireflies. This enabled them to monitor the movement of ApoB complexes in larval zebrafish. Their approach is so sensitive it can be used to measure lipoproteins in an almost microscopic droplet of blood, allowing researchers to perform many of the same medical tests that are conducted on humans in tiny zebrafish larvae.

"Statin drugs have helped a lot of people and saved many lives, but folks still die of cardiovascular disease every year, so there is an urgent need for new medical strategies to understand and prevent arterial plaque buildup," said Farber. "Our LipoGlo system allows us to study ApoB in a tiny larval zebrafish, enabling us to try thousands of potential pharmaceuticals and to find the needle in a haystack that could be the next treatment for this terrible disease. This type of whole-animal screening is not possible in any other vertebrate"

Currently, doctors in the US determine the risk of arteriosclerosis indirectly by measuring the blood concentrations of lipoprotein components like fat and cholesterol. But it's an imperfect tool that can, in some cases, underestimate the risks.

LipoGlo allows Farber and his team to directly observe the concentration, size, and distribution of lipoproteins in vanishingly small samples of material so that they can eventually elucidate ways to fight the risks of heart disease.

Using this system, Thierer, Farber, and the Mayo Clinic's Stephen Ekker also discovered a mysterious gene called pla2g12b, which has a huge impact on both the size and number of ApoB-containing lipoproteins. It is still unclear how exactly this gene works, but further investigation could help the team understand why heart disease runs in families or point to a new strategy for controlling the number of lipoproteins in the bloodstream.

"Although there is much more work to be done to fully understand the processes underlying atherosclerosis, these findings show that our LipoGLo tool has the power to transform our understanding of lipoprotein biology, which will have important implications for future strategies to treat heart disease," concluded Farber.

DALLAS, July 30, 2019 - Less-invasive procedures to open severely-clogged leg arteries were as good at helping people survive and avoid amputation as more invasive open surgeries, according to a study reported in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal.

The most severe form of clogged leg arteries - critical limb ischemia - may result in slow healing leg wounds, gangrene, or the need for amputation. The study notes that the incidence of critical limb ischemia has continued to rise with the aging U.S. population. By the year 2050 it is estimated that the number of patients who undergo amputation will more than double from 1.6 million, to 3.6 million.

"The question has been whether to first offer an open surgery or an endovascular procedure to patients with critical limb ischemia. Each strategy has its benefits, but it is unclear which one first is optimal and we wanted to gain a better understanding of what the current outcomes were," said Jonathan Lin, M.D., a surgery resident in the department of surgery at UC Davis Health.

In an open surgery, a section of vein from the patient (or a synthetic material if there is no appropriate vein available) is used to bypass the blockage and provide an alternative route for the blood to reach the lower leg and foot. In a less invasive endovascular procedure, the physician gains access to the inside of the artery with a thin, flexible tube and wire that is inserted through a small incision in the groin and guided to the blocked area. After the clogged area is opened, it can be supported and propped open by inserting a medicine-coated wire mesh tube.

Open procedures require a hospital stay and about a month of recovery. Endovascular procedures can be done on an outpatient basis and may be performed on patients who are not healthy enough for open surgery.

Investigators examined records of more than 16,000 patients (59% male, average age 71 years). Patients had undergone either open bypass first (36%) or an endovascular procedure first (64%) for critical limb ischemia at non-government hospitals in California between 2005 and 2013.

Compared with patients who received open surgery first, researchers found that, during the study period, those who were first treated with an endovascular procedure had a longer period of amputation-free survival and were:

less likely to require a major amputation - below or above the knee, during the study;
however slightly more likely to require another procedure or surgery to restore blood flow;
no more likely to die, although at the time of their procedures many had serious medical conditions such as kidney failure, congestive heart failure, and diabetes.
"The data here suggest that, in the grand scheme of things, an endovascular-first approach is at least not producing a worse result," Lin said. "Regardless, the type of therapy a patient will receive needs to be a decision that patients and their physicians arrive at together. Critical limb ischemia is usually not an emergency and there is time to determine the most appropriate course of therapy. "

The study was limited by not having information on medical factors (such as the severity of their wounds and whether they had a long and wide enough vein to perform a bypass) that might have influenced whether patients were treated with open surgery or an endovascular procedure. The patient population was also limited to specific hospitals in California.

CAMBRIDGE, MA -- More than 15 million colonoscopies are performed in the United States every year, and in at least 20 percent of those, gastroenterologists end up removing precancerous growths from the colon. Eliminating these early-stage lesions, known as polyps, is the best way to prevent colon cancer from developing.

To reduce the risk of tearing the colon during this procedure, doctors often inject a saline solution into the space below the lesion, forming a "cushion" that lifts the polyp so that it's easier to remove safely. However, this cushion doesn't last long.

MIT researchers have now devised an alternative -- a solution that can be injected as a liquid but turns into a solid gel once it reaches the tissue, creating a more stable and longer-lasting cushion.

"That really makes a huge difference to the gastroenterologist who is performing the procedure, to ensure that there's a stable area that they can then resect using endoscopic tools," says Giovanni Traverso, an assistant professor in MIT's Department of Mechanical Engineering and a gastroenterologist at Brigham and Women's Hospital.

Traverso is the senior author of the study, which appears in the July 30 issue of Advanced Science. The lead authors of the study are former MIT postdocs Yan Pang and Jinyao Liu. Other authors include MIT undergraduate Zaina Moussa, technical associate Joy Collins, former technician Shane McDonnell, Division of Comparative Medicine veterinarian Alison Hayward, Brigham and Women's Hospital gastroenterologist Kunal Jajoo, and David H. Koch Institute Professor Robert Langer.

A stable cushion

While many colon polyps are harmless, some can eventually become cancerous if not removed. Gastroenterologists often perform this procedure during a routine colonoscopy, using a lasso-like tool to snare the tissue before cutting it off.

This procedure carries some risk of tearing the lining of the colon, which is why doctors usually inject saline into the area just below the lining, called the submucosal space, to lift the polyp away from the surface of the colon.

"What that does is separate those tissue layers briefly, and it gives one a little bit of a raised area so it's easier to snare the lesion," Traverso says. "The challenge is that saline dissipates very quickly, so we don't always have enough time to go in and intervene, and may need to reinject saline."

Complex lesions can take 10 to 20 minutes to remove, or even longer, but the saline cushion only lasts for a few minutes. Researchers have tried to make the cushions longer-lived by adding thickening agents such as gelatin and cellulose, but those are very difficult to inject through the narrow needle that is used for the procedure.

To overcome that, the MIT team decided to create a shear-thinning gel. These materials are semisolid gels under normal conditions, but when force is applied to them, their viscosity decreases and they flow more easily. This means that the material can be easily injected through a narrow needle, then turn back into a solid gel once it exits into the colon tissue.

Shear-thinning gels can be made from many different types of materials. For this purpose, the researchers decided on a combination of two biocompatible materials that can form gels -- Laponite, a powdery clay used in cosmetics and other products, and alginate, a polysaccharide derived from algae.

"We chose these materials because they are biocompatible and they allow us to tune the flowing behavior of the resulting gels," Pang says.

Using these materials, the researchers created a shear-thinning gel that could be injected and form a stable cushion for more than an hour, in pigs. This would give gastroenterologists much more time to remove any polyps.

"Otherwise, you inject the saline, then you change tools, and by the time you're ready the tissue is kind of flat again. It becomes really difficult to resect things safely," Traverso says.

Controlling viscosity

By varying the composition of the gel components, the researchers can control features such as the viscosity, which influences how long the cushion remains stable. If made to last longer, this kind of injectable gel could be useful for applications such as narrowing the GI tract, which could be used to prevent acid reflux or to help with weight loss by making people feel full. It could also potentially be used to deliver drugs to the intestinal tract, Traverso says.

The researchers also found that the material had no harmful side effects in pigs, and they hope to begin trials in human patients within the next three to five years.

"This is something we think can get into patients fairly quickly," Traverso says. "We're really excited about moving it forward."

An IMAS-led study of seabirds that had ingested plastic debris has revealed a range of non-lethal impacts on their health and physiology.

While seabird deaths due to swallowing plastic debris or becoming entangled in it have received global attention, the non-lethal effects on seabirds that survive plastic ingestion are less well-known.

The study led by IMAS' Dr Jennifer Lavers and published in the journal Environmental Science & Technology has found that plastic ingestion can have a significant negative impact even on superficially healthy seabirds.

The research, which included scientists from Lord Howe Island Museum and the UK's Natural History Museum, analysed blood and plastic samples collected from Flesh-footed Shearwaters on Lord Howe Island.

"Flesh-footed Shearwaters populations are declining across the south west Pacific Ocean and Western Australia's south coast," Dr Lavers said.

"Plastic ingestion has been implicated in this decline but the mechanisms by which it affects shearwaters are poorly understood.

"Our study found that birds which ingested plastic had reduced blood calcium levels, body mass, wing length, and head and bill length.

"The presence of plastic also had a negative impact on the birds' kidney function, causing a higher concentration of uric acid, as well as on their cholesterol and enzymes."

Dr Lavers said the study found that the simple presence of plastic was enough to cause negative consequences, regardless of the amount.

"Our data did not show a significant relationship between the volume of plastic ingested and the health of individuals, suggesting that any plastic ingestion is sufficient to have an impact.

"Until now there has been scant information on the blood composition of seabirds in the wild, many of which have been identified as threatened species.

"Understanding how individual seabirds are affected is also further complicated by the fact they spend little time on land or at breeding colonies, and most mortalities occur at sea where the causes of death are often unknown.

"The complex range of issues that face seabirds - from habitat loss and climate change to fishing and marine pollution - make it vital that we better understand the impact of particular challenges such as plastic debris," Dr Lavers said.

Massive hemorrhage, or excessive bleeding, is a potentially preventable yet a major cause of death in trauma patients.

An immediate and well-balanced transfusion of blood components, such as platelets and red blood cells (RBCs) which, respectively form clots to stop bleeding and deliver oxygen to tissues and organs for proper function, becomes crucial for their survival.

Unfortunately, however, blood products may not always be in stock in case of an emergency, such as when a serious car accident involving many drivers and passengers occurs, because they cannot be preserved for long. For instance, a pack of RBCs can only be stored for 3 weeks at 2-6°C. This becomes only four days at room temperature for a platelet concentrate, and it must be constantly shaken in a shaker.

To act as substitutes for these components, a Japanese research team successfully resuscitated rabbits with coagulopathy, or an impaired ability to form blood clots, from severe hemorrhage shock by using two different nanoparticles; one with hemostatic potential and the other with an oxygen-carrying potential.

Shinji Takeoka of Waseda University said, "Our findings suggest not only that the nanoparticles we developed have excellent preservation property but also that the combination therapy using the hemostatic nanoparticles and the oxygen-carrying nanoparticles are comparable to conventional transfusion."

This study, published in Transfusion, is the first to report a combination therapy using two different types of functional nanoparticles.

"In this experiment, the research team penetrated the liver of rabbits with abnormally low levels of platelets to induce massive hemorrhage and administered the hemostatic nanoparticles developed in a previous study while blocking the bleeding site immediately after injury," Manabu Kinoshita of the National Defense Medical College Japan explains. "After five minutes, clotting was confirmed, and the oxygen-carrying nanoparticles were given to help the rabbits recover from anemia due to blood loss."

As a result, six out of the ten rabbits treated by this new combination therapy survived in comparison to the seven out of ten by conventional transfusion of platelet and RBC concentrates, showing similar hemorrhage control.

Hiromi Sakai of Nara Medical University said, "The hemostatic particles we developed can be stored for about one year at room temperature, with no shaking required. The same goes for oxygen-carrying nanoparticles. Also, the oxygen-carrying nanoparticles do not need any kind of blood typing or cross-match tests."

The team believes that the combination therapy using these nanoparticles will be effective for both in-hospital care and pre-hospital resuscitation.

Additionally, because blood supply is anticipated to decrease in countries with a low birthrate and an aging population such as Japan, the team hopes that the nanoparticles will be used for practical application in the future to save lives of patients who require massive transfusion in emergency trauma care.

UNIVERSITY PARK, Pa. - The devastating consequences of the opioid crisis are far-reaching in the United States, impacting public health as well as social and economic welfare. Penn State researchers recently collaborated to address the issue in a supplement of The American Journal of Managed Care titled "Deaths, Dollars, and Diverted Resources: Examining the Heavy Price of the Opioid Epidemic."

According to Dennis Scanlon, distinguished professor of health policy and administration and director of the Center for Health Care and Policy Research at Penn State, the articles and commentaries in the special issue focus on the costs to governments, notably state governments.

"State and local governments have long shouldered the burden of the opioid epidemic and its costs to individuals and families. They are at ground zero for the epidemic, where services for those being harmed by opioids are significant and costly, spanning well beyond healthcare for treatment and prevention."

Scanlon, along with Christopher Hollenbeak, professor of health policy and administration at Penn State, authored the introduction to the special issue, noting "We take an opportunity to raise several important broader questions we believe have not received enough attention but are critically important for learning from the current opioid epidemic and preventing the potential burdens that could be associated with the next epidemic."

Topics in this special issue are diverse and include the costs of the opioid crisis on employment and labor market productivity, burdens on the child welfare system and special education, the increased costs to the criminal justice system, and the economic burden on state Medicaid programs.

"The supplement fulfills our initial goal of exploring the effects of the opioid crisis on societal costs," Scanlon explained. "Each article in this special issue presents complex cost analyses of the implications of opioid misuse, shedding new light on the opioid epidemic at the state level, and adds to a growing body of literature about the opioid epidemic."

For example, researchers found that between 2000 and 2016, opioid misuse reduced state tax revenue by over $11 billion, including approximately $10 billion in lost income tax revenue and almost $2 billion in lost sales tax revenue. In another paper, researchers found that between 2007 and 2016, total costs to Pennsylvania's criminal justice system from the opioid crisis was over $526 million.

Meanwhile, total Medicaid costs associated with opioid use disorder more than tripled between 1999 and 2103, reaching more than $3 billion. Additionally, total annual education costs for children born in Pennsylvania with neonatal abstinence syndrome associated with maternal use of prescription opioids was estimated at over $1 million. Finally, researchers also found increased costs of almost $3 billion to the child welfare system from 2011 to 2016.

"Due to these costs, every American has suffered and will continue to suffer from resources diverted to the epidemic that could have been made available for a more productive societal use," said Scanlon.

Another unique aspect of the issue is the strong Penn State presence, as all authors are either faculty or staff or current or former graduate students. Additionally, one of the commentaries is co-authored by the Commonwealth of Pennsylvania Secretary of Health Rachel Levine, who provides further perspective into the opioid crisis at the state level.

Moving house during the first three months of pregnancy is linked to a heightened risk of premature birth and low birthweight as well as a slightly higher risk of a smaller than expected size baby, finds US research published online in the Journal of Epidemiology & Community Health.

Moving house during childhood is associated with poorer health in children, but despite being a frequent occurrence, little is known about the potential health impact of a house move during pregnancy.

To try and rectify this, the researchers analysed birth certificate data for babies born in Washington state, USA, between 2007 and 2014 to mothers aged at least 18.

They randomly selected 30,000 women who had moved during the first three months of pregnancy??known as the first trimester??and matched them with 120,000 randomly selected women of the same birth year, but who hadn't moved house during early pregnancy.

The first trimester was chosen because previous research has suggested that major stressors during early pregnancy have a greater impact on the health of the baby than those experienced later on in the pregnancy.

The final analysis included 28,011 women who had moved early in pregnancy and 112,451 who hadn't.

Women who moved early in pregnancy were likely to be younger, to be less well educated, to live in areas with lower average levels of household income and to have had other children than women who hadn't moved. They were also more likely to be unmarried and to have smoked during their pregnancy.

These are all potential risk factors for the outcomes the researchers were looking at: low birthweight; premature birth; and smaller than expected size babies.

But after taking account of these potentially influential factors, a house move during the first three months of pregnancy was associated with a 37% heightened risk of low birthweight (6.4% vs 4.5%) and a 42% heightened risk of premature birth (9.1% vs 6.4%) compared with those who didn't move during this period.

A house move in the first trimester was also associated with a slightly increased (9%) risk of giving birth to a smaller than expected size baby (9.8% vs 8.7%).

These differences were seen across women in all social and economic strata.

The researchers weren't able to explore the potential reasons behind their findings, but interruptions to healthcare, the physical strain of moving, disruptions to social support, and a biological stress reaction may all be possible triggers, the researchers suggest.

This is an observational study, and as such, can't establish cause. Although the study included a large number of women, the researchers weren't able to establish the reasons for the move or whether the women moved into more or less desirable areas, all of which may have influenced the results.

"Despite these limitations, our results yield important insights regarding moving during pregnancy," write the researchers.

"Regardless of whether the negative impact of moving is driven by the stress from the move itself, stressful situations leading to a move, or disruption of care because of the move, asking patients about plans to move and using that as an opportunity to counsel patients on stress mitigating techniques and care continuity may be beneficial," they conclude.

AUGUSTA, Ga. (July 30, 2019) - It's the proportionality of a newborn -- a measure that includes both birthweight and length -- that may best tell doctors whether a child is born with an increased risk for heart problems later in life, investigators report.

Birthweight, while important, tells only part of the story of fetal growth, while the additional consideration of length, gives a more complete picture of both fetal growth and growth trajectory, says Dr. Brian Stansfield, neonatologist at the Medical College of Georgia and Children's Hospital of Georgia at Augusta University.

Measures called ponderal index, or PI, as well as the more widely used body mass index, or BMI, which both account for height and weight, likely provide a more accurate indication of fetal growth and what's ahead for the child, says Stansfield, corresponding author of the study the journal Early Human Development.

The new study indicates that a low PI or low BMI at birth, much like high cholesterol or high blood pressure, should be considered a risk that needs attention and intervention, says Stansfield who is also a research clinician in MCG's Vascular Biology Center.

Historically, birthweight has been the focus of studies connecting early life to later health consequences.

"When you look at birthweight alone, you are looking at a measure at a single point in time, which is a big problem when it comes to projecting out," says Stansfield.

It's known that perinatal growth -- which is affected by numerous factors from genetics to environmental ones like the mother's health and habits like smoking, nutrition and gestational diabetes -- has important implications for heart development, and animal and human studies have associated low birthweight with heart problems and death.

MCG investigators hypothesized that a baby's PI or BMI at birth would provide a much better indicator of heart development and future function than just birthweight.

They found in a group of 379 healthy adolescents, that a low PI -- where increases in height and weight are out of sync during development-- was most associated with an increase in the size of the major pumping chamber of the heart, the left ventricle, which is considered a risk for future cardiovascular disease.

The findings further suggest that factors that impact fetal growth also can alter heart development, changes that may have a permanent, negative impact on heart function and cardiovascular health as adults, they write.

They also indicate that proportionality can help differentiate babies who are born small because of their genetics -- smaller parents tend to have smaller babies, for example -- and those who fail to reach their in utero growth potential for other reasons.

"What we are trying to do is understand how do we categorize these children at birth so that we know who to watch more closely and ideally intervene earlier to help offset some of these risks," Stansfield says.

While his study found that a low PI had the highest association with risk factors for heart problems, the more widely used BMI is also a good tool, he notes. BMI accounts for length, by dividing birthweight by birth length to the second power, while PI gives length even more emphasis by using the power of three.

"We believe our findings are a call to pediatricians to be even more diligent in measuring and noting birthweight and length parameters," Stansfield says of his typically exceedingly thorough colleagues. They also are a call to adult primary care providers to be aware that this very early measure of height and weight can provide lifelong insight into an individual's risk of heart and other disease, he says. Digital health records should help doctors and patients alike find and keep up with these early statistics and ideally intervene before trouble starts, he notes.

Additionally, they are another reminder to mothers-to-be to abstain from smoking, alcohol and drugs; eat right; and exercise safely during pregnancy to try to ensure a healthy environment for their developing child, Stansfield says. He notes that even the genetics a baby inherits can be altered for better or worse through what he experiences during development.

Risks for health problems like heart disease are a confluence of genetics and environmental risks and those environmental risks also start in utero, he says.

For this study, they looked at 379 healthy black and white adolescents ages 14-18 from the Augusta, Georgia area. Parents provided their children's birthweight and length, which were used by investigators to calculate a BMI and PI.

Two-dimensional echocardiography was used to noninvasively look at the children's left ventricle for telltale indicators of hypertrophy like thickening of the walls and less blood being pumped out.

Then, in what appears to be the first study to do this, they looked at relationships between birthweight and birth BMI and PI and the structure and function of the left ventricle in the children.

Other measures also were done, like the Tanner scale, which looks more specifically at pubertal development. The investigators also assessed factors like socioeconomic status and physical activity, including the children wearing monitors to track physical movement for seven days.

Stansfield notes that at the time of their follow up for this study, about 25% of the adolescents had obesity or were overweight and most were on an upward trajectory with their BMI, which is not good.

Children with an upward trajectory had about a 30% likelihood they would become obese versus those with a downward trajectory, who have about a 5% likelihood.

There was also about a 40% increase in visceral adiposity -- fat around the belly and the organs inside the abdominal cavity, which is considered particularly unhealthy -- in adolescents with the upward versus downward BMI trajectory. Those children also were much more likely to have a higher systolic pressure -- the top number of a blood pressure which indicates the pressure inside arteries when the heart is contracting.

While more work is needed to put all the pieces together, proportionality also may help identify babies who appear, at least at birth, to be headed toward good heart health, Stansfield says.

Lab animal studies indicate that cardiac mass is mostly determined at birth, and production of heart cells, or cardiomyocytes, that make up the heart rapidly diminishes after birth so, to get larger, the heart cells you are born with have to enlarge, called hypertrophy, which is not considered normal growth. Enlargement of the left ventricle typically results from the heart having to work too hard against, for example, high pressure inside blood vessels, and can result in heart failure.

MCG investigators reported last year in the journal Pediatric Research that fetal growth restriction in Guinea pigs suppresses the production of and increased the death of cardiomyocytes, and led to hypertrophy of cardiomyocytes that were present and other disruptions of the heart's normal architecture.

The risk of other chronic disease, like obesity and diabetes, also has now been linked to low birthweight but the cardiovascular system seems particularly impacted by perinatal growth, the investigators say. In fact, by week five, the baby's heart has begun to develop, and it's during this critical period of development that the baby is most at risk for birth defects from factors like alcohol consumption by the mother and some medicines.

Highlights

Brain aneurysms were detected by pre-symptomatic screening in 9% of patients with autosomal dominant polycystic kidney disease, more frequently in those with a history of hypertension and smoking.

Very few patients experienced aneurysmal ruptures, but the overall rupture rate was approximately 5 times higher than in the general population.

Washington, DC (July 30, 2019) -- Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts, as well as abnormalities outside the kidneys, including brain aneurysms--or weaknesses in blood vessels in the brain that balloon and fill with blood and may later rupture. A new study appearing in CJASN investigated whether patients with ADPKD should be routinely screened for brain aneurysms.

For the study, Vincente E. Torres, MD, PhD (Mayo Clinic) and his colleagues examined the medical records of 812 patients with ADPKD who were evaluated between 1989 and 2017 and underwent brain imaging tests despite having no neurological symptoms.

Among the major findings:

94 brain aneurysms were diagnosed in 75 of the 812 (9%) patients who underwent screening. None of the aneurysms ruptured over an average follow-up of 9 years.

Gender, age, race, and genetics related to ADPKD were similar in the groups with and without aneurysms, but hypertension and a history of smoking were more frequent in the aneurysm group.

29% of patients with aneurysms vs. 11% of those without aneurysms had a family history of subarachnoid hemorrhage, a type of stroke caused by bleeding into the space surrounding the brain.

Among patients who had evidence of aneurysms at the initial screening, new brain aneurysms were detected in 5 patients during an average follow-up of 8 years, and none of the aneurysms ruptured.

Among 135 of the 737 patients with no brain aneurysms detected at the first screening who underwent additional screening, 3 patients developed aneurysms over an average follow-up of 7 years, and 2 patients had a brain aneurysm rupture. Both patients had significant risk factors for brain aneurysm development and rupture.

The investigators noted that their results do not allow a firm conclusion on whether widespread or selective screening for brain aneurysms is beneficial in ADPKD. A large prospective study would be necessary to determine the benefits and costs of such strategies.

"Our approach has been to recommend screening for patients with ADPKD who have a family history of aneurysm. We also recommend screening to patients with ADPKD before major elective surgeries (including transplantation), those with high risk occupations, and those who after being properly informed on the available data wish to be screened for reassurance," said Dr. Torres. "We educate our patients on the importance of correcting conditions that have been associated with aneurysmal development and/or rupture, particularly smoking and inadequately controlled hypertension. The results our study do not provide a reason for changing our current approach".

In an accompanying editorial, Ivana Kuo, PhD (Loyola University School of Medicine) and Arlene Chapman, MD (University of Chicago) noted that "this report provides some incremental confirmatory information regarding the increased frequency of intracranial aneurysm, the traditional characteristics of intracranial aneurysm in ADPKD similar to the general population, and a significant need for more mechanistic studies to determine how central a role the ADPKD proteins play in intracranial aneurysm formation."

In an accompanying Patient Voice editorial, Kevin Fowler shared his first-hand experiences with ADPKD and his opinion of the study.

Women with pre-eclampsia during pregnancy have a five-fold increased risk of end stage kidney disease (ESKD) later in life compared to women who don't develop pre-eclampsia during pregnancy, according to a new study published this week in PLOS Medicine by Ali Khashan of University College Cork, Ireland, and colleagues at the Karolinska Institute, Sweden and Liverpool University, UK.

As the prevalence of kidney disease has risen over recent years, it has become clear that more women have pre-dialysis kidney disease than men. Reproductive history, including the development of pre-eclampsia during pregnancy, has been hypothesized to play a role. In the new study, researchers analyzed data from the Swedish Medical Birth Register on 1,366,441 healthy women with 2,665,320 singleton live births in Sweden between 1982 and 2012.

The data revealed that women who had pre-eclampsia in at least one pregnancy were nearly five times more likely to have ESKD than women who had never had pre-eclampsia (hazard ratio 4.96; 95%CI 3.89-6.32). The incidence rate of ESKD per 100,000 person-years was 1.85 (95%CI 1.66-2.05) among women with no history of pre-eclampsia and 12.35 (95%CI 9.61-15.88) among women with a history of pre-eclampsia. Moreover, the association was independent of other factors including maternal age and education, and diagnoses of renal disease or cardiovascular disease before pregnancy.

The new paper "shows that pre-eclampsia is a sex-specific, independent risk factor for the subsequent development of ESKD," the authors say. "However, it should be noted that the overall ESKD risk remains small. Whether screening or preventative strategies will reduce the risk of ESKD in women with adverse pregnancy outcomes is worthy of further investigation."

BOSTON, July 30, 2019 -- In laboratory tests, a compound found in soybeans blocked damage to the lining of blood vessels in the heart and circulatory system and may someday provide a way to prevent the cardiovascular side effects of recreational and medical marijuana use, according to preliminary research presented at the American Heart Association's Basic Cardiovascular Sciences 2019 Scientific Sessions.

Marijuana is the most widely used illicit drug worldwide and is increasingly being made legal for recreational and medicinal purposes. However, there have been studies that link marijuana smoking to an increased risk of heart attack and stroke.

There can also be cardiovascular side effects, including changes in heart rate and blood pressure, when people take FDA-approved medications containing a synthetic version of delta-9-tetrahydrocannabinol (THC) -- the main compound in marijuana that gives the sensation of being high.

"These medications are prescribed to reduce the nausea and vomiting induced by chemotherapy and to increase appetite in certain people with acquired immune deficiency syndrome," said Tzu-Tan "Thomas" Wei, Ph.D., the study's lead author and assistant professor of pharmacology in the College of Medicine at National Taiwan University in Taipei City. "The goal of our studies is to investigate the mechanisms of marijuana-induced damage and discover new drugs to prevent those side effects."

The effects of THC occur after it binds to one of two cannabinoid receptors (CB1 and CB2) that are found throughout the brain and body and are also acted on by naturally occurring cannabinoids.

In the current study, the researchers used endothelial cells (like those that line blood vessels) derived from the stem cells of five healthy people. Exposing the cells to THC, they found that:

THC exposure induced inflammation and oxidative stress, which are known to affect the inner linings of blood vessels and are associated with the development of heart disease.

Lab techniques that block access to the CB1 receptor by THC eliminated the effects of THC exposure on endothelial cells.

Treatment with JW-1, an antioxidant compound found in soybeans, eliminated the effects of THC exposure.

In addition, the researchers used a laboratory technique called wire myography to examine the response of mouse arteries to THC, finding that JW-1 blocked THC's negative effects on the function of the inner lining.

An earlier attempt to gain health benefits from blocking the CB1 receptor proved problematic.

"Previously, a drug that blocked CB1 was approved in Europe for the treatment of obesity, but it had to be withdrawn because of severe psychiatric side effects," Wei said. "In contrast, as an antioxidant, JW-1 may have neuroprotective effects. Discovering a new way to protect blood vessels without psychiatric side effects would be clinically important with the rapid growth of cannabis use worldwide."

The researchers are currently extending their research by testing cells derived from regular marijuana users and those who smoke both cigarettes and marijuana. In addition, they are looking at the impact of THC along with the other main component of marijuana, cannabidiol.

"Meanwhile, if you have heart disease, talk to your doctor before you use marijuana or one of the synthetic THC-containing medications," Wei said. "Marijuana may cause more severe effects on the cardiovascular system in those with pre-existing heart disease."

Researchers at the University of Illinois at Chicago have identified a molecular switch that causes immune cells called macrophages to clean up cellular debris caused by infections instead of contributing to inflammation and tissue injury. Their findings are reported in the journal Proceedings of the National Academy of Sciences.

Macrophages are a type of immune cell found throughout the body. These cells can produce inflammation, which is good in moderation because inflammatory signals bring other immune cells to a specific location to clear an infection. However, when inflammation gets out of control, as it can in cases of inflammatory diseases, it can cause excess cellular and tissue damage, contributing to a vicious cycle that is very difficult to reverse. But macrophages also play a significant role in reducing inflammation when they engulf cellular debris or foreign microbes that contribute to inflammation. The mechanism behind macrophages' ability to switch back and forth between these two diametrically opposed roles has long-puzzled scientists.

Researchers led by Saroj Nepal, research assistant professor in the department of pharmacology at the UIC College of Medicine, have found that a molecule called Gas6 is required to induce macrophages to perform their anti-inflammatory role by engulfing and digesting cellular debris that can contribute to inflammation. The molecule could serve as a potential drug target for drug makers interested in coaxing the cells toward their anti-inflammatory state to help treat people.

In a mouse model of acute lung injury, Nepal and colleagues found that lung macrophages expressed both inflammatory and anti-inflammatory proteins. One of the anti-inflammatory proteins was Gas6. In a mouse model of acute lung injury where the animals' macrophages were artificially depleted of Gas6, clearance of inflammatory molecules and proteins in the lungs was severely impaired, and the inflammation could not be resolved. When they artificially boosted levels of Gas6 in the mouse macrophages, inflammation was resolved much faster than in mice with normal macrophages.

"Harnessing the anti-inflammatory function of macrophages using the Gas6 switch holds great potential for treating diseases ranging from heart disease to cancer to rheumatoid arthritis, where inflammation is a key underlying feature," Nepal said.

Moving to a new residence during the first three months of pregnancy is linked to a heightened risk of premature birth and low birthweight, as well as a slightly higher risk of a smaller-than-expected-size baby, according to new research from the University of Washington published online today in the Journal of Epidemiology & Community Health.

Still, it's too soon to raise warning flags.

"I don't think we have enough information to make any specific recommendations about moving during pregnancy at this point, but I'm hopeful that our study will draw attention to moving as a risk factor worth investigating in more detail," said Julia Bond, the lead author who conducted the research while at the UW School of Public Health.

Little is known about the potential health impact of a house move during pregnancy. To try to  rectify this, the researchers analyzed birth certificate data for babies born in Washington state between 2007 and 2014 to mothers who were 18 or older.

The researchers randomly selected 30,000 women who had moved during the first three months of pregnancy, known as the first trimester, and compared them with 120,000 randomly selected women of the same birth year, but who hadn't moved during early pregnancy.

The first trimester was chosen because previous research has suggested that major stressors during early pregnancy have a greater impact on the health of the baby than those experienced later on in the pregnancy.

The final analysis included 28,011 women who had moved early in pregnancy and 112,451 who hadn't.

Women who moved early in pregnancy were likely to be younger, to be less educated, to have lower levels of household income and to have had other children than women who hadn't moved. Researchers noted that this cohort also was more likely to be unmarried and to have smoked during their pregnancy.

These circumstances and behaviors are all potential risk factors for the outcomes the researchers were looking at: low birthweight; premature birth; and smaller-than-expected-size babies.

After taking account of these potentially influential factors, a house move during the first three months of pregnancy was associated with a 37% heightened risk of low birthweight and a 42% heightened risk of premature birth compared with those who didn't move during this period.

A house move in the first trimester was also associated with a slightly increased risk of giving birth to a smaller-than-expected-size baby.

These differences were seen across women in all social and economic strata that was analyzed.

As an observational study, researchers can't establish cause. The researchers were not able to explore the potential reasons behind their findings, but interruptions to health care, the physical strain of moving, disruptions to social support systems, and a biological stress reaction may all be possible triggers, according to the report.

Although the study included a large number of women, the researchers weren't able to establish the reasons for the participants' moves or whether they moved into more or less desirable areas, which may have influenced the results.

"Despite these limitations, our results yield important insights regarding moving during pregnancy," the researchers write in the report. "Regardless of whether the negative impact of moving is driven by the stress from the move itself, stressful situations leading to a move, or disruption of care because of the move, asking patients about plans to move and using that as an opportunity to counsel patients on stress-mitigating techniques and care continuity may be beneficial."

A research collaboration led by scientists from institutions in Japan including Tokyo University of Agriculture and Technology (TUAT) has developed a new experimental cancer model for dog bladder cancer. Urine samples were used for a 3D cell culture method called organoid culture. This method will allow us to quickly determine the proper chemotherapy and to identify new biomarkers of both dog and human bladder cancer in the near future.

The researchers published their results on July 23rd in Cancer Science.

About 0.01% of humans suffer from bladder cancer. The most common symptom of cancer is blood in the urine and pain during urination. In the United States, 80,470 people are diagnosed with bladder cancer in 2019 and 17,670 are dead. About 90% of all bladder cancers are transitional cell carcinoma, which is usually invasive. In case of dogs, this cancer is detected very late, resulting in poor survival.

"For dogs, bladder cancer should be diagnosed as early as possible," said Tatsuya Usui, DVM, Ph.D., corresponding author on the paper and senior assistant professor in the Laboratory of Veterinary Pharmacology, Department of Veterinary Medicine at TUAT in Japan. "It was, however, very hard to grow bladder cancer cells on flat dishes, which is called a traditional 2D cell culture method." Those researchers then tried a 3D cell culture method called organoid culture. They collected urine samples from bladder cancer dogs and successfully grew bladder cancer cells in urine using this culture system. These cells grown in the 3D cell culture express the same set of genes as the original cancer tissues do.

"Those results encouraged us to test anti-cancer drugs on cells grown in the 3D cell culture. As we expected, the sensitivity of each drug can be easily monitored, " said Usui. "It is now possible that bladder cancer cells from each dog using this system can be treated by several anti-cancer drugs. We can then find which drug is more effective for each dog in the lab before actual treatment. So we would like to apply the system of urine sample-derived dog bladder cancer 3D culture to precision veterinary medicine. In addition, we opened a new avenue for establishing the novel therapeutic strategy against urological cancer in both dog and human."