Body

A personalised active lifestyle programme for employees with metabolic syndrome (who are at high risk of heart disease, stroke, and type 2 diabetes) that uses wearable activity trackers, a smartphone app, and face-to-face sessions with exercise coaches, can reduce disease severity in both men and women in various occupations, according to a randomised trial of over 300 workers published in The Lancet Public Health journal.

Moreover, improvements in exercise capacity, anxiety and depression, and quality of life from being more physically active were associated with participants feeling more able to work and being more productive.

"By equipping participants with a wearable activity tracker we were able to guide and support individuals regardless of where they worked or lived", says Dr Sven Haufe from Hannover Medical School in Germany who led the research. "With the high acceptance of recommended activity and mobile health technologies, and a drop-out rate similar to that seen in other exercise programmes, this type of intervention has huge potential to reduce disease risk, while improving mental health, work ability, and productivity for the large and growing number of employees at high risk of cardiovascular and metabolic disease in an ageing workforce."1

"Offering similar programmes to the broader workforce could ease the healthcare burden and economic costs arising from metabolic syndrome conditions that already affect 1 in 4 adults worldwide (over a billion people)."1

Individuals are diagnosed with metabolic syndrome when they have at least three of its five risk factors--a large amount of abdominal body fat, low levels of high-density-lipoprotein cholesterol, high levels of fat (triglycerides) in the blood, high blood pressure, or high blood sugar levels. Metabolic syndrome increases the chances of developing heart disease, stroke, and type 2 diabetes, but it is also linked with rising costs as a result of sick leave and lost productivity.

Despite the growing epidemics of obesity and metabolic syndrome and an ageing workforce, evidence for the effectiveness of physical activity interventions on work ability in individuals at higher risk of disease is lacking.

The study included 314 volunteers in various occupations (manual/office/shift/full-time) with metabolic syndrome from the main Volkswagen factory in Germany. Participants were randomly assigned to the 6-month lifestyle programme focusing on regular exercise (160 adults), or a control group where participants were not given any specific lifestyle recommendations and carried on as normal (154).

Participants in the exercise group wore a fitness tracker bracelet and received personalised exercise, nutrition, and stress management recommendations at regular face-to-face meetings with an exercise coach and via a smartphone app, with the aim of doing 150 minutes of moderately-intense physical activity a week for 6 months. Activities were adapted based on activity-monitor data.

The researchers measured the change in metabolic syndrome severity adjusted for sex and ethnicity--with high scores representing an increased risk for, or severity of, metabolic syndrome. All participants underwent medical examinations and completed questionnaires about their health-related quality of life, level of anxiety and depression, amount of physical activity, and work ability at the start of the trial and again 6 months later.

Overall, 274 (87%) participants were included in the analysis. The exercise group did an average of 147 minutes moderate intensity exercise per week over 6 months.

After 6 months, the average metabolic score in the exercise group was significantly reduced compared with the control group (0.93 before the intervention and 0.63 after 6 months vs 0.95 and 0.90)--with substantial improvements in four of the five risk factors for metabolic syndrome (waist circumference, triglycerides, blood sugar, and blood pressure) compared with controls (table 2).

Results also showed parallel increases in self-reported work ability (score 0-49) in the exercise group (36.9 before intervention and 39.0 after 6 months), but not in the control group (37.6 and 38.1). Importantly, longer duration of physical activity each week was linked with greater improvement in work ability over 6 months.

Eleven adverse events were reported in the exercise group (orthopaedic [8 events], Chron´s disease diagnosis [1], heart attack [1], renal colic diagnosis [1]), and one in the control group (chronic obstructive pulmonary disease diagnosis). Only one event was deemed directly related to the intervention--one participant in the exercise group reported accidently twisting his ankle during running training. Overall, more participants in the exercise group dropped out of the study compared to the control group (28 vs 12).

The authors note several limitations, including that unmeasured confounding (ie, differences in unmeasured factors which may have affected the health outcomes of the study) such as nutrition and smoking may have influenced results. They also point out that most of participants were men (86%) and white, which could limit the generalisability of the findings.

Discussing the implications of the findings in a linked Comment, Professor Alex Burdorf from Erasmus Medical Center Rotterdam, The Netherlands says, "The health promotion programme by Haufe and colleagues shows great promise for developing more effective preventive interventions on unhealthy behaviours. Given the reported effectiveness with moderate effect sizes after 6 months, this intervention is not the magic solution for combating health-related loss of work ability. Further improvements are required to create a healthy workforce. Promising avenues are multicomponent interventions that address unhealthy behaviours simultaneously and interventions that ensure that strenuous working conditions and unhealthy behaviours are equally targeted. The application of modern technologies in mHealth and eHealth will provide excellent opportunities for dynamic intervention programmes that overcome the traditional barriers of insufficient reach, uptake and sustainability of large-scale health promotion programmes."

GALVESTON, Texas - A new study from The University of Texas Medical Branch at Galveston has further documented how muscles are affected by reduced gravity conditions during space flight missions and uncovered how exercise and hormone treatments can be tailored to minimize muscle loss for individual space travelers. The findings are available in PLOS One.

NASA has recently announced that it will allow private citizens to visit the International Space Station. The growing number of space travelers underscores the need to understand the impact of reduced gravity on the human body.

"The study has given us the ability to identify biomarkers that predict how susceptible each individual is to muscle function decline and how effectively different exercise and hormone treatments can combat the atrophy," said senior author Randall Urban, UTMB chief research officer and professor in the department of internal medicine.

Senior author Melinda Sheffield-Moore, professor in the Texas T&M department of health and kinesiology and UTMB department of internal medicine, said, "This new ability may allow scientists to personalize space medicine by designing specific exercise and/or hormone intervention programs for each astronaut on Earth before they embark on a long-term mission to space."

Space flight-related losses in muscle mass and strength are a key concern for long space exploration missions. The muscle loss during space flight largely stems from fact that weight bearing muscles don't work as hard in reduced gravity conditions. While in space, people exercise in an effort to counter this muscle loss, but it cannot completely prevent muscle atrophy. So, researchers are searching for additional interventions that compliment inflight exercise.

The effects of long-term muscle inactivity can be investigated with extended bed rest. In the study, 24 healthy male participants were placed on bed rest for 70 days. During the bed rest period, some of the men followed an exercise regimen and blindly received either testosterone supplements or a placebo while a control group remained in the bed without any exercise training or supplements. Throughout the study, the researchers collected muscle biopsies to analyze the proteins within the muscle tissue.

The researchers uncovered several changes to the men's muscle proteins during the bed rest period that were blunted or reversed with exercise, which appeared to drive a healthier protein organization within the muscle fibers. The testosterone supplements prompted further protein changes that promoted muscle growth beyond that of exercise alone.

"The unique insights we've gained on muscle proteins during extended bed rest could someday be applied to predict changes to muscle mass/strength in various situations and then develop a personalized program of exercises and hormonal countermeasures," said senior author E. Lichar Dillon, UTMB assistant professor in the department of internal medicine.

New Orleans, LA - In the first study of its kind, LSU Health New Orleans researchers report that women's pre-pregnancy overweight or obesity produces changes in breast milk, which can affect infant growth. The research findings are published in PLOS ONE, available online here.

"The importance of this study is that it demonstrates that breast milk contents can vary depending on mother's weight status at the time of conception and further impact the growth and development of breastfeeding infants," says Henry Nuss, PhD, Assistant Research Professor of Behavioral & Community Health Sciences at LSU Health New Orleans School of Public Health and lead author.

"Childhood obesity rates in the US have increased significantly in recent decades," notes Melinda Sothern, PhD, Professor of Behavioral & Community Health Sciences at LSU Health New Orleans School of Public Health. "Although many studies have shown that breastfeeding may be protective against excessive weight gain during early life, we do not fully understand why."

Breast milk contains pro-inflammatory proteins such as tumor necrosis factor alpha (TNF-α) and interleukin-six (IL-6), as well as hormones like insulin and leptin, and anti-inflammatory polyunsaturated fatty acids, such as omega-3 (DHA) and omega-6 (EPA). If and how their interaction may influence infant growth has been unknown.

The research team set out to discover the interrelationships between these compounds in blood and breast milk in early postpartum women with normal BMIs and with overweight/obesity before pregnancy to determine if these components correlated to infant growth measures at age 4-8 weeks.

They compared polyunsaturated fatty acids, inflammatory markers and hormones to infant weight, length, head circumference and percent fat mass at 4-8 weeks postpartum in the same group of 33 women. The researchers found that pro-inflammatory qualities of breast milk were associated with infant growth measures regardless of maternal pre-pregnancy BMI. However, infants born to women with overweight or obesity demonstrated less responsive growth to breast milk.

"Infants who are born to mothers of unhealthy weight status may be metabolically programmed to have a less favorable growth response to breast milk," Dr. Nuss adds. "These finding suggest that women of childbearing age who anticipate having a child should consider their weight status as a potential risk factor for adverse growth outcomes."

Research conducted at the University of Campinas (UNICAMP) in São Paulo State, Brazil, shows that vigorous physical exercise such as strength and weight training can reduce accumulated liver fat and improve blood sugar control in obese and diabetic individuals in a short time span, even before significant weight loss occurs.

In experiments with mice, researchers at UNICAMP's Molecular Biology of Exercise Laboratory (LaBMEx) found that two weeks of such exercise was sufficient to modify gene expression in liver tissue in ways that "burned" more stored lipids and contributed to the treatment of nonalcoholic fatty liver disease. Cellular insulin signaling in tissue improved, and hepatic synthesis of glucose decreased.

The results of the study, which was supported by São Paulo Research Foundation - FAPESP, are published in the Journal of Endocrinology.

"Everyone knows physical exercise helps control disease. Our research focuses on how and why this is so, on the mechanisms involved. If we can discover a key protein whose levels rise or fall with training, we'll have taken a step toward the development of drugs that mimic some of the benefits of physical exercise," said Leandro Pereira de Moura, a professor at UNICAMP's School of Applied Sciences and the principal investigator of the study.

Moura explained that excess fat in the liver causes local inflammation, which makes liver cells less sensitive to the action of insulin. This condition can progress to cirrhosis and eventually to liver failure.

"In obese individuals at cardiometabolic risk, reducing liver fat is vital to help control diabetes," Moura told. "The liver should produce glucose only under fasting conditions, but if insulin signaling in tissue is impaired, the liver releases glucose into the blood stream even after ingestion of carbohydrate, when insulin levels are high, and this raises the level of blood sugar."

Strength training for mice

To investigate the effect of strength training on the liver, an experiment involving three groups of mice was performed. The control group, which was fed a standard diet (4% fat), remained lean and sedentary. The second and third groups were fed a hyperlipidemic diet (35% fat) for 14 weeks, long enough for the animals to become obese and diabetic. The second group remained sedentary, while the third group was submitted to a moderate strength training exercise protocol for 15 days after becoming obese and diabetic.

The exercise protocol consisted of climbing a staircase with a weight attached to the tail. Each day, the mice climbed the stairs 20 times at 90-second intervals. According to Moura, the protocol was designed to mimic strength training in humans.

"Before we began the experiment, we conducted tests to determine the maximum load each animal could bear. We used a weight corresponding to 70% of this limit in the exercise sessions. Our group had previously shown overtraining can contribute significantly to the development of nonalcoholic fatty liver disease. Excessively strenuous exercise can do more harm than good," Moura said.

The researchers opted for a short exercise protocol of only 15 days to demonstrate that the benefits observed were directly linked to strength training and not to the secondary effects of weight loss.

In fact, the researchers found that although the mice submitted to exercise training were still obese at the end of the 15-day period, their fasting blood sugar levels were normal, whereas the mice in the sedentary obese group remained diabetic until the end of the experiment.

An analysis of liver tissue showed a 25%-30% reduction in local fat in the group that performed the exercise protocol compared with the fat level of the sedentary obese group. The quantity of proinflammatory proteins was also reduced in the exercise group, and yet the mice in that group still had approximately 150% more liver fat than the control group.

Gluconeogenesis

In fasting conditions, the liver is the main organ responsible for maintaining adequate blood sugar levels. In the context of diabetes, control of gluconeogenesis (endogenous glucose production) is absent as a result of insulin resistance, and the individual can become hyperglycemic.

To evaluate the effect of strength exercise on the control of hepatic gluconeogenesis, the researchers tested the animals for tolerance of pyruvate, the main substrate used by the liver to produce glucose.

"The test consisted basically of administering pyruvate to the mice and measuring the amount of glucose produced by the liver," Moura explained. "We found that the trained mice produced less glucose than the sedentary obese mice even though they received the same amount of substrate. This showed that the trained animal's liver underwent metabolic alterations that made it more sensitive to insulin."

Next, the researchers investigated the mechanism by which exercise reduced liver fat. To do this, the researchers analyzed the tissue expression of genes associated with lipogenesis (synthesis of fatty acids and triglycerides, contributing to the accumulation of fat) and lipolysis (breakdown of lipids for use as an energy source by the organism).

"We compared the sedentary obese mice with the exercised mice by means of gene and protein analyses to evaluate the synthesis and oxidation of liver fat," Moura said. "We observed a tendency towards more liver fat accumulation in the sedentary mice."

He added that an important contribution of the study was its demonstration that strength exercise promoted beneficial alterations in tissue that was not directly acted upon by skeletomuscular contractions.

"Our next step will be to find out how this communication between muscles and liver is processed. Our hypothesis is that a protein called clusterin may be involved," he said.

If the rise in clusterin levels induced by physical exercise is shown to be beneficial, Moura said, treatments with synthetic alternatives could be tested.

An estimated half of Ebola virus disease outbreaks have gone undetected since it was discovered in 1976, according to research published in PLOS Neglected Tropical Diseases. Although these tend to affect fewer than five patients, the study, led by Emma Glennon at Cambridge University, highlights the need for improved detection and rapid response, in order that outbreaks of Ebola and other public health threats are detected early and consistently.

The authors used three independent datasets from the 2013-16 Ebola outbreak in West Africa: in a district of Sierra Leone, in the city of Conakry in Guinea, and throughout the whole region whole region of the outbreak. Taking the properties of person-to person disease transmission, the team simulated realistic outbreak size distributions and compared them to reported outbreak sizes. Their median estimates suggest that at least half of Ebola outbreaks have gone undetected and this could represent well over 100 patient cases. The research also found that an individual patient's probability of detection is dependent on the size of the cluster of cases, with less than 10% chance of detecting a single-case event.

This is the first study to quantitatively estimate the number of undetected Ebola outbreaks and makes the case for greater investment in primary health care and local surveillance. Most undetected cases are handled locally, where core health infrastructure often lacks basic provisions for infectious disease diagnosis and control. Supporting public health and sanitation infrastructure in areas where outbreaks occur could prevent small outbreaks growing into larger events. Increasing local capacity to accurately diagnose and treat Ebola and other infectious diseases has the potential to improve surveillance and increase early detection of all outbreaks.

The burgeoning field of personal genetics appeals to people who want to learn more about themselves, their family and their propensity for diseases. More and more consumers are using services like 23andMe to learn about their genetic blueprint.

Included with most of these services is the ability for users to download their "raw" genetic data, which can be further analyzed using third-party apps. But little is known about how and why consumers are using these apps, or about a variety of potential risks associated with these apps -- such as false positives about health information or unknowingly linking a family history to an unsolved crime.

"It's the proverbial 'wild West' of genetic interpretation," said Sarah Nelson, a University of Washington research scientist in the Department of Biostatistics who recently completed her doctorate in the School of Public Health. She's the lead author of a new paper, "Third-party genetic interpretation tools: a mixed-methods study of consumer motivation and behavior," that was published today in American Journal of Human Genetics.

The team surveyed more than 1,000 people who had paid to obtain their genetic profile through a service like 23andMe or AncestryDNA. Most respondents reported that they downloaded data and went on to use a third-party application like Promethease or GEDmatch.

"We found that individuals who are initially motivated to learn about ancestry and genealogy frequently end up engaging with health interpretations of their genetic data, too. This has implications for the regulation of such testing and interpretation practices," said S. Malia Fullerton, associate professor of bioethics and humanities, UW School of Medicine, and the senior author of the paper.

The study found that nearly all consumers who took the survey (89%) download their raw data and more than half of those who downloaded also used third-party tools (56%) to research both genealogical and ancestry information on third-party sites.

But third-party interpretation is largely unregulated and there are potential risks for consumers, Nelson said. And there are unanswered questions: What did you consent to? What do you think your data is going to be used for?

It's often unclear what happens to the consumer data once it's provided to a third-party tool. There are privacy risks, and even the chance that the genetic data may help law enforcement solve crimes. Researchers worry about accuracy, data privacy, reliability and the nation's limited health resources.

False positives for health conditions can also cause emotional strain and put pressure on an already taxed health care system. People may find out about potentially serious diseases without much context or a support system.

On the other hand, third-party tools can also enable crowdsourced research and encourage people to learn about genetics.

Overall, Nelson is pleased that more people are taking an interest in genomics, but more research is needed on how people are using their information.

"We just had very little data on this," Nelson said.

New University of Alberta research is paving the way for the first medical treatment to help protect people from cardiovascular disease by boosting the body's natural defences.

In a new study, U of A cardiologist Gavin Oudit and his research team found a link between a peptide called apelin and a reduction of abdominal aortic aneurysms that was shown to dramatically reduce mortality in mice.

Oudit's team is hoping to replicate those results in patients suffering from, or at risk for, cardiovascular disease, particularly abdominal aortic aneurysms--and has established a biotech startup to commercialize their discovery.

In a series of tests using mice with aortic aneurysms and aneurysm specimens from humans, the team--which also includes U of A scientists John Vederas and Zamaneh Kassiri--found a significant health improvement for mice treated with apelin versus those who were not: none of the mice that were treated died, whereas 50 per cent of the untreated mice did.

Current treatment for aortic aneurysms is limited to behaviour changes like quitting smoking, or surgical repair. There are no medical or pharmaceutical treatments that have been effective at reducing the growth rate of aortic aneurysms, but Oudit is hoping to change that with a synthetic form of apelin that can be delivered to patients intravenously.

For Oudit, who is also director of the Heart Function Clinic at the Mazankowski Alberta Heart Institute, the fight against cardiovascular diseases can be broken down into 'good guys'--like apelin, a naturally occurring peptide found in several organs such as the heart, liver, brain and lungs--and 'bad guys,' hormones or chemicals in the body that may need to be reduced or blocked so a patient can be healthier.

"We've become very good at blocking the bad guys, particularly using drugs like ACE inhibitors or beta blockers, to treat symptoms," Oudit said. "But our research has focused on developing a method to enhance the good guys, to make them work better and protect people from cardiovascular disease in the first place, including heart attacks and heart failure."

Although apelin showed promise as a treatment option, the team had to overcome the challenge of creating a stable version that wasn't immediately broken down by other enzymes in the body. The team identified the enzymes that attack and degrade apelin and then developed a way to protect the apelin molecule to prevent the enzymes from breaking it down too quickly. That process took the team five years, Oudit said, and it resulted in a synthetic version of apelin that went from taking minutes to break down, to days.

"This is chemical engineering at its best," he said. "We've engineered this analogue that is markedly resistant to breakdown and when we use it in our animal models, we've shown we can completely protect them from (cardiovascular) disease. Zero mortality."

While Oudit's team focused on abdominal aortic aneurysms in the study, the researchers say they've seen evidence that the apelin analogue can help in other areas of the body as well.

"We've seen (the analogue have) exciting effects in the kidneys for renal failure, in the heart for heart failure, in the rest of the cardiovascular system and in pulmonary arterial hypertension (vascular disease in the lungs)," Oudit said.

"What we've created is essentially the insulin for the cardiovascular system."

Oudit predicts that in as little as two years, his team will have a version of the apelin analogue they will be able to test on humans. It is the driving force behind PEARKO Therapeutics Inc., a new biotech startup Oudit founded in collaboration with TEC Edmonton. Currently, the company is seeking investors and promoting the clinical applicability of the apelin analogue.

"We're on a mission to get this to patients as soon as possible," Oudit said. "It's exciting because we completely drove the discovery and design of these apelin analogues.

"I think this is a great example of how translational research can start from the molecule and progress to the animal model so we can get an understanding of its clinical applicability, and from there hopefully turn it into new therapies for our patients."

Educated and married American moms are more likely to try to time their pregnancy so that they have their first baby in the spring, according to new research from the University of Exeter Business School in the UK.

The study provides new evidence that the probability of a first baby being born in the spring is significantly linked to the mother's age, education, marital status and whether or not they're a smoker.

The study also found that were it possible to pay to guarantee a spring birth, on average a married woman aged between 20-45 would be willing to part with $877 USD to achieve it.

"Our work has discovered that there really is a desire to give birth in the spring in the US," said Professor Sonia Oreffice, who is a Professor of Economics. "This is often to do with the health of mom and baby because spring and summer are the furthest away from the peak of influenza cases and other germs.

"Knowing parents are making these choices for their first child, coupled with the fact that overall the most prevalent birth season is summer, helps policy-makers to better design policies targeting job flexibility, parenthood and child health and development."

The research was also carried out by Damian Clarke, Associate Professor, Universidad de Santiago de Chile & IZA and Professor Climent Quintana-Domeque of the University of Exeter, using data from US birth certificates, US Census data and a series of surveys with mothers. It specifically looked at the choices made around when to have a first baby, because there is often a far wider range of factors which influence parents' decision making when considering subsequent children.

"We also found that women in certain occupations - teachers, library workers and those in the training sector were more likely to aim for a spring baby," added Professor Oreffice. "We believe this is because women are trying to link their summer vacation to their short US maternity leave in order to spend more time with their baby."

Unmarried mothers who had not listed the father's name on their child's birth certificate did not show any of the above patterns; reflecting that these pregnancies are the most likely to be unplanned. The same was true for those moms who had used Assisted Reproductive Technology (ART) such as IVF, to conceive. The researchers also noted a drop in the number of December conceptions for ART births in both younger and older mothers, suggesting a link with the fertility clinics' Christmas closures.

In 2010, Professor Liliya Ziganshina (Head of Cochrane Russia), one of the co-authors of the paper, partook in a study on access to medicines with expert advice and methodology support from the World Health Organization (WHO) and Health Action International (HAI, Amsterdam). Later, in 2014, another co-author, Chinara M. Razzakova, continued this important study for her PhD thesis at Kazan Federal University.

Reliable information on prices and availability of medicines is the main foundation for improving access to medicines through development of public policy and evidence-based programs. The analysis of medicine price changes in the pharmaceutical market and price components makes it possible for governments of different countries to evaluate the success and consistency of their policies on price regulation and their measures on price containment.

Reliable information on medicine prices makes it possible for governments to compare their health expenditures with those of neighboring countries of the same level of development. Until 2001, there was no single international methodology for access to medicines studies; the research conducted at that time used methodologies that did not allow full assessment or international comparisons. It was difficult to compare the results of different studies among themselves due to the difference in applied methodologies.

In 2001, HAI in association with the WHO created a joint project and developed a comprehensive methodology to measure medicine prices, their availability and affordability to compare results across countries and at different time periods. To date, the second edition of the results has been published and is in the public domain.

The information collected using WHO/HAI methodology serves as an evidence base for governments. It is also a starting point for developing and changing governmental policies to improve public access to information about medicine pricing.

In this study, the authors looked at the availability and affordability of 95 medicines. These included 30 medicines from the standard list recommended by WHO/HAI methodology, used for international comparisons, and 65 cardiovascular drugs selected and added to the research project based on the importance of the burden of cardiovascular diseases at the national level. 71 of the 95 medicines were included on the Russian Essential Medicines List. For each selected medicine, information was collected on the originator brand and the lowest priced generic both in public and private pharmacies. The researchers looked at physical availability on the day of study and prices for concrete pre-specified pharmaceutical products.

We compared local prices with reference prices at the Management Sciences for Health website https://www.msh.org/ by calculating median price ratios and determined affordability of medicines by calculating the cost of treatment of acute and chronic diseases following national standards relative to the salary of the lowest paid worker.

Since 2009-2010, various price containing mechanisms have been implemented in the Russian Federation, such as decreeing of maximum wholesale and retail mark-ups and registration of the maximum selling price of medicines from the list of Essential Medicines. Various projects and strategies have been introduced to support domestic pharmaceutical industry. The Federal Target Program "Development of the pharmaceutical and medicinal industry of the Russian Federation until 2020 and beyond" (Pharma 2020) was adopted. In this regard, the authors analyzed prices and medicines availability and affordability in 2015 to document the changes since 2011.

There was a marked decrease in prices in 2015 compared to 2011. The prices of the lowest priced generics, both retail and wholesale, were closer to reference prices in 2015 and even lower, that is, they became acceptable in accordance with the recommendations of WHO/HAI methodology.

So far, two papers have been produced, and a training manual on the WHO/HAI methodology for pharmacology students of Kazan Federal University was created. The team plans to finalize price analysis for 2010-2018 and make the results publicly available.

Some of the most common traits among patients with cartilage issues in the knee are excluding them from participating in clinical trials because the trial outcomes might not yield the optimum results for new methods of cartilage regeneration, according to a Penn Medicine study published in Regenerative Medicine. Researchers testing the new methods tend to only include the patients most likely to succeed with the fewest complications, but if some of these trials could be safely opened up to different kinds of patients -- such as those older than 55 or younger than 18, or those who knee joints don't align perfectly -- the results could be much more robust and reflective of the patient population being treated. In the team's paper, they also highlighted therapies that hold special promise for the excluded populations, such as the use of "scaffolding" to promote cartilage growth.

"We challenge the orthopaedic field to think about whether therapies could work for patients other than the 'perfect' candidate. And if these therapies don't work for those groups, what can we do, as an alternative, to help them?'" said co-senior author Robert Mauck, PhD, a professor of Orthopaedic Surgery and director of the McKay Orthopaedic Research Laboratory at Penn Medicine. "The populations that are affected by these knee defects are larger than those being evaluated, so we're examining what can be done to correct that, keeping an eye toward developing studies that are more inclusive of the broader population."

Within clinical testing for new cartilage regeneration therapies and techniques, the populations can be characterized as having "green knees" or "red knees." Green knees are the joints that are expected to benefit the most with the fewest setbacks from the particular form of cartilage regeneration being tested. Red knees, on the other hand, have defects or certain features that might make patients more susceptible to complications or slower recoveries.

"In many clinical trials, researchers will work to see whether or not a therapy works as the main endpoint. What our study suggests is that, once the safety and efficacy of a particular therapy or technique is established, clinical trial teams should be thinking about evaluating it in populations who would get the most benefit," Mauck said. "When it comes to cartilage regeneration, I think sometimes these therapies need to be pushed to the limit in order to evaluate them more thoroughly and give doctors more context on what conditions they might work best for, as well as what outcomes to expect in those who aren't perfect."

Mauck and his team, which was co-led by James L. Carey, MD, an associate professor of Orthopaedic Surgery and director of the Penn Medicine Center for Cartilage Repair and Osteochondritis, found that extremely common conditions are often never included in cartilage regeneration clinical trials. Cartilage regeneration procedures are appealing because they create a living biological tissue that can remodel and function over the patient's life, as opposed to the metals or plastics used in total knee replacement that begin to wear as soon as they're implanted. The researchers searched the ClinicalTrials.gov database and examined 33 regeneration trials and discovered that half excluded patients over 55 years old or under 18. Almost 60 percent excluded patients for having lesions greater than eight square centimeters in size, 64 percent excluded patients with more than one cartilage lesion, and 79 percent excluded patients with osteoarthritis.

Many studies also "bottleneck" because they have difficulty finding enough "green knees" to participate, Carey said. He suggested using different study structures to include wider population and overcome bottleneck issues.

"In prospective cohort studies, everyone is enrolled and they're observed at endpoints over time, like two, five and 10 years down the line," Carey said. "Through this, you can look back and determine what the predictors of success and failure are. For example, you could look at a patient that had knee malalignment that was corrected, which is typically excluded now, and see how much of a factor it is in the success or failure of a therapy compared to the optimal candidate."

The researchers pointed to therapies identified as having most promise for different "red knee" conditions. For patients older than 55, a technique to clear out cells that have stopped dividing could lead to better results. Or, for larger defects, such as lesions larger than 8 square centimeters, 3D-printed tissues could provide a lifelong alternative to full knee replacement.

"We want to provide more patients with the opportunity to repair their joint instead of defaulting to completely replacing it," Carey said. "Cartilage defects don't occur in isolation. Having more clinical data on a wider range of factors will spur more innovation and open up the door for a variety of ways to repair joints."

More than half of patients with relapsed multiple myeloma treated with carfilzomib experienced cardiac issues during treatment, according to a multi-institutional study published June 12 in Journal of Clinical Oncology. The study recommends that patients undergo a detailed cardiovascular history before being prescribed carfilzomib and then be monitored with natriuretic peptide testing, an indicator for heart failure.

"This study was an important research endeavor between hematology and cardiology to study the predictive risk factors for cardiotoxicity with carfilzomib," said the study's lead author, Robert Frank Cornell, MD, assistant professor of Medicine at Vanderbilt University Medical Center and clinical director of Plasma Cell Disorders at Vanderbilt-Ingram Cancer Center. "This drug is an important and effective treatment option for patients with myeloma. Importantly, we recommend patients have routine monitoring with BNP or NTproBNP during treatment as elevations with these were highly predictive of cardiac events."

The study looked at two proteasome inhibitor therapies, carfilzomib and bortezomib. While prior studies have demonstrated a modest increase in cardiovascular adverse events (CVAEs) with carfilzomib, this study monitored patients for predictors of CVAEs and found a greater incidence, with 51% of patients experiencing CVAEs, including heart failure, hypertension, arrhythmia, acute coronary syndrome, pulmonary hypertension and venous thromboembolism. The incidence of CVAEs with bortezomib therapy was substantially lower, accounting for 17% of patients. However, bortezomib is no longer a first-line therapy for relapsed multiple myeloma. The study enrolled 95 patients, 65 of whom received carfilzomib and 30 receiving bortezomib

The majority of CVAEs, 86%, occurred within the first three months of therapy. In most cases, the cardiac issues were manageable, so patients were able to resume treatment. The majority of CVAEs cases were temporary, with natriuretic peptides returning to near-baseline levels just over three weeks after reaching peak levels. More investigation is needed to determine why this occurs, Cornell said.

A study on the pain at the base of the thumb conducted in the University of Malaga has evidenced that a continuous use of the mobile phone, especially among young people, goes hand in hand with new pathologies of this finger.

This research, carried out in cooperation with a group from Italy (Fondazione Don Carlo Gnocchi) and another from the USA (Gannon University), has identified a generational change in the use of the thumb due to the influence of new technologies.

"We have discovered a direct correlation between people's occupation and the cause of thumb pain", explains Raquel Cantero, Professor of the UMA Department of Physiotherapy, who adds that, therefore, our daily activities are engendering changes in the physical position of this finger, which may have an influence on its future evolution.

"The pathologies are changing. Atrophied thumbs are more and more frequent in our practice; in fact, we already talk about the i-Phone tendonitis", says the researcher of the UMA Faculty of Health Sciences.

In this regard, the expert points out that, from a young age, the pinch grip position of the hand is not used as much as before, and at school, with touchscreens, writing is less frequent, so the thumb is also used to a lesser extent.

Changes in the evolution of the hand

These changes in the use of the thumb have led the professor of the UMA to predict alterations in the evolution of the hand itself. A new line of research which first hypotheses were outlined in the article "The hominid thumb and its influence on the employment during evolution", published in the scientific journal Reumatismo.

"Looking at what happened in primates' brain when they came down from trees and their brain structure changed as they began to use their hands to carry out different functions, we wonder if the passage of time will not be such a milestone nowadays due to this change in the use of the thumb, the key finger involved in the pressure and functionality of the human hand", explains Cantero.

Professor Cantero of the University of Malaga is going to participate next June 17th in the International Congress for Hand Therapy, held in Berlin until June 21st. A meeting where Cantero is going to present these thumb-related issues and analyze how to ease pain through minimally invasive techniques and specific exercise programs.

Using sound vibrations and pulses of near-infrared light, a Rutgers University scientist has developed a new "virtual biopsy" device that can quickly determine a skin lesion's depth and potential malignancy without using a scalpel.

The ability to analyze a skin tumor non-invasively could make biopsies much less risky and distressing to patients, according to a report in Wiley Online Library. Currently, physicians who perform surgical biopsies often don't know the extent of a lesion - and whether it will be necessary to refer the patient to a specialist for extensive tissue removal or plastic surgery - until surgery has already begun.

The first-of-its-kind experimental procedure, called vibrational optical coherence tomography (VOCT), creates a 3-D map of the legion's width and depth under the skin with a tiny laser diode. It also uses soundwaves to test the lesion's density and stiffness since cancer cells are stiffer than healthy cells. An inch-long speaker applies audible soundwaves against the skin to measure the skin's vibrations and determine whether the lesion is malignant.

"This procedure can be completed in 15 minutes with no discomfort to the patient, who feels no sensation from the light or the nearly inaudible sound. It's a significant improvement over surgical biopsies, which are invasive, expensive and time consuming," said lead researcher Frederick Silver, a professor of pathology and laboratory at Rutgers Robert Wood Johnson Medical School.

The study found that a prototype VOCT device, which awaits FDA approval for large-scale testing, is able to accurately distinguish between healthy skin and different types of skin lesions and carcinomas. The researchers tested the device over six months on four skin excisions and on eight volunteers without skin lesions. Further studies are needed to fine-tune the device's ability to identify a lesion's borders and areas of greatest density and stiffness, which would allow physicians to remove tumors with minimally invasive surgery.

The age of one-size-fits-all medicine is fading. Taking its place is an era of personalized medicine - the practice of tailoring disease prevention, diagnosis, and treatment to patients as individuals. Many cancers, for example, are resistant to conventional therapies but respond to medications that target specific cancer-causing genetic mutations. Scientists and clinicians at Children's Hospital Los Angeles developed a comprehensive genetic testing panel called OncoKids® to detect genetic markers that respond to targeted therapies. This technological advance has connected patients with life-saving clinical trials and medications.

Personalized medicine has expanded its capabilities as technology has grown. Scientists are now using a technology called metagenomic next-generation sequencing, or mNGS, to rapidly test clinical samples. This powerful assay can quickly compare unknown genetic material from a patient sample against thousands of known pathogen genomes. "Basically, we can determine the cause of the disease, whether it's a virus, bacteria, or something else," says Jeffrey Bender, MD, a physician specializing in infectious diseases at CHLA. "If it has genetic material, this test can identify the infection and provide information that allows us to select a treatment specific to fight it."

Now that science has the capability to sequence and compare genomes, it is becoming clear that genomic testing can, and should be, used to identify infectious pathogens. This is especially important in diseases that could stem from multiple potential causes. For example, meningitis and encephalitis are serious central nervous system conditions that often arise from infection. Proper and timely diagnoses of these infections are critical so that patients can receive treatments before complications develop. But many types of pathogens - bacteria, viruses, fungi, and parasites - can cause meningitis and encephalitis, making targeted testing difficult. Though laboratories can test samples for a handful of possible culprits, there is a limit to the number of pathogens they can test for at one time. Negative results can delay treatments and leave doctors, patients, and families searching for answers.

Now, clinicians at CHLA and sites nationwide are showing that broader genetic testing can deliver answers that standard laboratory tests fail to provide. Instead of one particular target, mNGS testing quickly compares sample genetic material to thousands of targets. Dr. Bender and Jennifer Dien Bard, PhD, Director of the Clinical Microbiology and Virology Laboratory at CHLA, participated in a multi-center clinical trial to evaluate the clinical use of mNGS testing in pediatric patients with suspected meningitis or encephalitis.

Their study, highlighted today in the New England Journal of Medicine showed that this 'agnostic' testing could lead to treatments for infections that were not identified using standard testing methods. More than 200 patients at 8 hospitals, including CHLA, were enrolled in this year-long study. Cerebrospinal fluid was sampled from patients who presented with meningitis- or encephalitis-like symptoms. Samples were then analyzed using either standard laboratory testing or mNGS. Out of 58 total diagnoses, sequencing identified 13 infections - more than 20% - that were not detected in standard clinical testing.

Dr. Dien Bard and her colleagues in the Center for Personalized Medicine envision a future in which these agnostic, genomic assays are integrated into routine clinical care. "The trial showed just how sequencing technology can really have a positive clinical impact on patients. In just this study alone, thirteen infections were diagnosed solely because of this technology," she says. "That's thirteen additional families who got answers."

HERSHEY, Pa. -- To diagnose and treat diseases like cancer, scientists and doctors must understand how cells respond to different medical conditions and treatments. Researchers have developed a new way to study disease at the cellular level.

Dr. Keith Cheng, distinguished professor of pathology, pharmacology and biochemistry and molecular biology at Penn State College of Medicine, and a team of X-ray imaging physicists at the University of Chicago, have developed a new, 3D tissue imaging technique, called X-ray histotomography. The technique allows researchers to study the details of cells in a tissue sample without having to cut it into slices. And that could lead to better diagnosis and treatment for a variety of diseases, including cancer.

"The quantitative and objective measurements made possible by histotomography could potentially allow us to distinguish between subtypes of cancer and other diseases that presently look the same using traditional histology so that they may be more appropriately treated," Cheng said.

Traditional histology involves taking thin slices of tissues from patients, staining them, and examining them for irregular features under a microscope. Physical sectioning of the sample introduces tissue loss and distortion that leads to incomplete sampling and imperfect visualizations. According to researchers, X-ray histotomography avoids these problems and allows the three-dimensional features of cells like shape and volume to be measured accurately.

Over 10 years, Cheng and his team developed the technique by combining the principles of human computer tomography (CT) scanning and histology to image small organisms and tissues at a greater resolution in 3D.

"X-ray histotomography uses the same principles as a human CT scan," Cheng said. "CT involves shooting a series of X-rays of a subject, each at a slightly different angle. A computer program then uses the set of x-rays to create a 3D image."

The Cheng lab had previously used micro-CT, a smaller-scale version of human CT, to image small organisms and tissues. University of Chicago's Patrick La Rivière, associate professor of radiology, introduced Cheng to the use of a powerful x-ray source, the synchrotron, which allowed the research team to enhance their micro-CT scanning with increased resolution and faster imaging times. The synchrotron-based micro-CT might help pathologists someday answer questions like:

What are the individual characteristics of the disease the patient has? How many diseased cells are there? What are the individualized treatment options based on what I'm seeing?

The technology needed to answer questions like those was not available commercially, Cheng said, so he and a team of engineers, physicists, data scientists and biologists set out to develop the technique themselves.

After a decade of optimizing the sample preparation and imaging, the team created 3D reconstructions of young zebrafish that can be examined from the whole organism down to a cellular level. Zebrafish were chosen to develop this technology because their size from larvae to adults is nearly the same as samples used by physicians to evaluate cancerous tumors.

According to Cheng, researchers and clinicians can now examine features like 3D shape, volume, location and number of cells that previously couldn't be studied using traditional histology. The technique will allow pathologists to study a full tissue sample after it has been stained and prepared. It is no longer necessary to cut a single slice of tissue out of the entire sample.

Clinical scientists can evaluate microscopic and three-dimensional features of cells due to the increased clarity and resolution of the images.

"The beauty and complexity of the tissue I saw was mind-bending," Cheng said of the images released in the journal eLife with the research on June 11.

Computational tools combined with the imaging allow the size, shape, volume and density of cells to be calculated and cataloged. This ability enables the characteristics of disease pathology to be studied in a novel way that may improve clinical care and facilitate drug discovery.

Advances in computer technology allow the large image files of the zebrafish - at 100 gigabytes each - to be processed and viewed. Researchers can examine the traits of disease at the organ system, tissue or cellular level simultaneously, slice-by-slice or in 3D context. They may even be able to see and interact with the cellular structure of organisms using the same technology used by virtual reality gamers.

Future research by the Cheng team aims to increase the resolution, sample size, throughput, analytical power and accessibility of the technique.