Category: Medical Research & Technology

Categories : Gender Medical Research & TechnologyTags :

Biological Research Often Incorrectly Reports Sex Differences

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An analysis of published studies from a range of biological specialties shows that when data are reported by sex, critical statistical analyses are often missing and the findings are likely to be reported in misleading ways.

The analysis was published in the journal eLife.

“We found that when researchers report that males and females respond differently to a manipulation such as a drug treatment, 70% of the time the researchers have not actually compared those responses statistically at all,” said senior author Donna Maney, a professor of neuroscience in Emory’s Department of Psychology. “In other words, an alarming percentage of claims of sex differences are not backed by sufficient evidence.”

In the articles lacking the proper evidence, she added, sex-specific effects were claimed almost 90% of the time. In contrast, authors that tested statistically for sex-specific effects only reported them 63% of the time.

”Our results suggest that researchers are predisposed to finding sex differences and that sex-specific effects are likely over-reported in the literature,” Prof Maney said.

The problem is so pervasive not even her own work was safe. “Once I realised how prevalent it is, I went back and checked my own published articles and there it was,” she said. “I myself have claimed a sex difference without comparing males and females statistically.”

Prof Maney stressed that the problem should not be discounted; it is becoming increasingly serious, she said, because of mounting pressure from funding agencies and journals to study both sexes, and interest from the medical community to develop sex-specific treatments.

Better training and oversight are needed to ensure scientific rigor in research on sex differences, the authors wrote: “We call upon funding agencies, journal editors and our colleagues to raise the bar when it comes to testing for and reporting sex differences.”

Historically, biomedical research has often included just one sex, usually biased toward males. In recent decades, laws have been passed requiring US medical research to include females in clinical trials and report the sex of human participants or animal subjects.

“If you’re trying to model anything relevant to a general population, you should include both sexes,” Prof Maney explained. “There are a lot of ways that animals can vary, and sex is one of them. Leaving out half of the population makes a study less rigorous.”

As more studies consider sex-based differences, Maney adds, it is important to ensure that the methods underlying their analyses are sound.

For the analysis, Prof Maney and co-author Yesenia Garcia-Sifuentes, PhD candidate, looked at 147 studies published in 2019 to see what is used for evidence of sex differences. The studies ranged across nine different biological disciplines, including field studies on giraffes and immune responses in humans.

The studies that were analysed all included both males and females and separated the data by sex. Garcia-Sifuentes and Prof Maney found that the sexes were compared, either statistically or by assertion, in 80% of the articles. Of those articles, sex differences were reported in 70% of them and of those treated as a major finding in about half.

Statistical errors were seen in some studies, with a significant difference for one sex but not the other counted as a difference between them.  The problem with that approach is that the statistical tests conducted on each sex can’t give “yes” or “no” answers about whether the treatment had an effect.

“Comparing the outcome of two independent tests is like comparing a ‘maybe so’ with an ‘I don’t know’ or ‘too soon to tell,'” Maney explains. “You’re just guessing. To show actual evidence that the response to treatment differed between females and males, you need to show statistically that the effect of treatment depended on sex. That is, to claim a ‘sex-specific’ effect, you must demonstrate that the effect in one sex was statistically different from the effect in the other.”

Conversely, their analysis also encountered strategies that could mask sex differences, such as pooling data from males and females without testing for a difference.

“At this moment in history, the stakes are high,” Maney says. “Misreported findings may affect health care decisions in dangerous ways. Particularly in cases where sex-based differences may be used to determine what treatment someone gets for a particular condition, we need to proceed cautiously. We need to hold ourselves to a very high standard when it comes to scientific rigor.”

Source: EurekAlert!

Categories : Medical Research & TechnologyTags :

New Type of Skin Cell Reveals Secrets of Inflammation

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The surprise discovery of a new type of cell explains how distress to the skin early in life may prime a person for inflammatory skin disease later, according to a new study in Nature. This finding will likely lead to treatments for autoimmune disorders like scleroderma, and inform understanding of inflammatory disease.

“The results reinforce the idea that what you’re exposed to initially may have lasting ramifications,” said lead researcher Michael Rosenblum, MD, PhD. “It appears that early exposure to inflammation can, through these cells we discovered, imprint an ability for tissues to develop inflammatory disease later in life.”

The team came across this new type of cell while investigating the effects of certain actions known to evoke immune response in mice. One of these actions involved knocking out a group of skin cells that suppress the immune system. Without that regulation, said Dr Rosenblum, a unique cell was observed that seemed to act as a shelter for pathogenic immune cells not typically seen in skin tissues.

“We had to knock out one cell population to see that they were controlling the growth and capacity of these other, unknown cells,” he said, noting that the new cells only became apparent in the tissue exposed to inflammatory triggers. “What normally would be a deserted island on the skin was now inhabited by all these strangers,” he said.

The team dubbed these strangers ‘TIFFs’ (Th2-interacting fascial fibroblasts) after the Th2 immune cells that they help to house. The location of TIFFs in the skin suggests that they belong to a group of cells that make up the fibrous connective tissue that is fascia, said lead author Ian Boothby, a graduate student in Dr Rosenblum’s lab.

“Because most organs have fascia of some sort, what we’re learning about TIFFs in skin may well be widely applicable to the rest of the body, meaning that these cells may play a role in a huge number of inflammatory diseases,” he said.

Boothby and Dr Rosenblum when skin without regulatory cells receives inflammatory triggers, the TIFFs spread like wildfire and become a sort of holding pen for the Th2 immune cells. Later in life, when there is even a small insult to the skin, Dr Rosenblum said, the TIFFs open their floodgates, unleashing the Th2 cells.

It seems that, through these cells, early exposure to inflammalation can leave a life-long imprint.

“All you need to do is push the immune system just a little bit, with a wound or with stress, to unleash all the pathogenic cells living in these TIFFs and create an exaggerated inflammatory response,” he said.

The researchers hypothesise that the exaggerated response may manifest as the creation of fibroses in the fascia, the driving force behind inflammatory skin diseases such as scleroderma.

To confirm the presence of TIFFs in human skin, the team obtained samples from volunteers with eosinophilic fasciitis (EF), a rare inflammatory disorder in which eosinophils build up in the skin fascia, the fibrous tissue between the skin and the muscles below it.

Comparing the EF samples to those of healthy skin, the researchers found TIFFs in both, but looked completely different. In healthy skin, the fascia forms a thin, spidery network between fat cells, while in the EF skin sample, the cells had expanded to form thick bands of fibrous tissue.

Revealing the mysteries of inflammation
TIFFs appear to be present in every organ, said Dr Rosenblum, usually found in the fascia surrounding major organs and serve a role in maintaining structure. They’re also prone to interacting with immune cells. He postulates that TIFFs might have evolved as a sort of emergency brigade in case of injury, able to jump-start repair in the case of internal injury.

“In patients with scleroderma or other fibrosing diseases like EF, that repair program may be kind of co-opted, resulting in this chronic wound-healing response,” said Dr Rosenblum. “If we can understand the biology of these cells, we can come in with drugs that revert them back to what they’re supposed to be doing.”

Source: University of California San Francisco

Categories : Medical Research & Technology Skeletal SystemTags :

Atmospheric Plasma Device Boosts Bone Regeneration

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Scientists in Japan have developed a plasma device that promotes bone regeneration in fractures.

Unlike blood plasma, plasma here refers to the fourth state of matter, effectively a highly ionised gas, which has been long investigated as an effective surgical scalpel which cauterises tissue as it cuts. Other recent applications of plasma technology include surface sterilisation.

Now, a new type of plasma device, termed non-thermal atmospheric pressure plasma (NTAPP), was successfully tested in healing of bone fractures in animal bone defect models. It is cooler than most plasmas that are typically used. In a study published in PLOS ONE, researchers from Osaka City University detailed their findings using the technology in this world-first application.

Acceleration of cell growth
“NTAPP is considered a new therapeutic method,” said first author Akiyoshi Shimatani, “as it has been shown to accelerate cell growth when applied at low enough levels.” He explained that in an ambient atmosphere it can generate highly reactive oxygen and nitrogen species (RONS) which can be directly exposed to tissues.

Indirect treatments have shown the potential advantages of plasma in supporting the creation of stem cells that cause reactive oxygen species and in inducing osteogenic differentiation and bone formation, however, as the team points out there is no report on directly using NTAPP for bone fracture therapy. “Direct exposure of NTAPP is a key part of this study” states Jun-Seok Oh, professor at the OCU Graduate School of Engineering and advisor to the study, “It required a device specifically designed to generate and deliver RONS to areas of the bone defect ‘effectively’.”

The research group developed a pencil-like plasma device that can effectively generate and deliver RONS to an animal model with a well-established critical bone defect, allowing the team to search for the optimal exposure conditions. Comparing groups that were treated with NTAPP for 5, 10, and 15 minutes to control groups with no plasma administered, micro-CT images at eight weeks showed the 10-minute treatment time as the most successful bone regeneration with 1.51 times larger bone volume than the control group.

Since micro-CT images could not determine whether a bone defect has been filled with new bone, tissue or both, the team also ran a histological analysis and confirmed bone defects in the groups treated with plasma were in fact filled with new bone, and had no tissue or gaps like the control groups.

Precision therapy
The biological effect of plasma, like other therapies, depends on the treatment dose delivered into the targets. Although future research will be needed to clarify why the study saw the most bone regeneration during the 10-minute treatment period, surface wettability is understood to promote greater cell spreading and adhesion to biomaterials and implants. Hiroaki Nakamura, professor at the Graduate School of Medicine explained: “We wondered if something similar was occurring where we saw a strong generation of new bone. And we found that compared to the control group, bone surface of the plasma-treated group as statistically and significantly more hydrophilic.”

The research team hopes the plasma device they developed can be applied for surgical use.

Source: Osaka City University

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‘Sutrodes’ Could Treat Spleen Conditions Using Electricity

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Using a flexible ‘sutrode’ – a combination of suture and electrode – a group of researchers has advanced a way to treat spleen conditions by applying only electrical current.

Electroceuticals, where electrical stimulation is used to modify biological functions, could minimally invasively treat medical conditions and result in few side effects.  

The work, which appears in the Nature Journal of Communications Biology, builds on previous studies when the team introduced the sutrode to the world just over a year ago. This graphene-based electrode is an electrical stimulation device that could replace the use of pharmaceuticals to treat a range of medical conditions. The sutrode, created using a technique called fibre wet spinning, has an electrode’s electrical properties and a suture’s mechanical properties.

“The flexibility and superb sensitivity of the sutrode is allowing us to expand our understanding of how the nervous system controls main body organs, a critical step towards developing advanced therapies in bioelectronic medicines,” reported the study leader, Professor Romero-Ortega. “Our collaborative work uncovered that the spleen is controlled by different terminal nerves, and that the sutrode can be used to control them, increasing the precision in which the function of this organ can be modulated.”

Paper co-author professor Gordon Wallace said the sutrode can be integrated with delicate neural systems to monitor neural activity.

“This work has widespread implications for regulating the function of the spleen, particularly the efficient regulation of the immune response for electroceutical treatment of range of diseases,” said Prof Wallace. “We have highlighted the ongoing need to develop systems with increased fidelity and spatial resolution. This will not only bring practical applications to the forefront but will enable the unattainable exploration of the human neural system.”

The work also reveals the ability to simultaneously interrogate the four individual neural inputs into the spleen. This new technical and biological achievement will not only bring about practical applications, but also enable a previously unattainable exploration of the human neural system.

Source: University of Houston

Categories : Cancer Medical Research & TechnologyTags :

Telemedicine Popular Among People with Cancer Undergoing Radiotherapy

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Researchers reviewing patient surveys before and during the COVID pandemic found that nearly half preferred telemedicine and that general patient satisfaction scores were equally high for both video conferencing and office visits.

The study, published in the Journal of the National Comprehensive Cancer Network, assessed patient satisfaction and preferences for telemedicine. It found that 45% of people with cancer preferred telemedicine, while 34% preferred office visits, and 21% had no preference.

The researchers reviewed survey responses from 1077 radiation oncology patients across seven centres, with questionnaires based on office and telemedicine visits between December 2019 and June 2020. In terms of patient satisfaction, most reported either no difference or improvement with telemedicine overall (91%) compared to office visits, with similar results for their confidence in their physician (90%), understanding their treatment plans (88%), and confidence their cancer will be treated appropriately (87%).

Co-lead author Narek Shaverdian, MD, MSK Department of Radiation Oncology said: “These findings provide some evidence that there is a role for telemedicine beyond the COVID-19 pandemic and that it can be a particularly useful tool for certain patients – especially those who may have challenges coming on-site for an appointment. Giving patients flexibility and options by being able to see them both in-person and through telemedicine can improve access to care.”

Notably, two-thirds of respondents considered telemedicine to be a superior option when it came to treatment-related costs, such as travel and lost wages.

Co-lead author Erin F. Gillespie, MD, MSK Department of Radiation Oncology said, “An individual visit to the physician’s office can be costly—including transportation, parking, and time off from other activities. Telemedicine takes away most of this cost and inconvenience, and could therefore reduce the overall burden of engaging with the healthcare system. Also, the ability for family and friends to join the conversation from any location can be game-changing.”

The researchers found patient responses varied significantly between video conferencing versus audio. Patients who had telephone-only appointments were more likely to say they thought they would benefit more from an in-person visit.

“Telemedicine can be a resource to increase access to care, but only if patients have and can use these video capabilities,” said Dr. Shaverdian. “There is so much that you learn just by seeing a patient and using visual cues to guide a discussion. A voice-only encounter with a patient you’ve never met before is challenging.”

“Digital tools like telemedicine have the unfortunate potential consequence of paradoxically increasing disparities in access to care,” noted Dr. Gillespie. “But the counter to that is there will be some disadvantaged patients that would not have accessed the system at all, either due to technologic barriers or travel time, and now can connect at least by phone, which is an important and positive change.”

Source: National Comprehensive Cancer Network

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Scientists Discover a New Sense for Sugars

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In a study published in PLOS ONE, scientists report the identification of a new human sensory ability to detect sugars in the mouth with a kind of a molecular ‘calorie detector’. It could help explain why artificially sweetened beverages just don’t have the same appeal as ones containing sugar.

“Our mouth can identify when a sweetener has the potential to deliver calories versus a non-caloric sweetener, which cannot,” said first author Paul Breslin, PhD, a Monell investigator and a professor of Nutritional Sciences at Rutgers University.

The paper describes the first-in-human demonstration of a signaling pathway that uses the sugar glucose, a component of table sugar and high fructose corn syrup, to signal the presence of calories, in addition to the well-studied sweet-taste receptor in taste buds. Glucose is present in many foods, and has been consumed by humans in the form of honey, fruit and other sugar-rich foods.

“Humans love fruit and sugar, as do many other apes, which obtain most of their calories from sugar,” said Prof Breslin.

Recent findings from Monell showed taste bud cells in mice could identify when a sweetener has calories to burn, which prompted the researchers to see whether the ability to sense glucose in the human mouth may also involve this additional pathway. The team wanted to know if the calorie detector is functional, and if it could affect our responses to dietary sugar.

“Now that we know this calorie-detecting taste system is operating in humans, it could help explain the overall preference for sugared beverages over non-caloric sweetener beverages,” said Prof Breslin.

In a series of three human-taste experiments, the team compared oral glucose sensitivity to the ability to sense the artificial sweetener sucralose and to a special form of glucose that cannot be metabolised. “Overall, there are two sweet-sensing pathways in the mouth: one for sweet taste, and another for detecting potential energy-burning sugars,” said coauthor Linda J. Flammer, PhD, a senior research associate at Monell.

The fact that diet fizzy drinks never captured a major share of the beverage market always puzzled Prof Breslin, but he now has a hint: “Diet drinks are not as satisfying as sugared beverages. As a public health initiative, might we get beverages and foods with lower sugar levels to be more rewarding? Now that we know there is this second glucose-sensing system in the mouth, maybe we can tap into it to make healthier beverages that people enjoy drinking.”

Sugar calories are sensed in the gut and blood after swallowing, but this study shows that sugars are identified as different from non-caloric sweeteners in the mouth. “It is remarkable that we evolved a mechanism not only to taste oral sugars as sweet, but also to sense that they have a metabolic or caloric signal,” said Breslin. “This means that the mouth is much smarter than we realised and that it will be difficult to trick it by simply providing non-caloric sweeteners.”

Source: Monell Chemical Senses Center

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Upgrading the Diagnostic Power of Dipsticks

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Popularly known as ‘dipsticks’, lateral flow assays (LFAs) have long been a standard point-of-care testing system, and continue to grow in popularity, especially in developing countries.

These disposable, paper-based diagnostic devices are inexpensive, readily available, have a long shelf life, and they’re fast, typically delivering results in under 20 minutes. They’re also easy to use at home, most commonly for pregnancy tests but also now for COVID.

“These tests have been extremely popular for years, mainly because they are so simple to use. You don’t send anything to the lab or clinic because these tests don’t require any external equipment to operate. This is an advantage,” said engineering researcher Fatih Sarioglu at the Georgia Institute of Technology. “But there also is a disadvantage. There are limitations to what they can do.”

Sarioglu and his team are overcoming the limitations of LFAs with development of a flow control technology, turning these simple tests into complex biomedical assays.

Their research is outlined in two papers in Science Advances and ACS Sensors. One explains the development of their technology and the other applies the technology in a toolkit to diagnose SARS-CoV-2, as well as influenza.

LFAs make use of capillary liquid flow to detect analytes. Sarioglu explained that conventional LFAs are not practical for performing multi-step assays – capillary flow precludes them from coordinating a complex process involving the application of multiple reagents in a specific sequence with specific delays in between.

The researchers describe a technique to control capillary flow by imprinting roadblocks on a laminated paper with water insoluble ink. The blocked liquid flow is thus manipulated into a void formed at the interface of the ink-infused paper and the polymer tape laminate. By modifying the roadblocks, the researchers can essentially set the time it takes for a void to form – creating timers that hold capillary flow for a desired period.

“By strategically imprinting these timers, we can program the assays to coordinate different capillary flows,” said Sarioglu, professor in the School of Electrical and Computer Engineering. “That enables multiple liquids to be introduced, and multistep chemical reactions, with optimal incubation times – so, we can perform complex, automated assays that otherwise would normally have to be performed in laboratories. This takes us beyond the conventional LFA.”

For the user, the new dipstick test works the same way as the reliable standard – a sample is added at one end and the results present themselves minutes later in living color(s) at the other end. Sarioglu and his colleagues simply enhanced and expanded the process in between.

Basically, they drew patterns on paper – a dipstick – and created immunoassays that rival other diagnostic tests requiring labs and extra equipment, in the effective detection of pathogenic targets like Zika virus, HIV, hepatitis B virus, or malaria, among others.

The paper in ACS Sensors describes a PCR-based point-of-care toolkit based on the lab’s flow technology. The assay is programmed to run a sequence of chemical reactions to detect SARS-CoV-2 and/or influenza A and influenza B. A traditionally labour-intensive genetic assay can now be done on a disposable platform which will enable frequent, on-demand self-testing, filling a critical need to track and contain outbreaks.

The lab is studying the technology’s application for other assays targeting other pathogens, with plans to publish in the coming months. Sarioglu is optimistic about the work’s potential.

“We believe this flow technology research will have widespread impact,” he said. “This kind of dipstick test is so commonly used by the public for biomedical testing, and now it can be translated into other applications that we do not traditionally consider to be cut out for these simple tests.”

Source: Georgia Institute of Technology

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Dental Acid Damage Imaged in Real Time

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Researchers have developed a new technique to improve understanding of how acid damages teeth over time at the microstructural level, creating a clear picture of how the damage happens. 

Dentine forms the main bulk of human teeth and supports the enamel, which covers the crown surface, helping to make teeth strong and resilient, but acids from dental plaque can cause tooth decay affecting the dental structure’s integrity. This research aims to develop knowledge that leads to new treatments that can restore the structure and function of dentine.

Using in situ synchrotron X-ray microtomography to scan dentine samples while they were being treated with acid, researchers built clear 3D images of dentine’s internal structure with sub-micrometre resolution (a micrometre being one-thousandth of a millimetre). By analysing these images over the six hours of the experiment, the researchers conducted the first-ever time-resolved 3D study (otherwise known as 4D studies) of the dentine microstructural changes caused by acid.

The study, published in Dental Materials, shows that acid dissolves minerals in different structures of dentine at different rates. 

Research leader Dr Tan Sui, Senior Lecturer in Materials Engineering at the University of Surrey, known for her work creating improved bio-inspired materials, said:

“Relatively little is known about how exactly acid damages the dentine inside our teeth at a microstructural level. This new research technique changes that and opens the possibility of helping identify new ways to protect dental tissues and develop new treatments.”

Source: University of Surrey

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Most Trials in Clinical Practice Hold Up Over Time

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According to a new paper in Family Practice, medical practice can often be undermined by later research, randomised trials relevant to primary care generally hold up over time.

Medical reversal describes a problem whereby new research causes doctors to stop using a popular medication, procedure or test based on previous evidence. Vinayak Prasad, associate professor at the University of California, San Francisco, had found that up to 46% of original studies on adopted medical practices led to a reversal or shift in evidence of effect.

Evidence-based medicine lets doctors be confident when their decisions are grounded in high quality research. But decisions supported by robust evidence from randomised controlled trials can be reversed. For example, although aspirin is prescribed commonly to prevent cardiovascular disease, new studies indicate this treatment is unlikely to be effective.

Researchers studied the extent to which evidence from randomised control trials relevant to primary care were contradicted in subsequent research. Examining 408 randomised controlled trials from 2002 to 2005 relevant to primary care, the researchers found that over 12-17 years of follow up time, there were just 35 occurrences of evidence reversal, or roughly two a year. About nine in ten of such randomised control trials were not reversed.

“Conclusions from randomised trials relevant to primary care that also meet criteria for validity are stable over time,” said study lead author Christian Ruchon.

Source: EurekAlert!

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Muscles are Timekeepers for the Liver

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Researchers have found that skeletal muscles play a large part in regulating the liver’s biological clock. The findings were published in Science Advances.

The circadian rhythm is coordinated by the brain at a general level, but each organ or tissue is also subjected to specific regulation, adjusting to time to optimise their processes. However it was not known how the liver “knows” whether it is day or night.

The liver’s main role is digestion, mainly of fats and sugars: the brain is the main consumer of sugar while skeletal muscle is the main consumer of fat.

Scientists at IRB Barcelona discovered a surprising relationship: that it is skeletal muscle which regulates liver function and determines fat metabolism. Skeletal muscle accomplishes this by secreting a that is transported to the liver through serum is responsible for modulating around 35% of the metabolic functions of the liver. The remaining basal functions of this organ and others related to carbohydrate metabolism are independent of muscle activity and are regulated by the basal circadian rhythm from the brain.

“It’s a very nice discovery because it is the first demonstration of the need for communication between the circadian clocks of tissues and organs outside the brain, and we can see that this communication between muscle and liver is altered by aging,” said study leader Dr Salvador Aznar-Benitah at IRB Barcelona. “When we get older, cells stop obeying the biological clock and begin to perform functions in a non-optimal manner, leading to errors that cause tissues to age.”

The researcher’s results show that the liver does not independently regulate the metabolism of fats and that it is muscle that sends the message that it is time to switch on fatty acid metabolism and how it should go about this. “We didn’t expect to find this connection between the liver and muscle because it wasn’t known previously, but, on second thought, it makes complete sense that fat management is coordinated by one of its main consumers,” said Dr Aznar-Benitah. Carbohydrate metabolism meanwhile is dependent on the basal coordination exercised by the brain.

Source: Institute for Research in Biomedicine (IRB Barcelona)