Body

(LOS ANGELES) - Successful tissue regeneration can have major benefits in healing injuries or replacing portions of diseased or damaged tissue in bone, skin, the nervous system and in organs such as the muscle, kidney, liver, lung and heart. But the effectiveness of the body's own system for repairing such damage can vary greatly, depending on the kind of tissue involved and its location. Tissue engineers have been working to address these limitations by creating substances called biomaterials, which can be used in various ways to boost the body's ability to heal. In a recent publication in Nature Reviews Materials, Ali Khademhosseini, Ph.D., Director and CEO of the Terasaki Institute, and colleagues discuss the use of biomaterials for tissue regeneration.

When using biomaterials, there are two broad approaches that are commonly used. In the first and more traditional approach, biomaterials are mixed with appropriate cells and biomolecules outside of the body and implanted afterward into the injured area. The implanted construct is then allowed to develop into tissue that will function and regenerate as a replacement for the damaged tissue. In the second approach, specially-designed biomaterials are created without the addition of cells before implantation into the body. The implanted materials are designed to stimulate and enhance the body's own cellular and chemical healing mechanisms to produce regenerated tissue.

Both approaches can be effective, but there are distinct advantages to the second approach; this has spurred a recent trend towards its usage. Since the procedure does not involve the use of living cells in formulating the biomaterials, its implantation into the body is not subject to as many regulatory barriers. There are also more biomaterials systems available for clinical use with such an approach, and this lends itself towards designing a variety of biomaterials to promote and regulate the many events that are part of the body's natural healing process.

When an injury occurs to the body, there are three stages of events which occur: inflammation, new tissue formation and tissue remodeling. In the inflammation stage, a variety of immune cells move to the site of injury, removing dead cells and signs of infection and sending out signals for the recruitment of additional cells needed to replace the damaged ones. In the second stage, the recruited cells begin to reproduce and form a cellular matrix at the site, supported by a network of blood vessels. In the third stage, the matrix is reorganized and re-synthesized, to create new tissue.

Researchers can design biomaterials which affect events at any of these stages. One method of accomplishing this is by varying the physical and chemical characteristics of the biomaterials. These factors greatly influence cellular function, migration and proliferation. Physical characteristics such as stiffness, pore size and distribution, surface texture and degradation rate of the biomaterials can be manipulated to facilitate the recruitment of the body's own restorative cells to the injury site. The chemical properties of the biomaterials can also be manipulated to present biomolecules which will stimulate the recruited cells to grow and reproduce.

Another important influence of biomaterials is in its use of "reprogramming" the body's regenerative cells at the genetic level. Biomaterials can be created that will deliver factors that will control the gene expression needed to change cells from one type to another. Other factors may be delivered which will result in the production of proteins needed in tissue repair. Still other factors may be delivered by biomaterials via nanoparticles carrying gene-editing tools. These tools can perform precise genetic editing within the cells involved in the healing process.

Advancements made in biomaterial manufacturing, such as in 3D printing, and the diversification of its biomaterials, or bio-inks, have increased the ability to more precisely create complex or custom constructs for implantation. Many more advances in this area are likely to occur in the near future.

Recent progress made in the development of biomaterials has increased its potential for use in augmenting the body's natural abilities. Future methods in characterizing biomaterials' performance, such as artificial intelligence platforms and "omics" techniques, can provide further insight at the molecular level. Moving in this direction can lead to an increased success in developing the next generation of bio-responsive materials.

"Leveraging the regenerative potential of the human body via engineered biomaterials is a simple and effective approach to replace injured or diseased tissues. Thus, the development of next-generation of bio-responsive materials to regulate behavior of endogenous cells is expected to play a key role for in situ tissue regeneration," said Akhilesh K. Gaharwar, Ph.D., first author of the study and Associate Professor of the Department of Biomedical Engineering at Texas A&M University.

"It is anticipated that as we learn more about the biological mechanisms regulating the body, it will enable the development of even better biomaterials for tissue regeneration," said Khademhosseini, "This research area is an essential component of multiple thrusts within the Terasaki Institute and is likely to change the future of medicine."

WEST LAFAYETTE, Ind. -- Researchers at Vanderbilt University Medical Center, Purdue University and the University of Wisconsin-Madison have isolated human monoclonal antibodies that potentially can prevent a rare but devastating polio-like illness in children linked to a respiratory viral infection.

The illness, called acute flaccid myelitis (AFM), causes sudden weakness in the arms and legs following a fever or respiratory illness. More than 600 cases have been identified since the U.S. Centers for Disease Control and Prevention began tracking the disease in 2014.

There is no specific treatment for AFM, which tends to strike in the late summer or early fall and which has been associated with some deaths. However, the disease has recently been linked to a group of respiratory viruses called enterovirus D68 (EV-D68).

Researchers at the Vanderbilt Vaccine Center isolated antibody-producing blood cells from the blood of children who had previously been infected by EV-D68. By fusing the blood cells to fast-growing myeloma cells, the researchers were able to generate a panel of monoclonal antibodies that potently neutralized the virus in laboratory studies.

Colleagues at Purdue determined the structure of the antibodies, which shed light on how they specifically recognize and bind to EV-D68. One of the antibodies protected mice from respiratory and neurologic disease when given either before or after infection by the enterovirus.

Comments from researchers

"We were excited to isolate potent human antibodies that inhibit this devastating polio-like virus, and these studies will form the basis for taking them forward to clinical trials," Dr. James Crowe, director, Vanderbilt Vaccine Center; Ann Scott Carell Chair and professor of Pediatrics and Pathology, Microbiology and Immunology in the Vanderbilt University School of Medicine.

"Studying infectious disease from a very basic level and applying the results in an animal model of disease is very powerful; hopefully, our studies will translate to a future therapeutic for this disease in children," Richard Kuhn, Purdue's Trent and Judith Anderson Distinguished Professor in Science; Krenicki Family Director, Purdue Institute of Inflammation, Immunology and Infectious Disease

Preeclampsia is a devastating disorder that occurs very suddenly in the second half of pregnancy and causes severe health problems for both mother and baby. Preeclampsia also increases the risk of developing life-long chronic diseases such as diabetes and heart disease.

The discovery of two novel biomarkers, called FKBPL and CD44, has the potential to change the way the condition is managed according to research published in the Journal of Clinical Endocrinology and Metabolism. Preeclampsia can cause high blood pressure and organ failure in mothers and lead to preterm births and even stillbirth.

Senior author, Dr Lana McClements from the University of Technology Sydney, said the biomarkers can be used to diagnose and assess the risk of getting preeclampsia in both early and late pregnancy, "in women who otherwise appear healthy".

"There are two main types of preeclampsia: early-onset preeclampsia diagnosed before 34 weeks of a pregnancy and late-onset preeclampsia diagnosed from 34 weeks onwards," Dr McClements said.

"The vast majority of the current screening and monitoring strategies are focused on early-onset preeclampsia, which comprises only 10-15% of all preeclampsia cases, whereas late preeclampsia has been largely neglected," she said.

The researchers say the two biomarkers are particularly useful for diagnosing cases of late-onset preeclampsia, between the second and third trimester, a period that currently lacks reliable biomarkers.

" The biomarkers allow the prediction of irregular placenta or maternal vascular function, which are key underlying causes of preeclampsia.

"This could lead to the early diagnosis and prevention of severe preeclampsia and associated complications including death, therefore also giving insight into disease mechanisms and possible treatment targets," Dr McClements said.

The research also has potential to enhance the development of therapeutics to treat preeclampsia because the increase in one of the biomarkers, FKBPL, can be inhibited by mesenchymal stem cells potentially stopping the development of preeclampsia.

" This is why we are so excited by the discovery. In addition to their use in diagnosis, FKBPL and CD44 also show potential as drug and cell therapy targets of emerging treatments for preeclampsia, which offers hope for a future cure to this terrible disorder," Dr McClements said.

There has been a surge in domestic child abuse during the coronavirus pandemic, suggests the experience of one specialist UK children's hospital, reported in Archives of Disease in Childhood.

In just one month, the number of new cases rose by 1493% compared with the same period in the previous three years, pointing to a "silent pandemic" in 2020, suggest the authors.

They compared the numbers of new cases of head injury caused by physical abuse among very young children seen between 23 March and 23 April this year and the same period in 2017, 2018, and 2019.

March 23 marked the start of lockdown and a period of national self-isolation in the UK in a bid to curb the spread of SARS-CoV-2, the virus that causes COVID-19 infection.

Ten children (six boys and four girls) with suspected abusive head trauma presented for treatment during March-April. Their ages ranged from 17 days to 13 months old.

This figure compares with an average of 0.67 cases a month for the same period in 2017, 2018, and 2019, representing an increase of 1493% in 2020, say the authors.

The symptoms prompting a hospital visit included colic (persistent crying for no obvious reason) in 5 of the infants; breathing issues (apnoea) and loss of consciousness in 4; seizures in 2; extensive bruising in 5; swollen scalp in 5; and marks caused by repeated picking at the skin (excoriation) in 1 child.

The infants were comprehensively assessed. This included head, spine, and skeletal scans, as well detailed eye and whole body checks.

The results revealed blood pooling in the brain (subdural haemorrhage) in 6 infants; brain swelling in 4; bruising of the brain tissue (parenchymal contusion) in 4; skull fractures in 4; a bleed on the brain (subarachnoid haemorrhage) in 3; and bone fractures elsewhere in 3 of the infants.

The infants' families all lived in areas of significant social and economic deprivation. And there's a complex interplay between abuse, mental health, substance misuse and socioeconomic factors, the authors point out.

Two of the parents had a history of criminal activity; 3 had mental health issues; and 4 had financial worries, factors likely to heighten the risk of abusive behaviour, say the authors.

"Our cohort is aligned to the literature in its portrayal of socioeconomic deprivation and parental vulnerability as significant risk factors for abuse, both of which may be exacerbated as a result of the stresses imposed by quarantine measures," they write.

And the fact that children are spending more time with their parents as a result and that there will have been less interaction with reporting bodies will have only added to these risks, they suggest.

This case series represents the experience at just one specialist children's hospital in England, but it echoes the reports coming out of countries enforcing similar measures to the UK during this pandemic, note the authors.

And the figures are likely to be an underestimate of the scale of the problem, they warn.

"This sobering figure is likely under-represented due to public avoidance of hospitals at this time," they write. "Notably two parents in our cohort cited fears of contracting SARS-CoV-2 as a reason for delayed presentation."

And they conclude: "Hence, in the background of the intensely public SARS-CoV-2 pandemic, a more silent pandemic is occurring, of which the medical community must remain astutely aware."

Dr Alison Steele, Officer for Child Protection at the Royal College of Paediatrics and Child Health, which co-owns Archives of Disease in Childhood with BMJ, commented: "This is an extremely concerning report. It is important to find out if the huge rise in suspected non-accidental head injury reported at this specialist hospital is being seen by other hospitals across the country."

She added: "Many of these children will have been brought into hospital because there were obvious signs that the child was very unwell, but we are also extremely worried about children who are not being seen because their physical injuries or other forms of abuse or neglect are more easily hidden."

And she warned: "There is a very real danger that, under lockdown, children are falling through the safety net because of reduced access to support services and fewer opportunities for people outside the family to sound the alarm."

What The Viewpoint Says: How surgical global health programs are affected by the COVID pandemic and why global surgical outreach models may need to be rehashed are discussed in this article.

Authors: Parsa P. Salehi, M.D., of the Yale University School of Medicine in New Haven, Connecticut, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoto.2020.1520)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

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What The Viewpoint Says: How the COVID-19 pandemic can reshape care in patients with cancer to focus on discouraging unnecessary in-person visits, testing and low-value treatments is discussed in this article.

Authors: Bishal Gyawali, M.D., Ph.D., of Queen's University in Kingston, Ontario, Canada, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoncol.2020.2404)

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New research from The University of Queensland has found that women who have hot flushes and night sweats after menopause are 70 per cent more likely to have heart attacks, angina and strokes.

School of Public Health PhD student Dr Dongshan Zhu has found women of any age who experience hot flushes and night sweats, also known as vasomotor symptoms or VMS, are more likely to experience non-fatal cardiovascular events.

"Until now, it's been unclear if VMS is associated with cardiovascular disease, but now we know it to be true," Dr Zhu said.

"Further, VMS before menopause increases a woman's chance of cardiovascular events by 40 per cent."

Dr Zhu also found that the risk of cardiovascular events was more related to the severity of the hot flushes and night sweats rather than the frequency or duration.

"We found that women with severe VMS were more than twice as likely to experience a non-fatal cardiovascular event compared with women who had no symptoms," he said.

Dr Zhu used data from InterLACE, a major collaboration of 25 studies of more than 500,000 women around the world.

Senior author on the study Professor Gita Mishra said the findings may have important clinical implications.

"This research helps to identify women who are at a higher risk for the development of cardiovascular events and who may need close monitoring in clinical practice," Professor Mishra said.

Better still: living algae can be used as biocatalysts for certain substances, and they bring the co-substrate along, producing it in an environmentally friendly manner through photosynthesis. The team published its report in Algal Research on 17. June 2020.

It's a question of 3D structure

Many chemical substances in cosmetics, food or medicines can assume slightly different three-dimensional structures, with only one of them generating the desired fragrance or medical effect. The chemical production of the right substances is often not environmentally friendly, as it requires high temperatures or special solvents. In nature, however, certain proteins do exist that produce the required product at mild temperatures and in water. In the process, they often generate exactly the 3D structure of the substance that is needed by the industry.

These so-called old yellow enzymes, OYEs for short, owe their name to their naturally yellow colour. They occur in bacteria, fungi and plants, are in part well studied and offer considerable potential for a bio-based economy. However, they have one disadvantage: in order to carry out their reaction, they need the co-substrate NADPH (nicotinamide adenine dinucleotide phosphate). In living cells, this small molecule is generated through metabolic processes, whereas its chemical production is very expensive; as a result, the commercial use of OYEs is thwarted.

OYEs from unicellular green algae: two birds with one stone

The research team from Bochum has discovered several OYEs in unicellular green algae. "For a broad application, industry needs OYEs that can also produce unusual molecules," explains Professor Thomas Happe, Head of the Photobiotechnology research group at RUB. "Algae possess very complex metabolic pathways and are therefore ideal sources for novel biocatalysts." The researchers analysed algal OYEs in the test tube and showed that they are able to convert many commercially viable substances. "The exciting thing is that living algae can also carry out the reactions needed in the industry," points out PhD student Stefanie Böhmer, lead author of the study. "Since algae produce NADPH using photosynthesis, i.e. with sunlight, the co-substrate of the OYEs is supplied in an environmentally friendly and cost-effective way."

Promising collaboration

The authors point out that the study demonstrates the importance of the collaboration between researchers from different disciplines, and that the industry can be a valuable partner who initiates basic research. Four researches from the Research Training Group "Micon - Microbial substrate conversion", which is funded by the German Research Foundation, contributed their expertise to the study. The project was the brainchild of Solarbioproducts Ruhr, a spin-off established by Wirtschaftsförderungsgesellschaft Herne and Thomas Happe with the aim of developing concepts for environmentally friendly algae biotechnologies. "We have taken a big step towards a green industry," concludes Happe. "This would not have been possible without collaboration."

Healing with the help of marine organisms is no utopia. Already 12 life-saving drugs, e.g. against cancer, have been developed from marine organisms and their symbiotic microbiota. Their high potential for drug development is hampered by the lengthy and costly discovery process. The research group of the Marine Natural Product Chemistry Research Unit at GEOMAR Helmholtz Centre for Ocean Research Kiel, supported by computer-aided automated approaches, has now successfully discovered marine molecules as potential remedies against infections and skin cancer in an alga and its fungal symbiont originating from the Kiel Fjord.

The search process for marine active ingredients starts with the extraction of marine macro- and microorganisms, followed by the purification and characterization of their novel and bioactive chemical constituents, which are intended to be used for the development of new therapeutics. "One of the biggest pitfalls in drug research is the isolation of already described natural molecules, using the 'classical' bioactivity-guided isolation process", explains Prof. Dr. Deniz Tasdemir, head of Research Unit Marine Natural Product Chemistry at GEOMAR and GEOMAR Centre for Marine Biotechnology. "This approach is complicated and often prone to failures", Dr. Tasdemir continues.

In her research group, she addressed this problem through automated, computer-based approaches in combination with bioactivity screenings. In a one-year study, it was found that the brown alga Fucus vesiculosus (bladder wrack) from the Kiel Fjord, inhibits the pathogenic bacterium Methicillin-resistant Staphylococcus aureus (MRSA), which causes hospital infections.

"Algorithm-based bioinformatics strategies and machine learning tools have enabled us to map the massive metabolome of brown alga and at the same time predict the molecular clusters responsible for their antibiotic activity", said Dr. Larissa Büdenbender, a former postdoctoral fellow in Prof. Tasdemir's group and first author of one of the two articles now published in the journal Marine Drugs. The algorithms applied in this study group together the molecular families in complex networks based on their chemical similarity scores in mass spectrometry analyses, and together with in silico machine learning tools, help us to chemically identify the known and new compounds already in the extract. After the first rapid chemical fractionation step of the extract, a bioinformatic programme is used to predict the bioactivity score of molecules according to their relative abundance in the fractions. These bioactive compounds are isolated. "The classical discovery approach from extraction to characterization of bioactive ingredients of the alga would normally take 3-4 years. These automated tools helped us to accelerate the targeted discovery of new natural antibiotics down to some months", emphasizes Prof. Tasdemir.

"In nature, bladder wrack is often under strong pressure from fouling and biofilm formation by millions of microorganisms found in seawater. Therefore, membrane-bound compounds, as we identified in this study, are of high ecological importance for self-protection of the alga. Such molecules, which perform a critical function in natural space, often display related activities against human pathogens. Since bladder wrack is an edible seaweed, such activities make it an attractive candidate not only as a source of drugs, but also for food supplements or food protection", says Prof. Tasdemir. Next, we will be investigating the application potential of bladder wrack in food industry.

Many fungi also live in symbiosis on the surfaces and inside of seaweed. These are also promising sources for the discovery and development of new drugs. Bicheng Fan, a PhD student of Professor Tasdemir, has isolated more than 120 symbiotic fungi from bladder wrack and has studied the fungus Pyrenochaetopsis sp. in detail, as it efficiently kills melanoma-type skin cancer cells with low cytotoxicity and has a very rich chemical inventory. Bicheng also used computer-aided automated approaches to isolate special molecules with a rare chemical scaffold. The study was also recently published in Marine Drugs.

According to Prof Tasdemir, this is only the second chemical study on the previously completely unexplored fungal genus Pyrenochaetopsis. "Fungi, which we isolated from bladder wrack and fermented in optimized laboratory conditions, are an established source of natural anti-cancer agents. We have found several novel natural products here, which we named as pyrenosetins A and B, that have a high potential for fighting skin cancer", the chemist continues.

"Nature is the source of more than half of all modern medicines that we use today. Access to the revolutionary genomics, metabolomics, bioinformatics and machine learning tools will enable, in an unprecedented way, new and rapid discovery of marine compounds, and more rational and efficient use for subsequent drug development with industrial partners"," Professor Tasdemir concludes.

New technique in which drugs make bacteria glow could help fight antibiotic resistance

A new technique could help reduce antibiotic prescribing by predicting which drugs could be effective in fighting bacteria within minutes.

Scientists at the University of Exeter have developed the method, which allows users to see whether a bacterium is likely to respond to antibiotics. The research is currently in early stages of development, and the team hope the miniaturised devices they use for this research could one day be based in clinics, reducing the number of different antibiotics prescribed to patients.

The technique works by examining whether fluorescent qualities of the antibiotics are taken up by bacteria. If so, the bacteria glow brighter under the microscope, revealing that the antibiotic has infiltrated the membrane and could be effective. The research, published in the journal Lab on a Chip, could contribute to efforts to reduce prescribing, and also enable the development of more effective antibiotics, to help fight the global threat of antibiotic resistance.

Antibiotic resistance is recognised as a major global threat. As these drugs increasingly fail to work, around 10 million people are predicted to die annually of infections by 2050.

The new technique uses a special microscope and a miniaturised device into which a sample of the bacteria is injected, along with the antibiotic. To date, the team has used the antibiotic ofloxacin, which glows fluorescent under ultraviolet light. Bacteria also glow when the antibiotic is taken up. However, if they remain dark, the antibiotic has no chance of working and killing the bacteria.

Dr Stefano Pagliara, a biophysicist in the Living Systems Institute, leading this research at the University of Exeter, said: "We're really excited about the potential for this technique to make a meaningful reduction in prescribing, helping to fight the global threat of antibiotic resistance. At the moment, it can take days for clinicians to get a lab result, which involves growing bacteria, but there is still some guess work involved. Our technique could reduce the use of multiple antibiotics to try and fight a bacterial infection."

Dr Jehangir Cama, an industry research fellow at the Living Systems Institute, who performed the experimental work of this research, said: "Our next step is to further develop this exciting new method by combining it with more advanced microscopy techniques, to see where exactly the antibiotics go when they enter the bacteria."

The team is now working on expanding the technique, by manipulating the fluorescent qualities of other forms of antibiotics so they can work in the same way. Further research in this area has been funded by QUEX, a partnership between the University of Exeter and The University of Queensland in Australia. The Queensland team, led by Dr Mark Blaskovich, Director of the Centre for Superbug Solutions at the Institute for Molecular Bioscience, is developing fluorescent versions of other antibiotics so they can be tested in a similar manner. Blaskovich adds "I am enthused about the opportunities to improve our fundamental understanding of the interactions between antibiotics and bacteria and how this leads to antimicrobial resistance, by combining our novel antibiotic-derived probes with the cutting edge single cell analysis capabilities of the Exeter group".

WASHINGTON--Health care providers may unintentionally expose patients to endocrine- disrupting chemicals (EDCs) by prescribing certain medications and using medical supplies, according to a perspective published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

Exposure to EDCs, chemicals that disrupt the body's natural hormones, is most often associated with industrial pollution, contaminated food and water, or personal and home care products. Less appreciated is the fact that some medications and medical devices also contain these harmful chemicals. This includes both prescribed and over-the-counter medications as well as medical equipment used in the hospital, including among the most vulnerable patients in the neonatal intensive care unit. Unfortunately, most healthcare providers are unaware of these risks, and patients are unaware of their exposure.

"Through the prescribing of medications and the use of medical supplies, health care providers expose patients to chemicals that can disrupt the body's natural hormones," said the study's lead author, Robert Michael Sargis, M.D., Ph.D., of the University of Illinois at Chicago in Chicago, Ill. "In order to provide ethically sound medical care, the health care community must be made aware of these risks, manufacturers must strive to identify and eliminate endocrine-disrupting chemicals from their products, and patients must be empowered with knowledge and options to make informed decisions that limit their exposure to potentially harmful chemicals. As clinicians, we have an ethical imperative to act on this issue to protect our patients."

The authors are calling on physicians to become educated about their role in exposing patients to these chemicals. They express the need for better patient education and a commitment on the part of physicians to live up to their ethical mandates to discuss the risks of EDC exposure. Regulatory agencies and manufacturers also need to identify and eliminate EDCs in medications and medical devices and develop safer alternatives.

"As health care providers, we need to do a better job of limiting the threats of chemical exposures to our patients' health by ending our complicity in mediating those exposures," Sargis said.

In a newly published experimental study, the consumption of dietary fibre from oat and rye brans supported the growth of beneficial gut microbiota, which in turn ameliorated cholesterol metabolism, enhanced gut barrier function and reduced hepatic inflammation. In addition, diets enriched with oat or rye bran were shown to attenuate weight gain. The effects of oat and rye were partly different, but both were beneficial for health.

The study was conducted within the research collaboration between the Institute of Public Health and Clinical Nutrition of the University of Eastern Finland, VTT Technical Research Centre of Finland and the School of Biological Sciences of The University of Hong Kong.

The health benefits of oat, rye and other whole grain products have been widely studied, and their use has been associated with decreased inflammation and improved glucose, lipid and adipose tissue metabolism in human and animal experimental research. In addition, they have been linked to a decreased risk of obesity, metabolic syndrome, cardiovascular diseases and type 2 diabetes. Different dietary fibres are also known to have differing health effects.

Until recently, the mechanisms underlying the health effects or oat and rye bran fibres have not been well understood. Dietary fibre is known to induce changes in gut microbiota function and to thus modulate gut environment in a beneficial manner. How this modulation is associated with metabolic pathways is, however, largely unclear. The aim of this experimental study was to investigate differences in metabolites produced by gut microbiota and their interactions with host metabolism in response to supplementation with oat and rye bran fibres.

The study was an animal experiment during which mice were fed a high-fat Western diet for 17 weeks. Two groups were fed the same diet enriched with 10% of either oat or rye bran. Among the various gut microbial metabolites, this study focused on those especially relevant to the development of fatty liver disease, which is often associated with obesity. Thus, microbial metabolites were assessed by measuring cecal short chain fatty acids (SCFAs), ileal and fecal bile acids, and the expression of genes related to tryptophan metabolism.

The findings suggest that both brans have the capacity to create a favourable environment in the gut by supporting the growth of beneficial microbes. The abundance of Lactobacillus genera was increased in the oat group, whereas Bifidobacterium genera was increased in the rye group. Via these microbiota changes, oats modified bile acid-related receptor function and rye modified bile acid production, which led to an improved cholesterol metabolism. Both bran fibres enhanced the production of SCFAs, leading to improved gut integrity, reduced liver inflammation, and diversion of tryptophan metabolism to a more beneficial pathway, that is, from serotonin synthesis to microbial indole production. In addition, both oat and rye supplementation were shown to attenuate weight gain associated with a high-fat diet.

Researchers at the University of Tasmania's Menzies Institute for Medical Research and the School of Medicine have added an arsenal of new tools (video link) to their repertoire for fighting the insidious Devil Facial Tumour Disease.

A paper published today in the prestigious Science Advances journal outlines new cost-effective technology that can be used for advanced immunology studies in Tasmanian devils.

Immunotherapy has transformed the way cancer is treated in the past decade, but little is known about its potential in other species. Lead author on the study, Dr Andrew Flies, said that around 40% of humans and Tasmanian Devils develop cancer in their lifetime.

Tasmanian devils are also afflicted with two different transmissible cancers that have killed thousands of devils.

"We developed a simple cut-and-paste reagent development method that can be applied to any vertebrate species and show that immune pathways are conserved across 160 million years of evolution."

"The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can serve as models for understanding cancer and immunological tolerance."

This system was used to show that many key Tasmanian devil immune proteins look the same as they do in the human immune system. We also showed that we could find tumour cells in blood, which could shed light on how cancer invades organs and kills devils.

The versatility of the system was demonstrated by replicating a nanobody (aka tiny antibody) that binds to a key human immune checkpoint protein, and thus demonstrated that the new system can be used for any animal species.

Director of the Menzies Institute for Medical Research, Distinguished Professor Alison Venn, said this research was vital for a Tasmanian icon.

"These new tools allow us to accelerate our devil immunology and vaccine research to help save the Tasmanian devil."

What The Study Did: Researchers investigated the association between the stage of breast cancer at diagnosis and the insurance status, age and race/ethnicity of patients before and after the expansion of Medicaid under the Affordable Care Act.

Authors: Tristen S. Park, M.D., of the Yale University School of Medicine in New Haven, Connecticut, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamasurg.2020.1495)

Editor's Note: Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Patient and public voices were "regrettably" absent in the early stages of the covid-19 pandemic, but must now move centre stage, argue experts in The BMJ today.

Patient Partnership Editor Tessa Richards, Patient Editor Henry Sowcroft, and the members of The BMJs International Patient and Public Advisory Panel, acknowledge that decisions had to be made fast, but say "policy makers' choice of expert advisers excluded those with expertise rooted in lived experience - patients, families, and frontline health and social care professionals."

This was regrettable, they say. "Their input would have helped to mitigate the predictable adverse effects of massive service reconfiguration and lockdown, and emphasised the need for clarity on which services would be suspended and which would remain accessible."

But while patient and civil society advocacy groups may have lacked seats on expert committees, they have taken the lead in providing information, advice, and support for their communities, note the authors.

For instance, they have lobbied for a voice in policy making, for a focus on inequalities, and for policies to take account of the reality of people's lives. They have also accumulated a wealth of information from the patient community on the physical, mental, social and economic effects of the pandemic, effects that highlight the urgency of restoring essential medical services and the need for a comprehensive public health response.

So why were the voices of patients and the public tuned out, they ask?

Despite decades of activism, they argue that public and patient involvement is still largely seen as "nice to have" but non-essential. "The resources, skills, views, priorities, and preferences of patients, carers, and the communities which support them are not well recognised, valued, or systematically used to improve care."

They urge health leaders to listen to and engage with patient advocates, organisations and civil society networks who are "primed to inform joint learning from the pandemic and help shape post-covid services."

And they say more collaborative platforms to unite patient communities with professional groups should be established to ensure that public and patient involvement "becomes irreversibly embedded in decision making."

Providing people with full online access to personal health records and test results "will improve the quality and safety of care, and raise health literacy on both sides of the professional fence," they add.

Finally, they say mutual understanding and respect is essential in any partnership, and patient leadership must be taken seriously by both health professionals and patients.

They conclude: "Covid-19 has precipitated a global health crisis, plunged the world into economic recession, put the spotlight on structural inequalities, including racism, and galvanised the call for action on climate change. The knowledge to confront these challenges needs to be co-produced. Patient involvement must be taken seriously, embedded robustly, and never sidelined again."

In 2014, The BMJ launched its patient and public partnership strategy to encourage doctors and patients and those who care for them to work together as partners to improve healthcare. Since then, input from patients has been an integral part of how the journal works and thinks.

The BMJ's collection of patient and public perspectives on the pandemic can be found here: https://blogs.bmj.com/bmj/category/patient-perspectives/