Culture

Bottom Line: Researchers compared long-term quality of life and patient satisfaction among those patients who were treated with antibiotics or who had their appendix removed for uncomplicated acute appendicitis. Evidence in recent years has indicated antibiotic treatment is a safe and efficient alternative to appendectomy. This study was a seven-year follow-up of a randomized clinical trial in Finland of patients with uncomplicated acute appendicitis who underwent appendectomy or who received antibiotics. The follow-up included 423 patients who completed questionnaires regarding quality of life and their level of satisfaction with the treatment received. Researchers found no difference between treatment groups in patient-rated quality of life or in satisfaction with the treatment if it was successful. Patients taking antibiotics who later had an appendectomy were less satisfied than patients with successful antibiotic or appendectomy treatments. Limitations of the study include use in the initial trial of an open surgical approach for appendectomy since laparoscopic appendectomy is the current standard associated with shorter hospital stays and less postoperative pain.

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

Authors: Paulina Salminen, M.D., Ph.D., of Turku University Hospital, Turku, Finland, and coauthors

(doi:10.1001/jamasurg.2019.6028)

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

What The Study Did: Researchers compared treatment and survival rates between African American and white women following early detection with mammography of triple-negative breast cancer. African American women have a higher rate of death from breast cancer compared with white women, a disparity partly explained by a higher rate of this aggressive breast cancer.

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

Authors: Lisa A. Newman, M.D., M.P.H., of Weill Cornell Medicine in New York, is the corresponding author.

(doi:10.1001/jamasurg.2019.6032)

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

What The Study Did: The large health care system Kaiser Permanente Northern California provides universal screening for prenatal cannabis use in women during pregnancy by self-report and urine toxicology testing. This observational study used data to examine the association of depression, anxiety, and trauma diagnoses and symptoms with cannabis use by women during pregnancy.

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

Authors: Kelly C. Young-Wolff, Ph.D., M.P.H., of Kaiser Permanente Northern California in Oakland, is the corresponding author.

(10.1001/jamanetworkopen.2019.21333)

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.

What The Study Did: This analysis estimated the health and economic consequences of indoor tanning regulations, such as banning indoor tanning devices or prohibiting their use by minors, in North America and Europe compared with current levels of use.

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

Authors: Louisa G. Gordon, Ph.D., of QIMR Berghofer Medical Research Institute in Brisbane, Australia, is the corresponding author.

(doi:10.1001/jamadermatol.2020.0001)

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

New research has identified a clear accountability gap in the current Freedom of Information (FOI) legislation when it comes to outsourced public services.

The research, which focused on outsourcing through Private Finance Initiative (PFI), found high levels of non-disclosure due either to refusal/partial refusal or non-response to FOIs.

The University of Leeds researchers are now calling for extensive reform to current FOI laws to ensure proper public scrutiny, which they believe is especially important when it comes to vital safety information and the conditions of schools, hospitals and flats.

Study lead author Megan Waugh, a PhD researcher at Leeds, said: "The current FOI Act is not fit for purpose for this recent age of outsourcing. Through the Private Finance Initiative, the private sector became increasingly responsible for outsourced public services and government expenditure.

"Our FOI requests were submitted to public authorities with PFI contracts, including government departments, NHS trusts, councils and police and fire authorities, but we struggled to unlock important information about PFI schemes."

During 2016 and 2017, Megan Waugh and Dr Stuart Hodkinson from the School of Geography at Leeds submitted 687 FOI requests.

They covered 678 of the 715 operational PFI projects in the UK, and 315 of the total 331 public authorities involved, amounting to a 95% coverage of contracts and authorities.

The study, published in Parliamentary Affairs, shows that for 42% of the requests no information whatsoever was provided, and only 24% resulted in full disclosure.

In more than half the cases, authorities failed to respond within the statutory 20-day period - exceeding the legal limit under FOI guidelines. Only 5% of late responses provided a legal justification for doing so.

In many instances, the study highlights how researchers were unable to gain access to basic information such as the number and location of buildings or sites across PFI schemes.

Subjects of the FOIs also included requests for details of safety audits on public buildings and details of financial penalties for poor performance on PFI contracts.

The study also found an over reliance of non-exemptions as reasons for withholding information, such as legal exemptions or expense. This, the researchers argue, raises concerns about the tactics being employed to avoid engaging with public interest arguments.

Megan Waugh continued: "Safety concerns, controversies and criticism have plagued PFI projects over several decades.

"The absence of systematic client or government monitoring of PFI contracts, as well as the lack of open data about each project, means we have become increasingly reliant on FOI and other legislation to find out important information about PFI schemes.

"But this research has raised serious questions about the suitability and effectiveness of the UK's current legislation as an accountability tool."

Study co-author Dr Stuart Hodkinson, Associate Professor in the School of Geography, said: "The profound difficulty in uncovering even the most basic information about PFI contracts shines a light on the current accountability vacuum for PFI schemes.

"FOI legislation should provide the means by which the public can find, among other things, important information regarding the safety of their living and workplaces. Our findings show that currently the law is too weak to be effective and is being flagrantly ignored by public bodies."

Although PFI has fallen out of favour since 2010 and future PFI schemes were officially ended in the UK's October 2018 budget, there are currently more than 700 PFI schemes operating nationally, with a combined capital value of £59 billion and total contractual payments worth £309 billion over the period 1990 to 2050.

The researchers call for legislative and regulatory reform to be extended to cover large private firms responsible for public services and that PFI contracts should be accessible and published online.

Additionally, they recommend new enforcement powers should be included to enable the Information Commissioner to challenge tactics used by public authorities that are withholding information that is deemed to be in the public interest.

Andrew Slaughter, the Labour Hammersmith MP who has campaigned for better FOI laws, said: "This research makes the case for comprehensive reform of Freedom of Information legislation 20 years after the original Act was passed.

"There is growing support for updating the Freedom of Information Act to take account of the growth in outsourcing - in Parliament, in wider society and from the Information Commissioner's Office. This paper provides the evidence and analysis to support the campaign.

"I hope the new Government will look seriously at reforming and improving public access to information."

PHILADELPHA -- Machine learning is helping Penn Medicine researchers identify the size and shape of brain networks in individual children, which may be useful for understanding psychiatric disorders. In a new study published today in the journal Neuron, a multidisciplinary team showed how brain networks unique to each child can predict cognition. The study--which used machine learning techniques to analyze the functional magnetic resonance imaging (fMRI) scans of nearly 700 children, adolescents, and young adults--is the first to show that functional neuroanatomy can vary greatly among kids, and is refined during development.

The human brain has a pattern of folds and ridges on its surface that provide physical landmarks for finding brain areas. The functional networks that govern cognition have long been studied in humans by lining up activation patterns--the software of the brain--to the hardware of these physical landmarks. However, this process assumes that the functions of the brain are located on the same landmarks in each person. This works well for many simple brain systems, for example, the motor system controlling movement is usually right next to the same specific fold in each person. However, multiple recent studies in adults have shown this is not the case for more complex brain systems responsible for executive function--a set of mental processes which includes self-control and attention. In these systems, the functional networks do not always line up with the brain's physical landmarks of folds and ridges. Instead, each adult has their own specific layout. Until now, it was unknown how such person-specific networks might change as kids grow up, or relate to executive function.

"The exciting part of this work is that we are now able to identify the spatial layout of these functional networks in individual kids, rather than looking at everyone using the same 'one size fits all' approach," said senior author Theodore D. Satterthwaite, MD, an assistant professor of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania. "Like adults, we found that functional neuroanatomy varies quite a lot among different kids--each child has a unique pattern. Also like adults, the networks that vary the most between kids are the same executive networks responsible for regulating the sorts of behaviors that can often land adolescents in hot water, like risk taking and impulsivity."

To study how functional networks develop in children and supports executive function, the team analyzed a large sample of adolescents and young adults (693 participants, ages 8 to 23). These participants completed 27 minutes of fMRI scanning as part of the Philadelphia Neurodevelopmental Cohort (PNC) a large study that was funded by the National Institute of Mental Health. Machine learning techniques developed by the laboratory of Yong Fan, PhD, an assistant professor of Radiology at Penn and co-author on the paper, allowed the team to map 17 functional networks in individual children, rather than relying on the average location of these networks.

The researchers then examined how these functional networks evolved over adolescence, and were related to performance on a battery of cognitive tests. The team found that the functional neuroanatomy of these networks was refined with age, and allowed the researchers to predict how old a child with a high degree of accuracy.

"The spatial layout of these networks predicted how good kids were at executive tasks," said Zaixu Cui, PhD, a post-doctoral fellow in Satterthwaite's lab and the paper's first author. "Kids who have more 'real estate' on their cortex devoted to networks responsible for executive function in fact performed better on these complex tasks." In contrast, youth with lower executive function had less of their cortex devoted to these executive networks.

Taken together, these results offer a new account of developmental plasticity and diversity and highlight the potential for progress in personalized diagnostics and therapeutics, the authors said.

"The findings lead us to interesting questions regarding the developmental biology of how these networks are formed, and also offer potential for personalizing neuromodulatory treatments, such as brain stimulation for depression or attention problems," said Satterthwaite. "How are these systems laid down in the first place? Can we get a better response for our patients if we use neuromodulation that is targeted using their own personal networks? Focusing on the unique features of each person's brain may provide an imporant way forward."

NEW YORK, NY (February 19, 2020) - A global community of over 150 scientists studying the primate brain has released a blueprint for developing more complete "wiring diagrams" of how the brain works that may ultimately improve understanding of many brain disorders.

In a new paper published in the journal Neuron, participants in a Global Collaboration (entitled the PRIMatE Data Exchange: PRIME-DE) reveal an exciting vision for how primate brain imaging can help to accelerate landmark discoveries in neuroscience and medical breakthrough of direct relevance to humans. PRIME-DE is an open science program of the International Neuroimaging Data-sharing Initiative of the Child Mind Institute.

Through highly collaborative global efforts such as the Human Connectome Project, the human neuroimaging community has matured. However, important information about how the brain works often cannot be obtained in humans.

Until recently, there has been little global collaboration focused on nonhuman primate brain imaging. If this can be achieved, it will allow better direct translation of information from animal research to humans and accelerate breakthroughs in biomedicine. In sum, everyone benefits when the global community shares for greater openness and puts forward a vision to stimulate scientific discovery around the world.

To accelerate the pace of progress, the PRIME-DE initiative recently established a repository of openly shared data and assembled a vibrant international community of scientists for a Global Collaboration workshop hosted by the Wellcome Trust in London last September 2019. Additional funding support for early career investigators was provided by the BRAIN Initiative, Kavli Foundation, and National Institute of Mental Health. The resulting paper, "Accelerating the Evolution of Nonhuman Primate Neuroimaging," summarizes the vision and goals of the global community.

The authors write that the community can dramatically accelerate the pace of progress if these commitments are made across the globe:

Increasing the Quality of Brain Imaging. The community can establish data quality and minimal specifications for brain imaging acquisition to increase shared data value across the world.

International Regulations and Public Engagement. International institutions and regulators can work together to support global collaboration, openly communicate the importance of the work with animals and the high levels of care of research with both human and nonhuman animals.

Harnessing the Latest Technology. Adopting the latest technology is required for generating important insights from these large amounts of data, maximizing benefits for science and medicine.

The paper also outlines the community ambitions to openly share thousands of datasets and the development of a large-scale, multimodal resource to directly complement the Human Connectome Project and to bridge to information that cannot be obtained in humans.

"Primate neuroimaging has remained largely piecemeal and single-lab driven, causing most scientists to struggle to amass datasets consisting of even 10 to 20 individuals, whereas the human-imaging community now aim for thousands," write co-authors Michael Milham, MD, PhD, vice president of research at the Child Mind Institute and director of the Center for Biomedical Imaging and Neuromodulation at the Nathan S. Kline Institute for Psychiatric Research; and Christopher I. Petkov, PhD, professor of comparative neuropsychology at Newcastle University Medical School. "If this global collaboration blueprint serves as a litmus test of what the future will bring, exciting advances and discoveries not possible to achieve in a single laboratory or country will soon become evident by global collaboration."

SINGAPORE, 20 February 2020 - Publishing in the prestigious New England Journal of Medicine today, an international research collaboration led by Professor Tazeen H. Jafar from the Health Services and Systems Research Programme at Duke-NUS Medical School, Singapore, has found that a low-cost, multi-component intervention comprising home visits by community healthcare workers to monitor blood pressure (BP) and provide lifestyle coaching, coupled with physician training and coordination with the public health care infrastructure, led to clinically meaningful reductions in BP as well better BP control in the intervention group.

Uncontrolled hypertension, a major risk factor for cardiovascular and kidney diseases, is a leading cause of death globally. In rural parts of low- and middle-income countries, particularly in Asia, where health systems are suboptimal, one in four adults suffers from hypertension - 70 per cent of which is uncontrolled - leading to some of the highest death rates from both cardiovascular and kidney diseases.

At the end of the study, the decline in mean systolic BP was 5 mmHg greater in the intervention group versus the control group, which received the usual care. Reduction in mean diastolic BP and BP control (

"A sustained 5 mmHg reduction in systolic BP at a community level historically translates into about a 30 per cent reduction in death and disability from cardiovascular disease," said Professor Jafar, who is also a Professor of Global Health at the Duke Global Health Institute (DGHI), USA. "Our study demonstrates that an intervention led by community health workers and delivered using the existing healthcare systems in Bangladesh, Pakistan, and Sri Lanka can lead to clinically meaningful reductions in BP as well as confer additional benefits - all at a low cost."

"Community health workers are an integral part of the primary care infrastructure for the successful door to door delivery of maternal and child healthcare in South Asia - as well as China, Mexico, and Africa," Prof Jafar added. "Our findings show that community health workers can have an equally important role in managing hypertension."

The multi-country Control of Blood Pressure and Risk Attenuation - Bangladesh, Pakistan, Sri Lanka (COBRA-BPS) study is a cluster randomised trial that evaluated the effectiveness of the multi-component intervention among 2,550 individuals with hypertension living in 30 rural communities in the three South Asian countries over two years.

The study is funded by the Joint Global Health Trials scheme, which includes the Medical Research Council, the UK Department for International Development (DFID), the National Institute for Health Research (NIHR) and the Wellcome Trust. The COBRA-BPS study is led by Prof Jafar and her team at Duke-NUS Medical School, with data management and statistical analysis supported by the Singapore Clinical Research Institute (SCRI), in partnership with Dr Aliya Naheed from the International Centre for Diarrhoeal Diseases Research, Bangladesh (ICDDR,B), Dr Imtiaz Jehan from Aga Khan University, Pakistan, and Prof Asita de Silva from the University of Kelaniya, Sri Lanka.

This is the first multi-country trial of its kind and, as such, serves as a model of South-South collaboration. While there are differences in the health systems and some population characteristics in the countries involved, BP control rates are uniformly poor in all of them. Nonetheless, the study found that similar results were achieved in all three countries with the standardised strategies, suggesting that the intervention has validity in different settings.

National advisory committees (NACs) have been established in the three countries, with representatives from professional societies, public health groups, public agencies, relevant pharmaceutical companies and non-governmental organisations. Discussions with provincial health departments and NACs are ongoing to facilitate the scale-up of the intervention in the three countries.

Dr Aliya Naheed, the study's country principal investigator in Bangladesh and a co-author, said, "Uncontrolled hypertension is a major cause of cardiovascular disease, especially stroke, in Bangladesh. The COBRA-BPS strategies of community-health-worker-driven home-based monitoring of BP using a digital BP monitor, promotion of a healthy lifestyle, and referral have created a high demand for much-needed quality hypertension care services in rural Bangladesh."

Dr Imtiaz Jehan, the study's country principal investigator in Pakistan and a co-author, said, "Uncontrolled hypertension and lack of awareness of the disease are alarmingly high in Pakistan. Controlling BP through lifestyle modification and antihypertensive therapy can be the single most important way to prevent the rising rates of cardiovascular disease and deaths in Pakistan. This trial provides timely evidence for sustainable, low-cost and pragmatic solutions for effective BP control that can be integrated into our public primary healthcare system of community health workers and referrals to basic health units through standardised training and task shifting."

Prof H. Asita de Silva, the study's country principal investigator in Sri Lanka and a co-author, said, "Despite having access to effective medicines free of charge through State healthcare institutions in Sri Lanka, only about 25 per cent of those treated achieve BP control. Traditional approaches to health service delivery, reliant on people presenting to clinics, are clearly not good enough. Instead, innovative models of cardiovascular care must incorporate primary healthcare strategies that enhance reach to underserved populations. COBRA-BPS has demonstrated that a community-level intervention delivered by our dedicated community health workers can significantly improve BP control."

A formal cost-effectiveness analysis is currently underway by Prof Eric Finkelstein, a health economist at Duke-NUS and DGHI. Early estimates by the study group suggest that scaling up the COBRA-BPS intervention nationally in the three countries would cost less than US$11 per patient annually.

"The public health implications of our findings are significant," Prof Jafar added. "A low-cost programme like ours could be adapted and scaled up in many other settings globally, using the existing healthcare infrastructure to reduce the growing burden of uncontrolled hypertension and potentially save millions of lives, as well as reduce suffering from heart attacks, strokes, heart failure and kidney disease."

The preliminary findings of the trial were shared at the American Heart Association Scientific Sessions 2019 held on 16-18 November, 2019, in Philadelphia, USA.

AURORA, Colo. (Feb. 19, 2020) - A novel, four-week parenting rotation designed for pediatric residents has dramatically increased the amount of time resident parents can spend at home with their babies, according to a study by researchers at the University of Colorado Anschutz Medical Campus.

The elective, created in 2010 by physicians at the University of Colorado School of Medicine, was set up to address the lack of maternity leave for doctors in residency programs, a time when many get pregnant.

The new study, published this week in the journal Academic Pediatrics, is the first to examine the results of the program.

"When we first created this elective, our residents had to take vacation days, about four weeks, if they wanted time off with their newborns," said the study's first author Dr. Melanie Cree-Green, MD, PhD, a pediatric endocrinologist and assistant professor at the CU School of Medicine. "Some took unpaid Family and Medical Leave combined with vacation time. For some, this meant not being able to pay back student loans. Others faced career setbacks."

Working with her father, Jonathan Cree, MD, MA, a family medicine residency program director, and fellow physicians at CU Anschutz, including Adam Rosenberg, MD, CU pediatric residency program director, Cree-Green created an at-home, non-core elective that turned the experience of parenting into a structured training experience for residents.

"When Melanie approached me about this, it seemed the right thing to do," said Rosenberg. "It was a win-win situation. Now our goal is to expand our efforts to insure all of our trainees 12 weeks of paid leave."

Cree-Green, who also works at the Center for Women's Health Research at CU Anschutz, said her aim was to increase paid time at home for new parents, "while capitalizing on the experience of parenting as a unique educational opportunity for residents."

The elective, approved by the pediatric residency curriculum committee, included the following: 1) reading five articles on neonatal subjects including rashes, circumcision, maternal depression and lactation. 2) Preparing a presentation for other pediatric residents on some aspect of pediatrics they learned as a parent. 3) Reviewing a popular parenting book. 4) Attending a well-child check, a breastfeeding consultation visit. 5) Writing an essay from the perspective of a parent on how such visits might change their approach as a physician.

All residents (mothers and partners) who had a new child, either biologic or adopted, could take the elective.

"We found that implementation of a parenting elective providing up to four weeks of paid time at home, significantly improved income and academic outcomes in pediatric residents, while markedly increasing resident time devoted to parenting," the study reported. "In mothers, the minimum time away from the hospital tripled and nearly all resident mothers had more than seven weeks at home."

Before the elective, none of the fathers or partners took more than a week at home and some took no leave at all. Afterward, 100% took leave with a mean time of four weeks. The extra time at home benefited the doctors in many ways including allowing for the establishment and maintenance of breastfeeding, important to fetal health. Shorter leave is associated with failing to establish and early cessation of breastfeeding.

Cree-Green said the program has been a clear success at a time when more and more women are entering medicine and the needs of their families are becoming more apparent. For years, she said, women physicians have lagged behind in maternal leave, salary equity and other areas.

"Physicians are trained to put the patient first," she said. "Physician wellness has always taken a back seat to that. It has never been a priority, but there is a growing consensus that it must be."

She has been asked by numerous other medical institutions to share the details of the elective. Pediatrics, she said, is just the beginning.

"I would like to see this elective expanded to other specialties like Ob/Gyn, psychiatry and family medicine," Cree-Green said. "In fact, I believe it should be explored in all types of residency to improve personal, financial and professional outcomes in medical trainees."

Researchers from The George Institute for Global Health at the University of Oxford have found that while having high cholesterol levels does not influence your risk of aortic or mitral valve regurgitation, it does increase your risk of developing another major heart valve disease - aortic stenosis.

Aortic stenosis is the most common form of heart valve disease in developed countries and is thought to affect 2-7% of those over the age of 65 [1]. The disease is characterised by restricted blood flow through the valve, with affected individuals commonly experiencing symptoms such as chest pain, shortness of breath, heart palpitations and, in more severe cases, collapse and loss of consciousness.

The study team used a state-of-the-art method called Mendelian randomization to determine this causal effect. At fertilisation (the union of a human egg and sperm cell), we are all randomly allocated genes that are known to be associated with health-related characteristics in later life; in this case either normal or high cholesterol levels. Researchers were therefore able to categorise the study population by genetically-determined cholesterol level and then directly compare outcomes in terms of onset of aortic stenosis.

"Until recently, aortic stenosis has been widely considered a degenerative disorder associated with ageing with no recommended medical guidance for its prevention. Management has, therefore, focused largely on valve replacement surgery or catheter intervention," said Milad Nazarzadeh who led the research using data from the UK Biobank.

These management options are associated with significant complications and procedural costs estimated at £10,000 for valve replacement surgery and £16,000 for catheter intervention in the UK [2].

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: "Aortic stenosis is the narrowing of the aortic valve, the 'door' between the main pumping chamber of the heart - the left ventricle - and the body's main blood vessel - the aorta. This study shows that having high levels of 'bad' LDL cholesterol in the blood stream for a prolonged amount of time could increase your risk of developing the condition, putting extra strain on your heart to pump blood around the whole body.

"It's important that we know whether our cholesterol levels are in a healthy range or not. The good news is that getting access to these numbers is easy. Everyone between the ages of 40-74 is eligible for a free NHS health check, which assesses your risk of developing heart and circulatory diseases and includes a cholesterol measurement - a service we should all be taking advantage of."

Crucially, the evidence that high cholesterol is a risk factor for aortic stenosis presents clinicians with an opportunity to modify disease risk via preventative measures, for instance through the use of cholesterol-lowering medications such as statin therapy.

The model will permit to accelerate and reduce the price of the research, which is studying the mechanisms and the possible pharmacological targets for the neuronal alterations of this disease.

The earliest results of studies with this organism point to glial cells as a man responsible for the neurological damage caused by the disease.

Chromosome X-linked adrenoleukodystrophy (X ALD) is a rare genetic disease in which long-chain fatty acids accumulate in the blood and the nervous tissue, and where the myelin in the neurons is damaged. People who suffer from it (1 in 14,700 newborns) may have, among other things, brain and mobility problems, as well as hormonal disorders. The cause is a deficiency in the ABCD1 gene, which encodes the adrenoleukodystrophy protein (ALDP), which transports long-chain fatty acids to peroxisomes. These organelles play a very important role in lipid degradation and their subsequent cell use.

This work has identified and characterized the worm Caenorhabditis elegans (C. elegans) as a model of the disease, this model is deficient for the human analog protein (homologous) ALDP. The research team, co-led by Dr. Aurora Pujol and Esther Dalfó, analyzed the consequences of this deficit on a cellular level and found that, as in human and in existing mouse models, exists an accumulation of long-chain fatty acids, changes in lipid metabolism, oxidative imbalances in the mitochondria and neuronal disorders. The model will allow accelerating the study of this disease, for which there is currently no treatment.

The work, published in Free Radical Biology and Medicine, has involved ICREA researchers from the Bellvitge Biomedical Research Institute (IDIBELL), the Network Biomedical Research Center (CIBERER), the Neurosciences Institute of the Autonomous University of Barcelona (INc-UAB), the Faculty of Medicine of the University of Vic - Central University of Catalonia (UVic-UCC), the Kennedy Krieger Institute from Baltimore, the MRC Mitochondrial Biology Unit from Cambridge, and the Institute of Biomedicine from Seville (IBIS).

A valuable genetic tool

"This model of adrenoleukodystrophy in C. elegans is a very valuable genetic tool that will allow us to study the mechanisms involved in the disease and to find pharmacological targets faster than with other animal models, such as mice, which are much more complex and involve a costly and economically expensive process," says Esther Dalfó, who now is leading the C elegans models of diseases group between INC-UAB and the UVic-UCC.

The research team has obtained its first results, which, despite being preliminary, suggest that glial cells, which are in the brain together with neurons, would be the first responsible for the neurological alterations associated with the disease.

"This new animal model has helped us to confirm that oxidative stress caused by mitochondria (the energy-producing organelles of cells) is the major cause of neuronal damage in adrenoleukodystrophy, and this mechanism of damage is conserved from the worm to the patient. The data point to new therapeutic pathways, such as mitochondrial antioxidants in peroxisome disease", says Aurora Pujol ICREA professor at IDIBELL.

C. elegans, neurons and genes like humans

The earthworm C. elegans is widely used in biomedical research because, despite being simple and small (measuring only 1 mm), it has most of the most complex animal structures and share most of the metabolic pathways with us. Besides, 40% of its genome is homologous to our genes and has a representation of all the neural populations in the human brain.

The genetic manipulation of this organism to create transgenic models to the study of the disease, such as X ALD, is faster than with other animal models such as rats or mice. Overall, taking into account characteristics like body transparency, numerous reproductions -up to 300 descendants- and the low cost, make the C. elegans an ideal tool for lab use.

In ancient Greek mythology, Icarus' wax wings melted when he dared to fly too close to the sun. Now, researchers reporting in ACS Applied Materials & Interfaces have made artificial wings that are actually powered by the sun. The tiny wings, which can flap even faster than those of butterflies, could someday be used in robots or devices for solar energy harvesting, the researchers say. Watch a video of the flapping wings in action here.

Light-driven actuators -- devices that convert light directly into mechanical work -- have attracted attention because they are wireless and easy to control. However, to keep going, they usually require a high-intensity light source that can be turned on and off, or additional hardware. Ningyi Yuan, Jianning Ding and colleagues wanted to develop a flexible film that could convert natural sunlight into a flapping motion, without the need for additional hardware.

To make their device, which they called a flexible bio-butterfly-wing (FBBW), the researchers coated a thin polymer sheet with a nanocrystalline metallic film. When the team fixed one end of the FBBW strip to a support and shone simulated sunlight onto it, the temperature of the strip increased, and the free end curled up because of the large difference in thermal expansion between the metal and polymer layers. Then, the curved part of the FBBW shaded the metallic layer below, causing the temperature to drop and the strip to unfold. Continuous cycles of bending and unfolding produced a flapping motion that could exceed the frequency of actual butterfly wings. The team demonstrated the FBBW in a light-driven whirligig and sailboat, and in a device that converted sunlight into an electric current. It could someday be used in flying animal robots, among other applications, the researchers say.

McGill-led research shows that boys exhibiting inattention-hyperactivity at age 10 have a higher risk for traumatic brain injuries (TBIs) in adolescence and adulthood. Treatments to reduce these behaviours may decrease the risk for TBIs.

"Traumatic brain injuries are the leading cause of death and disability in children and young adults, but little is known about the factors that provoke them," says Guido Guberman, a doctoral and medical student in the Department of Neurology and Neurosurgery at McGill University. The study published in the Canadian Journal of Psychiatry is the first to show that childhood behaviours identified by teachers such as inattention-hyperactivity predicted subsequent traumatic brain injuries. The study also found that boys who sustained TBIs in childhood were at greater risk of sustaining TBIs in adolescence.

According to the researchers, TBIs occur in approximately 17% of males in the general population, yet there is little research about TBI prevention. To determine whether there is a link between inattention-hyperactivity and TBIs, they analyzed data from 724 Canadian males from age 6 to 34. They examined health files and collected information from parents when participants were aged six, then administered a questionnaire to the participants' teachers on classroom behaviours when the participants were aged 10 years.

"To avoid suffering and disability, prevention strategies are needed, for example promoting cyclist safety," says Guberman. "There are treatments that can decrease the severity of childhood inattention-hyperactivity and behavioural problems. Our results suggest that trials are necessary to determine whether these programs can also decrease the risk for subsequent traumatic brain injuries."

To many people, EPO rhymes with doping and cycling. But in fact, EPO is an important medical drug. This hormone works naturally in the body by stimulating red blood cell production. Patients suffering from anemia caused by for instance chronic kidney disease, AIDS or hematologic disorders can benefit immensely from EPO therapy. Furthermore, many cancer patients who are anemic from receiving chemotherapy are also in great need of EPO therapy. It is estimated that the market for EPO therapy is around 11 billion dollars annually.

Today, medical EPO is produced in mammalian cell lines using so-called recombinant DNA technology, where human genes are inserted to produce recombinant human EPO (rhEPO).

Recombinant human hormones such as EPO can be challenging to produce effectively, though, because they are quickly degraded by, amongst other things, the cells' own protein- and hormone-eating enzymes.

Using CRISPR technology, researchers from The Novo Nordisk Foundation Center for Biosustainability at Technical University of Denmark (DTU) have looked into how to reduce several cellular 'stressors' in order to improve production and product quality. This work has recently been published in the journal Metabolic Engineering.

The researchers found that by knocking out three genes involved in sugar group degradation and two involved in programmed cell death, they could improve production by 1.4-fold in Chinese Hamster Ovary (CHO) cells. Furthermore, the quality was greatly improved. The knockout cells contained around 40% of the most active EPO form, while the non-knockouts only contained around 2% of the most active EPO form (the highly sialylated EPO). The highly sialylated EPO form is important as it has the longest half-life. Only active EPO can treat conditions of anemia, so improving this feature is imperative in order to keep prices low and quality high.

How to avoid EPO degradation

The optimised cell line was actually designed to work in so-called fed-batch cultures, which is a way of feeding the cells continuously over the course of 10-14 days. Fed-batch is a commonly used method to make human hormones for various conditions and antibodies for cancer treatment.

But it is hard to produce EPO in fed-batch, because it is destroyed over time. Thus, EPO is nowadays produced in a 'one-feeding' manner (batch cultures), even though this method is less efficient. In order to do fed-batch cultures despite these obstacles, others have tried adding supplements to the mixture to avoid degradation. But with this new cell line, there is no need for workarounds, explains first author Tae Kwang Ha, Postdoc at The Novo Nordisk Foundation Center for Biosustainability:

"With our cell line, you don't have to add anything - it just works."

These results have only been shown at small scale, so scale-up is needed to see if cells perform equally well in big production tanks. But this research verifies that knockout of specific genes can definitely improve productivity and product quality in single cells.

Researchers from The Johns Hopkins Center for Fetal Therapy report new evidence that fetuses with severe congenital diaphragmatic hernia (CDH), a rare but life-threatening, lung-damaging condition, experience a significantly high rate of success for the fetal treatment known as FETO, if they and their mothers receive coordinated and highly experienced care in the same expert setting.

A report on the findings was published online, on Feb. 6, in the journal Obstetrics & Gynecology.

FETO -- fetoscopic tracheal balloon occlusion -- is a minimally invasive procedure in which a fetoscope is inserted through the abdominal wall into the uterus and then into the mouth of the fetus to place an inflatable balloon, to temporarily block the fetal trachea. The blockage allows lung fluids to build up behind the balloon, encouraging expansion of the airways and lung growth. The procedure improves the odds that fetuses with severe CDH acquire sufficient lung function after birth to lead a normal life.

"The primary cause of death in babies with CDH is that the lungs do not develop properly, and they cannot breathe outside the womb," says Ahmet Baschat, M.D., director of The Johns Hopkins Center for Fetal Therapy and professor of gynecology and obstetrics at the Johns Hopkins University School of Medicine.

Usually detected through a routine prenatal ultrasound, CDH is a rare condition that impairs lung development, affecting one in 3,000 live births. It is characterized by the partial or complete absence of the diaphragm -- the muscle that separates the chest from the abdomen -- resulting in a hole. The gap may permit organs that are usually in the abdomen, such as the bowel, the stomach and the liver, to push into the chest. This causes a hernia or bulge, a displacement that leaves too little space for fetal lungs to develop normally. The degree of lung damage is greatest for large hernias, where the liver herniates into the chest. After birth, surgical closure of the hole is possible, but the lung damage that has occurred before birth can make this condition fatal.

To assess the feasibility and impact on the health of mothers and babies after FETO therapy, Johns Hopkins researchers enrolled 14 women, all patients at The Johns Hopkins Center for Fetal Therapy, between May 2015 and June 2019. The women were an average of 28 weeks pregnant and an average of 33 years old.

For the study, Baschat and his team performed successful FETO balloon blockages on all 14 fetuses between 26 and 29 weeks of gestation. No procedure-related fetal or maternal complications occurred. The team removed the balloons at about 33 weeks of gestation, after a median 34 days of blockage.

The researchers say that FETO therapy produced favorable outcomes in the 14 infants born to the mothers in the study when performed in a single center setting, where prenatal and postnatal monitoring and care were highly coordinated.

"This is most likely due to prenatal management by a team with experience in fetal interventions, as well as maternal-fetal care in one single institution," says Baschat. "From the time of balloon insertion, we had a multidisciplinary team of fetal therapists, neonatologists, pediatric surgeons, pediatric ENTs and obstetric and pediatric anesthesiologists available for any emergency balloon removals and to make sure the fetuses' airways weren't obstructed in case of unplanned birth."

"FETO has been studied in the past, in the United States and abroad, in a randomized trial, a large feasibility study and several smaller studies, and while the overall approach was comparable to our study, we employed a deliberate strategy to minimize potential contributors to preterm birth associated with premature rupture of membranes," adds Baschat. Some of these strategies included treating the mothers with vaginal progesterone, avoiding the lower part of the uterus when inserting the fetoscope and aggressive treatment of preterm contractions.

A striking difference in the Johns Hopkins study, Baschat notes, is that delivery of the babies was at an average of 37 weeks of gestation, with no deliveries prior to 32 weeks; 7% of deliveries before 34 weeks and 43% prior to 37 weeks of gestation. This allowed all the infants to be candidates for extracorporeal membrane oxygenation (ECMO) -- an advanced life-support technique -- which may have been an important contributor to the survival of the infants.

Overall, babies were born about 30 days after balloon removal. All cases experienced a sustained increase in lung size, from 23.2% before blockage to 46.6% prior to birth. All 14 women delivered at The Johns Hopkins Hospital at a median gestational age of 39 weeks (range 33-39). Eight (57%) delivered at term (?37 weeks of gestation), after scheduled, induced labor. The majority of mothers (71%) delivered their baby vaginally.

"We've been able to achieve a really good safety protocol -- not only did the procedure result in lung expansion, but balloon removals were all scheduled; they were not emergency procedures," says Baschat.

Infant survival on day 28 was 93%, and the overall survival to 6 months or hospital discharge was 86%.

All of the babies had absence of the diaphragm on the side of the hernia and required surgical repair of the CDH using a patch, which was performed within the first week of life. The primary complication after surgery in three of the 14 babies (36%) was recurrence of diaphragmatic herniation, due to areas of the patch detaching from the chest wall as the infants grew in size.

"The study had the highest survival rate ever reported for these types of patients, with the lowest complication rate of FETO in terms of procedure risks, obstetric risks and fetal risks," says Baschat.

A randomized trial involving U.S. and European fetal therapy centers is underway; however, the researchers say they want to wait to see those results to decide on next steps. "Standardized prenatal and postnatal care appear to be complementary in achieving survival in these infants," says Baschat. "Anticipating possible obstetric complications and reactively providing prompt treatment may improve the chance for mothers to deliver at term." Meanwhile, the researchers are collaborating with other fetal therapy specialists to investigate how care-setting factors and management strategies can be optimized to apply them across other fetal therapy centers.