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Prenatal exposure to air pollution has been linked to various adverse effects on children's health, including lower birth weight and respiratory and neurodevelopmental problems. However, very little is known about how air pollution affects physical growth in the first years of life. A new study by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, has found an association between exposure to air pollution during pregnancy and delays in physical growth in the early years after birth.

The Spanish study, published in Environment International, analysed data from more than 1,700 mother-child pairs from Asturias, Gipuzkoa, Sabadell and Valencia enrolled in the birth cohort of the INMA Environment and Childhood Project.

The researchers estimated the exposure to nitrogen dioxide (NO2) and fine particulate matter (PM2.5)--two of the most common traffic-related air pollutants in cities--during the first trimester of pregnancy, using models based on levels of these pollutants measured in the study area. The evolution of the children's body mass index (BMI) from birth to age four years was recorded. Height and weight were measured at four years of age.

The results showed that greater exposure to particulate matter during the first trimester of pregnancy was associated with a higher risk of lower weight and body mass index at four years of age. Results for NO2 exposure were similar but did not reach statistical significance.

"This prospective study suggests that exposure to air pollution during pregnancy may be associated with delays in physical growth in the first years of life," commented ISGlobal researcher Serena Fossati, lead author of the study. "The implication of our findings is that prenatal exposure to air pollutants has a lasting effect on growth after birth and that this parameter should be followed up at later ages."

The biological mechanisms underpinning the adverse effects of air pollution on childhood growth "remain unclear", according to ISGlobal researcher Martine Vrijheid, the study coordinator. "The hypotheses we are considering include oxidative stress and inflammation, interference with thyroid hormones, induction of cell death due to DNA damage, and an increased risk of respiratory diseases and other health problems that could delay growth."

"What is clear is that the adverse effects of air pollution begin in the prenatal phase, so pregnant women should be considered a priority group in public health policies aimed at reducing the population's exposure to air pollution," concluded Vrijheid.

CLEVELAND, Ohio (April 22, 2020)--The increased prevalence of metabolic syndrome and osteoporosis in postmenopausal women has prompted multiple research studies to understand why. A new study from South Korea examined the association of socioeconomic status-related factors, unhealthy lifestyles, and diet-related factors with the coexistence of metabolic syndrome and osteoporosis. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Metabolic syndrome and osteoporosis not only adversely affect a woman's quality of life, but they also create significant financial burden. Previous studies have suggested that these health problems are affected by lifestyle, genetic, metabolic, nutrition, and hormone factors. In particular, smoking has been shown to impair calcium absorption. In addition, an inverse relationship has been identified between metabolic syndrome and the intake of carbohydrates, vitamins (A, C, and D), calcium, fruits, and dairy products. Similarly, osteoporosis has an inverse association with higher intakes of vitamin D, fish, and dairy products.

Although these relationships have been the focus of other studies, this study involving nearly 2,000 postmenopausal women between the ages of 45 and 65 is the first known to consider a woman's menopause status. Researchers found that 32.5% of study participants experienced both metabolic syndrome and osteoporosis. Health-related behavior (including physical activity, alcohol consumption, and smoking) and diet-related-factors (such as intake of nutrients, eating habits, and food insecurity) were evaluated to determine their effect on the prevalence of both metabolic syndrome and osteoporosis.

Researchers concluded that the coexistence of metabolic syndrome and osteoporosis was positively associated with insufficient dairy intake, lack of physical activity, and higher alcohol consumption. However, the effect was significantly dependent on socioeconomic factors such as education, household income, place of residence, and employment status. Women with low income and low education were more likely to have metabolic syndrome and osteoporosis. Conversely, women with high income and high education were 70% less likely to have these two health problems compared with a middle-income group. Additional research is suggested to identify controllable factors that could enhance the health of postmenopausal women.

Study results appear in the article, "Coexistence of metabolic syndrome and osteopenia associated with social inequalities and unhealthy lifestyle among postmenopausal women in South Korea: the 2008 to 2011 Korea National Health and Nutritional Examination Survey (KNHANES)."

"This study shows a link between socioeconomic-related factors, including poor diet, insufficient physical activity, and higher alcohol intake, and the presence of two conditions associated with significant quality-of-life and financial burdens in midlife women--metabolic syndrome and osteoporosis. Social inequalities may contribute to health inequities and, as the authors aptly point out, a larger social and political approach may be needed to adequately address these issues," says Dr. Stephanie Faubion, NAMS medical director.

Women who don't survive a rare and aggressive uterine cancer called uterine serous carcinoma, have high expression of a group of 73 genes, a score scientists say can help identify these women and improve their outcome.

"It is a very aggressive cancer," says Lynn Tran, MD/PhD student at the Medical College of Georgia at Augusta University and first author of the study in the journal Gynecologic Oncology.

More than half of women with uterine serous carcinoma, or USC, have more advanced stage 3 or 4 disease at diagnosis and about half the patients who have it die and die very quickly, Tran says. "The question was, can you tell who those half are?"

They found that women with high USC73 scores had the worst prognosis, highest cancer cell proliferation and progression rates, and lowest rates of complete response to standard therapy.

Their findings suggest USC73 score is a biomarker for both the identification of women who will not respond to standard therapy and for efficient clinical trials to find drugs that do work, says Dr. Jin-Xiong She, director of the MCG Center for Biotechnology and Genomic Medicine, Georgia Research Alliance Eminent Scholar in Genomic Medicine and the study's corresponding author.

Many of these 73 genes have functions important to cancer, like cell survival and migration. When they looked in detail at the cancer cell lines of patients with high expression of what they now call USC73, they found increased cell cycle progression and growth consistent with poor patient survival.

They don't know yet whether high USC73 is causative of the more aggressive version of this uterine cancer or just associated with it, but are continuing to pursue those answers.

"The difference in survival may be caused by something that we are not measuring, it just may be correlated to the things we are measuring," Tran says.

The genes they identified have not been consistently reported or described in another cancer but may well be a factor in others, they say, of their signature group.

As next steps, both a retrospective multicenter study, like the work they already have done, and a prospective clinical trial will be conducted to validate the clinical utility of the USC73 gene signature.

"If you can identify the patients who won't do well and have a very bad prognosis, you can test new drugs on this subset of patients," She says. "You are going to be able to figure out whether the drug(s) work or not with a much smaller sample size," a critical factor with such a rare cancer, he notes.

Tran and She say their basic science laboratory assessments can easily be translated to clinical settings with studies done right after surgery and before other therapies, like chemotherapy, begin.

Uterine cancer is generally more common in younger, Caucasian women who have not had children and have obesity. But the rare USC is notorious for affecting non-Caucasian, postmenopausal women who have had children, they say.

To better tailor treatment for these women, accurate predictors of patient survival and response to standard therapy are needed, they write.

So they looked at one of the larger groups of women ever examined with this rare cancer. Their extensive analysis looked at data from 58 patients in the publicly available National Cancer Institute and National Human Genome Research Institute's Cancer Genome Atlas Program, or TCGA, which includes matched normal samples. They also looked at data on 67 patients at the Georgia Cancer Center.

Genes are comprised of DNA which gets transcribed into RNA, a sort of middle man, which gets translated into proteins, which are a functional unit in the body that makes things happen. To analyze gene expression in these women's tumors they decided to focus on the middleman RNA, which they can measure more precisely than the end product protein, and consider a more reliable source.

The TCGA data was used to identify the RNA and genes, and their findings held in the Georgia Cancer Center patients.

A high USC73 score was found in 37.9% and 32.8% of the women in the TCGA and Georgia Cancer Center groups, respectively. A few of the genes were at very high levels in the tumors of some patients; in others all the genes were relatively high.

Tumor cells from patients with a high USC73 score proliferated more rapidly both in a laboratory dish and in patients. In fact, the cancer cells of patients with high levels of USC73 grew about twice as fast in the lab, She says.

When they looked at response to treatment, about 90% of patients with low levels of USC73 had a complete response. It was more like 50-50 in those with high levels. They suspect there are subtypes within the known subtype of USC that require a different treatment strategy.

There are ironies in that the pro-proliferative work of these 73 genes should really get the attention of chemotherapy, which is attracted to rapidly dividing cells, but the fact that the carboplatin/paclitaxel regimen doesn't work in so many women means it may be the wrong chemotherapy, She says. He notes the regimen was adopted from ovarian cancer with little evidence it would be very effective on uterine cancer.

While they don't know which drugs yet, they think there might be better choices for the nonresponders and already are trying out the effect of other drugs on USC cells in a dish.

They also are looking upstream for master regulator transcription factors that control gene expression to see if at least some can safely be turned off or down, She says.

They note that this group of 73 genes are likely functioning at a low level in a healthy individuals in support of cells with a naturally high turnover rate like skin and hair cells and those that line the gastrointestinal tract.

"Your gut is regenerating, your hair is growing, you want these to be active," She says. In fact, they have already overexpressed a molecule upstream and cells in a laboratory dish died in response.

The uterus, which sheds its lining monthly during menstruation, is a definite high-cell turnover area so while these genes are active there normally, the scientists selected the 73 suspects on differences between activity in normal and cancerous tissue. "There is a baseline level but we are saying this is much higher," says Tran.

Endometrial cancer it the most common gynecologic malignancy and over half the deaths are caused by the uncommon subtype USC.

Standard therapy for these women includes surgery, followed by the chemotherapy drugs carboplatin and paclitaxel, and potentially internal or external radiation.

Mutations in a handful of genes have been found in this cancer but trials that target those mutations have not improved survival, the scientists say. Other molecular markers have been identified but not pursued clinically.

The national TCGA has extensive patient data including different molecules in a patient's tumor, their treatment, how their disease presented in clinic, metastasis and where the cancer spread, and how long they survived, Tran says.

The current NHS regulations for charging those not ordinarily resident in the UK for treatment, such as migrants and short term visitors, are 'unworkable' and harmful to the wider health system, concludes an analysis of survey responses, published in BMJ Paediatrics Open.

The rules are poorly understood and applied by healthcare staff, the responses show, which include several examples of the harmful impact of denying or delaying care to those that need it.

UK Legislation in the past few years has narrowed the eligibility criteria for free healthcare and changed the tariffs applicable, particularly in England.

The UK is out of step with several other comparable European countries in applying more restrictive access to healthcare for undocumented migrant children.

To try and find out what impact these changes might be having on health, and to gauge clinicians' understanding of, and attitudes towards, the regulations, the authors surveyed children's health practitioners working in the UK in January and February 2019.

Some 220 healthcare professionals from all four UK countries responded, with doctors making up the bulk of respondents (44.5%).

The analysis was based on 200 responses, more than two thirds of which (69.5%) came from practitioners working in Greater London, an area with more migrants than other UK regions.

Most respondents didn't feel confident interpreting and applying the charging regulations.

Over half (53%) of respondents said they weren't confident about what constituted urgent or immediately necessary care, which exempts people from upfront charging.

Several groups are exempt from the charging regulations: asylum seekers; refugees; human trafficking victims; and looked after children. Charges don't apply to emergency or primary care.

Most respondents didn't feel confident about which circumstances, conditions, or groups were exempt from charging.

The survey also uncovered cases of children and families being deterred from accessing care despite being exempt and other cases where charging was inappropriately applied .

Six out of 10 (60%) felt that charging migrants for NHS care was unfair, while a similar proportion (58%) felt that healthcare professionals shouldn't be involved in charging.

More than 80% of respondents weren't sure that they would be covered by their indemnity insurers or their professional regulator, should a patient come to harm as a result of their interpretation of the rules.

Three out of four (76%) felt the regulations needed to be independently reviewed, and a similar proportion felt they needed further training on the regulations (72%).

A third of respondents said they knew of examples of how the charging regulations had adversely affected health and care. These included:

19 cases of patients and their families afraid to access care for fear of being saddled with unaffordable bills, criminalisation, or deportation

18 cases of migrants avoiding care, including screening

11 cases of care being delayed or denied to pregnant women and children and victims of trafficking

12 cases of potentially avoidable health complications

Numerous cases of eligible patients being incorrectly billed or threatened with charging

Many respondents felt the charging regulations were placing an undue burden on the health system, and especially those staff working within it.

The regulations not only run counter to the professional duties stated by their regulator, but also their own personal values and those of the NHS, respondents said. And they felt that the rules widened existing health inequalities.

"Our results do not support the argument that harm could be eliminated simply through improved staff awareness or 'better' implementation of regulations," say the authors.

"Our survey results also highlight a breach of the UK's commitment to the [United Nations Convention on the Rights of the Child], as we have recorded clear examples of violations to Article 24 on children's right to good health and healthcare access," they point out.

And they conclude: "We believe there is sufficient evidence of harm to health and wellbeing for the current NHS charging regulations to be revoked, thereby restoring the UK's commitment to universal health coverage."

A paper published in the Journal of Biomedical Optics (JBO), "Imaging hydroxyapatite in sub-retinal pigment epithelial deposits by fluorescence lifetime imaging microscopy with tetracycline staining," demonstrates a potential new diagnostic option for catching a degenerative eye disease in its earliest stages.

Tiny deposits of lipids, proteins, and minerals, sometimes known as drusen, can collect under the retina. They may indicate a person's risk of developing age-related macular degeneration (AMD), so enhanced and early detection is a current clinical need. The initial findings presented in the paper show a new way to achieve molecular contrast based upon sub-retinal mineral deposits. The approach uses a well-known property of the tetracycline-family of antibiotics - their propensity to stain teeth and bones - making visible the smallest of mineral deposits. Utilizing human cadaver retinas containing drusen, the researchers used fluorescence lifetime imaging microscopy (FLIM) to measure the light emission from tetracycline staining within those ocular mineral deposits.

According to JBO Editor-in-Chief, SPIE Fellow, and MacLean Professor of Engineering at Dartmouth Brian W. Pogue, the novel use of FLIM to harness the properties of a common antibiotic marks an exciting approach to molecular imaging in the eye, and opens up the potential for developing a diagnostic test for early transition to eye disease: "Eye diseases are typically diagnosed by shape, blood flow, or morphology changes in the retina, but this fluorescence test could be more sensitive because the signal is highly specific. It can be used to detect very small molecular mineral deposits that cannot be seen well otherwise and detect them early in the disease process. Since this is a first study, a lot more work needs to be done to make this a real human diagnostic test, but the concept that a common antibiotic could be used in this way, to reveal small mineral deposits, is a very important fundamental discovery."

Wheat feeds the world. According to the FAO, wheat is one of the world's main crops, both in terms of extent and production, as well as being one of the main sources of carbohydrates and vegetable protein in the human diet. The quest for genetic improvement in wheat, leading to varieties that are more resistant to issues brought about by climate change or certain pests, responds to the need to keep feeding people.

Genetic improvement programs can span decades and entail studying genetic mechanisms of wheat in order to better understand them and hence accomplish more effective research in this field. In this context, a research team made up of Professor Miguel Aguilar, from the Department of Botany, Ecology and Plant Physiology at the University of Cordoba, along with José Garrido and Pilar Prieto, both researchers at the Institute for Sustainable Agriculture (abbreviated to IAS - CSIC in Spanish), was able to further our knowledge of these procedures. They published the set of reliable reference genes in wheat meiosis.

Meiosis is the division process that generates gametes or reproductive cells. During meiosis, chromosome association and genetic recombination occur. These are vital processes for a plant's fertility. Reference genes or normalizing genes are genes whose expression does not change during the biological processes under study. So, these kinds of genes work as a constant in order to be sure that any change of expression observed in other genes can be significantly correlated with the studied process.

The absence of validated reference genes that can be used to study wheat meiosis is what led this team to seek the set of genes that can provide precise measurements of the expression of other genes during the process of meiosis in durum wheat, used to make pasta, and common wheat, used to make bread. This discovery will be useful for future scientific research focused on the genetic improvement of wheat.

Using the recently sequenced and assembled complete wheat genome as a basis, the research team used the quantitative PCR technique (used to amplify DNA sequences) to test and analyze the stability of certain genes and likewise determine how many are needed for the results to be reliable. The reference genes obtained were duplicated or were part of a gene family, so the real challenge for the team was to identify the specific members that can be used as reference genes in gene expression during meiosis. Lastly, two new genes were identified: cyclic phosphodiesterase-like gene and salt tolerant protein gene.

This set of genes helps us to understant how meiosis works and how we can manipulate it, which could revolutionize agriculture, since it would allow for manipulating chromosome associations and using genes from other species in wheat. All this to continue the job of feeding the world.

Scientists at Queen Mary University of London and the University of Roehampton, London, have discovered that patients suffering from obsessive compulsive disorder (OCD) have increased levels of a protein called Immuno-moodulin (Imood) in their lymphocytes, a type of immune cell.

Mice with high levels of this protein were also found to exhibit behaviours that are characteristic of anxiety and stress, such as digging and excessive grooming.

When the researchers treated the mice with an antibody that neutralised Imood, the animals' anxiety levels reduced.

The findings have led the researchers to file a patent application for the antibody and they are now working with a drug company to develop a potential treatment for human patients.

"There is mounting evidence that the immune system plays an important role in mental disorders," said Professor Fulvio D'Acquisto, a professor of immunology at the University of Roehampton and honorary professor of Immunopharmacology at Queen Mary University of London, who led the research. "And in fact people with auto-immune diseases are known to have higher than average rates of mental health disorders such as anxiety, depression and OCD. Our findings overturn a lot of the conventional thinking about mental health disorders being solely caused by the central nervous system."

Professor D'Acquisto, whose findings are published in the journal Brain Behavior and Immunity, first identified Imood by chance while studying a different protein called Annexin-A1 and the role it plays in autoimmune diseases such as multiple sclerosis and lupus.

He had created transgenic mice to over-express this protein in their T-cells, one of the main cells responsible for the development of autoimmune diseases, but found the mice showed more anxiety than normal. When he and his team analysed the genes expressed in the animals' T-cells, they discovered one gene in particular was especially active. The protein produced from this gene was what they eventually named Immuno-moodulin, or Imood.

When the anxious mice were given an antibody that blocked Imood, their behaviour returned to normal in a couple of days.

The researchers tested the immune cells from 23 patients with OCD and 20 healthy volunteers. They found Imood expression was around six times higher in the OCD patients.

Other recent research by scientists elsewhere have also found the same protein may also play a role in Attention-Deficit/Hyperactivity Disorder.

Professor D'Acquisto believes Imood does not directly regulate brain functions in a classical way, for example by changing the levels of chemical signals in neurons. Instead, it may influence genes in brain cells that have been linked to mental disorders like OCD.

"This is work we still have to do to understand the role of Imood," he said. "We also want to do more work with larger samples of patients to see if we can replicate what we saw in the small number we looked at in our study."

In the meantime, Professor D'Acquisto and Dr Dianne Cooper, a Senior Lecturer at Queen Mary University of London, are working with the biopharmaceutical company UCB to develop antibodies against Imood that can be used in humans and to understand how this could be used to treat patients with mental disorders.

"It is early still, but the discovery of antibodies - instead of the classical chemical drugs - for the treatment of mental disorders could radically change the life of these patients as we foresee a reduced chance of side effects," he said. Professor D'Acquisto estimates it could take up to five years before a treatment can be taken to clinical trials.

In order to plan a dental implant operation and the implant size and position, dentists need to know the exact location of the mandibular canal, a canal located in both sides of the lower jaw that contains the alveolar nerve.

The lower jaw is an anatomically complex structure and medical experts use X-ray and computer tomography (CT) models to detect and diagnose such structures. Typically, dentists and radiologists define the location of the mandibular canals manually from the X-ray or CT scans, which makes the task laborious and time-consuming. That is why an automatized way to do this could make their work and placement of dental implants much easier.

To bring a solution to this problem, researchers at the Finnish Center for Artificial Intelligence FCAI, Tampere University Hospital, Planmeca and the Alan Turing Institute developed a new model that accurately and automatically shows the exact location of mandibular canals. The model is based on training and using deep neural networks. The researchers trained the model by using a dataset consisting of 3D cone beam CT (CBCT) scans.

The model is based on a fully convolutional architecture, which makes it as fast and data-efficient as possible. Based on the research results, this type of a deep learning model can localise the mandibular canals highly accurately. It surpasses the statistical shape models, which have thus far been the best, automatized method to localise the mandibular canals.

In simple cases - when the patient does not have any special conditions, such as osteoporosis - the model is as accurate as a human specialist. Most patients that visit a dentist fall into this category. 'In more complex cases, one may need to adjust the estimate, so we are not yet talking about a fully stand-alone system,' says Joel Jaskari, Doctoral Candidate and the first author of the research paper.

Using Artificial Intelligence has another clear advantage, namely the fact that the machine performs the job equally fast and accurately every time. 'The aim of this research work is not, however, to replace radiologists but to make their job faster and more efficient so that they will have time to focus on the most complex cases,' adds Professor Kimmo Kaski.

Planmeca, a Finnish company developing, manufacturing and marketing dental equipment, 2D and 3D imaging equipment and software, collaborates with FCAI. The company is currently integrating the presented model into its dedicated software, to be used with Planmeca 3D tomography equipment.

The research results were recently published in the prestigious publication series Scientific Reports. Link to the research article: https://www.nature.com/articles/s41598-020-62321-3

With stressed hospital services, and concerns about the spread of COVID-19, experts are reminding carers of children and young people of the importance of adhering to supported chronic condition self-management plans from the safety of their home.

Telehealth options, use of home-monitoring devices, keeping regular medical appointments and positive reinforcement from carers and health professionals are new ways to keep supported self-management plans on track, says Flinders PhD researcher Nicole Saxby, lead author on a study of key tools for program maintenance.

This is particularly vital for chronic conditions of childhood such as asthma, cystic fibrosis, congenital heart disease, diabetes, mental illness, as well as those with experience of childhood cancer or disability.

Ms Saxby, is lead author on a new publication in Patient Education and Counseling (Elsevier) with colleagues from, Royal Hobart Hospital, Flinders University and the University of Tasmania.

"From what we are seeing in Australia and overseas, significantly fewer children are presenting to hospitals or making contact with health professionals due to concerns about COVID-19," Ms Saxby says.

"There is a great need to empower children and their families to actively manage their own health, particularly if they're not keeping up their appointments.

"During periods of isolation, it is very important to watch for any early signs of a child's health starting to deteriorate. Children and young people cannot self-manage their health themselves, They will need different levels of support from their caregivers and health professionals."

The research has resulted in a new clinical resource called 'Partners in Health: Self-Management Consensus List for Children and Young People' which aims to provides easy-to-follow guidelines for safe and effective self-management practices - including methodology, care components and considerations for specific developmental groups

"Collaborative care with GPs and other health professions can be challenged by the needs of acute care during the pandemic," says Flinders University Dr Saxby from her current position as dietitian and Statewide Paediatric Cystic Fibrosis Coordinator at the Royal Hobart Hospital in Tasmania. "We certainly don't want people with chronic conditions to become victims of the current situation."

Ways paediatric health services can use technology to communicate and educate children and their families include assessments via screen and digital connection to the home medical monitoring devices, frequent emails, and home visits by nurses and allied health professionals.

"As well, cystic fibrosis centres across Australia are looking at deploying devices that patients can use in their own homes to monitor lung function trends, which clinicians can review via a confidential portal," Ms Saxby says.

"During the COVID-19 crisis, it's also important our children and adolescents with health conditions to socialise with others - and social media networks such as Facebook groups is just one way to keep in touch."

Flinders Professor Sharon Lawn adds that chronic condition self-management approaches designed for adults may not fit with the needs of children with chronic conditions and their families.

"Children are not just little adults," she says. "These findings offer health services and professionals fresh insights into the transitions these children and their families must navigate as part of supported self-management," Professor Lawn says.

Scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and the Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD) in Madrid have demonstrated that a proteins present in early atheroma plaques--accumulations of cholesterol in the wall of arteries--could be used as a biomarker to detect atherosclerosis in the subclinical phase, before the appearance of symptoms.

The study, published today in the Journal of American College of Cardiology (JACC), concludes that activation of the complement system is one of the most characteristic molecular changes taking place in the early development of atherosclerotic plaques. The study shows that plasma levels of the complement system protein C5 could be used to identify individuals with subclinical atherosclerosis in a noninvasive way and at minimal cost. "Early identification of the disease would help to select individuals who would benefit from more costly noninvasive imaging analysis to get a more precise estimate of their cardiovascular risk," explained Dr Jesús Vázquez, head of the Cardiovascular Proteomics Laboratory at the CNIC and one of the coordinators of the study.

Cardiovascular disease is one of the biggest public health problems in the world. Spanish national institute of statistics data show that in 2018 around 121,000 people died from cardiovascular disease in Spain. Cardiovascular disease can trigger a heart attack or stroke, making it one of the leading causes of death in the world. "These events are due to the formation of atheroma plaques in the arteries, a process known as atherosclerosis," explained study co-coordinator Dr José Luis Martín-Ventura of the IIS-FJD. "Atheroma plaques can rupture, releasing their contents and triggering the blood clotting cascade and the formation of clots that block blood flow."

Atherosclerosis before these events is usually asymptomatic, and its underlying causes are poorly understood. "Current treatments are based on controlling major cardiovascular risk factors: high blood cholesterol, elevated blood glucose, hypertension, smoking, physical inactivity, and so on. However, these values of these parameters is limited value because even people who don't have these risk factors have cardiovascular events," explained Dr Martín-Ventura.

PESA CNIC-SANTANDER

The new study forms part of the PESA CNIC-SANTANDER project (Progression and Early detection of Subclinical Atherosclerosis). This major project, a partnership between the CNIC and Santander Bank, studies the development of atherosclerotic plaques in 3 arterial territories: the carotid arteries, the abdominal aorta, and the iliofemoral arteries. PESA studies these arteries in a population of asymptomatic, healthy Santander Bank workers between the ages of 40 and 54 at the time of recruitment. PESA CNIC-SANTANDER is providing important information about the high prevalence of subclinical atherosclerosis in the general population and the need to detect it early.

On the new JACC study, the researchers studied the mechanisms underlying the early development of atheroma plaques, with the aim of identifying new diagnostic biomarkers.

The research team designed a detailed study of the molecular composition of plaques in their initial stages, using the latest technology for massive proteomics screening. The study showed that, in their earliest stages, atheroma plaques accumulate proteins of the complement system. Complement activation is a key component of the immune system, and could induce changes in inflammatory cells in the plaque, promoting its progression. "These results give us new clues about the mechanisms underlying atherosclerosis and suggest that the circulating levels of complement proteins might be used to detect the presence of atherosclerosis," said Dr Vázquez.

The authors measured the levels of C5, an important complement protein, in blood samples of 360 participants in the PESA CNIC-SANTANDER project. This analysis showed that the blood concentration of C5 is higher in individuals with more than 2 atherosclerotic plaques. The findings were then validated in an independent study of 400 asymptomatic men and women.

The authors conclude that complement activation is a key molecular alteration in the first stages of the development of atherosclerotic plaques and that plasma C5 could be used to screen for individuals with subclinical atherosclerosis, thus helping to select those who would benefit from more costly imaging analysis to obtain a more precise picture of their cardiovascular risk.

A new study led by the University of Bristol has shown a common eye condition, glaucoma, could be successfully treated with a single injection using gene therapy, which would improve treatment options, effectiveness and quality of life for many patients.

Glaucoma affects over 64 million people worldwide and is a leading cause of irreversible blindness. It is usually caused by fluid building up in the front part of the eye, which increases pressure inside the eye and progressively damages the nerves responsible for sight. Current treatments include either eye drops, laser or surgery, all of which have limitations and disadvantages.

The research team led by academics at the Bristol Medical School: Translational Health Sciences tested a new approach that could provide additional treatment options and benefits. Their findings are published in the journal Molecular Therapy.

The researchers designed a gene therapy and demonstrated proof of concept using experimental mouse models of glaucoma and human donor tissue.

The treatment targeted part of the eye called the ciliary body, which produces the fluid that maintains pressure within the eye. Using the latest gene editing technology called CRISPR, a gene called Aquaporin 1 in the ciliary body was inactivated leading to reduced eye pressure.

Dr Colin Chu, Visiting Senior Research Fellow in the Bristol Medical School: Translational Health Sciences and corresponding author, said: "Currently there is no cure for glaucoma, which can lead to loss of vision if the disease is not diagnosed and treated early.

"We hope to advance towards clinical trials for this new treatment in the near future. If it's successful it could allow a long-term treatment of glaucoma with a single eye injection, which would improve the quality of life for many patients whilst saving the NHS time and money."

The academics are currently in discussion with industry partners to support further laboratory work and rapidly progress this new treatment option towards clinical trials.

New Rochelle, NY, April 21, 2020--Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic. The article describing these experiences and providing perspectives on the future application of tele-diabetes is published in Diabetes Technology & Therapeutics (DTT), a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here (https://www.liebertpub.com/doi/10.1089/dia.2020.0161) to read the full-text article free on the Diabetes Technology & Therapeutics (DTT) website.

The article entitled "Managing New-Onset Type 1 Diabetes During COVID-19 Pandemic: Challenges and Opportunities" is coauthored by DTT Editor-in-Chief Satish Garg, University of Colorado (Aurora), David Rodbard, Biomedical Informatics Consultants LLC (Potomac, Maryland), Irl Hirsch, University of Washington (Seattle), and Gregory Forlenza, University of Colorado (Aurora).

The first patient was a 20-year-old who was treated in the hospital for a few days and then managed virtually. He was treated with multiple daily injections of insulin and a continuous glucose monitor, with data upload to his caregivers to facilitate virtual management of his diabetes. The physician adjusted his insulin dose every day. His initial time-in-range (TIR) was 16%, which improved to 58% after 2 weeks of virtual management, and at 3 weeks the TIR was at 90%.

The second patient was a 12-month-old who was started on an insulin pump and a continuous glucose monitor. The family was taught how to upload the insulin pump data via their home computer, using a software account linked to the hospital. The continuous glucose monitor was set up on a cell phone worn by the child on a fanny pack, with remote monitoring by both the parents and continuous connectivity to software linked to the hospital account. The physician made daily dose adjustments via phone or email based on the data received.

"The COVID-19 pandemic has forced many providers to look for alternative approaches to manage high-risk patients with new-onset type 1 diabetes through Telehealth, especially by employing new technologies like Dexcom G6 CGM and Clarity App. Since many of the long-standing regulations were removed during this pandemic along with similar reimbursements for Tele-visits, Telehealth, or Virtual patient visits, these have become a popular method of delivering care for both new-onset patients with type 1 diabetes and for established patients, with similar or even better outcomes," says DTT Editor-in-Chief Satish Garg, MD, Professor of Medicine and Pediatrics at the University of Colorado Denver (Aurora).

A new tool that predicts risk of death and admission to a long-term care facility for patients with dementia may help conversations between health care providers, patients and their families, according to new research in CMAJ (Canadian Medical Association Journal).

The recent tragic outbreaks of COVID-19 in long-term care homes highlight the need to have care discussions with residents and their caregivers.

"The majority of residents in long-term care homes have been diagnosed with dementia. Our study shows that the survival of many people with dementia is poor. It may be that many would choose care that focuses on comfort care and quality of life should they become acutely ill," says Dr. Peter Tanuseputro, a family physician and researcher with the Bruyère Research Institute, the Ottawa Hospital Research Institute and ICES, Ottawa, Ontario.

"We have developed a tool that asks simple questions about a person at the time of dementia diagnosis and translates it to the chance of dying and of entering a nursing home over the next 5 years. This information can be used in conversations about what to expect," says Dr. Tanuseputro. "For newly diagnosed dementia patients and their families, personalized information about their trajectory may be helpful to plan for the future, including advance care planning and planning for additional supports."

The study used linked data from ICES on more than 108 000 people living in the community in Ontario who were newly diagnosed with dementia from 2010 through 2012.

Researchers found that more than half of individuals (55%) died within 5 years -- comparable to many cancers -- and almost half of those who died (28%) lived in institutions. Only 1 in 4 people were still alive and living in the community 5 years after diagnosis.

Older age, male sex and presence of chronic obstructive pulmonary disease (COPD), congestive heart failure and kidney failure at the time of diagnosis of dementia were the most important factors that predicted death and admission to long-term care. The impact of organ failure on prognosis in people with dementia has not been well documented in other studies.

The researchers used data from the paper to develop an online dementia calculator https://www.individualizedhealth.ca/dementia-tool.

Dementia is a progressive, life-limiting illness, and personalized information about survival and potential transition into long-term care facilities like nursing homes can help patients and care providers with prognosis and planning. This is, however, not always done, perhaps partly because easily accessible tools have not been available. The global prevalence of dementia is increasing and is expected to triple by 2050.

"For patients, families and caregivers, these conversations can be difficult and too often they don't happen at all," says Dr. Tanuseputro. "If we can help patients and families understand what is likely to happen to their health, and what the next few years may hold, it can help with planning, perhaps provide some peace of mind, and ensure they maximize the quality of life remaining."

A related ICES infographic will be available on publication here https://www.ices.on.ca/Publications/Infographics.

"Five-year risk of admission to long-term care home and death for older adults given a new diagnosis of dementia: a population-based retrospective cohort study" is published April 20, 2020.

Early GP referrals are likely to lead to cancer patients surviving longer, a study by King's College London and funded by the National Institute for Health Research (NIHR) has found.

The analysis of 1.4million cancer patients in England published today in the British Journal of General Practice, led by King's College London and Public Health England (PHE), found that cancer patients from the highest referring GP practices had a lower mortality rate. Cancer patients from these same practices were also more likely to be diagnosed at an earlier stage for breast, lung and prostate cancer.

Dr Thomas Round, from King's College London and PHE said: "As a GP, considering a cancer diagnosis is not easy. A typical full time GP would have 8-9 new cancer cases per year but sees many patients who have symptoms which could be due to cancer. The urgent referral, or two-week wait pathway, is very helpful for both patients, with potentially worrying symptoms, and their GPs who can fast track them to have a specialist review or tests. This research shows that GPs are referring substantially more patients with suspected cancer, which is making a real impact in improving cancer outcomes in the NHS."

1 in 2 of us will be diagnosed with cancer in our lifetimes, with over 360,000 new cases and 165,000 cancer deaths per year in the UK. However similar countries have better cancer survival rates, with potentially 5,000-10,000 avoidable cancer deaths per year in the UK if our survival rates matched those in other countries. Early diagnosis is a key component to increasing cancer survival rates.

If a GP suspects a patient has cancer, they can fast-track refer them to be seen by a specialist or have a specialist test within two weeks. Urgent referrals have increased to more than 2 million per year in England, with an average GP making 50-60 referrals per year.

The research, which looked at cases of breast, lung, prostrate and colorectal cancers using data from the National Cancer Registry, supports the increases seen in primary care referrals and access to diagnostic tests, which allows more cancers to be diagnosed. This has also led to the number of people diagnosed with cancer following an A&E presentation, who are more likely to have worse outcomes, to drop from 1 in 4 to less than 1 in 5.

Dr Round said: "Clearly the current COVID19 situation is putting a significant strain on health services, including for potentially serious conditions, such as suspected cancer referrals and cancer treatment once diagnosed. This is clearly a worrying time for patients and NHS staff. We have some reports of patients delaying seeking help because they think their GP practice or A&E departments are closed. This is not the case, with GP practices adapting with use of telephone, video and online appointments. It is important if patients are experiencing worrying symptoms to contact their GP practice. Whilst the assessments may be different, and NHS capacity is stretched, we are still trying to facilitate urgent two week wait referrals in collaboration with our hospital colleagues. With approximately 450 cancer deaths per day in the UK it's important that we continue urgent referrals, diagnosis and treatment for cancer patients."

This work is in collaboration with PHE's National Cancer Registration and Analysis Service (NCRAS) and uses data that has been provided by patients and collected by the NHS as part of their care and support. The data is collated, maintained and quality assured by the National Cancer Registration and Analysis Service, which is part of Public Health England (PHE).

KANSAS CITY, MO--Drug resistance is a major obstacle in cancer treatment--leading to relapse for many patients. In a new study, published online April 20, 2020, in Nature Cell Biology, researchers from the Stowers Institute for Medical Research, Children's Mercy Kansas City, and The University of Kansas Cancer Center report on a promising new strategy to overcome drug resistance in leukemia, using targeted doses of the widely-used chemotherapy drug doxorubicin.

The study's researchers found that low doses of the anthracycline antibiotic doxorubicin inhibit the interaction between two molecular pathways that work closely together to promote tumor growth and resistance to therapy. The targeted approach also clears the way for cancer-targeting immune cells to do their work, an unexpected and novel finding, according to the study authors.

"In low doses, doxorubicin actually stimulated the immune system, in contrast with the typical clinical doses, which were immunosuppressive, killing healthy immune cells indiscriminately," says John M. Perry, PhD, a researcher with the Children's Mercy Research Institute at Children's Mercy. He completed his postdoctoral work at Stowers and is first author of the report.

The findings are the result of a decade-spanning collaborative effort among researchers at the Stowers Institute, Children's Mercy, The University of Kansas Cancer Center and other institutions, evolving from their studies on how normal, healthy stem cells self-renew.

Early in their studies, Stowers Institute Investigator Linheng Li, PhD, and Research Specialist Xi He, MD, showed that the protein kinase Akt could enhance Wnt signaling via phosphorylating beta-catenin, thus promoting tumorigenesis in the gut. Perry further investigated the Wnt/beta-catenin and PI3K/Akt pathways in the hematopoietic (blood-forming) system. Using a mouse model with genetic modifications of the Wnt/beta-catenin and PI3K/Akt pathways, Perry found that the two pathways cooperate to drive stem cell renewal, thus resulting in excessive blood-forming stem cell production. But instead of just expanding the stem cells, the permanent activation of the pathways caused the mice also to develop leukemia. Intrigued, the researchers shifted their focus to inhibiting interaction between those same pathways to target leukemia stem cells.

Many drugs that directly target the Wnt/beta-catenin or PI3K/Akt pathways eventually fail because cancer cells evolve resistance to them, and broadly-acting chemotherapeutic drugs can have harsh side effects and systemic toxicity. The researchers collaborated with Scott Weir, PhD, and Anuradha Roy, PhD, at The University of Kansas (KU) Cancer Center, to search for an alternative among the compounds cataloged in the center's small molecule library.

"Our idea was to find a drug with the goal of blocking the interaction between Wnt/beta-catenin and PI3K/Akt and reduce the toxicity," says Li, who serves as liaison between Stowers and the KU Cancer Center and co-leads the center's cancer biology research program.

The team conducted high-throughput drug screening, which showed that doxorubicin did the best job of inhibiting the interaction between the two pathways. They found that the drug's inhibitory powers worked at low doses, which offers an advantage over administering it at high doses as a chemotherapeutic drug where it can cause lasting heart damage in some patients.

Samples collected from pediatric leukemia patients at Children's Mercy were also central to the study. A diagnostic sample was collected from each patient before and after chemotherapy treatment to compare therapy-resistant leukemia stem cells to therapy-sensitive leukemia stem cells. Then the samples were transplanted into mice to test whether they developed leukemia and whether low-dose doxorubicin treatment improved their survival and reduced leukemia development.

"We found that mice receiving patient sample transplants with therapy-resistant leukemia stem cells rapidly developed leukemia, but low-dose doxorubicin treatment improved survival by reducing leukemia stem cells," Perry says. "However, mice receiving patient sample transplants that did not contain therapy-resistant leukemia stem cells did not respond to low-dose doxorubicin treatment. These results showed that chemoresistant leukemia stem cells from patients could be functionally reduced with low-dose doxorubicin treatment, at least in an in vivo animal model assay."

After successful testing in mouse models, the researchers worked with Tara Lin, MD, at the KU Cancer Center to conduct a small-scale clinical trial to test low-dose anthracycline treatment on adults with treatment-resistant acute myeloid leukemia (AML). The trial used daunorubicin, a chemotherapy drug in the same class as doxorubicin, which is widely used in treating AML. Bone marrow was collected immediately prior to treatment and again post-treatment. Half of the study participants responded to the treatment and had reduced numbers of leukemia stem cells exhibiting the Akt-activated beta-catenin biomarker.

In addition to these encouraging results, the overarching study also revealed surprising insights into immune escape--a hallmark of cancer development in which cancerous cells evade the immune system and proliferate. Mechanistically, they found that leukemia stem cells express multiple proteins known as immune checkpoints, which turn off immune responses that might otherwise recognize and eliminate leukemia stem cells. Another team member, Fang Tao, PhD, uncovered that beta-catenin binds to multiple immune checkpoint gene loci. Low-dose doxorubicin treatment reduced expression of these immune checkpoints, including PD-L1, TIM3, and CD24, which exposed otherwise resistant leukemia stem cells to immune-mediated cell killing.

Going forward, at Children's Mercy, Perry is conducting further research to understand ways to screen other drugs that synergize with low-dose doxorubicin to kill resistant cells while reactivating anticancer immunity in pediatric patients. His team has recently launched a clinical trial on low-dose doxorubicin in pediatric patients. At Stowers, the Li Lab is investigating similar strategies for overcoming cancer therapy resistance in solid tumor cancers including breast cancer, glioblastoma, and colon cancer.

"The research holds promise as a more effective strategy to overcome cancer therapy resistance and immune escape that can be used in combination with other cancer therapies including chemotherapy, radiation, and immunotherapy for patients with leukemia and other types of cancer," Li says.

Low-dose doxorubicin also avoids the harsh side effects of high-dose doxorubicin, potentially offering patients a better quality of life. In high doses, doxorubicin damages the heart muscle. Even when patients survive long-term, highly toxic anticancer treatments often cause long-term health problems and reduced life expectancy.

"Pediatric patients should live another half-century or more, so we need to do a better job of ensuring not only long-term survival, but healthy and productive lives," Perry says.