miércoles, 31 de octubre de 2018

Study on how blood clots form and clear could make pancreatic cancer more treatable

Download PDF Copy

Reviewed by James Ives, MPsychOct 31 2018

You're experiencing jaundice, abdominal pain or constipation. And by then, you may be too late. Pancreatic cancer symptoms often arrive after the cancer has already spread, making the disease one of the leading causes of cancer deaths in the U.S.

However, a team of researchers believes that targeting how blood clots form and are naturally cleared could make the cancer more treatable.

The team - which includes researchers from Purdue University, the Cincinnati Children's Hospital, the Indiana University School of Medicine and the University of North Carolina School of Medicine at Chapel Hill - is studying the relationship between clots and pancreatic tumors in both animal and human tissue samples through the support of a $4 million grant from the National Institutes of Health.

What the team finds could lead to improved therapies for patients suffering from pancreatic tumors.

"Pancreatic cancer promotes blood clot formation, and then these clots make the cancer develop faster, which prevents drugs from controlling tumor growth," said Bumsoo Han, professor of mechanical engineering at Purdue University and program leader of the Purdue University Center for Cancer Research.

"Our idea is to study this process by use of engineered tumor models mimicking the pancreatic duct," he said.

The work aligns with Purdue's Giant Leaps celebration, acknowledging the university's global advancements made in health, longevity and quality of life as part of Purdue's 150th anniversary. This is one of the four themes of the yearlong celebration's Ideas Festival, designed to showcase Purdue as an intellectual center solving real-world issues.

The project is based on the initial findings of Matthew Flick, a member of the faculty at Cincinnati Children's Hospital and former Ph.D. student in biological sciences at Purdue, that pancreatic tumors and blood clots are linked through bi-directional mechanisms that promote both pancreatic cancer growth and blood clot formation.

Han's group built a tiny device with "microfluidic" channels that host pancreatic duct tissue samples beneath a microslide. The device takes information from these samples to simulate with greater detail how cancer develops from the pancreatic duct and invades surrounding tissue.

The microfluidic device will assist in defining key mechanisms of pancreatic cancer growth and blood clot formation. Validation studies will be performed by Flick's group to confirm tumor growth findings in mouse models, while Melissa Fishel's group at the IU School of Medicine and Melvin and Bren Simon Cancer Center will perform the same using patient samples. Alisa Wolberg's group at UNC Chapel Hill will further validate identified mechanisms of cancer-driven blood clot formation in animal and patient samples.

Each member of the team is contributing equally to the project. The NIH grant will facilitate future work on the study of these mechanisms and translation of the findings into new treatments.

A patent has been issued for the microfluidic device technology.

Source:

https://www.purdue.edu/newsroom/releases/2018/Q4/research-on-clots-could-make-pancreatic-cancer-more-treatable.html

Research highlights lack of data on European children's nutrient intake levels

Download PDF Copy

Reviewed by James Ives, MPsychOct 31 2018

Only a third of European countries have robust reporting on child and adolescent nutrient intakes, new research shows. This highlights the potential lack of data to inform the design and monitoring of nutritional policies in some parts of Europe.

To better understand energy levels and the nutrient intakes currently consumed by European children, an international team led by the University of Leeds, in collaboration with the World Health Organization's (WHO) Regional Office for Europe, reviewed national diet surveys from the 53 European Member States. They found the majority of the reporting gaps were in Central and Eastern European countries, meaning potential nutritional issues in certain countries may be undetected or underestimated.

Lead author Holly Rippin, a postgraduate researcher from the School of Food Science and Nutrition, said: "The lack of available data for child nutrient intake is concerning. It makes it extremely difficult to identify vulnerable groups, compare nutrient intakes between countries and provide evidence for policies that could improve health. It's similar to trying to describe a complex watercolour when large sections haven't been painted in yet."

The study, published in Nutrition Research Reviews, shows:

Only around 30 per cent of countries reported nutrient intake data by gender and age group for children and adolescents.
Age groupings varied across counties and several counties did not report nutrients in all age groups or reported on different types of nutrients.
Many countries did not separate intake amounts for girls and boys in the youngest age groups.

Holly Rippin said: "Our assessment also showed a significant amount of under-reporting, which means certain nutrition-related problems, such as deficiencies or overconsumption, could be underestimated and possibly just the tip of the iceberg with so many countries intakes unknown."

The WHO European Food and Nutrition Action Plan encourages Member States to strengthen and expand nationally representative diet and nutrition surveys. However, national diet survey provision across Europe is inconsistent and less than two thirds of WHO European countries have nationally representative diet surveys.

Holly Rippin added: "Insufficient data and the inability to compare countries and age groups highlights the pressing need to dedicate resources to dietary surveillance and harmonize methodologies and approaches in nutrient reporting throughout the WHO European region.

"The worry is that it is extremely difficult to design suitable and locally-appropriate nutrition policies in countries without sufficient data. Easily accessed, robust data is critical in tailoring policies to meet national needs and improve diets across Europe."

Falling short of WHO recommended nutrient intakes

The team assessed the limited available data from the national diet surveys against nutrient intakes recommended by WHO. While inconsistent reporting across and within countries hindered comparisons, the study identified some key areas of concern and in particular found that the average intakes for children reported in the majority of countries, including the UK, did not meet most of the WHO recommended nutrient intakes.

Co-author Janet Cade, professor of nutritional epidemiology and public health at Leeds, said: "Our findings indicate that a Europe-wide policy focus could improve intakes of iron, vitamin D, and total folate while also reducing sodium and free sugar intake. A focus on iron and vitamin D intake would be especially beneficial for girls and children over the age of 10 .

"Iron is a particular issue for adolescent girls. The survey data showed low iron intakes in the vast majority of countries. Adolescent girls continue to be at greater risk of iron-deficiency anemia, which is associated with reduced intellectual and immune function.

"Although a variety of evidence is required to inform national interventions, accurately identifying key dietary trends could help prevent childhood nutrient deficiencies that can cause health issues that extend well into adulthood."

The WHO European Food and Nutrition Action Plan already identifies several of the nutrients highlighted in the report as areas of concern, such as iron and vitamin D, although it refers to all ages rather than specifically children. The Action Plan also calls for the promotion of healthy diets through the reduction in sodium, saturated fats, and free sugars.

Co-author Dr Jayne Hutchinson, also from the School of Food Science and Nutrition at Leeds, said: "The WHO European Food and Nutrition Action Plan is making a concentrated effort to improve nutrient intake across Europe and identifying any additional areas of concern is an important part of advancing these efforts.

"Our research shows there are still other areas of concern that need to be better understood and addressed, such as omega fats for which reported intakes were low. Omega fats have important functions for health and studies suggest they may help lower the risk of heart disease and depression.

"Identifying these trends allows for the potential to develop targeted policy and guidance, for example encouraging public education on sources of omega fats.

"Despite the current lack of data, national nutrition and health surveys remain the best source of information on dietary risk factors. It's vital that government and health bodies should continue to invest and improve efforts to conduct national dietary surveys in a standardized format with a full range of nutrient intakes."

Dr Joao Breda is a study co-author and Programme Manager for Nutrition at WHO Europe and Head of the WHO European Office for the Prevention and Control of Noncommunicable Diseases. He said: "Dietary surveys should be the foundation for all nutrition policies in a country. In many cases, our efforts to support countries in achieving the Sustainable Development Goals are constrained by a lack of data.

"Commitment by countries and funders to support the better availability of dietary intake data will help the public health community target policies and interventions to eradicate all forms of malnutrition, including both the remaining pockets of under-nutrition in the region and the rising rates of overweight and unhealthy diets."

Source:

http://www.leeds.ac.uk/

3 Harvard scientists receive Allen awards for work in neuroimmunology, developmental biology, cancer

Download PDF Copy

Reviewed by James Ives, MPsychOct 31 2018

Three Harvard Medical School scientists have received the prestigious Allen Distinguished Investigator awards for their work in the fields of neuroimmunology, developmental biology and cancer.

The awardees, neurobiologist Chenghua Gu, systems biologist Marc Kirschner and cancer researcher David Weinstock, will each receive $1.5 million in research support over three years. Weinstock will share his award with biological engineer Scott Manalis of MIT.

The awards, conferred by the Paul G. Allen Frontiers Group, support research that aims to bring new clarity to knowledge of the biology of human aging.

Gu, professor of neurobiology at Harvard Medical School, receives the award in recognition of her pioneering work studying the brain vasculature in relation to neuroimmunology, an emerging field that explores the intersection of the nervous and immune systems. Her work has yielded valuable insights into our fundamental understanding of the unique features of the brain vasculature including the blood brain barrier, which provides a safe and homeostatic brain environment that is essential for proper neural function. This award will extend Gu's investigations into how vascular cells receive and transmit signals between the body's immune system and the brain.

Kirschner, the John Franklin Enders University Professor of Systems Biology and founding head of the Harvard Medical School Department of Systems Biology, is being recognized for his mold-breaking approaches to studying how cells divide, live and die. His research takes a large-picture, systematic approach to understanding the biology of early development and aging, the two processes that bookend the lives of all living creatures. Although development and aging are usually studied in separate scientific disciplines, Kirschner integrates them. Using the water flea as a model organism, Kirschner employs systems biology and machine learning approaches to uncover how cellular circuitry drives both development and aging and where they might overlap. This award will support his continuing efforts to advance understanding of embryonic development and aging.

Weinstock, associate professor of medicine at Harvard Medical School and attending physician at Dana-Farber Cancer Institute, studies the molecular origins of cancer and how cells repair their damaged DNA. Weinstock and collaborator, Manilis, are receiving the award for their work into the mechanisms that fuel drug-resistance and propel recurrence in a class of cancers known as lymphomas, which affect various white blood cells. The team's ultimate quest is to understand why some people with lymphoma are cured while others relapse and to identify ways to prevent the return of the disease. To do so, Weinstock and Manilis will start out by studying the handful of residual lymphoma cells that linger on even after patients go into remission and aim to define what renders these leftover cells resistant to treatment.

The Allen Distinguished Investigator program began in 2010 to fund early-stage research that is less likely to receive support from traditional funding sources but has the potential to significantly advance understanding of biology. The latest round of awards brings the total number of awards to 69.

Source:

https://hms.harvard.edu/news/3-hms-scientists-receive-prestigious-allen-awards

Newly developed technology can predict large volumes of unknown biochemical reactions

Download PDF Copy

Reviewed by James Ives, MPsychOct 31 2018

Fujitsu Laboratories Ltd., the Insight Centre for Data Analytics, a data analytics research institution based in Ireland, and Fujitsu (Ireland) Limited today announced the development of a technology that makes it possible to predict large volumes of unknown chemical reactions, about twice as many as the conventional procedure. In serious diseases, including cancer, it is common for there to be abnormalities in phosphorylation reactions, which are chemical reactions that occur between proteins. Accordingly, there are high expectations that clarifying phosphorylation reactions will lead to effective treatments. At present, however, because only a few phosphorylation reactions have been identified, there has been a problem in predicting large volumes of phosphorylation reactions caused by combinations of unknown proteins. Now, by building a knowledge graph that can encompass an overview of the interrelations between proteins, it is possible to check the relationship between new proteins where phosphorylation reactions can be predicted. In this way, this technology will contribute to the advancement of medicine, as it can be expected to be useful on the front lines of drug discovery research, and have customized applications in the field of precision medicine.

Development Background

Biological systems within the body are maintained by exchanges of information through the chemical reactions of various proteins within cells. In recent years, science has come to understand that many serious diseases, such as cancer, are partially caused by abnormalities in phosphorylation reactions, which are representative of the chemical reactions between proteins. If pharmaceuticals that repaired abnormal phosphorylation reactions could be developed, that would enable more effective treatments. At present, however, only a few phosphorylation reactions are well understood, so there is a need for the discovery of unknown phosphorylation reactions, and to enrich the data on phosphorylation reactions.

Issues

Phosphorylation reactions are chemical reactions in which a protein attaches a phosphoryl group to the amino acids that make up another protein. In order to discover them, it is necessary to check the combinations of proteins that cause phosphorylation reactions through biological experiments. Nonetheless, as there are more than about 800,000 possible combinations just with proteins, and because significant costs and time are required for biological experiments, it is necessary to right from the start predict high-probability combinations. It is known that whether a phosphorylation reaction will occur depends on the structure of the amino acid sequence that makes up the protein. AI technology is therefore already being used to predict new phosphorylation reactions by training the AI on the structure of amino acid sequences that are already known to cause phosphorylation reactions. While this technology can predict reactions in which the structure of the amino acid sequence is similar to those that are known to cause phosphorylation reactions, it has not been capable of predicting those in which the structure of the amino acid sequence is significantly different from the already known phosphorylation reactions.

About the Newly Developed Technology

According to recent medical research, there is a phenomenon in which proteins that have undergone reactions may phosphorylate other proteins in a chain reaction (chained information), and this may be the key to predicting new, unknown phosphorylation reactions related to that phenomenon. Based on such research, Fujitsu Laboratories, the Insight Centre, and Fujitsu Ireland have now included not only structural information about amino acid sequences in the knowledge graph, but also chained information. The organizations have developed a technology (patent pending) to represent the complex patterns of chemical reactions as optimized attributes, which are attached to the lines in the knowledge graph. As these attributes were tailored to the sophisticated construction by the knowledge graph, they can lead to highly accurate prediction results. Conventionally, the relationship between proteins could only be checked through a single link in the chain. Yet by comprehensively displaying the relationship between proteins as connections of phosphorylation reactions (chained information), it becomes possible to clarify the positioning of the various proteins from a holistic perspective, and to predict unknown relationships.

Effects

When this technology was tested using evaluation data, the model was trained on phosphorylation reactions (9,802 reactions), and predicted 11,581,940 new phosphorylation reactions. This showed its capability in predicting about twice as many phosphorylation reactions compared to conventional technology that trained AI on the structure of amino acid sequences, without significant change to prediction accuracy. In addition, in order to test whether phosphorylation reactions predicted using this technology could actually occur within a living being, tests were conducted by Systems Biology Ireland, an Irish biological research institution and a joint research partner, using mass spectrometry equipment and antibodies. In this test, experts in biology selected and tested a few phosphorylation reaction prediction results for proteins related to cancer, and were able to confirm nine phosphorylation reactions, of which eight were reactions that could not have been predicted with conventional technology. Systems Biology Ireland (SBI) director Walter Kolch, a world leading authority on systems biology research, said about these results "Combining Fujitsu's knowledge graph technology with SBI's understanding of biological networks, we have developed a new computational method that can predict which kinase phosphorylates which substrates. The method is accurate and could discover previously unknown phosphorylation sites, a major step forward for new drug development and more focused precision medicine."

Future Plans

By combining data on new phosphorylation reactions predicted by this technology with other biomedical data, it is expected to connect the chemical reactions from the causes of a disease (abnormalities in phosphorylation reactions) to the disease's symptoms, which can then be provided to those on the front lines of research as useful information in drug discovery. The effectiveness of treatments for diseases such as cancer can vary widely between patients. This technology, however, is expected to clarify the individual variation in the effects of treatments, contributing to the promotion of medicine tailored to individual patients. Fujitsu Laboratories, the Insight Centre, and Fujitsu Ireland will continue to further improve the accuracy of this technology to process biomedical data with knowledge graphs, extending the technology to biomedical projects at Fujitsu Limited in fiscal 2018. Moreover, by incorporating this technology into Fujitsu's AI technology, including Fujitsu Human Centric AI Zinrai, the organizations plan to accelerate the biomedical business.

Source:

http://www.fujitsu.com/global/about/resources/news/press-releases/2018/1031-04.html

Alzheimer's Association's Part the Cloud program funds innovative research on brain cells

Download PDF Copy

Reviewed by James Ives, MPsychOct 31 2018

Innovative research aimed to possibly rejuvenate brain cells will be explored by six international researchers with the goal of discovering effective drugs for people with early stage Alzheimer's disease and other dementias. All of the research is being funded by the Alzheimer's Association's Part the Cloud to RESCUE (REverse, reStore, Cease and UndErstand) Brain Cell Degeneration in Alzheimer's disease program.

Each of the awardees will receive $1 million over two years to support their research. Since 2012, Part the Cloud has raised more than $29 million to invest in the Alzheimer's Association research grants. These are "high risk" science projects that need seed funding as the researchers test their ideas and build initial supportive data. The supportive data will allow scientists to seek broader funding from the National Institutes of Health or other sources for larger clinical trials to more definitively test safety and effectiveness.

The grants are funded through the Alzheimer's Association's Part the Cloud program. The primary focus is to advance pioneering ideas for early phase human trials - Phase I or Phase 2a proof of concept - targeting brain cell health in Alzheimer's. The destruction of the brain's nerve cells causes memory failure, personality changes, problems carrying out daily activities and other symptoms of Alzheimer's disease dementia.

"Currently, there are no truly effective treatments or preventions for Alzheimer's disease," said Maria C. Carrillo, Ph.D., Alzheimer's Association chief science officer. "With the aging of the global population, the urgency has never been greater to change that situation and the sooner the better."

"These Part the Cloud to RESCUE grants encourage discovery and development of a wide range of interventions that might someday be viable treatments for people with or at risk for Alzheimer's. We are expanding the Alzheimer's drug pipeline at the front end - Phase 1 and 2 clinical trials - where it is most desperately needed," Carrillo said. "The research funded by these grants will not only advance possible treatments, but also accelerate our understanding of processes associated with Alzheimer's and related dementias, as well as other diseases that impact the brain."

The new grants are awarded to:

Roberta Diaz Brinton, Ph.D., University of Arizona (Tucson, AZ)

This phase 2a study will test whether allopregnanolone, an important hormone in brain function, is able to restore brain cell function in people with Alzheimer's.

Rafael de la Torre, Pharm.D., Ph.D., Hospital del Mar Medical Research Institute (Barcelona, Spain)

A phase 1 study to test the ability of high dose epigallocatechin gallate (EGCG), an organic compound found in green tea with antioxidant and anti-inflammatory properties known to regulate insulin signals in cells, to reverse cognitive changes in people with early stage Alzheimer's. The study also includes a lifestyle intervention of diet, exercise and cognitive training that will be tested with the EGCG in a low income, low education community.

Xue Hua, Ph.D., M3 Biotechnology, Inc (Seattle, WA)

This phase 2 proof-of-concept study will evaluate NDX-1017 to determine its potential to treat Alzheimer's disease and dementia. NDX-1017 is a novel compound focused on regeneration, with a potential to slow, halt or reverse the effects of Alzheimer's disease, rather than only alleviating symptoms.

Paul A. Newhouse, M.D., Vanderbilt University (Nashville, TN)

A phase 2a study of a new drug, M1-PAM VU319, to improve brain cell communications that could boost memory and attention in people with mild cognitive impairment (MCI). This phase 2a clinical trial will test the drug for the first time in people with MCI.

Stephen M. Strittmatter, M.D., Ph.D., Yale University (New Haven, CT)

Targeting a relatively new approach, this phase 1b study will test a compound, mGluR5 SAM, to target brain cell communication systems for improved brain cell health.

Intent-to-Fund: Raymond Tesi, M.D., INmune Bio (La Jolla, CA)

This phase 1 study will evaluate a new compound, XPRO1595, which aims to reduce inflammation and reverse brain cell death.

Part the Cloud was founded by philanthropist Michaela "Mikey" Hoag after losing her father to younger-onset Alzheimer's. In partnership with the Alzheimer's Association, the Part the Cloud movement addresses the critical need to support promising early phase clinical trials to help accelerate the transition of findings from the laboratory into possible therapies.

Part the Cloud is a research funding effort from the Alzheimer's Association, the world's leading nonprofit funder of Alzheimer's and dementia research. The Association is currently investing over $160 million in more than 450 projects in 25 countries. Since 1982, the Association has invested over $435 million to more than 2,900 scientific investigations.

Source:

https://www.alz.org/

Study: Only one in 30 children does recommended amount of daily physical activity

Download PDF Copy

Reviewed by James Ives, MPsychOct 31 2018

Only one in 30 children does the recommended amount of daily physical activity, new research suggests.

Guidelines from the Chief Medical Officer say people aged five to 18 should do at least 60 minutes of "moderate-to-vigorous intensity physical activity" every day.

Previous research has often used less than seven days of data on children's activity and created an average based on that.

But a study by the universities of Exeter and Plymouth of Year Five children (aged nine or ten) found that although almost a third (30.6%) achieved an average of 60 minutes per day, just 3.2% did so every day.

Activity levels among girls were even lower, with just 1.2% hitting the 60-minute daily target - compared to 5.5% of boys.

"Previous studies based on average activity are likely to have overestimated the percentage of children meeting the recommendations," said Dr Lisa Price, of the University of Exeter.

"Our findings suggest that just under a third of children are achieving an average of 60 minutes per day, but only 3.2% meet the 60-minute target every day.

"We were surprised to find such a big difference.

"We don't know whether averaging 60 minutes a day will be different in terms of health outcomes compared to 60 minutes daily - more research is needed to look into this.

"We do know that most children aren't doing enough physical activity, and that this has consequences not just in childhood but in adulthood too."

The data was gathered from 807 Year Five children from 32 schools in Devon, with a full seven days of data gathered on each child using an activity tracker watch.

Previous studies collecting activity data have been limited by the ability to obtain a full seven days of data, so this study has some of the most robust data on nine and ten year olds' activity.

The research was carried out as part of the Healthy Lifestyles Programme, an innovative school-based obesity prevention trial that encouraged children and their families to live healthier lives.

The programme is funded by the National Institute for Health Research (NIHR).

The paper, published in the Journal of Physical Activity and Health, is entitled: "Are we overestimating physical activity prevalence in children?"

Source:

https://www.exeter.ac.uk/

Study finds 7 out of 10 European workers are not adequately hydrated

Download PDF Copy

Reviewed by James Ives, MPsychOct 31 2018

A newly published scientific paper indicates that occupational safety and daily day performance in 7 out of 10 workers, from several European industries, is negatively affected by a combination of heat stress and failure to maintain water balance. The study combines field observations and motor-cognitive testing in the lab, and was conducted by the Pan-European Heat-Shield project coordinated by researchers from Department of Nutrition, Exercise and Sports at University of Copenhagen.

The importance of preventing dehydration has received much attention in health and work-safety advisories, as well as highlighted in the media during hot periods. It is therefore astonishing that 7 out of 10 workers are not adequately hydrated already at the onset of work.

"The very high prevalence of dehydration was a surprise to us, and the potential influence on workers cognitive function and motor performance in key industries is quite problematic, because it markedly increase the risk of making mistakes and therefore threaten both safety and productivity," says professor Lars Nybo from the Department of Nutrition, Exercise and Sports at University of Copenhagen, and project coordinator for Heat-Shield.

A threat to productivity and safety

During the previous two years, the Heat-Shield project has assessed hydration status at the onset and end of work shift across five different European industries. The study included 139 workers from four different countries; Denmark, Cyprus, Greece and Spain, and respectively working as manufacturing workers (in the aluminum industry) or as agricultural workers, police officers, tourism workers and construction workers.

The study combines field data with advanced testing of cognitive and motor function, and demonstrate how the combination of dehydration and occupational heat stress is a significant threat to productivity and safety. The impaired cognitive and motor task performance will be problematic in many occupations, as they rely on the workers cognitive function e.g. their ability to keep focus on task and react appropriately to occupational challenges.

For agricultural workers dehydration is a problem that aggravates during work shifts, but across all industries it is mainly failure to rehydrate from day to day that causes a state of mild to moderate dehydration. In itself a health problem, however when combined with heat stress it markedly influenced the ability to perform complex tasks. This may indeed influence productivity, but especially it can be a threat to safety at work places with high environmental temperatures.

Risk of larger problems in the near future

Andreas Flouris, Associate Professor at the University of Thessaly, Greece, and head of the field studies conducted in Southern Europe emphasizes that the problem can be even bigger in the near future: "This is already a problem under the current conditions. However, facing a future with more frequent heat waves it is of utmost importance for workers to adopt better hydration habits and for companies to develop effective hydration strategies."

Considering that many occupational tasks as handling of industrial machinery, driving, harvesting etc. rely on alertness and the ability to integrate multiple input and react appropriately, it is of great importance to emphasize the importance of informing on the consequences of dehydration and the needs for adopting appropriate prevention.

These findings let us suggest that prevention plans with implementation of suitable and more effective hydration and rehydration strategies are warranted at work places to minimize the negative effects of dehydration on workers performance, when they are exposed to occupational heat stress.

Source:

https://nexs.ku.dk/english/news/2018/european-workers-fail-to-maintain-water-balance/