Researchers find method to develop blood stem cells used to treat patients with cancer

Researchers find method to develop blood stem cells used to treat patients with cancer -

A team of scientists from the University of Colorado School of Medicine reported breakthrough discovery of a process of increasing the production of stem cells used to treat cancer patients. These results could have implications that go beyond cancer, including treatments for innate immune and metabolic conditions, and autoimmune diseases.

In an article published on 29 August PLOS ONE , researchers from Charles C. Gates Center regenerative medicine and stem cell biology and taiga Biotechnologies, Inc. said they have uncovered key molecular code that appears to regulate the ability of blood stem cells to reproduce and maintain their stem-like characteristics.

The team developed the protein products that can be directly administered to blood stem cells to encourage them to multiply without permanent genetic changes.

"The use of stem cells to treat cancer patients facing bone marrow transplant has been a common practice for four decades," said Yosef Refaeli, Ph.D., professor associate of Dermatology and a major scientific study. "The biggest challenge, however, was to find an adequate supply of stem cells that help patients fight infection after the procedure."

Gates Stem Cell Center director Dennis Roop, Ph.D., recognized the importance of the work team.

"Researchers have long tried to increase the number of blood stem cells in a laboratory," said Roop. "Most of these approaches have been limited by the nature of the resulting cells or insufficient of cells produced. "

the technology described in PLOS ONE Article worked with stem cells from blood obtained from cord blood, adult bone marrow or adult peripheral blood .

"the ability to multiply blood stem cells from a source in a dish will be critical to the adoption of this new technology in clinical," said Brian Turner, Ph.D., MHS, scientific director of Taiga Biotechnologies. Dr Turner is also one of the lead authors of the paper.

the goal now is to move laboratory technology in clinical trials. Taiga Biotechnologies is putting first in human clinical trials with stem blood cell expansion approaches described in the article. Clinical applications of expanded human blood stem cells varies conditions of primary immunodeficiencies, such as SCID and sickle cell anemia, metabolic diseases such as Hurler syndrome and Gaucher. Autoimmune diseases that may be affected include severe multiple sclerosis and lupus. And the types of cancer that could be treated as a result of this research include leukemia, lymphoma, myeloma and other solid tumor types.

MGH researchers discover how obesity increases inflammation, desmoplasia in PDAC patients

MGH researchers discover how obesity increases inflammation, desmoplasia in PDAC patients -

Massachusetts General Hospital (MGH) investigators discovered the mechanism by which obesity increases inflammation and desmoplasia - an accumulation of connective tissue - in the most common type of pancreatic cancer. In their report, published online in The discovery of cancer , the researchers describe how interactions between fat cells, immune cells and connective tissue cells in obese people stimulate a micro-environment that promotes the progression of the tumor, while blocking the response to chemotherapy. They also identify a treatment strategy that can inhibit the process.

"We evaluated the effects of obesity on many aspects of tumor growth, progression and treatment response in several animal models of pancreatic ductal adenocarcinoma and confirmed our findings in samples from patients cancer, "says Dai Fukumura, MD, PhD, of the Steele Laboratory biology of the tumor in the MGH department of radiation oncology, co-lead author of the study." Along with the research that obese mouse tumors or patients had high levels of adipocytes or fat cells and desmoplasia, two tumors fuel growth and interfere with treatment response, we also identified the underlying cause. "

Pancreatic adenocarcinoma ductal (PDAC) is the fourth leading cause of cancer death worldwide, and more than half of patients diagnosed with PDAC are overweight or obese. Among patients with PDAC, more obesity than double the already high risk death. Previous research by the MGH team and others have shown that PDAC is characterized by high desmoplasia - a tissue overproduction of extracellular matrix by pancreatic stellate cells - which promotes both survival and cell migration cancer and blocks the penetration of chemotherapeutic drugs in tumors. Obesity itself is known to contribute to desmoplasia, with the expansion of adipose tissue leading to inflammation and fibrosis and fat accumulation in normal pancreas, which also causes inflammation.

The experience of the team found that high desmoplasia in obese mouse models of PDAC was caused by the activation of stellate cells of the pancreas in type 1 antiogensin II receptor (AT1) Track signaling. This activation was favored by the production of interleukin-1 beta (IL-1ß) both by fat cells and immune cells called neutrophils in and around tumors. AT1 inhibit signaling with losartan, which is used clinically to treat hypertension, reduced desmoplasia and tumor growth associated with obesity and increased response to chemotherapy in the obese mouse model, but not in animals of normal weight. Analysis of human PDAC patients tumors revealed deposits of desmoplasia and fat increased only in samples from obese patients, and data from more than 300 patients showed that excess weight was associated with a reduced the response of patients to chemotherapy.

João Incio, MD, PhD, of the Steele Laboratory, lead author of the study, said: "Understanding how obesity affects pancreatic cancer can help us to identify biomarkers - such as body weight and increased fibrosis levels of the tumor - that can identify patients who AT1 blockers or IL-1 antibodies would be more beneficial. Since FDA approved versions of the two agents are readily available, this strategy could be easily translated into the clinic. In addition, the body weight of incorporation in the design of preclinical studies may better reflect the lack of response to conventional chemotherapeutic drugs. "

author

Co-principal Rakesh K. Jain, PhD, director of the Steele Laboratory, added:" With the majority of patients with pancreatic cancer overweight or obese at diagnosis, uncovering potential therapeutic targets in the mechanisms linking obesity with poor cancer prognosis is the first step towards the development of remedies that could disrupt that association and to significantly improve patient outcomes. Targeting inflammation and fibrosis holds the promise of improving clinical outcomes for this large group of cancer patients. "

Iron scientists launch of the new initiative of £ 6 million to find better ways to prevent cancer

Iron scientists launch of the new initiative of £ 6 million to find better ways to prevent cancer -

Scientists from the University of Queen help lead a new initiative of £ 6 million to find better ways to prevent cancer.

new initiative, led by Cancer Research UK with investments of the BUPA Foundation matching aims to support advanced research to find better ways to prevent cancer.

It is estimated that more than four out of ten cases of cancer could be prevented by lifestyle changes, such as not smoking, maintaining a healthy body weight, cut back on alcohol, healthy eating , staying active and staying safe in the sun.

Professor Frank Kee, who heads the UKCRC Centre of Excellence for Public Health Research in Northern Ireland at Queen's University, was invited to join the International Advisory Board (IAB) of the prevention initiative of the new cancer Research UK / cancer Foundation Bupa.

Professor Kee, the School of Medicine, Dentistry and Biomedical Sciences at Queen's, said: "advance knowledge and change lives is at the heart of what we do at the University Queen. I am honored to be part of this initiative to do so. It is a tribute to the CRUK BUPA and a bold new initiative like this has been developed. It shows how key donors want to support the science of prevention and the value they place in the kind of collaborations between disciplines that are necessary for the fight against cancer. Capacity building in this area is essential if new discoveries are always translate into better outcomes for patients and the population. "

" I am delighted to have the opportunity to work with Professor Linda Bauld, the new Cancer Research UK Champion and prevention with the IAB, and I am delighted to see the fruits of this initiative in the coming years. "

Professor Kee also spoke of creativity in science in the last week of first event sandpit" for the new Cancer Research initiative UK / Bupa Foundation cancer prevention in Oxford.

quarry allowed early career researchers across the country from a variety of backgrounds to work with research users and stakeholders to generate new ideas that could lead to new interventions for cancer prevention.

Dr Helen Coleman, Cancer Research UK Fellow and professor at UKCRC Centre of Excellence to the Queen joined the "sandbox" as one of the mentors and facilitators for participants early career researchers was able to share her experience working within different disciplines to conduct new term prospects in the science of prevention.

Molecule thought to indicate cancer prognosis may have dark side, research shows

Molecule thought to indicate cancer prognosis may have dark side, research shows -

A molecule that during the last 20 years was supposed to be a good prognostic indicator in tumors has been shown to have a dark side by new research from the universities of Manchester, Athens and collaborators, published recently in Nature Cell Biology .

The molecule p21WAF1 / Cip1 (p21 or for short) is often found in combination with a so-called "master tumor suppressor" p53. That gave doctors traditionally an indication that there is a good prognosis for cancer -. The presence of p21 indicating that the p53 tumor suppressor will lead to a less aggressive tumor

However, the new study presented evidence that turns this assumption on its head. Scientists from the University of Manchester, part of the Manchester Cancer Research Centre, together with international collaborators, especially at the University of Athens, has shown that in tumors where p53 molecule is deficient, p21 dramatically increases ability of tumors to grow and spread in the body

Professor Paul Townsend, one of the lead authors and lead author, Professor Vassilis Gorgoulis, honorary professor at Manchester, and the teacher- Director, University of Athens, said :. "There are years being exposed to much sun was thought to be one of the best ways to be healthy before we realized the harmful effects of too much could have.

"This protein has a similar effect. When the wild type p53 activity is lost, the excess of p21 production was far from good. This protein was previously thought benign turns out to have a dark side. "

The results are the result of five years' study in p21, originally, to develop treatments that increase its presence and Supress tumors. While conducting this investigation, international research team noted that in the p53 deficient tumors increased p21 was done correlate aggressive behavior. this led them to suspect a different opportunity of how the molecule worked in tumors.

in reality, p21works by deregulate DNA replication machinery and trigger what is called replication stress. this causes genomic instability, a key characteristic of cancer.

new findings open the possibility of treatment being developed that against p21, an avenue of research that has not been explored before

teachers Townsend added: ". We now know that p21, p53 triggered when control is a factor in the appearance of danger signs of replicating cells found in aggressive tumors. Although it goes against what we have known to date, it offers the hope of developing new treatments for cancer in the years to come. "

Genetic testing in melanoma: an interview with Dr. Diane McDowell, US Medical Affairs Lead, Oncology GSK

Genetic testing in melanoma: an interview with Dr. Diane McDowell, US Medical Affairs Lead, Oncology GSK -

Interview by April Cashin-Garbutt , BA Hons (Cantab)

insights of industry Dr. . Diane McDowell US medical Affairs Lead, Oncology GSK

please can you give a brief history of genetic tests?

Genetic testing, commonly used process of looking for changes in genes or chromosomes of a person that may be associated with diseases or specific conditions ⁱ predates President Richard Nixon declared war against cancer with the passage of the 1971 National cancer Act ⁱⁱ

the first genetic tests helped to detect abnormalities in genes unique causing rare inherited disorders such as cystic fibrosis ⁱⁱⁱ , sickle cell anemia and Tay-Sachs disease. ^iv in the 1980s, researchers began to better understand the role of genes in cancer ^v , with the first genetic test for breast cancer and ovarian cancer being introduced in the mid 190s ^vi

in recent years, the variety of tests has greatly expanded. ⁱⁱ With genetic testing today, medical professionals can determine the risk of developing certain diseases a person, confirm suspected diagnosis, detect when an individual can pass a genetic mutation to its children, or filter out patients who are unlikely to respond to certain therapies ⁱ for diseases such as melanoma.

What conditions is an available genetic test for?

Today, genetic testing is available for more than 2,000 rare and common diseases. ^viii Although oncology is an area that has received a significant amount of attention and research funding, experts predict that in the long term, immunology, central nervous system diseases infectious and cardiovascular disease are active research areas in the field of genetic testing and personalized medicine.

Why is the application of genetic testing for melanoma occurred most recently?

over the past 20 years, growth in the knowledge of the molecular biology and cancer genetics has not only enriched our understanding of how tumors develop, but we also taught that each tumor is the same. We have known for some time that genetic mutations can affect the way cells grow and divide. Some mutations can cause cells to grow out of control, which can lead to cancer. ⁱ

In order to apply genetic testing for melanoma, it was necessary to first gain an understanding of the genetic mutations associated with this particular illness. 02 marked a turning stage IV melanoma point when "Mutations in the BRAF Gene gene in human cancer" was published in the journal Nature . ^viii

The research, funded by the Cancer Genome Project Trust Sanger Institute Wellcome, studied the MAP kinase (MAPK) and describes the somatic activating mutations of the BRAF protein in melanoma ^ix , allowing cancer cells to grow and spread. Thank you to these early research, we can now genetically differentiate at least three subtypes of tumors associated with melanoma, the most common being those with BRAF V0 mutations.

Can tests genetic current for melanoma to determine the two types of mutations - inherited and acquired

cancers such as melanoma may be inherited (germline) mutations or those somatic, or acquired environmental factors ;? still other mutations may have no identifiable cause. ^x

The research identified high-risk susceptibility genes thought to be associated with melanoma, including CDKN2A, CDK4 and associated BRCA1 protein (BAP -1). ^xi Although the test is available to determine germline mutations in CDKN2A, ^xii such mutations are rare ^xiii and there are no clinical utility clear for this. Test

There are two main molecular signaling pathways that can contribute to somatic development of melanoma. activated protein kinase mitogen (MAPK) pathway and the phosphoinositide 3-kinase (PI3K) paths ^xiv As mentioned above, the MAPK pathway, which is dysregulated in many melanomas, contains genes such that BRAF and RNA that may be somatically mutated. ^xv

About half of all people with metastatic melanoma have a BRAF V0 mutation. BRAF V0E mutations V0K and represent approximately 70 percent and 23 percent, respectively, of patients with V0 mutation, ^xvi and can be detected in a tumor through genetic testing. Such a test approved by the FDA is the THxID® - BRAF, for which GSK has worked with the in vitro diagnostics company bioMérieux.

What percentage of melanoma cases are caused by acquired mutations linked to sun exposure?

Over 0 percent of melanoma cases have been linked to sun exposure. ^xvii Only about 10 percent of melanoma cases can be attributed to germline genetic mutations that are passed through a family from generation to generation. ^{xviii xix}

At what stage are genetic tests for melanoma usually done?

The National Clinical Practice Guidelines in Oncology Comprehensive Cancer Network® recommend for melanoma genetic testing be performed at diagnosis of metastatic melanoma.

If a health care provider contemplates the treatment of a patient with a metastatic melanoma with a targeted therapy, they must be tested to determine if their tumor shows a mutation in the gene.

once the melanoma mutation of a patient has been identified, they may find that they are a candidate for a targeted therapy with this particular mutation. ^xx

What genetic testing results can have impact?

Patients receiving a positive diagnosis for a specific mutation in their melanoma tumor can work with their doctor to identify specific targeted therapies that may be available and decide on a treatment plan that is best for them.

a better understanding of the molecular basis of melanoma presented a great opportunity for new and more targeted approaches for the treatment, reducing the number of patients who can not take real advantage for therapy.

combinations of targeted therapies, such as combining Tafinlar® (dabrafenib) and Mekinist® (trametinib) which was approved by the FDA in January 2014, will be an important part of the personalized medicine strategy results from genetic testing.

what do you think the future for genetic testing in melanoma and how GSK plan to add to that?

Our belief is that science and technology continue to evolve, the future of genetic testing to expand beyond a single test for a single transformation to a multi-complexed evaluate an approach large number of genes simultaneously.

One of the biggest breakthroughs in technology terms is the reduction of the execution time and the cost of sequencing, which may eventually help to identify other genes of interest to inform personalized treatment for patients.

genetic test will also have a greater role in the pharmaceutical industry R & D, as well; a 2013 analysis by McKinsey found that, at present, almost half of active preclinical and Phase I in the pharmaceutical pipeline associated the diagnosis, especially in oncology, immunology and CNS. Oncology is one of the most active areas of research for genetic testing and personalized medicine. ^xxi

When we Tafinlar® (dabrafenib) and Mekinist® (trametinib) on the market, we took a very scientific approach and focus combined agents in phase I before receive confirmation of Phase II data. We now see this trend continues, with mixed programs that start much earlier in Phase I.

At GSK, we design studies of populations with very specific patient in mind that most of chance to get some kind of therapeutic benefit. At the heart of this ensures that we can effectively identify these patients using the right type of diagnosis.

About Dr. Diane McDowell

Diane McDowell, MD was a Howard Hughes Scholar at the State University of Pennsylvania, where she earned a Bachelor of Science in Microbiology . She also received a medical degree from the School of Medicine at Temple University.

After medical school, Diane completed a general surgery residency at the Medical School and a fellowship in surgical oncology at Fox Chase Cancer Center of the University of Tulane.

After a year in private practice as a general surgeon and breast cancer, Diane moved to Bristol-Myers Squibb, where she worked as Director of US Medical Affairs focusing on the breast and cancer liver.

she served as the European headquarters BMS temporary illness Zone Head for Oncology in the EU markets on melanoma and CML before moving to Global Medical Affairs, where she concentrated on lung cancer.

before joining GSK, Diane was a director of global clinical research at Bristol-Myers Squibb and was responsible for melanoma and lung cancer trials.

Currently, Diane is the leader of medical affairs in the United States for both Tafinlar® (dabrafenib) and Mekinist® (trametinib) for GSK.

A native of Pittsburgh, Pennsylvania, Diane now lives in Philadelphia with her husband and son.

where readers find more information?

For more information on genetic testing in cancers like melanoma, there are a number of organizations with useful information, including the National Cancer Institute of the National Institutes of Health and the National Institute for human genome research at the National Institutes of Health.

ⁱ American Cancer Society. "The genetic testing for cancer: What you need to know." Http://www.cancer.org/acs/groups/cid/documents/webcontent/002548-pdf.pdf. Accessed Page 2 March 17, 2014.
(p.2), paragraph 2, 1-3 lines.
(p. 2.3) Pages 2-3, paragraphs 3-12.
(p.1) Page 1, paragraph 5, 1-3 lines.

ⁱⁱ National Cancer Institute. "1971 National Cancer Act" http://dtp.nci.nih.gov/timeline/noflash/milestones/M4_Nixon.htm. Accessed Page 1 June 9, 2014.
(p.1) paragraph 3, lines 1-4.

ⁱⁱⁱ National Institute for Human Genome Research. "genetic testing rules." Http://www.genome.gov/10002335. Accessed Page 1 June 9, 2014.
(p.1), paragraph 3, lines 1-2.
(p.1) Page 1, paragraph 3, lines 2-5.

^iv science Progress. "A brief history of genetic testing." Http://scienceprogress.org/08/05/a-brief-history-of-genetic-testing/. Accessed Page 2 June 9, 2014.
(p.2), paragraph 2-4.

^v Cancer Research UK "Stalking the BRCA genes." http://scienceblog.cancerresearchuk.org/2012/02/28/high-impact-science-tracking-down-the-brca-genes-part-1/. Accessed June 9, 2014.
(p 2) Page 2, paragraph 7, lines 1-2

^iv Myriad Genetics "Brief History of Myriad." Https .: //www.myriad.com/about-myriad/history/. Accessed June 9, 2014.
(p. 1) Page 1, paragraph 4, lines 1-2

^vii Fact sheet "NIH genetic Testing :. How it is used for Healthcare. "Http://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=43. Accessed June 9, 2014.
(p. 1) Page 1, paragraph 6.

^viii Nature. "Mutations of the BRAF gene in human cancer." Http://www.ncbi.nlm.nih.gov/pubmed/22453012. Accessed June 9, 2014.

^ix Fricker, J. "new era in metastatic melanoma" Molecular Oncology .
(p. 2) Page 2, right column, paragraph 7.

^x American Cancer Society. "What changes?" http://www.cancer.org/cancer/cancercauses/geneticsandcancer/oncogenesandtumorsuppressorgenes/oncogenes-tumor-suppressor-genes-and-cancer-what-are-mutations. Accessed June 9, 2014.
(p.1) Page 1, paragraphs 3-4.

^xi Gangadhar, Tara., Schuchter, Lynn. "Explosion recent progress in melanoma mangament catalyst for change in the future direction of research" 1. June 2014. http://am.asco.org/recent-explosion-progress-melanoma-management-catalyst-change-future-directions-research. Accessed on page 2 9 June 2014
(p. 2), paragraph 4, lines 1-6.

^xii National Cancer Institute. "Cancer Genetics skin." http://www.cancer.gov/cancertopics/pdq/genetics/skin/HealthProfessional/page4#Section_393~~number=plural. Accessed June 9, 2014.
(p. 14) Page 14, paragraph 5, line 1.

^xiii Robert, C. Rouiller, J., C. Kannengiesser et al. "Study of BRAF mutations in melanoma and nevi mutation patients germline CDKN2A gene in the" Journal of Clinical Oncology. 06 . http://meeting.ascopubs.org/cgi/content/short/24/18_suppl/10075.Accessed June 16, 2014.

^xiv Vultur A, J Villanueva , Herlyn M. "targeting BRAF in Advanced melanoma: a first step towards Manageable disease." Clin Cancer Res 2011: 1658 :. 63
(pp. 1658) page 1658, left column, paragraph 2.

^xv Banerji, U., Affolter, A. Judson, I., et al. "BRAF mutations and RNA in melanoma :. potential relationship to clinical response to HSP0 inhibitors". Mol Cancer Ther 08.
(p.1) Page 1, right column, paragraph 2.

^xvi JA Jakob, RL Bassett, CS Ng , et al. "State NRAS Mutation is an independent prognostic factor in metastatic melanoma." Cancer. 2012; 4014-23.
(p.3) Page 3, Table 1, Line3-4.

^xvii Kumar, K., Angelini, S., Czene, K. "BRAF mutations in melanoma metastatic A possible association with clinical outcome." Clin Cancer Res . August 9, 03; 3362
(p.1) Page 1, right column, paragraph 3, lines 2-4

^xvii American Cancer Society. "Oncogenes, tumor suppressor genes, and cancer." Http://www.cancer.org/acs/groups/cid/documents/webcontent/002550-pdf.pdf. Accessed April 18, 2014.
(p. 2) Page 2, paragraph 4, line 1.

^xix American Cancer Society. "The melanoma skin cancer." Http://www.cancer.org/acs/groups/cid/documents/webcontent/0030-pdf.pdf. Accessed April 18, 2014.
(p.8 ) Page 8, paragraph 8, lines 2-3

^xix Cancer Network NCCN comprehensive national clinical practice Guidelines in oncology (NCCN Guidelines®):... Melanoma version 3 ;. 2014
Pages E-ME, MS-7, MS-15 and MS-16

^xxi McKinsey and Company. "personalized medicine :. The way forward ".
(p.2) Page 2, paragraph 5, lines 8-9

Connectome imaging may help predict the severity of language deficits after stoke

Connectome imaging may help predict the severity of language deficits after stoke -

loss or impairment of the ability to speak is one of the most feared complications of race - a face of about 20% of stroke patients. Language, as one of the most complex functions of the brain, are not sitting in a region of the brain only, but involves linkages between many areas.

In an article published in the June 22, 2016 issue of Journal of Neuroscience , researchers at the Medical University of South Carolina (MUSC) and the University of Carolina South (USC) report that the mapping of all connections of white matter of the brain after a stroke, in addition to the imaging of areas of cortical tissue lesions, could better predict which patients will have language deficits and severity of these deficits will. All brain connections is called connectome.

"Imaging the connectome patients after stroke allows identification of individual signatures brain organization that can be used to predict the nature and severity of language deficits and could one day be used to guide the treatment, "said neurologist MUSC Health Leonardo Bonilha MD, Ph.D., lead author of Journal of Neuroscience article, whose laboratory focuses on connectome imaging, in particular as regards loss language after a stroke. Grigory Yourganov, Ph.D., is the first author of the article. Julius Fridriksson Dr. Chris Rorden, Ph.D., and Ezequiel Gleichgerrcht, Ph.D., researchers from aphasia at USC who recently received funding from the NIH to establish a center for the study aphasia recovery and which are longtime collaborators laboratory Bonilha, are also authors of the paper.

This study is one of the first to use the whole brain connectome imaging to examine how disruption of white matter connectivity after stroke affect language abilities. White beam material fibers are insulated son that connect an area of ​​the brain other. The white matter is referred to the myelin sheath (insulation) covering many axons (son) that make up the fiber bundles.

"If you have two areas of the brain and both of them have to work together to perform a function and the injury of the race takes the axons that connect these areas of the brain - the two areas are intact but the communication between them is disturbed and therefore there is a malfunction, "said Yourganov

Currently, structural magnetic. resonance imaging (MRI) is used after stroke to assess the damage in the cortical tissue - the gray matter of the brain. However, the extent of cortical damage often does not match the severity of language deficits.

"stroke patients often have significant impairments in excess of the amount of cortical damage," said Bonilha. "It is also difficult to predict how a patient will recover according to the single cortical lesion. "

-based Connectome imaging could be a useful addition to the evaluation of damage to brain connections after stroke and to guide rehabilitation therapy?

the study by Bonilha has taken an important first step towards answering these questions. the study, which enrolled 0 patients to MUSC and USC aphasic because suddenly occurring not less than six months before, evaluated four areas related to speech / language using the Western aphasia Battery - speech fluency, listening comprehension, repetition word, and the designation orally. - as well as an executive summary of the global aphasia Within two days of evaluation behaviors, each of the patients underwent imaging studies -. Both T1- and T2-weighted MRI, generally used after stroke to map cortical damage and diffusion imaging, used for mapping connectome

The team then used a type of machine learning algorithm - Support vector regression (SVR) - for analyzing imaging results and make predictions about the language deficits of each patient. In essence, an algorithm was created that could make the WAB score is a relevant characteristic imaging damage to the gray matter by structural MRI or relevant feature for imaging Connectome white bundles of fibers of the material brain . The team used 89 of the 0 patients as training sets for SVR and then used the algorithm to predict default language / conservation at the 0th patient. This was done for each of the 0 patients and each patient, for both structural features identified by MRI and imaging connectome.

The prediction accuracy of the WAB scoring algorithm for each patient was then evaluated by comparing the result determined by the WAB behavioral tests. Connectome-comparative analysis was as accurate as the mapping of the cortical lesion to predict the scores of WAB. In fact, it was better predict the auditory comprehension scores than was based imaging lesions using structural MRI, and only slightly less accurate in predicting speech fluency, word repetition, and naming scores .

The study demonstrates that the damage to the white matter bundles of fibers that connect brain regions play a role beyond cortical lesions in language disorders following stroke. In addition, this study also found that the connections in the parietal region of the brain are particularly important for the function of language, in particular mastery. This region is less likely to suffer damage after a stroke, even in patients who suffer from aphasia, suggesting that damage or preservation of brain connections in the region could play a key role in determining who experience aphasia and who will have the best chances of recovery. The integrity of these connections can not be mapped to the vector structural MRIs, but can now be evaluated using a connectome comparative analysis. Suggests

The results of the study that the connectome comparative analysis could be used to inform a more individualized approach to stroke care. Because the algorithms developed using these patients in the study as a whole training are generalizable to a larger population of the race, benchmarking connectome-could one day be used to identify the distinctive features of the race each patient - which connections were lost and preserved-- and the algorithm can be used to predict the type and severity of language and the recovery potential problems. This information could then be used to direct rehabilitation therapy to improve outcomes.

"For much more accurately mapping the individual pattern of structural brain connectivity in a stroke survivor, we can determine the integrity of neural networks and to better understand what has been wronged and how it refers to language skills that are lost, "said Bonilha." This is, broadly stated, a measure of brain stroke health. It is the reason individual signature could also be used to inform the Custom potential for recovery with treatment and therapy guidance to focus on deficient network components. "

effects of palliative care for the first makers of medical study of its kind survey, caregivers

effects of palliative care for the first makers of medical study of its kind survey, caregivers -

Shannon Carson, MD, professor of medicine and chief of the division of pulmonary diseases and Critical Care Medicine at the UNC School of Medicine and co-principal investigator Judith Nelson, MD, JD, at Memorial Sloan Kettering Cancer Center, and Christopher Cox, MD, of Duke University, conducted a four-year term the first-of its kind clinical study on the effects of palliative care for medical decision makers.

results, published July 5 in the Journal of the American Medical Association ( JAMA ) show that intensive care units in New York and Carolina North hospital, where the study was conducted, communication condition and family support that was at least as adequate as specialized interventions (palliative care) for families of chronically ill patients in the intensive care unit. The researchers focused on the study of the psychological distress of caregivers and decision makers for patients with chronic serious illness, which is defined as dependence on a respirator for more than a week.

"We have long known that patients experiencing chronic severe disease have a very difficult time because of complications of their disease, long dependence on life support, and long hospitalizations," said Carson.

These things also make it difficult and stressful for family members, caregivers, and policy makers -. which are often the same people

"It is very disruptive to their lives and work, and - to complicate matters even more - we rely on them to help a lot of -Make decision. It is very stressful for family members, "said Carson. "As a critical care physicians, we sometimes worry that we do not provide or are not able to provide the support and information that families need to help this decision in the most effective ways. "

In trying to determine what could be done to keep families better informed and possibly reduce the associated stress and relieve anxiety, Carson examined whether providing support for palliative care specialists would be beneficial . Participants in the study were randomized 365 families makers for 250 ICU patients with chronic severe disease

"We were hoping to have families come together with palliative care doctors. - At least a few once -would help families cope better down the line, "said Carson. "And so two family members randomized us meet the doctors and nurses in palliative care during the illness of their family member, or they received usual care, all the information they received was of critical care clinicians. - doctors and nurses

"what we found is that there was no advantage to having these additional meetings with clinicians in palliative care. We found that the support and communication provided by the ICU team was quite good. We concluded that if it was an interesting idea and I hope useful, for now it seems that the support from intensive care physicians regular is at least as adequate as the additional support of palliative care " said Mr. Carson.

In addition, no difference was observed in the number of days a patient was in the hospital or the patient time spent on a ventilator or other therapeutic interventions.

"as an intensivist, I find that to be a positive conclusion," he said. "We are at least as good as the gold standard in this context. He reassured. While we can always do better in communication, we at least do as well as anyone can. We will still need to consult the palliative care for difficult situations, but routine consultations for all chronically critically ill patients will not be necessary. "

Loyola, ABHS partner to expand pediatric services in the Chicago area

Loyola, ABHS partner to expand pediatric services in the Chicago area -

Alexian Brothers Health System (ABHS) Arlington Heights, Ill., And the health system Loyola University (Loyola) of Maywood, Ill., have partnered to expand the scope and reach of their lines of pediatric services in the Chicago area.

This new affiliation will benefit patients by building and developing the strengths of the clinical program of each health system, making them more available to the communities we serve, said Patricia Cassidy, ABHS Vice -President and Chief strategy.

The affiliation will ABHS and Loyola to offer a full range of pediatric specialties and increase access to pediatric sub -Specialists, which can often be difficult to find, said Cassidy.

"Access to high-quality pediatric clinical programs in a coordinated care network is a vision of our two organizations share, says Daniel Post, senior vice president, Clinical Programs and Business Development Manager, at Loyola. The Pediatric Affiliates Loyola and Alexian Brothers provide patients and referring physicians to improve access to high-quality programs in their communities.

Cancer patients need better treatment for depression

Cancer patients need better treatment for depression -

By Sally Robertson , B.Sc.

the results of three research studies have shown that nearly three quarters of cancer patients with major depression do not receive treatment for their depression and a newly developed medical program has proven more effective than standard treatment in reducing depression in these patients.

As indicated in The Lancet Psychiatry , an analysis of data from more than 21,000 patients in clinics in Scotland, UK, found that the prevalence of major depression in patients cancer ranged from 6% in those with genitourinary cancer to 13% in people with lung cancer. However, nearly three quarters of patients with major depression were not receiving treatment to solve the problem.

"major depression is very common in people with cancer and the discovery may -being surprising is that most of it goes untreated, "says lead author Michael Sharpe, University of Oxford, who adds that" the result with usual care is poor. "

a second article published in the Lancet , reports on the results form the oncology-2 randomized trial SMaRT which examined the effects of a new medical program called "depression care for people with cancer" ( DCPC). This systematic program integrates the care of specialized oncology nurses and psychiatrists with the patient's cancer care involves the use of two antidepressants and psychological therapy.

trial, which involved 500 patients with major depression, but a good prognosis of cancer, showed that DCPC was significantly more effective in treating depression than standard care. . At 6 months, the severity of the depression was at least halved in 62% of those who received DCPC, against only 17% of those who received standard care

Sharpe said:

the huge advantage that DCPC provides for patients with cancer and depression shows what we can achieve for patients if we take as much care with the treatment of their depression as we do with the treatment of their cancer

another study published in the Lancet Oncology describes a version of the DCPC which was adjusted for lung cancer patients with major depression who had a bad rather than good prognosis cancer. For 32 weeks, followed by 142 patients, adjusted DCPC was considered much more effective for improving depression patients than usual care was.

"We have described a new approach to depressed cancer management patients is based on the shortcomings of usual care and integrated care against cancer, which really are quite spectacular effects in prognosis patient and also efficacy in poor prognosis patients, "says Sharpe.

Wistar Institute and its partners receive HIV treatment research grant to test new immunotherapies

Wistar Institute and its partners receive HIV treatment research grant to test new immunotherapies -

The Wistar Institute is pleased to announce that the National Institutes of Health (NIH) has awarded a nearly $ 23 million Martin Delaney Collaboratory for issuing cure HIV research at BEAT HIV: Delaney Collaboratory to cure HIV-1 infection in combination immunotherapy (BEAT HIV Delaney), a consortium of top HIV researchers led by co PIs Luis J. Montaner, DVM, D.Phil. , director of the HIV-1 Immunopathogenesis laboratory at Wistar Institute Vaccine Center and James L. Riley, PhD , Professor research associate at the Perelman School of Medicine at the University of Pennsylvania.

BEAT HIV Delaney Project based in Philadelphia is one of six grants from the Delaney initiative, joining a very select group of teams to advance global efforts aimed at the develop a remedy against the US HIV. The five-year award promotes a partnership of preeminent over 30 major HIV researchers at The Wistar Institute, the University of Pennsylvania, Philadelphia FIGHT, Rockefeller University, VA San Diego Healthcare System, Johns Hopkins University, the University of Nebraska-Lincoln and the University of Utah working with government, non-profit, and industry partners to test combinations of several novel immunotherapies in new pre-clinical research and clinical trials.

with 37 million people currently living with HIV worldwide and 17 million antiretroviral therapy reception, Martin Delaney Collaboratory cure for HIV research initiative reflects the interest in seeking treatment of HIV that has grown into a global priority over the last five years and follows the call of President Obama to increase research HIV treatment.

"stigma, economic burden on society, pressure on health care resources, and pure toll on human life throughout the world makes finding a cure an absolute priority," Montaner said. "Together, we rely on established efforts of our teams to go forward and make the next stages of transformation which bring us an HIV cure."

Three Pillars Research
integration three distinct areas of study objectives BEAT HIV Delaney project are to investigate where HIV hides after clinical strategies and test new treatment for a cure for HIV eliminating the hidden virus. The first area of ​​study or "pillar" will determine where and how HIV hides so that researchers can better assess whether the proposed clinical strategies can eradicate the virus. This pillar connects three research teams will measure HIV in the body, how HIV persists after treatment, access new areas in the body that have not been studied before where HIV can hide, and distinguish HIV by "fingerprinting" or "barcoding" to determine the fate of each infected cell. The research team BEAT HIV Delaney plans to develop clear criteria for evaluating the reduction of the virus beyond what is measured in the clinic.

The second pillar focuses on boosting the immune system with which we are all born (innate immunity) through a combination immunotherapy approach using highly potent antibodies against HIV with interferon pegylated alpha 2b. The researchers plan to conduct the first human clinical trial combining these two treatment strategies (which were tested separately and showed activity in reducing HIV in humans) with the hope that the innate immune system boosted power with unique antibodies to target cells infected with HIV will achieve greater reductions in HIV than seen previously. In addition, researchers will seek to develop new DNA-based delivery systems that can make administering HIV treatment easier and more effective by transfusions.

The third pillar will bring together two promising gene therapy strategies independently tested in humans, with the goal of engineering, growth and administration of killer cells which are entitled only to find and kill cells infected with HIV. The proposed gene therapy strategy is based on the success of small human trials of killer T cells (chimeric Antigen Receptor [CAR] T cell therapy). Previous studies have shown that killer T cells can be generated and administered safely. The research team will repeat the studies and for the first time to save the new killer cells to attack by HIV when "activated" by removing the CCR5 protein. The HIV virus needs this protein to infect and kill the killer cells, removing it can "protect" killer cells so they can continue to proliferate and kill cells infected with HIV. The ability of cells not to be affected by HIV in the absence of CCR5 has been shown clinically, but this strategy has not yet been attached to the gene therapy in the manufacture of killer cells.

"The results of this trial are expected to show for the first time that the long-term effects of these killer cells can be looking and the eradication of HIV," said Riley.

Scientists identify a new sustainable approach to make more stem cell cord blood

Scientists identify a new sustainable approach to make more stem cell cord blood -

The international scientific community of stem cells, co-led in Canada by Dr. John Dick and the Netherlands by Dr. Gerald de Haan, discovered the switch to leverage the power of cord blood and potentially increase the supply of stem cells for cancer patients requiring transplantation therapy to fight against their disease.

conclusions proof of concept, published online today in Cell Stem Cell (http://dx.doi.org/10.1016/j.stem.2016.06.008) provide a viable new approach to make more stem cells from cord blood, which is available through public cord blood bank, said the co-principal investigator John Dick, Senior scientist, Cancer Centre Princess Margaret, University Health Network (UHN). Dr. Dick is also a Professor, Department of Molecular Genetics, University of Toronto and holds a Canada Research Chair in Stem Cell Biology. The co-principal investigator on the cells was scientific Gerald Haan strains, Co-Scientific Director, European Institute of Biology of Aging, University Medical Center Groningen, the Netherlands. Dr. Dick talks about their common search https://youtu.be/cpEmKnjkb9s.

"Stem cells are rare in cord blood and often there is not enough present in a typical collection to be useful for human transplantation. the aim is to find ways to make more of them and allow more patients to make use of the therapy of blood stem cells, "says Dr. Dick." Our discovery shows a method that could be exploited over the long term in a clinical therapy and we took advantage of cord blood is collected in various public banks that are now growing across the country. "

Currently, patients need a stem cell transplant are paired with an adult donor immune system is compatible with services of international registry. But around the world, thousands of patients are unable to get stem cell needed to fight against blood cancers like leukemia because there is no donor match.

"About 40,000 people receive stem cell transplants every year, but this represents only about a third of patients who need this therapy," says Dr. Dick. "That's why there is a big push in research to explore the cord blood as a source because it is readily available and increases the possibility of finding tissue matches. the key is to develop cells from cord blood stem for many more samples available answer this need. And we're making progress. "

Although there is much research on the expansion of the few stem cells in cord blood, Dick de Haan teams took a different approach. When a stem cell divides it makes a lot of progenitor cells immediately downstream that retain key properties to be able to develop in each of the 10 types of mature blood cells, but they lost the critical capacity for self-renewal (keep on the replenishment of stem cell pool) that all true stem cells possess.

in the laboratory, analysis of mouse and human models of blood development, the teams discovered that microRNA (TRIM-125a) is a genetic switch that is normally in the cells stem and control self-renewal ; it normally goes off in progenitor cells.

"Our work shows that if we throw artificially switch in these cells downstream, we can equip them with stemness and they essentially become stem cells can be maintained in the long term," says Dr. Dick

in 2011, Dr. isolated Dick a human blood stem cell in its purest form. - as a single stem cell capable of regenerating the entire blood system, providing a more detailed system roadmap development of human blood, and opening the door to capture the power of these life-producing cells to treat cancer and other debilitating diseases more effectively.

FDA approves use of Imbruvica to treat patients with chronic lymphocytic leukemia

FDA approves use of Imbruvica to treat patients with chronic lymphocytic leukemia -

The Food and Drug Administration of the United States today expanded the use approved Imbruvica (Ibrutinib) to treat patients with chronic lymphocytic leukemia (CLL) which carry a deletion in chromosome 17 (17p deletion), which is associated with poor response to standard treatment for CLL. Imbruvica received a breakthrough therapy designation for this use.

The FDA also approved new labeling to indicate the Imbruvica clinical benefit in CLL treatment was verified. In February 2014, Imbruvica received accelerated approval to treat CLL based on its effect on the overall response rate. New results from clinical trials examining the progression-free survival and overall survival confirmed the clinical benefit of the drug.

One type of non-Hodgkin lymphoma, CLL is a disease of the rare bone marrow blood and bone that usually gets worse slowly over time, causing a gradual increase in the number of white blood cells, lymphocytes B cells or B. the National cancer Institute estimates that 15.720 Americans will be diagnosed and 4,0 will die of CLL in 2014. Imbruvica works by blocking the enzyme that allows cancer cells to grow and divide.

"We continue to see progress in the availability of therapies to treat chronic lymphocytic leukemia, especially for people in difficult to treat patients," said Richard Pazdur, MD, director of the Office of Hematology and oncology Products in the FDA's Center for evaluation and drug research. "Imbruvica is the fourth drug approved to treat CLL who received a breakthrough therapy designation, reflecting the promise of advanced therapy designation program and demonstrate the commitment of the FDA to work collaboratively with companies to speed the development, review and approval of these important new medicines. "

the other three drugs approved to treat CLL who received the breakthrough designations are Gazyva (obinutuzumab) in November 2013, Arzerra ( ofatumumab) in April 2014 and Zydelig (idelalisib) in July 2014. the request for accelerated approval Imbruvica to treat CLL has received advanced therapy appointment.

approval for Imbruvica actions today are based on a clinical study of 391 previously untreated participants, 127 of them had CLL with 17p deletion. Participants were randomized to receive Arzerra Imbruvica or until progression or side effects of the disease has become intolerable.

participants treated Imbruvica

The trial was stopped early for efficacy after a pre-planned interim analysis showed experienced a reduction of 78 percent in the risk of disease progression or death (survival without progression). The results also showed a reduction of 57 percent the risk of death (overall survival) in participants treated with Imbruvica. Of the 127 participants who had CLL with 17p deletion, those treated with Imbruvica experienced a 75 percent risk of disease progression or death.

The most common side effects associated with Imbruvica observed in the clinical study include low levels of platelets in the blood (thrombocytopenia), reduced infection-fighting cells called neutrophils white blood cells (neutropenia) , diarrhea, low red blood cells (anemia), tiredness, pain in the muscles and bones (musculoskeletal pain), upper respiratory tract infection, rash, nausea and fever (pyrexia) .

new use Imbruvica approved more than two months before the drug user prescription Date object fresh product of 7 October 2014, the date the FDA was expected to complete consideration of the demand for drugs . The FDA reviewed the application of Imbruvica for this new use in the review program of the Agency's priorities, which provides for an expedited review of drugs intended to treat a serious disease or condition, and, if approved, would offer a significant improvement compared to marketed products.

Imbruvica also received accelerated approval in November 2013 for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. Clinical studies to verify and describe the clinical benefit of Imbruvica in lymphoma mantle cell are underway.

Imbruvica is co-marketed by Pharmacyclics, based in Sunnyvale, Calif., And Janssen Biotech, based in Horsham, Penn.

The FDA, an agency of the US Department of Health and Human Services, protects the public health by ensuring the safety, efficacy and security of human and veterinary drugs, vaccines and other biological products for human use and medical devices. The agency is also responsible for the safety and security of supply of our nation food, cosmetics, dietary supplements, products that emit an electron beam and regulation of tobacco products.

Scientists capture new calcium molecules shuttle pictures related to aggressive cancers

Scientists capture new calcium molecules shuttle pictures related to aggressive cancers

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new scientific images have captured a molecule of calcium shuttle that has been linked to aggressive cancers. The three-dimensional structure may help researchers develop new therapies and diagnostic tools for diseases that are caused by a malfunction in calcium absorption.

The laboratory Alexander Sobolevsky at Columbia University Medical Center studied a family of proteins called "transient receptor potential (TRP)" channels. These proteins line surfaces within the body, such as the intestine and forming pores that allow calcium through a dense barrier lipids and proteins called the membrane to reach the interior of the cell.

"scientists have discovered a variant of TRP channel, called TRPV6 is present in excessive amounts in the tumor cells of certain cancer patients, "says lead author Alexander Sobolevsky, PhD, is assistant professor in the Department of molecular biophysics and Biochemistry at Columbia University Medical Center. "And patients who have higher amounts of TRPV6 seem to have a more aggressive form of the disease."

To discover how these guide calcium channel in the cell, and how the disease can occur when this process becomes unregulated laboratory Sobolevsky used a technique called X-ray crystallography This process involved growing crystals of TRPV6 and exposing them to a X-ray beam scientists then used the diffraction pattern produced by X-rays to map a 3D model of the protein

structure - . Which represents a unique frozen canal - reveals that the pore TRPV6 surface is lined with negative charges. This configuration helps to attract calcium ions, which are positively charged. Calcium ions are then mixed to a location inside the pore, up to three molecules at a time, as they pass through the cell.

"In the future, we could use this model to design drugs that can target certain types of tumor cells by plugging TRP channels on their surfaces," says Sobolevsky.

usually, calcium ingested from our food is used by the body to regulate a variety of processes, including the heartbeat, muscle twitching, and signaling the brain. In addition to various forms of cancer, the modified calcium absorption and TRPV6 expression has also been associated with Crohn's disease and kidney stone disease in mouse models. Further research is needed to determine the extent of modification of the TRP channel activity leads to disease progression.

The TRPV6 structure was published in a recent issue of Nature .

The mice lacking specific protein live longer lives with less disease related to age

The mice lacking specific protein live longer lives with less disease related to age -

While developing a new drug against cancer, researchers the Wistar Institute have discovered that mice lacking a particular protein are living longer lives with less age-related diseases. Mice that lack the TRAP-1 protein, showed less degeneration age-related tissue, obesity and the formation of spontaneous tumors compared to normal mice. Their findings could change the way scientists consider the metabolic networks in cells.

In healthy cells, TRAP-1 is an important regulator of the metabolism and has been shown to regulate the production of energy in the mitochondria, organelles that chemically produce useful energy for the cell. In the mitochondria of cancer cells, TRAP-1 is universally surplus.

The report of the Wistar team, which appears in the journal Cell Reports (available online), shows how mice "knockout" high to lack the protein Trappist 1 offset this loss by switching to alternative mechanisms for cellular energy.

"We see this amazing change in TRAP-1 knockout mice, they showed fewer signs of aging and are less likely to develop cancer," said Dario C. Altieri. MD, and Robert Penny Fox Distinguished Professor and Director of the Centre National cancer Institute designated cancer of the Wistar Institute. "our findings provide unexpected explanation of how TRAP-1 and related proteins regulate metabolism within our cells."

"We usually are connecting the reprogramming of metabolic pathways with human diseases such as cancer," said Altieri. "what we did not expect to see mice were healthier with fewer tumors."

Altieri and colleagues created knockout mice TRAP-1 as part of their ongoing investigation into their new drug, Gamitrinib, designed the proteins in the mitochondria of tumor cells. TRAP-1 is a member of the heat shock 0 (HSP0) family of proteins, which are "chaperone" proteins that guide the physical formation of other proteins and serve a regulatory function in mitochondria. Tumors using HSP0 protein, as TRAP-1, to help survive the therapeutic attack.

"In tumors, the TRAP-1 loss is devastating, triggering a series of catastrophic defects, including metabolic problems that result ultimately in the death of tumor cells," said Altieri. "The mice lacking TRAP-1 from the beginning, however, have three weeks in the womb for the loss of the protein."

The researchers found that, in their knockout mouse, loss of TRAP-1 causes mitochondrial proteins to misfold, which then triggers a compensatory response that causes cells to consume more oxygen and metabolize more sugar. This causes mitochondria in knockout mice to produce deregulated levels of ATP, the chemical used as a source of energy to power all molecular reactions everyday that allow a cell to function.

This increased mitochondrial activity actually creates a moderate boost oxidative stress ( "free radical damage") and damage of the associated DNA. Although DNA damage may seem cons-productive for longevity and good health, low levels of DNA damage effectively reduces the growth of cell proliferation slows down to allow natural repair mechanisms of the cell to take effect.

According to Altieri, their findings provide a mechanistic foundation for the role of chaperone molecules, such as HSP0 in regulating mitochondrial bioenergetics in cells how to produce and use chemical energy they need to survive and grow. their results explain some conflicting results in the literature concerning the regulation of bioenergetic and dramatically show how compensation mechanisms can occur when these molecules chaperones are taken out of the equation.

"Our results strengthen the case for targeting HSP0 in tumor cells, but it also opens up a fascinating range of issues that can affect the metabolism and longevity," said Altieri. "I predict that the knockout mice TRAP-1 will be a valuable tool for answering these questions."

Researchers devise transport capsule containing E. coli to help fight pneumococcal diseases

Researchers devise transport capsule containing E. coli to help fight pneumococcal diseases -

Most people recoil at the idea of ​​ingesting E. coli . But if headlines bacteria could be used to fight against the disease?

Researchers are experimenting with harmless strains of E. coli - yes, the majority of E. coli are safe and important for healthy human digestion - work for reach this goal. Specifically, they have developed a E. coli based transport capsule designed to help new generation vaccines are more effective and more efficient than current vaccines.

The research, described in (link to insert study) of the study published today (1 July) in the journal science advances , highlights the success of the capsule the fight against pneumococcal disease, an infection that can cause pneumonia, septicemia, ear infections and meningitis.

"It is somewhat ironic given you here about E. coli , but there are many strains of bacteria, most of which are quite normal in the body that have great potential in the fight against the disease, "said Blaine A. Pfeifer, PhD, associate professor of chemistry and bioengineering at the University of Buffalo School of engineering and Applied Sciences.

Pfeifer is the lead co-leader of the study author and his former student Charles H. Jones, Ph.D., who directs the marketing efforts of the biotech CEO and founder of Buffalo, New York-based startup Abcombi . Biosciences

the core of the capsule is harmless E. coli Around the bacteria, the researchers wrapped a synthetic polymer. - called poly (amino ester beta) - as a fence chain link. the positive charged polymer associated with the cell wall of bacteria responsible negatively, creating a sort of hybrid capsule.

To test the capsule, the researchers then inserted a vaccine based on proteins, was also marketed by Abcombi, designed to fight against pneumococcal disease. The results, when tested in mice, were impressive

The hybrid design of the capsule provided :.

• Both passive and active targeting of specific immune cells called antigen presenting cells that trigger an immune response.
• Natural and multicomponent adjuvant properties that enhance the body's immune response.
• dual intracellular delivery mechanisms to direct a particular immune response.
• Simultaneous production and delivery of components (antigens) needed for a vaccine.
• high vaccine protection capabilities against pneumococcal disease.

It is also relatively inexpensive to create and flexible in terms of use. For example, the capsule may be used as a delivery device of therapies that target cancer, infectious diseases of viral origin and based on other diseases.

Study reveals complex mechanisms involved in enzyme that regulates DNA replication

Study reveals complex mechanisms involved in enzyme that regulates DNA replication -

In a study published today in Genes & Development, Dr. Christian Speck of group DNA Replication MRC clinical sciences Centre, in collaboration with Brookhaven National Laboratory (BNL), New York, reveal the complex mechanisms involved in enzyme that regulates DNA replication during cell division. By developing a sophisticated system using synthetic, chemical and structural biology approaches, the study reveals how a key enzyme involved in the replication of genetic information through DNA embraces a closed system, which opens at specific positions to a highly regulated replication process. This work improves the current understanding of an essential biological process and suggests a way to stop cell division in diseases such as cancer.

When a cell divides, the genetic information is duplicated in a process known as replication name of DNA. To do so, a "replication machine is assembled on top of the DNA before duplication. A known protein complex under ORC recognizes DNA replication origin beginning of the process. Then, an enzyme, MCM2-7 helicase, whose role consists in unwinding and to separate the two strands of the DNA helix, is loaded onto DNA by the ORC system of the machine. The helicase is an enzyme-shaped ring composed of six subunits (hexamer), although how the ring structure opens and encircles the DNA, until now, remained a mystery.

initial theories in the field helicase assumed to exist in a conformation in open ring. Speck The team argued that this would probably lead to DNA replication poorly regulated without control or specificity. To examine the helicase activity in more detail at BNL Sun Jingchuan used an electron microscope and found, contrary to initial theories helicase actually existed as a closed conformation ring.

To determine where in the six subunits, the helicase opens to encompass DNA, the team generated links that blocked the opening at different positions cycle. They found that if they blocked a specific interface between MCM2 and MCM5, DNA could not enter. A small molecule called rapamycin brings together the links; a molecular switch may be used to control the entry of DNA to the MCM ring and subsequent DNA replication. "Both in the context of our in vitro and in vivo, we showed that the opening of the interface MCM2 / MCM5 helicase loading is essential for DNA," says Christian.

"The field has known for some time that DNA can pass through the ring MCM2-7, but was never sure MCM subunits are used for regulated helicase loading. by designing an elegant experience, Speck laboratory has now shown once and for all that the MCM2-5 is the only entry point for DNA, "says associate Huilin Li at BNL.

in eukaryotes, the helicase MCM2-7 hexamer form a double (with another unit MCM2-7) when loaded on the DNA. in this study, the group has also set the long-standing dispute over whether the helicase is actually loaded as one hexamer, which then dimerizes or is loaded as a dimer to the offset. They concluded that the helicase is actually loaded as one hexamer before forming a double hexamer.

in a successful collaboration that exploits the expertise of electron microscopy with BNL chemical biology and genetics expert at the MRC clinical sciences Centre, the study focuses on key issues describing the processes involved in DNA replication. "Our work is aimed at understanding the molecular mechanism of DNA replication at a fundamental level. Yet our findings could have important implications, perhaps pointing to new ways to fight against cancer, because the DNA duplication is a prime target for inhibiting the growth of cancer cells, "said Christian.

CT scans annual repetition can eliminate the need for a biopsy or surgery in NNW

CT scans annual repetition can eliminate the need for a biopsy or surgery in NNW -

calculated annual low-dose tomography (CT) screening may eliminate the need a biopsy or surgery in nonsolid pulmonary nodules, according to a new study published online in the journal Radiology .

nonsolid nodules (NSN) are usually symptomless growths in the lung. Their name derives from the fact that the normal lung tissue is visible through the nodule on a CT image. NSN are becoming a more frequent finding in the wake of recent guidelines from the Centers for Medicare & Medicaid Services (CMS), which recommended a CT of annual screening for long-term smokers. Surgical removal is a treatment option, though NNW are rarely life threatening.

"When biopsy a nodule nonsolid, it is usually pre-malignant, non-invasive, or due to other causes, such as infection or fibrosis," co-author said Claudia I. Henschke, MD, Ph.D., of the department of radiology at Mount Sinai School of Medicine in New York.

in a study previously published in Radiology, Dr. Henschke and colleagues analyzed data from more than 57,000 participants in the International Programme early lung cancer (I-ELCAP), a global initiative to reduce lung cancer mortality. They concluded that NNW of any size could be followed with annual repeat CT scans, all the cancers found were at a very early stage and deaths among the study group are not due to these cancers.

For the new study, the researchers sought to validate the I-ELCAP results by examining data from the National Lung Screening Trial (NLST), a large trial that compared low-dose CT with chest X-rays for the detection of lung cancer. They searched the NLST database to identify all the participants who had at least one NSN on a scanner, and then died of lung cancer.

Among the 26.722 participants in 2534, or 9.4 percent, had one or more NNO. Among them, 48 died of lung cancer. Twenty-one of the 48 had no NSN in the cancerous lobe of the lung. A review of the remaining 27 cases found that death was unlikely to be caused by the NSN, as annual monitoring was done.

"The causes of death in this group were likely due to another solid nodule or solid portion in the same lobe of the lung," said study lead author Rowena Yip, MPH, senior biostatistician at Mount Sinai School of Medicine. "in one death linked to a growing nonsolid nodule, TB long before the diagnosis was more than three years."

the new findings and previous research, could help cost replacement patients, complications and stress of the biopsy and unnecessary surgery.

"We think we have enough data now to say that these nodules can safely be followed by annual analysis CT and should not be biopsied or treated immediately, "Dr. Henschke said." Survival remains 100 percent as nodules remain nonsolid, and for those who do ultimately progress, the monitoring interval one year is short enough that they remain fully curable. "

NNW Some go on to develop solid components, a change associated with a higher risk of invasive cancer. The Mount Sinai researchers plan to study these solid nodules part to learn more about optimal screening intervals and help improve opportunities for people with lung cancer, the leading cause of cancer death in men and women . Current screening guidelines cover only about 18 percent of people who eventually die from lung cancer, Dr. Henschke said, and leave out an important group :. people who have had long-term exposure to secondhand smoke

"We are hoping that, by making it more effective screening, we will convince CMS to expand slowly guidelines to include other at risk, including those exposed to secondhand smoke, "said Yip.

drugs against osteoporosis may not protect women against breast cancer

drugs against osteoporosis may not protect women against breast cancer -

Osteoporosis drugs called bisphosphonates may not protect women against breast cancer as had been thought, according to a new study by researchers at UC San Francisco (UCSF).

The protective effect of drugs was widely accepted after several observational studies have shown that women who have them were less likely to have breast cancer.

But when the researchers evaluated the effect of two drugs most used osteoporosis - sold under brand names Fosamax and Reclast - in two large randomized clinical trials, drug or women protected by the breast cancer osteoporosis. The results were published August 11, 2014, in JAMA Internal Medicine .

The researchers said the link found in previous observational studies between taking drugs and having a lower incidence of breast cancer may be due to a third factor, low estrogen.

Since having low estrogen two weakens bones and protects against most breast cancers, the most likely women to be prescribed drugs for osteoporosis are generally also lower risk for cancer breast.

"They may have seen a lower risk of breast cancer in women using bisphosphonates in previous observational studies because these women had a lower risk of breast cancer to begin" said Trisha Hue, PhD, lead author of the study.

"post-menopausal women with osteoporosis usually have low estrogen levels," said Hue, an epidemiologist with the Centre coordination of San Francisco, a partnership between the CPMC and UCSF research Institute Department of epidemiology and Biostatistics. "the lower estrogen levels are strongly associated with a lower risk of breast cancer."

Steven Cummings, MD, co-author of the paper, a UCSF professor emeritus of medicine and director of the San Francisco coordinating Center, said women should not take these drugs thinking they will protect against the breast cancer.

"postmenopausal women should continue taking these drugs to prevent fractures, but they should not use bisphosphonates for prevention of primary breast cancer," said Cummings, Senior Investigator the research Institute CPMC.

data analyzed in the study come from two clinical trials, double-blind, placebo-controlled. in both trials, women who received bisphosphonates impacted slightly higher, but not statistically significant for breast cancer.

the Fracture Intervention trial (FIT) randomly assigned 6,459 US women 55 to 81 to alendronate or placebo for a follow average of 3.8 years, 1.8 percent of women who received the drug for breast cancer developed, while 1.5 percent of those who received placebo developed the disease

the health outcomes and impact reduced with zoledronic acid once a year-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned to 7.765 US women, Canada, Asia, Europe and South America 65 to 89 at the annual zoledronic acid by intravenous or placebo for a mean follow-up of 2.8 years; 0.87 percent of women who received the drug for breast cancer developed, while 0.77 percent of those who received placebo developed the disease.

Women in both studies who had recurrent breast cancer or breast cancer reported history were excluded from the analysis.

omics whole genome data can improve the accuracy of breast cancer survival predictions

omics whole genome data can improve the accuracy of breast cancer survival predictions -

accurate predictions of whether a tumor is likely to spread would help clinicians and patients choose the best treatment. But current methods fall short of the required accuracy. A new study reveals that the samples of primary profiling of tumors using genomic technologies can improve the accuracy of predictions of breast cancer survival compared to single clinical information. The study was published in the journal GENETIC , a publication of the American Genetics Society.

Although this method is not ready for use in the clinic, shows evidence of principle study that survival predictions increase when they incorporate detailed data on which genes are active in samples of tumor relative to non-cancerous tissue from the same patient. This is also true for the methylation data of the whole genome, which maps the parts of DNA that carry "tags" that molecular activation influences gene. If developed for use in the clinic, the approach could save some patients from unnecessary chemotherapy.

After surgery, about 80% of breast cancer patients are treated with adjuvant therapies, including chemotherapy and radiotherapy. These treatments often have serious long-term side effects, including heart damage, infertility, memory problems, and a higher risk of developing a new independent cancer. But not all patients necessarily need adjuvant therapy; Breast cancer is estimated to recur or metastasize in 40% of patients, which suggests that a significant number of patients suffer side effects unnecessarily. For now, the widespread use of adjuvant therapy remains inevitable because we can not predict which primary tumors may metastasize and become fatal, and that will stay put.

Today, doctors use a variety of clinical information to help choose the best treatment for an individual patient, including the patient's age and ethnicity, size of the tumor, the type of cell it arises, how it evolved (stage), and the presence of different types of receptors and other molecular signatures of tumor cells (subtype of cancer). To help narrow down the choices of treatment, several commercial tests estimate that the risk of cancer recurrence by measuring the activity (expression) of a set of genes that influence cancer progression. For example, the panel Oncotype DX widely available expression analysis of 21 genes in tumor samples and is recommended for patients with certain types of breast cancer.

But cancer is a complex disease and its behavior is likely affected by thousands of genes. Advances in genomic technology mean it is now possible to measure the gene expression of the tumor through the entire genome. Samples may also be contoured for a variety of other measures of genome-wide, including the variation in the DNA (e.g., deletions or mutations) and methylation. The authors of the new study examined whether these genomic data, either alone or in combination, could actually improve forecasts of breast cancer survival.

"Instead of pre-selection that handful of genes could better predict survival, we used data of all genes in the cancer cell --approximately 17,000 in our study - and let our model calculation select those information, "says study leader Ana I. Vazquez Michigan State University

in. test their approach, Vazquez and his colleagues used data from the Cancer Genome Atlas, a national Institutes of Health project that the profiles of several types of genome-wide data in thousands of cancer samples. the samples are matched normal tissue from the same individual, as well as clinical database for the patient. the polished team in primary breast cancer samples from 285 patients who had adequate clinical monitoring information to allow the team to analyze the survival rate.

the authors used this data set to build calculation models that predict the outcome of a patient (eg survival) using different types of data. They compared the performance of these models using cross-validation. In this method, data is randomly divided into two: one part is used to build and edit a predictive model, and the other part is used to test the accuracy of the model runs. This procedure is repeated hundreds of times to new divisions random data, and the results are marked to reveal the model is more reliable predictions.

This showed that the gene expression of the entire genome data were better predictors of survival than one source of information currently used by doctors, including cancer stage (how advanced the cancer east) and molecular subtype (eg, hormone receptor status). By combining gene expression data with clinical data provided better predictions that all clinical predictors together. The data of gene expression of the entire genome also outperformed the forecasts made with genes in DX Oncotype panel in the subset of patients who met the criteria for the panel. Oncotype DX is a well validated test used in the clinic since 04.

Data only methylation was also more predictive than any standard clinical information, and have also improved most predictions when combined with clinical data . Finally, by combining clinical information, gene expression of the entire genome, and Methylation data provided the most predictive models examined in the study.

"Overall, we can conclude that the forecasts continue to improve as you add data 'omics" said Vazquez. "This gives us promising leads in genomics for the future implementation of the clinic."

Not all types of information across the genome were as predictive as gene expression data or methylation, the team found. the prediction accuracy from clinical data was not affected by the addition of genomic profiles of microRNAs, small molecules that can influence gene expression. And although the accuracy was improved by combining clinical data with genomic profiles of a particular type of DNA change (known as a variation of the number of copies), the improvement was much smaller than the gains provided by gene expression or methylation data.

None of the models can not accurately predict survival. Vazquez said that although the method is promising, a major limitation of the study was the small number of samples available for developing the models. To be applied by clinicians, the method should be validated using the thousands of patient data, rather than hundreds. His team is also studying how to incorporate other factors into their models, including treatment regimens. Ultimately, this can help physicians and patients responding to the best course of treatment with the individual characteristics of each tumor.

Researchers identify early predictors of rehospitalization in patients with COPD

Researchers identify early predictors of rehospitalization in patients with COPD -

Researchers at the University of Texas Medical Branch at Galveston have identified predictors in early readmission patients hospitalized for chronic obstructive pulmonary disease complications. This study was recently published in Annals of the American Thoracic Society .

In a nationwide analysis of over 8,000 patients commercially insured adults with COPD, the UTMB researchers concluded that several modifiable factors, such requirements as applicable on the discharge and follow soon after the hospital discharge were associated with lower likelihood of early readmission.

COPD is a major public health problem that affects 12 to 24 million people and is the third leading cause of death in the United States. Each year, thousands of people have outbreaks of acute COPD requiring hospitalization. About 20 percent of these patients require readmission within 30 days of discharge.

High rates of hospital readmissions and differences in rates can result from factors specific patient, including the severity of COPD and the presence of other aggravating health problems, factors from health-care providers and the quality of care and monitoring outpatient and availability of reference subspecialty. These early readmissions lead to overuse of health care resources and impose a heavy financial burden.

hospital readmissions reduction has been a goal of the Affordable Care Act and accountable care organizations. In 09, the US Centers for Medicare and Medicaid Services began publicly report the 30-day readmission rates for heart attacks, pneumonia and congestive heart failure, quality performance measurement. In 2012, CMS began to cut Medicare payments to hospitals with high readmission rates for patients admitted to these conditions. Since October 2014, COPD will be added to this list.

"This study analyzed a national sample with robust design methods for confirming patient factors as an early readmission predictor after first hospitalization for COPD, as well as to show how a combination of different factors may independently contribute to early readmission, "said lead author Dr. Roozbeh Sharif. "Managing Director-stick line and early monitoring has the potential to reduce early rehospitalization among patients with COPD," said Sharif.

COPD patients with co-existing congestive heart failure, lung cancer, anxiety, depression or osteoporosis was associated with a higher probability of early readmission. health care provider and system factors, including the requirements for inhaler bronchodilators, oral corticosteroids, antibiotics and discharge the early outpatient follow-up after discharge were associated with a lower likelihood of readmission.

This study suggests that strategies to reduce readmissions shortly after hospital COPD flare-ups are likely to be most effective when they go beyond the quality of care specific to COPD in 'hospital.

The results of these works have received international attention. It was presented at the World Conference CHEST in Madrid, Spain in March 2014 and was quoted at the annual conference of the American Thoracic Society in May 2014.

relaxing acupressure improves fatigue levels in survivors of breast cancer

relaxing acupressure improves fatigue levels in survivors of breast cancer -

acupressure reduced persistent fatigue in women who had been treated for breast cancer a new study.

fatigue is one of the most common long-term effects of breast cancer treatment. About a third of women suffer from moderate to severe fatigue until 10 years after the end of treatment.

The study, published in JAMA Oncology, found acupressure reduces fatigue by 27 percent to 34 percent over six weeks. Two-thirds of women who do relaxing acupressure, some type of healing method, reached normal levels of fatigue.

"Fatigue is a symptom underestimated a large number of chronic diseases, especially cancer. It has a significant impact on quality of life. Acupressure is easy to learn and patients can do themselves, "says study author Suzanna Zick, ND, MPH, research associate professor of family medicine at the University of Michigan.

acupressure is derived from Traditional Chinese Medicine. It involves applying . pressure with the fingers, thumbs or device at specific points on the body the researchers tested two types of acupressure: relaxing acupressure, which is traditionally used to treat insomnia, and stimulating acupressure, which is used to increase energy. the two techniques differ in which points on the body are stimulated.

researcher recruited 424 breast cancer survivors from the register of Michigan tumors. participants were randomized to relaxing acupressure, stimulating acupressure or usual care, which includes typical sleep management techniques. Women have learned to find and stimulate acupressure points so that they can perform at home once a day for six weeks.

At the end of the trial, the two acupressure treatments resulted in significant, sustained improvements tiredness. But only relaxing acupressure measures also improved sleep quality, such as disturbed sleep, and overall quality of life.

Previous studies suggest acupuncture may help curb fatigue. But acupuncture is often not covered by insurance, the more it requires that people go to a practitioner once or twice a week for at least six weeks.

acupressure, on the other hand, proved in this study to be easy to learn and can be done at home.

Study participants were 15 minutes of training, and have been able to pinpoint the correct acupressure points and applying the right amount of pressure. Some women have reported minor bruising to acupressure sites. About 12 percent of participants discontinued the study because they felt it was too time intensive.

"Given the short training to learn acupressure, this intervention could be a low cost option for the treatment of fatigue," said Zick.

Researchers are developing a mobile application to teach acupressure. They will also investigate why acupressure impacts fatigue and if it is also effective for patients in active treatment and cancers other than breast.

Weight loss improves physical health but takes toll on mental health

Weight loss improves physical health but takes toll on mental health -

weight loss significantly improves physical health, but the effects on mental health are less simple, find new UCL research funded by Cancer research UK.

in a study of 1,979 adults overweight and obese in the UK, people who lost 5% or more of their initial body weight over four years showed significant changes in markers of physical health but were more likely to report depressive mood than those who remained within 5% of their initial weight.

The research, published in PLOS ONE , highlights the need to consider mental health to physical health side during weight loss. It has been shown that clinical trials of weight loss to improve the mood of the participants, but it could be the result of the environment rather than weight loss itself, the effects are observed early in treatment and are not related to the measurement of the weight loss.

It is important to note that this new result does not mean that weight loss necessarily mean depression directly, such as depression and weight loss may share a common cause. However, it shows that weight loss outside the framework of the clinical trial can be expected to improve mood and raises questions about the psychological impact of weight loss.

The data are from the Longitudinal Study of Aging, a British study of English adults aged 50 years or more, and excluded participants with a diagnosis of clinical depression or debilitating illness. Depressed mood and overall well-being were assessed using standard questionnaires and weight was measured by trained nurses.

Among the 1,979 overweight and obese participants, 278 (14%) have lost at least 5% of their initial body weight with a mean weight loss of 6.8 kg per person. Before adjusting serious health problems and major life events such as bereavement, which can cause weight loss and depressed mood, people who lost weight were 78% more likely to report mood depressed. After controlling for these, the increased likelihood of depressed mood remained significant at 52%.

"We do not want to discourage anyone from trying to lose weight, which has enormous physical benefits, but people should not expect weight loss to instantly improve all aspects of life" says lead author Dr Sarah Jackson (UCL epidemiology and public health). "Aspirational Advertising by diet brands can give people unrealistic expectations about weight loss. They often promise improvements instant life, can not be supported in the reality for many people. people should be realistic about weight loss and be ready for the challenges.

"Resist the ever present temptation of unhealthy food in modern society takes a mental toll, because it requires considerable commitment and may involve missing out on enjoyable activities. Anyone who has ever been on a diet would be to understand how this could affect welfare. However, the mood may improve once target weight is reached and the focus is on weight maintenance. Our data only cover a period of four years and it would be interesting to see how the mood changes once people settle into their lower weight.

"Health professionals should monitor the mental and physical health of patients when recommending or respond to weight loss, and provide support if necessary. People trying to lose weight should be aware of the challenges and do not be afraid to ask for support, be it friends, family or health professionals. "

lead author Professor Jane Wardle, director of the health Behaviour Centre Cancer Research UK to UCL, said: ". A recent survey in the UK found that 60% of adults overweight and obese in the UK are trying to lose weight There are obvious advantages in terms of physical health, which our study confirmed those lost weight obtained a blood pressure reduction and serum triglycerides .. significantly reduce the risk of heart disease However, patients and physicians should be aware that there is no immediate psychological advantage and there may be an increased risk of depression. "

Researchers discover wars2 role for the gene in the process of angiogenesis

Researchers discover wars2 role for the gene in the process of angiogenesis -

In a study conducted by Duke-NUS Medical School (Duke-NUS) and the National Heart Centre Singapore (NHCS), researchers have discovered a new gene that controls blood vessel formation. This work presents a potential new therapeutic target for cancer and heart disease, and was published in the journal, Nature Communications , July 8, 2016.

The blood vessels form a network throughout the body to provide the nutrients needed to maintain tissues and organs alive and healthy. The formation of this network is controlled by a process called angiogenesis. Inhibition of angiogenesis is typically targeted in cancer development process that aims to starve tumors of nutrients necessary for their survival. In the heart, increased angiogenesis can help the function of the heart pump.

For the first time, a team led by Professor Stuart Cook at Duke-NUS, discovered a role for the gene, wars2 in the process of angiogenesis. Mr. Mao Wang, a doctoral student at Duke-NUS University, is co-first author of the study along with Dr. Patrick Sips, associate researcher at Brigham and Women's Hospital and Harvard Medical School. Together, they confirmed the importance of wars2 for angiogenesis in rats and zebrafish.

"By using different genetic techniques, we inhibited wars2 function in rats and zebrafish, and the resulting animals showed insufficient blood vessel formation in the heart and elsewhere in the body, "Mr. Wang described.

To confirm the involvement of wars2 in angiogenesis, the researchers increased the wars2 effect and showed that the formation of blood vessels was enhanced. Specifically, they were able to determine that wars2 plays an important role in providing adequate endothelial cells, the building blocks of blood vessels, for angiogenesis.

"Angiogenesis is essential for sustaining life and providing nutrients to all parts of the body," said Professor Cook, Tanoto Foundation professor of cardiovascular medicine at Duke University Medical Center SingHealth-NUS. "Find a way to control angiogenesis not only provides a target for developing anti-cancer therapies, but can also be useful in hungry even the growth of abnormal blood vessels elsewhere in the body, such as diabetic retinopathy. " Prof Cook is also the director of cardiovascular and metabolic research at Duke-NUS Program.

Ultimately, wars2 provides researchers and pharmaceutical companies a new fresh target for developing treatments for diseases characterized by abnormal blood vessel growth that can be more effective and specific or complementary to it which is currently available.

The articles describe the barriers to, the potential for greater adoption of managing complex care

The articles describe the barriers to, the potential for greater adoption of managing complex care -

The care of patients with complex medical needs is widely considered one of the key factors has increased the health of US costs, and it is generally accepted that 10 to 15 percent of Medicare patients represent 65 to 75 percent of all Medicare spending. Many of the country's largest health care organizations have been adopting the complex care management strategy - assembling multidisciplinary teams of physicians, nurses, pharmacists, mental health professionals and others with services coordinated by care managers who work closely with patients and their families.

perspective in an article in the August 7 New England Journal of Medicine and a brief question Commonwealth Fund released today, two Massachusetts General Hospital (MGH) physicians and their authors describe cooperation best practices based on interviews with leaders of 18 complex care management programs, discuss barriers to wider adoption of managing complex care and describe possible strategies to overcome these barriers.

"Not only can fully meet the needs of complex care patients keep healthier, but it can also reduce costs by avoiding emergency department visits and unnecessary hospitalizations," says Clemens Hong, MD , MPH, of the MGH Division of General medicine, corresponding author of the NEJM paper. "in our part of Perspective, we wanted to clarify some of the needs and challenges of establishing the management of complex care and review possible solutions if you work in a large integrated health system in Boston or a small doctor's office in rural Arkansas. "

The report of the Commonwealth Fund, Hong and his co-authors - Timothy Ferris, MD, MPH, vice president, health management of the population, at MGH and Partners HealthCare System and Allison Siegel , MPH, formerly with the Stoeckle Center for primary care innovation at MGH. - examine the characteristics of effective care management programs Foremost among these are the close cooperation of care managers with all suppliers taking . care for a complex patient They note that small, one and two primary care physicians may lack the resources to manage complex care in cases like this, regional organizations -.

in Article NEJM, Hong, Ferris and Melinda Abrams, vice president can provide the infrastructure for the management of care remains closely linked to suppliers known to patients. - public or private, reform of the delivery system, the Fund Commonwealth noted that the main obstacle to wider adoption of care management is the system of remuneration payment services, offering little or no support for essential care management functions. Instead, reimbursement systems that provide global payments covering all services requires a complex patient or those who share cost savings between the payers and providers can have better options. Another option that offers, for a monthly fee of patient care management could encourage the participation of suppliers unable to bear the financial risks of international payments agreements. Other obstacles include the startup costs associated with staff training and new information technologies which could be covered by additional payments. Unrealistic expectations for a rapid return on investment could be addressed by increasing the duration of payer-provider contracts.

The MGH embarked on care management in 06, a Center for Medicare and Medicaid Services (CMS) -sponsored demonstration project that enrolled 2500 patients at high risk in its first phase. Through the coordination of care nurse managers who worked closely with registered patients and their doctors, the program realized a net annual savings of 7 percent and a return on investment of $ 2.65 for every dollar at least spent. CMS has renewed the project in 09, and now more than 10,000 complex patients in eastern Massachusetts have a care manager in the Partners HealthCare Integrated Care Management Program.

"We have many small practices in the Partners system that often not enough complex patients to invest in complex care management resources themselves," said Hong "as a system of integrated delivery, Partners has the ability to support these practices by providing care managers who can work two or three days a week in many different practices. Not all the complex patient needs for each service while sharing resources that are deployed only when and where necessary can achieve significant economies of scale. "

He and his co-authors also note the need for more information on how best to match the program design different practice settings; programs and training standards; and advanced analytics and information technology to help identify appropriate patients, provide real-time data and improve workflow. Increasing evidence on the savings provided by complex care management should increase its adoption, that compensation programs not only for themselves, but also to improve health outcomes and reduce fragmentation of patient care .