#Uncovering the Spread of Bacteria in Pneumonia Northwestern Medicine scientists have discovered the role a toxin produced by a pneumonia-causing bacterium plays in the spread of infection from the lungs to the bloodstream in hospitalized patients. rior to this study,
it was a mystery how the bacteria escaped from the lungs into the bloodstream, said Alan Hauser, M d.,Ph d,
. professor in Microbiology-Immunology and Medicine-Infectious disease. hese findings lay the foundation for future studies to further understand the mechanisms for how the escape to the bloodstream occurs.
In a paper published in PLOS Pathogens Dr. Hauser and his team used a mouse model of Pseudomonas aeruginosa (PA) pneumonia to examine how the bacterium uses its secretion system to inject a toxin, called Exos, into cells.
Exos has previously been linked to a higher incidence of infections spreading to the blood. f we can understand this at a higher level of detail,
perhaps we will be able to design inhibitors that can be flushed into the bloodstream or the lung of a person who has PA pneumonia and block this process.
If we can block these processes, we may be able to prevent bacteria from disseminating to the bloodstream during pneumonia,
said Dr. Hauser, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
They collaborated with the Center for Advanced Microscopy to use a novel imaging technique to identify cells injected with Exos.
This method allowed them to uncover that Exos was injected not only into white blood cells, but also epithelial cells that form a barrier between the lung and the bloodstream.
Dr. Hauser also found that injection of the toxin occurred in specific regions which they labeled ields of cell injectionor FOCI. e got a surprising result,
that the epithelial cells weren randomly being injected, but they were being injected in FOCI within the lungs,
Furthermore, they determined that increased FOCI size was associated with enhanced disruption of the barrier between the lungs and bloodstream and ultimately the spreading of the bacteria in to the blood. his injection of Exos results in breakdown of a barrier between the pulmonary space and the vascular space,
Next, Dr. Hauser plans to continue studying the mechanism of how Exos leads to the formation of FOCI. his research might have implications for other bacteria that frequently cause pneumonia
Scientists from the University of Nottingham in England have discovered a fully man-made substrate that could produce billions of human embryonic stem cells and move laboratory-based research to industrial-scale biomedicine.
Stem cells are being investigated to fight a number of diseases, and have even recently been considered as an option to treat mitochondrial disease,
as the Los angeles times reported. Morgan Alexander, professor of biomedical surfaces in the School of Pharmacy at the University of Nottingham
and Chris Denning, professor of stem cell biology in the School of medicine led the research project, iscovery of a Novel Polymer for Human Pluripotent Stem Cell Expansion and Multilineage Differentiation. he possibilities for regenerative medicine are still being reached in the form of clinical trials,
Alexander said in a news release. hat we are doing here is paving the way for the manufacture of stem cells in large numbers
when those therapies are proved to be safe and effective. Potentially, the material could benefit clinical use in the treatment of the heart, liver and brain
according to the release. Professor Denning said: he field of regenerative medicine has snowballed in the last five years
and over the coming five years a lot more patients will be receiving stem cell treatments. Clinical trials are still in the very early stages.
However, with this kind of product, if we can get it commercialized and validated by the regulators it could be helping patients in two to three years.
#Treatment Failure in Parasite Infection Tied to Virustwo new studies explain why some parasite infections,
The findings, available online in The Journal of Infectious diseases, suggest that simple changes in current treatments could improve the lives of millions of people sickened by parasite infections. ur findings may mean that treatment for Leishmania infections could be improved significantly by determining
said Stephen Beverley, Ph d.,senior author of one of the studies and the Marvin A. Brennecke Professor and head of the Department of Molecular Microbiology at Washington University School of medicine in St louis. n the future,
Beverley team focused on infections in Bolivia and Peru, while the other team, led by Catherine Ronet,
Ph d.,of the University of Lausanne in Switzerland, worked with colleagues studying patients in French guiana.``
```Leishmaniasis is mainly spread by sand flies. Depending on the parasite species, symptoms of infection may include large skin lesions, fever, swelling of the spleen and liver,
and sometimes disfigurement and death. The virus carried by the parasite is called Leishmaniavirus, or LRV1.
In earlier research in animals, the scientists found that Leishmania causes more severe infections when the parasite is infected with LRV1.
Bolivia and Belgium examined data on 97 leishmaniasis patients. These were gathered through a project on drug resistance,
funded by the European commission and led by co-author Jean-Claude Dujardin, Ph d.,of the Institute of Tropical Medicine, Antwerp, Belgium. n Peru,
leishmaniasis is common in people who work in agriculture and forestry, said lead author Vanessa Adaui, Ph d,
. of the Cayetano Heredia University in Peru. edical resources are often very scarce in the communities where these people work,
and although infections typically are not fatal, they can lead to significant scarring, social stigmatization and economic loss. ll over the world,
treatment failure is a major obstacle to the control of infectious diseases like leishmaniasis, said Dujardin. t is of uppermost importance to understand the factors contributing to this failure to better tackle it.
The researchers found that treatment failed to cure more than 50 percent of patients with parasites infected with the LRV1 virus
. But the failure rate was only 24 percent in patients with parasites that were free of the virus. The standard treatment for leishmaniasis differs based on the parasite species that causes the infection
and varies by location. In French guiana for example, patients are treated with pentamidine; in Peru and Bolivia, they receive a class of drugs called pentavalent antimonials.
Parasites infected with the virus were harder to cure, he said. Based on the new research, it may be possible to develop clinical tests to identify virus-infected parasites.
The scientists are investigating how viral infection makes leishmaniasis more difficult to cure. According to Beverley, the parasites infected with the virus may be interacting with patientsimmune systems in a way that disrupts treatment.
Another, more likely possibility is that an increase in parasites spurred by the virus may make it more challenging for treatment to completely eliminate the parasites. number of other human parasites bear viral infections that are reminiscent of LRV1 in Leishmania,
#Software Turns Smartphones into Tools for Medical Research Jody Kearns doesn't like to spend time obsessing about her Parkinson's disease.
But she still works, drives and tries to live a normal life. Yet since she enrolled in a clinical study that uses her iphone to gather information about her condition,
Kearns has been diligently taking a series of tests three times a day. She taps the phone's screen in a certain pattern, records a spoken phrase and walks a short distance while the phone's motion sensors measure her gait."
"The thing with Parkinson's disease is there's not much you can do about it, "she said of the nervous-system disorder,
which can be managed but has no cure.""So when I heard about this, I thought,
`I can do this.'"'"Smartphone apps are the latest tools to emerge from the intersection of health care and Silicon valley,
where tech companies are also working on new ways of bringing patients and doctors together online, applying massive computing power to analyze DNA and even developing ingestible"smart"pills for detecting cancer.
More than 75,000 people have enrolled in health studies that use specialized iphone apps, built with software Apple Inc. developed to help turn the popular smartphone into a research tool.
Once enrolled, iphone owners use the apps to submit data on a daily basis, by answering a few survey questions
or using the iphone's built-in sensors to measure their symptoms. Scientists overseeing the studies say the apps could transform medical research by helping them collect information more frequently and from more people, across larger and more diverse regions,
than they're able to reach with traditional health studies. A smartphone"is a great platform for research,
"said Dr. Michael Mcconnell, a Stanford university cardiologist, who's using an app to study heart disease."
"It's one thing that people have with them every day.""While the studies are in early stages,
researchers also say a smartphone's microphone, motion sensors and touchscreen can take precise readings that,
in some cases, may be more reliable than a doctor's observations. These can be correlated with other health or fitness data and even environmental conditions, such as smog levels, based on the phone's GPS locater.
Others have had similar ideas. Google Inc. says it's developing a health-tracking wristband specifically designed for medical studies.
Researchers also have tried limited studies that gather data from apps on Android phones. But if smartphones hold great promise for medical research
experts say there are issues to consider when turning vast numbers of people into walking test subjects.
The most important is safeguarding privacy and the data that's collected, according to ethics experts.
In addition, researchers say apps must be designed to ask questions that produce useful information, without overloading participants
or making them lose interest after a few weeks. Study organizers also acknowledge that iphone owners tend to be more affluent and not necessarily an accurate mirror of the world's population.
Apple had created previously software called Healthkit for apps that track iphone owners'health statistics and exercise habits.
Senior vice president Jeff Williams said the company wants to help scientists by creating additional software for more specialized apps
using the iphone's capabilities and vast user base-estimated at 70 million or more in North america alone."
"This is advancing research and helping to democratize medicine, "Williams said in an interview. Apple launched its Researchkit program in March with five apps to investigate Parkinson's, asthma, heart disease, diabetes and breast cancer.
A sixth app was released last month to collect information for a long-term health study of gays and lesbians by the University of California,
San francisco. Williams said more are being developed. For scientists, a smartphone app is a relatively inexpensive way to reach thousands of people living in different settings and geographic areas.
Traditional studies may only draw a few hundred participants said Dr. Ray Dorsey, a University of Rochester neurologist who's leading the Parkinson's app study called mpower."
"Participating in clinical studies is often a burden, "he explained.""You have to live near where the study's being conducted.
You have to be able to take time off work and go in for frequent assessments.""Smartphones also offer the ability to collect precise readings, Dorsey added.
One test in the Parkinson's study measures the speed at which participants tap their fingers in a particular sequence on the iphone's touchscreen.
Dorsey said that's more objective than a process still used in clinics, where doctors watch patients tap their fingers
and assign them a numerical score. Some apps rely on participants to provide data. Elizabeth Ortiz, a 48-year-old New york nurse with asthma, measures her lung power each day by breathing into an inexpensive plastic device.
She types the results into the Asthma Health app which also asks if she's had difficulty breathing or sleeping,
or taken medication that day.""I'm a Latina woman and there's a high rate of asthma in my community,
"said Ortiz, who said she already used her iphone"constantly"for things like banking and email."
"I figured that participating would help my family and friends, and anyone else who suffers from asthma."
"None of the apps test experimental drugs or surgeries. Instead, they're designed to explore such questions as how diseases develop
or how sufferers respond to stress, exercise or standard treatment regimens. Stanford's Mcconnell said he also wants to study the effect of giving participants feedback on their progress,
or reminders about exercise and medication. In the future, researchers might be able to incorporate data from participants'hospital records,
said Mcconnell. But first, he added, they must build a track record of safeguarding data they collect."
"We need to get to the stage where we've passed the privacy test and made sure that people feel comfortable with this."
"Toward that end, the enrollment process for each app requires participants to read an explanation of how their information will be used, before giving formal consent.
The studies all promise to meet federal health confidentiality rules and remove identifying information from other data that's collected.
Apple says it won't have access to any data or use it for commercial purposes. Some studies will always require in-person interaction or supervision by a doctor,
experts say. But by reaching more people and gathering more data, advocates say smartphone apps can help doctors answer more subtle questions about a disease."
"Diseases like asthma are complicated very. They're not caused by a single gene or environmental influence,"said Eric Schadt,
a genomics professor who's using an iphone app to study asthma at New york's Icahn School of medicine at Mount sinai."
"The only hope you have of really going further in resolving this disease is for researchers to get to more people
#In CRISPR Advance, Scientists Successfully Edit Human T cells In a project spearheaded by investigators at UC San francisco,
scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Because these immune-system cells play important roles in a wide range of diseases, from diabetes to AIDS to cancer, the achievement provides a versatile new tool for research on T cell function,
as well as a path toward CRISPR/Cas9-based therapies for many serious health problems. Using their novel approach,
the scientists were able to disable a protein on the T-cell surface called CXCR4, which can be exploited by HIV
when the virus infects T cells and causes AIDS. The group also successfully shut down PD-1,
a protein that has attracted intense interest in the burgeoning field of cancer immunotherapy, as scientists have shown that using drugs to block PD-1 coaxes T cells to attack tumors.
The CRISPR/Cas9 system has captured the imagination of both scientists and the general public, because it makes it possible to easily
and inexpensively edit genetic information in virtually any organism. T cells, which circulate in the blood, are an obvious candidate for medical applications of the technology,
as these cells not only stand at the center of many disease processes, but could be gathered easily from patients,
edited with CRISPR/Cas9, then returned to the body to exert therapeutic effects. But in practice, editing T cell genomes with CRISPR/Cas9 has proved surprisingly difficult,
said Alexander Marson, Ph d.,a UCSF Sandler Fellow, and senior and co-corresponding author of the new study. enome editing in human T cells has been a notable challenge for the field,
Marson said. o we spent the past year and a half trying to optimize editing in functional T cells.
There are a lot of potential therapeutic applications and we want to make sure wee driving this as hard as we can.
The new work was done under the auspices of the Innovative Genomics Initiative (IGI), a joint UC Berkeley-UCSF program co-directed by Berkeley Jennifer Doudna, Ph d,
. who is renowned world for her pioneering research on CRISPR/Cas9, and Jonathan Weissman, Ph d.,professor of cellular and molecular pharmacology at UCSF and a Howard hughes medical institute (HHMI) investigator.
Marson is an affiliate member of the IGI. Doudna, professor of chemistry and of cell and molecular biology at Berkeley,
and an HHMI investigator, said that the research is a significant step forward in bringing the power of CRISPR/Cas9 editing to human biology
and medicine. t been great to be part of this exciting collaboration, and I look forward to seeing the insights from this work used to help patients in the future,
said Doudna, co-corresponding author of the new paper. Cas9, an enzyme in the CRISPR system that makes cuts in DNA
and allows new genetic sequences to be inserted, has generally been introduced into cells using viruses or circular bits of DNA called plasmids.
Then, in a separate step a genetic construct known as single-GUIDE RNA, which steers Cas9 to the specific spots in DNA where cuts are desired,
is placed also into the cells. Until recently, however, editing human T cells with CRISPR/Cas9 has been inefficient,
with only a relatively small percentage of cells being modified successfully. And while scientists have had some success in switching off genes by inserting
or deleting random sequences, they have not yet been able to use CRISPR/Cas9 to paste in
(or nock in specific new sequences to correct mutations in T cells. As will be reported online in Proceedings of the National Academy of Sciences during the week of July 27
2015, a team led by first authors Kathrin Schumann, Ph d.,a postdoctoral fellow in Marson laboratory,
and Steven Lin, Ph d.,a postdoctoral fellow in the Doudna lab, cracked these problems by streamlining the delivery of Cas9 and single-GUIDE RNA to cells.
In lab dishes, the group assembled Cas9 ribonucleoproteins, or RNPS, which combine the Cas9 protein with single-GUIDE RNA.
and eventually for therapeutic use. e tried for a long time to introduce Cas9 with plasmids or lentiviruses,
He hopes that Cas9-based therapies for T cell-related disorders, which include autoimmune diseases as well as immunodeficiencies such as ubble boy disease,
will enter the clinic in the future. here actually well-trodden ground putting modified T cells into patients.
There are companies out there already doing it and figuring out the safety profile, so there increasing clinical infrastructure that we could potentially piggyback on as we work out more details of genome editing,
Marson said. think CRISPR-edited T cells will eventually go into patients, and it would be wrong not to think about the steps we need to take to get there safely and effectively.
and the Howard hughes medical institute t
#New Knowledge: Parkinson's disease May Begin In The Gut, Aarhus University Study A major epidemiological registry-based study from Aarhus University and Aarhus University Hospital indicates that Parkinson's disease begins in the gastrointestinal tract.
The study is the largest in the field so far. The chronic neurodegenerative Parkinson disease affects an increasing number of people.
However, scientists still do not know why some people develop Parkinson's disease. Now researchers from Aarhus University and Aarhus University Hospital have taken an important step towards a better understanding of the disease.
New research indicates that Parkinson's disease may begin in the gastrointestinal tract and spread through the vagus nerve to the brain."
"We have conducted a registry study of almost 15,000 patients who have had the vagus nerve in their stomach severed.
Between approximately 1970-1995 this procedure was a very common method of ulcer treatment. If it really is correct that Parkinson's starts in the gut and spreads through the vagus nerve,
then these vagotomy patients should naturally be protected against developing Parkinson's disease, "explains postdoc at Aarhus University Elisabeth Svensson on the hypothesis behind the study.
A hypothesis that turned out to be correct:""Our study shows that patients who have had the the entire vagus nerve severed were protected against Parkinson's disease.
Their risk was halved after 20 years. However, patients who had had only a small part of the vagus nerve severed where not protected.
This also fits the hypothesis that the disease process is strongly dependent on a fully or partially intact vagus nerve to be able to reach
and affect the brain, "she says. The research project has just been published in the internationally recognised journal Annals of Neurology.
The first clinical examination The research has presented strong evidence that Parkinson's disease begins in the gastrointestinal tract and spreads via the vagus nerve to the brain.
Many patients have suffered also from gastrointestinal symptoms before the Parkinson's diagnosis is made.""Patients with Parkinson's disease are constipated often many years before they receive the diagnosis,
which may be an early marker of the link between neurologic and gastroenterologic pathology related to the vagus nerve,"says Elisabeth Svensson.
Previous hypotheses about the relationship between Parkinson's and the vagus nerve have led to animal studies and cell studies in the field.
However, the current study is the first and largest epidemiological study in humans. The research project is an important piece of the puzzle in terms of the causes of the disease.
In the future the researchers expect to be able to use the new knowledge to identify risk factors for Parkinson's disease
and thus prevent the disease.""Now that we have found an association between the vagus nerve and the development of Parkinson's disease,
it is important to carry out research into the factors that may trigger this neurological degeneration,
so that we can prevent the development of the disease. To be able to do this will naturally be a major breakthrough,
"says Elisabeth Svensson. Facts Parkinson's disease is a chronic and neurodegenerative disease which affects approx. 1 out of every 1, 000 people.
The first signs of the disease are seen most often between the ages of 50-60.
The researchers carried out a registry study involving 14 883 patients who had undergone a vagotomy.
The research project was supported by the Danish Parkinson's disease Association and PROCRIN (Program for Clinical Research Infrastructure
#Disabled People Pilot A Robot Remotely With Their Thoughts, Ecole Polytechnique Federale de Lausanne Study Disabled People Pilot A Robot Remotely With Their Thoughts Using a telepresence system developed at EPFL,
19 people including nine quadriplegics were able to remotely control a robot located in one of the university laboratories.
This multi-year research project aims to give a measure of independence to paralysed people.
This technology has shown that it works well and is easy to use. For someone suffering from paralysis or limited mobility, visiting with other people is extremely difficult.
A team of researchers at the Defitech Foundation Chair in Brain-Machine Interface (CNBI headed by José del R. Millán,
has however been working on a revolutionary brain-machine approach in order to restore a sense of independence to the disabled.
The idea is to remotely control a robot from home with one's thoughts. The research, involving numerous subjects located in different countries, produced excellent results in both human and technical terms.
each of the subjects put on an electrode-studded hat capable of analysing their brain signals. They then instructed the robot to move,
transmitting their instructions in real time via internet from their home country. By virtue of its video camera, screen and wheels, the robot, located in an EPFL laboratory, was able to film itself as it moved
while displaying the face of the remote pilot via Skype. The person at the controls,
as if moving in place of the robot, was able to interact with whoever the robot crossed paths with. ach of the 9 subjects with disabilities managed to remotely control the robot with ease after less than 10 days of training,
said Professor Millán. Shared control between human and machine The brain-machine interface developed by the researchers goes even further.
The robot is able to avoid obstacles by itself, even when it is told not to.
and the computer, allowing the pilot to rest while navigating. No difference between healthy and disabled subjects In the end
Mature technology available The positive results of this research bring to a close the European project called TOBI (Tools for Brain-Computer Interaction
Will robots soon become a fact of daily life for people suffering from a disability?
Too soon to say, according to Professor Millán . or this to happen, insurance companies will have to help finance these technologies. ey,
check out all the engineering jobs. Post your resume today t
#Enriched Blood cells Preserve Cognition In Mice With Features Of Alzheimer's disease, Cedars-Sinai Medical center Study Enriched Blood cells Preserve Cognition In Mice With Features Of Alzheimer's disease Los angeles-July 6,
2015 Cedars-Sinai researchers have tested successfully two new methods for preserving cognition in laboratory mice that exhibit features of Alzheimer's disease by using white blood cells from bone marrow
and a drug for multiple sclerosis to control immune response in the brain. Under the two approaches, immune cells from outside the brain were found to travel in greater numbers through the blood into the brain.
The study showed measurable benefits in mice an encouraging step toward further testing of these potentially powerful strategies in human trials.
Researchers point out that the brain's own immune cells are critical for its healthy function.
During the progression of Alzheimer's disease, these cells are found to be defective. In this study, the researchers discovered that immune cells infiltrating the brain from the blood effectively resisted various abnormalities associated with the condition."
"These cells appear to work in the brain in several ways to counter the negative effects associated with Alzheimer's disease,
"said Maya Koronyo-Hamaoui, Phd, assistant professor of neurosurgery and biomedical sciences at Cedars-Sinai, and the senior author of the article published in Brain, a journal of Oxford university Press."
"The increasing incidence of Alzheimer's disease and the lack of any effective therapy make it imperative to explore new strategies, especially those that can target multiple abnormalities in such a complicated disease,"Koronyo-Hamaoui added.
In Alzheimer's disease, a protein fragment known as amyloid-beta builds up at the synapses of neurons the point where neuron-to-neuron communication occurs.
As a result, synapses are lost and cognitive function becomes severely impaired. Immune cells in the brain that are exposed to increasing concentrations of the toxic protein fragment deteriorate
and lose their ability to attack and clear away the buildup. Over time these cells themselves go awry,
contributing to harmful inflammation and becoming toxic to the neurons. During the course of the disease, cells that support the brain's structure and function also fail at the cellular and molecular levels,
steadily impairing memory and learning functions. In efforts to boost an effective immune response, the Cedars-Sinai scientists have devised ways to"recruit"white blood cells known as monocytes from bone marrow to attack the protein fragments
and preserve the synapses. The researchers evaluated two such methods and their therapeutic potential. In one, they extracted a specific type of monocytes from the bone marrow of healthy young mice
and injected the cells into the tail veins of sick mice once a month. A second group of sick mice received weekly under-the-skin injections of glatiramer acetate,
an FDA-approved drug used for the treatment of multiple sclerosis; the drug has been shown to foster the migration of white blood cells from the bloodstream to the brain.
A third group received both treatments. All three groups experienced a substantial decrease in Alzheimer's-like pathology and symptoms.
The varied approaches were effective in"recruiting"protective monocytes to"lesion sites"in the brain,
removing protein fragments and reducing harmful inflammation through the secretion of chemicals that regulate immunity at the molecular level,
said Koronyo-Hamaoui, the head of Cedars-Sinai's neuroimmunology laboratory at themaxine Dunitz Neurosurgical Institute and a faculty member in the Department of Neurosurgery and Department of Biomedical sciences.
In this study glatiramer acetate was further found to profoundly affect monocytes'function, she added.""This study provides the evidence that a subgroup of unmodified monocytes,
extracted from the bone marrow of healthy mouse donors and grafted into the bloodstream, can migrate into the brains of sick mice,
directly clear abnormal protein accumulation and preserve cognitive function,"said Yosef Koronyo, the article's first author and a research associate in the Department of Neurosurgery.
Koronyo added that the study gives unprecedented details about monocyte numbers migrating into brain lesion sites
and the compounds they secrete, and shows that the body's natural monocytes can have direct effects on the integrity of synapses.
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