Antimicrobial resistance is drastically rising

The world is experiencing unprecedented economic growth in low- and middle-income countries. An increasing number of people in India, China, Latin America and Africa have become wealthier, and this is reflected in their consumption of meat and dairy products. In Africa, meat consumption has risen by more than half; in Asia and Latin America it is up by two-thirds.

To meet this growing demand, animal husbandry has been intensified, with among other things, an increased reliance on the use of antimicrobials. Farmers use antimicrobials to treat and prevent infections for animals raised in crowded conditions but these drugs are also used to increase weight gain, and thus improve profitability.

This excessive and indiscriminate use of antimicrobials has serious consequences: the proportion of bacteria resistant to antimicrobials is rapidly increasing around the world. Drugs are losing their efficacy, with important consequences for the health of animals but also potentially for humans.

Mapping resistance hotspots

Low- and middle income countries have limited surveillance capacities to track antimicrobial use and resistance on farms. Antimicrobial use is typically less regulated and documented there than in wealthy industrialized countries with established surveillance systems.

The team of researchers led by Thomas Van Boeckel, SNF Assistant Professor of Health Geography and Policy at ETH Zurich, has recently published a map of antimicrobial resistance in animals in low- and middle-income countries in the journal Science.

The team assembled a large literature database and found out where, and in which animals species resistance occurred for the common foodborne bacteria Salmonella, E. coli, Campylobacter and Staphylococcus.

According to this study, the regions associated with high rates of antimicrobial resistance in animals are northeast China, northeast India, southern Brazil, Iran and Turkey. In these countries, the bacteria listed above are now resistant to a large number of drug that are used not only in animals but also in human medicine. An important finding of the study is that so far, few resistance hotspots have emerged in Africa with the exception of Nigeria and the surroundings of Johannesburg.

The highest resistance rates were associated with the antimicrobials most frequently used in animals: tetracyclines, sulphonamides, penicillins and quinolones. In certain regions, these compounds have almost completely lost their efficacy to treat infections.

Alarming trend in multi-drug resistance

The researchers introduced a new index to track the evolution of resistance to multiple drugs: the proportion of drugs tested in each region with resistance rates higher than 50%. Globally, this index has almost tripled for chicken and pigs over the last 20 years. Currently, one third of drugs fail 50% of the time in chicken and one quarter of drug fail in 50% of the time in pigs.

"This alarming trend shows that the drugs used in animal farming are rapidly losing their efficacy," Van Boeckel says. This will affect the sustainability of the animal industry and potentially the health of consumers.

It is of particular concern that antimicrobial resistance is rising in developing and emerging countries because this is where meat consumption is growing the fastest, while access to veterinary antimicrobials remains largely unregulated. "Antimicrobial resistance is a global problem. There is little point in making considerable efforts to reduce it on one side of the world if it is increasing dramatically on the other side," the ETH researcher says.

Input from thousands of studies

For their current study, the team of researchers from ETH, Princeton University and the Free University of Brussels gathered thousands of publications as well as unpublished veterinary reports from around the world. The researchers used this database to produce the maps of antimicrobial resistance.

However, the maps do not cover the entire research area; there are large gaps in particular in South America, which researchers attribute to a lack of publicly available data. "There are hardly any official figures or data from large parts of South America," says co-author and ETH postdoctoral fellow Joao Pires. He said this surprised him, as much more data is available from some African countries , despite resources for conducting surveys being more limited than in South America.

Open-access web platform

The team has created an open-access web platform resistancebank.org to share their findings and gather additional data on resistance in animals. For example, veterinarians and state-authorities can upload data on resistance in their region to the platform and share it with other people who are interested.

Van Boeckel hopes that scientists from countries with more limited resources for whom publishing cost in academic journal can be a barrier will be able to share their findings and get recognition for their work on the platform. "In this way, we can ensure that the data is not just stuffed away in a drawer" he says, "because there are many relevant findings lying dormant, especially in Africa or India, that would complete the global picture of resistance that we try to draw in this first assessment. The platform could also help donors to identify the regions most affected by resistance in order to be able to finance specific interventions.

As meat production continues to rise, the web platform could help target interventions against AMR and assist a transition to more sustainable farming practices in low- and middle-income countries. "The rich countries of the Global North, where antimicrobials have been used since the 1950s, should help make the transition a success," says Van Boeckel.

How the eyes might be windows to the risk of Alzheimer's disease

Closeup of senior woman's eye

Alzheimer's disease (AD) begins to alter and damage the brain years -- even decades -- before symptoms appear, making early identification of AD risk paramount to slowing its progression.

In a new study published online in the September 9, 2019 issue of the Neurobiology of Aging, scientists at University of California San Diego School of Medicine say that, with further developments, measuring how quickly a person's pupil dilates while they are taking cognitive tests may be a low-cost, low-invasive method to aid in screening individuals at increased genetic risk for AD before cognitive decline begins.

In recent years, researchers investigating the pathology of AD have primarily directed their attention at two causative or contributory factors: the accumulation of protein plaques in the brain called amyloid-beta and tangles of a protein called tau. Both have been linked to damaging and killing neurons, resulting in progressive cognitive dysfunction.

The new study focuses on pupillary responses which are driven by the locus coeruleus (LC), a cluster of neurons in the brainstem involved in regulating arousal and also modulating cognitive function. Tau is the earliest occurring known biomarker for AD; it first appears in the LC; and it is more strongly associated with cognition than amyloid-beta. The study was led by first author William S. Kremen, PhD, and senior author Carol E. Franz, PhD, both professors of psychiatry and co-directors of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine.

The LC drives pupillary response -- the changing diameter of the eyes' pupils -- during cognitive tasks. (Pupils get bigger the more difficult the brain task.) In previously published work, the researchers had reported that adults with mild cognitive impairment, often a precursor to AD, displayed greater pupil dilation and cognitive effort than cognitively normal individuals, even if both groups produced equivalent results. Critically, in the latest paper, the scientists link pupillary dilation responses with identified AD risk genes.

"Given the evidence linking pupillary responses, LC and tau and the association between pupillary response and AD polygenic risk scores (an aggregate accounting of factors to determine an individual's inherited AD risk), these results are proof-of-concept that measuring pupillary response during cognitive tasks could be another screening tool to detect Alzheimer's before symptom appear," said Kremen.

Source :- Science Daily

Commonly used antibiotics may lead to heart problems

Antibiotic pills illustration

Scientists have shown for the first time a link between two types of heart problems and one of the most commonly prescribed classes of antibiotics.

In a study published today in the Journal of the American College of Cardiology, researchers at the University of British Columbia (UBC) in partnership with the Provincial Health Services Authority's (PHSA) Therapeutic Evaluation Unit found that current users of fluoroquinolone antibiotics, such as Ciprofloxacin or Cipro, face a 2.4 times greater risk of developing aortic and mitral regurgitation, where the blood backflows into the heart, compared to patients who take amoxicillin, a different type of antibiotic. The greatest risk is within 30 days of use.

Recent studies have also linked the same class of antibiotics to other heart problems.

Some physicians favour fluoroquinolones over other antibiotics for their broad spectrum of antibacterial activity and high oral absorption, which is as effective as intravenous, or IV, treatment.

"You can send patients home with a once-a-day pill," said Mahyar Etminan, lead author and associate professor of ophthalmology and visual sciences in the faculty of medicine at UBC. "This class of antibiotics is very convenient, but for the majority of cases, especially community-related infections, they're not really needed. The inappropriate prescribing may cause both antibiotic resistance as well as serious heart problems."

The researchers hope their study helps inform the public and physicians that if patients present with cardiac issues, where no other cause has been discovered, fluoroquinolone antibiotics could potentially be a cause.

"One of the key objectives of the Therapeutic Evaluation Unit is to evaluate different drugs and health technologies to determine whether they enhance the quality of care delivered by our programs or improve patient outcomes," said Dr. Bruce Carleton, director of the unit and research investigator at BC Children's Hospital, a program of PHSA. "This study highlights the need to be thoughtful when prescribing antibiotics, which can sometimes cause harm. As a result of this work, we will continue working with the BC Antimicrobial Stewardship Committee to ensure the appropriate prescribing of this class of antibiotics to patients across British Columbia, and reduce inappropriate prescribing."

For the study, scientists analyzed data from the U.S. Food and Drug Administration's adverse reporting system. They also analyzed a massive private insurance health claims database in the U.S. that captures demographics, drug identification, dose prescribed and treatment duration. Researchers identified 12,505 cases of valvular regurgitation with 125,020 case-control subjects in a random sample of more than nine million patients. They defined current fluoroquinolone exposure as an active prescription or 30 days prior to the adverse event, recent exposure as within days 31 to 60, and past exposure as within 61 to 365 days prior to an incident. Scientists compared fluoroquinolone use with amoxicillin and azithromycin.

The results showed that the risk of aortic and mitral regurgitation, blood backflow into the heart, is highest with current use, followed by recent use. They saw no increased risk aortic and mitral regurgitation with past use.

Etminan hopes that if other studies confirm these findings, regulatory agencies would add the risk of aortic and mitral regurgitation to their alerts as potential side effects and that the results would prompt physicians to use other classes of antibiotics as the first line of defense for uncomplicated infections.

This study was funded and conducted by the department of ophthalmology and the Therapeutic Evaluation Unit at the Provincial Health Services Authority.

Source :- Science Daily

A smart artificial hand for amputees merges user and robotic control

EPFL scientists are developing new approaches for improved control of robotic hands -- in particular for amputees -- that combines individual finger control and automation for improved grasping and manipulation. This interdisciplinary proof-of-concept between neuroengineering and robotics was successfully tested on three amputees and seven healthy subjects. The results are published in today's issue of Nature Machine Intelligence.

The technology merges two concepts from two different fields. Implementing them both together had never been done before for robotic hand control, and contributes to the emerging field of shared control in neuroprosthetics.

One concept, from neuroengineering, involves deciphering intended finger movement from muscular activity on the amputee's stump for individual finger control of the prosthetic hand which has never before been done. The other, from robotics, allows the robotic hand to help take hold of objects and maintain contact with them for robust grasping.

"When you hold an object in your hand, and it starts to slip, you only have a couple of milliseconds to react," explains Aude Billard who leads EPFL's Learning Algorithms and Systems Laboratory. "The robotic hand has the ability to react within 400 milliseconds. Equipped with pressure sensors all along the fingers, it can react and stabilize the object before the brain can actually perceive that the object is slipping. "

How shared control works

The algorithm first learns how to decode user intention and translates this into finger movement of the prosthetic hand. The amputee must perform a series of hand movements in order to train the algorithm that uses machine learning. Sensors placed on the amputee's stump detect muscular activity, and the algorithm learns which hand movements correspond to which patterns of muscular activity. Once the user's intended finger movements are understood, this information can be used to control individual fingers of the prosthetic hand.

"Because muscle signals can be noisy, we need a machine learning algorithm that extracts meaningful activity from those muscles and interprets them into movements," says Katie Zhuang first author of the publication.

Next, the scientists engineered the algorithm so that robotic automation kicks in when the user tries to grasp an object. The algorithm tells the prosthetic hand to close its fingers when an object is in contact with sensors on the surface of the prosthetic hand. This automatic grasping is an adaptation from a previous study for robotic arms designed to deduce the shape of objects and grasp them based on tactile information alone, without the help of visual signals.

Many challenges remain to engineer the algorithm before it can be implemented in a commercially available prosthetic hand for amputees. For now, the algorithm is still being tested on a robot provided by an external party.

"Our shared approach to control robotic hands could be used in several neuroprosthetic applications such as bionic hand prostheses and brain-to-machine interfaces, increasing the clinical impact and usability of these devices," Silvestro Micera, EPFL's Bertarelli Foundation Chair in Translational Neuroengineering, and Professor of Bioelectronics at Scuola Superiore Sant'Anna.

Source :- Science Daily

FDA phase 1 trial shows hydrogel to repair heart is safe to inject in humans -- a first

Heart attack

Ventrix, a University of California San Diego spin-off company, has successfully conducted a first-in-human, FDA-approved Phase 1 clinical trial of an injectable hydrogel that aims to repair damage and restore cardiac function in heart failure patients who previously suffered a heart attack.

The trial is the first to test a hydrogel designed to repair cardiac tissue. It is also the first to test a hydrogel made from the natural scaffolding of cardiac muscle tissue, also known as extracellular matrix, or ECM. This is significant because ECM hydrogels have been shown in preclinical studies to potentially be effective for other conditions, such as poor blood circulation due to peripheral artery disease. The trial showed that the hydrogel, known as VentriGel, can be safely injected via catheter into patients who had suffered a heart attack in the past 2 to 36 months.

"Although the study was designed to evaluate safety and feasibility and not designed to show whether VentriGel effectively helps improve heart function, we observed some improvements in patients," said Karen Christman, the paper's senior author and a professor of bioengineering in the Jacobs School of Engineering and the Institute of Engineering in Medicine at UC San Diego. "For example, patients could walk longer distances. We also observed signs of improving heart function in patients who experienced a heart attack more than one year prior to treatment."

Researchers from Ventrix, led by Christman, report their findings in the Sept. 11 issue of the Journal of the American College of Cardiology: Basic to Translational Science. Dr. Jay Traverse at Minneapolis Heart Institute was the lead clinical investigator.

There are an estimated 785,000 new heart attack cases in the United States each year, with no established treatment for repairing the resulting damage to cardiac tissue. After a heart attack, scar tissue develops, which diminishes muscle function and leads to heart failure. This is where VentriGel comes in. Once injected in damaged cardiac muscle, VentriGel forms a scaffold that acts as a reparative environment where healthy cells migrate, leading to increases in cardiac muscle, less scar tissue, and improvements in heart function.

VentriGel was invented by Christman and her team, then licensed from UC San Diego and developed by Ventrix, Inc, which was cofounded by CEO Adam Kinsey and Christman.

VentriGel is made from cardiac connective tissue taken from pigs, which is stripped of heart muscle cells through a cleansing process. It is then freeze-dried and milled into powder form, and then liquefied into a fluid that can be easily injected into heart muscle in a minimally invasive procedure that does not require surgery. Once it hits body temperature, the liquid turns into a semi-solid, porous gel.

The Phase 1 trial evaluated the gel in 15 patients who sustained moderate damage in the left ventricle chamber of the heart following a heart attack. Each patient received up to 18 injections of VentriGel into the damaged region via catheter. Researchers followed the patients for six months after treatment. All patients completed the full follow-up.

Twelve of the 15 patients were men. All 15 were experiencing mild to moderate heart failure following a heart attack. Half had suffered a heart attack within the past year.

Patients took a six-minute walking test as well as a heart function assessment and a heart health questionnaire before the injections. They retook the tests three and six months later. In addition, patients underwent an MRI at three and six months after the procedures.

Ventrix is now gearing up for a Phase 2 clinical trial that will expand on this successful first-in-human study. They are planning a larger, randomized trial that will evaluate how effectively VentriGel can improve cardiac function and quality of life for patients experiencing heart failure.

Source :- Science Daily