Body

What The Study Did: About 3,800 adults 40 and older in South Korea participating in a national health survey were included in this analysis that examined associations between hearing loss and a test of their ability to retain balance. Age-related hearing loss affects the inner ear, which may increase the risk of dizziness.

Authors: Sung-Won Chae, M.D., Ph.D., of Korea University Medicine in Seoul, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamaoto.2020.0293)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

Non-Hodgkin lymphoma (NHL) is a group of cancers that originate in the lymph nodes and affect white blood cells of the immune system called B cells. In NHL, B cells grow out of control and create tumors in the lymph nodes, spleen, or other tissues. According to the American Cancer Society, about 80,000 people will be diagnosed with NHL in 2020, and 20,000 will die of it.

Today, immunotherapy is one of the most promising treatment for cancer patients. Unlike radio- or chemo- therapies, immunotherapy aims to "switch on" the patient's own immune system to attack and eliminate the tumor. However, tumors, including NHL, often mutate to make themselves invisible to the immune system or even exploit interactions with immune cells to grow.

A team of researchers led by Elisa Oricchio at EPFL have now identified one of the mechanisms used by NHL to hijack the immune system. The scientists found that certain patients with NHL have a mutated and over-activated form of a protein called cathepsin S. This protein is responsible for cutting other proteins into small fragments that are then exposed on the surface of tumor cells. These fragments mediate communications between cancer and immune cells.

"When cathepsin S is active, cancer cells interact with immune cells called CD4+ T-cells, which help the tumor to grow, while they maintain social distance with CD8+ T-cells, which would attack and kill the tumor," explains Elie Dheilly, one of the lead authors of the study.

The identification of this duplicitous relationship between cancer cells and T-cells prompted the researchers to genetically eliminate cathepsin S to understand how tumor growth would be affected.

Inhibiting cathepsin S reduced tumor growth by inverting the communication with T-cells: CD8+ T-cells were now attacking the tumor, while CD4+ T-cells were kept at bay. This happens by inducing something called "antigen diversification", which generates a different population of fragments helping T-cells to identify and kill tumor cells.

"We think that cathepsin S could represent an important therapeutic target," says Elisa Oricchio. "Inducing antigen diversification is an attractive therapeutic strategy to increase tumor immunogenicity and enhance response to immunotherapies in lymphoma but possibly also in other tumor types."

During the study, Elena Battistello, co-lead author, developed a new imaging technique to specifically measure the activity of cathepsin S. Using this technique, Oricchio and her team have identified and further developed new inhibitors (patent application filed) that could be used to improve the treatment of patients diagnosed with NHL.

Sophia Antipolis - 24 April 2020: Lost football games may trigger heart attacks in male fans, according to research presented today on EAPC Essentials 4 You, a scientific platform of the European Society of Cardiology (ESC).

"Our study shows that poor results from the local professional football team coincided with more heart attacks in male residents," said study author Dr. Lukasz Kuzma of the Medical University of Bialystok, Poland. "The findings suggest that the mental and emotional stress of defeat can provoke cardiac events."

The study examined the connection between performance of the Jagiellonia Bialystok football team and admissions for acute coronary syndromes. The club is known for its large group of avid supporters - an average of 17,174 per match in the 2016/17 season - who strongly identify themselves with the team.

The study included 10,529 patients with acute coronary syndromes (heart attack and unstable angina) admitted to the Clinical Hospital of Medical University of Bialystok in 2007 to 2018. This was the only centre in the city with 24-hour invasive cardiology services during this period. The average age of patients was 66.6 years and 62% were men.

The team played 451 national and European matches during the study period. The day after the team lost a home game, there was a 27% rise in male admissions for acute coronary syndromes. No association was found in women.

"Strong emotions can induce heart attacks and our study indicates that losing a home game can affect supporters," said Dr. Kuzma. "Fans, particularly men with unhealthy lifestyles, should take up regular exercise and avoid smoking and excessive alcohol consumption. These steps are the key to supporting your favourite team as long as you wish without damaging your own health."

OAK BROOK, Ill. (April 23, 2020) - A new expert panel consensus statement published simultaneously today in the journals Radiology: Imaging Cancer, Chest and the Journal of the American College of Radiology provides guidance to clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic.

In many parts of the world, the COVID-19 public health crisis has stressed the health care system close to or even past its breaking point. Hospital resources are focused on the immediate needs of patients suffering from the disease, particularly those who are critically ill. The strain on health care systems and the need to control the virus using containment and mitigation has impacted the care of patients with other common medical disorders.

Clinicians have been forced to balance the risk of delaying potentially necessary exams against the risk of exposing patients to the virus in hospital settings or exposing health care workers to patients who may be asymptomatic carriers of the disease. This is further complicated by the re-allocation of resources, including hospital personnel, to evaluate and treat patients with COVID-19.

"The potential risk of exposure or transmission during routine care, as well as the diversion of resources to help combat the pandemic, has forced clinicians to make decisions about the timing of care," said Peter J. Mazzone, M.D., M.P.H., FCCP, director of the Lung Cancer Program and Lung Cancer Screening Program for the Cleveland Clinic Respiratory Institute. "This document provides guidance that we hope will help with these decisions. It outlines acceptable variances from standard practice during the pandemic and provides items to consider that could influence the decisions for a given patient."

Performing a lung cancer screening exam or the evaluation of lung nodules both carry additional risk during the COVID-19 pandemic. There is added risk to the patient, other patients and health care providers from exposure to the health care environment and the contact that occurs during testing. Recovery from surgical resection may be influenced by asymptomatic carriage of the virus. These added risks may upset the balance of benefit and harm struck by current (pre-COVID) guideline recommendations. There is also a shift in health care resources, toward canceling elective procedures and imaging, in areas where

COVID-19 is surging, or where systems are preparing for a surge, making it more difficult to adhere to available guidelines. These exposure risks and resource constraints have led the Centers for Disease Control and Prevention (CDC) to suggest that non-urgent care be deferred.

To date, clinicians and hospital systems have been independently determining how to modify their screening and lung nodule management programs during the pandemic. The consensus statement was developed to provide expert opinion to clinicians regarding the performance of lung cancer screening and the management of patients with lung nodules in a manner that is consistent with current CDC COVID-19 guidance.

Three project leaders and 21 panel members participated in developing the consensus statement. Their specialties included pulmonology, thoracic radiology and thoracic surgery. Twelve scenarios were developed, each with a statement requiring a vote. The voting results for all statements exceeded the threshold of 70% of panel members voting agree or strongly agree. Scenarios recommendations and notes are included in the report.

Consensus was unanimous for recommendations to delay baseline or repeat annual screening, and over 95% of panelists agreed to delay the evaluation of pulmonary nodules detected incidentally or by screening that have a low probability of cancer or are likely to be an indolent cancer.

Consensus was less uniform but still strong for recommendations to delay or modify the evaluation and management of patients with nodules measuring greater than 8 millimeters in average diameter.

The authors note that these recommendations are not "one-size-fits-all" and state that patient preferences should be considered in all of the scenarios, because individual patients are likely to differ in how they perceive the potential benefits and harms associated with delayed or modified evaluation and management.

The paper points out that due to the fluidity of the situation, it is not possible at this time to determine when it will be advisable to return to usual care practices.

"We hope these statements are helpful and provide some reassurance and direction to individuals who are eligible for lung cancer screening, patients with lung nodules, and the clinicians who care for them," the authors conclude.

RSNA is committed to connecting radiologists and the radiology community to the most timely and useful COVID-19 information and resources. RSNA's COVID-19 Resources page houses the latest guidance, original research, image collection and more. The page will be updated on an ongoing basis.

Researchers at the Federal University of São Carlos (UFSCar) in Sorocaba (state of São Paulo, Brazil) have developed a technique to diagnose early-stage multiple sclerosis, a disease of the central nervous system, and distinguish it from neuromyelitis optica, a rare yet severe autoimmune inflammatory process also affecting the central nervous system.

The immune system of a person with these diseases produces antibodies that attack and damage part of the myelin sheath, an insulating layer that protects nerves, including those in the brain and spinal cord, and aids the transmission of electrical impulses. Permanent lesions form in brain regions over time.

Using a nanobiosensor originally developed to detect herbicides, heavy metals and other pollutants, the UFSCar group created a method for observing myelin basic protein (MBP) peptides interacting with antibodies in samples from patients under an atomic force microscope (AFM).

“Atomic force spectroscopy can detect the presence of specific antibodies for each of these two diseases in cerebrospinal fluid and blood serum. If the antibodies are attracted by the peptides deposited on the sensor during the test, this is a sign that the patient has the disease. The device is highly sensitive and can detect a small amount of antibodies, so the method can diagnose the disease at an early stage,” said Fabio de Lima Leite, a researcher in UFSCar’s Science and Technology for Sustainability Center and last author of an article on the method published in UltraMicroscopy.

Leite began researching nanobiosensors over ten years ago with a Young Investigator Grant from FAPESP and has since continued to study the subject as a principal investigator for UFSCar’s Nanoneurobiophysics Research Group (GNN).

His main motivation for shifting his research focus from detecting herbicides to identifying antibodies was the difficulty in diagnosing demyelinating and neurodegenerative disorders. Multiple sclerosis is usually diagnosed clinically on the basis of symptoms reported by the patient and by MRI scanning to identify lesions in certain brain regions.

“Our method is more accurate, avoiding diagnostic errors, as well as being cheaper. An AFM can cost about 20,000 dollars, whereas an MRI machine costs upwards of 400,000 dollars,” Leite said.

For researchers, the earlier these diseases are diagnosed, the sooner treatment can begin with less risk of complications. “There’s no cure, but early diagnosis can give patients quality of life and better treatment,” said Ariana de Souza Moraes, a researcher at UFSCar and a coauthor of the article.

In the study, the researchers used serum and cerebrospinal fluid from patients who were at different stages of multiple sclerosis and receiving treatment at the hospital run by São Paulo State University’s Botucatu Medical School (FMB-UNESP) under the responsibility of Doralina Guimarães Brum, a researcher at the school, and Paulo Diniz da Gama, a neurologist affiliated with the Pontifical Catholic University of São Paulo (PUC-SP) in Sorocaba.

The samples were purified by Luís Antonio Peroni’s firm RheaBiotech with FAPESP’s support under its Innovative Research in Small Business Program (PIPE).

To develop the sensor, it was necessary to synthesize MBP peptides. This was done at the University of São Paulo’s Peptide Chemistry Laboratory, headed by Maria Teresa Machini.

“The cerebrospinal fluid and serum were purified, leaving only antibodies in each sample. This enabled us to detect specific antibodies for multiple sclerosis, such as anti-MBP 85-99. If these antibodies are circulating in a patient, they probably have multiple sclerosis. Our next step in the study is to produce a sensor that doesn’t require purified samples,” Leite said.

In another study published recently in Scientific Reports, UFSCar researchers identified patients with neuromyelitis optica and distinguished them from patients with multiple sclerosis. “A biomarker for the disease exists, so it was possible to detect the anti-aquaporin 4 antibody in patient samples by the same method as that used to detect multiple sclerosis,” Moraes said.

Neuromyelitis optica can currently be diagnosed by ELISA (enzyme-linked immunosorbent assay), a widely available method that is inexpensive and hence affordable for most patients. “However, this method isn’t as sensitive as the nanoimmunosensor and can’t detect the disease in its early stages,” Moraes said.

Another advantage of the sensor is that it can distinguish the two diseases, avoiding a common diagnostic error. “The two disorders have similar symptoms but different action mechanisms and treatments,” Moraes said. “An immunomodulator is recommended for one and an immunosuppressant for the other. An incorrect diagnosis can aggravate the disease. If a patient with neuromyelitis optica is treated for multiple sclerosis, optic nerve inflammation is accelerated and can’t be reversed. The sensor is expected to represent a major advance for patients with demyelinating disorders.”

CHAMPAIGN, Ill. -- Most viral test kits rely on labor- and time-intensive laboratory preparation and analysis techniques; for example, tests for the novel coronavirus can take days to detect the virus from nasal swabs. Now, researchers have demonstrated an inexpensive yet sensitive smartphone-based testing device for viral and bacterial pathogens that takes about 30 minutes to complete. The roughly $50 smartphone accessory could reduce the pressure on testing laboratories during a pandemic such as COVID-19.

The results of the new multi-institutional study, led by University of Illinois at Urbana-Champaign electrical and computer engineering professor Brian Cunningham and bioengineering professor Rashid Bashir, are reported in the journal Lab on a Chip.

"The challenges associated with rapid pathogen testing contribute to a lot of uncertainty regarding which individuals are quarantined and a whole host of other health and economic issues," Cunningham said.

The study began with the goal of detecting a panel of viral and bacterial pathogens in horses, including those that cause severe respiratory illnesses similar to those presented in COVID-19, the researchers said.

"Horse pathogens can lead to devastating diseases in animal populations, of course, but one reason we work with them has to do with safety. The horse pathogens in our study are harmless to humans," Cunningham said.

The new testing device is comprised of a small cartridge containing testing reagents and a port to insert a nasal extract or blood sample, the researchers said. The whole unit clips to a smartphone.

Inside the cartridge, the reagents break open a pathogen's outer shell to gain access to its RNA. A primer molecule then amplifies the genetic material into many millions of copies in about 10 or 15 minutes, the researchers said. A fluorescent dye stains the copies and glows green when illuminated by blue LED light, which is then detected by the smartphone's camera.

"This test can be performed rapidly on passengers before getting on a flight, on people going to a theme park or before events like a conference or concert," Cunningham said. "Cloud computing via a smartphone application could allow a negative test result to be registered with event organizers or as part of a boarding pass for a flight. Or, a person in quarantine could give themselves daily tests, register the results with a doctor, and then know when it's safe to come out and rejoin society."

There are a few preparatory steps currently performed outside of the device, and the team is working on a cartridge that has all of the reagents needed to be a fully integrated system. Other researchers at the U. of I. are using the novel coronavirus genome to create a mobile test for COVID-19, and making an easily manufactured cartridge that Cunningham said would improve testing efforts.

CORVALLIS, Ore. - Supplements containing vitamins C and D and other micronutrients, sometimes in amounts exceeding the federally recommended levels, are a safe, effective and low-cost means of helping your immune system fight off COVID-19 and other acute respiratory tract diseases, an Oregon State University researcher says.

Findings were published today in the journal Nutrients.

Adrian Gombart of OSU's Linus Pauling Institute and collaborators at the University of Southampton (United Kingdom), the University of Otago (New Zealand) and University Medical Center (The Netherlands) say public health officials should issue a clear set of nutritional recommendations to complement messages about the role of hand washing and vaccinations in preventing the spread of infections.

"Around the world, acute respiratory tract infections kill more than 2.5 million people every year," said Gombart, professor of biochemistry and biophysics in the OSU College of Science and a principal investigator at the Linus Pauling Institute. "Meanwhile, there's a wealth of data that shows the role that good nutrition plays in supporting the immune system. As a society we need to be doing a better job of getting that message across along with the other important, more common messages."

Specific vitamins, minerals and fatty acids have key jobs to play in helping your immune system, he says. In particular vitamin C, vitamin D, zinc, and an omega-3 fatty acid found in fish, docosahexaenoic acid, also known as DHA, are critical for immune function.

"The roles that vitamins C and D play in immunity are particularly well known," he said. "Vitamin C has roles in several aspects of immunity, including the growth and function of immune cells and antibody production. Vitamin D receptors on immune cells also affect their function. This means that vitamin D profoundly influences your response to infections.

"The problem is that people simply aren't eating enough of these nutrients. This could destroy your resistance to infections. Consequently, we will see an increase in disease and all of the extra burdens that go along with that increase."

That's why the researchers are urging not only a daily multivitamin, but doses of 200 milligrams or more of vitamin C (higher than the suggested federal guidelines of 75 milligrams for men and 50 for women) and 2,000 international units of vitamin D, rather than the 400 to 800 recommended depending on age.

The stakes are huge, Gombart notes. Every year, influenza alone hospitalizes millions and kills several hundred thousand worldwide.

"A number of standard public health practices have been developed to help limit the spread and impact of respiratory viruses: regular hand washing, avoiding those showing symptoms of infection, and covering coughs," Gombart said. "And for certain viruses like influenza, there are annual vaccination campaigns."

There is no doubt that vaccines, when available, can be effective, but they're not foolproof, he says.

Gombart emphasizes that current public health practices - stressing social distancing, hygiene and vaccinations - are important and effective but in need of complementary strategies. A nutritional focus on the immune system could help minimize the impact of many kinds of infections.

"The present situation with COVID-19 and the number of people dying from other respiratory infections make it clear that we are not doing enough," he said. "We strongly encourage public health officials to include nutritional strategies in their arsenal."

Timely research from Newcastle Hospitals and University has shown that the rate of infection among NHS staff treating patients is no higher than for those in non-clinical roles.

These findings, published today in The Lancet, may offer some reassurance to NHS staff on the frontline.

The work has been carried out by researchers and medics at the Newcastle Upon Tyne Hospitals NHS Foundation Trust and Newcastle University, UK - the key findings are:

1. Delivering staff testing during the pandemic is feasible.

2. The rates of positive tests in patient-facing staff were no higher than in those staff in clerical or administrative roles who have no patient contact.

3. The data provides a unique insight into the COVID-19 epidemic in England. The growth in cases clearly "flattened" after the introduction of social distancing measures.

Dr Christopher Duncan, Research Fellow at Newcastle University and Honorary Consultant in Infectious Diseases within Newcastle Hospitals, corresponding author of the article, who led the research, said: "An efficient and robust system of testing has enabled 1,414 health care workers to return more rapidly to NHS service in Newcastle in the last three weeks, the vast majority returning directly into patient care."

Dr Lucia Pareja-Cebrian, Director of Infection Prevention and Control within Newcastle Hospitals NHS Foundation Trust, who is also an author of the report, said: "The safety of our staff during the COVID pandemic has always been paramount and we're proud that in Newcastle, we have been a leader in staff testing from the very beginning of this crisis.

"Testing symptomatic staff has allowed us to identify cases early and we're able to provide support immediately to those who have become infected with coronavirus, advising that they self-isolate from others until their symptoms disappear. This means that their families and contacts remain safe. It's important to us that we continue to test symptomatic staff to protect our patients, our staff and their families and loved ones.

"We continue to work hard and to learn from the research so we improve what we do, and we now also provide testing and advice to household contacts of our staff to ensure we continue to protect them and our patients."

Testing

The research demonstrates how testing of NHS staff at volume is possible during a pandemic, with the development of an efficient model which returns results to staff within 48 hours of their initial contact.

From 10th to 31st March, the Trust tested 1,654 staff and in the subsequent two weeks not covered in this report, they have doubled this number. They tested mainly hospital employees from two hospitals in Newcastle, but also local GPs in Newcastle and employees of the North East Ambulance Service.

Staff contact Occupational Health by email and after an initial symptom screen, those with possible symptoms (new continuous cough and/or fever) are given an appointment within 24 hours for the standard PCR test (RdRP assay developed by Public Health England) in a designated screening pod, staffed by trained nurses. They are provided with written advice about self-isolation and receive an email with their test result within the next 24 hours.

Rate of positive tests

Data on the roles of 1,029 of the staff tested was used to identify three groups - those that were directly patient-facing e.g. nurses, doctors, allied health professionals, porters; non-patient facing but potentially at higher risk of an infection caught in a hospital (nosocomial exposure) e.g. domestic and laboratory staff; and finally, non-clinical staff e.g. clerical, administrative, information technology, secretarial etc.

Comparison of the rates of those who tested positive showed no evidence of a significant difference between the three groups. This suggests that transmission of SARS-CoV-2 from patients to NHS staff may reflect wider patterns of SARS-CoV-2 transmission in the community - and is consistent with observations in China, where staff testing was widespread.

The researchers found rates of infection of 15.4% among directly patient facing staff; 16.3% among those non-patient facing, but in roles with a potentially higher risk; and 18.4% among non-clinical staff.

Given that non-clinical staff had similar positivity rates to 'frontline' staff, the researchers conclude that current isolation protocols and personal protective equipment appear sufficient to prevent hospital transmission.

The team admit limitations to the data as they were unable to identify roles among all of the staff tested. The small number of non-clinical staff tested also meant that it was not possible to meaningfully compare transmission dynamics between these groups, where more complex patterns may exist, but studies are ongoing.

Flattening following social distancing

Initially, rates of positive tests for Covid-19 were relatively low, at 5% on 10/11th March, but rose steadily throughout the testing period, to 20% on 30/31st March. There was a period of exponential growth from 10th March until around the 24th March with a doubling time of 2.2 days.

However, from around the 24th March onwards, when the UK Government introduced further social distancing measures, the rate of increase appeared linear.

Although it is not possible to assign causality, it seems plausible that these measures have reduced community transmission of SARS-CoV-2 in the Newcastle region.

Dr Duncan is part of Newcastle Health Innovation Partners (NHIP), a recently designated National Institute for Health Research - NHS England / Improvement Academic Health Science Centre bringing the region's world-class research, NHS and city partners together. He adds: "Beyond the obvious benefits of protecting staff and helping return NHS workers to the frontline, we think that testing might have additional positive impacts on health behaviour.

"For example, it may provide healthcare workers with the confidence that they can self-isolate with mild symptoms, knowing that a rapid negative result will enable them to return to work in a timely manner. This might lessen the desire of staff with mild symptoms to 'soldier on', in fear of abandoning colleagues for between seven and 14 days, so inadvertently contributing to the spread of the disease."

Any health care provider or Trust looking for further information on the setting up of the testing system that is not provided in the academic paper should contact: Dr Elizabeth Murphy, Consultant in Occupational Medicine, Newcastle Hospitals NHS Foundation Trust.

DALLAS – April 22, 2020 – A new protocol using highly sensitive blood tests to determine whether someone is having a heart attack can reduce wait times and overcrowding in emergency departments, according to a new study from UT Southwestern Medical Center.

The findings, published online today in JAMA Open, are particularly meaningful during the current coronavirus pandemic when many people with chest pain may be fearful of going to the hospital.

“Patients are more reluctant to come to the ER with heart-related symptoms during the COVID-19 outbreak. We do not want those with medical emergencies to avoid the hospital due to concern for risk from the virus,” says cardiologist Rebecca Vigen, M.D., assistant professor of internal medicine at UT Southwestern.

The research team led by Vigen found that a new protocol for using high sensitivity cardiac troponin testing can improve efficiency in the ER by more quickly determining which patients are not having a heart attack. Troponins are proteins released when the heart muscle has been damaged. The protocol incorporates the HEART score – history, electrocardiogram, age, risk factors, and troponin – an emergency department risk assessment tool that guides decisions on discharge and stress testing. 

According to the Centers for Disease Control and Prevention, chest pain is the most common reason for trips to the ER, resulting in 7 million annual visits. 

“Our innovative strategy allowed us to ‘rule out’ heart attacks within one hour in more than half of the patients who were tested. This process is safe and improves the efficiency of evaluating patients with possible heart attacks,” says James de Lemos, M.D., professor of internal medicine at UT Southwestern and co-author of the study.

“Emergency room overcrowding has become an urgent health priority that is even more pressing in the current COVID-19 pandemic. Given the large size of the study and its performance during routine operations in our county hospital, we think the findings would apply to many busy U.S. emergency rooms,” de Lemos adds. 

The new protocol was first implemented in December 2017 at Parkland Memorial Hospital, a major safety net hospital in Dallas, and then in October 2018 at UT  Southwestern’s William P. Clements Jr. University Hospital. The study included 31,543 emergency room patients at Parkland from Jan. 1, 2017, to Oct. 16, 2018. Their mean age was 54, the population was racially and ethnically diverse, and 48 percent were women. 

PROVIDENCE, R.I. [Brown University] -- Researchers have discovered a promising new strategy for combating malaria, a mosquito-borne parasite that claims nearly a half-million lives each year.

For a study reported in the journal Nature, researchers screened blood samples from children who had natural immune resistance to severe malaria infection. The study identified an antibody to a particular malaria protein, called PfGARP, that appears to protect resistant children from severe disease. Lab tests showed that antibodies to PfGARP seem to activate a malarial self-destruct mechanism, causing parasite cells living inside human red blood cells to undergo a form of programmed cell death.

The team is hopeful that vaccinating individuals with PfGARP to generate anti-PfGARP antibodies, or directly infusing anti-PfGARP antibodies, would protect them against severe malaria. The team developed preliminary versions of those vaccines, and testing in nonhuman primates has shown promise, the researchers report.

"We demonstrated in two independent studies in nonhuman primates that vaccination with PfGARP protects against a lethal malaria parasite," said study senior author Dr. Jonathan Kurtis, a professor at the Warren Alpert Medical School of Brown University and laboratory director of the Center for International Health Research at Rhode Island Hospital. "What's exciting is that this is a vaccination strategy that attacks malaria in a way that it has never been attacked before -- one in which the parasite becomes complicit in its own demise. We are hopeful that this vaccine, perhaps combined with other malarial antigens, will translate into a strategy that can help prevent severe malaria in people."

Testing of a human vaccine is likely years away, the researchers say, and there's no way to be certain it will work. But the team is hopeful that the approach taken in this study, which looks for the factors that contribute to naturally occurring disease resistance, will prove effective where other approaches have not.

Searching for antibodies

The results described in this new paper were nearly 20 years in the making, beginning with epidemiological research led by Michal Fried and Patrick Duffy of the National Institutes of Health. Starting around 2001, they began recruiting cohorts of children in Tanzania. The kids were enrolled at birth and followed for years to see who among them developed an acquired immune response to malaria.

"There was a ton of hard epidemiological work that went into simply identifying which kids were resistant and which weren't," Kurtis said. "Only after we knew their resistance levels could we use this information to identify the parasite targets that were recognized by antibodies made only by the resistant kids but not by the susceptible kids."

For this latest research, the team selected 12 resistant and 14 susceptible children from the Tanzanian cohort. The researchers looked at blood samples taken from the children around age two, when naturally acquired immunity seems to develop. Using a sophisticated method to introduce malaria proteins to each blood sample one by one, the researchers could look for any antibodies to a particular protein that were present in the resistant samples and not in the susceptible samples. That work identified PfGARP as a potential factor in conferring resistance.

Having identified PfGARP, the researchers then examined whether antibody responses to PfGARP were associated with resistance in a larger sample of 246 children. They found that children without anti-PfGARP antibodies were at 2.5 times higher risk of severe malaria compared to those who had the antibody.

"Kill switch"

The next step was trying to understand how anti-PfGARP antibodies affect the parasite. A series of laboratory experiments showed that the PfGARP protein is produced by malarial trophozoite cells, which live and feed off of nutrients inside red blood cells. The protein is then transported to the outer membrane of the red blood cell, where it makes the parasite cell vulnerable to the antibody.

"It's a kill switch," Kurtis said. "When the antibody binds to the protein, it sends a signal that tells the trophozoite to shrivel up and die. When we introduce the antibody to samples in petri dishes, we end up with 98% or 99% dead parasites."

The activity of the protein begs the question of why an organism would evolve such a self-destruct mechanism. Kurtis thinks it might have evolved as a means of sensing when the parasite's host is in distress.

"It's not necessarily in a parasite's best interest to kill its host," Kurtis said. "Keeping the host infected but alive means more chances for the parasite to reproduce. So what this might be is a means of sensing a host in distress and then reducing parasite load accordingly."

The anti-PfGARP antibody hijacks that evolved system and turns it against the parasite.

Having shown that PfGARP antibodies kill the parasite, the researchers developed two types of PfGARP vaccines. Both of those were shown to be protective in nonhuman primates exposed to a human form of malaria.

A new strategy

Previous efforts to develop vaccines against malaria have met with limited success. But the researchers involved in this latest work say there's reason to believe this new strategy may succeed where others have failed. That's because it attacks the parasite at a different point in the infection cycle from other vaccines.

When an infected mosquito bites someone, it injects thread-like cells called sporozoites, which travel through the bloodstream to the liver. There, the parasite morphs into a different type of cell called merozoites that exit the liver in large quantities to infect red blood cells. Once they've invaded red blood cells, the parasites morph again into trophozoites, which feed off of the nutrients inside the cell before they burst out to start the cycle again.

An existing vaccine that targets the first stage -- aiming to prevent infection of the liver -- has had limited success. That's partly, Kurtis says, because the time window to intervene is so small.

"It takes five minutes for the parasite to go from the mosquito to the liver," he said. "Because it's so quick, the amount of antibody needed to stop it is huge. And if just one sporozoite gets in, you've got malaria."

This new vaccine targets the trophozoite stage, which lasts up to a day, Kurtis says. The researchers are hopeful that the longer window for intervention will reduce the amount of antibody needed to kill the parasite, and thereby make for a more effective vaccine.

"This gives us 24 hours as opposed to 5 minutes to intervene," Kurtis said. "During that time, the parasite expresses PfGARP -- a kill switch. We have designed a vaccine that activates it."

The researchers plan to continue testing different versions of the vaccine in animal models and ultimately to begin human trials in the coming years.

"This was an incredible team effort involving infectious disease experts, pathologists, epidemiologists, geneticists and molecular biologists," Kurtis said. "It really took all of these people to make this possible, and we're hopeful that the end result will be a vaccine that can save lives."

What The Study Did: Recently reported pediatric cases of SARS-CoV-2 from China and Singapore are assessed to evaluate clinical features, diagnostic tests, current therapeutic management and prognosis.

Authors: Amelia Licari, M.D., of the University of Pavia in Italy, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2020.1467)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

April 22, 2020 -- A new qualitative study by researchers at Columbia University Mailman School of Public Health found that the majority of women living with HIV would endorse a monthly long acting injectable (LAI) antiretroviral therapy over current daily pills. LAI HIV therapy has completed Phase III trials and is awaiting Food and Drug Administration approval. Study participants were recruited from the Women's Interagency HIV Study - the largest national study of women living with and at risk for HIV infection. Over half of the 59 women interviewed (56 percent) would choose LAI HIV therapy over daily pills for reasons of convenience, privacy, and perceived effectiveness: in contrast, 34 percent would prefer daily oral pills and 10 percent would prefer neither. This study is the first to exclusively explore women's interest in LAI HIV therapy, and one of the first among a non-clinical trial sample, who more accurately represents the population that will be using LAI HIV therapy. The findings are published in JAIDS: Journal of Acquired Immune Deficiency Syndrome.

"Adherence to antiretroviral therapy is imperative for viral suppression and reducing HIV transmission, but many people living with HIV report difficultly sustaining long-term adherence over the lifespan," said Morgan Philbin, PhD, assistant professor of sociomedical sciences at Columbia Mailman School. We found that long acting injectable antiretroviral therapy was a compelling option among the women we interviewed."

The researchers conducted 59 in-depth interviews with women living with HIV in six Women's Interagency HIV Study (WIHS) sites: New York, Chicago, Washington DC, Atlanta, Chapel Hill, and San Francisco from November 2017 - October 2018. The women received care at university settings that will be among the first to administer LAI antiretroviral therapy once it is approved; none of these women were enrolled in clinical trials for LAI HIV therapy.

Nearly one-quarter of people living with HIV in the United States are women. Of these, 89 percent know their diagnosis, 65 percent receive care, and 51 percent are virally suppressed. Women living with HIV have historically been underrepresented in HIV treatment research, including trials for LAI HIV therapy. "It is therefore imperative to understand their interest in this new technology, since it has the potential to transform HIV treatment," said Philbin.

The mostly male participants in ATLAS and FLAIR LAI ART trials reported a high preference (97 percent in FLAIR, 91 percent in ATLAS) for LAI over daily oral pills and said the side effects -- including fatigue, fever, headache and nausea -- rarely led to trial discontinuation.

While the majority of women in the Columbia University-led WIHS study would also prefer LAI HIV therapy over daily pills, they also raised significant challenges. This includes more frequent doctors' visits (every month versus ever 3 or 4 months) and related transportation barriers, a distrust of new and perceived untested technologies and frustration that LAI would relieve some--but not all--of their current pill burden, noted the researchers.

"Our study demonstrated that women living with HIV are open to long acting injectable antiretroviral therapy, and many believe it will provide distinct benefits over daily pills," noted Philbin. "However, women also described challenges unique to them as women that would need to be addressed in order to ensure that they fully benefit from these new technologies, including the role of children and childbearing, caregiving responsibilities and long histories of medical mistrust. As a result, we want to highlight the need to incorporate women into the process of LAI ART roll out to ensure their inclusion."

The current COVID-19 pandemic has caused global disruption on many levels affecting not only health care, but also economies and educational institutions.

In an article titled "Public Health and COVID-19: From Response to Recovery" Dr. Jim James proposes some solutions which could minimize the socio-economic devastation and, at the same time, optimize the medical response.

According to Dr. James "Since early January the world has been transfixed with COVID-19 and the response to it. Guided by predictive models, produced without knowing key parameters, generating worst-case estimates we have created a global pandemic of fear. Governmental responses have led to the imposition of extreme interventions that have resulted in severe socio-economic damage the results of which will negatively impact Public Health outcomes now and in the future. This is especially true with the imposition of full lock downs as opposed to the use of targeted, risk-adjusted interventions with far less damage to the economic infrastructure. Additionally, a review of global nation-level data shows equal or better COVID-19 outcomes for those using partial as opposed to full lock-downs."

LEBANON, NH - Most breast cancers utilize the female hormone estrogen to grow, so drug-induced estrogen deprivation is used as a treatment in many patients. However, cancer will recur in one-third of these patients. A research team at Dartmouth's and Dartmouth-Hitchcock's Norris Cotton Cancer Center, led by Todd W. Miller, PhD, is trying to understand why dormant breast cancer cells survive despite being starved of estrogen. The team discovered that an anti-diabetes drug, metformin, which is being tested in many clinical trials as an anti-cancer agent, actually activated fat metabolism that protected dormant breast cancer cells during estrogen deprivation. The findings suggest that the drug has context-dependent effects on cancer cells. The results, entitled "AMPK activation by metformin promotes survival of dormant ER+ breast cancer cells," are newly published online in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Metformin activates AMPK, which is a metabolic sensor that signals cells to make energy. Miller's team found that breast cancer cells survived estrogen deprivation through activation of AMPK. "A major output of AMPK is activation of fat breakdown to produce energy, which we observed in dormant cancer cells," says Miller. "Drugs that block fat breakdown are used to treat patients with angina (chest pain). Treatment of mice with anti-angina drugs decreased dormant cancer cell numbers."

Knowledge that metformin has context-dependent effects on cancer cells will inform a better understanding of ongoing and prior clinical trials testing metformin, and help shape the design of trials moving forward. "Our study indicates that the development of drugs targeting fat metabolism is warranted for breast cancer. Most excitingly, anti-angina drugs that block fat metabolism may be quickly repurposed as potential treatments for cancer and tested in clinical trials," says Miller.

Next steps include clinical trials testing drugs that block fat metabolism in breast cancer. "We're also designing preclinical studies to further dissect the roles of fat metabolism in breast and other cancers, with the goal of identifying more refined therapeutic targets that will selectively kill cancer cells and not harm healthy cells," notes Miller.

Irvine, CA - April 22, 2020 - A new study explains how cocaine modifies functions in the brain revealing a potential target for therapies aimed at treating cocaine addiction. The study was published this week in Cell Reports.

Researchers from the University of California, Irvine have demonstrated that a key receptor for dopamine, called D2 (D2R), intervenes in the mechanism through which cocaine modifies functions in the striatum, a region of the brain responsible for the psychomotor and rewarding effects of drugs like cocaine, directly involved in the process of addiction.

"In our study, we show that D2R signaling over cholinergic interneurons (ChIs) and acetylcholine (Ach) release exerts a major control in the striatum, which is required for the normal functioning of striatal circuits," said Emiliana Borrelli, PhD, a professor of microbiology and molecular genetics, pharmaceutical sciences, and member of the Center for Epigenetics and Metabolism at the UCI School of Medicine.

"Cocaine use drastically elevates dopamine levels in the striatum, and causes the dopamine D2 receptor (D2R) to inhibit striatal acetylcholine signaling, resulting in cocaine-induced changes in behavior and the striatal genomic response," said Borrelli. "By genetic ablation of D2R in cholinergic interneurons, we disrupt the dopamine-mediated inhibition of these neurons and reduce the addictive effects of drugs like cocaine."

The study indicates that D2R activation in cholinergic interneurons is indeed central to the control of striatal neuronal circuits and significantly affects the motor and cellular responses to cocaine.

"Our study emphasizes the importance of the dopaminergic control on striatal responses to psychostimulants and may pave the way for future therapeutic strategies to treat substance use disorders," said Borrelli.

Cocaine is a psychomotor stimulant that when ingested stimulates the central nervous system increasing motor activity and producing euphoria, excitement, and a feeling of reward. Understanding how psychomotor stimulants modify striatal functions is critical to fighting addiction to this drug.

According to the American Addiction Centers, nearly a million American adults (over age 12) struggled with a cocaine use disorder in 2017. The Foundation for a Drug Free World, states cocaine is one of the most dangerous drugs known to man. Once a person begins taking the drug, it has proven almost impossible to become free of its grip physically and mentally. Physically it stimulates key receptors (at nerve endings that sense changes in the body) within the brain that, in turn, create a sense of well-being to which users quickly develop a tolerance. Only higher dosages and more frequent use can bring about the same effect.