Publisher Health

Researchers have developed a blood test that detects Parkinson’s disease, potentially establishing a way to help diagnose the condition before nervous system damage worsens.
A new blood-based diagnostic test would be a major advancement for Parkinson’s disease, which afflicts 10 million people worldwide and is the second-most common neurodegenerative disease after Alzheimer’s. Led by a team of Duke Health neuroscientists, the study appears Aug. 30 in the journal Science Translational Medicine.
“Currently, Parkinson’s disease is diagnosed largely based on clinical symptoms after significant neurological damage has already occurred,” said senior author Laurie Sanders, Ph.D., an associate professor in Duke School of Medicine’s departments of Neurology and Pathology and member of the Duke Center for Neurodegeneration and Neurotherapeutics.
“A simple blood test would allow us to diagnose the disease earlier and start therapies sooner,” Sanders said. “Additionally, a clear-cut diagnosis would accurately identify patients who could participate in drug studies, leading to the development of better treatments and potentially even cures.”
As a biomarker for their diagnostic tool, Sanders and colleagues focused on DNA damage in the mitochondria. Mitochondria are factories within cells that convert raw energy into a form that powers cells. They contain their own DNA, which can undergo damage separately from the nuclear DNA that encodes most of an organism’s genome.
Earlier studies have associated mitochondrial DNA damage with an increased risk of Parkinson’s disease, and the Duke-led team had previously reported an accumulation of mitochondrial DNA damage specifically in the brain tissue of deceased Parkinson’s patients.
Using polymerase chain reaction (PCR) technology, the Duke team developed an assay that successfully quantified higher levels of mitochondrial DNA damage in blood cells collected from patients with Parkinson’s disease compared to people without the disease.

Research teams at University of Galway and Massachusetts Institute of Technology (MIT) have detailed a breakthrough in medical device technology that could lead to intelligent, long-lasting, tailored treatment for patients thanks to soft robotics and artificial intelligence.
The transatlantic partnership has created a smart implantable device that can administer a drug — while also sensing when it is beginning to be rejected — and use AI to change the shape of the device to maintain drug dosage and simultaneously bypass scar tissue build up.
The study was published in the journal Science Robotics.
Implantable medical device technologies offer promise to unlock advanced therapeutic interventions in healthcare, such as insulin release to treat diabetes, but a major issue holding back such devices is the patient’s reaction to a foreign body.
Dr Rachel Beatty, University of Galway, and co-lead author on the study, explained: “The technology which we have developed, by using soft robotics, advances the potential of implantable devices to be in a patient’s body for extended periods, providing long-lasting therapeutic action. Imagine a therapeutic implant that can also sense its environment and respond as needed using AI — this approach could generate revolutionary changes in implantable drug delivery for a range of chronic diseases.”
The University of Galway-MIT research team originally developed first-generation flexible devices, known as soft robotic implants, to improve drug delivery and reduce fibrosis. Despite that success, the team regard the technology as one-size-fits-all, as it did not account for how individual patients react and respond differently, or for the progressive nature of fibrosis, where scar tissue builds around the device, encapsulating it, impeding and blocking its purpose, eventually forcing it to fail.
The latest research, published today in Science Robotics, demonstrates how they have significantly advanced the technology — using AI — making it responsive to the implant environment with the potential to be longer lasting by defending against the body’s natural urge to reject a foreign body.

Antibiotic-resistant bacteria get extra nutrients and thrive when the drugs kill ‘good’ bacteria in the gut.
This is according to new research led by Imperial College London scientists, which could lead to better patient risk assessment and ‘microbiome therapeutics’ treatments to help combat antibiotic-resistant bacteria.
Some antibiotics target specific bacteria, but some are ‘broad spectrum’, meaning they can kill a wide range of bacteria including both ‘bad’ pathogenic bacteria that cause infections and ‘good’ bacteria that live in our guts and help with digestion and other processes.
Carbapenems are broad-spectrum antibiotics that are strong but often used as a last resort, due to their negative impacts on beneficial bacteria. Some pathogenic bacteria in the class Enterobacteriaceae however are even resistant to carbapenems, including strains of E. coli. These pathogenic bacteria colonise the gut but can spread to other sites in the body, causing difficult-to-treat infections such as bloodstream infections or recurrent urinary tract infections.
Now, a new study shows how these resistant bacteria thrive after antibiotic use, allowing them to multiply in the gut, forming a ‘reservoir’ of disease-causing bacteria. The results are published in Nature Communications.
More nutrients, less impairment
To determine the effect of antibiotics, the team tested them on samples of human faeces in the lab, alongside experiments in mice and lab tests of carbapenem-resistant Enterobacteriaceae (CRE).

A new study by researchers from Mass General Brigham further illustrates that when it comes to risk of Alzheimer’s disease, even genetically determined forms of the disease, genetics is only one piece of the puzzle. Researchers investigated the influence of genetics and educational attainment on cognitive decline by studying data from 675 people who carry a mutation that predisposes them to early onset Alzheimer’s disease. Carriers of this mutation — known as PSEN1 E280A — have a median age of 49 for onset of dementia. The team found that among carriers who also carried a second mutation that puts them at heightened risk — APOE e4 — had an accelerated age of onset of cognitive decline. Among carriers who had an APOE e2 mutation — known to be protective — age of onset was delayed.
The team also assessed the effect of educational attainment on cognitive function among PSEN1 E280A mutation carriers, including those who carried different APOE genotypes. They found that higher educational attainment — that is, more years of education — was associated with preserved cognitive ability particularly for those at highest genetic risk.
“Higher educational attainment may have a protective effect against cognitive impairment, even in the presence of strong genetic risk factors,” said corresponding author Yakeel Quiroz PhD, a clinical neuropsychologist and neuroimaging researcher, director of the Familial Dementia Neuroimaging Lab in the Departments of Psychiatry and Neurology at Massachusetts General Hospital. “Despite the additional risk conferred by APOEe4, the strongest genetic risk factor for sporadic Alzheimer’s disease, our results suggest that educational attainment may be a critical mechanism of cognitive reserve in familial Alzheimer’s disease.”
The research team included investigators from Massachusetts General Hospital, Brigham and Women’s Hospital, Mass Eye and Ear, and national and international collaborators.

The NewsWomen who became pregnant after infertility treatment were more likely to have a stroke in the year following the birth when compared with women who conceived naturally, scientists reported on Wednesday in the largest study of its kind.Stroke risk was elevated in the first 30 days after delivery among the women who had undergone treatments, and the odds continued to rise through the year after childbirth. But the absolute numbers remained very low, the researchers emphasized: just 37 stroke hospitalizations for every 100,000 women who underwent treatment.There is no need for alarm, the lead author said in an interview. But women seeking treatment should be made aware of a possible link.Getty ImagesWhy It Matters:The United States has the highest maternal mortality rate in the developed world. Strokes account for about 7.5 percent of pregnancy-related deaths.At the same time, use of assisted reproductive technology has risen dramatically over the past 10 years. About 2 percent of births in the United States involve infertility treatment of some kind, according to the paper.In the new study, researchers defined these measures to include intrauterine insemination, assisted reproductive technology, use of a surrogate and fertility preservation procedures.While infertility treatments are generally safe, some studies have linked them to increased risks during pregnancy, including higher rates of pre-eclampsia — a potentially deadly complication involving extremely high blood pressure — as well as placental abnormalities and preterm birth.BackgroundPrevious studies of stroke after infertility treatments have yielded mixed results. The new study, published in JAMA Network, is believed to be the largest to examine the risk of hospitalization for stroke among these women.It analyzed the health outcomes of 31 million patients who had a hospital delivery in 28 states between 2010 and 2018, including 287,813 who had undergone infertility treatments.The risk of a hemorrhagic stroke — bleeding in the brain — was twice as high among women who had undergone fertility treatment, compared to those who did not, the study found.The odds of an ischemic stroke, which occurs when the blood supply to the brain is interrupted, was 55 percent greater, compared with women who conceived naturally.These results are not the final word on the subject, however.Just a few weeks ago, the journal JAMA Cardiology published a study that examined long-term health outcomes among women in four Scandinavian countries who had received infertility treatments, and found no evidence of an increased risk for cardiovascular disease.That study was much smaller, however, including only 2.4 million women.The new research did not include data about important risk factors for stroke, such as smoking, body mass index and hypertension. The scientists took steps to account for the missing data and still found a heightened risk, said the paper’s senior author, Cande V. Ananth, chief of epidemiology and biostatistics at the Robert Wood Johnson Medical School in New Jersey.What’s NextIn an interview, Dr. Ananth outlined three possible explanations for a link between stroke and infertility treatment.“We know that women who receive infertility treatment have certain vascular complications, typically an increased risk of pre-eclampsia and placental abruption,” he said.Second, infertility treatments can bring physiological changes, he said. Patients often receive large amounts of estrogen, for example, which can lead to increased blood clotting, a strong risk factor for stroke, he said.Third, he added, “is that people who receive the treatment receive it for a reason. Perhaps there are different biological characteristics” among women seeking treatment, he said.Still, stroke remains very infrequent among women after childbirth, whether they received treatments or not, Dr. Ananth said. “Patients should be aware of the impending risks and counseled appropriately,” he said.

Scientists at the University of Colorado Anschutz Medical Campus have made a `paradigm shifting’ discovery on the mechanisms required for learning and memory that could lead to new therapies for Alzheimer’s disease and potentially Down syndrome.
The study was published Wednesday in the journal Nature.
For over 30 years, researchers believed that LTP or long-term potentiation, which is crucial for learning and memory, required enzymatic actions by an enzyme known as CaMKII.
But a team of researchers led by Ulli Bayer, PhD, professor of pharmacology at the University of Colorado School of Medicine, found that LTP requires structural not enzymatic functions of CaMKII.
That’s significant, Bayer said, because it opens the door to the therapeutic use of a new class of inhibitors that target only the enzymatic activity of CaMKII, but not the structural functions required for memory and learning.
Previous studies by Bayer’s laboratory showed that inhibiting enzymatic CaMKII activity protects against some of the effects of amyloid-beta (Abeta) plaques in the brain, a hallmark of Alzheimer’s disease (AD).
The researchers found one group of inhibitors that protected from the Abeta effects without impairing LTP, making it potentially useful in treating a number of brain diseases without debilitating side effects.

A member of an important class of ion channel proteins can transiently rearrange itself into a larger structure with dramatically altered properties, according to a study led by researchers at Weill Cornell Medicine. The discovery is a significant advance in cell biology, likely solves a long-standing mystery about an unusual feature of some ion channels and has implications for the development of drugs targeting these proteins and for drug delivery.
Ion channels are ubiquitous in the cell membranes of higher organisms. They conduct small, charged molecules called ions into or out of cells, in order to regulate cell activity. They are necessary for most biological functions, from sensation to cognition to heartbeat. Although about 15 percent of pharmaceuticals work by targeting ion channels, scientists could target them more effectively if they knew more about the dynamics of their complex structures.
In the study, published Aug. 30 in Nature, the researchers examined the structural dynamics of an ion channel called TRPV3. They discovered an uncommon but striking structural rearrangement in which TRPV3, normally a “tetramer” made of four identical protein subunits, becomes a five-protein “pentamer.” The researchers found strong evidence that this structural rearrangement underlies a hitherto unexplained ion-channel phenomenon called pore dilation.
“These findings open up a broad new avenue of research on the workings of ion channels,” said study senior author Dr. Simon Scheuring, a professor of physiology and biophysics in anesthesiology at Weill Cornell Medicine.
The study’s first author was Dr. Shifra Lansky, a postdoctoral research associate in the Scheuring lab in the Department of Anesthesiology. The work was performed in collaboration with Dr. Crina Nimigean’s lab in the Department of Anesthesiology at Weill Cornell Medicine.
TRPV3 is an ion channel that is involved in the sensing of warm temperatures, skin health, itch, hair growth, and other functions throughout the body. It belongs to the larger family of TRP ion channels, which have numerous biological roles in higher organisms. Drs. Scheuring and Lansky and their colleagues initially set out to map TRPV3’s structural dynamics — how its structure changes as it opens and closes its channel — using an advanced tool called high-speed atomic-force microscopy.
To the researchers’ surprise, they soon discovered that TRPV3, normally a tetramer, occasionally assembles itself into a pentamer, and can exist in this uncommon state for only about three minutes.

An existing blood cancer drug has shown promise in killing ‘silent’ HIV cells and delaying reinfections — a significant pre-clinical discovery that could lead to a future cure for the disease.
Hidden HIV cells, known as latent infection, are responsible for the virus permanently remaining in the body and cannot be treated by current therapy options. These hibernating, infected cells are the reason why people living with HIV require life-long treatment to suppress the virus.
Led by WEHI and The Peter Doherty Institute for Infection and Immunity (Doherty Institute) — leading medical research institutes in Melbourne, Australia — the landmark study is being translated into a new clinical trial to assess whether the blood cancer treatment can be repurposed to offer a pathway towards an HIV cure.
At a glance A joint WEHI and Doherty Institute study finds the cancer drug venetoclax — based on a groundbreaking research discovery at WEHI — can kill hibernating HIV-infected cells and, crucially, delay the virus from re-emerging. While current treatments can suppress the virus, they cannot target hibernating HIV-infected cells and permanently prevent the virus from coming back. A clinical trial based on the findings will launch in Denmark and Australia, to test whether venetoclax can be used as a potential pathway to develop a cure for HIV.An estimated 39 million people worldwide are living with HIV, including more than 29,400 Australians.
Antiretroviral therapy (ART) is the standard of care treatment given to people living with HIV and is highly effective. But the medication cannot target hibernating HIV-infected cells, meaning it can only suppress the virus — not cure it.
ART for people living with HIV is life-long: if a person stops taking this medication, hibernating HIV-infected cells will reactivate within a very short timeframe, leading to a resurgence of the virus.

When an immunocompromised person’s system begins to recover and produce more white blood cells, it’s usually a good thing — unless they develop a potentially deadly inflammatory condition. New research from the University of Illinois Urbana-Champaign has found that the pulmonary distress often associated with the condition is caused not by damage to the lungs, but by newly populated T-cells infiltrating the brain.
Knowing this mechanism of action can help researchers and physicians better understand the illness and provide new treatment targets, said study leader Makoto Inoue, a professor of comparative biosciences at Illinois. The study was published in the journal Nature Communications.
Cryptococcus-associated immune reconstitution inflammatory syndrome, known as C-IRIS, happens when an immunocompromised patient is unknowingly infected with the fungus Cryptococcus. Once the patient’s immune system begins to rebuild, creating more T-cells, the infection sparks systemic inflammation.
C-IRIS frequently affects patients receiving antiretroviral therapy, recovering from chemotherapy, or recovering from a transplant, and also has been known to affect postpartum women or patients with multiple sclerosis — yet it remains difficult to diagnose, requiring ruling out other causes first, said study co-author Jinyan Zhou, a graduate student researcher at Illinois.
Wanting to understand more about the condition and its progression, the researchers developed a mouse model of the disease. To achieve this, they give injections of T-cells to immune-deficient mice preinfected with Cryptococcus, simulating what happens when the immune system starts producing higher levels of T-cells after being suppressed. The symptoms the mice developed — such as inflammation, fluid in the brain and pulmonary dysfunction — were in line with those of human patients.
“We saw a high number of T-cells infiltrating the brains in conjunction with the presence of pulmonary dysfunctions, so that told us they could be connected,” Zhou said. “In healthy conditions, there shouldn’t be that many T-cells in the brain, because those cells should primarily exist in the periphery with a small number of T-cells doing patrol and surveillance within the brain.”
When the researchers investigated further, they uncovered a chain of events leading the T-cells to invade the brain and affect breathing. The receptor CCR5 is implicated in HIV and cancer, and also found on the surface of T-cells. When the T-cell populations started to rise in the mice, the receptor promoted the white blood cells’ infiltration into the brain. In addition, the T-cells that had infiltrated the brain produced high amounts of two molecules known to cause damage to neurons in the regions of the brain that control respiratory function.

Disrupted connections between memory and appetite regulating brain circuits are directly proportional to body mass index (BMI), notably in patients who suffer from disordered or overeating that can lead to obesity, such as binge eating disorder (BED), according to new research from the Perelman School of Medicine at the University of Pennsylvania. Published today in Nature, the research notes that individuals who are obese have impaired connections between the dorsolateral hippocampus (dlHPC) and the lateral hypothalamus (LH), which may impact their ability to control or regulate emotional responses when anticipating rewarding meals or treats.
“These findings underscore that some individual’s brains can be fundamentally different in regions that increase the risk for obesity,” senior author, Casey Halpern, MD, an associate professor of Neurosurgery and Chief of Stereotactic and Functional Neurosurgery at Penn Medicine and the Corporal Michael J. Crescenz Veterans Affairs Medical Center. “Conditions like disordered eating and obesity are a lot more complicated than simply managing self-control and eating healthier. What these individuals need is not more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”
The dlHPC is located in the region of the brain that processes memory, and the LH is in the region of the brain that is responsible for keeping the body in a stable state, called homeostasis. Previous research has found an association with loss of function in the human hippocampus in individuals with obesity and related disordered eating, like BED. However, outside of imaging techniques such as magnetic resonance imaging (MRI), the role of the hippocampus has been difficult to study in humans with obesity and related eating disorders.
In this study, researchers were able to evaluate patients whose brains were already being monitored electrically in the Epilepsy Monitoring Unit. Researchers monitored brain activity as patients anticipated and then received a sweet treat (a chocolate milkshake). They found that both the dlHPC and the LH activated simultaneously when participants anticipated receiving the rewarding meal. These researchers confirmed using stimulation techniques pioneered by coauthors, Kai Miller, MD, PhD, and Dora Hermes Miller, PhD, from Mayo Clinic, that this specific zone of the hippocampus, the dlHPC, and LH exhibited extremely strong connectivity, as well.
In individuals with obesity, researchers found that the impairment of this hypothalamus-hippocampus circuit was directly proportional to their BMI. That is, in participants with a high BMI, the connection was even more disturbed.
To further validate the connection, Halpern’s team used a technique called “brain clearing,” to analyze brain tissue. The technique revealed melanin-concentrating hormone, a hormone known to regulate feeding behavior that is produced in the LH. They found the presence of MCH in the dlHPC, and nowhere else, confirming a link between the two regions.
“The hippocampus has never been targeted to treat obesity, or the disordered eating that can sometimes cause obesity,” said Halpern. “We hope to be able to use this research to both identify which individuals who are likely to develop obesity later in life, and to develop novel therapies — both invasive and not — to help improve function of this critical circuit that seems to go awry in patients who are obese.”
This research was funded by the Foundation for OCD Research, the National Institute of Health (R01 MH124760, K23 MH106794, R01 NS095985), the Natural Sciences and Engineering Research Council of Canada (#40306) and the Canadian Institutes of Health Research (#41916).