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February 8, 2019
Digest
Blood Test Shows Promise for Early Detection of Severe Lung-Transplant Rejection

Researchers have developed a simple blood test that can detect when a newly transplanted lung is being rejected by a patient, even when no outward signs of the rejection are evident. The test could make it possible for doctors to intervene faster to prevent or slow down so-called chronic rejection— which is severe, irreversible and often deadly—in those first critical months after lung transplanta­tion. Researchers believe this same test might also be useful for monitoring rejection in other types of organ transplants. The work was funded by NHLBI; the study’s findings were published Jan. 22 in EBioMedicine, a publication of The Lancet.

“This test solves a long-standing problem in lung transplants: detection of hidden signs of rejection,” said Dr. Hannah Valantine, co-leader of the study and lead investigator of NHLBI’s Laboratory of Organ Transplant Genomics in the Cardiovascular Branch. “We’re very excited about its potential to save lives, especially in the wake of a critical shortage of donor organs.”

The test relies on DNA sequencing, Valantine explained, and as such, represents a great example of personalized medicine, as it will allow doctors to tailor transplant treatments to those individuals who are at highest risk for rejection.

Lung transplant recipients have the shortest survival rates among patients who get solid organ transplantation of any kind—only about half live past 5 years. Lung transplant recipients face a high incidence of chronic rejection, which occurs when the body’s immune system attacks the transplanted organ. Existing tools for detecting signs of rejection, such as biopsy, either require the removal of small amounts of lung tissue or are not sensitive enough to discern the severity of the rejection. The new test, called the donor-derived cell-free DNA test, appears to overcome those challenges.

Smoking Linked to Higher Risk of PAD in African Americans

Smoking Linked to Higher Risk of PAD in African Americans
IMAGE: NIKKYTOK/ISTOCK

African Americans who smoke appear to be at greater risk for peripheral artery disease, or PAD, new research has found. Additionally, the findings suggest that smoking intensity—how many ciga­rettes a day and for how many years—also affects the likelihood of getting the disease.

PAD affects 8 million to 12 million people in the United States and 202 million worldwide, especially those ages 50 and older. It develops when arteries in the legs become clogged with plaque, fatty deposits that limit blood flow to the legs. Clogged arteries in the legs can cause symptoms such as claudication, pain due to too little blood flow, and increased risk for heart attack and stroke.

The impact of cigarette smoking on PAD has been understudied in African Americans, even though PAD is nearly three times more prevalent in African Americans than in whites. The current study looked at the relationship between smoking and PAD in participants in the Jackson Heart Study, the largest single site cohort study investigating cardiovascular disease in African Americans.

The new research, as well as the Jackson Heart Study, are funded by NHLBI and NIMHD. The new findings appear in the January issue of the Journal of the American Heart Association.

“These findings demonstrate that smoking is associated with PAD in a dose-dependent manner,” said lead researcher Dr. Donald Clark III, an assistant professor of medicine at the University of Mississippi Medical Center. “This is particularly important in the African-American community and supports the evaluation of smoking-cessation efforts to reduce the impact of PAD in this population.”

Temperature-Stable Experimental TB Vaccine Enters Clinical Testing

Vaccinations have begun in a phase 1 human clini­cal trial testing a freeze-dried, temperature-stable formulation of an experimental tuberculosis (TB) vaccine candidate. The trial is being conducted at the Saint Louis University School of Medicine Center for Vaccine Development and will enroll as many as 48 healthy adult volunteers ages 18 to 55. The experimental vaccine, called ID93, was developed by scientists at the Infectious Disease Research Institute in Seattle; NIAID is supporting the trial through a contract to IDRI.

ID93 is a recombinant vaccine candidate made from four proteins of Mycobacterium tuberculosis (the bacterium that causes TB). Many vaccines require a temperature-controlled system during transport, which can be costly and logistically challenging. Freeze-dried powder vaccines can be distributed at a cheaper cost to remote, low-resource settings. The powder formulations are mixed with sterile water for administering with a needle and syringe.

Investigators are examining if a powder formula­tion combining ID93 and the adjuvant GLA-SE (an immune response-stimulating protein) in a single vial, reconstituted with sterile water, is as effective at inducing an immune response in participants as the previously tested two-vial combination of powdered ID93 and liquid GLA-SE.

“Tuberculosis remains the leading infectious cause of death worldwide and a highly effective vaccine would be a crucial tool in ending this pandemic,” said NIAID director Dr. Anthony Fauci. “A vaccine that did not require a cold chain could be much more easily distributed to communities in need.”

New Findings Reveal Surprising Role of the Cerebellum in Reward, Social Behaviors

New Findings Reveal Surprising Role of the Cerebellum in Reward, Social Behaviors
IMAGE: ISTOCK

A new study in rodents has shown that the brain’s cerebellum—known to play a role in motor coordination—also helps control the brain’s reward circuitry. Researchers found a direct neural connection from the cerebellum to the ventral tegmental area (VTA) of the brain, which is an area long known to be involved in reward processing and encoding. These findings, pub­lished in Science, demonstrate for the first time that the brain’s cerebellum plays a role in controlling reward and social preference behavior and sheds new light on the brain circuits critical to the affective and social dysfunction seen across multiple psychiatric disorders. The research was funded by NIMH.

“This type of research is fundamental to deepening our understanding of how brain circuit activity relates to mental illnesses,” said NIMH director Dr. Joshua Gordon. “Findings like the ones described in this paper help us learn more about how the brain works, a key first step on the path towards developing new treatments.”

The cerebellum plays a well-recognized role in the coordination and regulation of motor activity. However, research has also suggested that this brain area contributes to a host of non-motor func­tions. For example, abnormalities in the cerebellum have been linked to autism, schizophrenia and substance use disorders and brain activation in the cerebellum has been linked to motivation, social and emotional behaviors and reward learning, each of which can be disrupted in psychiatric disorders.

These earlier findings led Dr. Kamran Khodakhah of Albert Einstein College of Medicine and colleagues to wonder if there was a direct con­nection between the cerebellum and the VTA—a brain structure involved in controlling reward and motivational behaviors. To examine this, the researchers used a technique called optogenetics, in which the neurons of animals are genetically modified, so they can be controlled using pulses of light. The researchers used this technique in mice, activating neurons in the cerebellum that connected to the VTA. The researchers found that activating the cerebellar neurons led to increased activation in the VTA of mice, indicating a working connection between these two brain structures.

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