Monitoring mitochondria: Laser device tells whether oxygen is sufficient

Shining a laser-based device on a tissue or organ may someday allow doctors to assess whether it’s getting enough oxygen, a team reports today in the journal Science Translational Medicine.

Placed near the heart, the device can potentially predict life-threatening cardiac arrest in critically ill heart patients, according to tests in animal models. The technology was developed through a collaboration between Boston Children’s Hospital and device maker Pendar Technologies (Cambridge, Mass.).

“With current technologies, we cannot predict when a patient’s heart will stop,” says John Kheir, MD, of Boston Children’s Heart Center, who co-led the study. “We can examine heart function on the echocardiogram and measure blood pressure, but until the last second, the heart can compensate quite well for low oxygen conditions. Once cardiac arrest occurs, its consequences can be life-long, even when patients recover.”

In critically ill patients with compromised circulation or breathing, oxygen delivery is often impaired. The new device measures, in real time, whether enough oxygen is reaching the mitochondria, the organelles that provide cells with energy.

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In search of young medical geneticists

Nina Gold, MD, is Chief Resident of Medical Genetics at Boston Children’s Hospital.

During a quiet stretch of my final year in medical school, I read Sir Arthur Conan Doyle’s Sherlock Holmes stories. A master observer, the detective found secrets in wrinkles of clothes, tints of hair, scents of perfume, never satisfied until the truth was revealed. Sherlock was, simply, an expert diagnostician.

In the spring of 2014, I became the first student in my medical school to pursue residency training in a combined pediatrics and medical genetics program. Like Sherlock, pediatric geneticists are stalwart investigators. They are often called into a case long after other consultants and tasked with bringing a family’s diagnostic odyssey to an end. But unlike the emotionally obtuse fictional detective, geneticists must describe their findings with empathy and clarity to concerned families after they solve a mystery.

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Pediatric devices wanted: Boston Children’s Hospital and the Boston Pediatric Device Consortium launch $250,000 challenge

Boston Pediatric Device Strategic Partner Challenge opens

There’s generally little incentive for industry to develop medical devices for children: The pediatric market is small (most children are healthy) and clinical trials are harder to do in children.

“Innovation in medical devices with the potential to improve the health of children and adolescents continues to lag in comparison to those for adults,” says Pedro del Nido, MD, leader of the Boston Pediatric Device Consortium and Chief of Cardiac Surgery at Boston Children’s Hospital. 

This week, the Innovation and Digital Health Accelerator (IDHA) at Boston Children’s Hospital and the Boston Pediatric Device Consortium (BPDC) announced a national challenge to try to remedy this problem. The Boston Pediatric Device Strategic Partner Challenge will award up to $50,000 to entrepreneurs and innovators seeking to create novel pediatric medical devices, from a total pool of up to $250,000.

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To monitor health, simply trip the ‘nanoswitches’

WATCH: DNA nanoswitches change shape in the presence of biomarkers. The shape change is revealed in a process called gel electrophoresis. Credit: Wyss Institute at Harvard University

“Nanoswitches” — engineered, shape-changing strands of DNA — could shake up the way we monitor our health, according to new research. Faster, easier, cheaper and more sensitive tests based on these tools — used in the lab or at point of care — could indicate the presence of disease, infection and even genetic variabilities as subtle as a single-gene mutation.

“One critical application in both basic research and clinical practice is the detection of biomarkers in our bodies, which convey vital information about our current health,” says lead researcher Wesley Wong, PhD, of Boston Children’s Hospital Program in Cellular and Molecular Medicine (PCMM). “However, current methods tend to be either cheap and easy or highly sensitive, but generally not both.”

That’s why Wong and his team have adapted their DNA nanoswitch technology — previously demonstrated to aid drug discovery and the measure of biochemical interactions — into a new platform that they call the nanoswitch-linked immunosorbent assay (NLISA) for fast, sensitive and specific protein detection. It’s described this week in the Proceedings of the National Academy of Sciences.

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Moulage meets medicine: Making simulations feel real with special effects makeup

medical moulage - Maeve Geary at work
Photo: Katherine C. Cohen/Boston Children’s Hospital

Maeve Geary, BDes, to our knowledge, is the first PhD candidate to specialize in medical special effects simulation. A native of Belfast, Ireland, she completed a Bachelor of Design degree in Special Effects Development at the University of Bolton (Manchester, England). She has been with Boston Children’s Hospital’s Simulator Program, SIMPeds, since April 2016. At SIMPeds, she has contributed to a variety of custom “trainers” and is exploring whether increasing the realistic look and feel of mannequins impacts training and trainees’ ability to learn. Recently, she led the development of a trainer for urinary catheterization in infants — complete with visually and haptically accurate genitals, urethral opening and fat rolls.

It’s now apparent that treating medical mannequins with greater visual and haptic realism makes medical simulation training more effective for clinicians. Moulage, or special effects makeup, is an important part of making simulations feel real.

Here’s a quick tutorial in some very basic effects achieved with simple, readily available drugstore ingredients. Although much of my research is on complex fabrication techniques adapted from the film and television industry, these techniques are simple and accessible to all. (If you’re in Boston, attend our live demos this week!)

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3D organoids and RNA sequencing reveal the crosstalk driving lung cell formation

lung disease
A healthy lung must maintain two key cell populations: airway cells (left), and alveolar epithelial cells (right). (Joo-Hyeon Lee)

To stay healthy, our lungs have to maintain two key populations of cells: the alveolar epithelial cells, which make up the little sacs where gas exchange takes place, and bronchiolar epithelial cells (also known as airway cells) that are lined with smooth muscle.

“We asked, how does a stem cell know whether it wants to make an airway or an alveolar cell?” says Carla Kim, PhD, of the Stem Cell Research Program at Boston Children’s Hospital.

Figuring this out could help in developing new treatments for such lung disorders as asthma and emphysema, manipulating the natural system for treatment purposes.

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“Vampires” may have been real people with this blood disorder

Mural of Vlad the Impaler, who was accused of being a vampire. Perhaps, instead, he suffered from a blood disorder called porphyria.Porphyrias, a group of eight known blood disorders, affect the body’s molecular machinery for making heme, which is a component of the oxygen-transporting protein, hemoglobin. When heme binds with iron, it gives blood its hallmark red color.

The different genetic variations that affect heme production give rise to different clinical presentations of porphyria — including one form that may be responsible for vampire folklore.

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Bad to the bone: New light on the brain’s venous system… and on craniosynostosis

cerebral veins and skull development in a normal child
Normal skull and brain venous development in a young child (courtesy Tischfield et al).

A recent study rocked the neuroscience world by demonstrating what in retrospect seems obvious: the brain has its own lymphatic system to help remove waste. A new study, from the laboratory of Elizabeth Engle, MD, at Boston Children’s Hospital, sheds light on another critical, little-studied part of the brain’s drainage system: the dural cerebral veins that remove and reabsorb excess cerebrospinal fluid.

The story of these vessels, the cover article in the next Developmental Cell, is a great example of lab scientists and physicians joining to make fundamental discoveries in biology. Strangely, critical clues come from children with craniosynostosis, a congenital malformation in which the skull plates fuse together too early in prenatal development, resulting in abnormal head shapes and, often, neurologic complications.

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Immune gene guards against type 1 diabetes by changing the microbiome. Do early antibiotics undercut its effects?

type 1 diabetes microbiome antibiotics

The health of our immune system is increasingly linked with the health of our intestinal bacteria. A mouse study from Harvard Medical School now hammers this home for autoimmune disorders, in which the body attacks its own cells. It looked specifically at type 1 diabetes, in which the body destroys the cells that make insulin.

Scientists have long known that the human leukocyte antigen (HLA) complex of proteins (also known as the major histocompatibility complex, or MHC) keep autoimmune responses in check. Certain common variants of the HLA/MHC genes are known to protect against a type 1 diabetes. But until now, how these genes prevent autoimmune reactions has been a mystery.

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Landmark moment for science as the FDA approves a gene therapy for the first time

Leukemia blast cells, which could now be destroyed using a first-of-its-kind, FDA-approved gene therapy called CAR-T cell therapy
Leukemia blast cells.

Today, the Food and Drug Administration approved a gene therapy known as CAR T-cell therapy that genetically modifies a patient’s own cells to help them combat pediatric acute lymphoblastic leukemia (ALL), the most common childhood cancer. It is the first gene therapy to be approved by the FDA.

“This represents the progression of the field of gene therapy, which has been developing over the last 30 years,” says gene therapy pioneer David A. Williams, MD, who is chief scientific officer of Boston Children’s Hospital and president of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. “It’s a realization of what we envisioned to be molecular medicine when this research started. The vision — that we could alter cells in a way to cure disease — is now coming true.”

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