Author: Nancy Fliesler

When neglected children enter adolescence: A cautionary tale about family separation

child neglect / child deprivation
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Many migrant children separated from their parents at the U.S. border, some of them very young, have landed in shelters where they often experience stress, neglect and minimal social and cognitive stimulation. The latest findings of the long-running Bucharest Early Intervention Project (BEIP), involving children in Romanian orphanages, tells a cautionary tale about the psychiatric and social risks of long-term deprivation and separation from parents.

BEIP has shown that children reared in very stark institutional settings, with severe social deprivation and neglect, are at risk for cognitive problems, depression, anxiety, disruptive behavior and attention-deficit hyperactivity disorder. But BEIP has also shown that placing children with quality foster families can mitigate some of these effects, if it’s done early.

The new BEIP study, published this week by JAMA Psychiatry, asked what happens to the mental health of institutionalized children as they transition to adolescence. Outcomes at ages 8, 12 and 16 suggest diverging trajectories between children who remained in institutions versus those randomly chosen for placement with carefully vetted foster families.

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Can we teach heart cells to grow up?

normal and mutant cardiomyocytes
A mutant heart muscle cell (in green) surrounded by normal cells. The mutant cell lacks Srf, a master maturation gene. It is unable to grow in size and lacks the fine membrane invaginations that help coordinate muscle contractions (appearing as vertical striations in the normal cells). (IMAGE: GUO Y; ET AL. NAT COMMS 9 #3837 (2018).]

Scientists around the world have been trying to replace damaged heart tissue using lab-made heart-muscle cells, either injecting them into the heart or applying patches laced with the cells. But results to date have been underwhelming.

“If you make cardiomyocytes in a dish from pluripotent stem cells, they will engraft in the heart and form muscle,” says William Pu, MD, director of Basic and Translational Cardiovascular Research at Boston Children’s Hospital. “But the muscle doesn’t work very well because the myocytes are stuck in an immature stage.”

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Science Seen: Using Twitter to map hospitals’ stance toward LGBT patients

Hswen Y et al. Social Science & Medicine Oct 2018. DOI: 10.1016/j.socscimed.2018.08.031  

How sensitive are hospitals to the needs of lesbian, gay, bisexual and transgender (LGBT) patients? In a 2010 survey by Lambda Legal, 70 percent of transgender patients and 56 percent of gay/lesbian/bisexual patients reported discrimination from health care providers. Clinicians refused to provide needed care, refused to touch them or used excessive precautions, blamed them for their health status, were verbally abusive or were physically violent.

A new exploratory study, published in the October issue of Social Science & Medicine, turned to social media for a view from the ground. The researchers, Yulin Hswen of Harvard T.H. Chan School of Public Health and Jared Hawkins, PhD, MMSc, of Boston Children’s Hospital’s Informatics Program, analyzed 1,856 publicly available tweets from 2015-2017.

“Information from social media and other online sources can help us gain authentic and unsolicited accounts from vulnerable patient groups, like LGBT individuals who are not typically represented,” says Hswen.

Based on the tweets, the team determined which hospitals were more supportive of LGBT patients (the blue dots in the above map) and which were less supportive (the red dots).

The identified tweets included Twitter handles from 653 hospitals and contained LGBT-related terms: LGBT, transgender, trans, intersex, sex change, transisbeautiful, tranny, drag queen, preferred pronoun, transhealth, genderodyssey, cis, gay, lesbian, queer, rainbowhealth, gender fluid, homosexual, bisexual, homo, homophob and transphobe. A tweet classed as supportive might read, “@Hospital is hosting a LGBT resource fair;” a negative tweet might read: “Having sex with men does not mean I deserve less @Hospital.”

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Getting closer to cracking HIV’s envelope protein

missing segment of HIV envelope could be target for HIV vaccine
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For 30 years, researchers have tried to develop an HIV vaccine that would stop the virus from gaining a foothold in the body — before it attaches to T cells and slowly weakens the immune system.

“It has been extremely challenging to induce effective antibody responses against HIV-1,” says Bing Chen, PhD, who researches HIV’s molecular mechanisms at Boston Children’s Hospital.

HIV offers just one target for a vaccine to mimic to trigger protective antibodies: the envelope protein on its surface. Scientists have been struggling to capture the complex protein’s precise structure — and specifically, its structure before the virus fuses with the T-cell membrane.

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In zebrafish, a way to find new cancer therapies, targeting tumor promoters

A new study suggests the power of zebrafish as tools for cancer drug discovery (PHOTO: KATHERINE C. COHEN)

The lab of Leonard Zon, MD, has long been interested in making blood stem cells in quantity for therapeutic purposes. To test for their presence in zebrafish, their go-to research model, they turned to the MYB gene, a marker of blood stem cells. To spot the cells, Joseph Mandelbaum, a PhD candidate in the lab, attached a fluorescent green tag to MYB that made it easily visible in transparent zebrafish embryos.

“It was a real workhorse line for us,” says Zon, who directs the Stem Cell Research Program at Boston Children’s Hospital.

In addition to being a marker of blood stem cells, MYB is an oncogene. About five years ago, Zon was having lunch at a cancer meeting and, serendipitously, sat next to Jeff Kaufman, who was also interested in MYB. Kaufman was excited to hear about Zon’s fluorescing MYB zebrafish, which can be studied at scale and are surprisingly similar to humans genetically.

“Have you ever heard of adenoid cystic carcinoma?” he asked Zon.

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Neurons from the brain amplify touch sensation. Could they be targeted to treat neuropathic pain?

neuropathic pain amplification circuit
CREDIT: ALBAN LATREMOLIERE/BOSTON CHILDREN’S HOSPITAL/JOHNS HOPKINS

Neuropathic pain is a hard-to-treat chronic pain condition caused by nervous system damage. For people affected, the lightest touch can be intensely painful. A study in today’s Nature may open up a new angle on treatment — and could help explain why mind-body techniques can sometimes help people manage their pain.

“We know that mental activities of the higher brain — cognition, memory, fear, anxiety — can cause you to feel more or less pain,” notes Clifford Woolf, MB, BCh, PhD, director of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “Now we’ve confirmed a physiological pathway that may be responsible for the extent of the pain. We have identified a volume control in the brain for pain — now we need to learn how to switch it off.”

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Tracking the elusive genes that cause strabismus

strabismus genes
(PHOTO: ADOBE STOCK)

Strabismus is a common condition in which the eyes do not align properly, turning inward, outward, upward or downward. Two to four percent of children have some form of it. Some cases can be treated with glasses or eye patching; other cases require eye muscle surgery. But the treatments don’t address the root causes of strabismus, which experts believe is neurologic.

For decades, Elizabeth Engle, MD, in Boston Children’s Hospital’s F.M. Kirby Neurobiology Center, has been studying rare forms of strabismus, such as Duane syndrome, in which strabismus is caused by limited eye movements. Her lab has identified a variety of genes that, when mutated, disrupt the development of cranial nerves that innervate the eye muscles. These genetic findings have led to many insights about motor neurons and how they develop and grow.

More recently, with postdoctoral research fellow Sherin Shabaan, MD, PhD, Engle’s lab has been gathering families with common, non-paralytic strabismus, in which both eyes have a full, normal range of motion yet do not line up properly.

Such “garden variety” forms of strabismus have been much harder to pin down genetically.

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‘See through,’ high-resolution EEG recording array gives a better glimpse of the brain

Transparent microelectrodes allow EEG recording at the single-neuron level, with simultaneous 2-photon optical imaging of calcium activity.
Transparent microelectrodes allow EEG recording at the single-neuron level, with simultaneous 2-photon optical imaging of calcium activity. (CREDIT: Yi Qiang et al. Sci. Adv. 4, eaat0626 (2018).)

Electroencephalography (EEG), which records electrical discharges in the brain, is a well-established technique for measuring brain activity. But current EEG electrode arrays, even placed directly on the brain, cannot distinguish the activity of different types of brain cells, instead averaging signals from a general area. Nor is it possible to easily compare EEG data with brain imaging data.

A collaboration between neuroscientist Michela Fagiolini, PhD at Boston Children’s Hospital and engineer Hui Fang, PhD at Northeastern University has led to a highly miniaturized, see-through EEG device. It promises to be much more useful for understanding the brain’s workings.

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Gene active before birth regulates brain folding, speech motor development

SCN3A, linked to polymicrogyria, regulates speech motor development
ILLUSTRATIONS: RICHARD SMITH/BOSTON CHILDREN’S HOSPITAL

A handful of families from around the world with a rare brain malformation called polymicrogyria have led scientists to discover a new gene that helps us speak and swallow.

The gene, SCN3A, is turned “on” primarily during fetal brain development. When it’s mutated, a language area of the brain known as the perisylvian cortex develops multiple abnormally small folds, appearing bumpy. People with polymicrogyria in this region often have impaired oral motor development, including difficulties with swallowing, tongue movement and articulating words — especially if the polymicrogyria affects both sides of the brain.

The new study, published today in Neuron, ties together human genetics, measurements of electrical currents generated by neurons, studies of ferrets and more to start to connect the dots between SCN3A, the brain malformation and the oral motor impairment.

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Sounding out the protein that enables us to hear

The proposed structure of the TMC1 protein (not to scale), superimposed over rows of hair cells in the mouse inner ear. The yellow portions indicate the amino acid substitutions used to identify the location of the pore that admits ions into the cell. (CREDIT: Bifeng Pan et al., Neuron 2018, https://doi.org/10.1016/j.neuron.2018.07.033)

In 2011, a team led by Jeffrey Holt, PhD, demonstrated that a protein called TMC1 is required for hearing and balance, following the 2002 discovery that mutations in the TMC1 gene cause deafness. Holt’s team proposed that TMC1 proteins form channels that enable electrically charged ions such as calcium and potassium to enter the delicate hair cells of the inner ear. This, in turn, enables the cells to convert sound waves and head movement into electrical signals that talk to the brain.

In a new study published today in Neuron, Holt and colleagues teamed with the lab of David Corey, PhD, at Harvard Medical School. Together, they confirmed TMC1’s essential role in hearing, ending a 40-year quest, and mapped out its working parts.

Working with living hair cells in mice, they made substitutions in 17 amino acids within the TMC1 protein, one at a time, to see which substitutions altered hair cells’ ability to respond to stimuli and allow the flow of ions. Eleven amino acid substitutions altered the influx of ions, and five did so dramatically, reducing ion flow by up to 80 percent. One substitution blocked calcium flow completely, thereby revealing the location of the pore within TMC1 that enables ion influx.

Down the road, the study could have implications for reversing hearing loss, which affects more than 460 million people worldwide.

“To design optimal treatments for hearing loss, we need to know the molecules and their structures where disease-causing malfunctions arise, and our findings are an important step in that direction,” Holt said in this press release from Harvard Medical School.

Read more about Holt’s work.

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