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Genes Causing Osteoporosis, Residents’ Longer Work Shifts, Pediatric Spinal Deformity, Ventilation Strategy for Preterm Infants, Pediatric Cell Atlas

Published on April 5, 2019 in Cornerstone Blog · Last updated 1 month ago


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As spring slowly arrives here in Philadelphia, take a deep breath of fresh air and catch up on our research that’s been making publishing news. This week we’re covering genes that cause osteoporosis, the effects of longer work shifts for first-year residents, and the project to map every cell in a child’s body. You’ll also learn about respiratory support in preterm infants and research results that Children’s Hospital of Philadelphia investigators published in the Public Library of Science (PLOS) One.

Risk Genes for Osteoporosis May Lead to Future Treatments

Scientists have harnessed powerful data analysis tools and three-dimensional studies of genomic geography to implicate new risk genes for osteoporosis, the chronic bone-weakening condition that affects millions of people. Knowing the causative genes may later open the door to more effective treatments.

“Identifying a disease’s actual underlying cause often helps to steer us toward correct, targeted treatments,” said study leader Struan Grant, PhD, co-director of the Center for Spatial and Functional Genomics (CSFG) at CHOP. “We have identified two novel genes that affect bone-forming cells relevant to fractures and osteoporosis. Furthermore, the research methods we used could be applied more broadly to other diseases with a genetic component.”

The study pinpointed two novel genes, ING3 and EPDR1, which in turn revealed strong effects on human osteoblasts — bone-forming cells derived from mesenchymal stem cells.

“While we’re not ruling out other possible causative genes in these regions, the ING3 gene particularly stood out because we found that the genetic signal at this region was the strongest one associated with bone density at the wrist — the major site of fracture in children,” said genetics researcher Alessandra Chesi, PhD, also from CHOP, who was the first author, along with three additional joint first authors.

Read more about the study, published March 19, in Nature Communications in a CHOP press release.

Patient Safety Not Impeded by Residents’ Longer Work Shifts

Patient safety did not decline when first-year residents in dozens of U.S. adult hospitals worked shifts longer than 16 hours, according to research led by Jeffrey Silber, MD, PhD, director of the Center for Outcomes Research at CHOP. The findings appeared last month in the New England Journal of Medicine. The carefully designed study offered “reassuring evidence that a more flexible approach to shift length does not pose significant risks to patients, compared to the conventional duty hours,” Dr. Silber said.

In 2011, the Accreditation Council for Graduate Medical Education established standards that limited first-year residents to work shifts of 16 hours per day and 80 hours per week. The researchers compared patient outcomes under those shift limits to outcomes under a system that allowed longer work shifts within the overall 80-hour weekly limit.

Overall, there was no significant difference between either group in patient mortality over 30 days. Likewise, there were no adverse effects on other patient safety outcomes. 

Learn more about the study in CHOP News.

CHOP Researchers Look for New Ways to Detect Pediatric Spinal Deformity

Study collaborators in the Division of Orthopaedics and the Department of Radiology at CHOP reported on a new method for clinicians to gain information regarding the true curvature of the spine from clinically available medical images. Until now, a time-consuming image processing was required to obtain this information.

Research led by Saba Pasha, PhD, director of Orthopaedic Engineering in the Division of Orthopaedics at CHOP, appeared online in Public Library of Science (PLOS) One. The findings emphasized the importance of “characterizing the pairs of the sagittal and frontal curves as they related to a true 3D classification of the spine.”

“The aim of this study was to develop a method that can provide adequate information regarding the patients’ spinal deformity that fits in the busy clinical practice,” Dr. Pasha said. “The application of machine learning and artificial intelligence shows exciting future for patient care in the field of pediatric spinal deformity.”

For more information see the findings in PLOS ONE or go to CHOP News.

Standard Treatment Lung Inflation Prevails for Extremely Preterm Infants

A new study published in the Journal of the American Medical Association revealed that for extremely premature infants, the standard treatment for lung inflation — intermittent positive pressure ventilation — provided better outcome than sustained inflations.

“Preterm infants with weak respiratory muscles and liquid-filled lungs struggle to aerate their lungs, leaving them at risk of complications, including bronchopulmonary dysplasia (BPD), which is associated with a lot of long-term problems,” said Haresh Kirpalani, MD, neonatologist at CHOP and the study’s lead author. “We hypothesized that establishing adequate lung volume quickly in these infants could reduce the risk of BPD. This was possible using sustained inflations at delivery, as these appeared beneficial in animal models, and in smaller prior human studies. However, in our larger randomized trial, in the smallest and most vulnerable preterm infants, this proved not to be the case.

“Additional research is needed to address how best to treat these infants at delivery, to reduce their risk of extreme side effects of a very early birth,” Dr. Kirpalani added.

For more details of the study findings, see CHOP’s press release.

Pediatric Cell Atlas to Provide Window Into Child Health and Disease

The Pediatric Cell Atlas (PCA) is a powerful new resource for fine-grained scientific understanding of human growth and development. Drawing on dramatic recent advances in technology, the Atlas will offer an unprecedented window into the unique biology of children by benchmarking healthy and abnormal tissues at the level of single cells — the basic units of biology.

“Pediatricians are familiar with the mantra that ‘children are not just small adults,’” said Deanne Taylor, PhD, director of Bioinformatics in the Department of Biomedical and Health Informatics at CHOP and a research assistant professor of Pediatrics in the Perelman School of Medicine at Penn. “Children’s diseases, symptoms, outcomes, and therapies are often age-dependent, along with differences in physiology, presentation, and drug responses compared to those occurring in adults. With this Atlas, we’ll have a standard reference tool showing, at different ages, which cells are doing the work for a child to grow healthily.”

Dr. Taylor is the first and corresponding author of an open-access perspective article on the PCA in the journal Developmental Cell, appearing online March 28. One of her co-first authors is Kai Tan, PhD, CHOP Cancer Center researcher and associate professor of Pediatrics at Penn. The PCA aims to bring together a global coalition of pediatric researchers to create this high-definition view of children’s health, according to Dr. Taylor.

The PCA will be part of a broader international consortium, the Human Cell Atlas (HCA), sharing data researchers worldwide. It will store data in the HCA’s repository, with associated biobanking and data repositories in different centers available to biological researchers.

“Ultimately, researchers would leverage knowledge from single-cell data into a deeper understanding of organ development and function, to better inform precision treatments to advance children’s health,” Dr. Taylor said.

See the CHOP press release or WHYY article for more information.


Catch up on our headlines from our March 22 In the News:

  • Mitochondrial Disease-Causing Gene has Varied Effects
  • Antibody-drug Conjugate Efficacious Against Cell Surface Protein
  • Maternal Depression and Stress in the NICU and at 5 Years
  • Young Drivers with Visual Impairments Not More Likely to Crash
  • Study Reveals Trends in Pediatric Opioid Prescriptions

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