Publications by authors named "Samantha Butler"

57 Publications

Care of hospitalized infants and their families during the COVID-19 pandemic: an international survey.

J Perinatol 2021 Mar 23. Epub 2021 Mar 23.

Fairfield University, Egan School of Nursing and Health Studies, Fairfield, CT, USA.

This research study explored changes in family-centered care practices for hospitalized infants and families due to the COVID-19 pandemic. This exploratory descriptive study used a 49-item online survey, distributed to health care professionals working with hospitalized infants and families. The sample consisted of 96 participants from 22 countries. Prior to the COVID-19 pandemic, 87% of units welcomed families and 92% encouraged skin-to-skin care. During the pandemic, family presence was restricted in 83% of units, while participation in infant care was restricted in 32%. Medium-sized (20-40 beds) units applied less restriction than small (<20 beds) units (p = 0.03). Units with single-family rooms that did not restrict parental presence, implemented fewer restrictions regarding parents' active participation in care (p = 0.02). Restrictions to families were not affected by geographic infection rates or developmental care education of health care professionals. Restrictions during the pandemic increased separation between the infant and family.
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http://dx.doi.org/10.1038/s41372-021-00960-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985585PMC
March 2021

Dorsal commissural axon guidance in the developing spinal cord.

Curr Top Dev Biol 2021 19;142:197-231. Epub 2020 Nov 19.

Department of Neurobiology, University of California, Los Angeles, CA, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, United States. Electronic address:

Commissural axons have been a key model system for identifying axon guidance signals in vertebrates. This review summarizes the current thinking about the molecular and cellular mechanisms that establish a specific commissural neural circuit: the dI1 neurons in the developing spinal cord. We assess the contribution of long- and short-range signaling while sequentially following the developmental timeline from the birth of dI1 neurons, to the extension of commissural axons first circumferentially and then contralaterally into the ventral funiculus.
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http://dx.doi.org/10.1016/bs.ctdb.2020.10.009DOI Listing
November 2020

Derivation of dorsal spinal sensory interneurons from human pluripotent stem cells.

STAR Protoc 2021 Mar 3;2(1):100319. Epub 2021 Feb 3.

Department of Neurobiology, University of California Los Angeles, Los Angeles, CA 90095, USA.

We describe two differentiation protocols to derive sensory spinal interneurons (INs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). In protocol 1, we use retinoic acid (RA) to induce pain, itch, and heat mediating dI4/dI6 interneurons, and in protocol 2, RA with bone morphogenetic protein 4 (RA+BMP4) is used to induce proprioceptive dI1s and mechanosensory dI3s in hPSC cultures. These protocols provide an important step toward developing therapies for regaining sensation in spinal cord injury patients. For complete details on the use and execution of this protocol, please refer to Gupta et al. (2018).
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http://dx.doi.org/10.1016/j.xpro.2021.100319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890043PMC
March 2021

Comparison of the effectiveness of position change for patients with pain and vascular complications after transfemoral coronary angiography: a randomized clinical trial.

BMC Cardiovasc Disord 2021 Feb 25;21(1):114. Epub 2021 Feb 25.

Medical-Surgical Department, Faculty of Nursing, Aja University of Medical Sciences, Tehran, Iran.

Background: Prolonged immobilization after transfemoral coronary angiography (TFA) may cause pain and vascular complications in patients. This study aimed to evaluate the effectiveness of a change in position to decrease pain and vascular complications for patients after TFA.

Methods: This randomized clinical trial was conducted in 2020. Purposive sampling of 72 eligible patients undergoing TFA were selected and randomly assigned to either an experimental or control group. Patients in the experimental group (EG) were placed in a supine position for 2 h after angiography, followed by a semi-seated position with the bed angle gradually increased to 45° over 4 h. Patients in the control group (CG) remained in the supine position for 6 h. Vital signs, groin, back and leg pain, hematoma, hemorrhage, and urinary retention were assessed in both groups before, immediately after, and over 6 h after angiography. The Visual Analogue Scale was used to measure pain, the Christensen scale to measure hematoma, counting bloody gases to measure hemorrhage, and patient self-rating to determine urinary retention.

Results: There was no significant difference between EG and CG on score of groin (2.69 ± 1.00 vs. 2.61 ± 1.00, P = 0.74), back (2.19 ± 0.98 vs. 2.47 ± 0.87, P = 0.21), and leg pain (2.14 ± 0.71 vs. 2.50 ± 1.08, P = 0.27) before the TFA. However, from the second hour to the sixth hour after the TFA, the pain in the EG was significantly less than the CG (P < 0.001). So that pain in the groin (1.36 ± 0.48 vs. 3.28 ± 0.81), back (1.25 ± 0.50 vs. 3.81 ± 1.06), and leg (1.44 ± 0.55 vs. 3.28 ± 0.81) for the EG patients was significantly less than the CG in the sixth hour after TFA (P < 0.001). No patients experienced hematoma. No differences were noted between groups in hemorrhage and urinary retention.

Conclusions: Position change to a semi-seated position in patients after TFA is effective and safe for reduction of pain without increasing vascular complications.

Trial Registration: Iranian Registry of Clinical Trials: IRCT registration number: IRCT20200410047011N1, Registration date: 30/04/2020.
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http://dx.doi.org/10.1186/s12872-021-01922-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908805PMC
February 2021

Disruptions in the development of feeding for infants with congenital heart disease.

Cardiol Young 2021 Apr 11;31(4):589-596. Epub 2020 Dec 11.

Harvard Medical School, Boston Children's Hospital, Boston, MA, United States.

Congenital heart disease (CHD) is the most common birth defect for infants born in the United States, with approximately 36,000 affected infants born annually. While mortality rates for children with CHD have significantly declined, there is a growing population of individuals with CHD living into adulthood prompting the need to optimise long-term development and quality of life. For infants with CHD, pre- and post-surgery, there is an increased risk of developmental challenges and feeding difficulties. Feeding challenges carry profound implications for the quality of life for individuals with CHD and their families as they impact short- and long-term neurodevelopment related to growth and nutrition, sensory regulation, and social-emotional bonding with parents and other caregivers. Oral feeding challenges in children with CHD are often the result of medical complications, delayed transition to oral feeding, reduced stamina, oral feeding refusal, developmental delay, and consequences of the overwhelming intensive care unit (ICU) environment. This article aims to characterise the disruptions in feeding development for infants with CHD and describe neurodevelopmental factors that may contribute to short- and long-term oral feeding difficulties.
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http://dx.doi.org/10.1017/S1047951120004382DOI Listing
April 2021

Neurodevelopmental evaluation strategies for children with congenital heart disease aged birth through 5 years: recommendations from the cardiac neurodevelopmental outcome collaborative.

Cardiol Young 2020 Nov 4;30(11):1609-1622. Epub 2020 Nov 4.

Department of Cardiology, Children's National Hospital, Washington, DC, USA.

This paper provides specific guidelines for the neurodevelopmental evaluation of children aged birth through 5 years with complex congenital heart disease. There is wide recognition that children with congenital heart disease are at high risk for neurodevelopmental impairments that are first apparent in infancy and often persist as children mature. Impairments among children with complex congenital heart disease cross developmental domains and affect multiple functional abilities. The guidelines provided are derived from the substantial body of research generated over the past 30 years describing the characteristic developmental profiles and the long-term trajectories of children surviving with complex congenital heart conditions. The content and the timing of the guidelines are consistent with the 2012 American Heart Association and the American Academy of Pediatrics scientific statement documenting the need for ongoing developmental monitoring and assessment from infancy through adolescence. The specific guidelines offered in this article were developed by a multidisciplinary clinical research team affiliated with the Cardiac Neurodevelopmental Outcome Collaborative, a not-for-profit organisation established to determine and implement best neurodevelopmental practices for children with congenital heart disease. The guidelines are designed for use in clinical and research applications and offer an abbreviated core protocol and an extended version that expands the scope of the evaluation. The guidelines emphasise the value of early risk identification, use of evidence-based assessment instruments, consideration of family and cultural preferences, and the importance of providing multidimensional community-based services to remediate risk.
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http://dx.doi.org/10.1017/S1047951120003534DOI Listing
November 2020

The Effect of Semirecumbent and Right Lateral Positions on the Gastric Residual Volume of Mechanically Ventilated, Critically Ill Patients.

J Nurs Res 2020 Aug;28(4):e108

PhD, Associate Professor, Faculty of Nursing, Community Health Department, Aja University of Medical Sciences, Tehran, Iran.

Background: Delay in stomach discharge is a challenge for patients who are tube fed and may result in serious side effects such as pneumonia and malnutrition.

Purpose: This study was designed to determine the respective effects of the semirecumbent (SR) supine and right lateral (RL) with a flatbed positions on the gastric residual volume (GRV) of mechanically ventilated, critically ill adult patients.

Methods: A randomized, crossover clinical trial design was used to investigate GRV in 36 critically ill, ventilated adult patients who were hospitalized in the intensive care unit. GRV was measured at 3 hours after three consecutive feedings. GRV was first measured in all of the participants in the supine position; after which, participants were randomly assigned into one of two therapeutic positioning groups (Group A: assessment in the SR position and then the RL position; Group B: assessment in the RL position and then the SR position).

Results: GRV was significantly lower in both the SR and RL positions than in the supine position. GRV in the SR and RL positions did not vary significantly. The in-group measurements for GRV did not significantly differ for any of the three positions. In Group A, GRV was significantly lower at each subsequent measurement point.

Conclusion/implications For Practice: Positioning patients in the RL and SR positions rather than in the supine position is an effective strategy to reduce GRV. Furthermore, placing patients in either the RL or SR position is an effective intervention to promote faster digestion and feedings.
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http://dx.doi.org/10.1097/jnr.0000000000000377DOI Listing
August 2020

Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skin.

Dev Biol 2020 08 19;464(1):71-87. Epub 2020 Apr 19.

Departments of Genetics and Development, and Dermatology, Columbia University Medical Center, New York, NY, 10032, USA; Department of Systems Biology, Harvard Medical School, Boston, MA, 02115, USA. Electronic address:

Animal development and homeostasis depend on precise temporal and spatial intercellular signaling. Components shared between signaling pathways, generally thought to decrease specificity, paradoxically can also provide a solution to pathway coordination. Here we show that the Bone Morphogenetic Protein (BMP) and Wnt signaling pathways share Apcdd1 as a common inhibitor and that Apcdd1 is a taxon-restricted gene with novel domains and signaling functions. Previously, we showed that Apcdd1 inhibits Wnt signaling (Shimomura et al., 2010), here we find that Apcdd1 potently inhibits BMP signaling in body axis formation and neural differentiation in chicken, frog, zebrafish. Furthermore, we find that Apcdd1 has an evolutionarily novel protein domain. Our results from experiments and modeling suggest that Apcdd1 may coordinate the outputs of two signaling pathways that are central to animal development and human disease.
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http://dx.doi.org/10.1016/j.ydbio.2020.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307705PMC
August 2020

A Collaborative Learning Assessment of Developmental Care Practices for Infants in the Cardiac Intensive Care Unit.

J Pediatr 2020 05 5;220:93-100. Epub 2020 Mar 5.

Department of Neuropsychology, Children's Healthcare of Atlanta, Atlanta, GA.

Objective: Assess differences in approaches to and provision of developmental care for infants undergoing surgery for congenital heart disease.

Study Design: A collaborative learning approach was used to stratify, assess, and compare individualized developmental care practices among multidisciplinary teams at 6 pediatric heart centers. Round robin site visits were completed with structured site visit goals and postvisit reporting. Practices of the hosting site were assessed by the visiting team and reviewed along with center self-assessments across specific domains including pain management, environment, cue-based care, and family based care coordination.

Results: Developmental care for infants in the cardiac intensive care unit (CICU) varies at both a center and individual level. Differences in care are primarily driven by variations in infrastructure and resources, composition of multidisciplinary teams, education of team members, and use of developmental care champions. Management of pain follows a protocol in most cardiac intensive care units, but the environment varies across centers, and the provision of cue-based infant care and family-based care coordination varies widely both within and across centers. The project led to proposed changes in clinical care and center infrastructure at each participating site.

Conclusions: A collaborative learning design fostered rapid dissemination, comparison, and sharing of strategies to approach a complex multidisciplinary care paradigm. Our assessment of experiences revealed marked variability across and within centers. The collaborative findings were a first step toward strategies to quantify and measure developmental care practices in the cardiac intensive care unit to assess the association of complex inpatient practices with long-term neurodevelopmental outcomes.
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http://dx.doi.org/10.1016/j.jpeds.2020.01.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186140PMC
May 2020

The Cofilin/Limk1 Pathway Controls the Growth Rate of Both Developing and Regenerating Motor Axons.

J Neurosci 2019 11 2;39(47):9316-9327. Epub 2019 Oct 2.

Department of Neurobiology,

Regenerating axons often have to grow considerable distances to reestablish circuits, making functional recovery a lengthy process. One solution to this problem would be to co-opt the "temporal" guidance mechanisms that control the rate of axon growth during development to accelerate the rate at which nerves regenerate in adults. We have previously found that the loss of Limk1, a negative regulator of cofilin, accelerates the rate of spinal commissural axon growth. Here, we use mouse models to show that spinal motor axon outgrowth is similarly promoted by the loss of Limk1, suggesting that temporal guidance mechanisms are widely used during development. Furthermore, we find that the regulation of cofilin activity is an acute response to nerve injury in the peripheral nervous system. Within hours of a sciatic nerve injury, the level of phosphorylated cofilin dramatically increases at the lesion site, in a Limk1-dependent manner. This response may be a major constraint on the rate of peripheral nerve regeneration. Proof-of-principle experiments show that elevating cofilin activity, through the loss of Limk1, results in faster sciatic nerve growth, and improved recovery of some sensory and motor function. The studies shed light on an endogenous, shared mechanism that controls the rate at which developing and regenerating axons grow. An understanding of these mechanisms is key for developing therapies to reduce painful recovery times for nerve-injury patients, by accelerating the rate at which damaged nerves reconnect with their synaptic targets.
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http://dx.doi.org/10.1523/JNEUROSCI.0648-19.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867821PMC
November 2019

New perspectives on the mechanisms establishing the dorsal-ventral axis of the spinal cord.

Curr Top Dev Biol 2019 26;132:417-450. Epub 2018 Dec 26.

Department of Neurobiology, University of California, Los Angeles, CA, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, United States. Electronic address:

Distinct classes of neurons arise at different positions along the dorsal-ventral axis of the spinal cord leading to spinal neurons being segregated along this axis according to their physiological properties and functions. Thus, the neurons associated with motor control are generally located in, or adjacent to, the ventral horn whereas the interneurons (INs) that mediate sensory activities are present within the dorsal horn. Here, we review classic and recent studies examining the developmental mechanisms that establish the dorsal-ventral axis in the embryonic spinal cord. Intriguingly, while the cellular organization of the dorsal and ventral halves of the spinal cord looks superficially similar during early development, the underlying molecular mechanisms that establish dorsal vs ventral patterning are markedly distinct. For example, the ventral spinal cord is patterned by the actions of a single growth factor, sonic hedgehog (Shh) acting as a morphogen, i.e., concentration-dependent signal. Recent studies have shed light on the mechanisms by which the spatial and temporal gradient of Shh is transduced by cells to elicit the generation of different classes of ventral INs, and motor neurons (MNs). In contrast, the dorsal spinal cord is patterned by the action of multiple factors, most notably by members of the bone morphogenetic protein (BMP) and Wnt families. While less is known about dorsal patterning, recent studies have suggested that the BMPs do not act as morphogens to specify dorsal IN identities as previously proposed, rather each BMP has signal-specific activities. Finally, we consider the promise that elucidation of these mechanisms holds for neural repair.
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http://dx.doi.org/10.1016/bs.ctdb.2018.12.010DOI Listing
August 2019

Anal Intraepithelial Neoplasia from a Pathologists Point of View.

Clin Colon Rectal Surg 2018 Nov 2;31(6):328-335. Epub 2018 Nov 2.

Department of Pathology and Laboratory Services, San Antonio Military Medical Center, Ft. Sam Houston, Texas.

Anal squamous cell carcinoma is a relatively rare diagnosis, but its incidence has continued to rise. Anal squamous cell carcinoma and its precursor lesion, anal intraepithelial neoplasia (AIN), are human papillomavirus (HPV)-associated squamous neoplasias. High-risk HPV subtypes cause cellular proliferation in the anal transformation zone mucosa leading to similar dysplastic changes as seen in the cervix. Unified cytologic and histologic classification systems have emerged for all HPV-associated squamous lesions of the lower anogenital tract due to recent advancements in the understanding of these lesions. P16 immunohistochemical stain, a biomarker for HPV, is recommended in the diagnosis of HPV-associated lesions. The unity of terminology will aid in communication between pathologists and clinicians, ultimately leading to improved patient care.
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http://dx.doi.org/10.1055/s-0038-1668102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214808PMC
November 2018

Parent Engagement Correlates With Parent and Preterm Infant Oxytocin Release During Skin-to-Skin Contact.

Adv Neonatal Care 2019 Feb;19(1):73-79

School of Nursing, University of Connecticut, Storrs (Drs Vittner and Ms Makris); School of Nursing, University of Texas Health Science Center San Antonio, San Antonio, Texas (Dr. McGrath) Connecticut Children's Medical Center, Hartford (Drs Vittner and Brownell and Ms Smith); Boston Children's Hospital, Boston, Massachusetts (Dr Butler); Harvard Medical School, Harvard University, Boston, Massachusetts (Dr Butler); and School of Nursing, South Dakota State University, Brookings (Dr Samra).

Background: Preterm infants remain increasingly neurodevelopmentally disadvantaged. Parental touch, especially during skin-to-skin contact (SSC), has potential to reduce adverse consequences.

Purpose: To examine relationships between parental engagement and salivary oxytocin and cortisol levels for parents participating in SSC intervention.

Methods: A randomized crossover design study was conducted in a neonatal intensive care unit; 28 stable preterm infants, mothers, and fathers participated. Parental engagement was measured using the Parental Risk Evaluation Engagement Model Instrument (PREEMI) prior to hospital discharge. Saliva samples for oxytocin and cortisol levels were collected 15-minute pre-SSC, 60-minute during-SSC, and 45-minute post-SSC.

Results: Data were analyzed using Pearson's correlation to measure relationships between parental engagement composite scores and salivary oxytocin and cortisol levels. A significant negative correlation between paternal engagement and paternal oxytocin levels (r = -0.43; P = .03) and a significant negative correlation between infant oxytocin levels and maternal engagement (r = -0.54; P = .004) were present. Adjusted linear regression models demonstrated that as infant oxytocin levels increased during SSC, maternal engagement scores significantly decreased at discharge (β = -.04; P = .01). Linear regression, adjusting for infant oxytocin and cortisol levels, showed that as paternal oxytocin levels increased, there was a significant decrease in paternal engagement (β = -.16; P = .03) and as paternal cortisol levels increased, there was a significant decrease in paternal engagement (β = -68.97; P =.05).

Implications For Practice: Significant relationships exist between parental engagement and salivary oxytocin and cortisol levels. Defining parent engagement facilitates identification of parent risks and needs for intervention to optimize preterm outcomes.

Implications For Research: The PREEMI can serve as a standardized instrument to examine parent engagement.
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http://dx.doi.org/10.1097/ANC.0000000000000558DOI Listing
February 2019

Neurodevelopmental assessment of infants with congenital heart disease in the early postoperative period.

Congenit Heart Dis 2019 Mar 15;14(2):236-245. Epub 2018 Oct 15.

Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.

Objective: Mortality rates for children with congenital heart disease (CHD) have significantly declined, resulting in a growing population with associated neurodevelopmental disabilities. American Heart Association guidelines recommend systematic developmental screening for children with CHD. The present study describes results of inpatient newborn neurodevelopmental assessment of infants after open heart surgery.

Outcome Measures: We evaluated the neurodevelopment of a convenience sample of high-risk infants following cardiac surgery but before hospital discharge using an adaptation of the Newborn Behavioral Observation. Factor analysis examined relationships among assessment items and consolidated them into domains of development.

Results: We assessed 237 infants at a median of 11 days (interquartile range [IQR]: 7-19 days) after cardiac surgery and median corrected age of 21 days (IQR: 13-33 days). Autonomic regulation was minimally stressed or well organized in 14% of infants. Upper and lower muscle tone was appropriate in 33% and 35%, respectively. Appropriate response to social stimulation ranged between 7% and 12% depending on task, and state regulation was well organized in 14%. The vast majority (87%) required enhanced examiner facilitation for participation. Factor analyses of assessment items aligned into four domains of development (autonomic, motor, oral motor, and attention organization).

Conclusion: At discharge, postoperative infants with CHD had impairments in autonomic, motor, attention, and state regulation following cardiac surgery. Findings highlight the challenges faced by children with CHD relative to healthy peers, suggesting that neurodevelopmental follow-up and intervention should begin early in infancy.
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http://dx.doi.org/10.1111/chd.12686DOI Listing
March 2019

Individualized Family-Centered Developmental Care: An Essential Model to Address the Unique Needs of Infants With Congenital Heart Disease.

J Cardiovasc Nurs 2019 Jan/Feb;34(1):85-93

Amy Lisanti, PhD, RN, CCNS, CCRN-K NRSA Postdoctoral Fellow, University of Pennsylvania School of Nursing; and Clinical Nurse Specialist/Nurse Scientist, Cardiac Nursing at Children's Hospital of Philadelphia, Pennsylvania. Dorothy Vittner, PhD, RN Nurse Scientist, Connecticut Children's Medical Center, Hartford; and Faculty, School of Nursing and an Assistant Professor, University of Connecticut School of Nursing, Storrs. Barbara Medoff-Cooper, PhD, RN Professor, Univeristy of Pennsylvania School of Nursing, Philadelphia. Jennifer Fogel, M.S.CCC-SLP/L Pediatric Speech Language Pathologist, Advocate Children's Hospital, Oak Lawn, Illinois. Gil Wernovsky, MD Senior Consultant in Cardiac Critical Care and Pediatric Cardiology, Children's National Health System, Washington, District of Columbia. Samantha Butler, PhD Developmental and Clinical Psychologist Director, Boston Children's; and Assistant Professor in Psychiatry, Harvard Medical School, Boston, Massachusetts.

Background: Infants born with critical congenital heart disease (cCHD) who require surgical intervention in the newborn period are often hospitalized in a cardiac intensive care unit (CICU). Cardiac surgery and the CICU environment are traumatic to infants and their families. Infants are exposed to overwhelming stress, which can result in increased pain, physiologic instability, behavioral disorganization, disrupted attachment, and altered brain development. Individualized Family-centered Developmental Care (IFDC) is a model that can address the unique needs and developmental challenges of infants with cCHD.

Purpose: The purpose of this article is to (1) clearly describe the uniqueness of the infant with cCHD, including the medical, neurological, and parental challenges, and (2) propose methods to apply IFDC to support recovery of infants with cCHD in the CICU.

Conclusions: The experiences in the CICU shape the developing brain and alter recovery and healing, thus adversely impacting development. Individualized Family-centered Developmental Care is a promising model of care that nurses can integrate into the CICU to promote neuroprotection and development. Nurses can effectively integrate IFDC into the CICU by understanding the unique characteristics of infants with cCHD and applying IFDC interventions that include both maturity and recovery perspectives.

Clinical Implications: The incorporation of IFDC interventions is essential for the infant with cCHD and should be a standard of care. Applying IFDC with a recovery perspective in all aspects of caregiving will provide opportunities for individualization of care and parent engagement, allowing infants in the CICU to recover from surgery while supporting both short- and long-term neurodevelopment.
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http://dx.doi.org/10.1097/JCN.0000000000000546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283700PMC
March 2020

Advanced fabrication of biosensor on detection of Glypican-1 using S-Acetylmercaptosuccinic anhydride (SAMSA) modification of antibody.

Sci Rep 2018 09 10;8(1):13541. Epub 2018 Sep 10.

Department of Chemical and Biomolecular Engineering, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106, USA.

Glypican-1 (GPC-1) has been recognized as biomarker of pancreatic cancer. Quantification of GPC-1 level is also pivotal to breast cancer and prostate cancer's patients. We hereby report the first biosensor for GPC-1 detection. Instead of using crosslinking technique and surface immobilization of antibody, we applied a novel method for biosensor fabrication, using S-Acetylmercaptosuccinic anhydride (SAMSA) to modify the Anti-GPC-1 producing a thiol-linked Anti-GPC-1. The thiol-linked Anti-GPC-1 was then directly formed a single-layer antibody layer on the gold biosensor, minimizing the biosensor preparation steps significantly. Time of Flight Secondary Ions Mass Spectroscopy (TOF-SIMS) characterization verified the thiol-linked antibody layer and demonstrated a unique perspective for surface protein characterization. Differential pulse voltammetry (DPV) was applied to quantify GPC-1 antigen in undiluted human serum with a concentration range of 5,000 pg/µL to 100 pg/µL. The performance of this newly designed biosensor was also compared with modified self-assembled monolayer system fabricated biosensor, demonstrating the high-sensitivity and high-reproducibility of the SAMSA modified antibody based biosensor. This simple fabrication method can also expand to detection of other biomolecules. The simplified operation process shows great potential in clinical application development.
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http://dx.doi.org/10.1038/s41598-018-31994-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131508PMC
September 2018

Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells.

Stem Cell Reports 2018 02 11;10(2):390-405. Epub 2018 Jan 11.

Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Cellular replacement therapies for neurological conditions use human embryonic stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to replace damaged or diseased populations of neurons. For the spinal cord, significant progress has been made generating the in-vitro-derived motor neurons required to restore coordinated movement. However, there is as yet no protocol to generate in-vitro-derived sensory interneurons (INs), which permit perception of the environment. Here, we report on the development of a directed differentiation protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally relevant factors, retinoic acid in combination with bone morphogenetic protein 4, can be used to generate three classes of sensory INs: the proprioceptive dI1s, the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence state of the neural progenitors, which changes over time. This protocol will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients.
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http://dx.doi.org/10.1016/j.stemcr.2017.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832443PMC
February 2018

BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activities.

Elife 2017 09 19;6. Epub 2017 Sep 19.

Department of Neurobiology, University of California, Los Angeles, United States.

The Bone Morphogenetic Protein (BMP) family reiteratively signals to direct disparate cellular fates throughout embryogenesis. In the developing dorsal spinal cord, multiple BMPs are required to specify sensory interneurons (INs). Previous studies suggested that the BMPs act as concentration-dependent morphogens to direct IN identity, analogous to the manner in which sonic hedgehog patterns the ventral spinal cord. However, it remains unresolved how multiple BMPs would cooperate to establish a unified morphogen gradient. Our studies support an alternative model: BMPs have signal-specific activities directing particular IN fates. Using chicken and mouse models, we show that the identity, not concentration, of the BMP ligand directs distinct dorsal identities. Individual BMPs promote progenitor patterning or neuronal differentiation by their activation of different type I BMP receptors and distinct modulations of the cell cycle. Together, this study shows that a 'mix and match' code of BMP signaling results in distinct classes of sensory INs.
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http://dx.doi.org/10.7554/eLife.30647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605194PMC
September 2017

Filling a significant gap in the cardiac ICU: implementation of individualised developmental care.

Cardiol Young 2017 Nov 7;27(9):1797-1806. Epub 2017 Aug 7.

4Department of Cardiovascular and Critical Care Programs,Boston Children's Hospital,Boston,Massachusetts,United States of America.

Mortality rates among children with CHD have significantly declined, although the incidence of neurological abnormalities and neurodevelopmental impairment has increased. Research has focussed on outcomes, with limited attention on prevention and intervention. Although some developmental differences and challenges seen in children with CHD are explained by the cumulative effect of medical complications associated with CHD, many sequelae are not easily explained by medical complications alone. Although cardiac intensive care is lifesaving, it creates high levels of environmental and tactile stimulation, which potentially contribute to adverse neurodevelopmental outcomes. The therapeutic method of individualised developmental care, such as the Newborn Individualized Developmental Care and Assessment Program, provides early support and preventive intervention based on each child's behavioural signals of stress, comfort, and strength. Implementing developmental care practices in a cardiac ICU requires a thoughtful and well-planned approach to ensure successful adoption of practice changes. This paper reviews how developmental care was introduced in a paediatric inpatient cardiac service through multidisciplinary collaborative staff education, clinician support, child neurodevelopment assessment, parent support, and research initiatives. Given the known risk for children with CHD, cardiac medical professionals must shift their focus to not only assuring the child's survival but also optimising development through individualised developmental care in the cardiac ICU.
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http://dx.doi.org/10.1017/S1047951117001469DOI Listing
November 2017

Netrin1 establishes multiple boundaries for axon growth in the developing spinal cord.

Dev Biol 2017 10 3;430(1):177-187. Epub 2017 Aug 3.

Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, United States; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, United States; Neuroscience Interdisciplinary Graduate Program, University of California, Los Angeles, Los Angeles, CA 90095, United States. Electronic address:

The canonical model for netrin1 function proposed that it acted as a long-range chemotropic axon guidance cue. In the developing spinal cord, floor-plate (FP)-derived netrin1 was thought to act as a diffusible attractant to draw commissural axons to the ventral midline. However, our recent studies have shown that netrin1 is dispensable in the FP for axon guidance. We have rather found that netrin1 acts locally: netrin1 is produced by neural progenitor cells (NPCs) in the ventricular zone (VZ), and deposited on the pial surface as a haptotactic adhesive substrate that guides Dcc axon growth. Here, we further demonstrate that this netrin1 pial-substrate has an early role orienting pioneering spinal axons, directing them to extend ventrally. However, as development proceeds, commissural axons choose to grow around a boundary of netrin1 expressing cells in VZ, instead of continuing to extend alongside the netrin1 pial-substrate in the ventral spinal cord. This observation suggests netrin1 may supply a more complex activity than pure adhesion, with netrin1-expressing cells also supplying a growth boundary for axons. Supporting this possibility, we have observed that additional domains of netrin1 expression arise adjacent to the dorsal root entry zone (DREZ) in E12.5 mice that are also required to sculpt axonal growth. Together, our studies suggest that netrin1 provides "hederal" boundaries: a local growth substrate that promotes axon extension, while also preventing local innervation of netrin1-expressing domains.
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http://dx.doi.org/10.1016/j.ydbio.2017.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786155PMC
October 2017

Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord.

Neuron 2017 May 21;94(4):790-799.e3. Epub 2017 Apr 21.

Department of Neurobiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Neuroscience Interdisciplinary Graduate Program, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Netrin1 has been proposed to act from the floor plate (FP) as a long-range diffusible chemoattractant for commissural axons in the embryonic spinal cord. However, netrin1 mRNA and protein are also present in neural progenitors within the ventricular zone (VZ), raising the question of which source of netrin1 promotes ventrally directed axon growth. Here, we use genetic approaches in mice to selectively remove netrin from different regions of the spinal cord. Our analyses show that the FP is not the source of netrin1 directing axons to the ventral midline, while local VZ-supplied netrin1 is required for this step. Furthermore, rather than being present in a gradient, netrin1 protein accumulates on the pial surface adjacent to the path of commissural axon extension. Thus, netrin1 does not act as a long-range secreted chemoattractant for commissural spinal axons but instead promotes ventrally directed axon outgrowth by haptotaxis, i.e., directed growth along an adhesive surface.
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http://dx.doi.org/10.1016/j.neuron.2017.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576449PMC
May 2017

Developmental Care in North American Pediatric Cardiac Intensive Care Units: Survey of Current Practices.

Adv Neonatal Care 2016 Jun;16(3):211-9

Pediatrics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, and Nemours Cardiac Center, Alfred I. duPont Hospital for Children, Wilmington, Delaware (Dr Sood); Johns Hopkins Medicine International, Baltimore, Maryland (Ms Berends); Pediatrics, University of Michigan Medical School, Ann Arbor, and C.S. Mott Children's Hospital, Ann Arbor, Michigan (Dr Butcher); Cardiac Nursing, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (Dr Lisanti); Pediatric Nursing, University of Pennsylvania School of Nursing, Philadelphia (Dr Medoff-Cooper); Pediatrics and Psychiatry, Harvard Medical School, and Division of Developmental Medicine, Boston Children's Hospital, Boston, Massachusetts (Dr Singer); Pediatrics, School of Medicine, University of Missouri-Kansas City, and Division of Developmental and Behavioral Sciences, Children's Mercy, Kansas City, Missouri (Dr Willen); and Psychiatry, Harvard Medical School, and Department of Psychiatry, Boston Children's Hospital, Boston, Massachusetts (Dr Butler).

Background: Developmental care practices across pediatric cardiac intensive care units (CICUs) have not previously been described.

Purpose: To characterize current developmental care practices in North American CICUs.

Methods: A 47-item online survey of developmental care practices was developed and sent to 35 dedicated pediatric CICUs. Staff members who were knowledgeable about developmental care practices in the CICU completed the survey.

Findings/results: Completed surveys were received from 28 CICUs (80% response rate). Eighty-nine percent reported targeted efforts to promote developmental care, but only 50% and 43% reported having a developmental care committee and holding developmental rounds, respectively. Many CICUs provide darkness for sleep (86%) and indirect lighting for alertness (71%), but fewer provide low levels of sound (43%), television restrictions (43%), or designated quiet times (21%). Attempts to cluster care (82%) and support self-soothing during difficult procedures (86%) were commonly reported, but parental involvement in these activities is not consistently encouraged. All CICUs engage in infant holding, but practices vary on the basis of medical status and only 46% have formal holding policies.

Implications For Practice: Implementation of developmental care in the CICU requires a well-planned process to ensure successful adoption of practice changes, beginning with a strong commitment from leadership and a focus on staff education, family support, value of parents as the primary caregivers, and policies to increase consistency of practice.

Implications For Research: Future studies should examine the short- and long-term effects of developmental care practices on infants born with congenital heart disease and cared for in a pediatric CICU.
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http://dx.doi.org/10.1097/ANC.0000000000000264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659348PMC
June 2016

Image of the month: Pseudomelanosis duodeni and Strongyloides stercoralis.

Am J Gastroenterol 2015 Dec;110(12):1651

Brooke Army Medical Center, San Antonio, Texas, USA.

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http://dx.doi.org/10.1038/ajg.2015.113DOI Listing
December 2015

Utility of reflexive gomori methenamine silver and Acid-fast bacillus staining on bronchoalveolar lavage specimens.

Lab Med 2015 ;46(1):4-7

Pathology and Area Laboratory Services, Brooke Army Medical Center, San Antonio, Texas

Objective: Reflexive testing of bronchoalveolar lavage (BAL) specimens with Gomori methenamine silver (GMS) and acid-fast bacillus (AFB) stains is not routinely performed by most institutions. Instead, these stains are usually ordered to evaluate for the presence of fungal elements and/or acid-fast organisms if initial histopathologic assessment suggests the presence of these pathogens. Our institution, however, performs these stains on all BAL specimens. Thus, we sought to determine whether this practice was cost effective, considering the turnaround time and diagnostic efficacy of these tests.

Methods: We retrospectively reviewed 488 BAL specimens performed at two military healthcare institutions over a 2-year period and performed a cost analysis with review of the impact on turnaround time.

Results: Of the 488 cases, we identified only 3 (~0.6%) with infections by acid-fast or fungal organisms, at an estimated total cost of $12,151.20 and an average delay of 3.0 to 3.5 hours for slide preparation.

Conclusion: Our results suggest that in a largely young and healthy population such as ours, it may be more feasible to perform these stains on BAL specimens on a case-by-case basis rather than automatically on every specimen, to control costs and enhance productivity.
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http://dx.doi.org/10.1309/LMLJHG4E2UZKD7RGDOI Listing
July 2016

Neuronal organization: unsticking the cadherin code.

Curr Biol 2014 Dec 1;24(23):R1127-9. Epub 2014 Dec 1.

Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. Electronic address:

Hindbrain cranial motor neurons are organized into discrete functional clusters. A new study demonstrates that coalescence of these nuclei is driven by the expression of distinct combinations of cadherin adhesion molecules by each motor neuron group.
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http://dx.doi.org/10.1016/j.cub.2014.10.034DOI Listing
December 2014

From classical to current: analyzing peripheral nervous system and spinal cord lineage and fate.

Dev Biol 2015 Feb 24;398(2):135-46. Epub 2014 Oct 24.

Department of Neurobiology, TLSB 3129, 610 Charles E Young Drive East, University of California, Los Angeles, Los Angeles, CA 90095-7239, USA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address:

During vertebrate development, the central (CNS) and peripheral nervous systems (PNS) arise from the neural plate. Cells at the margin of the neural plate give rise to neural crest cells, which migrate extensively throughout the embryo, contributing to the majority of neurons and all of the glia of the PNS. The rest of the neural plate invaginates to form the neural tube, which expands to form the brain and spinal cord. The emergence of molecular cloning techniques and identification of fluorophores like Green Fluorescent Protein (GFP), together with transgenic and electroporation technologies, have made it possible to easily visualize the cellular and molecular events in play during nervous system formation. These lineage-tracing techniques have precisely demonstrated the migratory pathways followed by neural crest cells and increased knowledge about their differentiation into PNS derivatives. Similarly, in the spinal cord, lineage-tracing techniques have led to a greater understanding of the regional organization of multiple classes of neural progenitor and post-mitotic neurons along the different axes of the spinal cord and how these distinct classes of neurons assemble into the specific neural circuits required to realize their various functions. Here, we review how both classical and modern lineage and marker analyses have expanded our knowledge of early peripheral nervous system and spinal cord development.
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http://dx.doi.org/10.1016/j.ydbio.2014.09.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845735PMC
February 2015

Preference for infant-directed speech in preterm infants.

Infant Behav Dev 2014 Nov 8;37(4):505-11. Epub 2014 Jul 8.

Department of Psychology, University of Massachusetts Amherst, United States. Electronic address:

The current study explores the effects of exposure to maternal voice on infant sucking in preterm infants. Twenty-four preterm infants averaging 35 weeks gestational age were divided randomly into two groups. A contingency between high-amplitude sucking and presentation of maternal voice was instituted for one group while the other group served as a yoked control. No significant differences were observed in sucking of the two groups, but the degree of pitch modulation of the maternal voice predicted an increase in the rate of infant sucking.
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http://dx.doi.org/10.1016/j.infbeh.2014.06.007DOI Listing
November 2014

PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors.

PLoS Biol 2013 Oct 8;11(10):e1001676. Epub 2013 Oct 8.

Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America ; Broad Center for Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America ; Molecular Biology Interdepartmental Graduate Program, David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America.

Distinct classes of neurons and glial cells in the developing spinal cord arise at specific times and in specific quantities from spatially discrete neural progenitor domains. Thus, adjacent domains can exhibit marked differences in their proliferative potential and timing of differentiation. However, remarkably little is known about the mechanisms that account for this regional control. Here, we show that the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF) plays a critical role shaping patterns of neuronal differentiation by gating the expression of Fibroblast Growth Factor (FGF) Receptor 3 and responsiveness of progenitors to FGFs. PLZF elevation increases FGFR3 expression and STAT3 pathway activity, suppresses neurogenesis, and biases progenitors towards glial cell production. In contrast, PLZF loss reduces FGFR3 levels, leading to premature neuronal differentiation. Together, these findings reveal a novel transcriptional strategy for spatially tuning the responsiveness of distinct neural progenitor groups to broadly distributed mitogenic signals in the embryonic environment.
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http://dx.doi.org/10.1371/journal.pbio.1001676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792860PMC
October 2013