The brachial plexus is a network of nerves that exit the spinal cord from the C5-T1 nerve roots and provide all motor and sensory function to the arm from the shoulder to the fingers. Injury to the brachial plexus due to traction forces during labor and/or delivery causing the nerves to stretch or tear occurs in 0.9 out of 1000 live births. As many as 30% of infants with brachial plexus birth injury (BPBI) have paralysis or weakness in one arm resulting in lifelong impairment in arm function with joint contractures, the shortening of tendons, ligaments and muscles, leading to reduced range of motion (ROM), being a common complication and major source of disability. A primary goal of early management of BPBI is to use passive range of motion (PROM) (stretching) to improve and/or maintaining shoulder ROM due to the known risk of shoulder contracture within the first year of life. Infants who develop contractures face challenges in overall sensory-motor development and are less able to participate in meaningful occupations and activities of daily living due to limited upper extremity ROM. They are also at risk for subsequent surgeries throughout their lives. Occupational therapy practitioners (OTPs) and physicians who specialize in treating infants with BPBI recommend caregivers to perform PROM at every diaper change, which is every 1-3 hours in the first months of life, and every 4-6 hours by age one. A survey study by one of the investigators on this proposed project found that 85% of OTPs who specialize in BPBI make this recommendation for performing PROM at every diaper change; however, there is no research to support this frequency to prevent or decrease contractures. Clinical observations suggest that infants who receive consistent daily PROM seem to avoid development of shoulder contractures while those who receive no or infrequent PROM seem to develop early and significant contractures. In a retrospective pilot study we found that children whose parents consistently performed PROM two times daily starting before age two months were less likely to develop shoulder contractures than children whose parents were inconsistent in performing PROM. These findings, along with our clinical observations suggest that frequency of PROM might be less important than consistency. In order to assess the efficacy of different levels of frequency (e.g., at every diaper change vs. two times per day), it is imperative to identify methods that support caregivers in performing PROM every day. Therefore, the proposed study will pilot a caregiver training method which, if successful in facilitating daily adherence, will be used as part of a larger planned study that will compare differences in recommended frequencies of stretching.
In a survey study and scoping literature review performed by one of the co-investigators on this project, caregiver adherence to home therapy recommendations was found to be facilitated by confidence in the training they received and by their confidence in ability to carry-out recommendations; lack of confidence in performing the home therapy recommendations was found to be a common barrier. Therefore, the objective of the proposed work is to assess the efficacy of a pilot training protocol for caregivers of infants with BPBI. Our central hypothesis is that the pilot training protocol will improve caregiver efficacy and increase their confidence in performing the recommended PROM/stretching procedure, thus facilitating adherence which we hope to later demonstrate will decrease the risk of shoulder contracture in infants with BPBI. The significance of this work is that it will evaluate and provide evidence for the use of the pilot training protocol so that this training protocol can later be used in a larger study on the efficacy of different frequencies of PROM to reduce the development of shoulder contracture in infants with BPBI, and thus contribute to developing evidenced-based standards of care for this population.
The objectives of this clinical trial are to:
1. determine whether caregivers who receive a pilot training protocol for performing PROM demonstrate improved efficacy in performing PROM compared to caregivers who receive standard training
2. determine whether caregivers who receive a pilot training protocol for performing PROM demonstrate improved self-confidence in performing PROM compared to caregivers who receive standard training
3. determine whether caregivers who receive a pilot training protocol for performing PROM report better daily adherence to daily PROM compared to caregivers who receive standard training

开始日期2024-11-04

申办/合作机构

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

[+1]

NCT06269926 / Not yet recruitingN/AIIT

Cognitive Behavioral Therapy for Chronic Pain in Adults with Cerebral Palsy

The purpose of this study is to understand if cognitive behavioral therapy can improve pain-related thought patterns and pain-related impairment in adults with cerebral palsy.

开始日期2024-11-01

申办/合作机构

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

[+1]

NCT06312358 / Enrolling by invitationN/AIIT

Centering Community Partnerships to Facilitate Scaling Up of Infant Achievements for Community Implementation

The goal of the research study is to increase teachers' implementation of evidence-based practices in Early Head Start classrooms through the delivery of a professional development (PD) training intervention. The main questions that the study aims to answer are:
1. Does teacher participation in a PD intervention improve the use of evidence-based practices from pre- to posttest?
2. To what extent is the PD intervention feasible to implement in an established child care program?
3. To what extent is the PD program acceptable to teachers?
Participants will attend PD workshops and participate in content-related job-embedded coaching sessions during the implementation of the study.

开始日期2024-04-01

申办/合作机构

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

[+1]

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项与 Hugo W. Moser Research Institute at Kennedy Krieger, Inc. 相关的文献（医药）

2024-05-01·Annals of Neurology

Levodopa Impairs the Energy Metabolism of the Basal Ganglia In Vivo

Article

作者: Steinhardt, Julia ; Brüggemann, Norbert ; Güber, Theresia ; Prasuhn, Jannik ; Schiefen, Tanja ; Wilms, Britta ; Henkel, Julia ; Uter, Jan

ObjectiveOne proposed mechanism of disease progression in Parkinson's disease includes the interplay of endogenous dopamine toxicity and mitochondrial dysfunction. However, the in‐vivo effects of exogenous dopamine administration on cerebral bioenergetics are unknown.MethodsWe performed a double‐blinded, cross‐over, placebo‐controlled trial. Participants received either 200/50 mg levodopa/benserazide or a placebo and vice versa on the second study visit. Clinical assessments and multimodal neuroimaging were performed, including 31phosphorus magnetic resonance spectroscopy of the basal ganglia and the midbrain.ResultsIn total, 20 (6 female) patients with Parkinson's disease and 22 sex‐ and age‐matched healthy controls (10 female) were enrolled. Treatment with levodopa/benserazide but not with placebo resulted in a substantial reduction of high‐energy phosphorus‐containing metabolites in the basal ganglia (patients with Parkinson's disease: −40%; healthy controls: −39%) but not in the midbrain. There were no differences in high‐energy phosphorus‐containing metabolites for patients with Parkinson's disease compared to healthy controls in the OFF state and treatment response.InterpretationExogenously administered levodopa/benserazide strongly interferes with basal ganglia high‐energy phosphorus‐containing metabolite levels in both groups. The lack of effects on midbrain levels suggests that the observed changes are limited to the site of dopamine action. ANN NEUROL 2024;95:849–857

2024-04-01·Advanced Science

Lymphocyte‐Activation Gene 3 Facilitates Pathological Tau Neuron‐to‐Neuron Transmission

Article

作者: Jia, Hongpeng ; Chen, Chan ; Dawson, Ted M ; Wang, Anthony ; Peng, Weiyi ; Katakam, Sruthi ; Redding-Ochoa, Javier ; Troncoso, Juan C ; Chen, Rong ; Jin, Lingtao ; Ying, Mingyao ; Kimura, Yasuyoshi ; Jeong, Deok ; Zhang, Shu ; Workman, Creg J ; Wong, Philip C ; Rastegar, Cyrus ; Nauen, David W ; Yang, Xiuli ; Vignali, Dario A A ; Pletinkova, Olga ; Mao, Xiaobo ; Kumbhar, Ramhari ; Dawson, Valina L ; Gadhave, Kundlik ; Behensky, Adam ; Wang, Liang ; Wang, Hu ; Kuo, Grace ; Kotha, Sumasri

AbstractThe spread of prion‐like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern that correlates with disease severity. Clinical observation combined with complementary experimental studies has shown that Tau preformed fibrils (PFF) are prion‐like seeds that propagate pathology by entering cells and templating misfolding and aggregation of endogenous Tau. While several cell surface receptors of Tau are known, they are not specific to the fibrillar form of Tau. Moreover, the underlying cellular mechanisms of Tau PFF spreading remain poorly understood. Here, it is shown that the lymphocyte‐activation gene 3 (Lag3) is a cell surface receptor that binds to PFF but not the monomer of Tau. Deletion of Lag3 or inhibition of Lag3 in primary cortical neurons significantly reduces the internalization of Tau PFF and subsequent Tau propagation and neuron‐to‐neuron transmission. Propagation of Tau pathology and behavioral deficits induced by injection of Tau PFF in the hippocampus and overlying cortex are attenuated in mice lacking Lag3 selectively in neurons. These results identify neuronal Lag3 as a receptor of pathologic Tau in the brain，and for AD and related Tauopathies, a therapeutic target.

2024-01-01·Heliyon

Microarray analysis of lncRNAs and mRNAs in spinal cord contusion rats with iPSC-derived A2B5+ oligodendrocyte precursor cells transplantation

Article

作者: Liu, Su ; Xiong, Liu-Lin ; Wang, Ting-Hua ; Han, Xue-Fei ; Zhang, Lan-Chun ; Chen, Li ; Yuan, Hao ; Shi, Lan-Lan

Spinal cord injury (SCI) is a severe complication of spinal trauma with high disability and mortality rates. Effective therapeutic methods to alleviate neurobehavioural deficits in patients with SCI are still lacking. In this study, we established a spinal cord contusion (SCC) model in adult Sprague Dawley rats. Induced pluripotent stem cell-derived A2B5⁺ oligodendrocyte precursor cells (iP-A2B5⁺OPCs) were obtained from mouse embryonic fibroblasts and injected into the lesion sites of SCC rats. Serological testing and magnetic resonance imaging were employed to determine the effect of iP-A2B5⁺OPCs cell therapy. The Basso-Beattie-Bresnahan score and inclined plane test were performed on days 1, 3, 7, and 14 after cell transplantation, respectively. Differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) were detected by microarray analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyse the biological functions of these lncRNAs and mRNAs. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify variations in the expression of crucial target genes. The results demonstrated that induced pluripotent stem cells exhibited embryonic stem cell-like morphology and could differentiate into diverse neural cells dominated by oligodendrocytes. The neurobehavioural performance of rats treated with iP-A2B5⁺OPCs transplantation was better than that of rats with SCC without cell transplantation. Notably, we found that 22 lncRNAs and 42 mRNAs were concurrently altered after cell transplantation, and the key lncRNA (NR_037671) and target gene (Cntnap5a) were identified in the iP-A2B5⁺OPCs group. Moreover, RT-qPCR revealed that iP-A2B5⁺OPCs transplantation reversed the downregulation of NR_037671 induced by SCC. Our findings indicated that iP-A2B5⁺OPCs transplantation effectively improves neurological function recovery after SCC, and the mechanism might be related to alterations in the expression of lncRNAs and mRNAs, such as NR_037671 and Cntnap5a.

项与 Hugo W. Moser Research Institute at Kennedy Krieger, Inc. 相关的新闻（医药）

2024-05-14

·PRNewswire

Maryland Stem Cell Research Commission Announces $15.4 Million in Awards to Accelerate Cures

48 scientists receive funding from the Maryland Stem Cell Research Fund to further research COLUMBIA, Md., May 14, 2024 /PRNewswire/ -- The Maryland Stem Cell Research Commission ("Commission") is pleased to announce the next round of awards granting a total of more than $15.4 million. These awards are aimed at fostering groundbreaking research to enhance and propel stem cell treatments and technologies across Maryland. Continue Reading 48 scientists receive funding from the Maryland Stem Cell Research Fund to further research Post this Ruchika Nijhara, Ph.D., executive director of Maryland Stem Cell Research Fund (MSCRF) Several esteemed scientists from various Maryland-based research institutions and companies have been selected as recipients in this grant cycle. Among the 48 distinguished awardees are academic researchers from prestigious institutions such as Johns Hopkins University; University of Maryland, Baltimore: University of Maryland, College Park; Lieber Institute for Brain Development; and the Hugo W. Moser Research Institute at Kennedy Krieger. Commercial sector entities like Seraxis Inc., Theradaptive, Inc., HOHCells, LLC, Agnos Therapeutics, Inc., and Reprocell U.S.A., Inc. were also awarded grants. These pioneering researchers are addressing a wide array of medical conditions, ranging from sickle cell anemia, type I diabetes, cancer, dental diseases and chronic pain to diseases directed to skin, heart, bone, blood, digestive and central nervous system diseases. Awardees submitted their proposals in response to the Commission's Request for Applications (RFAs) for the second funding round of fiscal year 2024. Earlier in the fiscal year, the Commission also allocated nearly $4 million in additional research grants. "The caliber of applications received during this funding cycle was exceptional, resulting in a highly competitive selection process," remarked Diane Hoffmann, chair of the Commission. "We are excited to provide support to the recipients of this second round, with their proposals spanning early-stage research to clinical trials to building manufacturing capabilities. These awards truly embody the purpose and mission of the Maryland Stem Cell Research Fund." "The increase in the number of applications submitted underscores the heightened research and development activity in stem cell-based technologies in Maryland," said Ruchika Nijhara, Ph.D., executive director of Maryland Stem Cell Research Fund (MSCRF). "This emphasizes the importance of continuing to foster and strengthen the stem cell and regenerative medicine ecosystem in our state and beyond. With new strategic initiatives, we aim to foster collaboration between the private and public sectors, strengthening the ecosystem and accelerating the development of impactful medical solutions that can transform human lives." The second round of MSCRF awards for the 2024 fiscal year includes the following: Launch : These awards are to encourage new and new-to-the-field faculty to bring innovative research and technology to the regenerative medicine field. Totaling $2,797,553, the Launch Award recipients are Gianluca Ursini, Ph.D. and Tomoyo Sawada, Ph.D. from the Lieber Institute for Brain Development; Renyuan Bai, Ph.D. from the Hugo W. Moser Research Institute at Kennedy Krieger; Man-Kyo Chung, Ph.D. from the University of Maryland, Baltimore; Li Yan, Ph.D. from the University of Maryland, College Park; and Payam Mohassel, Ph.D., Chun-Hyun Na, Ph.D. and Allen Eghrari, Ph.D. from Johns Hopkins University. Commercialization : These awards are for Maryland-based companies to develop new human stem cell-based products. Totaling $1,692,428, the Commercialization Award recipients are Jean-Philippe Richard, Ph.D. from Reprocell, U.S.A., Inc.; Mandeep Singh, Ph.D. from Agnos Therapeutics, Inc.; Xiaoming He, Ph.D. from HOH Cells, LLC; and William Rust, Ph.D. from Seraxis, Inc. Clinical: This award is for universities/research institutes or companies that wish to conduct human stem cell-based clinical trials in the State of Maryland. Totaling $1,650,000, the Clinical Award recipients are Luis Garza, Ph.D. from Johns Hopkins University and Luis Alvarez, Ph.D. from Theradaptive Inc. Validation: This award supports faculty at Maryland-based universities/research institutes with intellectual property (IP) for human stem cell-based technologies that require additional validation. Totaling $500,000 the validation award recipients are Curt Civin, Ph.D. from the University of Maryland, Baltimore and Xinzhong Dong, Ph.D. from Johns Hopkins University. Discovery : These awards fund innovative ideas to develop novel human stem cell-based technologies and cures. Totaling $7,158,174, the Discovery Award recipients include Chulan Kwon, Ph.D., Emmanouil Tampakakis, Ph.D., Gabsang Lee, Ph.D., Hiromi Sesaki, Ph.D., Thomas Johnson, Ph.D., Xiaobo Mao, Ph.D., Charlotte Sumner, Ph.D., S. Amer Riazuddin, Ph.D., Zack Wang, Ph.D., Byoung Chol Oh, Ph.D., Sashank Reddy, Ph.D., Vasilki Machairak, Ph.D. and Annie Kathuria, Ph.D. from Johns Hopkins University; and Raphael Meier, Ph.D., Ivy Dick, Ph.D., Xiaofeng Jia, Ph.D., Yajie Liang, Ph.D., Miroslaw Janowski, Ph.D., Graeme Woodworth, Ph.D., Chengyan Chu, Ph.D. and Iris Lindberg, Ph.D. from the University of Maryland, Baltimore. Post-Doctoral Fellowship : These awards support exceptional post-doctoral fellows conducting research in Maryland. Totaling $1,300,000, award recipients include Neelima Thottappillil, Ph.D., Cristina Zivko, Ph.D., Mohit Kwatra, Ph.D., Feiyu Yang, Ph.D., Heng Zhao, Ph.D. and Ridzky Yuda, Ph.D. from Johns Hopkins University; Jinghui Wang, Ph.D. and Shalini Sharma, Ph.D. from the University of Maryland, Baltimore; and Niannian Xu, Ph.D. and Wenshen Wang, Ph.D. from the Hugo W. Moser Research Institute at Kennedy Krieger. Manufacturing Assistance : These awards provide companies with funding to support the manufacturing processes/infrastructure of stem cell therapy products in Maryland. Totaling $344,402, the Manufacturing Assistance Award recipient is Evelyn Chukwurah from Reprocell, U.S.A., Inc. Governor Wes Moore and the Maryland General Assembly have earmarked $20.5 million for fiscal year 2025 to support the MSCRF, reaffirming the state's enduring dedication to promoting innovative research in stem cell and regenerative medicine within Maryland. "This sustained financial backing is essential for propelling capital and time-intensive stem cell technologies from bench to bedside," said Nijhara. The Commission is gearing up to release Requests for Applications (RFAs) for its first round of FY25 funding and anticipates an acceleration of pioneering research and innovative cures through the various programs of MSCRF. More information about all current MSCRF awardees is available at . About the Maryland Stem Cell Research Commission The Maryland Stem Cell Research Commission is focused on identifying and funding cutting-edge research and innovation in the field of regenerative medicine in Maryland. Our Accelerating Cures initiative comprises programs that help transition human stem cell-based technologies from the bench to the bedside as well as mechanisms to build and grow stem cell companies in Maryland. Visit us at to learn more about our funding opportunities. About TEDCO TEDCO, the Maryland Technology Development Corporation, enhances economic empowerment growth through the fostering of an inclusive entrepreneurial innovation ecosystem. TEDCO identifies, invests in, and helps grow technology and life science-based companies in Maryland. Learn more at . MSCRF Contact Ruchika Nijhara, Executive Director, MSCRF, [email protected] Media Contact Tammi Thomas, Chief Development & Marketing Officer, TEDCO, [email protected] SOURCE Maryland Stem Cell Research Commission