Publications by authors named "Erin Smith"

237 Publications

Gene therapy for aromatic L-amino acid decarboxylase deficiency by MR-guided direct delivery of AAV2-AADC to midbrain dopaminergic neurons.

Nat Commun 2021 07 12;12(1):4251. Epub 2021 Jul 12.

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder characterized by deficient synthesis of dopamine and serotonin. It presents in early infancy, and causes severe developmental disability and lifelong motor, behavioral, and autonomic symptoms including oculogyric crises (OGC), sleep disorder, and mood disturbance. We investigated the safety and efficacy of delivery of a viral vector expressing AADC (AAV2-hAADC) to the midbrain in children with AADC deficiency (ClinicalTrials.gov Identifier NCT02852213). Seven (7) children, aged 4-9 years underwent convection-enhanced delivery (CED) of AAV2-hAADC to the bilateral substantia nigra (SN) and ventral tegmental area (VTA) (total infusion volume: 80 µL per hemisphere) in 2 dose cohorts: 1.3 × 10 vg (n = 3), and 4.2 × 10 vg (n = 4). Primary aims were to demonstrate the safety of the procedure and document biomarker evidence of restoration of brain AADC activity. Secondary aims were to assess clinical improvement in symptoms and motor function. Direct bilateral infusion of AAV2-hAADC was safe, well-tolerated and achieved target coverage of 98% and 70% of the SN and VTA, respectively. Dopamine metabolism was increased in all subjects and FDOPA uptake was enhanced within the midbrain and the striatum. OGC resolved completely in 6 of 7 subjects by Month 3 post-surgery. Twelve (12) months after surgery, 6/7 subjects gained normal head control and 4/7 could sit independently. At 18 months, 2 subjects could walk with 2-hand support. Both the primary and secondary endpoints of the study were met. Midbrain gene delivery in children with AADC deficiency is feasible and safe, and leads to clinical improvements in symptoms and motor function.
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http://dx.doi.org/10.1038/s41467-021-24524-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275582PMC
July 2021

Advancing human genetics research and drug discovery through exome sequencing of the UK Biobank.

Nat Genet 2021 Jul 28;53(7):942-948. Epub 2021 Jun 28.

Alnylam Pharmaceuticals, Cambridge, MA, USA.

The UK Biobank Exome Sequencing Consortium (UKB-ESC) is a private-public partnership between the UK Biobank (UKB) and eight biopharmaceutical companies that will complete the sequencing of exomes for all ~500,000 UKB participants. Here, we describe the early results from ~200,000 UKB participants and the features of this project that enabled its success. The biopharmaceutical industry has increasingly used human genetics to improve success in drug discovery. Recognizing the need for large-scale human genetics data, as well as the unique value of the data access and contribution terms of the UKB, the UKB-ESC was formed. As a result, exome data from 200,643 UKB enrollees are now available. These data include ~10 million exonic variants-a rich resource of rare coding variation that is particularly valuable for drug discovery. The UKB-ESC precompetitive collaboration has further strengthened academic and industry ties and has provided teams with an opportunity to interact with and learn from the wider research community.
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http://dx.doi.org/10.1038/s41588-021-00885-0DOI Listing
July 2021

Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals.

Am J Hum Genet 2021 07 3;108(7):1350-1355. Epub 2021 Jun 3.

Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB2 0AA, UK.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.
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http://dx.doi.org/10.1016/j.ajhg.2021.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173480PMC
July 2021

Parkinson's Symptoms and Caregiver Affiliate Stigma: A Multinational Study.

Curr Alzheimer Res 2021 Jun 7. Epub 2021 Jun 7.

Hospital Civil Fray Antonio Alcalde, University of Guadalajara, Americana, 44160 Guadalajara, Jal., Mexico.

Background And Objective: Research has documented the stigma that individuals with degenerative neurological diseases experience, but caregivers also experience stigma by associa- tion (i.e., affiliate stigma). In order to shed light on the stigma of caregivers of people with degener- ative neurological diseases, the current study aimed to explore cross-cultural differences in the pre- valence of Parkinson's disease (PD) caregiver affiliate stigma, as well as the relationship between PD symptoms and caregiver affiliate stigma. Applications for Alzheimer's disease are discussed.

Method: Survey data were collected in PD clinics at public, academic medical centers. Informal caregivers of an individual with PD from the US (n = 105) and from Mexico (n = 148) participated in the study. Caregivers completed a questionnaire that included the MDS Unified PD Rating Scale to describe the symptoms of the individual with PD, as well as the Affiliate Stigma Scale and demo- graphic information.

Results: A series of multiple regressions was run to examine whether PD symptoms were associat- ed with affiliate stigma and if these differed by country. These regressions suggested that different patterns of PD symptoms predicted affiliate stigma in each country. Stigma was higher in the US compared to Mexico, and the relationship between bowel/bladder symptoms and affiliate stigma was significantly stronger in the US.

Conclusions: Symptoms of individuals with neurodegenerative diseases are related to affiliate stig- ma experienced by caregivers, and these relationships may differ cross-culturally. Negative public attitudes concerning bowl and bladder issues and the physical symptoms that accompany PD re- main a source of stigma for caregivers and families, particularly in the US. Interventions for care- givers of individuals with neurodegenerative diseases should include strategies for coping with stig- ma concerning bladder and bowel problems, as well as other physical and mental health issues.Recent Advances in Anti-Infective Drug Discovery.
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http://dx.doi.org/10.2174/1567205018666210608100917DOI Listing
June 2021

The effect of socially supportive church ministry on children's prosocial behavior: An experimental study of Latin American Protestant Congregations.

J Prev Interv Community 2021 May 19:1-18. Epub 2021 May 19.

Division of Online and Professional Studies, California Baptist University, Riverside, CA, USA.

The church is commonly assumed to scaffold individuals' socially supportive relationships and prosocial behavior. If true, that would make the church an important support for individual development and community change, facilitating and fostering healthy relationships and positive interactions with others. In this study, we analyzed experimental data collected from 30 churches in three Latin American countries to assess the impact of an intervention targeting relational ministry practices on 6- to 14-year-old children's perceived support and prosocial behavior. Data were collected from children before ( = 710) and after ( = 612) the intervention in treatment ( 25 churches) and control ( = 5 churches) conditions. Results indicated that the introduction of socially supportive practices in church children's ministries increased children's prosocial behavior, an effect mediated by changes in perceived support. Implications for children's development and the church as a means of community change are discussed.
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http://dx.doi.org/10.1080/10852352.2021.1924591DOI Listing
May 2021

Building brain capital.

Neuron 2021 05;109(9):1430-1432

Organisation for Economic Co-operation and Development (OECD), Paris, France.

Brains are indispensable drivers of human progress. Why not invest more heavily in them? We seek to place Brain Capital at the center of a new narrative to fuel economic and societal recovery and resilience.
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http://dx.doi.org/10.1016/j.neuron.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240507PMC
May 2021

Systematic review on effects of bioenergy from edible versus inedible feedstocks on food security.

NPJ Sci Food 2021 May 4;5(1). Epub 2021 May 4.

Department of Biological Systems Engineering, University of Wisconsin-Madison, Madison, WI, USA.

Achieving food security is a critical challenge of the Anthropocene that may conflict with environmental and societal goals such as increased energy access. The "fuel versus food" debate coupled with climate mitigation efforts has given rise to next-generation biofuels. Findings of this systematic review indicate just over half of the studies (56% of 224 publications) reported a negative impact of bioenergy production on food security. However, no relationship was found between bioenergy feedstocks that are edible versus inedible and food security (P value = 0.15). A strong relationship was found between bioenergy and type of food security parameter (P value < 0.001), sociodemographic index of study location (P value = 0.001), spatial scale (P value < 0.001), and temporal scale (P value = 0.017). Programs and policies focused on bioenergy and climate mitigation should monitor multiple food security parameters at various scales over the long term toward achieving diverse sustainability goals.
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http://dx.doi.org/10.1038/s41538-021-00091-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096942PMC
May 2021

Supporting the Mental Health and Well-Being of First Responders from Career to Retirement: A Scoping Review.

Prehosp Disaster Med 2021 Aug 30;36(4):475-480. Epub 2021 Apr 30.

Edith Cowan University, School of Medical and Health Sciences, JoondalupWestern Australia, Australia.

Introduction: First responders are at greater risk of mental ill health and compromised well-being compared to the general population. It is important to identify strategies that will be effective in supporting mental health, both during and after the first responder's career.

Methods: A scoping review was conducted using the PubMed database (1966 to October 1, 2020) and the Google Scholar database (October 1, 2020) using relevant search terms, truncation symbols, and Boolean combination functions. The reference lists of all relevant publications were also reviewed to identify further publications.

Results: A total of 172 publications were retrieved by the combined search strategies. Of these, 56 met the inclusion criteria and informed the results of this overview paper. These publications identified that strategies supporting first responder mental health and well-being need to break down stigma and build resilience. Normalizing conversations around mental health is integral for increasing help-seeking behaviors, both during a first responder's career and in retirement. Organizations should consider the implementation of both pre-retirement and post-retirement support strategies to improve mental health and well-being.

Conclusion: Strategies for supporting mental health and well-being need to be implemented early in the first responder career and reinforced throughout and into retirement. They should utilize holistic approaches which encourage "reaching in" rather than placing an onus on first responders to "reach out" when they are in crisis.
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http://dx.doi.org/10.1017/S1049023X21000431DOI Listing
August 2021

A C. elegans genome-wide RNAi screen for altered levamisole sensitivity identifies genes required for muscle function.

G3 (Bethesda) 2021 04;11(4)

Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

At the neuromuscular junction (NMJ), postsynaptic ionotropic acetylcholine receptors (AChRs) transduce a chemical signal released from a cholinergic motor neuron into an electrical signal to induce muscle contraction. To identify regulators of postsynaptic function, we conducted a genome-wide RNAi screen for genes required for proper response to levamisole, a pharmacological agonist of ionotropic L-AChRs at the Caenorhabditis elegans NMJ. A total of 117 gene knockdowns were found to cause levamisole hypersensitivity, while 18 resulted in levamisole resistance. Our screen identified conserved genes important for muscle function including some that are mutated in congenital myasthenic syndrome, congenital muscular dystrophy, congenital myopathy, myotonic dystrophy, and mitochondrial myopathy. Of the genes found in the screen, we further investigated those predicted to play a role in endocytosis of cell surface receptors. Loss of the Epsin homolog epn-1 caused levamisole hypersensitivity and had opposing effects on the levels of postsynaptic L-AChRs and GABAA receptors, resulting in increased and decreased abundance, respectively. We also examined other genes that resulted in a levamisole-hypersensitive phenotype when knocked down including gas-1, which functions in Complex I of the mitochondrial electron transport chain. Consistent with altered ATP synthesis impacting levamisole response, treatment of wild-type animals with levamisole resulted in L-AChR-dependent depletion of ATP levels. These results suggest that the paralytic effects of levamisole ultimately lead to metabolic exhaustion.
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http://dx.doi.org/10.1093/g3journal/jkab047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049432PMC
April 2021

Identification of rare and common regulatory variants in pluripotent cells using population-scale transcriptomics.

Nat Genet 2021 03 4;53(3):313-321. Epub 2021 Mar 4.

European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK.

Induced pluripotent stem cells (iPSCs) are an established cellular system to study the impact of genetic variants in derived cell types and developmental contexts. However, in their pluripotent state, the disease impact of genetic variants is less well known. Here, we integrate data from 1,367 human iPSC lines to comprehensively map common and rare regulatory variants in human pluripotent cells. Using this population-scale resource, we report hundreds of new colocalization events for human traits specific to iPSCs, and find increased power to identify rare regulatory variants compared with somatic tissues. Finally, we demonstrate how iPSCs enable the identification of causal genes for rare diseases.
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http://dx.doi.org/10.1038/s41588-021-00800-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944648PMC
March 2021

Brain Health Living Labs.

Am J Geriatr Psychiatry 2021 Jul 1;29(7):698-703. Epub 2020 Dec 1.

Global Brain Health Institute, University of California (WD, HAE), San Francisco (UCSF), CA; Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation (MB, HAE), School of Medicine, Barwon Health, Geelong, Australia; Department of Psychiatry (MB, HAE), University of Melbourne, Melbourne, Victoria, Australia; Discipline of Psychiatry, School of Medicine (HAE), The University of Adelaide, Adelaide, South Australia, Australia; Brainstorm Lab for Mental Health Innovation (HAE), Stanford University, Palo Alto, CA. Electronic address:

We call on geriatric brain health care providers, executives and entrepreneurs to embrace our Brain Health Living Lab model-a user-centered, iterative ecosystem, integrating concurrent clinical care, research and innovation processes.
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http://dx.doi.org/10.1016/j.jagp.2020.11.010DOI Listing
July 2021

Friend Support and the Parenting of Latina Adolescent Mothers: The Moderating Role of Maternal Age.

J Child Fam Stud 2020 May 8;29(5):1444-1457. Epub 2019 Nov 8.

Susquehanna University, Selinsgrove, PA.

Objectives: This study examined the role of maternal age in the relation between social support from friends and parenting adjustment in a sample of young Latina mothers and their 18-month-old children (=168).

Methods: Hierarchical multiple regression analyses tested friend social support types (emotional, socializing, child care) as differential predictors of maternal behavior (sensitivity, cognitive growth-fostering, detachment) displayed during mother-child play interactions. To consider maternal development, the moderating role of maternal age on these associations was tested.

Results: The relations between friend emotional and child care support and parenting were moderated by maternal age. Emotional support was related to the use of more growth-fostering parenting behaviors for older (≥ 19.5 yrs.), but not for younger Latina mothers. Child care support from friends was related to the display of more detachment and less cognitive growth-fostering behaviors among the younger (≤ 18.7 yrs.) mothers only. Immigrant mothers reported significantly less overall friend support and emotional support than mothers born in the mainland U.S.

Conclusions: The findings emphasize the importance of assessing the types of friend support as separate measures in an ecological context that takes into account mothers' generational and developmental level.
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http://dx.doi.org/10.1007/s10826-019-01647-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732155PMC
May 2020

Backpack health reduces data-sharing barriers between the medical community and individuals with rare diseases.

Am J Med Genet C Semin Med Genet 2021 03 5;187(1):7-13. Epub 2020 Dec 5.

Backpack Health, Boston, Massachusetts, USA.

Technology has changed the way we approach medical care: health data is constantly being generated, medical discoveries are progressing more rapidly, and individuals are more connected across the world than ever before. Backpack Health is a global personal health record platform that harnesses the power of technology to connect users to their primary health data sources, the medical community, and researchers. By syncing with existing patient portals, health data can be stored on the Backpack Health platform and easily accessed and controlled by users in one connected interface. Individuals manage and collate their current and past conditions, genetic test results, symptoms, medications, procedures, labs, and other health data. Users are empowered to disseminate their information to clinicians, researchers, foundations, and pharmaceutical and biotechnology companies they connect with through the Backpack Health application. Here, we describe how two rare disease advocacy groups, The Marfan Foundation and Project Alive, utilize Backpack Health to connect with their target populations. Through secure transfer of pseudonymized data, groups can query their members to improve understanding of clinical features and to facilitate meaningful research. Responses to the groups' surveys show strong member engagement with high completion rates and increases in new Backpack Health users when surveys are deployed. Data from these surveys have been published and used to better inform clinical outcomes for treatment trials. By connecting users directly to the foundations, clinicians, researchers, and industry partners working on their condition, Backpack Health is instrumental in fast-tracking medical discoveries and treatment for rare diseases.
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http://dx.doi.org/10.1002/ajmg.c.31868DOI Listing
March 2021

Assessing the challenges to women's access and implementation of text messages for nutrition behaviour change in rural Tanzania.

Public Health Nutr 2021 Apr 29;24(6):1478-1491. Epub 2020 Oct 29.

Global Alliance for Improved Nutrition, Geneva, Switzerland.

Objective: This process evaluation aimed to understand factors affecting the implementation of a government-sponsored short message service (SMS) programme for delivering nutrition information to rural populations, including message access, acceptability and putting messages into action.

Design: The study was nested within a larger randomised controlled trial. Cross-sectional data collection included structured surveys and in-depth interviews. Data were analysed for key trends and themes using Stata and ATLAS.ti software.

Setting: The study took place in Tanzania's Mtwara region.

Participants: Surveys were conducted with 205 women and 93 men already enrolled in the randomised controlled trial. A sub-set of 30 women and 14 men participated in the in-depth interviews.

Results: Among women relying on a spouse's phone, sharing arrangements impeded regular SMS access; men were commonly away from home, forgot to share SMS or did not share them in women's preferred way. Phone-owning women faced challenges related to charging their phones and defective handsets. Once SMS were delivered, most participants viewed them as trustworthy and comprehensible. However, economic conditions limited the feasibility of applying certain recommendations, such as feeding meat to toddlers. A sub-set of participants concurrently enrolled in an interpersonal counselling (IPC) intervention indicated that the SMS provided reminders of lessons learned during the IPC; yet, the SMS did not help participants contextualise information and overcome the challenges of putting that information into practice.

Conclusions: The challenges to accessing and implementing SMS services highlighted here suggest that such platforms may work well as one component of a comprehensive nutrition intervention, yet not as an isolated effort.
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http://dx.doi.org/10.1017/S1368980020003742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025099PMC
April 2021

Facial nerve management in patients with malignant skull base tumors.

J Neurooncol 2020 Dec 28;150(3):493-500. Epub 2020 Oct 28.

Facial Paralysis Institute, Center for Advanced Facial Plastic Surgery, Beverly Hills, CA, USA.

Introduction: The course of the facial nerve through the cerebellopontine angle, temporal bone, and parotid gland puts the nerve at risk in cases of malignancy. In contrast to Bell's palsy, which presents with acute facial paralysis, malignancies cause gradual or fluctuating weakness.

Methods: We review malignancies affecting the facial nerve, including those involving the temporal bone, parotid gland, and cerebellopontine angle, in addition to metastatic disease. Intraoperative management of the facial nerve and long term management of facial palsy are reviewed.

Results: Intraoperative management of the facial nerve in cases of skull base malignancy may involve extensive exposure, mobilization, or rerouting of the nerve. In cases of nerve sacrifice, primary neurorrhaphy or interposition grafting may be used. Cranial nerve substitution, gracilis free functional muscle transfer, and orthodromic temporalis tendon transfer are management options for long term facial paralysis.

Conclusion: Temporal bone, parotid gland, and cerebellopontine angle malignancies pose a tremendous risk to the facial nerve. When possible, the facial nerve is preserved. If the facial nerve is sacrificed, static and dynamic reanimation strategies are used to enhance facial function.
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http://dx.doi.org/10.1007/s11060-020-03635-0DOI Listing
December 2020

Obesity in children and adolescents: An overview.

Nursing 2020 Nov;50(11):60-66

At Kingsborough Community College in Brooklyn, N.Y., Sarah A. Browne-Bradwisch is a Jonas Veterans Scholar; Catherine Mooney is an assistant professor; Debra Scaccia is an assistant professor; and Erin Murphy Smith is an associate professor and deputy chairperson, as well as the assistant director of nursing at Richmond University Medical Center in Staten Island, N.Y.

Childhood obesity is an epidemic in the US. This article discusses the evolution, prevention, and associated physical and psychosocial consequences of and interventions for obesity in the pediatric population.
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http://dx.doi.org/10.1097/01.NURSE.0000718908.20119.01DOI Listing
November 2020

Toileting Abilities Survey as a surrogate outcome measure for cognitive function: Findings from neuronopathic mucopolysaccharidosis II patients treated with idursulfase and intrathecal idursulfase.

Mol Genet Metab Rep 2020 Dec 21;25:100669. Epub 2020 Oct 21.

Doulots, LLC, Minneapolis, MN, USA.

An outcome measure of toileting skills, the Toileting Abilities Survey or TAS, with sensitivity to detect change in a neurodegenerative disorder such as MPS II, was developed. The TAS was used in a research study of patients ( = 86) with the neuronopathic form of MPS II to measure treatment benefit of intrathecal idursulfase. Treatment with idursulfase and intrathecal idursulfase is associated with significantly higher individual and overall toileting skills versus treatment with idursulfase alone.
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http://dx.doi.org/10.1016/j.ymgmr.2020.100669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578548PMC
December 2020

Detecting subtle mobility changes among older adults: the Quantitative Timed Up and Go test.

Aging Clin Exp Res 2021 Aug 23;33(8):2157-2164. Epub 2020 Oct 23.

School of Public Health, Physiotherapy and Sports Science, University College Dublin, Health Sciences, Belfield, Dublin 4, Ireland.

Background: The Quantitative Timed Up and Go (QTUG) test uses wearable sensors, containing a triaxial accelerometer and an add-on triaxial gyroscope, to quantify performance during the TUG test with potential to capture more minor changes in mobility.

Aims: To examine the responsiveness, minimum detectable change (MDC) and observed effect size of QTUG in a cohort of socially active adults aged 50 years and over participating in a structured community exercise program.

Methods: 54 participants (91% females, mean age 63.6 ± 6.5 years) completed repeated QTUG testing under single- and dual-task conditions. Responsiveness of the QTUG was assessed by correlation of change in standard TUG with QTUG change (Pearson's correlation coefficient). MDC and effect sizes (standardized mean difference and Cohen's d) were also calculated for QTUG.

Results: There was a strong positive correlation between change in the standard TUG and change in QTUG (single task r = 0.91, p < 0.001). MDC in QTUG was calculated as 0.77 (Sd, 1.39; ICC 0.96) seconds (single task) and 2.33 (Sd 2.18; ICC 0.85) seconds (dual task). Several QTUG parameters showed improvements in mean values with small effect sizes (sit -to-stand transition time d = 0.418; walk time d = 0.398; cadence d = 0.306, swing time d = 0.314; step time d = 0.479; gait velocity d = 0.365; time to reach turn d = 0.322) under single-task conditions and with a moderate effect size (d = 0.549) in time taken to turn under the dual-task condition.

Conclusion: Initial evidence of QTUG's responsiveness to change in mobility in active middle to older age adults has been demonstrated with small to moderate effect sizes observed in specific QTUG parameters.
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http://dx.doi.org/10.1007/s40520-020-01733-7DOI Listing
August 2021

Real-Time Effort Driven Ventilator Management: A Pilot Study.

Pediatr Crit Care Med 2020 11;21(11):933-940

Department of Anesthesiology and Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA.

Objectives: Mechanical ventilation of patients with acute respiratory distress syndrome should balance lung and diaphragm protective principles, which may be difficult to achieve in routine clinical practice. Through a Phase I clinical trial, we sought to determine whether a computerized decision support-based protocol (real-time effort-driven ventilator management) is feasible to implement, results in improved acceptance for lung and diaphragm protective ventilation, and improves clinical outcomes over historical controls.

Design: Interventional nonblinded pilot study.

Setting: PICU.

Patients: Mechanically ventilated children with acute respiratory distress syndrome.

Interventions: A computerized decision support tool was tested which prioritized lung-protective management of peak inspiratory pressure-positive end-expiratory pressure, positive end-expiratory pressure/FIO2, and ventilatory rate. Esophageal manometry was used to maintain patient effort in a physiologic range. Protocol acceptance was reported, and enrolled patients were matched 4:1 with respect to age, initial oxygenation index, and percentage of immune compromise to historical control patients for outcome analysis.

Measurements And Main Results: Thirty-two patients were included. Acceptance of protocol recommendations was over 75%. One-hundred twenty-eight matched historical controls were used for analysis. Compared with historical controls, patients treated with real-time effort-driven ventilator management received lower peak inspiratory pressure-positive end-expiratory pressure and tidal volume, and higher positive end-expiratory pressure when FIO2 was greater than 0.60. Real-time effort-driven ventilator management was associated with 6 more ventilator-free days, shorter duration until the first spontaneous breathing trial and 3 fewer days on mechanical ventilation among survivors (all p ≤ 0.05) in comparison with historical controls, while maintaining no difference in the rate of reintubation.

Conclusions: A computerized decision support-based protocol prioritizing lung-protective ventilation balanced with reduction of controlled ventilation to maintain physiologic levels of patient effort can be implemented and may be associated with shorter duration of ventilation.
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http://dx.doi.org/10.1097/PCC.0000000000002556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609612PMC
November 2020

Promoting Tech Transfer Between Space and Global Mental Health.

Aerosp Med Hum Perform 2020 Sep;91(9):737-745

Numerous issues in mental health benefit from technological innovation. An example involves the mental health challenges of long-duration spaceflight (such as a Mars mission), including prolonged confinement, microgravity, and different sunlight exposure lengths. Persisting on Earth are global mental health challenges stemming from disease burdens, limited interview-based diagnostic systems, trial-and-error treatment approaches, and suboptimal access. There is potential for cross-pollinating solutions between these seemingly disparate challenges using a range of emerging technologies such as sensors, omics, and big data. In this review, we highlight the bidirectional value of mental health technology transfer aimed to address issues both on Earth and in space. We prepared a systematic review of studies pertaining to mental health technological innovation and space medicine. For Earth mental health technologies translatable to long-duration space missions, we cite several example technologies, including device-based psychotherapy and social support, conversational agents aka chatbots, and nutritional and physical activity focused mental health. Space technologies translatable to Earth mental health include remote sensing devices, global navigation satellite systems, satellite communications, chronotherapies, and nutritional advances. There is a rich history of space technologies informing Earth technological trends, including general health care on Earth, and vice versa. To avoid the traditional happenstance approach that results in delays, missed opportunities, and increased cost, and to improve outcomes for both Earth and space utilization of these technologies, we propose increased dialogue and training opportunities to enhance innovation and outcomes.
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http://dx.doi.org/10.3357/AMHP.5589.2020DOI Listing
September 2020

Fructose Consumption During Pregnancy Influences Milk Lipid Composition and Offspring Lipid Profiles in Guinea Pigs.

Front Endocrinol (Lausanne) 2020 11;11:550. Epub 2020 Aug 11.

Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand.

Excess dietary fructose is a major public health concern (1-4). Evidence shows increased fructose intake can cause insulin resistance, hepatic lipogenesis, hypertriglyceridemia, obesity and non-alcoholic fatty liver disease (NAFLD) (5-9). However, little is known about the effects of fructose during pregnancy and its influence on offspring development and predisposition to later-life disease. To determine whether moderately increased maternal fructose intake could have health consequences on offspring, we have investigated the effects of 10% w/v fructose water intake during preconception and pregnancy. Female Dunkin Hartley guinea pigs were fed a control diet (CD) or fructose diet (FD;10% kcal from fructose) 60 days prior to mating and throughout gestation. Offspring were culled at weaning, day 21 (d21). Compared to CD dams, FD dams had altered glucose metabolism and increased milk free fatty acid content. Matsuda-DeFronzo insulin sensitivity index (M-ISI) from OGTT plasma showed no significant difference in whole-body insulin sensitivity between FD and CD dams 60 days post-dietary intervention and during midgestation. Fetal exposure to increased maternal fructose resulted in offspring with significantly altered serum free fatty acids at days 0, 7, 14, and 21 [including pentadecanoic acid (15:0), dma16:0, margaric acid (17:0) palmitoleic acid, total omega-7 and total saturates], increased levels of uric acid and triglycerides were also observed at d21. We have demonstrated that increased fructose intake during pregnancy can cause significant changes in maternal metabolic function and milk composition, which alters offspring metabolism. Taken together, these changes in pregnancy outcomes and feto-maternal condition may underlie their offspring's predisposition to metabolic dysfunction during later-life.
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http://dx.doi.org/10.3389/fendo.2020.00550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431635PMC
June 2021

Next Steps to Grow the Bioeconomy.

Health Secur 2020 Jul/Aug;18(4):297-302

Erin Smith, JD, MPH, is Senior Vice President of Government Affairs and Policy; and James Diggans, PhD, is Head of Biosecurity; both at Twist Bioscience, South San Francisco, CA.

The bioeconomy in the United States represents a significant proportion of total economic output and is poised to grow even more rapidly over the next decade. Global competition is increasing, and the United States must work to ensure we maintain global leadership in this field. In this commentary, we outline policy recommendations in 6 topic areas. Taken together, these recommendations call on government, academia, and private industry to collaborate, both domestically and internationally, to grow and secure the current and future bioeconomy in the United States.
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http://dx.doi.org/10.1089/hs.2020.0012DOI Listing
May 2021

Living the core nursing values.

Nursing 2020 08;50(8):40-42

Erin Murphy Smith is an assistant professor of nursing and the deputy chair of the nursing department at Kingsborough Community College of the City University of New York in Staten Island, N.Y.

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http://dx.doi.org/10.1097/01.NURSE.0000659392.87604.2bDOI Listing
August 2020

Utilization of mental health services in pediatric patients surviving penetrating trauma resulting from interpersonal violence.

Am J Surg 2021 01 8;221(1):233-239. Epub 2020 Jul 8.

Boston University School of Medicine, 72 E Concord St, Boston, MA, 02118, USA. Electronic address:

Background: Violent trauma has lasting psychological impacts. Our institution's Community Violence Response Team (CVRT) offers mental health services to trauma victims. We characterized implementation and determined factors associated with utilization by pediatric survivors of interpersonal violence-related penetrating trauma.

Methods: Analysis included survivors (0-21 years) of violent penetrating injury at our institution (2011-2017). Injury and demographic data were collected. Nonparametric regression models determined factors associated with utilization.

Results: There was initial rapid uptake of CVRT (2011-2013) after which it plateaued, serving >80% of eligible patients (2017). White race and higher injury severity were associated with receipt and duration of services. In post-hoc analysis, race was found to be associated with continued treatment but not with initial consultation.

Conclusion: Successful implementation required three years, aiding >80% of patients. CVRT is a blueprint to strengthen existing violence intervention programs. Efforts should be made to ensure that barriers to providing care, including those related to race, are overcome.
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http://dx.doi.org/10.1016/j.amjsurg.2020.06.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736092PMC
January 2021

Cross-cultural differences in Parkinson's disease caregiving and burden between the United States and Mexico.

Brain Behav 2020 09 18;10(9):e01753. Epub 2020 Jul 18.

Master of Neuropsychology, Neurosciences Department, University of Guadalajara, Guadalajara, Mexico.

Introduction: Given the rapidly aging population in both the United States and Mexico, rates of Parkinson's disease (PD) are likely to rise in both countries, suggesting that the number of individuals providing informal care will also increase, and the healthcare system will have to consider the burden this places upon caregivers. Therefore, the purpose of the current study was to examine differences in PD caregiving and burden between the United States and Mexico.

Methods: Data were collected from PD caregivers in the Parkinson's Clinic at the Hospital Civil Fray Antonio Alcalde in Guadalajara, Mexico (N = 148) and the Parkinson's and Movement Disorders Center at Virginia Commonwealth University in Richmond, Virginia (N = 105) regarding caregiver demographics and self-reported burden.

Results: Despite considerably more time spent in caregiving duties, higher rates in unemployment or underemployment, and lower education levels, Mexican PD caregivers reported significantly less personal strain and role strain than did their United States counterparts. Even after controlling for these and other demographic differences between the two sites, the differences in caregiver burden remained.

Conclusions: Latino cultural values in Mexico encouraging the importance of caring for family members with PD and respecting elders may promote caregiving and even make it a point of cultural pride, helping to overcome potential negative effects on caregivers seen in the United States. The scientific and medical communities should view caregiving as a culturally embedded and potentially positive role, rather than predominantly as burdensome as frequently conceptualized in Western or Eurocentric cultures.
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http://dx.doi.org/10.1002/brb3.1753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507106PMC
September 2020

Predictors of Alcohol Use in Safety-Net Primary Care: Classism, Religiosity, and Race.

J Addict 2020 16;2020:5916318. Epub 2020 Jun 16.

Virginia Commonwealth University, Richmond, VA, USA.

Class-based discrimination may impact problematic drinking in low-income populations, which may be buffered by personal religiosity. However, little is known how race may impact this association. The purpose of this study was to examine racial differences in the effect of class-based discrimination on problematic drinking as moderated by comfort with God and determine if there were conditional direct effects of class-based discrimination on problematic drinking by race. In this cross-sectional study, participants ( = 189) were patients of an urban, safety-net primary care clinic who completed questionnaires assessing experiences of class-based discrimination, attitudes toward God, and alcohol use. Data were collected from 2015 to 2016 and analyzed using the Hayes PROCESS macro. There was a significant main effect for class-based discrimination predicting problematic drinking. Two-way interaction analyses identified a significant comfort with God by race interaction with greater comfort with God associated with less problematic drinking among white but not black respondents. Conditional direct effects showed that experiences of class-based discrimination were associated with problematic drinking at low and moderate but not high levels of comfort with God in black participants, whereas none were observed for white participants. This study provides insight on how personal religiosity, class-based discrimination, and race may intertwine to shape problematic alcohol use in primarily low-income, urban patients. Clinicians' awareness of risk and protective factors, as well as how race tempers the effects of such factors, is vital in providing better care for this population.
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http://dx.doi.org/10.1155/2020/5916318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317315PMC
June 2020

Do Paramedics Have a Professional Obligation to Work During a Pandemic? A Qualitative Exploration of Community Member Expectations.

Disaster Med Public Health Prep 2020 Jun 24;14(3):406-412. Epub 2020 Jun 24.

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.

Objectives: Previous research has identified a lack of clarification regarding paramedic professional obligation to work. Understanding community expectations of paramedics will provide some clarity around this issue. The objective of this research was to explore the expectations of a sample of Australian community members regarding the professional obligation of paramedics to respond during pandemics.

Methods: The authors used qualitative methods to gather Australian community member perspectives immediately before the onset of the coronavirus disease 2019 (COVID-19) pandemic. Focus groups were used for data collection, and a thematic analysis was conducted.

Results: The findings revealed 9 key themes: context of obligation (normal operations versus crisis situation), hierarchy of obligation (individual versus organizational obligation), risk acceptability, acceptable occupational risk (it's part of the job), access to personal protective equipment, legal and ethical guidelines, education and training, safety, and acceptable limitations to obligation. The factors identified as being acceptable limitations to professional obligation are presented as further sub-themes: physical health, mental health, and competing personal obligations.

Conclusions: The issue of professional obligation must be addressed by ambulance services as a matter of urgency, especially in light of the COVID-19 coronavirus pandemic. Further research is recommended to understand how community member expectations evolve during and after the COVID-19 coronavirus pandemic.
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http://dx.doi.org/10.1017/dmp.2020.212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360940PMC
June 2020

Discovery and quality analysis of a comprehensive set of structural variants and short tandem repeats.

Nat Commun 2020 06 10;11(1):2928. Epub 2020 Jun 10.

Department of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA.

Structural variants (SVs) and short tandem repeats (STRs) are important sources of genetic diversity but are not routinely analyzed in genetic studies because they are difficult to accurately identify and genotype. Because SVs and STRs range in size and type, it is necessary to apply multiple algorithms that incorporate different types of evidence from sequencing data and employ complex filtering strategies to discover a comprehensive set of high-quality and reproducible variants. Here we assemble a set of 719 deep whole genome sequencing (WGS) samples (mean 42×) from 477 distinct individuals which we use to discover and genotype a wide spectrum of SV and STR variants using five algorithms. We use 177 unique pairs of genetic replicates to identify factors that affect variant call reproducibility and develop a systematic filtering strategy to create of one of the most complete and well characterized maps of SVs and STRs to date.
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http://dx.doi.org/10.1038/s41467-020-16481-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287045PMC
June 2020

Properties of structural variants and short tandem repeats associated with gene expression and complex traits.

Nat Commun 2020 06 10;11(1):2927. Epub 2020 Jun 10.

Institute of Genomic Medicine, University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.

Structural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA variants which vastly differ in their sizes and distributions across the genome. Here, we identify genomic features of SV classes and STRs that are associated with gene expression and complex traits, including their locations relative to eGenes, likelihood of being associated with multiple eGenes, associated eGene types (e.g., coding, noncoding, level of evolutionary constraint), effect sizes, linkage disequilibrium with tagging single nucleotide variants used in GWAS, and likelihood of being associated with GWAS traits. We identify a set of high-impact SVs/STRs associated with the expression of three or more eGenes via chromatin loops and show that they are highly enriched for being associated with GWAS traits. Our study provides insights into the genomic properties of structural variant classes and short tandem repeats that are associated with gene expression and human traits.
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http://dx.doi.org/10.1038/s41467-020-16482-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286898PMC
June 2020
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