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Heightened reliance on the cerebral cortex for postural stability with aging is well-known, yet the cortical mechanisms for balance control, particularly in relation to balance function, remain unclear. Here we aimed to investigate motor cortical activity in relation to the level of balance challenge presented during reactive balance recovery and identify circuit-specific interactions between motor cortex and prefrontal or somatosensory regions in relation to metrics of balance function that predict fall risk. Using electroencephalography, we assessed motor cortical beta power, and beta coherence during balance reactions to perturbations in older adults. We found that individuals with greater motor cortical beta power evoked following standing balance perturbations demonstrated lower general clinical balance function. Individual older adults demonstrated a wide range of cortical responses during balance reactions at the same perturbation magnitude, showing no group-level change in prefrontal- or somatosensory-motor coherence in response to perturbations. However, older adults with the highest prefrontal-motor coherence during the post-perturbation, but not pre-perturbation, period showed greater cognitive dual-task interference (DTI) and elicited stepping reactions at lower perturbation magnitudes. Our results support motor cortical beta activity as a potential biomarker for individual level of balance challenge and implicate prefrontal-motor cortical networks in distinct aspects of balance control involving response inhibition of reactive stepping in older adults. Cortical network activity during balance may provide a neural target for precision-medicine efforts aimed at fall prevention with aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Palmer, Payne, Ting and Borich.)

Context: Optimal surgical care for older adults with life-threatening conditions, with high risk of poor perioperative outcomes and morality in the months after surgery, should incorporate an understanding of the patient's treatment goals and preferences. However, little research has explored the patient perspective of decision making and advanced care planning during an emergency surgery episode., Objectives: We sought to better understand older patients' lived experience making decisions to undergo emergency general surgery (EGS) and perceptions of perioperative advance care planning (ACP)., Methods: Adults aged 65 and older who underwent one of seven common EGS procedures with lengths of stay more than five days at three Boston-area hospitals were included. Semistructured phone interviews were conducted three months postdischarge. Transcripts were reviewed and coded independently by surgeons and palliative care physicians to identify themes., Results: About 31 patients were interviewed. Patients viewed the decision for surgery as a choice of life over death and valued prolonging life. They felt there was no choice but to proceed with surgery but reported that participation in decision making was limited because of severe symptoms, time constraints, and confused thinking. Despite recently surviving a life-threatening illness, patients had not reconsidered their wishes for the future and preferred to avoid future ACP., Conclusion: Older patients who survived a life-threatening illness and EGS report receiving goal-concordant care in the moment that relieved symptoms and prolonged life but had not considered future care. Interventions to facilitate postoperative ACP should be targeted to this vulnerable group of older adults., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

JNJ-42165279 is a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of fatty acid amides (FAA) including anandamide (AEA), palmitoylethanolamide (PEA), and N-oleoylethanolamide (OEA). We assessed the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of treatment with JNJ-42165279 in subjects with social anxiety disorder (SAD). This was a multicenter, double-blind, placebo-controlled study randomizing subjects to 12 weeks of treatment with either JNJ-42165279 (25 mg daily) or placebo (PBO). The primary endpoint was the change in the Liebowitz Social Anxiety Scale (LSAS) total score from baseline to end of study. Secondary endpoints included the Hamilton Anxiety Scale (HAM-A), Hamilton Depression Rating Scale (HDRS 17 ), and the Clinical Global Impression-Improvement (CGI-I). Samples were collected for plasma concentration of AEA, PEA, OEA, and JNJ-42165279. A total of 149 subjects were enrolled with a mean baseline LSAS total score of 102.6 (SD 16.84). The mean change from baseline (SD) in LSAS total score at week 12 was numerically greater for JNJ-42165279: -29.4 (27.47) compared to PBO: -22.4 (23.57) but not significant. The percentage of subjects with ≥30% improvement from baseline in the LSAS total score was significantly higher for JNJ-42165279 (42.4%) compared to PBO (23.6%) (p value = 0.04). The percentage of subjects with a CGI-I score of much or very much improved was also significantly higher for JNJ-42165279 (44.1%) than for PBO (23.6%) (p value = 0.02). The drug was well tolerated. JNJ-42165279 appears to elicit an anxiolytic effect in subjects with SAD although trough concentrations with 25 mg once daily appeared to be insufficient to completely inhibit FAAH activity which may have led to suboptimal efficacy. ClinicalTrials.gov Identifier: NCT02432703.

Background and Objectives: Nursing homes pose unique challenges for implementation of research and quality improvement (QI). We previously demonstrated successful implementation of a nursing home-led intervention to improve relationships between frontline staff and residents in 6 U.S. Department of Veterans Affairs (VA) Community Living Centers (CLCs). This article discusses early adaptations made to the intervention and its implementation to enhance frontline staff participation., Research Design and Methods: This is a formative evaluation of intervention implementation at the first 2 participating CLCs. Formative evidence-including site visitors' field notes, implementation facilitation records, and semistructured frontline staff interviews-were collected throughout the study period. Data analysis was informed by the Capability, Opportunity, Motivation, and Behavior model of behavior change., Results: Adaptations were made to 5 a priori intervention implementation strategies: (a) training leaders, (b) training frontline staff, (c) adapting the intervention to meet local needs, (d) auditing and providing feedback, and (e) implementation facilitation. On the basis of a 6-month implementation period at the first CLC, we identified elements of the intervention and aspects of the implementation strategies that could be adapted to facilitate frontline staff participation at the second CLC., Discussion and Implications: Incremental implementation, paired with ongoing formative evaluation, proved critical to enhancing capability, opportunity, and motivation among frontline staff. In elucidating what was required to initiate and sustain the nursing home-led intervention, we provide a blueprint for responding to emergent challenges when performing research and QI in the nursing home setting., (Published by Oxford University Press on behalf of The Gerontological Society of America 2020.)

Cortical beta oscillations (13-30 Hz) reflect sensorimotor processing, but are not well understood in balance recovery. We hypothesized that sensorimotor cortical activity would increase under challenging balance conditions. We predicted greater beta power when balance was challenged, either by more difficult perturbations or by lower balance ability. In 19 young adults, we measured beta power over motor cortical areas (electroencephalography, Cz electrode) during three magnitudes of backward support -surface translations. Peak beta power was measured during early (50-150 ms), late (150-250 ms), and overall (0-400 ms) time bins, and wavelet-based analyses quantified the time course of evoked beta power. An ANOVA was used to compare peak beta power across perturbation magnitudes in each time bin. We further tested the association between perturbation-evoked beta power and individual balance ability measured in a challenging beam walking task. Beta power increased ~50 ms after perturbation, and to a greater extent in larger perturbations. Lower individual balance ability was associated with greater beta power in only the late (150-250 ms) time bin. These findings demonstrate greater sensorimotor cortical engagement under more challenging balance conditions, which may provide a biomarker for reduced automaticity in balance control that could be used in populations with neurological impairments.

A series of mechanism-based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with fused bicyclic diamine cores is described. In contrast to compounds built around a piperazine core, most of the fused bicyclic diamine bearing analogs prepared exhibited greater potency against rFAAH than the human enzyme. Several compounds equipotent against both species were identified and profiled in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Coronavirus disease 2019 (COVID-19) pneumonia is associated to systemic hyper-inflammation and abnormal coagulation profile. D-dimer elevation is particularly frequent, and values higher than 1μg/mL have been associated with disease severity and in-hospital mortality. Previous retrospective studies found a high pulmonary embolism (PE) prevalence, however, it should be highlighted that diagnoses were only completed when PE was clinically suspected., Material and Methods: Single-center prospective cohort study. Between April 6th and April 17th 2020, consecutive confirmed cases of COVID-19 pneumonia with D-dimer >1 μg/mL underwent computed tomography pulmonary angiography (CTPA) to investigate the presence and magnitude of PE. Demographic and laboratory data, comorbidities, CTPA scores, administered treatments, and, clinical outcomes were analysed and compared between patients with and without PE., Results: Thirty consecutive patients (11 women) were included. PE was diagnosed in 15 patients (50%). In patients with PE, emboli were located mainly in segmental arteries (86%) and bilaterally (60%). Patients with PE were significantly older (median age 67.0 (IQR 63.0-73.0) vs. 57.0 (IQR 48.0-69.0) years, p = .048) and did not differ in sex or risk factors for thromboembolic disease from the non-PE group. D-dimer, platelet count, and, C reactive protein values were significantly higher among PE patients. D-dimer values correlated with the radiologic magnitude of PE (p<0.001)., Conclusions: Patients with COVID-19 pneumonia and D-dimer values higher than 1 μg/mL presented a high prevalence of PE, regardless of clinical suspicion. We consider that these findings could contribute to improve the prognosis of patients with COVID-19 pneumonia, by initiating anticoagulant therapy when a PE is found., Competing Interests: The authors have declared that no competing interests exist.

Context: Dementia marks an increasingly prevalent terminal illness for which palliative care, including spiritual care, could improve quality of life. Research gaps exist in understanding the intersection of dementia, spirituality, and palliative care., Objectives: We conducted the first scoping review examining the nature and breadth of peer-reviewed studies across these three topics to guide future research., Methods: The scoping review followed methods from The Joanna Briggs Institute Reviewers' Manual (2015). We developed a priori a scoping review protocol outlining the population, concept, and context for study; data sources; search strategy; inclusion/exclusion criteria; and procedure for screening, extracting, and analyzing data., Results: The final sample consisted of 19 studies with the following themes: characterizing spiritual needs, preferences, and resources; characterizing palliative or spiritual care; predicting provision of spiritual care; and assessing spiritual care interventions. Eighteen studies were published in the past decade, and 11 studies were based in Europe. Most studies focused on long-term care settings, grouped stages of dementia or did not specify dementia stage, and investigated interventions indirectly related to spiritual care. Many studies were limited in sample size and generalizability/transferability and used less sophisticated research designs., Conclusion: Research across dementia, spirituality, and palliative care needs to examine settings beyond long-term care, distinct stages of dementia, and formal spiritual care interventions plus use rigorous study designs (e.g., randomized clinical trials). Such research could advance practice and policy that enhance quality of life for tens of millions of persons with dementia and their family members worldwide., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

All people experience aging, and the related physical and health changes, including changes in memory and brain function. These changes may become debilitating leading to an increase in dependence as people get older. Many external aids and tools have been developed to allow older adults and elderly patients to continue to live normal and comfortable lives. This mini-review describes some of the recent studies on cognitive decline and motor control impairment with the goal of advancing non-invasive brain computer interface (BCI) technologies to improve health and wellness of older adults and elderly patients. First, we describe the state of the art in cognitive prosthetics for psychiatric diseases. Then, we describe the state of the art of possible assistive BCI applications for controlling an exoskeleton, a wheelchair and smart home for elderly people with motor control impairments. The basic age-related brain and body changes, the effects of age on cognitive and motor abilities, and several BCI paradigms with typical tasks and outcomes are thoroughly described. We also discuss likely future trends and technologies to assist healthy older adults and elderly patients using innovative BCI applications with minimal technical oversight., (Copyright © 2020 Belkacem, Jamil, Palmer, Ouhbi and Chen.)

Swimming advisories are commonly posted at public beaches across the United States every year. In Iowa, weekly monitoring of public swimming areas at state and county beaches have resulted in the impairment of numerous lakes for fecal indicator bacteria (FIB) contamination, as detected by E. coli. An extensive study was established to assess the relationships between E. coli contamination of nearshore beach water environments, open lake conditions and beach sands in three recreational beach/lake systems currently impaired for FIB contamination across Iowa. A transect/grab sample based sampling design was implemented across the systems with collections spanning from April through October of 2015 and 2016. Collections of E. coli along water transects identified strong near to far shore gradients of decreasing concentrations in all systems. Results indicate that concentrations of E. coli observed in swimming waters consistently disassociate with concentrations in the broader lake environment. Swimming water E. coli concentrations correlated with elevated beach sand E. coli, samples collected from beach sands uncovered concentrations up to 86,500 times higher than adjacent swimming waters. Results from this study indicate that foreshore beach sands and other beach proximate FIB sources serve as the major contributing source for swimming zone advisories. The current methodology used by state and federal officials includes impairing entire lake waterbodies for FIB contamination of the swimming area. These impairment listings do not accurately reflect the condition(s) of the larger lake environment outside the swimming area and fail to account for beach proximate conditions in the assessment process. Further, this approach provides potentially misleading information to the public and may undermine implementation strategies deployed by resource managers aimed at addressing FIB contamination at recreational swimming areas. Views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the Iowa Department of Natural Resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The Stemina devTOX quickPredict platform is a human pluripotent stem cell-based assay that predicts the developmental toxicity potential based on changes in cellular metabolism following chemical exposure [Palmer, J. A., Smith, A. M., Egnash, L. A., Conard, K. R., West, P. R., Burrier, R. E., Donley, E. L. R., and Kirchner, F. R. (2013). Establishment and assessment of a new human embryonic stem cell-based biomarker assay for developmental toxicity screening. Birth Defects Res. B Dev. Reprod. Toxicol. 98, 343-363]. Using this assay, we screened 1065 ToxCast phase I and II chemicals in single-concentration or concentration-response for the targeted biomarker (ratio of ornithine to cystine secreted or consumed from the media). The dataset from the Stemina (STM) assay is annotated in the ToxCast portfolio as STM. Major findings from the analysis of ToxCast&#95;STM dataset include (1) 19% of 1065 chemicals yielded a prediction of developmental toxicity, (2) assay performance reached 79%-82% accuracy with high specificity (> 84%) but modest sensitivity (< 67%) when compared with in vivo animal models of human prenatal developmental toxicity, (3) sensitivity improved as more stringent weights of evidence requirements were applied to the animal studies, and (4) statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain. The results of this study will be useful to improving our ability to predict in vivo developmental toxicants based on in vitro data and in silico models., (Published by Oxford University Press on behalf of the Society of Toxicology 2020. This work is written by US Government employees and is in the public domain in the US.)

Implementing screening assays that identify functional and structural cardiotoxicity earlier in the drug development pipeline has the potential to improve safety and decrease the cost and time required to bring new drugs to market. In this study, a metabolic biomarker-based assay was developed that predicts the cardiotoxicity potential of a drug based on changes in the metabolism and viability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Assay development and testing was conducted in 2 phases: (1) biomarker identification and (2) targeted assay development. In the first phase, metabolomic data from hiPSC-CM spent media following exposure to 66 drugs were used to identify biomarkers that identified both functional and structural cardiotoxicants. Four metabolites that represent different metabolic pathways (arachidonic acid, lactic acid, 2'-deoxycytidine, and thymidine) were identified as indicators of cardiotoxicity. In phase 2, a targeted, exposure-based biomarker assay was developed that measured these metabolites and hiPSC-CM viability across an 8-point concentration curve. Metabolite-specific predictive thresholds for identifying the cardiotoxicity potential of a drug were established and optimized for balanced accuracy or sensitivity. When predictive thresholds were optimized for balanced accuracy, the assay predicted the cardiotoxicity potential of 81 drugs with 86% balanced accuracy, 83% sensitivity, and 90% specificity. Alternatively, optimizing the thresholds for sensitivity yields a balanced accuracy of 85%, 90% sensitivity, and 79% specificity. This new hiPSC-CM-based assay provides a paradigm that can identify structural and functional cardiotoxic drugs that could be used in conjunction with other endpoints to provide a more comprehensive evaluation of a drug's cardiotoxicity potential., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/objectives: This study aims to identify resident characteristics associated with being offered and subsequently shown an advance care planning (ACP) video in the Pragmatic Trial of Video Education in Nursing Homes (PROVEN) and if differences are driven by within- and/or between-facility differences., Design: Cross-sectional study, from March 1, 2016, to May 31, 2018., Setting: A total of 119 PROVEN intervention nursing homes (NHs)., Participants: A total of 43 303 new NH admissions., Measurements: Data came from the Minimum Data Set and an electronic record documenting whether a video was offered and shown to residents. We conduct both naïve logistic regression models and hierarchical logistic models, controlling for NH fixed effects, to examine the overall differences in offer and show rate by resident characteristics., Results: In naïve regression models, compared to white residents, black residents are 7.8 percentage point (pp) (95% confidence interval [CI] = -9.1 to -6.5 pp) less likely to be offered the video. These differences decrease to 1.3 pp (95% CI = -2.61 to -0.02 pp) when accounting for NH fixed effects. In fully adjusted models, black residents compared to white residents were 2.1 pp more likely to watch the video contingent on being offered (95% CI = 0.4-3.7 pp). Residents with cognitive impairment were less likely to be offered and shown the video., Conclusions: After controlling for NH fixed effects, there were smaller racial differences in being offered the video, but once offered, black residents were more likely to watch the video. This suggests that black residents are receptive to this type of ACP intervention but need to be given an opportunity to be exposed. J Am Geriatr Soc 68:603-608, 2020., (© 2019 The American Geriatrics Society.)

Background: The Pragmatic Trial of Video Education in Nursing Homes (PROVEN) is one of the first large pragmatic randomized clinical trials (pRCTs) to be conducted in U.S. nursing homes (N = 119 intervention and N = 241 control across two health-care systems). The trial aims to evaluate the effectiveness of a suite of videos to improve advance care planning (ACP) for nursing home patients. This report uses mixed methods to explore the optimal and suboptimal conditions necessary for implementation fidelity within pRCTs in nursing homes., Methods: PROVEN's protocol required designated facility champions to offer an ACP video to long-stay patients every 6 months during the 18-month implementation period. Champions completed a video status report, stored within electronic medical records, each time a video was offered. Data from the report were used to derive each facility's adherence rate (i.e., cumulative video offer). Qualitative interviews held after 15 months with champions were purposively sampled from facilities within the highest and lowest adherence rates (i.e., those in the top and bottom quintiles). Two researchers analyzed interview data thematically using a deductive approach based upon six domains of the revised Conceptual Framework for Implementation Fidelity (CFIF). Matrices were developed to compare coded narratives by domain across facility adherence status., Results: In total, 28 interviews involving 33 champions were analyzed. Different patterns were observed across high- versus low-adherence facilities for five CFIF domains. In low-adherence nursing homes, (1) there were limited implementation resources (Context), (2) there was often a perceived negative patient or family responsiveness to the program (Participant Responsiveness), and (3) champions were reticent in offering the videos (Recruitment). In high-adherence nursing homes, (1) there was more perceived patient and family willingness to engage in the program (Participant Responsiveness), (2) champions supplemented the video with ACP conversations (Quality of Delivery), (3) there were strategic approaches to recruitment (Recruitment), and (4) champions appreciated external facilitation (Strategies to Facilitate Implementation)., Conclusions: Critical lessons for implementing pRCTs in nursing homes emerged from this report: (1) flexible fidelity is important (i.e., delivering core elements of an intervention while permitting the adaptation of non-core elements), (2) reciprocal facilitation is vital (i.e., early and ongoing stakeholder engagement in research design and, reciprocally, researchers' and organizational leaders' ongoing support of the implementation), and (3) organizational and champion readiness should be formally assessed early and throughout implementation to facilitate remediation., Trial Registration: ClinicalTrials.gov, NCT02612688. Registered on 19 November 2015.

Adolescent age at time of transplant has been recognized as a risk factor for renal allograft loss. Increased risk for graft failure may persist from adolescence to young adulthood. Transfer of care is hypothesized as a risk factor for non-adherence and graft loss. We explored whether kidney allograft function declined at an accelerated rate after transfer of care to adult transplant centers and whether coefficient of variation of tacrolimus (CV TAC) trough levels predicted allograft loss. Single-center, retrospective chart review was performed for pediatric kidney transplant recipients who received transplants between 1999 and 2011. Change in eGFR pre- and post-transfer was performed via a linear mixed-effects model. CV TAC was calculated in transplant recipients with TAC data pre- and post-transfer. t test was performed to determine the difference between means of CV TAC in subjects with and without allograft loss following transfer of care. Of the 138 subjects who transferred to adult care, 47 subjects with data pre- and post-transfer demonstrated a decrease in the rate of eGFR decline post-transfer from 8.0 mL/min/1.73 m 2 per year to 2.1 mL/min/1.73 m 2 per year, an ~80% decrease in eGFR decline post-transfer (P = 0.01). Twenty-four subjects had CV TAC data pre- and post-transfer of care. Pretransfer CV TAC for subjects with allograft loss post-transfer was significantly higher than in subjects without allograft loss (49% vs 26%, P < 0.05). Transfer of care was not independently associated with acceleration in eGFR decline. CV TAC may aid in identifying patients at risk for allograft loss post-transfer., (© 2019 Wiley Periodicals, Inc.)

Background/Objective . We investigated interhemispheric interactions in stroke survivors by measuring transcranial magnetic stimulation (TMS)-evoked cortical coherence. We tested the effect of TMS on interhemispheric coherence during rest and active muscle contraction and compared coherence in stroke and older adults. We evaluated the relationships between interhemispheric coherence, paretic motor function, and the ipsilateral cortical silent period (iSP). Methods . Participants with (n = 19) and without (n = 14) chronic stroke either rested or maintained a contraction of the ipsilateral hand muscle during simultaneous recordings of evoked responses to TMS of the ipsilesional/nondominant (i/ndM1) and contralesional/dominant (c/dM1) primary motor cortex with EEG and in the hand muscle with EMG. We calculated pre- and post-TMS interhemispheric beta coherence (15-30 Hz) between motor areas in both conditions and the iSP duration during the active condition. Results . During active i/ndM1 TMS, interhemispheric coherence increased immediately following TMS in controls but not in stroke. Coherence during active cM1 TMS was greater than iM1 TMS in the stroke group. Coherence during active iM1 TMS was less in stroke participants and was negatively associated with measures of paretic arm motor function. Paretic iSP was longer compared with controls and negatively associated with clinical measures of manual dexterity. There was no relationship between coherence and. iSP for either group. No within- or between-group differences in coherence were observed at rest. Conclusions . TMS-evoked cortical coherence during hand muscle activation can index interhemispheric interactions associated with poststroke motor function and potentially offer new insights into neural mechanisms influencing functional recovery.

Tissue flaps are used to cover large/poorly healing wounds, but involve complex surgery and donor site morbidity. In this study a tissue flap is assembled using the mammalian body as a bioreactor to functionally connect an artery and vein to a human capillary network assembled from induced pluripotent stem cell-derived endothelial cells (hiPSC ECs). In vitro: Porous NovoSorb™ scaffolds (3 mm × 1.35 mm) were seeded with 200,000 hiPSC ECs ± 100,000 human vascular smooth muscle cells (hvSMC), and cultured for 1-3 days, with capillaries formed by 24 h which were CD31 + , VE-Cadherin + , EphB4 + , VEGFR2 + and Ki67 + , whilst hvSMCs (calponin + ) attached abluminally. In vivo: In SCID mice, bi-lateral epigastric vascular pedicles were isolated in a silicone chamber for a 3 week 'delay period' for pedicle capillary sprouting, then reopened, and two hiPSC EC ± hvSMCs seeded scaffolds transplanted over the pedicle. The chamber was either resealed (Group 1), or removed and surrounding tissue secured around the pedicle + scaffolds (Group 2), for 1 or 2 weeks. Human capillaries survived in vivo and were CD31 + , VE-Cadherin + and VEGFR2 + . Human vSMCs remained attached, and host mesenchymal cells also attached abluminally. Systemically injected FITC-dextran present in human capillary lumens indicated inosculation to host capillaries. Human iPSC EC capillary morphometric parameters at one week in vivo were equal to or higher than the same parameters measured in human abdominal skin. This 'proof of concept' study has demonstrated that bio-engineering an autologous human tissue flap based on hiPSC EC could minimize the use of donor flaps and has potential applications for complex wound coverage. STATEMENT OF SIGNIFICANCE: Tissue flaps, used for surgical reconstruction of wounds, require complex surgery, often associated with morbidity. Bio-engineering a simpler alternative, we assembled a human induced pluripotent stem cell derived endothelial cell (hiPSC ECs) capillary network in a porous scaffold in vitro, which when transplanted over a mouse vascular pedicle in vivo formed a functional tissue flap with mouse blood flow in the human capillaries. Therefore it is feasible to form an autologous tissue flap derived from a hiPSC EC capillary network assembled in vitro, and functionally connect to a vascular pedicle in vivo that could be utilized in complex wound repair for chronic or acute wounds., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The PRagmatic trial Of Video Education in Nursing homes (PROVEN) aims to test the effectiveness of an advance care planning (ACP) video intervention. Relatively little is known about the challenges associated with implementing ACP interventions in the nursing home (NH) setting, especially within a pragmatic trial. To address this research gap, this report sought to identify facilitators of and barriers to implementing PROVEN from the perspective of the Champions charged with introducing the ACP video program delivery to patients and families., Methods: In semi-structured telephone interviews at 4 and 15 months of the 18-month implementation period, ACP Champions at all PROVEN intervention facilities (N = 119) were asked about their perceptions of program implementation. Forty interviews were purposively sampled, transcribed, and analyzed using a hybrid deductive/inductive approach to thematic analysis incorporating the Consolidated Framework for Implementation Research's domains: Intervention Characteristics (IC), Inner Setting (IS), Characteristics of Individuals (CI), Outer Setting (OS), and Process (P)., Results: Implementation facilitators identified by Champions included: the intervention's adaptable mode of presentation and minimal time burden (IC) as well as the program's customizable delivery to patients and families and opportunity for group reflection on implementation among ACP Champions (P). Barriers included mandated protocol-driven aspects of the program (OS), limited time to deliver the intervention (IS), and lack of perceived relevance and emotional readiness for ACP amongst stakeholders (CI)., Conclusions: Despite the promise of PROVEN's intervention for improving ACP in nursing homes, unchangeable setting and characteristics of Champions, patients, and family members presented implementation barriers. Researchers need to engage all program participants (i.e., facility staff, patients, and families), in addition to corporate-level stakeholders, in early pragmatic trial design to minimize such obstacles. Further, despite the facilitating nature of PROVEN's implementation processes, the study encountered tension between scientific rigor and real-world demands. Researchers need to optimize the real-world authenticity of pragmatic trial design while avoiding excessive implementation protocol deviations., Trial Registration: ClinicalTrials.gov Identifier: NCT02612688. Registered 19 November 2015.

Background: Blended facilitation, which leverages the complementary skills and expertise of external and internal facilitators, is a powerful strategy that nursing stakeholders and researchers may use to improve implementation of quality improvement (QI) innovations and research performed in nursing homes., Problem: Nursing homes present myriad challenges (eg, time constraints, top-down flow of communication, high staff turnover) to QI implementation and research., Approach: This methods article describes the theory and practical application of blended facilitation and its components (external facilitation, internal facilitation, relationship building, and skill building), using examples from a mixed QI and research intervention in Veterans Health Administration nursing homes., Conclusions: Blended facilitation invites nursing home stakeholders to be equal partners in QI and research processes. Its intentional use may overcome many existing barriers to QI and research performed in nursing homes and, by strengthening relationships between researchers and stakeholders, may accelerate implementation of innovative care practices.

Objectives: Quality improvement (QI) may be a promising approach for staff to improve the quality of care in nursing homes. However, little is known about the challenges and facilitators to implementing QI interventions in nursing homes. This study examines staff perspectives on the implementation process., Design: We conducted semistructured interviews with staff involved in implementing an evidence-based QI intervention ("LOCK") to improve interactions between residents and staff through targeted staff behavior change. The LOCK intervention consists of 4 practices: (1) Learn from the bright spots, (2) Observe, (3) Collaborate in huddles, and (4) Keep it bite sized., Setting and Participants: We interviewed staff members in 6 Veterans Health Administration nursing homes [ie, Community Living Centers (CLCs)] via opportunistic and snowball sampling., Measures: The semistructured interviews were grounded in the Capability, Opportunity, Motivation, Behavior (COM-B) model of behavior change and covered staff experience, challenges, facilitators, and lessons learned during the implementation process. The interviews were analyzed using thematic content analysis., Results: Overall, staff accepted the intervention and appreciated the focus on the positives. Challenges fell largely within the categories of capability and opportunity and included difficulty finding time to complete intervention activities, inability to interpret data reports, need for ongoing training, and misunderstanding of study goals. Facilitators were largely within the motivation category, including incentives for participation, reinforcement of desired behavior, feasibility of intervention activities, and use of data to quantify improvements., Conclusions/implications: As QI programs become more common in nursing homes, it is critical that interventions are tailored for this unique setting. We identified barriers and facilitators of our intervention's implementation and learned that no challenge was insurmountable or derailed the implementation of LOCK. This ability of frontline staff to overcome implementation challenges may be attributed to LOCK's inherently motivational features. Future nursing home QI interventions should consider including built-in motivational components., (Published by Elsevier Inc.)

Objectives: Advance care planning (ACP) is important to ensure that nursing home (NH) residents receive care concordant with their goals. Video interventions have been developed to improve the process of ACP. Yet, little is known about which NH characteristics are associated with implementation of ACP video interventions in clinical practice. Our objective was to examine NH-level characteristics associated with the implementation of an ACP video intervention as part of the Pragmatic trial of Video Education in Nursing Homes (PROVEN) trial., Design: Cross-sectional study of NHs in PROVEN., Setting and Participants: 119 NHs randomized to receive the ACP video intervention., Measurements: The outcomes were the proportion of short- (<100 days) and long-stay (≥100 days) NH residents who were (1) offered to watch a video and (2) shown a video, aggregated to the NH-level, and measured using electronic forms of video offers. The association between outcomes and NH facility characteristics (eg, staffing, resident acuity) and participation in other aspects of the PROVEN trial (eg, monthly check-in calls) were estimated using multivariate linear regression models. NH characteristics were measured using data from Online Survey Certification and Reporting data, Long-term Care: Facts on Care in the US and NH Compare., Results: Offer rates were 69% [standard deviation (SD): 28] for short-stay and 56% (SD: 20) for long-stay residents. Show rates were 19% (SD: 21) for short-stay and 17% (SD: 17) for long-stay residents. After adjusting for NH characteristics, compared to 1-star NHs, higher star-rated NHs had higher offer rates. Champions' participation in check-in calls was positively associated with both outcomes for long-stay residents., Conclusions/implications: Lower-quality NHs seem unable to integrate a novel ACP video education program into routine care processes. Ongoing support for and engagement with NH staff to champion the intervention throughout implementation is important for the success of a pragmatic trial within NHs., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Repeated pairing of electrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) representation for a target muscle can induce neuroplastic adaptations in the human brain related to motor learning. The extent to which the motor state during this form of paired associative stimulation (PAS) influences the degree and mechanisms of neuroplasticity or motor learning is unclear. Here, we investigated the effect of volitional muscle contraction during PAS on: (1) measures of general corticomotor excitability and intracortical circuit excitability; and (2) motor performance and learning. We assessed measures of corticomotor excitability using TMS and motor skill performance during a serial reaction time task (SRTT) at baseline and at 0, 30, 60 min post-PAS. Participants completed a SRTT retention test 1 week following the first two PAS sessions. Following the PAS intervention where the hand muscle maintained an active muscle contraction (PAS ACTIVE ), there was lower short interval intracortical inhibition compared to PAS during a resting motor state (PAS REST ) and a sham PAS condition (PAS CONTROL ). SRTT performance improved within the session regardless of PAS condition. SRTT retention was greater following both PAS ACTIVE and PAS REST after 1 week compared to PAS CONTROL . These findings suggest that PAS may enhance motor learning retention and that motor state may be used to target different neural mechanisms of intracortical excitation and inhibition during PAS. This observation may be important to consider for the use of therapeutic noninvasive brain stimulation in neurologic patient populations.

Background: PRECIS-2 (PRagmatic Explanatory Continuum Indicator Summary-2) can assess how clinical trial design decisions (along the explanatory-pragmatic continuum) influence the applicability of trial results to intended stakeholders. The tool has been used to assess features of trials during the trial design phase and also upon completion. The ongoing PRagmatic trial Of Video Education in Nursing homes (PROVEN), which is evaluating the effectiveness of a suite of videos to improve advance care planning, is one of the first large pragmatic, cluster randomized trials within nursing home health care systems. While certain features of pragmatic trials remain static once designed (e.g., recruitment, outcomes), successful implementation of a system-wide program requires on-going evaluation and adaptation. This report's objectives were to apply PRECIS-2 in a novel manner during the actual conduct of the PROVEN trial to assess how dynamic adaptations shifted implementation to either a more explanatory or a more pragmatic approach., Methods: We assessed PROVEN's protocol as initially designed according to the three PRECIS-2 domains pertinent to implementation: (1) Organization, (2) Flexibility-Delivery, and (3) Flexibility-Adherence. We then applied this framework to conduct a formative evaluation of decisions made while the trial was ongoing to adapt the implementation approach along the pragmatic versus the explanatory continuum in response to emergent challenges., Results: Based on the PRECIS-2 rubric, the initial design of the PROVEN implementation approach reflected a hybrid of pragmatic and explanatory features. Most notably, within the Flexibility-Delivery, the trial had a relatively pragmatic approach to protocol delivery by front-line nursing home providers, balanced with a more explanatory approach to protocol monitoring enabled by the analytic capabilities of the research team. This more intensive monitoring proved critical in revealing implementation problems once the study began. Dynamic adaptations made in response to these challenges generally reflected shifts to more explanatory approaches within the Flexibility-Delivery and Flexibility-Adherence domains including ever more intensive compliance monitoring, as well as detailed coaching of front-line providers delivering the intervention by the research team., Conclusions: Pragmatic trials conducted in the nursing home setting may benefit from a more dynamic approach to implementation. Allowing fluidity between pragmatic and explanatory features may still preserve the trial's applicability to intended stakeholders' needs. PRECIS-2 provides a useful formative evaluation tool to assess these adaptations in "real-time.", Trial Registration: US National Library of Medicine, ClinicalTrials.gov, ID: NCT02612688 . Registered on 19 November 2015.

Background and Objectives: For nursing home residents, positive interactions with staff and engagement in daily life contribute meaningfully to quality of life. We sought to improve these aspects of person-centered care in an opportunistic snowball sample of six Veterans Health Administration nursing homes (e.g., Community Living Centers-CLCs) using an intervention that targeted staff behavior change, focusing on improving interactions between residents and staff and thereby ultimately aiming to improve resident engagement., Research Design and Methods: We grounded this mixed-methods study in the Capability, Opportunity, Motivation, Behavior (COM-B) model of behavior change. We implemented the intervention by (a) using a set of evidence-based practices for implementing quality improvement and (b) combining primarily CLC-based staff facilitation with some researcher-led facilitation. Validated resident and staff surveys and structured observations collected pre and post intervention, as well as semi-structured staff interviews conducted post intervention, helped assess intervention success., Results: Sixty-two CLC residents and 308 staff members responded to the surveys. Researchers conducted 1,490 discrete observations. Intervention implementation was associated with increased staff communication with residents during the provision of direct care and decreased negative staff interactions with residents. In the 66 interviews, staff consistently credited the intervention with helping them (a) develop awareness of the importance of identifying opportunities for engagement and (b) act to improve the quality of interactions between residents and staff., Discussion and Implications: The intervention proved feasible and influenced staff to make simple enhancements to their behaviors that improved resident-staff interactions and staff-assessed resident engagement.

Inhibition of fatty acid amide hydrolase (FAAH) potentiates endocannabinoid activity and is hypothesized to have therapeutic potential for mood and anxiety disorders and pain. The clinical profile of JNJ-42165279, an oral selective FAAH inhibitor, was assessed by investigating the pharmacokinetics, pharmacodynamics, safety, and binding to FAAH in the brain of healthy human volunteers. Concentrations of JNJ-42165279 (plasma, cerebrospinal fluid (CSF), urine) and fatty acid amides (FAA; plasma, CSF), and FAAH activity in leukocytes was determined in a phase I multiple ascending dose study. A positron emission tomography study with the FAAH tracer [ 11 C]MK3168 was conducted to determine brain FAAH occupancy after single and multiple doses of JNJ-42165279. JNJ-42165279 administration resulted in an increase in plasma and CSF FAA. Significant blocking of brain FAAH binding of [ 11 C]MK3168 was observed after pretreatment with JNJ-42165279. JNJ-42165279 produces potent central and peripheral FAAH inhibition. Saturation of brain FAAH occupancy occurred with doses ≥10 mg of JNJ-42165279. No safety concerns were identified., (© 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose of the Study: Implementing quality improvement (QI) programs in nursing homes continues to encounter significant challenges, despite recognized need. QI approaches provide nursing home staff with opportunities to collaborate on developing and testing strategies for improving care delivery. We present a theory-driven and user-friendly adaptable framework and facilitation package to overcome existing challenges and guide QI efforts in nursing homes., Design and Development: The framework is grounded in the foundational concepts of strengths-based learning, observation, relationship-based teams, efficiency, and organizational learning. We adapted these concepts to QI in the nursing home setting, creating the "LOCK" framework. The LOCK framework is currently being disseminated across the Veterans Health Administration., Results: The LOCK framework has five tenets: (a) Look for the bright spots, (b) Observe, (c) Collaborate in huddles, (d) Keep it bite-sized, and (e) facilitation. Each tenet is described. We also present a case study documenting how a fictional nursing home can implement the LOCK framework as part of a QI effort to improve engagement between staff and residents. The case study describes sample observations, processes, and outcomes. We also discuss practical applications for nursing home staff, the adaptability of LOCK for different QI projects, the specific role of facilitation, and lessons learned., Implications: The proposed framework complements national efforts to improve quality of care and quality of life for nursing home residents and may be valuable across long-term care settings and QI project types.

Background: Spiritual well-being enhances older persons' health status. Factors that optimize their spiritual well-being are not well-established., Objective: To describe spiritual needs attainment and identify factors associated with such attainment among community-dwelling older persons., Design: Cross-sectional., Setting: Sixty-five U.S. continuing care retirement communities or independent housing facilities., Subjects: 4077 persons entering the facilities between January 1, 2007 and November 30, 2016., Methods: Standardized Community Health Assessment and Wellness Survey instruments were used to determine the proportion of subjects reporting their spiritual needs were met. Multivariate logistic regression identified characteristics independently associated with this outcome., Results: Among the 4077 subjects (mean age 81.6 ± 7.5; male, 28.8%; and White race, 70.7%), 93.4% stated their spiritual needs were met. Factors independently associated with a greater likelihood of spiritual needs attainment were: satisfaction with life (adjusted odds ratio (AOR) 2.81, 95% confidence interval (CI) 2.00, 3.96; p < 0.001), feeling valued (AOR 2.51, 95% CI 1.61, 3.92; p < 0.001), strong and supportive family relationship (AOR 1.99, 95% CI 1.20, 3.29; p = 0.008), sufficient sleep (AOR 1.59, 95% CI 1.15, 2.19; p = 0.005), no pain (AOR 1.35, 95% CI 1.01, 1.82; p = 0.046), and having someone to talk to about death among those interested in doing so (AOR 0.39, 95% CI 0.29, 0.54; p < 0.001)., Conclusions: The majority of community-dwelling older persons reported their spiritual needs were met. Adequate sleep, pain relief, and having a person with whom to discuss death are potentially modifiable factors that may promote spiritual needs attainment in this population, which in turn, may improve their health outcomes., (Published by Elsevier B.V.)

Objectives: Federally mandated assessments of nursing home (NH) residents drive individualized care planning. Residents with cognitive impairment may not be able to meaningfully communicate their care needs and preferences during this process-a gap that may be partially addressed by involving surrogates. We describe the prevalence of family participation in the care planning process for long-stay NH residents with varying degrees of cognitive impairment., Design: Retrospective study using administrative data made available as part of an ongoing pragmatic cluster randomized controlled trial., Setting: A total of 292 NHs from 1 large for-profit NH system., Participants: Long-stay NH residents in 2016., Measurements: We identified all care planning assessments conducted in 2016 for long-stay NH residents. Cognitive functioning was defined using the Cognitive Function Scale. The Minimum Data Set was used to determine whether a resident, family member, and/or legal guardian participated in the assessment process. Certification and Survey Provider Enhance Reporting system data was used to identify facility-level correlates of family participation. Bivariate and multivariable hierarchical regression results are presented., Results: The analytic sample included 18,552 long-stay NH residents. Family member/representative participation varied by degree of resident cognitive impairment; 8% of residents with no cognitive impairment had family or representative participation in care planning during 2016, compared with 26% of residents with severe impairment. NHs with more social workers had greater family participation in care planning. Available NH characteristics do not explain most of the variation in family participation between NHs (residual intraclass correlation = .57)., Conclusions: Only a minority of family members and surrogates participate in NH care planning, even for residents with severe cognitive impairment. The association between social work staffing and participation suggests family involvement may be a measure of quality improvement capacity. Our findings suggest a lack of voice for a vulnerable population that may have implications on the quality of care received at the end of life., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

A central component of person-centered care, resident choice in daily life, has received little research attention in the U.S., Context: This study investigated nursing home staff experiences in realizing resident choice. Twenty-six qualitative staff interviews were conducted in an opportunistic sample from two Veterans Health Administration (VHA) Community Living Centers (CLCs, i.e., nursing homes) implementing the Green House Model. Thematic content analysis surfaced several key tensions at the intra-personal, inter-personal, and organizational levels. Most salient were staff mental models within the intra-personal level. Staff conveyed a lack of clarity on how to realize resident choice when faced with varying tensions, especially the competing goal of resident medical and safety needs. Staff-employed resolutions to resident choice-related tensions also emerged (e.g., preventive practices, staff reinforcement, and staff deliberation). This study offers specific and concrete insights on how resident choice in daily life, and thus resident quality of life, can be advanced., (Published by Elsevier Inc.)

Purpose of Study: To develop a structured observational tool, the Resident-centered Assessment of Interactions with Staff and Engagement tool (RAISE), to measure 2 critical, multi-faceted, organizational-level aspects of person-centered care (PCC) in nursing homes: (a) resident engagement and (b) the quality and frequency of staff-resident interactions., Design and Methods: In this multi-method psychometric development study, we conducted (a) 120 hr of ethnographic observations in one nursing home and (b) a targeted literature review to enable construct development. Two constructs for which no current structured observation measures existed emerged from this phase: nursing home resident-staff engagement and interaction. We developed the preliminary RAISE to measure these constructs and used the tool in 8 nursing homes at an average of 16 times. We conducted 8 iterative psychometric testing and refinement cycles with multi-disciplinary research team members. Each cycle consisted of observations using the draft tool, results review, and tool modification., Results: The final RAISE included a set of coding rules and procedures enabling simultaneously efficient, non-reactive, and representative quantitative measurement of the interaction and engagement components of nursing home life for staff and residents. It comprised 8 observational variables, each represented by extensive numeric codes. Raters achieved adequate to high reliability with all variables. There is preliminary evidence of face and construct validity via expert panel review., Implications: The RAISE represents a valuable step forward in the measurement of PCC, providing objective, reliable data based on systematic observation.

Background: Despite intensive rehabilitation efforts, most stroke survivors have persistent functional disability of the paretic arm and hand. These motor impairments may be due in part to maladaptive changes in structural and functional connections between brain regions. The following early stage clinical trial study protocol describes a noninvasive brain stimulation approach to target transcallosally mediated interhemispheric connections between the ipsi- and contralesional motor cortices (iM1 and cM1) using corticocortical paired associative stimulation (ihPAS). This clinical trial aims to characterize ihPAS-induced modulation of interhemispheric connectivity and the effect on motor skill performance and learning in chronic stroke survivors., Methods/design: A repeated-measures, cross-over design study will recruit 20 individuals post-stroke with chronic mild-moderate paretic arm impairment. Each participant will complete an active ihPAS and control ihPAS session. Assessments of cortical excitability and motor skill performance will be conducted prior to and at four time points following the ihPAS intervention. The primary outcome measures will be: TMS-evoked interhemispheric motor connectivity, corticomotor excitability, and response time on a modified serial reaction time task., Discussion/conclusion: The findings from this single-site early stage clinical trial will provide foundational results to inform the design of larger-scale, multisite clinical trials to evaluate the therapeutic potential of ihPAS-based neuromodulation for upper limb recovery after stroke. This trial is registered with NCT02465034.

Nonvascularized fat grafting is a valuable technique for soft tissue reconstruction but poor survival of fat in the host environment remains a problem. A process known as cell-assisted transfer is used to enhance fat graft retention by adding stromal vascular fraction, an adipose-derived stem cell (ASC) rich content to lipoaspirate. We have recently shown that the use of melatonin, a reactive oxygen species scavenger, protects human ASCs from hydrogen peroxide-induced oxidative stress and cell death in vitro but its role as a pharmacological adjunct in clinical fat grafting has not been studied. Herein, the effect of melatonin was examined on human ASCs in vitro using survival and functional assays including the MTT assay, CellTox Green assay, monolayer scratch assay as well as a human cytokine chemoluminescence, and tumour necrosis factor-α assay. Further, the effect of melatonin-treated fat grafts was tested in vivo with a murine model. Haematoxylin and eosin staining, perilipin and CD31 immunostaining were performed with morphometric analysis of adipose tissue. The results demonstrate that, in vitro, the addition of melatonin to ASCs significantly improved their cell-viability, promoted cell migration and preserved membrane integrity as compared to controls. In addition, it induced a potent anti-inflammatory response by downregulating acute inflammatory cytokines particularly tumour necrosis factor-α. For the first time, it is demonstrated in vivo that melatonin enhances fat graft volume retention by reducing inflammation and increasing the percentage of adipose volume within fat grafts with comparable volumes to that of cell-assisted lipotransfer. Based on these novel findings, melatonin may be a useful pharmacological adjunct in clinical fat grafting., (Copyright © 2017 John Wiley & Sons, Ltd.)

Amino acid biosynthesis pathways observed in nature typically require enzymes that are made with the amino acids they produce. For example, Escherichia coli produces cysteine from serine via two enzymes that contain cysteine: serine acetyltransferase (CysE) and O-acetylserine sulfhydrylase (CysK/CysM). To solve this chicken-and-egg problem, we substituted alternate amino acids in CysE, CysK and CysM for cysteine and methionine, which are the only two sulfur-containing proteinogenic amino acids. Using a cysteine-dependent auxotrophic E. coli strain, CysE function was rescued by cysteine-free and methionine-deficient enzymes, and CysM function was rescued by cysteine-free enzymes. CysK function, however, was not rescued in either case. Enzymatic assays showed that the enzymes responsible for rescuing the function in CysE and CysM also retained their activities in vitro. Additionally, substitution of the two highly conserved methionines in CysM decreased but did not eliminate overall activity. Engineering amino acid biosynthetic enzymes to lack the so-produced amino acids can provide insights into, and perhaps eventually fully recapitulate via a synthetic approach, the biogenesis of biotic amino acids.

Vascularization is a major hurdle for growing three-dimensional tissue engineered constructs. This study investigated the mechanisms involved in hypoxic preconditioning of primary rat myoblasts in vitro and their influence on local angiogenesis postimplantation. Primary rat myoblast cultures were exposed to 90 min hypoxia at <1% oxygen followed by normoxia for 24 h. Real time (RT) polymerase chain reaction evaluation indicated that 90 min hypoxia resulted in significant downregulation of miR-1 and miR-206 (p < 0.05) and angiopoietin-1 (p < 0.05) with upregulation of vascular endothelial growth factor-A (VEGF-A; p < 0.05). The miR-1 and angiopoietin-1 responses remained significantly downregulated after a 24 h rest phase. In addition, direct inhibition of miR-206 in L6 myoblasts caused a significant increase in VEGF-A expression (p < 0.05), further establishing that changes in VEGF-A expression are influenced by miR-206. Of the myogenic genes examined, MyoD was significantly upregulated, only after 24 h rest (p < 0.05). Preconditioned or control myoblasts were implanted with Matrigel™ into isolated bilateral tissue engineering chambers incorporating a flow-through epigastric vascular pedicle in severe combined immunodeficiency mice and the chamber tissue harvested 14 days later. Chambers implanted with preconditioned myoblasts had a significantly increased percentage volume of blood vessels (p = 0.0325) compared with chambers implanted with control myoblasts. Hypoxic preconditioned myoblasts promote vascularization of constructs via VEGF upregulation and downregulation of angiopoietin-1, miR-1 and miR-206. The relatively simple strategy of hypoxic preconditioning of implanted cells - including non-stem cell types - has broad, future applications in tissue engineering of skeletal muscle and other tissues, as a technique to significantly increase implant site angiogenesis., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Paired associative stimulation (PAS) combining repeated pairing of electrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) can induce neuroplastic adaptations in the human brain and enhance motor learning in neurologically-intact individuals. However, the extent to which PAS is an effective technique for inducing associative plasticity and improving motor function in individuals post-stroke is unclear., Objective: The objective of this pilot study was to investigate the effects of a single session of PAS to modulate corticomotor excitability and motor skill performance in individuals post-stroke., Methods: Seven individuals with chronic stroke completed two separate visits separated by at least one week. We assessed general corticomotor excitability, intracortical network activity and behavioral outcomes prior to and at three time points following PAS and compared these outcomes to those following a sham PAS condition (PASSHAM)., Results: Following PAS, we found increased general corticomotor excitability but no significant difference in behavioral measures between PAS conditions. There was a relationship between PAS-induced corticomotor excitability increase and enhanced motor skill performance across post-PAS testing time points., Conclusion: These results provide preliminary evidence for the potential of PAS to increase corticomotor excitability that could favorably impact motor skill performance in chronic individuals post-stroke and are an important first step for future studies investigating the clinical application and behavioral relevance of PAS interventions in post stroke patient populations.

The relative developmental toxicity potency of a series of retinoid analogues was evaluated using a human induced pluripotent stem (iPS) cell assay that measures changes in the biomarkers ornithine and cystine. Analogue potency was predicted, based on the assay endpoint of the ornithine/cystine (o/c) ratio, to be all-trans-retinoic acid>TTNPB>13-cis-retinoic acid≈9-cis-retinoic acid>acitretin>etretinate>retinol. These rankings correlate with in vivo data and demonstrate successful application of the assay to rank a series of related toxic and non-toxic compounds. The retinoic acid receptor α (RARα)-selective antagonist Ro 41-5253 inhibited the cystine perturbation caused by all-trans-retinoic acid, TTNPB, 13-cis-retinoic acid, 9-cis-retinoic acid, and acitretin. Ornithine was altered independent of RARα in all retinoids except acitretin. These results suggest a role for an RARα-mediated mechanism in retinoid-induced developmental toxicity through altered cystine metabolism., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Context: Delivering goal-directed care is a hallmark of high-quality palliative care, but requires an understanding of preferences., Objectives: To describe and identify factors associated with level of care preferences among proxies of nursing home (NH) residents with advanced dementia., Methods: NH residents with advanced dementia and their proxies (N = 402 dyads) were recruited from 62 Boston-area facilities as part of an ongoing randomized clinical trial. At baseline, all proxies were asked to select which level of care they felt the resident should receive: intensive, basic, or comfort care. Multivariable logistic regression identified resident and proxy factors associated with a preference for comfort care (vs. basic or intensive medical care)., Results: Proxy level of care preferences were: comfort, 62.2%; basic, 31.1%; and intensive medical care, 6.5%. In multivariable analyses, proxy perception that the resident had less than six months to live was most strongly associated with a preference for comfort-focused care (adjusted odds ratio 12.25, 95% CI 4.04-37.08). Additional factors significantly associated with a preference for comfort care included older resident age, worse resident cognitive impairment, and the proxy having been asked about goals of care preferences by a NH health care provider (adjusted odds ratio 1.71, 95% CI 1.07, 2.74)., Conclusion: Most proxies select comfort as the preferred level of care for NH residents with advanced dementia. Discussions regarding prognosis, as well as inquiry about goals of care, are modifiable factors that may promote a preference for comfort care in this population., (Copyright © 2017. Published by Elsevier Inc.)

Enhanced interpersonal relationships and meaningful resident engagement in daily life are central to nursing home cultural transformation, yet these critical components of person-centered care may be difficult for frontline staff to measure using traditional research instruments. To address the need for easy-to-use instruments to help nursing home staff members evaluate and improve person-centered care, the psychometric method of cognitive-based interviewing was used to adapt a structured observation instrument originally developed for researchers and nursing home surveyors. Twenty-eight staff members from 2 Veterans Health Administration (VHA) nursing homes participated in 1 of 3 rounds of cognitive-based interviews, using the instrument in real-life situations. Modifications to the original instrument were guided by a cognitive processing model of instrument refinement. Following 2 rounds of cognitive interviews, pretesting of the revised instrument, and another round of cognitive interviews, the resulting set of 3 short instruments mirrored the concepts of the original longer instrument but were significantly easier for frontline staff to understand and use. Final results indicated frontline staff found the revised instruments feasible to use and clinically relevant in measuring and improving the lived experience of a changing culture. This article provides a framework for developing or adapting other measurement tools for frontline culture change efforts in nursing homes, in addition to reporting on a practical set of instruments to measure aspects of person-centered care. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: Abnormal brain excitability influences recovery after stroke at which time a prolonged transcranial magnetic stimulation (TMS)-induced electromyographic silent period is thought to reflect abnormal inhibitory interneuron excitability. Cortical excitability can be probed directly during the silent period using concurrent electroencephalography (EEG) of TMS-evoked responses., Objective: The primary study objectives were to characterize TMS-evoked cortical potentials (TEPs) using EEG and to investigate associations with persistent hand and arm motor dysfunction in individuals with chronic stroke., Methods: Thirteen participants with chronic stroke-related mild-moderate arm motor impairment and 12 matched controls completed a single TMS-EEG cortical excitability assessment. TEPs recorded from the vertex during cortical silent period (CSP) assessment and while at rest were used to evaluate differences in cortical excitability between stroke and control participants. Associations between TEPs and CSP duration with measures of upper extremity motor behavior were investigated., Results: Significantly increased TEP component peak amplitudes and delayed latencies were observed for stroke participants compared with controls during CSP assessment and while at rest. Delayed early TEP component (P30) peak latencies during CSP assessment were associated with less manual dexterity. CSP duration was prolonged in stroke participants, and correlated with P30 peak latency and paretic arm dysfunction., Conclusions: Abnormal cortical excitability directly measured by early TMS-evoked EEG responses during CSP assessment suggests abnormal cortical inhibition is associated with hand dysfunction in chronic stroke. Further investigation of abnormal cortical inhibition in specific brain networks is necessary to characterize the salient neurophysiologic mechanisms contributing to persistent motor dysfunction after stroke.

Background: Cell-assisted lipotransfer has been promisingly applied to restore soft-tissue defects in plastic surgery; however, the harvesting of stromal vascular fraction increases morbidity and poses potential safety hazards. The authors investigated whether adding indomethacin, an antiinflammatory proadipogenic drug, to the fat graft at the time of transplantation would enhance the final graft volume compared with cell-assisted lipotransfer., Methods: In vitro, human adipose-derived stem cells were cultured in conditioned growth media supplemented with various doses of indomethacin to investigate adipogenesis and the expression of the adipogenic genes. In vivo, lipoaspirate mixed with stromal vascular fractions or indomethacin was injected into the dorsum of mice. Tissues were harvested at weeks 2, 4, and 12 to evaluate histologic changes., Results: In vitro, polymerase chain reaction analysis revealed that increased up-regulation of adipogenic genes and activation of the peroxisome proliferator-activated receptor-γ pathway. In vivo, the percentage volume of adipocytes in the indomethacin-assisted groups was higher than that in the lipoaspirate-alone (control) group at 12 weeks (p = 0.016), and was equivalent to the volume in the cell-assisted groups (p = 1.000). Indomethacin improved adipose volumes but had no effect on vascularity. A larger number of small adipocytes appeared in the treatment samples than in the controls at 2 weeks (p = 0.044) and 4 weeks (p = 0.021)., Conclusions: Pretreating lipoaspirate with indomethacin enhances the final volume retention of engrafted fat. This result is explained in part by increased adipogenesis and possibly by the inhibition of inflammatory responses.

Background: Recent research demonstrated that the symmetry of corticomotor drive with the paretic and nonparetic plantarflexor muscles was related to the biomechanical ankle moment strategy that people with chronic stroke used to achieve their greatest walking speeds. Rehabilitation strategies that promote corticomotor balance might improve poststroke walking mechanics and enhance functional ambulation., Objective: The study objectives were to test the effectiveness of a single session of gait training using functional electrical stimulation (FES) to improve plantarflexor corticomotor symmetry and plantarflexion ankle moment symmetry and to determine whether changes in corticomotor symmetry were related to changes in ankle moment symmetry within the session., Design: This was a repeated-measures crossover study., Methods: On separate days, 20 people with chronic stroke completed a session of treadmill walking either with or without the use of FES of their ankle dorsi- and plantarflexor muscles. We calculated plantarflexor corticomotor symmetry using transcranial magnetic stimulation and plantarflexion ankle moment symmetry during walking between the paretic and the nonparetic limbs before and after each session. We compared changes and tested relationships between corticomotor symmetry and ankle moment symmetry following each session., Results: Following the session with FES, there was an increase in plantarflexor corticomotor symmetry that was related to the observed increase in ankle moment symmetry. In contrast, following the session without FES, there were no changes in corticomotor symmetry or ankle moment symmetry., Limitations: No stratification was made on the basis of lesion size, location, or clinical severity., Conclusions: These findings demonstrate, for the first time (to our knowledge), the ability of a single session of gait training with FES to induce positive corticomotor plasticity in people in the chronic stage of stroke recovery. They also provide insight into the neurophysiologic mechanisms underlying improvements in biomechanical walking function., (© 2017 American Physical Therapy Association)

Quality of care in nursing homes has begun to address the importance of resident choice in daily life, yet there are no published tools to teach nursing home staff how to offer such choice. In the current study, a formative assessment tool was developed that can provide staff with detailed and concrete feedback on how to realize resident choice. The tool was created and refined through 22 hours of ethnographic observation in two Veterans Health Administration Community Living Centers (CLCs), 22 hours of developmental testing in two CLCs, review by a modified Delphi panel, and use of an algorithm to assess its logical structure. The resulting Supporting Choice Observational Tool (SCOT) documents how choice is or is not offered and is or is not enabled within a singular staff-resident interaction. SCOT findings could be used in clinical teaching, quality improvement, or research efforts intent on enhancing nursing home resident quality of life. [Res Gerontol Nurs. 2017; 10(3):129-138.]., (Copyright 2017, SLACK Incorporated.)

Imbalance of corticomotor excitability between the paretic and nonparetic limbs has been associated with the extent of upper extremity motor recovery poststroke, is greatly influenced by specific testing conditions such as the presence or absence of volitional muscle activation, and may vary across muscle groups. However, despite its clinical importance, poststroke corticomotor drive to lower extremity muscles has not been thoroughly investigated. Additionally, whereas conventional gait rehabilitation strategies for stroke survivors focus on paretic limb foot drop and dorsiflexion impairments, most contemporary literature has indicated that paretic limb propulsion and plantarflexion impairments are the most significant limiters to poststroke walking function. The purpose of this study was to compare corticomotor excitability of the dorsi- and plantarflexor muscles during resting and active conditions in individuals with good and poor poststroke walking recovery and in neurologically intact controls. We found that plantarflexor muscles showed reduced corticomotor symmetry between paretic and nonparetic limbs compared with dorsiflexor muscles in individuals with poor poststroke walking recovery during active muscle contraction but not during rest. Reduced plantarflexor corticomotor symmetry during active muscle contraction was a result of reduced corticomotor drive to the paretic muscles and enhanced corticomotor drive to the nonparetic muscles compared with the neurologically intact controls. These results demonstrate that atypical corticomotor drive exists in both the paretic and nonparetic lower limbs and implicate greater severity of corticomotor impairments to plantarflexor vs. dorsiflexor muscles during muscle activation in stroke survivors with poor walking recovery. NEW & NOTEWORTHY The present study observed that lower-limb corticomotor asymmetry resulted from both reduced paretic and enhanced nonparetic limb corticomotor excitability compared with neurologically intact controls. The most asymmetrical corticomotor drive was observed in the plantarflexor muscles of individuals with poor poststroke walking recovery. This suggests that neural function of dorsi- and plantarflexor muscles in both paretic and nonparetic limbs may play a role in poststroke walking function, which may have important implications when developing targeted poststroke rehabilitation programs to improve walking ability., (Copyright © 2017 the American Physiological Society.)

Recent rehabilitation approaches for individuals poststroke have focused on improving walking speed because it is a reliable measurement that is associated with quality of life. Previous studies have demonstrated that propulsion, the force used to propel the body forward, determines walking speed. However, there are several different ways of measuring propulsion and no studies have identified which measurement best reflects differences in walking speed. The primary purposes of this study were to determine for individuals poststroke, which measurement of propulsion (1) is most closely related to their self-selected walking speeds and (2) best reflects changes in walking speed within a session. Participants (N=43) with chronic poststroke hemiparesis walked at their self-selected and maximal walking speeds on a treadmill. Propulsive impulse, peak propulsive force, and mean propulsive value (propulsive impulse divided by duration) were analyzed. In addition, each participant׳s cadence was calculated. Pearson correlation coefficients were used to determine the relationships between different measurements of propulsion versus walking speed as well as changes in propulsion versus changes in walking speed. Stepwise linear regression was used to determine which measurement of propulsion best predicted walking speed and changes in walking speed. The results showed that all 3 measurements of propulsion were correlated to walking speed, with peak propulsive force showed the strongest correlation. Similarly, when participants increased their walking speeds, changes in peak propulsive forces showed the strongest correlation to changes in walking speed. In addition, multiplying each measurement by cadence improved the correlations. The present study suggests that measuring peak propulsive force and cadence may be most appropriate of the variables studied to characterize propulsion in individuals poststroke., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Pneumococcal vaccination rates among children receiving a kidney transplant remain suboptimal. Current practice guidelines in the United States recommend giving the PPSV23 after priming with the PCV13. We conducted a QI initiative to increase pneumococcal vaccine rates in our kidney transplant recipients by developing an age-based vaccine algorithm, obtaining vaccine records, and generating reminders for patients and clinicians. A monthly report from the EHR tracked outcomes. The process metric was missed vaccine opportunities, and the overall objective was to improve coverage with both the PCV13 and PPSV23. Over the first six months, we increased the percentage of visits where the vaccine was given from a baseline of 4% to 33%. However, by the end of the 12-month period, the percentage of eligible visits where the vaccine was given decreased to 8.7%. Nevertheless, over the 12-month observation period, we were able to increase the percentage of transplant patients receiving the PCV13 and PPSV23 from 6% to 52%. Utilizing an age-based algorithm and the electronic medical record, vaccine champions can track both missed visit opportunities and the number of vaccinated patients to improve pneumococcal immunization coverage for these high-risk patients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)