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The list of Curing Coma Campaign Collaborators included as a file in Supplementary Information has been updated. Flora Hammond, Raimund Helbok, and Naomi Niznick have been added to the list. Several spelling errors have been corrected. A revised file has been included.

Nucleotide changes in gene regulatory elements are important determinants of neuronal development and diseases. Using massively parallel reporter assays in primary human cells from mid-gestation cortex and cerebral organoids, we interrogated the cis-regulatory activity of 102,767 open chromatin regions, including thousands of sequences with cell type-specific accessibility and variants associated with brain gene regulation. In primary cells, we identified 46,802 active enhancer sequences and 164 variants that alter enhancer activity. Activity was comparable in organoids and primary cells, suggesting that organoids provide an adequate model for the developing cortex. Using deep learning we decoded the sequence basis and upstream regulators of enhancer activity. This work establishes a comprehensive catalog of functional gene regulatory elements and variants in human neuronal development.

Background: Person-centred services are inherently related to patients/caregivers' needs. However, the extent to which dysphagia services within Singapore meet consumer needs is largely unknown. Involving patients/caregivers in service evaluation/redesign deepens the understanding of consumer needs. This process also increases the success of implementing service enhancements through relevant and meaningful change. Aim: This study aimed to identify aspects of dysphagia services, within acute and subacute settings in Singapore, perceived as highly important and easy to change by patients/caregivers. Methods & Procedures: Using concept mapping methodology, 5 patients and 11 caregivers reflected on their experiences of receiving dysphagia care and proposed 59 unique suggestions to improve dysphagia services within Singapore. Then, each individual sorted the suggestions into groups based on similarity and rated each statement for its perceived importance and changeability for service enhancement. Data were analysed using multidimensional scaling, hierarchical cluster analysis, and bivariate analysis to generate clusters of conceptually similar suggestions and a prioritised list of suggestions for service enhancement. Results: Twelve clusters were identified, with most rated as more important than changeable for service improvement. Participants prioritised 23 (39%) of the suggestions as highly important and easy to change, and these focused on ensuring effective communication among consumers and healthcare team, enhancing patients and carers' access to support at home, increasing patients and carers' access to educational resources, and improving service quality and access through technology. Conclusion: These findings provide future directions on how to develop and implement dysphagia services in Singapore to better meet the needs of patients/caregivers.

Objective: To describe the outcomes (change in functional independence and discharge disposition) of patients who after liver transplantation received acute inpatient rehabilitation in a freestanding rehabilitation hospital. Design: A retrospective chart review was conducted of patients admitted to an acute inpatient rehabilitation hospital within 6 months of undergoing liver transplantation between January 2014 and December 2018. Change in function from rehabilitation admission to discharge was measured using FIM Change and FIM Efficiency. Setting: A freestanding rehabilitation hospital. Participants: 107 patients who underwent acute inpatient rehabilitation at a freestanding rehabilitation hospital within 6 months after liver transplantation who met inclusion criteria (N=107). Most were men (71.96%), and the mean age of the patient population was 62.15 years. Interventions: Acute inpatient rehabilitation consisting of at least 3 hours of therapy 5 days a week split between physical therapy, occupational therapy, and speech language pathology services. Main Outcome Measure: FIM Change, FIM Efficiency, Discharge Disposition. Results: Participants were found to have statistically significant positive FIM Change (P

We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.

BackgroundPost-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells.ResultsHere, the Brain Somatic Mosaicism Network conducts a coordinated, multi-institutional study to examine the ability of existing methods to detect simulated somatic single-nucleotide variants (SNVs) in DNA mixing experiments, generate multiple replicates of whole-genome sequencing data from the dorsolateral prefrontal cortex, other brain regions, dura mater, and dural fibroblasts of a single neurotypical individual, devise strategies to discover somatic SNVs, and apply various approaches to validate somatic SNVs. These efforts lead to the identification of 43 bona fide somatic SNVs that range in variant allele fractions from ~ 0.005 to ~ 0.28. Guided by these results, we devise best practices for calling mosaic SNVs from 250× whole-genome sequencing data in the accessible portion of the human genome that achieve 90% specificity and sensitivity. Finally, we demonstrate that analysis of multiple bulk DNA samples from a single individual allows the reconstruction of early developmental cell lineage trees.ConclusionsThis study provides a unified set of best practices to detect somatic SNVs in non-cancerous tissues. The data and methods are freely available to the scientific community and should serve as a guide to assess the contributions of somatic SNVs to neuropsychiatric diseases.

Abstract Somatic mosaicism is defined as an occurrence of two or more populations of cells having genomic sequences differing at given loci in an individual who is derived from a single zygote. It is a characteristic of multicellular organisms that plays a crucial role in normal development and disease. To study the nature and extent of somatic mosaicism in autism spectrum disorder, bipolar disorder, focal cortical dysplasia, schizophrenia, and Tourette syndrome, a multi-institutional consortium called the Brain Somatic Mosaicism Network (BSMN) was formed through the National Institute of Mental Health (NIMH). In addition to genomic data of affected and neurotypical brains, the BSMN also developed and validated a best practices somatic single nucleotide variant calling workflow through the analysis of reference brain tissue. These resources, which include >400 terabytes of data from 1087 subjects, are now available to the research community via the NIMH Data Archive (NDA) and are described here.

The Extended Glasgow Outcome Scale (GOSE) is accepted as the primary outcome measure in registrational studies for traumatic brain injury (TBI). The Disability Rating Scale (DRS) is used to assess functional progress from initial acute injury, through rehabilitation and reintegration into the community and life. For these reasons, the DRS is an alternative measure for assessing meaningful global outcomes in chronic TBI. The objective of this study was to determine the minimally clinically important difference (MCID) for the DRS in chronic TBI, by determining the magnitude of DRS change associated with the MCID for the GOSE of 1 point. This study is a retrospective analysis of the multi-center, prospective, longitudinal, Traumatic Brain Injury Model Systems National Database of persons with outcomes at 1, 2, and 5 years and every 5 years thereafter post-injury. Spearman's correlations for dynamic and static relationships between the DRS and GOSE were significant. For the 1-point MCID for the GOSE, the dynamic MCID estimate for the DRS of a ?0.68-point change was calculated as the mean DRS change associated with the difference of the GOSE score between year 1 and year 2 (score range, 3?8), using all persons in the study (n?=?11,102), whereas the exploratory static MCID estimate for the DRS of ?1.28 points was calculated from the slope of the best-fit line between the DRS and GOSE at year 1 follow-up (score range, 3?8; n?=?13,415). The final MCID for the DRS was calculated by using the triangulation method (i.e., the arithmetic mean of the dynamic and exploratory static MCID estimates), which resulted in a ?1.0-point change. The significant correlation between the DRS and GOSE has allowed for the establishment of a ?1.0-point MCID for the DRS, which supports the use of the DRS as an alternative primary outcome measure for chronic TBI research studies, including clinical trials.

Abstract Background data Ganglioneuroma is rare in children and often incidentally discovered. The transperitoneal laparoscopic approach is the surgical choice for most of the surgeons because of the familiar anatomy and the wider working spaces. However, a posterior retroperitoneal approach started to be used in pediatric population demonstrating to be safe and effective. Case presentation We present a case of a child with radiological finding of a right adrenal mass. Due to the increased risk of having a malignant transformation, a surgical resection was decided using a retroperitoneal approach. The adrenal mass was recognized and completely enucleated. The histopathological examination revealed a GN. Clinical course was uneventful with hospital discharge after 3 days. The outcome was evaluated by ultrasound examination performed 3–6 to 12–24 months and then annually. After 24 months, the patient is completely asymptomatic, and no adrenal masses in both sides have been detected. Conclusions The posterior retroperitoneoscopy permits a more direct exposure of the adrenal gland, without violating the peritoneum, and a close vision to the main vessels. We believe that this technique is a valid option for pediatric patients with small adrenal lesions.

This paper analyzes the role of Corporate Social Responsibility (CSR) in the hotel sector of Mérida State (Venezuela) and its contribution to the sociocultural dimension of local development. A theoretical framework is presented that supports the subsequent empirical analysis. Summary is made of the public policies related to CSR and the tourism sector, and the characteristics of the State of Merida where the tourism activity that is going to be analyzed is carried out. Next, the empirical part is developed. The managers of the hotels were surveyed, using a questionnaire adapted from indicators of the ETHOS Institute. Average values of the different items are obtained by dimensions, themes and indicators and a logistic regression model is applied. The Governance and Management dimension has high compliance with anti-corruption practices. In the Social dimension, three indicators are highly valued (relationship with consumers, monitoring the impact on human rights and relations with employees) and three less valued (support for the development of suppliers, commitment to the community and professional development). Additionally, three aspects of CSR contribute to the sociocultural dimension (vision and strategy, human rights and sustainable use of resources) and represent 58% of the larger hotels, with most category, and longest seniority.

Objective: Traumatic brain injury (TBI) clinical practice guidelines for pain management and rehabilitation support the use of nonpharmacologic complementary and integrative health (CIH) modalities, such as acupuncture for remediating pain. Barriers to delivering CIH modalities, such as acupuncture warrant examination. The objective of this study is to explore provider perspectives on challenges to accessing acupuncture treatment for chronic pain in persons with TBI and describe differences across health care settings. Setting: Civilian, Veterans Affairs (VA), and Department of Defense health care systems. Participants: Health care providers (n = 145) were recruited from November 2022 to March 2023 via email through professional organizations and health care systems. Design: Descriptive cross-sectional self-report online survey. Main Measures: A survey assessed barriers using a 5-point Likert scale (always a barrier to never a barrier) using the Levesque Access to Care framework. Results: Of the 137 participants who provided information on setting, 86 (63%) worked in civilian health care; 47 (34%) worked in the Department of VA; and 4 (2.6%) in the Department of Defense (8 were missing data). Overall, providers endorsed all ten items as being barriers to accessing acupuncture treatment. However, these barriers were more statistically more frequently reported for civilian providers compared with VA providers for six of the 10 items, including lack of caregiver support (p < 0.0001); own knowledge and understanding of the treatment (p = 0.0025); health care setting culture discourages the treatment (p = 0.0181); lack of qualified providers (p = 0.0467); insurance does not cover (p < 0.0001), and patient cannot afford (p < 0.0001). VA provider respondents were more likely to answer all six items, as "Rarely/Never a Barrier," while providers in a civilian setting were more likely to respond "Always/Frequently" or "Sometimes" a barrier. Conclusion: Results reflect the cultural, organizational, and structural differences that make acupuncture more accessible within the VA. understanding barriers to delivering care is critical to inform implementation strategy mapping efforts, to tailor strategies that are aimed to increase access and engagement with acupuncture treatment in civilian health care settings. [ABSTRACT FROM AUTHOR]

Objectives: Preliminary examination of emotional awareness/expression relationships with pain in people with traumatic brain injury (TBI) and chronic pain (CP) and exploration of psychological factors as mediators or moderators of these relationships. Methods: Cross-sectional study in adults (N = 59) with chronic TBI and CP using Toronto Alexithymia Scale-20 Difficulty Identifying and Describing Feelings subscales; Ambivalence over Emotional Expressiveness Questionnaire; Emotional Approach Coping Scale; PROMIS Pain Intensity and Pain Interference scales, Michigan Body Map (pain widespreadness); headache frequency; Pain Catastrophizing Scale; Brief Symptom Inventory-18 (psychological distress), and Post-traumatic Stress Checklist-Civilian. Results: Difficulty Identifying Feelings was positively associated with pain intensity, pain interference, and headache frequency. Difficulty Describing Feelings was positively correlated with pain interference and headache frequency. Emotional Approach Coping was inversely correlated with headache frequency. Emotional awareness/expression relationships with pain outcomes were mediated by Pain Catastrophizing; Difficulty Describing Feelings relationships with Pain Interference and headache frequency were mediated by psychological distress; and Difficulty Describing Feelings associations with Pain Interference were mediated by post-traumatic stress. No moderators were identified. Conclusion: These preliminary findings suggest that emotional awareness/expression is linked to pain in adults with TBI and CP, which may be connected via pain catastrophizing and psychological distress. If longitudinal studies with larger samples produce similar findings, researchers should explore training emotional awareness/expression for possible pain management after TBI. [ABSTRACT FROM AUTHOR]

Purpose: Patients and caregivers in Singapore experience issues managing dysphagia care at home following hospital discharge, and they prioritized improving access to postdischarge dysphagia care and support. Hence, a postdischarge dysphagia telehealth service was developed. This study aimed to evaluate the feasibility of this service by examining patient and service outcomes, preliminary costs, and consumer satisfaction. Method: Patients with dysphagia and their caregivers attended one or more telehealth sessions over the initial month post--hospital discharge. Reviews of dietary adherence and preparation, swallowing function, and therapy progress were conducted. If needed, clinical support and intervention were provided. Data related to patient and service outcomes, preliminary costs, and consumer satisfaction were collected and analyzed using descriptive statistics and content analysis. Results: Twenty patients attended 42 telehealth sessions. No support was provided during 10 sessions, minor support was provided during 13 sessions, and major support and intervention were provided to address patient and swallowing safety during 19 sessions. Out of 20 patients, 19 required support and intervention during the first week postdischarge, but they experienced fewer issues with each subsequent session. They were highly satisfied with the service. The average session duration was 29.6 min. No sessions were cancelled. This service can be delivered with minimal additional health service resources and at a low cost to consumers. Conclusions: This service is feasible, cost-effective, and well accepted by consumers. It facilitates early identification and management of swallowing and patient safety during the initial month post--hospital discharge. Wider implementation of this service model should be considered. Supplemental Material: https://doi.org/10.23641/asha.27327345 [ABSTRACT FROM AUTHOR]

There is growing evidence that long-term outcomes after traumatic brain injury (TBI) are more dynamic than stable. People continue to change, both improving and declining, many years postinjury. Research, practice, and medical education have not yet fully embraced the implications of TBI as a chronic, dynamic condition. In 2020, the National Institute on Disability Independent Living and Rehabilitation Research funded the BeHEALTHY project to develop a model for long-term support of persons with chronic brain injury. Based on initial reviews of the available evidence and expert input from researchers, clinicians, and persons with lived experience, the BeHEALTHY model was proposed. Among existing chronic disease treatment models, Wagner's Chronic Care Model was selected as a starting point, with several critical refinements. The BeHEALTHY model endorses a person-centered approach, recognizing the individual with brain injury, and their social support system, as the primary source of goals in care planning. The model also acknowledges the critical importance of self -management and the need for health care programs to actively promote self-direction by the person using their social supports. The model also recognizes that outcomes are not determined solely by the person and the injury incurred but also by the environment in which a person lives and recovers. The importance of integrating health care with community resources is underscored by embracing environmental influences as a shared responsibility of the community and the health care system. This article recounts the impetus for developing the BeHEALTHY model and describes those it is intended to serve and its structural features and core components. [ABSTRACT FROM AUTHOR]

Many clinicians believe that residual impairments due to traumatic brain injury (TBI) are static once initial recovery has plateaued. That is, the effects of the injury are not expected to change significantly over the remainder of a person's life. This assumption has been called into question by several independent longitudinal studies showing that the long-term course of TBI may be better characterized as dynamic rather than static. Health care services that recognize brain injury as a chronic condition would encourage education on self-management to improve or protect health, as well as proactive health care that anticipates common co-morbidities. Those who have had a TBI would be encouraged to engage in lifestyles that optimize wellness. Almost all developed countries commit additional public health resources to addressing chronic conditions. In the United States, specific benefits are available from health insurance plans, particularly Medicare and Medicaid, for persons experiencing chronic health conditions. Potentially the most important benefit would derive from health care practitioners becoming aware of the dynamic nature of chronic brain injury and thus being more attentive to how their patients could be better served to optimize improvement and minimize decline. Recognition of TBI as a chronic condition would not only focus more resources on problems associated with living with brain injury but would also enhance both the public's and professionals' awareness of how to optimize the health and well-being of persons living with the effects of TBI. [ABSTRACT FROM AUTHOR]