Temporal organization of narrative recall is present but attenuated in adults with hippocampal amnesia.

Studies of the impact of brain injury on memory processes often focus on the quantity and episodic richness of those recollections. Here, we argue that the organization of one's recollections offers critical insights into the impact of brain injury on functional memory. It is well-established in studies of word list memory that free recall of unrelated words exhibits a clear temporal organization. This temporal contiguity effect refers to the fact that the order in which word lists are recalled reflects the original presentation order. Little is known, however, about the organization of recall for semantically rich materials, nor how recall organization is impacted by hippocampal damage and memory impairment. The present research is the first study, to our knowledge, of temporal organization in semantically rich narratives in three groups: (1) Adults with bilateral hippocampal damage and severe declarative memory impairment, (2) adults with bilateral ventromedial prefrontal cortex (vmPFC) damage and no memory impairment, and (3) demographically matched non-brain-injured comparison participants. We find that although the narrative recall of adults with bilateral hippocampal damage reflected the temporal order in which those narratives were experienced above chance levels, their temporal contiguity effect was significantly attenuated relative to comparison groups. In contrast, individuals with vmPFC damage did not differ from non-brain-injured comparison participants in temporal contiguity. This pattern of group differences yields insights into the cognitive and neural systems that support the use of temporal organization in recall. These data provide evidence that the retrieval of temporal context in narrative recall is hippocampal-dependent, whereas damage to the vmPFC does not impair the temporal organization of narrative recall. This evidence of limited but demonstrable organization of memory in participants with hippocampal damage and amnesia speaks to the power of narrative structures in supporting meaningfully organized recall despite memory impairment.

Maternity Care Deserts in Louisiana and Breastfeeding Initiation.

BACKGROUND: Breastfeeding provides physical, psychological, and immunological benefits to both the mother and infant, but breastfeeding rates are suboptimal. The purpose of this study was to examine whether residing in a maternity care desert (a county with no hospital offering obstetric care and no OB/GYN or certified nurse midwife providers) was associated with lower breastfeeding rates among birthing people in Louisiana from 2019 to 2020. METHODS: Data provided by the March of Dimes were used to classify Louisiana parishes by level of access to maternity care. Using data on all live births provided by the Louisiana Office of Vital Records (n = 112,151), we fit adjusted modified Poisson regression models with generalized estimating equations and exploratory geospatial analysis to examine the association between place of residence and breastfeeding initiation and racial disparities in initiation. We conducted a secondary within-group analysis by fitting the fully adjusted model stratified by race/ethnicity for non-Hispanic white and non-Hispanic Black birthing people. RESULTS: We found that residing in a parish with limited (odds ratio [OR] = 0.87; 95% confidence interval [CI] [0.77, 0.99]) to no access (OR = 0.88; 95% CI [0.80, 0.97]) was significantly associated with lower breastfeeding initiation rates. The within-group analysis determined that both non-Hispanic Black and non-Hispanic white birthing people residing in a parish with limited or no maternity care access had lower breastfeeding initiation rates. CONCLUSION: Reducing rural and racial inequities in breastfeeding may require structural changes and investments in infrastructure to deliver pregnancy care.

Multilevel Barriers to Long-Acting Reversible Contraceptive Uptake: A Narrative Review.

Unintended pregnancies, which occur in almost half (45%) of all pregnancies in the United States, are associated with adverse health and social outcomes for the infant and the mother. The risk of unintended pregnancies is significantly reduced when women use long-acting reversible contraceptives (LARCs), namely intrauterine devices and implants. Although LARCs are highly acceptable to women at risk of unintended pregnancies, barriers to accessing LARCs hinder its uptake. These barriers are greater among racial and socioeconomic lines and persist within and across the intrapersonal, interpersonal, institutional, and policy levels. A synthesis of these barriers is unavailable in the current literature but would be beneficial to health care providers of reproductive-aged women, clinical managers, and policymakers seeking to provide equitable reproductive health care services. The aim of this narrative review was to aggregate these complex and overlapping barriers into a concise document that examines: (a) patient, provider, clinic, and policy factors associated with LARC access among populations at risk of unintended pregnancy and (b) the clinical implications of mitigating these barriers to provide equitable reproductive health care services. This review outlines numerous barriers to LARC uptake across multiple levels and demonstrates that LARC uptake is possible when the woman is informed of her contraceptive choices and when financial and clinical barriers are minimized. Equitable reproductive health care services entail unbiased counseling, a full range of contraceptive options, and patient autonomy in contraceptive choice.

A Tale of 8 Cities: Pediatric Critical Care Redeployment to Adult Care During Wave 1 of COVID-19.

BACKGROUND: Pediatric hospital resources including critical care faculty (intensivists) redeployed to provide care to adults in adult ICUs or repurposed PICUs during wave 1 of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVES: To determine the magnitude of pediatric hospital resource redeployment and the experience of pediatric intensivists who redeployed to provide critical care to adults with COVID-19. METHODS: A mixed methods study was conducted at 9 hospitals in 8 United States cities where pediatric resources were redeployed to provide care to critically ill adults with COVID-19. A survey of redeployed pediatric hospital resources and semistructured interviews of 40 redeployed pediatric intensivists were simultaneously conducted. Quantitative data were summarized as median (interquartile range) values. RESULTS: At study hospitals, there was expansion in adult ICU beds from a baseline median of 100 (86-107) to 205 (108-250). The median proportion (%) of redeployed faculty (88; 66-100), nurses (46; 10-100), respiratory therapists (48; 18-100), invasive ventilators (72; 0-100), and PICU beds (71; 0-100) was substantial. Though driven by a desire to help, faculty were challenged by unfamiliar ICU settings and culture, lack of knowledge of COVID-19 and fear of contracting it, limited supplies, exhaustion, and restricted family visitation. They recommended deliberate preparedness with interprofessional collaboration and cross-training, and establishment of a robust supply chain infrastructure for future public health emergencies and will redeploy again if asked. CONCLUSIONS: Pediatric resource redeployment was substantial and pediatric intensivists faced formidable challenges yet would readily redeploy again.

A review of trauma laparotomy at Christchurch Hospital.

AIM: Trauma is one of the leading causes for years of life lost in New Zealand. Its costs to acute care services alone amount to hundreds of millions per year, and it is the main contributor to years of life lost in patients under 40. Since 2016, the Canterbury Trauma Registry has been actively collecting data on all major traumas presenting to Christchurch hospital. This study will aim to define the demographics of trauma laparotomy patients presenting to Christchurch Hospital, and to assess the relationship between missed injuries (MI) on computed tomography (CT) imaging and time to theatre. METHODS: A retrospective study of trauma patient from June 2016 to February 2019. Data for major trauma patients were supplied from the Canterbury Trauma Registry. Data for minor trauma patients were individually selected from the online operative procedures registry. Non-parametric analysis was undertaken with an independent sample Kruskal-Wallis test alongside pairwise comparisons. RESULTS: Sixty trauma laparotomies were performed over 36 months, predominantly male gender (43/60) and under 40 years of age (39/60). Motor vehicle accident (31/60) and knife injuries (10/60) were the most common mechanisms. Fourty-three out of sixty patients received pre-operative CT scans. Fourty out of sixty patients received a CT scan within 2 hours. Large bowel injuries (four cases) and small bowel (three cases) were the most common missed injuries on pre-operative CT. Small bowel injuries are the predominate injury in blunt trauma while diaphragm and liver injuries predominated in penetrating trauma. Four patients did not undergo laparotomy within 24 hours. There is a statistically significant difference (p<0.001) in time to operating theatre between patients with no pre-operative CT and patients with no MI on CT and patients with MI on CT. There is no statistically significant difference (p<0.231) in time to operating theatre in patients with no MI on CT and patients with MI on CT. CONCLUSION: There is no statistically significant difference in time to operation between trauma laparotomy patients with no MI on pre-operative CT to patients with MI on pre-operative CT. There are recognisable injury patterns in trauma patients. There are delays in trauma patients receiving prompt CT imaging. CT imaging can miss life-threatening injury, close patient observation and further examination, and imaging or operative therapy may be required even if initial imaging is reassuring.

Are two occupational therapists better than one? Occupational therapists' perspectives of intra-disciplinary practice within community health.

INTRODUCTION: Intra-disciplinary practice is rarely discussed in occupational therapy and the broader health-care literature. Community-based occupational therapists often work autonomously in clients' homes and consequently have limited access to routine intra-disciplinary practices. Additionally, the community-based role covers a large scope of practice requiring comprehensive expertise. This study aimed to describe occupational therapists' perspectives on intra-disciplinary practice within community health settings. METHODS: This study utilised an online cross-sectional survey design, collecting quantitative and qualitative data to explore perspectives of occupational therapists working within Australian community health services. Quantitative data were analysed using descriptive statistics. Qualitative data were analysed using thematic analysis. Both forms of data were compared and contrasted. RESULTS/FINDINGS: Eighty occupational therapists completed the survey. Seventy-eight participants (97%) previously used or currently use intra-disciplinary practice in their workplace. Participants predominantly consult their peers when client needs are perceived as complex. Participants indicated that intra-disciplinary practice can benefit the client, therapist, and workplace. Enablers and barriers to the use of intra-disciplinary practice had overlapping themes, including access to therapists, attitudes towards intra-disciplinary practice, management support, and funding influences. Most participants expressed a desire to utilise intra-disciplinary practices (n = 70, 87%) and were also likely or extremely likely to incorporate it into their clinical work (n = 73, 91%). Participants who did not want to utilise intra-disciplinary practices or who were unsure provided reasons related to cost, practice inefficiencies, and being uncertain of the benefit. CONCLUSIONS: Occupational therapists perceive intra-disciplinary practice as beneficial for problem-solving and an opportunity for knowledge sharing that supports therapist confidence with clinical reasoning. Conversely, some therapists believe its use may lead to client confusion, a greater need for communication and coordination among therapists, and that power differentials between therapists may discourage equal collaboration. Greater understanding of intra-disciplinary practice will help guide how it is used and supported in community health settings.

MEMCONS: How Contemporaneous Note-Taking Shapes Memory for Conversation.

Written memoranda of conversations, or memcons, provide a near-contemporaneous record of what was said in conversation, and offer important insights into the activities of high-profile individuals. We assess the impact of writing a memcon on memory for conversation. Pairs of participants engaged in conversation and were asked to recall the contents of that conversation 1 week later. One participant in each pair memorialized the content of the interaction in a memcon shortly after the conversation. Participants who generated memcons recalled more details of the conversations than participants who did not, but the content of recall was equally and largely accurate for both participants. Remarkably, only 4.7% of the details of the conversation were recalled by both of the partners after a week delay. Contemporaneous note-taking appears to enhance memory for conversation by increasing the amount of information remembered but not the accuracy of that information. These findings have implications for evaluating the testimony of participants on conversations with major political or legal ramifications.

The COVID-19 pandemic's impact on all-cause mortality disparities in Medicare: By race, income, chronic health, mental/behavioral health, disability.

BACKGROUND: The Medicare-enrolled population is heterogeneous across race, ethnicity, age, dual eligibility, and a breadth of chronic health, mental and behavioral health, and disability-related conditions, which may be differentially impacted by the COVID-19 pandemic. OBJECTIVE: To quantify changes in all-cause mortality prior-to and in the first year of the COVID-19 pandemic across Medicare's different sociodemographic and health-condition subpopulations. METHODS: This observational, population-based study used stratified bivariate regression to investigate Medicare fee-for-service subpopulation differences in pre-pandemic (i.e., 2019 versus 2016) and pandemic-related (2020 versus 2019) changes in all-cause mortality. RESULTS: All-cause mortality in the combined Medicare-Advantage (i.e., managed care) and fee-for-service beneficiary population improved by a relative 1% in the ten years that preceded the COVID-19 pandemic, but then escalated by a relative 15.9% in 2020, the pandemic's first year. However, a closer look at Medicare's fee-for-service subpopulations reveals critical differences. All-cause mortality had actually been worsening prior to the pandemic among most psychiatric and disability-related condition groups, all race and ethnicity groups except White Non-Hispanic, and Medicare-Medicaid dual-eligible (i.e., low-income) beneficiaries. Many of these groups then experienced all-cause mortality spikes in 2020 that were over twice that of the overall Medicare fee-for-service population. Of all 61 chronic health conditions studied, beneficiaries with schizophrenia were the most adversely affected, with all-cause mortality increasing 38.4% between 2019 and 2020. CONCLUSION: This analysis reveals subpopulation differences in all-cause mortality trends, both prior to and in year-one of the COVID-19 pandemic, indicating that the events of 2020 exacerbated preexisting health-related inequities.

Inter-rater agreement when linking stroke interventions to the extended international classification of functioning, disability and health core set for stroke.

PURPOSE: To uncover the factors that influence inter-rater agreement when extracting stroke interventions from patient records and linking them to the relevant categories in the Extended International Classification of Functioning, Disability and Health Core Set for Stroke. METHOD: Using 10 patient files, two linkers independently extracted interventions and linked the target of the intervention to relevant functions in the ICF. The percentage agreement of extracted interventions and the ICF codes was calculated. Non-matching interventions and codes were further analysed to determine the reasons for poor agreement. RESULTS: A total of 518 interventions were extracted, with 44.01% agreement between the two linkers. Of the non-agree codes and interventions, 43.79% were due to mismatched ICF codes and 56.20% were due to mismatched interventions. Differences were due to linkers (a) extracting interventions from different parts of the patient note (b) differences in interpreting the target of the intervention, and (c) choosing a different code with similar meaning. CONCLUSION: Greater reliability when linking interventions to ICF codes can be achieved by; health services using a consistent progress note that uses ICF language, recording the intervention aim, linkers knowing the aims of each discipline's interventions and using multiple reliability checks and analysis to inform the linking method.Implications for rehabilitationLinking intervention targets to the ICF and to the ICHI is an emerging research field.Development of trustworthy inter-rater reliability methods is needed to achieve its potential to demonstrate the equity, quality and effectiveness of interventions.Independent linking of patient notes to the ICF can identify factors that impact inter-rater reliability.When writing patient notes, health professionals should use a consistent format that identifies the functional target of the intervention using ICF terms.

Keto-Bezoar: Adverse Event Related to Initiation of Ketogenic Diet in an Infant.

The ketogenic diet is frequently used as part of the treatment regimen for pediatric patients with refractory epilepsy. This diet is generally well tolerated, with constipation being the most described side effect. This case highlights a previously undocumented severe complication of a "keto-bezoar" formation related to the initiation of the ketogenic diet in a young infant.

Racial Differences in the Risk of Prenatal Depression Among Women Experiencing Childhood and Adult Stressors.

INTRODUCTION: Stress exposure during a woman's own childhood and adulthood likely elevate risk of prenatal depression (PND). However, most PND screening tools fail to assess for events prior to conception. This study examined the differential effects of adverse childhood experiences (ACE) and adult life stressors on PND. METHODS: This cross-sectional study was conducted among 199 racially diverse pregnant women, ages 18 to 43, recruited from clinics and ongoing university-based studies between 2012 and 2018. The ACE Scale assessed maternal childhood trauma exposure. Validated scales examining subjective stressors assessed for chronic adult stressors. PND was assessed with the Edinburgh Depression Scale, with the Rini Pregnancy-Related Anxiety Scale as a covariate. Associations were measured using multivariable linear regression modeling. Results were stratified by self-identified Black or white race. RESULTS: Among 199 participants, mean age was 26.8 years and 67.8% were Black. Controlling for age, race, education, and prenatal anxiety, all participants reporting both childhood trauma and adult stressors were at increased risk for PND (p < 0.0001). PND risk was increased among Black women with childhood stressors (p < 0.01) or three or more adult stressors (p < 0.0001) and among White women following any number of adult stressors (p < 0.001). DISCUSSION: These findings highlight the importance of cumulative exposure to stress and trauma across the life span as indicators of risk for PND. Black and white participants had differential development of risk, depending on timing and number of exposures. Prenatal depression risk screening during routine prenatal care should include an assessment of current and historical trauma and stressors.

Delivering Health Information to Parents via a Theory-Informed SMS-Based Intervention: Development and Results from a Pilot Study.

INTRODUCTION: Short message service (SMS), or text-based, health interventions offer a promising opportunity to deliver health education and have been shown to improve diet and exercise. However, few are theory-based or target low-income parents. This pilot study, informed by the Theory of Planned Behavior (TPB), primarily sought to determine if health education delivered via SMS was feasible and acceptable to low-income parents of young children. METHODS: Using a one-group, pre- to post-test study design to assess a 12-week SMS-based health education program, parents enrolled in a health-related program at an early childhood development center for low-income families were sent three text messages per week that corresponded to a weekly diet or physical activity-related theme. Surveys assessed pre-post changes in TPB constructs and collected program feedback. RESULTS: Among the 119 eligible parents invited to participate, 109 were sent all text messages for the duration of the study. Participants were mostly Black (98.9%), 25-39 years old (83.9%), female (93.8%), and in single-parent households (63.8%). More than half (n = 59) completed the pre-survey, answered a bi-directional program text, or completed the post-survey. Twelve participants completed both the pre- and post-survey and at least one bi-directional text. Post-survey results revealed that most participants liked the program design and enjoyed their experience with the program. CONCLUSIONS: SMS-based interventions can simplify delivery of health information to low-income parents of young children. Although engagement was low, retention was high, and feedback was largely positive.

Pleiotropic Effects of Statins: New Therapeutic Approaches to Chronic, Recurrent Infection by Staphylococcus aureus.

An emergent approach to bacterial infection is the use of host rather than bacterial-directed strategies. This approach has the potential to improve efficacy in especially challenging infection settings, including chronic, recurrent infection due to intracellular pathogens. For nearly two decades, the pleiotropic effects of statin drugs have been examined for therapeutic usefulness beyond the treatment of hypercholesterolemia. Interest originated after retrospective studies reported decreases in the risk of death due to bacteremia or sepsis for those on a statin regimen. Although subsequent clinical trials have yielded mixed results and earlier findings have been questioned for biased study design, in vitro and in vivo studies have provided clear evidence of protective mechanisms that include immunomodulatory effects and the inhibition of host cell invasion. Ultimately, the benefits of statins in an infection setting appear to require attention to the underlying host response and to the timing of the dosage. From this examination of statin efficacy, additional novel host-directed strategies may produce adjunctive therapeutic approaches for the treatment of infection where traditional antimicrobial therapy continues to yield poor outcomes. This review focuses on the opportunistic pathogen, Staphylococcus aureus, as a proof of principle in examining the promise and limitations of statins in recalcitrant infection.

State Abortion Policies and Maternal Death in the United States, 2015‒2018.

Objectives. To examine associations between state-level variation in abortion-restricting policies in 2015 and total maternal mortality (TMM), maternal mortality (MM), and late maternal mortality (LMM) from 2015 to 2018 in the United States. Methods. We derived an abortion policy composite index for each state based on 8 state-level abortion-restricting policies. We fit ecological state-level generalized linear Poisson regression models with robust standard errors to estimate 4-year TMM, MM, and LMM rate ratios and 95% confidence intervals (CIs) associated with a 1-unit increase in the abortion index, adjusting for state-level covariates. Results. States with the higher score of abortion policy composite index had a 7% increase in TMM (adjusted rate ratio [ARR] = 1.07; 95% CI = 1.02, 1.12) compared with states with lower abortion policy composite index, after we adjusted for state-level covariates. Among individual abortion policies, states with a licensed physician requirement had a 51% higher TMM (ARR = 1.51; 95% CI = 1.15, 1.99) and a 35% higher MM (ARR = 1.35; 95% CI = 1.09, 1.67), and states with restrictions on Medicaid coverage of abortion care had a 29% higher TMM (ARR = 1.29; 95% CI = 1.03, 1.61). Conclusions. Restricting access to abortion care at the state level may increase the risk for TMM.

Low but not moderate amounts of caffeine increase co-consumption of ethanol in C57BL/6J mice.

The increasingly popular combination of "energy drinks" containing high amounts of caffeine and alcohol has been shown to induce a stimulated, rather than sedated, state which may result in increased binge drinking and increased risk for alcohol-attributable accidents. We sought to examine consumption patterns of and withdrawal from alcohol and caffeine using a voluntary co-consumption animal model. Male and female adult C57BL/6J mice were given access to increasing doses of caffeine (0.01-0.05%) and/or alcohol (3-20%) in a two-bottle choice, intermittent access voluntary paradigm with fluid consumption recorded daily. Anxiety-like behavior during withdrawal was assessed via elevated plus maze or open field test in experiment 2. Increasing both alcohol and caffeine simultaneously in Experiment 1 resulted in no significant changes in co-consumption compared to mice given access to only alcohol or caffeine. Experiment 2 held caffeine concentration steady while slowly increasing alcohol content and resulted in mice consuming more alcohol when it was consumed in tandem with low dose caffeine. Both male and female mice consumed more caffeine when it was paired with alcohol; however, no significant differences were observed during withdrawal behavior. These results suggest that caffeine may dose-dependently positively influence alcohol consumption in mice and echo clinical literature suggesting that caffeine and alcohol together may result in a heightened state of stimulation and lead to further binge drinking. The intermittent access paradigm affords increased translational validity regarding investigations of alcohol and caffeine co-consumption and may be useful in identifying the neurobiological mechanisms concerning co-consumption of such substances.

Inner Nuclear Membrane Asi Ubiquitin Ligase Catalytic Subunits Asi1p and Asi3p, but not Asi2p, confer resistance to aminoglycoside hygromycin B in Saccharomyces cerevisiae.

The heterotrimeric Asi ubiquitin ligase (encoded by ASI1, ASI2, and ASI3) mediates protein degradation in the inner nuclear membrane in Saccharomyces cerevisiae. Asi1p and Asi3p possess catalytic domains, while Asi2p functions as an adaptor for a subset of Asi substrates. We hypothesized the Asi complex is an important mediator of protein quality control, and we predicted that Asi would be required for optimal growth in conditions associated with elevated abundance of aberrant proteins. Loss of Asi1p or Asi3p, but not Asi2p, sensitized yeast to hygromycin B, which promotes translational infidelity by distorting the ribosome A site. Surprisingly, loss of quality control ubiquitin ligase Hul5p did not sensitize yeast to hygromycin B. Our results are consistent with a prominent role for an Asi subcomplex that includes Asi1p and Asi3p (but not Asi2p) in protein quality control.

Exploring admissions for Maori presenting with major trauma at Christchurch Hospital.

Injury remains one of the leading causes of years of life lost worldwide. In 2015, the New Zealand Major Trauma Registry was developed to provide a comprehen-sive data registry within New Zealand for looking at the outcomes and determinants of major trauma. It has published yearly major trauma reports since its founding.

What a headache! Reviewing mild traumatic brain injury management in a new trauma service.

AIM: Mild traumatic brain injury (mild TBI) is a common, poorly managed condition with an underestimated impact and inadequate follow-up. This study aimed to assess local practice in terms of assessment and follow-up. METHODS: A retrospective review of all patients presenting to Christchurch Hospital between 1 August 2019 and 30 September 2019 with ICD-10 coded diagnosis of head trauma was conducted. Patients younger than 16 or older than 80 years who had a concurrent medical illness or who did not meet diagnostic criteria for mild TBI were excluded. This was to minimise diagnostic uncertainty where patients may have had mild TBI like symptoms due to alternate pathology. Primary outcomes included documentation of post-traumatic amnesia (PTA) with the Abbreviated Westmead Post-Traumatic Amnesia Scale (A-WPTAS), provision of mild TBI information, the proportion referred for follow-up and the proportion followed up at the mild TBI clinic. Demographic data included age, sex, ethnicity, mechanism of injury, admission service and rate of admission. RESULTS: A total of 525 patients were identified, with 239 patients included. Median age was 29 years (IQR 22-50) and 65.3% (n=156) were male. The most common mechanisms of injury were falls (25.5%, n=61) and assault (25.5%, n=61). The most-commonly recorded diagnosis was head injury (41.4%, n=99), followed by concussion (34.3%, n=82). A-WPTAS was documented for 4.2% of patients (n=10). The provision of written mild TBI advice to patients was documented in 61.5% of cases (n=147). On discharge, no follow-up was documented for 63.6% of patients (n=152). In those with documented follow-up, 23.4% (n=56) was with a general practitioner (GP) and 5.4% (n=13) were referred to mild TBI clinic. Review of Accident Corporation Commission (ACC) records identified claims for 80.3% (n=192) of the cohort. Of these, 11.5% (n=22) received a payment for mild TBI services and 2.1% (n=4) had their service provided by Christchurch Hospital. CONCLUSION: The results suggest that current management of mild TBI at Christchurch Hospital needs improvement. Accurate diagnostic coding allows patients to access ACC-funded clinics. The utilisation rates of these clinics confirm that the frequency of specialist follow-up is low, which is in keeping with the international literature. Furthermore, given the strongly predictive nature of post-traumatic amnesia for outcomes, the low rate of A-WPTAS assessment is concerning. These results suggest that a mild TBI protocol is needed to standardise assessment, management and follow-up.

Safe harbor-targeted CRISPR-Cas9 homology-independent targeted integration for multimodality reporter gene-based cell tracking.

Imaging reporter genes provides longitudinal information on the biodistribution, growth, and survival of engineered cells in vivo. A translational bottleneck to using reporter genes is the necessity to engineer cells with randomly integrating vectors. Here, we built homology-independent targeted integration (HITI) CRISPR-Cas9 minicircle donors for precise safe harbor-targeted knock-in of fluorescence, bioluminescence, and MRI (Oatp1a1) reporter genes. Our results showed greater knock-in efficiency using HITI vectors compared to homology-directed repair vectors. HITI clones demonstrated functional fluorescence and bioluminescence reporter activity as well as significant Oatp1a1-mediated uptake of the clinically approved MRI agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid. Contrast-enhanced MRI improved the conspicuity of both subcutaneous and metastatic Oatp1a1-expressing tumors before they became palpable or even readily visible on precontrast images. Our work demonstrates the first CRISPR-Cas9 HITI system for knock-in of large DNA donor constructs at a safe harbor locus, enabling multimodal longitudinal in vivo imaging of cells.