Programmable RNA sensing for cell monitoring and manipulation.

RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencing technologies and the massive accumulation of transcriptome datasets across the life sciences1,2, the dearth of technologies that use RNAs to observe and manipulate cell types remains a bottleneck in biology and medicine. Here we describe CellREADR (Cell access through RNA sensing by Endogenous ADAR), a programmable RNA-sensing technology that leverages RNA editing mediated by ADAR to couple the detection of cell-defining RNAs with the translation of effector proteins. Viral delivery of CellREADR conferred specific cell-type access in mouse and rat brains and in ex vivo human brain tissues. Furthermore, CellREADR enabled the recording and control of specific types of neurons in behaving mice. CellREADR thus highlights the potential for RNA-based monitoring and editing of animal cells in ways that are specific, versatile, simple and generalizable across organ systems and species, with wide applications in biology, biotechnology and programmable RNA medicine.

Clinical outcomes among initial survivors of cryptogenic new-onset refractory status epilepsy (NORSE).

OBJECTIVE: New-onset refractory status epilepticus (NORSE) is a rare but severe clinical syndrome. Despite rigorous evaluation, the underlying cause is unknown in 30%-50% of patients and treatment strategies are largely empirical. The aim of this study was to describe clinical outcomes in a cohort of well-phenotyped, thoroughly investigated patients who survived the initial phase of cryptogenic NORSE managed in specialist centers. METHODS: Well-characterized cases of cryptogenic NORSE were identified through the EPIGEN and Critical Care EEG Monitoring Research Consortia (CCEMRC) during the period 2005-2019. Treating epileptologists reported on post-NORSE survival rates and sequelae in patients after discharge from hospital. Among survivors >6 months post-discharge, we report the rates and severity of active epilepsy, global disability, vocational, and global cognitive and mental health outcomes. We attempt to identify determinants of outcome. RESULTS: Among 48 patients who survived the acute phase of NORSE to the point of discharge from hospital, 9 had died at last follow-up, of whom 7 died within 6 months of discharge from the tertiary care center. The remaining 39 patients had high rates of active epilepsy as well as vocational, cognitive, and psychiatric comorbidities. The epilepsy was usually multifocal and typically drug resistant. Only a minority of patients had a good functional outcome. Therapeutic interventions were heterogenous during the acute phase of the illness. There was no clear relationship between the nature of treatment and clinical outcomes. SIGNIFICANCE: Among survivors of cryptogenic NORSE, longer-term outcomes in most patients were life altering and often catastrophic. Treatment remains empirical and variable. There is a pressing need to understand the etiology of cryptogenic NORSE and to develop tailored treatment strategies.

Patterns & Predictors of Telehealth Utilization Among Individuals Who Use Substances: Implications for the Future of Virtual Behavioral Health Services.

Telehealth dramatically expanded during the COVID-19 pandemic, but there remains a dearth of literature examining how this service modality is utilized by individuals who use substances. This study examined patterns of telehealth use and individual level sources of variation among clients receiving counseling in an outpatient substance use clinic in early 2021 (n = 370). Univariate statistics described the percentage of counseling visits delivered via telehealth. OLS regression explored individual level demographic and clinical characteristics that predicted greater telehealth utilization. Overall, more than two thirds (86%) of counseling visits were conducted via telehealth. Individuals with unstable housing or with a co-occurring serious mental illness used less telehealth. Findings suggest that while telehealth appears to be an acceptable way to deliver substance use counseling, patterns varied among vulnerable subgroups. As telehealth becomes further integrated into behavioral health services delivery, it is critical to uncover sources of this variation and identify potential solutions.

The Impact of Structural Integration on Clinical Outcomes among Individuals with Serious Mental Illness and Chronic Illness.

Though considered a best practice, there is substantial variation in how integrated behavioral health (IBH) services are structured. This study examined the impact of IBH structure on health outcomes among individuals with serious mental illness (SMI) and chronic disease receiving care in community health centers (CHCs). Data from the ADVANCE network identified 8,548 individuals with co-occurring SMI diabetes and 16,600 with an SMI and hypertension. Logistic regression tested whether IBH type impacted disease specific health outcomes among these populations. Among those with diabetes or hypertension, colocated care was associated with better health outcomes related to HbA1c, blood pressure control, and BMI compared to less coordinated and unintegrated care, though there was significant variation in this relationship across SMI diagnoses. Results reflect that colocation of primary care and behavioral health may improve outcomes for individuals with bipolar disorder or major depression and chronic disease, but that CHC-based integrated care may not be optimized for individuals with schizophrenia.

The Impact of Delivery Reform on Health Information Exchange with Behavioral Health Providers: Results from a National Representative Survey of Ambulatory Physicians.

Health information exchange (HIE) is an effective way to coordinate care, but HIE between health and behavioral health providers is limited. Recent delivery reform models, including the Accountable Care Organization (ACO) and Patient Centered Medical Home (PCMH) prioritize interprofessional collaboration, but little is known about their impact on behavioral health HIE. This study explores whether delivery reform participation affects behavioral health HIE among ambulatory health providers using pooled 2015-2019 data from the National Electronic Health Record Survey, a nationally representative survey of ambulatory physicians' technology use (n = 8,703). The independent variable in this analysis was provider participation in ACO, PCMH, Hybrid ACO-PCMH, or standard care. The dependent variable was HIE with behavioral health providers. Chi square analysis estimated unweighted rates of behavioral health HIE across reform models. Logistic regression estimated the impact of delivery reform participation on rates of behavioral health HIE. Unweighted estimates indicated that Hybrid ACO-PCMH providers had the highest rates of HIE (n = 330, 33%). In the fully adjust model, rates of HIE were higher among ACO (AOR = 2.66, p < .01), PCMH (AOR = 4.73, p < .001) and Hybrid ACO-PCMH participants (AOR = 5.55, p < .001) compared to standard care, but they did not significantly vary between delivery models. Physicians infrequently engage in HIE with behavioral health providers. Compared to standard care, higher rates of HIE were found across all models of delivery reform. More work is needed to identify common elements of delivery reform models that are most effective in supporting this behavior.

Overabundant deer and invasive plants drive widespread regeneration debt in eastern United States national parks.

Advanced regeneration, in the form of tree seedlings and saplings, is critical for ensuring the long-term viability and resilience of forest ecosystems in the eastern United States. Lack of regeneration and/or compositional mismatch between regeneration and canopy layers, called regeneration debt, can lead to shifts in forest composition, structure, and, in extreme cases, forest loss. In this study, we examined status and trends in regeneration across 39 national parks from Virginia to Maine, spanning 12 years to apply the regeneration debt concept. We further refined the concept by adding new metrics and classifying results into easily interpreted categories adapted from the literature: imminent failure, probable failure, insecure, and secure. We then used model selection to determine the potential drivers most influencing patterns of regeneration debt. Status and trends indicated widespread regeneration debt in eastern national parks, with 27 of 39 parks classified as imminent or probable failure. Deer browse impact was consistently the strongest predictor of regeneration abundance. The most pervasive component of regeneration debt observed across parks was a sapling bottleneck, characterized by critically low sapling density of native canopy species and significant declines in native canopy sapling basal area or density for most parks. Regeneration mismatches also threaten forest resilience in many parks, where native canopy seedlings and saplings were outnumbered by native subcanopy species, particularly species that are less palatable deer browse. The devastating impact of emerald ash borer eliminating ash as a native canopy tree also drove regeneration mismatches in many parks that contain abundant ash regeneration, demonstrating the vulnerability of forests that lack diverse understories to invasive pests and pathogens. These findings underscore the critical importance of an integrated forest management approach that promotes an abundant and diverse regeneration layer. In most cases, this can only be achieved through long-term (i.e., multidecadal) management of white-tailed deer and invasive plants. Small-scale disturbances that increase structural complexity may also promote regeneration where stress from deer and invasive plants is minimal. Without immediate and sustained management intervention, the forest loss we are already observing may become a widespread pattern in eastern national parks and the broader region.

Acceptability of Health Information Exchange and Patient Portal Use in Depression Care Among Underrepresented Patients.

BACKGROUND: Depression is often untreated or undertreated, particularly among underrepresented groups, such as racial and ethnic minorities, and individuals of lower socioeconomic status. Electronic health information exchange (HIE) is a recommended practice to improve care coordination and encourage patient engagement in services, but it remains underutilized in depression care. Understanding factors affecting acceptance and adoption of this technology among underrepresented patient populations is needed to increase dissemination of HIE within mental health treatment. OBJECTIVE: The present study aims to identify patient barriers and facilitators towards the acceptance of HIE within the context of depression treatment and to examine how HIE impacts depression-related care coordination and patient activation. DESIGN: Semi-structured qualitative interviews were conducted with 27 patients. PARTICIPANTS: Respondents were English-speaking adults (> 18) receiving depression treatment within a large, safety-net primary care clinic. APPROACH: A grounded theory approach was used to code and analyze data for emergent themes. Thematic analysis was guided by the Unified Theory of Acceptance and Use of Technology, a leading informatics theory used to predict end-user adoption of technology. KEY RESULTS: Respondents reported that HIE made depression care more convenient, transparent, and trustworthy. Though respondents desired greater access to their health records, stigma surrounding depression inhibited acceptance of electronic communication and information sharing. Confusing electronic interface also diminished perceived benefits of HIE. CONCLUSION(S): Respondents desire greater transparency in their depression care. While HIE was perceived to improve the overall quality of depression care, stigma associated with mental illness undermined more robust adoption of this technology among underserved populations.

Two Cases of Monkeypox-Associated Encephalomyelitis - Colorado and the District of Columbia, July-August 2022.

Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak.

Long-term trends indicate that invasive plants are pervasive and increasing in eastern national parks.

While invasive plant distributions are relatively well known in the eastern United States, temporal changes in species distributions and interactions among species have received little attention. Managers are therefore left to make management decisions without knowing which species pose the greatest threats based on their ability to spread, persist and outcompete other invasive species. To fill this gap, we used the U.S. National Park Service's Inventory and Monitoring Program data collected from over 1,400 permanent forest plots spanning 12 yr and covering 39 eastern national parks to analyze invasive plant trends. We analyzed trends in abundance at multiple scales, including plot frequency, quadrat frequency, and average quadrat cover. We examined trends overall, by functional group, and by species. We detected considerably more increasing than decreasing trends in invasive plant abundance. In fact, 80% of the parks in our study had at least one significant increasing trend in invasive abundance over time. Where detected, significant negative trends tended to be herbaceous or graminoid species. However, these declines were often countered by roughly equivalent increases in invasive shrubs over the same time period, and we only detected overall declines in invasive abundance in two parks in our study. Present in over 30% of plots and responsible for the steepest and greatest number of significant increases, Japanese stiltgrass (Microstegium vimineum) was the most aggressive invader in our study and is a high management priority. Invasive shrubs, especially Japanese barberry (Berberis thunbergii), Japanese honeysuckle (Lonicera japonica), multiflora rose (Rosa multiflora), and wineberry (Rubus phoenicolasius), also increased across multiple parks, and sometimes at the expense of Japanese stiltgrass. Given the added risks to human health from tick-borne diseases, invasive shrubs are a high management priority. While these findings provide critical information to managers for species prioritization, they also demonstrate the incredible management challenge that invasive plants pose in protected areas, particularly since we documented few overall declines in invasive abundance. As parks work to overcome deferred maintenance of infrastructure, our findings suggest that deferred management of natural resources, particularly invasive species, requires similar attention and long-term commitment to reverse these widespread increasing invasive trends.

Understanding Health Talk in Behavioral Health Encounters: A Qualitative Analysis.

Although physical and behavioral health conditions commonly cooccur, best practices making behavioral health treatment responsive to clients' health needs are limited. Particularly little is known about how physical health is addressed by clinicians within routine therapeutic treatment. This study describes the frequency and type of health talk occurring within integrated behavioral health sessions, and explores how this talk functions within ongoing therapeutic work. Participants in this study included 51 dyads of clinical social workers (n = 13) and clients (n = 51) receiving therapy within an integrated community health and behavioral health center. Therapy sessions were recorded and transcribed verbatim. Content analysis determined the frequency and content of health talk in sessions. Thematic analysis was used to understand the function of health talk within these visits. Health talk occurred in 92% (n = 47) of sessions. Clients initiated the majority of discussions. Talk about sleep (40%, n = 19), diet/exercise (35%, n = 16), and chronic health conditions (28%, n = 13) were most common. Health talk either complimented or conflicted with therapeutic work, depending on the topic discussed and when it occurred during session. Health talk changed the scope of therapeutic work by integrating care coordination into routine practice. Health talk was pervasive and was frequently initiated by clients, signaling its relevance to clients' recovery. Providers leveraged heath talk to complement their therapeutic work, but these strategies were not universally applied. Care coordination activities were a part of routine therapy. Practice and policy changes that support a more interdisciplinary approach to clinical work are needed.

H19X-encoded miR-424(322)/-503 cluster: emerging roles in cell differentiation, proliferation, plasticity and metabolism.

miR-424(322)/-503 are mammal-specific members of the extended miR-15/107 microRNA family. They form a co-expression network with the imprinted lncRNA H19 in tetrapods. miR-424(322)/-503 regulate fundamental cellular processes including cell cycle, epithelial-to-mesenchymal transition, hypoxia and other stress response. They control tissue differentiation (cardiomyocyte, skeletal muscle, monocyte) and remodeling (mammary gland involution), and paradoxically participate in tumor initiation and progression. Expression of miR-424(322)/-503 is governed by unique mechanisms involving sex hormones. Here, we summarize current literature and provide a primer for future endeavors.

Whose System is it Anyway? How Clients and Providers Evaluate the Impact of Session EHR Use on Communication in Mental Health Treatment.

Electronic health records are common in mental health settings. While providers often express concern that in-session computing will damage client-provider communication, some work suggests that clients do not share this worry. As the majority of this research has been conducted in medical settings, less is known about how clients evaluate in session computing in mental health treatment, and whether this pattern of discordance persists in this setting. This study describes and compares the perceived impact of in-session computing on communication in mental health treatment from the clients and provider perspective, and examined sources of variation in client ratings. Thirteen providers and 53 clients participated in this study, representing 53 unique client-provider dyads. Results suggest that providers perceived in-session computing as more harmful to communication than clients. Client ratings varied by race, age and visit type but were not influenced by how often the computer was used during session.

Delivering person-centered care with an electronic health record.

BACKGROUND: Electronic health records are now widely adopted in medical and behavioral health settings. While they have the potential to improve the quality of care, the research findings on their impact on clinical practice and outcomes have been mixed. This study explores how the electronic health record and its stage of development influenced the implementation of person-centered care planning in community mental health clinics. METHODS: The study was set in five community mental health clinics which utilized an EHR and had been trained in person-centered care planning. Using an objective quantitative measure of fidelity, the study examined fidelity to PCCP across time and by stage of EHR development. Data from focus groups, interviews with clinic leaders and consultant reports was analyzed to explore the process of implementation and the role of the electronic health record. RESULTS: All clinics demonstrated an overall increase in PCCP fidelity at the conclusion of the study period but there were significant differences in PCCP fidelity among clinics with EHRs in different stages of development. Electronic health records emerged as a significant implementation factor in the qualitative data with clinics being unable to individualize service plans and encountering technical difficulties. Barriers to person-centered care included drop-down boxes and pre-determined outcomes. Clinic responses included customizing their record or developing workarounds. CONCLUSIONS: The study demonstrated the need to align the electronic health record with a person-centered approach which includes individualizing information and orienting service plans to personal life goals. The ability of clinics to be able to customize their records and balance the need for unique and aggregate information in the record is critical to improve both the provider experience and the quality of care. TRIAL REGISTRATION: Clinicaltrials.gov , NCT02299492 , registered on November 24, 2014.

Determinants of Long-Term Neurological Recovery Patterns Relative to Hospital Discharge Among Cardiac Arrest Survivors.

OBJECTIVE: To explore factors associated with neurological recovery at 1 year relative to hospital discharge after cardiac arrest. DESIGN: Observational, retrospective review of a prospectively collected cohort. SETTING: Medical or surgical ICUs in a single tertiary care center. PATIENTS: Older than 18 years, resuscitated following either in-hospital or out-of-hospital cardiac arrest and considered for targeted temperature management between 2007 and 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Logistic regressions to determine factors associated with a poor recovery pattern after 1 year, defined as persistent Cerebral Performance Category Score 3-4 or any worsening of Cerebral Performance Category Score relative to discharge status. In total, 30% (117/385) of patients survived to hospital discharge; among those discharged with Cerebral Performance Category Score 1, 2, 3, and 4, good recovery pattern was seen in 54.5%, 48.4%, 39.5%, and 0%, respectively. Significant variables showing trends in associations with a poor recovery pattern (62.5%) in a multivariate model were age more than 70 years (odds ratio, 4; 95% CIs, 1.1-15; p = 0.04), Hispanic ethnicity (odds ratio, 4; CI, 1.2-13; p = 0.02), and discharge disposition (home needing out-patient services (odds ratio, 1), home requiring no additional services (odds ratio, 0.15; CI, 0.03-0.8; p = 0.02), acute rehabilitation (odds ratio, 0.23; CI, 0.06-0.9; p = 0.04). CONCLUSIONS: Patients discharged with mild or moderate cerebral dysfunction sustained their risk of neurological worsening within 1 year of cardiac arrest. Old age, Hispanic ethnicity, and discharge disposition of home with out-patient services may be associated with a poor 1 year neurological recovery pattern after hospital discharge from cardiac arrest.

Do Providers Know What They Do Not Know? A Correlational Study of Knowledge Acquisition and Person-Centered Care.

Person-centered care (PCC) is a central feature of health care reform, yet the tools needed to deliver this practice have not been implemented consistently. Person-centered care planning (PCCP) is a treatment planning approach operationalizing the values of recovery. To better understand PCCP implementation, this study examined the relationship between recovery knowledge and self-reported PCCP behaviors among 224 community mental health center staff. Results indicated that increased knowledge decreased the likelihood of endorsing non-recovery implementation barriers and self-reporting a high level of PCCP implementation. Findings suggest that individuals have difficulty assessing their performance, and point to the importance of objective fidelity measures.

Integrating the Electronic Health Record into Behavioral Health Encounters: Strategies, Barriers, and Implications for Practice.

Despite increasing rates of electronic health record (EHR) adoption, the impact of these systems on the delivery of behavioral health treatment remains poorly understood. This qualitative study examined the experiences of 37 behavioral health providers using EHRs during face-to-face visits. Providers described environmental, relational and system related strategies that were used to meaningfully integrate EHRs into treatment and enhance the patient-centeredness of clinical encounters. Barriers to deploying these techniques were also identified. Results contribute to limited research exploring EHR use in behavioral health care, and provide important insight into how systems can be optimized within this context.

Historical changes in flowering phenology are governed by temperature × precipitation interactions in a widespread perennial herb in western North America.

For most species, a precise understanding of how climatic parameters determine the timing of seasonal life cycle stages is constrained by limited long-term data. Further, most long-term studies of plant phenology that have examined relationships between phenological timing and climate have been local in scale or have focused on single climatic parameters. Herbarium specimens, however, can expand the temporal and spatial coverage of phenological datasets. Using Trillium ovatum specimens collected over > 100 yr across its native range, we analyzed how seasonal climatic conditions (mean minimum temperature (Tmin ), mean maximum temperature and total precipitation (PPT)) affect flowering phenology. We then examined long-term changes in climatic conditions and in the timing of flowering across T. ovatum's range. Warmer Tmin advanced flowering, whereas higher PPT delayed flowering. However, Tmin and PPT were shown to interact: the advancing effect of warmer Tmin was strongest where PPT was highest, and the delaying effect of higher PPT was strongest where Tmin was coldest. The direction of temporal change in climatic parameters and in the timing of flowering was dependent on geographic location. Tmin , for example, decreased across the observation period in coastal regions, but increased in inland areas. Our results highlight the complex effects of climate and geographic location on phenology.

Tuning local calcium availability: cell-type-specific immobile calcium buffer capacity in hippocampal neurons.

It has remained difficult to ascribe a specific functional role to immobile or fixed intracellular calcium buffers in central neurons because the amount of these buffers is unknown. Here, we explicitly isolated the fixed buffer fraction by prolonged whole-cell patch-clamp dialysis and quantified its buffering capacity in murine hippocampal slices using confocal calcium imaging and the "added-buffer" approach. In dentate granule cells, the calcium binding ratio (κ) after complete washout of calbindin D28k (Cb), κfixed, displayed a substantial value of ∼100. In contrast, in CA1 oriens lacunosum moleculare (OLM) interneurons, which do not contain any known calcium-binding protein(s), κfixed amounted to only ∼30. Based on these values, a theoretical analysis of dendritic spread of calcium after local entry showed that fixed buffers, in the absence of mobile species, decrease intracellular calcium mobility 100- and 30-fold in granule cells and OLM cells, respectively, and thereby strongly slow calcium signals. Although the large κfixed alone strongly delays the spread of calcium in granule cells, this value optimizes the benefits of additionally expressing the mobile calcium binding protein Cb. With such high κfixed, Cb effectively increases the propagation velocity to levels seen in OLM cells and, contrary to expectation, does not affect the peak calcium concentration close to the source but sharpens the spatial and temporal calcium gradients. The data suggest that the amount of fixed buffers determines the temporal availability of calcium for calcium-binding partners and plays a pivotal role in setting the repertoire of cellular calcium signaling regimens.

Using Collaborative Documentation to Support Person-Centered Care in Substance Use Settings.

The delivery of person-centered care (PCC) is critical to promoting service engagement among individuals who use substances. Collaborative documentation (CD) is an emerging person-centered practice used in community mental health, but has not been evaluated in substance use settings. This qualitative study conducted focus groups with substance use treatment providers (n=22) in an outpatient clinic to examine the impact of CD on PCC and clinical quality. Rapid qualitative analysis methods were used to identify key themes. Participants reported that using CD reduced documentation time and helped build trust and better understand their clients. Using CD presented unique challenges and opportunities when used with mandated populations or those with complex symptoms. The importance of honoring clients' preference not to collaborate in care was a salient theme. Findings indicate that CD can promote PCC in substance use treatment. Targeted strategies to optimize CD for mandated and clinically complex populations are needed.

Impact of Collaborative Documentation on Completeness and Length of Clinical Notes in Behavioral Health Settings.

OBJECTIVE: This study aimed to examine differences in community mental health visit notes before and after initiation of collaborative documentation, a practice in which clinicians and consumers jointly document clinical encounters. METHODS: Using a clinical informatics approach, the authors sampled visit notes (N=1,875) from nine providers in one mental health clinic. The authors compared notes from before and after the implementation of collaborative documentation by using fixed-effects regression models, controlling for therapist-level effects. RESULTS: Significant changes in visit note structure were found after the implementation of collaborative documentation. Most sections (N=6 of 10) contained more information (i.e., higher word and character counts) after collaborative documentation implementation, but sections describing a client's feelings were less likely to have any content (OR=0.01, p<0.001). CONCLUSIONS: These findings demonstrate that collaborative documentation influences clinical notes, providing much-needed research about a widely adopted practice in community mental health settings.