An improved pathway for autonomous bioluminescence imaging in eukaryotes.

The discovery of the bioluminescence pathway in the fungus Neonothopanus nambi enabled engineering of eukaryotes with self-sustained luminescence. However, the brightness of luminescence in heterologous hosts was limited by performance of the native fungal enzymes. Here we report optimized versions of the pathway that enhance bioluminescence by one to two orders of magnitude in plant, fungal and mammalian hosts, and enable longitudinal video-rate imaging.

Intelligent electroactive material systems with self-adaptive mechanical memory and sequential logic.

By synthesizing the requisite functionalities of intelligence in an integrated material system, it may become possible to animate otherwise inanimate matter. A significant challenge in this vision is to continually sense, process, and memorize information in a decentralized way. Here, we introduce an approach that enables all such functionalities in a soft mechanical material system. By integrating nonvolatile memory with continuous processing, we develop a sequential logic-based material design framework. Soft, conductive networks interconnect with embedded electroactive actuators to enable self-adaptive behavior that facilitates autonomous toggling and counting. The design principles are scaled in processing complexity and memory capacity to develop a model 8-bit mechanical material that can solve linear algebraic equations based on analog mechanical inputs. The resulting material system operates continually to monitor the current mechanical configuration and to autonomously search for solutions within a desired error. The methods created in this work are a foundation for future synthetic general intelligence that can empower materials to autonomously react to diverse stimuli in their environment.

An optimized bioluminescent substrate for non-invasive imaging in the brain.

Bioluminescence imaging (BLI) allows non-invasive visualization of cells and biochemical events in vivo and thus has become an indispensable technique in biomedical research. However, BLI in the central nervous system remains challenging because luciferases show relatively poor performance in the brain with existing substrates. Here, we report the discovery of a NanoLuc substrate with improved brain performance, cephalofurimazine (CFz). CFz paired with Antares luciferase produces greater than 20-fold more signal from the brain than the standard combination of D-luciferin with firefly luciferase. At standard doses, Antares-CFz matches AkaLuc-AkaLumine/TokeOni in brightness, while occasional higher dosing of CFz can be performed to obtain threefold more signal. CFz should allow the growing number of NanoLuc-based indicators to be applied to the brain with high sensitivity. Using CFz, we achieve video-rate non-invasive imaging of Antares in brains of freely moving mice and demonstrate non-invasive calcium imaging of sensory-evoked activity in genetically defined neurons.

Implicit associations with non-suicidal self-injury: Examination in a clinical sample by borderline personality symptomatology.

OBJECTIVES: We examine correlates and predictors for implicit associations with non-suicidal self-injury (NSSI) with the Self-Injury Implicit Association Test (SI-IAT) in a treatment-seeking sample. We also examine group differences in the SI-IAT among those with low/none, moderate and high/clinically significant borderline personality disorder (BPD) symptomatology in a treatment-seeking sample. METHODS: Participants (N = 111; 58% female; 89% White; Mage = 30.25) completed the SI-IAT and self-report measures at two time points. RESULTS: Higher BPD symptom scores were significantly, positively correlated with implicit identification with NSSI, and predicted NSSI identity when controlling for depression indices, history of NSSI and other covariates. With Time 1 SI-IAT scores entered as a covariate, BPD scores no longer significantly predicted Time 2 SI-IAT scores. Individuals with moderate and high/clinically significant symptom counts of BPD had higher/stronger implicit associations with NSSI identity than those with no/low BPD symptoms. CONCLUSIONS: Individuals with symptoms of BPD may implicitly identify with NSSI more than other clinical groups; examination of implicit assessments in BPD in future research is needed to further explore implicit identification with NSSI in this patient group to further understand both cross-sectional and prospective relations.

A Novel Luciferase-Based Reporter Gene Technology for Simultaneous Optical and Radionuclide Imaging of Cells.

Multimodality reporter gene imaging combines the sensitivity, resolution and translational potential of two or more signals. The approach has not been widely adopted by the animal imaging community, mainly because its utility in this area is unproven. We developed a new complementation-based reporter gene system where the large component of split NanoLuc luciferase (LgBiT) presented on the surface of cells (TM-LgBiT) interacts with a radiotracer consisting of the high-affinity complementary HiBiT peptide labeled with a radionuclide. Radiotracer uptake could be imaged in mice using SPECT/CT and bioluminescence within two hours of implanting reporter-gene-expressing cells. Imaging data were validated by ex vivo biodistribution studies. Following the demonstration of complementation between the TM-LgBiT protein and HiBiT radiotracer, we validated the use of the technology in the highly specific in vivo multimodal imaging of cells. These findings highlight the potential of this new approach to facilitate the advancement of cell and gene therapies from bench to clinic.

Novel NanoLuc substrates enable bright two-population bioluminescence imaging in animals.

Sensitive detection of two biological events in vivo has long been a goal in bioluminescence imaging. Antares, a fusion of the luciferase NanoLuc to the orange fluorescent protein CyOFP, has emerged as a bright bioluminescent reporter with orthogonal substrate specificity to firefly luciferase (FLuc) and its derivatives such as AkaLuc. However, the brightness of Antares in mice is limited by the poor solubility and bioavailability of the NanoLuc substrate furimazine. Here, we report a new substrate, hydrofurimazine, whose enhanced aqueous solubility allows delivery of higher doses to mice. In the liver, Antares with hydrofurimazine exhibited similar brightness to AkaLuc with its substrate AkaLumine. Further chemical exploration generated a second substrate, fluorofurimazine, with even higher brightness in vivo. We used Antares with fluorofurimazine to track tumor size and AkaLuc with AkaLumine to visualize CAR-T cells within the same mice, demonstrating the ability to perform two-population imaging with these two luciferase systems.

Disrupting the Repeat Domain of Premelanosome Protein (PMEL) Produces Dysamyloidosis and Dystrophic Ocular Pigment Reflective of Pigmentary Glaucoma.

Pigmentary glaucoma has recently been associated with missense mutations in PMEL that are dominantly inherited and enriched in the protein's fascinating repeat domain. PMEL pathobiology is intriguing because PMEL forms functional amyloid in healthy eyes, and this PMEL amyloid acts to scaffold melanin deposition. This is an informative contradistinction to prominent neurodegenerative diseases where amyloid formation is neurotoxic and mutations cause a toxic gain of function called "amyloidosis". Preclinical animal models have failed to model this PMEL "dysamyloidosis" pathomechanism and instead cause recessively inherited ocular pigment defects via PMEL loss of function; they have not addressed the consequences of disrupting PMEL's repetitive region. Here, we use CRISPR to engineer a small in-frame mutation in the zebrafish homolog of PMEL that is predicted to subtly disrupt the protein's repetitive region. Homozygous mutant larvae displayed pigmentation phenotypes and altered eye morphogenesis similar to presumptive null larvae. Heterozygous mutants had disrupted eye morphogenesis and disrupted pigment deposition in their retinal melanosomes. The deficits in the pigment deposition of these young adult fish were not accompanied by any detectable glaucomatous changes in intraocular pressure or retinal morphology. Overall, the data provide important in vivo validation that subtle PMEL mutations can cause a dominantly inherited pigment pathology that aligns with the inheritance of pigmentary glaucoma patient pedigrees. These in vivo observations help to resolve controversy regarding the necessity of PMEL's repeat domain in pigmentation. The data foster an ongoing interest in an antithetical dysamyloidosis mechanism that, akin to the amyloidosis of devastating dementias, manifests as a slow progressive neurodegenerative disease.

Autosomal dominant non-syndromic hearing loss maps to DFNA33 (13q34) and co-segregates with splice and frameshift variants in ATP11A, a phospholipid flippase gene.

Sequencing exomes/genomes have been successful for identifying recessive genes; however, discovery of dominant genes including deafness genes (DFNA) remains challenging. We report a new DFNA gene, ATP11A, in a Newfoundland family with a variable form of bilateral sensorineural hearing loss (SNHL). Genome-wide SNP genotyping linked SNHL to DFNA33 (LOD = 4.77), a locus on 13q34 previously mapped in a German family with variable SNHL. Whole-genome sequencing identified 51 unremarkable positional variants on 13q34. Continuous clinical ascertainment identified several key recombination events and reduced the disease interval to 769 kb, excluding all but one variant. ATP11A (NC_000013.11: chr13:113534963G>A) is a novel variant predicted to be a cryptic donor splice site. RNA studies verified in silico predictions, revealing the retention of 153 bp of intron in the 3' UTR of several ATP11A isoforms. Two unresolved families from Israel were subsequently identified with a similar, variable form of SNHL and a novel duplication (NM_032189.3:c.3322_3327+2dupGTCCAGGT) in exon 28 of ATP11A extended exon 28 by 8 bp, leading to a frameshift and premature stop codon (p.Asn1110Valfs43Ter). ATP11A is a type of P4-ATPase that transports (flip) phospholipids from the outer to inner leaflet of cell membranes to maintain asymmetry. Haploinsufficiency of ATP11A, the phospholipid flippase that specially transports phosphatidylserine (PS) and phosphatidylethanolamine (PE), could leave cells with PS/PE at the extracellular side vulnerable to phagocytic degradation. Given that surface PS can be pharmaceutically targeted, hearing loss due to ATP11A could potentially be treated. It is also likely that ATP11A is the gene underlying DFNA33.

A pathogenic deletion in Forkhead Box L1 (FOXL1) identifies the first otosclerosis (OTSC) gene.

Otosclerosis is a bone disorder of the otic capsule and common form of late-onset hearing impairment. Considered a complex disease, little is known about its pathogenesis. Over the past 20 years, ten autosomal dominant loci (OTSC1-10) have been mapped but no genes identified. Herein, we map a new OTSC locus to a 9.96 Mb region within the FOX gene cluster on 16q24.1 and identify a 15 bp coding deletion in Forkhead Box L1 co-segregating with otosclerosis in a Caucasian family. Pre-operative phenotype ranges from moderate to severe hearing loss to profound sensorineural loss requiring a cochlear implant. Mutant FOXL1 is both transcribed and translated and correctly locates to the cell nucleus. However, the deletion of 5 residues in the C-terminus of mutant FOXL1 causes a complete loss of transcriptional activity due to loss of secondary (alpha helix) structure. FOXL1 (rs764026385) was identified in a second unrelated case on a shared background. We conclude that FOXL1 (rs764026385) is pathogenic and causes autosomal dominant otosclerosis and propose a key inhibitory role for wildtype Foxl1 in bone remodelling in the otic capsule. New insights into the molecular pathology of otosclerosis from this study provide molecular targets for non-invasive therapeutic interventions.

Modeling population effects of the Deepwater Horizon oil spill on a long-lived species.

The 2010 Deepwater Horizon (DWH) oil spill exposed common bottlenose dolphins (Tursiops truncatus) in Barataria Bay, Louisiana to heavy oiling that caused increased mortality and chronic disease and impaired reproduction in surviving dolphins. We conducted photographic surveys and veterinary assessments in the decade following the spill. We assigned a prognostic score (good, fair, guarded, poor, or grave) for each dolphin to provide a single integrated indicator of overall health, and we examined temporal trends in prognostic scores. We used expert elicitation to quantify the implications of trends for the proportion of the dolphins that would recover within their lifetime. We integrated expert elicitation, along with other new information, in a population dynamics model to predict the effects of observed health trends on demography. We compared the resulting population trajectory with that predicted under baseline (no spill) conditions. Disease conditions persisted and have recently worsened in dolphins that were presumably exposed to DWH oil: 78% of those assessed in 2018 had a guarded, poor, or grave prognosis. Dolphins born after the spill were in better health. We estimated that the population declined by 45% (95% CI 14-74) relative to baseline and will take 35 years (95% CI 18-67) to recover to 95% of baseline numbers. The sum of annual differences between baseline and injured population sizes (i.e., the lost cetacean years) was 30,993 (95% CI 6607-94,148). The population is currently at a minimum point in its recovery trajectory and is vulnerable to emerging threats, including planned ecosystem restoration efforts that are likely to be detrimental to the dolphins' survival. Our modeling framework demonstrates an approach for integrating different sources and types of data, highlights the utility of expert elicitation for indeterminable input parameters, and emphasizes the importance of considering and monitoring long-term health of long-lived species subject to environmental disasters. Article impact statement: Oil spills can have long-term consequences for the health of long-lived species; thus, effective restoration and monitoring are needed.

El derrame de petróleo Deepwater Horizon (DWH) en 2010 expuso gravemente a este hidrocarburo a los delfines (Tursiops truncatus) de la Bahía Barataria, Luisiana, causando un incremento en la mortalidad y en las enfermedades crónicas, y deteriorando la reproducción de los delfines sobrevivientes. Realizamos censos fotográficos y evaluaciones veterinarias durante la década posterior al derrame. Asignamos un puntaje pronóstico (bueno, favorable, moderado, malo, o grave) a cada delfín para proporcionar un indicador integrado único de la salud en general. También examinamos las tendencias temporales de estos puntajes. Usamos información de expertos para cuantificar las implicaciones de las tendencias para la proporción de delfines que se recuperaría dentro de su periodo de vida. Integramos esta información, junto con información nueva, a un modelo de dinámica poblacional para predecir los efectos sobre la demografía de las tendencias observadas en la salud. Comparamos la trayectoria poblacional resultante con aquella pronosticada bajo condiciones de línea base (sin derrame). Las condiciones de enfermedad persistieron y recientemente han empeorado en los delfines que supuestamente estuvieron expuestos al petróleo de DWH: 78% de aquellos evaluados en 2018 tuvieron un pronóstico moderado, malo o grave. Los delfines que nacieron después del derrame contaron con mejor salud. Estimamos que la población declinó en un 45% (95% CI 14-74) relativo a la línea base y tardará 35 años (95% CI 18-67) en recuperar el 95% de los números de línea base. La suma de las diferencias anuales entre el tamaño poblacional de línea base y el dañado (es decir, los años cetáceos perdidos) fue de 30,993 (95% CI 6,607-94,148). La población actualmente está en un punto mínimo de su trayectoria de recuperación y es vulnerable a las amenazas emergentes, incluyendo los esfuerzos de restauración ambiental planeada que probablemente sean nocivos para la supervivencia de los delfines. Nuestro marco de modelado demuestra una estrategia para la integración de diferentes fuentes y tipos de datos, resalta la utilidad de la información de expertos para los parámetros de aportación indeterminable, y enfatiza la importancia de la consideración y el monitoreo de la salud a largo plazo de las especies longevas sujetas a los desastres ambientales. Modelado de los Efectos Poblacionales del Derrame de Petróleo Deepwater Horizon sobre Especies Longevas.

Central Executive Network and Executive Function in Patients With Alzheimer's Disease and Healthy Individuals: Meta-Analysis of Structural and Functional MRI.

OBJECTIVE: The neural architecture of executive function is of interest given its utility as a transdiagnostic predictor of adaptive functioning. However, a gap exists in the meta-analytic literature assessing this relationship in neuropsychiatric populations, concordance between structural and functional architecture, and the relationship with neuropsychological assessment of executive function. Given the importance of the central executive network (CEN) in Alzheimer's disease, this population may be useful in understanding this relationship in Alzheimer's disease pathology. METHODS: A meta-analysis of studies (k=21) was conducted to elucidate the relationship between executive function and CEN for structural architecture (k=10; N=1,027) among patients with Alzheimer's disease (k=6; N=250) and healthy control subjects (HCs) (k=4; N=777) and for functional architecture (k=11; N=522) among patients with Alzheimer's disease (k=6; N=306) and HCs (k=5; N=216). Random-effects modeling was used to increase accuracy of conclusions about population means. RESULTS: Analyses revealed a positive brain-behavior relationship (pr=0.032, 95% CI=0.07, 0.54), although there was a lack of statistically significant heterogeneity between functional and structural neuroimaging (Q=9.89, p=0.971, I2=0.00%) and between the Alzheimer's and HC groups in functional (Q=8.18, p=0.612, I2=0.00%) and structural (Q=1.60, p=0.996, I2=0.00%) neuroimaging. Similarly, a lack of statistically significant heterogeneity was revealed between functional and structural neuroimaging among patients with Alzheimer's disease (Q=3.59, p=0.980, I2=0.00%) and HCs (Q=3.67, p=0.885, I2=0.00%). CONCLUSIONS: Structural and functional imaging in the CEN are predictive of executive function performance among patients with Alzheimer's disease and HCs. Regardless of how the CEN is affected, behavior is correlated to the degree to which the CEN is affected. Findings are significant in the context of methodological decisions in multimodal neuroimaging research.

Acoustic localization, validation, and characterization of Rice's whale calls.

The recently named Rice's whale in the Gulf of Mexico is one of the most endangered whales in the world, and improved knowledge of spatiotemporal occurrence patterns is needed to support their recovery and conservation. Passive acoustic monitoring methods for determining spatiotemporal occurrence patterns require identifying the species' call repertoire. Rice's whale call repertoire remains unvalidated though several potential call types have been identified. This study uses sonobuoys and passive acoustic tagging to validate the source of potential call types and to characterize Rice's whale calls. During concurrent visual and acoustic surveys, acoustic-directed approaches were conducted to obtain visual verifications of sources of localized sounds. Of 28 acoustic-directed approaches, 79% led to sightings of balaenopterid whales, of which 10 could be positively identified to species as Rice's whales. Long-moan calls, downsweep sequences, and tonal-sequences are attributed to Rice's whales based on these matches, while anthropogenic sources are ruled out. A potential new call type, the low-frequency downsweep sequence, is characterized from tagged Rice's whale recordings. The validation and characterization of the Rice's whale call repertoire provides foundational information needed to use passive acoustic monitoring for better understanding and conservation of these critically endangered whales.

Metacognitive beliefs about uncontrollability relate most strongly to health anxiety among US-based non-Latinx White primary care patients: Comparing strength of relations with US-based non-Latinx Black and Latinx primary care patients.

Metacognitive beliefs have emerged as important to health anxiety, particularly beliefs that health-related thoughts are uncontrollable. Preliminary research examining generalized worry indicates uncontrollability beliefs relate more strongly to anxiety among US-based self-identifying White relative to Black college students. The present study sought to extend that line of research by examining if metacognitive beliefs about the uncontrollability of health-related thoughts differentially relate to health anxiety among self-identifying non-Latinx Black (n = 123), Latinx (n = 104) and non-Latinx White (n = 80) US-based primary care patients. As predicted, although positive associations were seen across all three groups, beliefs that health-related thoughts are uncontrollable more strongly related to health anxiety among White patients compared to both Black and Latinx patients. Those differential relations held in multivariate analyses while statistically controlling for positive depression screening status, generalized anxiety symptom severity and medical morbidity. Although the effect size surrounding the differential relations was small in magnitude, the present results further support the notion that metacognitive beliefs about uncontrollability relate less strongly to anxiety among US-based ethnoracial minorities compared to White individuals. Potential reasons for the differential relations are discussed, along with additional areas for future research.

Toward a Point-of-Need Bioluminescence-Based Immunoassay Utilizing a Complete Shelf-Stable Reagent.

Enzyme-linked immunosorbent assays (ELISAs) are used extensively for the detection and quantification of biomolecules in clinical diagnostics as well as in basic research. Although broadly used, the inherent complexities of ELISAs preclude their utility for straightforward point-of-need testing, where speed and simplicity are essential. With this in mind, we developed a bioluminescence-based immunoassay format that provides a sensitive and simple method for detecting biomolecules in clinical samples. We utilized a ternary, split-NanoLuc luciferase complementation reporter consisting of two small peptides (11mer, 13mer) and a 17 kDa polypeptide combined with a luminogenic substrate to create a complete, shelf-stable add-and-read assay detection reagent. Directed evolution was used to optimize reporter constituent sequences to impart chemical and thermal stability, as well as solubility, while formulation optimization was applied to stabilize an all-in-one reagent that can be reconstituted in aqueous buffers or sample matrices. The result of these efforts is a robust, first-generation bioluminescence-based homogenous immunoassay reporter platform where all assay components can be configured into a stable lyophilized cake, supporting homogeneous, rapid, and sensitive one-step biomolecule quantification in complex human samples. This technology represents a promising alternative immunoassay format with significant potential to bring critical diagnostic molecular detection testing closer to the point-of-need.

The combination of health anxiety and somatic symptoms: a prospective predictor of healthcare usage in primary care.

Extant research provides equivocal conclusions if the combined presentation of health anxiety with severe somatic symptoms confers risk for greater future primary care usage. The present study further examined the combination of health anxiety and somatic symptoms as a predictor of healthcare usage in primary care. Using a prospective longitudinal design, a large sample (N = 530) of patients presenting for treatment at a community health center completed self-report measures assessing health anxiety and somatic symptom severity. A medical record review at the time of questionnaire administration and 1 year following that administration was completed to assess the frequency of medical visits during the preceding and subsequent year. As expected, the interactive effect between health anxiety and somatic symptom severity predicted greater subsequent year medical visits. Covariates included preceding year medical visits, sociodemographic variables, body mass index, smoking status, and depressive symptom severity. Simple effects indicated that health anxiety predicted greater subsequent year medical visits when coupled with relatively severe, but not mild, somatic symptoms. Assessing health anxiety and somatic symptom severity in primary care settings could be important for identifying individuals at risk for future frequent healthcare visits and who may benefit from intervention.

Association of Angiotensin-Converting Enzyme Inhibitors with Increased Mortality Among Patients with Isolated Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is associated with one-third of all deaths from trauma. Preinjury exposure to cardiovascular drugs may affect TBI outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) exacerbate brain cell damage and worsen functional outcomes in the laboratory setting. ß-blockers (BBs), however, appear to be associated with reduced mortality among patients with isolated TBI. OBJECTIVE: Examine the association between preinjury ACEI and BB use and clinical outcome among patients with isolated TBI. METHODS: A retrospective cohort study of patients age ≥ 40 years admitted to an academic level 1 trauma center with isolated TBI between January 2010 and December 2014 was performed. Isolated TBI was defined as a head Abbreviated Injury Scale (AIS) score ≥ 3, with chest, abdomen, and extremity AIS scores ≤ 2. Preinjury medication use was determined through chart review. All patients with concurrent BB use were initially excluded. In-hospital mortality was the primary measured outcome. RESULTS: Over the 5-year study period, 600 patients were identified with isolated TBI who were naive to BB use. There was significantly higher mortality (P = .04) among patients who received ACEI before injury (10 of 96; 10%) than among those who did not (25 of 504; 5%). A multivariate stepwise logistic regression analysis revealed a threefold increased risk of mortality in the ACEI cohort (P < .001), which was even greater than the twofold increased risk of mortality associated with an Injury Severity Score ≥ 16. A second analysis that included patients who received preinjury BBs (n = 98) demonstrated slightly reduced mortality in the ACEI cohort with only a twofold increased risk in multivariate analysis (P = .05). CONCLUSIONS: Preinjury exposure to ACEIs is associated with an increase in mortality among patients with isolated TBI. This effect is ameliorated in patients who receive BBs, which provides evidence that this class of medications may provide a protective benefit.

Automated classification of dolphin echolocation click types from the Gulf of Mexico.

Delphinids produce large numbers of short duration, broadband echolocation clicks which may be useful for species classification in passive acoustic monitoring efforts. A challenge in echolocation click classification is to overcome the many sources of variability to recognize underlying patterns across many detections. An automated unsupervised network-based classification method was developed to simulate the approach a human analyst uses when categorizing click types: Clusters of similar clicks were identified by incorporating multiple click characteristics (spectral shape and inter-click interval distributions) to distinguish within-type from between-type variation, and identify distinct, persistent click types. Once click types were established, an algorithm for classifying novel detections using existing clusters was tested. The automated classification method was applied to a dataset of 52 million clicks detected across five monitoring sites over two years in the Gulf of Mexico (GOM). Seven distinct click types were identified, one of which is known to be associated with an acoustically identifiable delphinid (Risso's dolphin) and six of which are not yet identified. All types occurred at multiple monitoring locations, but the relative occurrence of types varied, particularly between continental shelf and slope locations. Automatically-identified click types from autonomous seafloor recorders without verifiable species identification were compared with clicks detected on sea-surface towed hydrophone arrays in the presence of visually identified delphinid species. These comparisons suggest potential species identities for the animals producing some echolocation click types. The network-based classification method presented here is effective for rapid, unsupervised delphinid click classification across large datasets in which the click types may not be known a priori.

Somatic symptom severity among primary care patients who are obese: examining the unique contributions of anxiety sensitivity, discomfort intolerance, and health anxiety.

Prior research indicates the common presentation of somatic symptoms and obesity in primary care settings, as well as links between obesity and somatic symptoms. Anxiety sensitivity, discomfort intolerance, and health anxiety are three variables relevant to somatic symptoms. How those three variables relate to somatic symptom severity among individuals who are obese and the unique variance accounted for by each variable in somatic symptom severity remains unexamined. Among a large sample of primary care patients who are obese (N = 342), anxiety sensitivity, discomfort intolerance, and health anxiety collectively accounted for 35% of variance in somatic symptom severity beyond the effects of sociodemographic variables, body mass index, medical morbidity, and depression severity. Health anxiety accounted for the largest amount of unique variance in somatic symptom severity, potentially supporting the relevance of health anxiety to the presentation of increased somatic symptoms among patients who are obese.

Treadmill associated head injuries on the rise: an 18 year review of U.S. emergency room visits.

OBJECTIVE: The treadmill is the most commonly used aerobic exercise equipment with studies showing many gym-related injuries are attributed to treadmills. The purpose of this study is to examine the incidence of treadmill-associated head injuries within the US. METHODS: Retrospective data from 1997 to 2014 was collected via the National Electronic Injury Surveillance System, which provides annual es7timates of injuries associated with consumer products. Patients over 18 years who sustained treadmill-associated head injuries were included, and the estimated annual incidence was determined. RESULTS: An estimated 4929 patients presented to US emergency departments with a head injury while exercising on a treadmill between 1997 and 2014. A >1000% increase in the number of head injuries was observed over the study period (p-value <0.001). Patients over 50 had a 14 times greater risk of admission than younger patients (p-value <0.001). Injuries were greater in women than men. CONCLUSION: Our study demonstrates a significant increase treadmill-associated head injuries from 1997 to 2014. This phenomenon is most pronounced in older and female populations. The exact etiology of this large increase remains unclear. Education on the proper use of treadmills as well as further investigation into the cause of the increase are warranted.

Depression with Mixed Features in Adolescent Psychiatric Patients.

Depression with mixed features is poorly understood, especially in pediatric samples. This study compares symptoms and correlates of depressed adolescent inpatients with mixed features to inpatients with bipolar disorder and major depression. 407 adolescents were administered diagnostic interviews and self-reports, and 262 were categorized as Depression with Mixed Features (MXD; n = 38), Consensus Bipolar (CB; n = 79), or Depression Only (DO; n = 145). Demographic and morbidity information were collected via chart reviews. MXD adolescents evidenced elevated mania-related symptoms compared to DO adolescents. MXD adolescents had elevated Unusually Energetic symptoms and increases for six additional category B mania-related symptoms compared to CB adolescents. MXD adolescents met criteria for more comorbid disorders and reported elevated suicidality, anger, and trauma symptoms compared to CB and DO adolescents. Overall, MXD adolescents evidenced elevated symptomatology compared to other groups, suggesting mixed depression may represent a unique constellation of symptoms meriting further investigation.