Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions.

Members of the solute carrier (SLC) family of transporters are responsible for the cellular influx of a broad range of endogenous compounds and xenobiotics. These proteins are highly expressed in the gastrointestinal tract and eliminating organs such as the liver and kidney, and are considered to be of particular importance in governing drug absorption and elimination. Many of the same transporters are also expressed in a wide variety of organs targeted by clinically important anticancer drugs, directly affect cellular sensitivity to these agents, and indirectly influence treatment-related side effects. Furthermore, targeted intervention strategies involving the use of transport inhibitors have been recently developed, and have provided promising lead candidates for combinatorial therapies associated with decreased toxicity. Gaining a better understanding of the complex interplay between transporter-mediated on-target and off-target drug disposition will help guide the further development of these novel treatment strategies to prevent drug accumulation in toxicity-associated organs, and improve the safety of currently available treatment modalities. In this report, we provide an update on this rapidly emerging field with particular emphasis on anticancer drugs belonging to the classes of taxanes, platinum derivatives, nucleoside analogs, and anthracyclines.

Geri-Mobile Health: Feasibility of a VA Mental Health Mobile Apps Coaching Program for Older Veterans.

OBJECTIVES: This program evaluation examined the feasibility, acceptability, and preliminary effects of an individualized coaching program to help older Veterans use VA mental health mobile apps to address mental health and well-being goals. METHODS: The program delivers individual technical and clinical support to facilitate the use of mobile devices and VA apps. Participants completed assessments of mobile device proficiency, app use frequency, app comfort, quality of life, and mental health symptoms (completed by a subset, n = 11) pre- and post-participation. RESULTS: Of 24 enrollees, 17 completed the program and received an average of 7.58 (SD = 2.87) sessions including the initial assessment. Mobile device proficiency (t (16) = -3.80, p = .002) and number of days/week apps were used (t (16) = -2.34, p = .032) increased significantly from pre- to post-participation. Depressive and anxiety scores decreased significantly (t (10) = 3.16, p = .010; t (10) = 3.29, p = .008) among the subset completing those measures. Overall satisfaction was high; 100% reported they would recommend the program. CONCLUSIONS: Findings suggest the program is feasible, highly acceptable, and increases mobile device proficiency and use of apps. CLINICAL IMPLICATIONS: Coaching programs can equip older adults with the skills to use mental health apps.

Hidden morphological diversity among early tetrapods.

Phylogenetic analysis of early tetrapod evolution has resulted in a consensus across diverse data sets in which the tetrapod stem group is a relatively homogenous collection of medium- to large-sized animals showing a progressive loss of 'fish' characters as they become increasingly terrestrial, whereas the crown group demonstrates marked morphological diversity and disparity. The oldest fossil attributed to the tetrapod crown group is the highly specialized aïstopod Lethiscus stocki, which shows a small size, extreme axial elongation, loss of limbs, spool-shaped vertebral centra, and a skull with reduced centres of ossification, in common with an otherwise disparate group of small animals known as lepospondyls. Here we use micro-computed tomography of the only known specimen of Lethiscus to provide new information that strongly challenges this consensus. Digital dissection reveals extremely primitive cranial morphology, including a spiracular notch, a large remnant of the notochord within the braincase, an open ventral cranial fissure, an anteriorly restricted parasphenoid element, and Meckelian ossifications. The braincase is elongate and lies atop a dorsally projecting septum of the parasphenoid bone, similar to stem tetrapods such as embolomeres. This morphology is consistent in a second aïstopod, Coloraderpeton, although the details differ. Phylogenetic analysis, including critical new braincase data, places aïstopods deep on the tetrapod stem, whereas another major lepospondyl lineage is displaced into the amniotes. These results show that stem group tetrapods were much more diverse in their body plans than previously thought. Our study requires a change in commonly used calibration dates for molecular analyses, and emphasizes the importance of character sampling for early tetrapod evolutionary relationships.

Life Expectancy for White, Black, and Hispanic Race/Ethnicity in U.S. States: Trends and Disparities, 1990 to 2019.

BACKGROUND: Life expectancy (LE) differences within and between states by race/ethnicity have not been examined. OBJECTIVE: To estimate LE for selected race/ethnicity groups in states from 1990 to 2019. DESIGN: Cross-sectional time-series analysis. SETTING: United States. PARTICIPANTS: Deidentified death records and Census data were used to construct regression models with smoothed time series of mortality from 1990 to 2019. MEASUREMENTS: LE at birth, by sex and year, for subgroups of people reporting Hispanic, non-Hispanic Black, or non-Hispanic White race/ethnicity. RESULTS: Disparities in LE across states were 8.0 years for females and 12.2 years for males in 1990 and 7.9 years for females and 7.8 years for males in 2019. When race/ethnicity groups were accounted for, disparities across states were 20.7 years for females and 24.5 years for males in 1990, decreasing to 18.5 years for females and 23.7 years for males in 2019. Disparities across states increased within each race/ethnicity group between 1990 and 2019, with the largest increase for non-Hispanic White males and the smallest for Hispanic females. The disparity between race/ethnicity groups within states decreased for most of the 23 states with estimates for all 3 groups but increased for females in 7 states and males in 5 states. LIMITATION: Because of small sample size, LE was not estimated for 37 of 153 state-race/ethnicity groups. CONCLUSION: Disparity in LE across states was greater when race/ethnicity groups were considered. Disparities across all state-race/ethnicity groups in general have decreased over the past 3 decades. Within each race/ethnicity group, disparities across states have increased. Although racial/ethnic disparities decreased in most of the 23 states for which LE was estimated for all 3 groups, they increased for females in 7 states and males in 5 states. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Dobutamine-induced Takotsubo syndrome in a paediatric heart transplant patient.

Takotsubo syndrome is a potentially reversible cause of acute systolic dysfunction. Takotsubo syndrome is rare in children, with no reported dobutamine-induced cases to date. We present a 14-year-old male with prior history of heart transplantation, who developed Takotsubo syndrome during dobutamine stress echocardiography. We highlight the importance of its early recognition to ensure supportive measures with avoidance of inotropic medications.

Cephalad extraspinal spinal cord stimulator lead migration & salvage: A case report.

INTRODUCTION: Spinal cord stimulation is an important therapy option for the treatment of chronic neuropathic pain of spinal or peripheral etiology. As with any implantable device, complications may arise. These must be promptly identified and managed to maintain patients in successful therapy. CASE REPORT: We report an unusual case of cephalad and extraspinal lead migration requiring surgical intervention in order to salvage therapy. CONCLUSION: Lead migration is one of the most common complications of spinal cord stimulation, and left untreated can lead to loss of therapy and possible device explant. A strategy for correcting this issue is needed, and we present an unusual case to consider when faced with a loss of therapy from lead migration.

The Moderating Role of Pain Self-efficacy in the Relationships Among Caregiver Burden and Care Recipient Pain and Neuropsychiatric Symptoms in a Sample of Persons With Dementia.

Past research suggests relationships among dementia caregiver burden and care recipient pain and neuropsychiatric symptoms, but no prior work has examined the influence of pain self-efficacy on these associations. A sample of 502 dementia caregivers completed an online protocol assessing caregiver burden and care recipient neuropsychiatric symptoms, presence of pain, and pain self-efficacy in this cross-sectional, observational study. The indirect effect of neuropsychiatric symptoms on the relationship between pain and caregiver burden was significant. Pain self-efficacy significantly moderated the effect of pain on neuropsychiatric symptoms (P=0.04) and the direct association between pain and caregiver burden (P=0.004), but did not moderate the indirect effect. Future research should explore how pain influences neuropsychiatric symptoms, and whether improvement in pain self-efficacy in dementia care recipients attenuates the influence of pain on neuropsychiatric symptoms and caregiver burden in other samples.

Immobile Leaflets at Time of Bioprosthetic Valve Implantation: A Novel Risk Factor for Early Bioprosthetic Failure: A Novel Risk Factor for Early Bioprosthetic Failure.

OBJECTIVES: The clinical implications of finding immobile leaflet(s) at the time of bioprosthetic valve implantation but with acceptable prosthetic haemodynamics are uncertain. We sought to determine the characteristics of such patients and their impact on outcome. METHODS: Patients with immobile leaflet at the time of surgical bioprosthetic valve implantation were identified retrospectively by a systematic search of an institutional echocardiography database (2010-2020). Intraoperative echocardiograms were reviewed de-novo to confirm immobile leaflet(s) at the time of implantation. Cases were matched 1:2 to controls with normal bioprosthetic leaflets motion for age, sex, prosthesis position, prosthesis model, size, year of implantation, and pre-implantation left ventricular ejection fraction. Proportional hazards method was used to analyse the composite endpoint of stroke, valve thrombosis or re-intervention. RESULTS: Immobile leaflet at the time of bioprosthetic valve implantation were found in 26 patients (median age 71 ys 39% males) following tricuspid (n=13), mitral (n=11) and aortic (n=2) valve replacements; 96% received porcine prostheses; prosthesis size was 27 mm or larger in 92%. Immobile leaflet were recorded on intraoperative reports in 16 (62%) cases. It resulted in elevated gradient or mild-moderate prosthetic regurgitation in three (12%), but none led to immediate corrective action intraoperatively. At median follow-up of 21 (4-50) months, presence of immobile leaflet was associated with composite clinical endpoint of stroke, valve thrombosis or re-intervention (hazard ratio 6.8, 95% CI 1.8-25.2, p<0.01) compared to controls. CONCLUSION: Immobile leaflet immediately post-bioprosthetic valve implantation is frequently under-recognised intraoperatively and appears to be associated with early bioprosthetic dysfunction and worse clinical outcome.

Reformed Experimental Activities (REActivities): Gauging the Fidelity of Implementation in a Reformed Undergraduate Organic Chemistry Laboratory.

Reformed Experimental Activities (REActivities) is an innovative approach to the delivery of the traditional material in an undergraduate organic chemistry laboratory. To better understand the fidelity of implementing this pedagogy and what effects the framework of REActivities has on student-instructor interactions, an observational protocol study was employed. This paper also describes the Evaluation of Lab Instructor Time and Engagement (ELITE) observational instrument developed to evaluate instructional behaviors in a lab setting. The instrument was used in first semester undergraduate organic chemistry laboratories across seven universities to measure the robustness of the guided-inquiry materials when implemented and the nature of the instructor's interactions. The ELITE data was analyzed for laboratories delivered using REActivities and compared with expert delivery as well as with traditional expository methods. The data revealed that instructor behaviors when using REActivities were consistent and comparable and could be distinguished from traditional lab deliveries. The nature of the instructor's behaviors also showed a remarkably consistent trend for coded conceptual-based discussion when REActivities was employed, in contrast to the near absence of similar interactions when expository methods were employed for comparable laboratories.

Radiation dose reduction for 3D angiography images in pediatric and congenital cardiology.

OBJECTIVES: The purpose of this study was to investigate the influence of simulated reduced-dose three-dimensional angiography (3DA) on the accuracy and precision of linear measurements derived from 3DA datasets. BACKGROUND: Three-dimensional angiography is performed during X-ray guided interventional procedures to aid diagnosis and inform treatment strategies for children and adults with congenital heart disease. However, 3DA contributes substantially to patient radiation dose and may lead to an increased radiation-induced cancer risk. METHODS: Reduced-dose patient 3DA images were simulated by adding quantum noise to the 2D projection angiograms, then reconstructing the projection angiograms into the 3DA dataset. Dose reduction in the range 33-72% was simulated. Five observers performed 46 vessel diameter measurements along prespecified axes within 23 vessel segments from 11 patient 3DA datasets. Statistical tests were performed to assess the influence of radiation dose reduction on the accuracy and precision of vessel diameter measurements. RESULTS: Vessel diameter measurements were in the range 5.9- 22.7 mm. Considering all vessel segments and observers, the influence of dose level on the accuracy of diameter measurements was in the range 0.02 - 0.15 mm (p .05-.8). Interobserver variability increased modestly with vessel diameter, but was not influence by dose level (p = .52). The statistical test for observer recall bias was negative (p = .51). CONCLUSIONS: Simulated dose reduction up to 72% did not affect the accuracy or precision of the diameter measurements acquired from 3DA images. These findings may embolden 3DA radiation dose reduction for pediatric and congenital heart disease patients.

Varying roles of glucoregulatory function measures in postprandial cognition following milk consumption.

PURPOSE: Past work suggests milk consumption may facilitate cognition in children and college students with higher fasting glucose compared to other beverages (e.g., fruit juice). However, no studies have evaluated this phenomenon in adults, or considered other measures of glucoregulatory function. This open-label study assessed the role of glucoregulatory function in postprandial cognition after milk intake in adults. We hypothesized participants with lower fasting or post-consumption plasma glucose following a glucose excursion challenge (glucose response) would demonstrate better cognition following beverages of higher (juice) versus lower (milk) or no (water) glycemic content. METHODS: Forty-four nondiabetic, overnight-fasted adults attended three laboratory visits, ingesting 237 mL of 2% fat milk, apple juice, or water at each visit in a randomized, counterbalanced, crossover design. Participants completed cognitive testing (CNS Vital Signs) at baseline and 30, 90, and 150 min post-ingestion; primary outcomes were CNS Vital Signs composite scores. Fasting and post-consumption plasma glucose levels were assessed, with glucose response indexed as the change in plasma glucose from baseline to 30 min after juice (ΔGlucose). RESULTS: Mixed modeling revealed participants with higher fasting glucose demonstrated better complex attention after water versus juice at 30 min, but better performance after juice versus water at 150 min (p = 0.02). Participants with a larger ΔGlucose demonstrated better processing speed (p = 0.01) 30 min after milk versus water; this effect also reversed at 150 min. CONCLUSION: Different methods of measuring glucoregulatory function reveal its differing roles in postprandial cognition. Time since ingestion may also determine which beverages best optimize cognition.

Antegrade transseptal transcatheter aortic valve replacement: Back to the future?

Antegrade transseptal approach was utilized in the first human case of transcatheter aortic valve replacement (TAVR) and in the early phase of TAVR. Various challenges with the antegrade transseptal approach including procedural complexity, need for atrial septal crossing, and potential for injury to the mitral valve apparatus led it to being supplanted by other approaches. These challenges have now largely been mitigated as structural interventionalists routinely perform left atrial procedures. We report a case of antegrade transseptal TAVR using a large bore sheath placed in the mid left ventricle across the mitral orifice to protect the mitral valve apparatus and facilitate valve deployment. An 84-year-old man with heart failure symptoms was seen for severe aortic stenosis. The severity of peripheral arterial disease precluded femoral, axillary, carotid, or transcaval routes. After transseptal puncture and creation of an arteriovenous rail, a long 26-Fr sheath was advanced from the right femoral vein transseptally over the arteriovenous rail, past the mitral valve inflow to the mid left ventricular cavity. The sheath provided a stable platform with stable intraprocedure hemodynamics. Balloon valvuloplasty was performed in an antegrade manner, after which a 29-mm SAPIEN S3 prosthesis was advanced into the aortic valve position and deployed under rapid pacing. We observed no injury to the mitral leaflets or subvalvular apparatus after the procedure. The antegrade transseptal approach should be revisited as an option for patients at high surgical risk with no other suitable access site. The use of a large bore sheath facilitates this approach.

Perforating the GORE® CARDIOFORM septal occluder and atrial septal defect occluder to gain access to the left atrium.

OBJECTIVE: Perforate the expanded polytetrafluoroethylene membrane of the GORE® CARDIOFORM Septal Occluder (GSO) and GORE® CARDIOFORM ASD Occluder (GCA) after implantation. BACKGROUND: Percutaneous transseptal access to the left atrium is necessary for many structural and electrophysiological procedures. The potential need to access the left atrium may influence decision-making for patent foramen ovale or atrial septal defect closure. METHODS: Sixteen canines underwent implantation of equal number GSO or GCA devices. A transseptal crossing procedure was performed through the device 85 (±1) days postoccluder implantation. The crossing procedure was performed utilizing commercially available equipment: radiofrequency/SureFlex sheath and standard needle/Mullin's sheath. Progressive dilation of the perforation was performed to allow passage of a 12 French Mullin's sheath into the left atrium. RESULTS: Left atrial access was achieved in all cases. Postmortem analysis demonstrated passage through both occluder discs in all radiofrequency/SureFlex sheath cases (4 GSO, 4 GCA) and half of the standard needle/Mullin's sheath cases (3 GSO, 1 GCA). The remaining standard needle/Mullin's sheath cases demonstrated perforation through the right atrial disc but passage around the septal aspect of the left atrial disc, thus not perforating the left atrial disc. No acute embolic complications from the procedure were observed. CONCLUSIONS: Left atrial access may be achieved through the GSO or GCA devices after implantation and endothelialization. The combination of a radiofrequency needle and steerable sheath provides benefit over a standard needle and Mullin's sheath in accomplishing passage through both occluder discs.

New application of strontium isotopes reveals evidence of limited migratory behaviour in Late Cretaceous hadrosaurs.

Dinosaur migration patterns are very difficult to determine, often relying solely on the geographical distribution of fossils. Unfortunately, it is generally not possible to determine if a fossil taxon's geographical distribution is the result of migration or simply a wide distribution. Whereas some attempts have been made to use isotopic systems to determine migratory patterns in dinosaurs, these methods have yet to achieve wider usage in the study of dinosaur ecology. Here, we have used strontium isotope ratios from fossil enamel to reconstruct the movements of an individual hadrosaur from Dinosaur Provincial Park in Alberta, Canada. Results from this study are consistent with a range or migratory pattern between Dinosaur Provincial Park and a contemporaneous locality in the South Saskatchewan River area, Alberta, Canada. This represents a minimum distance of approximately 80 km, which is consistent with migrations seen in modern elephants. These results suggest the continent-wide distribution of some hadrosaur species in the Late Cretaceous of North America is not the result of extremely long-range migratory behaviours.

Biological sex and glucoregulation modulate postprandial cognition following dairy milk and fruit juice in healthy school-age children.

Objectives: Recent work suggests potential postprandial benefits for cognition and on-task behavior in children, depending on the macronutrients consumed, as well as individual differences such as sex and glucoregulation. We examined the effects of 1% milk versus apple juice on cognition and on-task behavior among healthy school-age children, predicting that milk would promote better performance and a greater presence of on-task behavior compared to juice. We also examined how sex and glucoregulation influenced cognition and behavior following each beverage.Methods: Eighty-four English-speaking children ages 8-12 (45 female, 39 male) attended two 0800 testing sessions after fasting overnight in a crossover design. Participant sessions were counterbalanced to include 237 mL of 1% milk or apple juice. Behavioral measures and complex attentional and executive function tasks were assessed at baseline, 30, 90, and 120 min post-ingestion. Outcomes were analyzed using repeated measures mixed models.Results: Participants with fasting glucose levels above 89.91 mg/dL responded more quickly in an inhibitory control paradigm following milk. Females performed faster on a vigilance task, but less accurately in a working memory paradigm after milk versus juice. No effects were found for on-task behavior.Discussion: Results demonstrated modulatory effects of glucoregulation and sex on postprandial cognition. Milk may improve cognitive performance in school-aged children with higher fasting glucose, and may be the optimal choice for speed among females, whereas juice may be better for accuracy. Future work should utilize designs incorporating glucoregulation and sex, and consider additional biological variables to better understand postprandial cognition and behavior in children.

Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis.

The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK) signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior.

The impact of stress on sleep: Pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders.

Sleep reactivity is the trait-like degree to which stress exposure disrupts sleep, resulting in difficulty falling and staying asleep. Individuals with highly reactive sleep systems experience drastic deterioration of sleep when stressed, whereas those with low sleep reactivity proceed largely unperturbed during stress. Research shows that genetics, familial history of insomnia, female gender and environmental stress influence how the sleep system responds to stress. Further work has identified neurobiological underpinnings for sleep reactivity involving disrupted cortical networks and dysregulation in the autonomic nervous system and hypothalamic-pituitary-adrenal axis. Sleep reactivity is most pathologically and clinically pertinent when in excess, such that high sleep reactivity predicts risk for future insomnia disorder, with early evidence suggesting high sleep reactivity corresponds to severe insomnia phenotypes (sleep onset insomnia and short sleep insomnia). High sleep reactivity is also linked to risk of shift-work disorder, depression and anxiety. Importantly, stress-related worry and rumination may exploit sensitive sleep systems, thereby augmenting the pathogenicity of sleep reactivity. With the development of cost-effective assessment of sleep reactivity, we can now identify individuals at risk of future insomnia, shift-work disorder and mental illness, thus identifying a target population for preventive intervention. Given that insomniacs with high sleep reactivity tend to present with severe insomnia phenotypes, patient sleep reactivity may inform triaging to different levels of treatment. Future research on sleep reactivity is needed to clarify its neurobiology, characterize its long-term prospective associations with insomnia and shift-work disorder phenotypes, and establish its prognostic value for mental illness and other non-sleep disorders.

Baseline glucoregulatory function moderates the effect of dairy milk and fruit juice on postprandial cognition in healthy young adults.

PURPOSE: Few studies have examined acute cognitive effects of dairy products. Prior work suggests baseline glucoregulatory function may moderate the relationship between macronutrient profile and postprandial cognition. This study examined the role of glucoregulatory function in postprandial cognition after milk, fruit juice, and a water control. We hypothesized juice would improve cognition in those with lower fasting glucose, while milk would improve cognition in those with higher fasting glucose. DESIGN: 86 non-diabetic, non-hypoglycemic young adults attended three 8 AM testing sessions after fasting overnight. Fasting glucose was assessed via fingerstick at each session. Participants consumed 8 oz of 1% milk (12 g carbohydrates), apple juice (29 g carbohydrates), or water in a randomized, counterbalanced order, and completed repeatable standard and running memory continuous performance (SCPT-vigilance; RMCPT-working memory) and go/no-go (GNG-inhibitory control) tasks 30, 90, and 120 min post-ingestion. RESULTS: Participants with fasting glucose above 107.69 mg/dL made significantly fewer GNG commission errors overall after milk versus water, while the converse was observed when fasting glucose was below 70.85 mg/dL (p = 0.003). At 30 min, participants with fasting glucose above 105.80 mg/dL made significantly more RMCPT correct responses per minute after milk versus juice, while the opposite occurred when fasting glucose was below 76.85 mg/dL (p = 0.006). For both tasks, differences greatened as fasting glucose increased or decreased beyond these upper and lower bounds, respectively. CONCLUSIONS: Consideration of baseline glucoregulatory function is crucial when assessing postprandial cognition, even in non-diabetic and non-hypoglycemic samples. Dairy milk may improve cognition in persons with higher fasting glucose.

Adult presentation of ALCAPA: Echo and CT diagnosis.

A healthy 20-year-old male presented with aborted sudden death. Both thoracic echocardiography and cardiac computed tomographic angiography demonstrated the characteristic findings of ALCAPA noting a dilated and tortuous right coronary artery, dilated coronary collateral arteries within the interventricular septum or along the surface of the heart, and visualization of the left coronary artery origin from the posterior aspect of the main pulmonary artery. Both imaging modalities demonstrated all three characteristic findings of this rare coronary anomaly and served as complementary imaging studies for surgical correction.

Less is more: Neural activity during very brief and clearly visible exposure to phobic stimuli.

Research on automatic processes in fear has emphasized the provocation of fear responses rather than their attenuation. We have previously shown that the repeated presentation of feared images without conscious awareness via backward masking reduces avoidance of a live tarantula in spider-phobic participants. Herein we investigated the neural basis for these adaptive effects of masked exposure. 21 spider-phobic and 21 control participants, identified by a psychiatric interview, fear questionnaire, and approaching a live tarantula, viewed stimuli in each of three conditions: (1) very brief exposure (VBE) to masked images of spiders, severely limited awareness; (2) clearly visible exposure (CVE) to spiders, full awareness; and (3) masked images of flowers (control), severely limited awareness. Only VBE to masked spiders generated neural activity more strongly in phobic than in control participants, within subcortical fear, attention, higher-order language, and vision systems. Moreover, VBE activated regions that support fear processing in phobic participants without causing them to experience fear consciously. Counter-intuitively, CVE to the same spiders generated stronger neural activity in control rather than phobic participants within these and other systems. CVE deactivated regions supporting fear regulation and caused phobic participants to experience fear. CVE-induced activations also correlated with measures of explicit fear ratings, whereas VBE-induced activations correlated with measures of implicit fear (color-naming interference of spider words). These multiple dissociations between the effects of VBE and CVE to spiders suggest that limiting awareness of exposure to phobic stimuli through visual masking paradoxically facilitates their processing, while simultaneously minimizing the experience of fear. Hum Brain Mapp 38:2466-2481, 2017. © 2017 Wiley Periodicals, Inc.