Aha! and D'oh! experiences enhance learning for incidental information-new evidence supports the insight memory advantage.

Research on creative problem-solving finds that solutions achieved via spontaneous insight (i.e., Aha! moment) are better remembered than solutions reached without this sense of epiphany, referred to as an "insight memory advantage." We hypothesized that the insight memory advantage can spread to incidental information encoded in the moments surrounding insight as well. Participants (N = 291) were first given Rebus puzzles. After they indicated that they had found a solution, but before they could submit this solution, they were presented with scholastic facts that were incidental and unrelated to the problem at hand. Participants indicated whether they reached the solution via either insight or a step-by-step analysis. Memory results showed better performance for incidental scholastic facts presented when problem solving was accompanied by a spontaneous (Aha! experience) and induced (D'oh! experience) insight compared with solutions reached with analysis. This finding suggests that the memory advantage for problems solved via insight spreads to other unrelated information encoded in close temporal proximity and has implications for novel techniques to enhance learning in educational settings.

Utility of scores to predict alcohol use after liver transplant (lt): take them with a grain of salt.

BACKGROUND AIMS: The Sustained Alcohol use post-Liver Transplant (SALT) and the High-Risk Alcohol Relapse (HRAR) scores were developed to predict return to alcohol use after liver transplant (LT) for alcohol associated liver disease (ALD). METHODS: A retrospective analysis of deceased donor LT 10/2018 to 4/2022 was performed. All patients (pts) underwent careful pre-LT psychosocial evaluation. Data on alcohol use, substance abuse, prior rehabilitation, and legal issues were collected. Post-LT, all were encouraged to participate in rehabilitation programs and underwent interval phosphatidylethanol (PeTH) testing. Pts with ALD were stratified by < or > 6 month sobriety prior to listing. Those with <6 month were further stratified as acute alcoholic hepatitis (AH) by NIAAA criteria and non-AH. The primary outcome was utility of the SALT (<5 vs. ≥5) and HRAR (<3 vs. ≥3) scores to predict return to alcohol use (+PeTH) within 1 year after LT. RESULTS: Of the 365 LT, 86 had > 6 month sobriety and 85 had <6 month sobriety; 41 with AH and 44 non-AH. In those with AH, the mean time of abstinence to LT was 58 days, and 71% failed prior rehabilitation. Following LT, return to drinking was similar in the AH (24%) compared to <6M non-AH (15%) and >6M ALD (22%). Only 4% had returned to heavy drinking. The accuracy of both the SALT and HRAR scores to predict return to alcohol was low (accuracy 61-63%) with poor sensitivity (46% and 37%), specificity (67-68%), positive predictive value (22-26%) with moderate negative predictive value (NPV) (81-83%), respectively with higher NPVs (95%) in predicting return to heavy drinking. CONCLUSIONS: Both SALT and HRAR scores had good NPV in identifying patients at low risk for recidivism.

Rewarded Extinction Increases Amygdalar Connectivity and Stabilizes Long-Term Memory Traces in the vmPFC.

Neurobiological evidence in rodents indicates that threat extinction incorporates reward neurocircuitry. Consequently, incorporating reward associations with an extinction memory may be an effective strategy to persistently attenuate threat responses. Moreover, while there is considerable research on the short-term effects of extinction strategies in humans, the long-term effects of extinction are rarely considered. In a within-subjects fMRI study with both female and male participants, we compared counterconditioning (CC; a form of rewarded-extinction) to standard extinction at recent (24 h) and remote (approximately one month) retrieval tests. Relative to standard extinction, rewarded extinction diminished 24-h relapse of arousal and threat expectancy, and reduced activity in brain regions associated with the appraisal and expression of threat (e.g., thalamus, insula, periaqueductal gray). The retrieval of reward-associated extinction memory was accompanied by functional connectivity between the amygdala and the ventral striatum, whereas the retrieval of standard-extinction memories was associated with connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC). One month later, the retrieval of both standard-extinction and rewarded-extinction was associated with amygdala-vmPFC connectivity. However, only rewarded extinction created a stable memory trace in the vmPFC, identified through overlapping multivariate patterns of fMRI activity from extinction to 24-h and one-month retrieval. These findings provide new evidence that reward may generate a more stable and enduring memory trace of attenuated threat in humans.SIGNIFICANCE STATEMENT Prevalent treatments for pathologic fear and anxiety are based on the principles of Pavlovian extinction. Unfortunately, extinction forms weak memories that only temporarily inhibit the retrieval of threat associations. Thus, to increase the translational relevance of extinction research, it is critical to investigate whether extinction can be augmented to form a more enduring memory, especially after long intervals. Here, we used a multiday fMRI paradigm in humans to compare the short-term and long-term neurobehavioral effects of aversive-to-appetitive counterconditioning (CC), a form of augmented extinction. Our results provide novel evidence that including an appetitive stimulus during extinction can reduce short-term threat relapse and stabilize the memory trace of extinction in the ventromedial prefrontal cortex (vmPFC), for at least one month after learning.

Counterconditioning reduces contextual renewal in a novel context but not in the acquisition context.

As extinction is a context-dependent form of learning, conditioned responses tend to return when the conditioned stimulus (CS) is encountered outside the extinction context, known as contextual renewal. Counterconditioning is a technique that may lead to a more persistent reduction of the conditioned response. However, the effects of aversive-to-appetitive counterconditioning on contextual renewal in rodent studies are mixed. Further, research in humans is sparse, particularly direct statistical comparisons between counterconditioning and standard extinction techniques within the same study. Using a causal associative learning framework (the allergist task) implemented online, we compared the effectiveness of counterconditioning to standard extinction in preventing the renewal of judgements on the allergic properties of different food items (CSs). In a between-subjects design, 328 participants first learned that particular food items (CSs) lead to an allergic reaction in a specific restaurant (context A). Next, one CS was extinguished (no allergic reaction) while another CS was counterconditioned (positive outcome) in restaurant B. Causal judgements of the allergic properties of food items occurred in either the response acquisition context (ABA group, N = 112), the response reduction context where extinction and counterconditioning had occurred (ABB group, N = 107), or a novel context (ABC group, N = 109). Results showed that counterconditioning, compared to extinction, diminished the renewal of causal judgements to the CS in a novel context (ABC group). Still, casual judgements returned for both counter-conditioned and extinguished CSs in the response acquisition context (ABA group). Counterconditioning and extinction were similarly effective at preventing recovery of causal judgements in the response reduction context (ABB group); however, only in context B did participants choose the counter-conditioned CS as less likely to cause an allergic reaction in comparison to the extinguished CS. These findings indicate scenarios in which counterconditioning is more effective than standard extinction at diminishing the return of threat associations, with implications for improving the generalization of safety learning.

Prediction of adolescent pelvis development using femoral head and acetabulum growth in a longitudinal radiographic study.

INTRODUCTION: Adolescent total hip arthroplasty (THA) is guarded partially due unclarity as to when pediatric hip joints reach full development. This study sought to identify when maximum acetabular and femoral head diameters are achieved with relation to chronological and skeletal age. MATERIALS AND METHODS: Consecutive femoral head and acetabular diameters were measured in a random sample of 54 female and 78 male subjects, which were queried from a historical collection of annual radiographs of children. Femoral head and triradiate physeal plates were scored according to Oxford bone parameters. RESULTS: At 14 years females had femoral diameters of 4.16 +/- 0.23 cm and acetabular diameters of 5.15 +/- 0.30 cm. At 16 years males had femoral diameters of 4.85 +/- 0.30 cm and acetabular diameters of 5.90 +/- 0.35 cm. In the year following maximal femoral Oxford scores, no significant change was seen in femur and acetabulum diameters in females and in femur diameters in males. In the year following maximal acetabular Oxford scores, there was a significant increase in both femur and acetabulum diameters in both females and males. CONCLUSIONS: Females on average reach maximum pelvis maturity at 14 years and males reach maximum pelvis maturity at 16 years. A closed femoral head was found to be a good marker of full hip growth, while a closed triradiate was not. This study provides anatomical data for surgeons to consider in assessing risk factors of THA failure in adolescents.

The effects of aversive-to-appetitive counterconditioning on implicit and explicit fear memory.

Counterconditioning (CC) is a form of retroactive interference that inhibits expression of learned behavior. But similar to extinction, CC can be a fairly weak and impermanent form of interference, and the original behavior is prone to relapse. Research on CC is limited, especially in humans, but prior studies suggest it is more effective than extinction at modifying some behaviors (e.g., preference or valence ratings) than others (e.g., physiological arousal). Here, we used a within-subjects design to compare the effects of aversive-to-appetitive CC versus standard extinction on two separate tests of long-term memory in human adults: implicit physiological arousal and explicit episodic memory. Participants underwent Pavlovian fear conditioning to two semantic categories (animals, tools) paired with an electric shock. Conditioned stimuli (i.e., category exemplars) from one category were then extinguished, while stimuli from the other category were paired with a positive outcome. Participants returned 24-h later for a test of skin conductance responses (SCR) to the conditioned exemplars, as well as a surprise recognition memory test for stimuli encoded the previous day. Results showed reduced SCRs at a test for unique stimuli from a category that had undergone CC, relative to stimuli from a category that had undergone standard extinction. Additionally, participants selectively remembered more stimuli encoded during CC than extinction. These results provide new evidence that aversive-to-appetitive CC, as compared to extinction, strengthens memory for items directly associated with a positive outcome, which may provide stronger retrieval competition against a fear memory at test to help diminish fear relapse.

States of epistemic curiosity interfere with memory for incidental scholastic facts.

Curiosity can be a powerful motivator to learn and retain new information. Evidence shows that high states of curiosity elicited by a specific source (i.e., a trivia question) can promote memory for incidental stimuli (non-target) presented close in time. The spreading effect of curiosity states on memory for other information has potential for educational applications. Specifically, it could provide techniques to improve learning for information that did not spark a sense of curiosity on its own. Here, we investigated how high states of curiosity induced through trivia questions affect memory performance for unrelated scholastic facts (e.g., scientific, English, or historical facts) presented in close temporal proximity to the trivia question. Across three task versions, participants viewed trivia questions closely followed in time by a scholastic fact unrelated to the trivia question, either just prior to or immediately following the answer to the trivia question. Participants then completed a surprise multiple-choice memory test (akin to a pop quiz) for the scholastic material. In all three task versions, memory performance was poorer for scholastic facts presented after trivia questions that had elicited high versus low levels of curiosity. These results contradict previous findings showing curiosity-enhanced memory for incidentally presented visual stimuli and suggest that target information that generates a high-curiosity state interferes with encoding complex and unrelated scholastic facts presented close in time.

Carbon Dioxide Reactivity Differentially Predicts Fear Expression After Extinction and Retrieval-Extinction in Rats.

Background: Cues present during a traumatic event may result in persistent fear responses. These responses can be attenuated through extinction learning, a core component of exposure therapy. Exposure/extinction is effective for some people, but not all. We recently demonstrated that carbon dioxide (CO2) reactivity predicts fear extinction memory and orexin activation and that orexin activation predicts fear extinction memory, which suggests that a CO2 challenge may enable identification of whether an individual is a good candidate for an extinction-based approach. Another method to attenuate conditioned responses, retrieval-extinction, renders the original associative memory labile via distinct neural mechanisms. The purpose of the current study was to examine whether we could replicate previous findings that retrieval-extinction is more effective than extinction at preventing the return of fear and that CO2 reactivity predicts fear memory after extinction. We also examined whether CO2 reactivity predicts fear memory after retrieval-extinction. Methods: Male rats first underwent a CO2 challenge and fear conditioning and were assigned to receive either standard extinction (n = 28) or retrieval-extinction (n = 28). Then, they underwent a long-term memory (LTM) test and a reinstatement test. Results: We found that retrieval-extinction resulted in lower freezing during extinction, LTM, and reinstatement than standard extinction. Using the best subset approach to linear regression, we found that CO2 reactivity predicted LTM after extinction and also predicted LTM after retrieval-extinction, although to a lesser degree. Conclusions: CO2 reactivity could be used as a screening tool to determine whether an individual may be a good candidate for an extinction-based therapeutic approach.

Extinction learning underlies exposure therapy, a treatment for anxiety disorders. However, not everyone benefits from exposure therapy, highlighting the need in developing approaches that may help predict which individuals will respond. We tested whether extinction or an alternative treatment called retrieval-extinction would be more effective at reducing conditioned fear responses in rats and whether the response to a carbon dioxide (CO₂) challenge would predict treatment response. We found that retrieval-extinction was more effective at reducing fear, and CO₂ reactivity was better at predicting the response to extinction. These findings could help improve treatment strategies for anxiety disorders.

Anaphylactic Shock to Intravenous Indocyanine Green During a Robotic Right Colectomy.

Intravenous indocyanine green (IV ICG) is regarded as a safe immunofluorescence agent used to assess bowel perfusion prior to creating bowel anastomoses and aids in ureter identification during intra-abdominal surgery. We report the first instance of anaphylactic shock to IV ICG after prior toleration of ICG via an intra-ureteral route. Shortly after administering IV ICG, our patient became hypotensive and hypoxic requiring chest compressions, vasoactive medications, and thoracostomy tubes prior to identifying the symptoms as an allergic reaction. Anaphylaxis is not a recognized side effect of ICG and was not immediately considered. As ICG becomes increasingly utilized as an immunofluorescence agent among surgical specialties, increased awareness and recognition of anaphylactic shock as a potential side effect of ICG may lead to expedited diagnoses, treatment, and more critical evaluation of indications for future use. Additionally, our patient first tolerated intra-ureteral administration without a systemic reaction, suggesting a possible sensitization mechanism.

Substance Use Among Physician Assistant Students: A National Study on the Prevalence of Alcohol, Tobacco, Illicit Substances, and Medication Use.

INTRODUCTION: The purpose of this study was to discover the substance use prevalence among physician assistant students (PA-S) compared with the age-relevant general US population and to examine the frequency of stress, burnout, anxiety, and depression during the didactic and clinical phases, while accounting for the impact of the COVID-19 pandemic. METHODS: A 20-item survey instrument was created. Self-reported data included demographics, anxiety, burnout, tobacco, illicit substances, and prescription medication use. Outcome-based inventories included a modified Perceived Stress Scale, Patient Health Questionnaire-2 (PHQ-2), and Alcohol Use Disorder Identification Test-Concise. The survey was emailed to all US programs (∼270 programs; ∼25,000 students), with 54 programs approving dissemination to their students (n∼4,760). RESULTS: Of the 1432 responses (30% response rate, 96% completion rate), the final validated sample was 1378 students (56.1% didactic, 43.8% clinical). When compared with the national population, PA-S prevalence for tobacco (5.2%) and illicit substance use (9.9%) were notably lower; alcohol (53.5%) was comparable; and prescription medication (7.0%) is only reported for PA students due to the lack of a national comparison. A higher frequency of substance use was observed during the didactic (52.5%) vs clinical (47.5%) phases. Stress was the dominant factor in both phases (93.5% didactic, 86.1% clinical). Respondents reported that the COVID-19 pandemic had minimal impact on reported rates, other than alcohol. DISCUSSION: Although PA-S substance use prevalence is at or below the national population, PA programs are encouraged to review their policies and provide conversations and resources for students who may have one or more risk factors and experience a negative effect from current substance use.

Leveraging a smartphone to perform time-gated luminescence measurements.

Empowered by advanced on-board sensors, high-performance optics packages and ever-increasing computational power, smartphones have democratized data generation, collection, and analysis. Building on this capacity, many platforms have been developed to enable its use as an optical sensing platform for colorimetric and fluorescence measurements. In this paper, we report the ability to enable a smartphone to perform laboratory quality time-resolved analysis of luminescent samples via the exploitation of the rolling shutter mechanism of the native CMOS imager. We achieve this by leveraging the smartphone's standard image capture applications, commercially available image analysis software, and housing the device within a UV-LED containing case. These low-cost modifications enable us to demonstrate the smartphone's analytical potential by performing tasks ranging from authentication and encryption to the interrogation of packaging, compounds, and physical phenomena. This approach underscores the power of repurposing existing technologies to extend the reach and inclusivity of scientific exploration, opening new avenues for data collection and analysis.

Predicting Reciprocal Thoracic Change, Proximal Junctional Kyphosis, and Revision Surgery in Adult Spinal Deformity.

BACKGROUND: Compensatory mechanisms in patients with adult spinal deformity (ASD) that lead to poor quality of life include positive sagittal balance and pelvic retroversion. The objective of this retrospective review was to identify demographic and radiographic parameters of sagittal alignment that are correlated with thoracic kyphosis (TK), PJK, and reoperation in patients undergoing surgical correction for ASD. METHODS: A single-center database of 155 patients with ASD undergoing surgery from 2008 to 2015 was reviewed. Patients >18 years old who underwent multilevel thoracolumbar fusion or fusion of thoracic vertebrae to the pelvis were included. Demographics and radiographic measurements of sagittal alignment were collected preoperatively, 6 weeks postoperatively, and 1 year postoperatively. Statistical analysis was performed to compare groups that did or did not develop change in thoracic kyphosis or PJK at early or late follow-up. Additionally, patients requiring reoperation were evaluated. RESULTS: Increased thoracic kyphosis was associated with older age, hypolordosis, and comorbid PJK. Early PJK was associated with older age, hypolordosis, and increased T1 pelvic angle. Reoperation was associated with older age, higher positive sagittal balance, hypolordosis, and pelvic retroversion; PJK and thoracic kyphosis did not increase risk for reoperation. CONCLUSIONS: Thoracic reciprocal change following surgical correction of ASD is highly associated with PJK, although neither increased risk of reoperation. PJK may be predicted by older age, hypolordosis, and increased T1 pelvic angle. Reoperation in patients with ASD is more likely in older patients with positive sagittal balance, a compensatory flat lower back, and compensatory pelvic retroversion.

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration.

The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.

[An Unusual Reason for Nocturia Combined with Cognitive Decline and Gait Disturbance]. / Nicht alltägliche Ursache der Nykturie bei demenzieller Entwicklung und Gangunsicherheit.

An Unusual Reason for Nocturia Combined with Cognitive Decline and Gait Disturbance Abstract. We present the case of a woman with frequency, nocturia, and painful bladder without urinary incontinence. Further examination showed cognitive decline and gait disturbance. A magnetic resonance imaging of the neurocranium showed normal pressure hydrocephalus. After lumbar puncture with cerebrospinal fluid evacuation the symptoms improved. The clinical triad of gait disturbance, cognitive decline and urinary symptoms like frequency with or without incontinence is typical for normal pressure hydrocephalus (Hakim-Adams triad).

Behavioral and neural processes in counterconditioning: Past and future directions.

Counterconditioning refers both to the technique and putative process by which behavior is modified through a new association with a stimulus of an opposite valence. Similar to extinction, counterconditioning is considered a form of inhibition that interferes with the expression of the originally learned response without erasing it. But whereas interest in extinction continues to rise, counterconditioning has received far less attention. Here, we provide an in-depth review of counterconditioning research and detail whether counterconditioning is any more effective than extinction at preventing relapse of the originally learned behavior. We consider the clinical implications of counterconditioning, describe recent neurobiological and neuroimaging research in this area, and consider future avenues in need of further investigation.

A rare case of Merkel cell carcinoma with ovarian metastasis.

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy that normally occurs in sun-exposed areas of the skin. Risk factors are immundeficency and Merkel cell polyomavirus.Treatment options are surgery, radiotherapy, chemotherapy and immunotherapy in clinical trials. CASE REPORT: We describe a case of an 80-year-old woman with ovarian metastasis of MCC six years after excision of a cutaneous MCC on the cheek. DISCUSSION: To our knowledge only three cases with ovarian metastasis of MCC have been described so far. Our case is the second with distant metastasis to the ovary spreading from a primary tumor in the skin of the head, in the other two cases the primary tumor was in the inguinal skin. CONCULSION: MCC is a highly aggressive cutaneous and mucosal malignancy with frequent recurrence, lymph node and distant metastases. There is no clear consensus how to treat metastatic disease.

CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD). Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS) phagocytosis by the retinal pigment epithelium (RPE) in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR) and CD36-/- mice). Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF) expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

Role of the chemokine receptor CX3CR1 in the mobilization of phagocytic retinal microglial cells.

We recently showed that subretinal CX3CR1-dependent microglial cell (MC) accumulation may lead to age-related macular degeneration. The fate of MC after engulfing retinal debris is poorly understood. Severe photoreceptor degeneration was observed 40days after exposure to bright light in CX3CR1-deficient but not control mice, and more MCs accumulated in the subretinal space of the former than the latter. To study the fate of subretinal MCs in CX3CR1 competent animals, we used a dystrophic rat model in which abundant subretinal MC accumulation is observed secondary to retinal degeneration. In dystrophic rats, MCs containing rhodopsin or rod outer segment (ROS) debris were found outside the outer retina at sites suggesting choroidal and ciliary egress. In conclusion, our data indicate that MC accumulation at injury sites is independent of CX3CR1 and precedes photoreceptor degeneration. The ectopic presence of rhodopsin-positive MCs suggests that CX3CR1 participates in MC egress from the outer retina.

Promoting mental health and well-being in Aboriginal contexts: successful elements of suicide prevention work.

ISSUE ADDRESSED: The Suicide Prevention in Country SA (SPICSA) initiative was funded by the South Australian Social Inclusion Initiative in response to concerns about the higher rates of self-harm and suicidal behaviour in regional areas across the State, particularly for young people and Aboriginal people. METHODS: A variety of strategies and resources were provided to facilitate coherence across the State, while ensuring local areas had flexibility to design initiatives that responded to their needs and directions. These strategies mirrored good practice elements for working in Aboriginal contexts. RESULTS: Successful community-driven activities were implemented in local areas that focused strongly on a health promotion approach, not just a prevention approach, and that engaged Aboriginal people effectively in the process. This resulted in learning and confirmation about suicide prevention work in Aboriginal contexts, including the value of community partners.