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The cell adhesion molecule Leucine-Rich Repeat Transmembrane neuronal protein 2 (LRRTM2) is crucial for synapse development and function. However, our understanding of its endogenous trafficking has been limited due to difficulties in manipulating its coding sequence (CDS) using standard genome editing techniques. Instead, we replaced the entire LRRTM2 CDS by adapting a two-guide CRISPR knock-in method, enabling complete control of LRRTM2. In primary rat hippocampal cultures dissociated from embryos of both sexes, N-terminally tagged, endogenous LRRTM2 was found in 80% of synapses, and synaptic LRRTM2 content correlated with PSD-95 and AMPAR levels. LRRTM2 was also enriched with AMPARs outside synapses, demonstrating the sensitivity of this method to detect relevant new biology. Finally, we leveraged total genomic control to increase the synaptic levels of LRRTM2 via simultaneous mutation of its C-terminal domain, which did not correspondingly increase AMPAR enrichment. The coding region of thousands of genes span lengths suitable for whole-CDS replacement, suggesting this simple approach will enable straightforward structure-function analysis in neurons. Significance Statement Synaptic cell adhesion molecules are transmembrane proteins vital for neurotransmission, and their genes are frequently linked to disease. Mechanistic studies are challenging, however, because overexpression alters their protein trafficking and perturbs neuronal function, yet traditional gene-editing techniques typically permit manipulation at just single sites. Here, we replaced the entire coding sequence (CDS) of the critical adhesion molecule Leucine-Rich Repeat Transmembrane protein 2 (LRRTM2) with a freely editable custom donor sequence, and made the approach even more versatile through introduction of knock-in-dependent cell markers. Using whole-CDS replacement, we discover new aspects of LRRTM2 subcellular distribution and test its role in regulating synaptic proteins. The approach should be suited to structure-function analysis of many other neuronal proteins in their endogenous genetic locus., (Copyright © 2025 the authors.)

Fluorescent reporters for glutamate release and postsynaptic Ca 2+ signaling are essential tools for quantifying synapse functional heterogeneity across neurons and circuits. However, leveraging these probes for neuroscience requires scalable experimental frameworks. Here, we devised a high-throughput approach to efficiently collect and analyze hundreds of optical recordings of glutamate release activity at presynaptic boutons in cultured rat hippocampal neurons. Boutons exhibited remarkable functional heterogeneity and could be separated into multiple functional classes based on their iGluSnFR3 responses to single action potentials, paired stimuli, and synaptic parameters derived from mean-variance analysis. Finally, we developed a novel all-optical assay of pre- and postsynaptic glutamatergic synapse function. We deployed iGluSnFR3 with a red-shifted, postsynaptically-targeted Ca 2+ sensor, enabling direct imaging and analysis of NMDA receptor-mediated synaptic transmission at large numbers of dendritic spines. This work enables direct observation of the flow of information at single synapses and should speed detailed investigations of synaptic functional heterogeneity.

Far-field (9.7-35.5 km) noise measurements were made during the fifth flight test of SpaceX's Starship Super Heavy, which included the first-ever booster catch. Key results involving launch and flyback sonic boom sound levels include (a) A-weighted sound exposure levels during launch are 18 dB less than predicted at 35 km; (b) the flyback sonic boom exceeds 10 psf at 10 km; and (c) comparing Starship launch noise to Space Launch System and Falcon 9 shows that Starship is substantially louder; the far-field noise produced during a Starship launch is at least ten times that of Falcon 9., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Introduction: Corticosteroid injection (CSI) for carpal tunnel syndrome is a common diagnostic and therapeutic procedure. Adverse effects of corticosteroid injections are infrequent, though rare cases of flexor tendon rupture have been documented., Presentation of Case: We present a case of a 67-year-old female with acute loss of left index finger flexion due to rupture of the left index flexor digitorum profundus (FDP) and the flexor digitorum superficialis (FDS) tendons and left long finger FDS tendon following numerous carpal tunnel corticosteroid injections. Intraoperatively, she was also found to have a complete rupture of the long finger FDS and partial rupture of the long finger FDP. Side-to-side tendon transfers were performed to restore the flexor tendon function., Discussion: The overall incidence of serious adverse effects in patients receiving CSIs for carpal tunnel syndrome, including flexor tendon rupture, intraneural injection or gangrene, is extremely low. Only three cases of flexor tendon ruptures following CSI for carpal tunnel syndrome have been reported in the literature. Given our patient's multiple CSIs per year over the course of 6 years, she may have been at increased risk of spontaneous tendon rupture given extra-articular CSIs can result in tendon rupture as a rare, but serious complication., Conclusion: This case demonstrates that flexor tendon ruptures are a possible, although rare, complication following steroid injections for carpal tunnel syndrome. Proper injection techniques should be used to minimize adverse effects., Competing Interests: Declaration of competing interest All authors disclose no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The act of recalling memories can paradoxically lead to the forgetting of other associated memories, a phenomenon known as retrieval-induced forgetting (RIF). Inhibitory control mechanisms, primarily mediated by the prefrontal cortex, are thought to contribute to RIF. In this study, we examined whether stimulating the medial prefrontal cortex (mPFC) with transcranial direct current stimulation modulates RIF and investigated the associated electrophysiological correlates. In a randomized study, 50 participants (27 males and 23 females) received either real or sham stimulation before performing retrieval practice on target memories. After retrieval practice, a final memory test to assess RIF was administered. We found that stimulation selectively increased the retrieval accuracy of competing memories, thereby decreasing RIF, while the retrieval accuracy of target memories remained unchanged. The reduction in RIF was associated with a more pronounced beta desynchronization within the left dorsolateral prefrontal cortex (left-DLPFC), in an early time window (<500 ms) after cue onset during retrieval practice. This led to a stronger beta desynchronization within the parietal cortex in a later time window, an established marker for successful memory retrieval. Together, our results establish the causal involvement of the mPFC in actively suppressing competing memories and demonstrate that while forgetting arises as a consequence of retrieving specific memories, these two processes are functionally independent. Our findings suggest that stimulation potentially disrupted inhibitory control processes, as evidenced by reduced RIF and stronger beta desynchronization in fronto-parietal brain regions during memory retrieval, although further research is needed to elucidate the specific mechanisms underlying this effect., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Khan et al.)

MAGUK scaffold proteins play a central role in maintaining and modulating synaptic signaling, providing a framework to retain and position receptors, signaling molecules, and other synaptic components. In particular, the MAGUKs SAP102 and PSD-95 are essential for synaptic function at distinct developmental timepoints and perform both overlapping and unique roles. While their similar structures allow for common binding partners, SAP102 is expressed earlier in synapse development and is required for synaptogenesis, whereas PSD-95 expression peaks later and is associated with synapse maturation. PSD-95 and other key synaptic proteins organize into subsynaptic nanodomains that have a significant impact on synaptic transmission, but the nanoscale organization of SAP102 is unknown. How SAP102 is organized within the synapse, and how it relates spatially to PSD-95 on a nanometer scale, could underlie its unique functions and impact how SAP102 scaffolds synaptic proteins. Here we used DNA-PAINT super-resolution microscopy to measure SAP102 nano-organization and its spatial relationship to PSD-95 at individual synapses in mixed-sex rat cultured neurons. We found that like PSD-95, SAP102 accumulates in high-density subsynaptic nanoclusters (NCs). However, SAP102 NCs were smaller and denser than PSD-95 NCs across development. Additionally, only a subset of SAP102 NCs co-organized with PSD-95, revealing MAGUK nanodomains within individual synapses containing either one or both proteins. These MAGUK nanodomain types had distinct NC properties and were differentially enriched with the presynaptic release protein Munc13-1. This organization into both shared and distinct subsynaptic nanodomains may underlie the ability of SAP102 and PSD-95 to perform both common and unique synaptic functions., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

During NASA X-59 quiet supersonic aircraft community response tests, low-boom recordings will contain contaminating noise from instrumentation and ambient acoustical sources. This noise can inflate sonic boom perception metrics by several decibels. This paper discusses the development and comparison of robust lowpass filtering techniques for removing contaminating noise effects from low-boom recordings. The two filters are a time-domain Butterworth-magnitude filter and a frequency-domain Brick Wall filter. Both filters successfully reduce noise contamination in metric calculations for simulated data with real-world contaminating noise and demonstrate comparable performance to a modified ISO 11204 correction. The Brick Wall filter's success indicates that further attempts to match boom spectrum high-frequency roll-off beyond the contaminating noise floor are unnecessary and have marginal improvements on final metric calculations. Additionally, the Butterworth filter removes statistical correlation between ambient and boom levels for a real-world flight campaign, adding evidence that these techniques also work on other boom shapes. Overall, both filters can produce accurate metric calculations with only a few hundred hertz of positive signal-to-noise ratio. This work describes methods for accurate metric calculations in the presence of moderate noise contamination that should benefit X-59 and future low-boom supersonic aircraft testing., (© 2024 Acoustical Society of America.)

Nanoscale protein organization within the active zone (AZ) and post-synaptic density (PSD) influences synaptic transmission. Nanoclusters of presynaptic Munc13-1 are associated with readily releasable pool size and neurotransmitter vesicle priming, while postsynaptic PSD-95 nanoclusters coordinate glutamate receptors across from release sites to control their opening probability. Nanocluster number, size, and protein density vary between synapse types and with development and plasticity, supporting a wide range of functional states at the synapse. Whether or how the receptors themselves control this critical architecture remains unclear. One prominent PSD molecular complex is the NMDA receptor (NMDAR). NMDARs coordinate several modes of signaling within synapses, giving them the potential to influence synaptic organization through direct protein interactions or through signaling. We found that loss of NMDARs results in larger synapses that contain smaller, denser, and more numerous PSD-95 nanoclusters. Intriguingly, NMDAR loss also generates retrograde reorganization of the active zone, resulting in denser, more numerous Munc13-1 nanoclusters, more of which are aligned with PSD-95 nanoclusters. Together, these changes to synaptic nanostructure predict stronger AMPA receptor-mediated transmission in the absence of NMDARs. Notably, while prolonged antagonism of NMDAR activity increases Munc13-1 density within nanoclusters, it does not fully recapitulate these trans-synaptic effects. Thus, our results confirm that NMDARs play an important role in maintaining pre- and postsynaptic nanostructure and suggest that both decreased NMDAR expression and suppressed NMDAR activity may exert distinct effects on synaptic function, yet through unique architectural mechanisms., Competing Interests: Conflicts of Interest: None

Tight coordination of the spatial relationships between protein complexes is required for cellular function. In neuronal synapses, many proteins responsible for neurotransmission organize into subsynaptic nanoclusters whose trans-cellular alignment modulates synaptic signal propagation. However, the spatial relationships between these proteins and NMDA receptors (NMDARs), which are required for learning and memory, remain undefined. Here, we mapped the relationship of key NMDAR subunits to reference proteins in the active zone and postsynaptic density using multiplexed super-resolution DNA-PAINT microscopy. GluN2A and GluN2B subunits formed nanoclusters with diverse configurations that, surprisingly, were not localized near presynaptic vesicle release sites marked by Munc13-1. However, a subset of presynaptic sites was configured to maintain NMDAR activation: these were internally denser, aligned with abundant PSD-95, and associated closely with specific NMDAR nanodomains. This work reveals a new principle regulating NMDAR signaling and suggests that synaptic functional architecture depends on assembly of multiprotein nanodomains whose interior construction is conditional on trans-cellular relationships.

Shigella spp. are the causative agents of bacterial dysentery and shigellosis, mainly in children living in developing countries. The study of Shigella entire life cycle in vivo and the evaluation of vaccine candidates' protective efficacy have been hampered by the lack of a suitable animal model of infection. None of the studies evaluated so far (rabbit, guinea pig, mouse) allowed the recapitulation of full shigellosis symptoms upon Shigella oral challenge. Historical reports have suggested that dysentery and scurvy are both metabolic diseases associated with ascorbate deficiency. Mammals, which are susceptible to Shigella infection (humans, non-human primates and guinea pigs) are among the few species unable to synthesize ascorbate. We optimized a low-ascorbate diet to induce moderate ascorbate deficiency, but not scurvy, in guinea pigs to investigate whether poor vitamin C status increases the progression of shigellosis. Moderate ascorbate deficiency increased shigellosis symptom severity during an extended period of time (up to 48 h) in all strains tested ( Shigella sonnei , Shigella flexneri 5a, and 2a). At late time points, an important influx of neutrophils was observed both within the disrupted colonic mucosa and in the luminal compartment, although Shigella was able to disseminate deep into the organ to reach the sub-mucosal layer and the bloodstream. Moreover, we found that ascorbate deficiency also increased Shigella penetration into the colon epithelium layer in a Gulo -/- mouse infection model. The use of these new rodent models of shigellosis opens new doors for the study of both Shigella infection strategies and immune responses to Shigella infection.

Anxiety, posttraumatic stress, and depression markedly increased worldwide during the COVID-19 pandemic. People with these conditions experience distressing intrusive thoughts, yet conventional therapies often urge them to avoid suppressing their thoughts because intrusions might rebound in intensity and frequency, worsening the disorders. In contrast, we hypothesized that training thought suppression would improve mental health. One hundred and twenty adults from 16 countries underwent 3 days of online training to suppress either fearful or neutral thoughts. No paradoxical increases in fears occurred. Instead, suppression reduced memory for suppressed fears and rendered them less vivid and anxiety provoking. After training, participants reported less anxiety, negative affect, and depression with the latter benefit persisting at 3 months. Participants high in trait anxiety and pandemic-related posttraumatic stress gained the largest and most durable mental health benefits. These findings challenge century-old wisdom that suppressing thoughts is maladaptive, offering an accessible approach to improving mental health.

The MAGUK family of scaffold proteins plays a central role in maintaining and modulating synaptic signaling, providing a framework to retain and position receptors, signaling molecules, and other synaptic components. Of these scaffold proteins, SAP102 and PSD-95 are essential for synaptic function at distinct developmental timepoints and perform overlapping as well as unique roles. While their similar structures allow for common binding partners, SAP102 is expressed earlier in synapse development and is required for synaptogenesis, whereas PSD-95 expression peaks later in development and is associated with synapse maturation. PSD-95 and other key synaptic proteins organize into subsynaptic nanodomains that have a significant impact on synaptic transmission, but the nanoscale organization of SAP102 is unknown. How SAP102 is organized within the synapse, and how it relates spatially to PSD-95 on a nanometer scale, could impact how SAP102 clusters synaptic proteins and underlie its ability to perform its unique functions. Here we used DNA-PAINT super-resolution microscopy to measure SAP102 nano-organization and its spatial relationship to PSD-95 at individual synapses. We found that like PSD-95, SAP102 accumulates in high-density subsynaptic nanoclusters. However, SAP102 nanoclusters were smaller and denser than PSD-95 nanoclusters across development. Additionally, only a subset of SAP102 nanoclusters co-organized with PSD-95, revealing that within individual synapses there are nanodomains that contain either one or both proteins. This organization into both shared and distinct subsynaptic nanodomains may underlie the ability of SAP102 and PSD-95 to perform both common and unique synaptic functions., Competing Interests: The authors declare no competing financial interests.

The ability to suppress unwelcome memories is important for productivity and well-being. Successful memory suppression is associated with hippocampal deactivations and a concomitant disruption of this region's functionality. Much of the previous neuroimaging literature exploring such suppression-related hippocampal modulations has focused on the region's negative coupling with the prefrontal cortex. Task-based changes in functional connectivity between the hippocampus and other brain regions still need further exploration. In the present study, we utilize psychophysiological interactions and seed connectome-based predictive modeling to investigate the relationship between the hippocampus and the rest of the brain as 134 participants attempted to suppress unwanted memories during the Think/No-Think task. The results show that during retrieval suppression, the right hippocampus exhibited decreased functional connectivity with visual cortical areas (lingual and cuneus gyrus), left nucleus accumbens and the brain-stem that predicted superior forgetting of unwanted memories on later memory tests. Validation tests verified that prediction performance was not an artifact of head motion or prediction method and that the negative features remained consistent across different brain parcellations. These findings suggest that systemic memory suppression involves more than the modulation of hippocampal activity-it alters functional connectivity patterns between the hippocampus and visual cortex, leading to successful forgetting., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Suppressing retrieval of unwanted memories can cause forgetting, an outcome often attributed to the recruitment of inhibitory control. This suppression-induced forgetting (SIF) generalizes to different cues used to test the suppressed content (cue-independence), a property taken as consistent with inhibition. But does cue-independent forgetting necessarily imply that a memory has been inhibited? Tomlinson et al. (Proc Natl Acad Sci 106:15588-15593, 2009) reported a surprising finding that pressing a button also led to cue-independent forgetting, which was taken as support for an alternative interference account. Here we investigated the role of inhibition in forgetting due to retrieval suppression and pressing buttons. We modified Tomlinson et al.'s procedure to examine an unusual feature they introduced that may have caused memory inhibition effects in their experiment: the omission of explicit task-cues. When tasks were uncued, we replicated the button-press forgetting effect; but when cued, pressing buttons caused no forgetting. Moreover, button-press forgetting partially reflects output-interference effects at test and not a lasting effect of interference. In contrast, SIF occurred regardless of these procedural changes. Collectively, these findings indicate that simply pressing a button does not induce forgetting, on its own, without confounding factors that introduce inhibition into the task and that inhibition likely underlies SIF., (© 2023. The Author(s).)

To improve understanding of super heavy-lift rocket acoustics, this letter documents initial findings from noise measurements during liftoff of the Space Launch System's Artemis-I mission. Overall sound pressure levels, waveform characteristics, and spectra are described at distances ranging from 1.5 to 5.2 km. Significant results include: (a) the solid rocket boosters' ignition overpressure is particularly intense in the direction of the pad flame trench exit; (b) post-liftoff maximum overall levels range from 127 to 136 dB, greater than pre-launch predictions; and (c) the average maximum one-third-octave spectral peak occurred at 20 Hz, causing significant deviation between flat and A-weighted levels.

Processes that might facilitate the forgetting of unwanted experiences typically require the actual or imagined re-exposure to reminders of the event, which is aversive and carries risks to people. But it is unclear whether awareness of aversive content is necessary for effective voluntary forgetting. Disrupting hippocampal function through retrieval suppression induces an amnesic shadow that impairs the encoding and stabilization of unrelated memories that are activated near in time to people's effort to suppress retrieval. Building on this mechanism, here we successfully disrupt retention of unpleasant memories by subliminally reactivating them within this amnesic shadow. Critically, whereas unconscious forgetting occurs on these affective memories, the amnesic shadow itself is induced by conscious suppression of unrelated and benign neutral memories, avoiding conscious re-exposure of unwelcome content. Combining the amnesic shadow with subliminal reactivation may offer a new approach to voluntary forgetting that bypasses the unpleasantness in conscious exposure to unwanted memories., (© 2022. The Author(s).)

Sonic boom measurements from recent flight tests have provided an opportunity to investigate effects of microphone installation on sonic boom waveforms, spectra, and metric levels in support of NASA X-59 flight test planning. While those flight tests used N-wave aircraft (F-18s), modeling studies were also conducted using source characteristics for a shaped low-boom aircraft. Of particular interest were the effects of receiver height on boom waveforms and metrics at elevated receiver positions, microphone installation, and local ground cover type. Reductions of more than 2 dB in A-weighted sound exposure level and perceived level were shown for 1.6 ft (0.48 m) microphone heights for 35º ray elevation angle. Measured and modeled results are described in this letter.

Active forgetting occurs in many species, but how behavioral control mechanisms influence which memories are forgotten remains unknown. We previously found that when rats need to retrieve a memory to guide exploration, it reduces later retention of other competing memories encoded in that environment. As with humans, this retrieval-induced forgetting relies on prefrontal control processes. Dopaminergic input to the prefrontal cortex is important for executive functions and cognitive flexibility. We found that, in a similar way, retrieval-induced forgetting of competing memories in male rats requires prefrontal dopamine signaling through D 1 receptors. Blockade of medial prefrontal cortex D 1 receptors as animals encountered a familiar object impaired active forgetting of competing object memories as measured on a later long-term memory test. Inactivation of the ventral tegmental area produced the same pattern of behavior, a pattern that could be reversed by concomitant activation of prefrontal D 1 receptors. We observed a bidirectional modulation of retrieval-induced forgetting by agonists and antagonists of D 1 receptors in the medial prefrontal cortex. These findings establish the essential role of prefrontal dopamine in the active forgetting of competing memories, contributing to the shaping of retention in response to the behavioral goals of an organism. SIGNIFICANCE STATEMENT Forgetting is a ubiquitous phenomenon that is actively promoted in many species. The very act of remembering some experiences can cause forgetting of others, in both humans and rats. This retrieval-induced forgetting process is thought to be driven by inhibitory control signals from the prefrontal cortex that target areas where the memories are stored. Here we started disentangling the neurochemical signals in the prefrontal cortex that are essential to retrieval-induced forgetting. We found that, in rats, the release of dopamine in this area, acting through D 1 receptors, was essential to causing active forgetting of competing memories. Inhibition of D 1 receptors impaired forgetting, while activation increased forgetting. These findings are important, because the mechanisms of active forgetting and their linkage to goal-directed behavior are only beginning to be understood., (Copyright © 2022 Gallo et al.)

The Saturn V is a monument to one of mankind's greatest achievements: the human Moon landings. However, online claims about this vehicle's impressive acoustics by well-meaning individuals are often based on misunderstood or incorrect data. This article, intended for both educators and enthusiasts, discusses topics related to rocket acoustics and documents what is known about the Saturn V's levels: overall power, maximum overall sound pressure, and peak pressure. The overall power level was approximately 204 dB re 1 pW, whereas its lesser sound pressure levels were impacted by source size, directivity, and propagation effects. As this article is part of a special issue on Education in Acoustics in The Journal of the Acoustical Society of America, supplementary Saturn V-related homework problems are included.

Background: Renal sympathetic denervation (RSD) provides a minimally invasive interventional treatment modality for patients with resistant hypertension. However, the post-operative outcomes remain a key area of investigation since its earliest clinical trials., Aim: To evaluate patient outcomes after RSD intervention among peer-reviewed patient cases., Methods: A systematic review of literature on MEDLINE, Google Scholar, and the Cochrane Database of Systematic Reviews for RSD case studies to assess post-operative hypertension readings and medical management., Results: Among 51 RSD cases, the post-operative RSD patients report an apparent reduction with a mean number of 3.1 antihypertensive medications. The mean systolic arterial blood pressure 1 year following RSD was 136.0 mmHg (95%CI: 118.7-153.3)., Conclusion: The apparent improvements in office systolic blood pressure after 12 month post-operative RSD can support the therapeutic potential of this intervention for blood pressure reduction. Additional studies which utilized a uniform methodology for blood pressure measurement can further support the findings of this systematic review., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

How do people limit awareness of unwanted memories? When such memories intrude, a control process engages the right DLPFC (rDLPFC) to inhibit hippocampal activity and stop retrieval. It remains unknown how the need for control is detected, and whether control operates proactively to prevent unwelcome memories from being retrieved, or responds reactively, to counteract intrusions. We hypothesized that dorsal ACC (dACC) detects the emergence of an unwanted trace in awareness and transmits the need for inhibitory control to rDLPFC. During a memory suppression task, we measured in humans (both sexes) trial-by-trial variations in the theta power and N2 amplitude of dACC, two EEG markers that are thought to reflect the need for control. With simultaneous EEG-fMRI recordings, we tracked interactions among dACC, rDLPFC, and hippocampus during suppression. We found a clear role of dACC in detecting the need for memory control and upregulating prefrontal inhibition. Importantly, we identified distinct early (300-450 ms) and late (500-700 ms) dACC contributions, suggesting both proactive control before recollection and reactive control in response to intrusions. Stronger early activity was associated with reduced hippocampal activity and diminished BOLD signal in dACC and rDLPFC, suggesting that preempting retrieval reduced overall control demands. In the later window, dACC activity was larger, and effective connectivity analyses revealed robust communication from dACC to rDLPFC and from rDLPFC to hippocampus, which are tied to successful forgetting. Together, our findings support a model in which dACC detects the emergence of unwanted content, triggering top-down inhibitory control, and in which rDLPFC countermands intruding thoughts that penetrate awareness. SIGNIFICANCE STATEMENT Preventing unwanted memories from coming to mind is an adaptive ability of humans. This ability relies on inhibitory control processes in the prefrontal cortex to modulate hippocampal retrieval processes. How and when reminders to unwelcome memories come to trigger prefrontal control mechanisms remains unknown. Here we acquired neuroimaging data with both high spatial and temporal resolution as participants suppressed specific memories. We found that the anterior cingulate cortex detects the need for memory control, responding both proactively to early warning signals about unwelcome content and reactively to intrusive thoughts themselves. When unwanted traces emerge in awareness, anterior cingulate communicates with prefrontal cortex and triggers top-down inhibitory control over the hippocampus through specific neural oscillatory networks., (Copyright © 2022 Crespo-García et al.)

Navigating novel, unpredicted service disruptions can be complex and unparalleled. To effectively handle service interruptions, board certified behavior analysts (BCBAs®) must make sound clinical decisions, comply with the Behavior Analyst Certification Board's Ethics Code for Behavior Analysts (2020a), and critically engage in ongoing risk/benefit assessments for each individual client. Unfortunately, most BCBAs do not receive coursework, training, or fieldwork supervision in advanced risk mitigation. Those who have been practicing longer may have more experience in organizational systems and mitigating risk; however, half of all BCBAs have been certified in the last 5 years and two thirds have been certified in the last 7 years (BACB, 2021). This rapid growth of the profession poses significant challenges in navigating novel situations outside of the practitioner's scope of competency and learning history. In this article, we present a systematic formalized approach to risk management through an organizational behavior management lens. The article includes a screening tool, a summary of the model, and case examples of ongoing risk assessment during unexpected service disruptions. This screener is designed to help BCBAs think critically and systematically as they consider social and contextual factors across stakeholders, the client's behavioral status and treatment needs, state policy and law, and professional and ethical obligations during the decision-making process., Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-021-00672-7., Competing Interests: Conflict of InterestWe have no conflicts of interest to disclose., (© Association for Behavior Analysis International 2022.)

Over the last two decades, inhibitory control has featured prominently in accounts of how humans and other organisms regulate their behaviour and thought. Previous work on how the brain stops actions and thoughts, however, has emphasised distinct prefrontal regions supporting these functions, suggesting domain-specific mechanisms. Here we show that stopping actions and thoughts recruits common regions in the right dorsolateral and ventrolateral prefrontal cortex to suppress diverse content, via dynamic targeting. Within each region, classifiers trained to distinguish action-stopping from action-execution also identify when people are suppressing their thoughts (and vice versa). Effective connectivity analysis reveals that both prefrontal regions contribute to action and thought stopping by targeting the motor cortex or the hippocampus, depending on the goal, to suppress their task-specific activity. These findings support the existence of a domain-general system that underlies inhibitory control and establish Dynamic Targeting as a mechanism enabling this ability., (© 2022. The Author(s).)

Neuroimaging has revealed robust interactions between the prefrontal cortex and the hippocampus when people stop memory retrieval. Efforts to stop retrieval can arise when people encounter reminders to unpleasant thoughts they prefer not to think about. Retrieval stopping suppresses hippocampal and amygdala activity, especially when cues elicit aversive memory intrusions, via a broad inhibitory control capacity enabling prepotent response suppression. Repeated retrieval stopping reduces intrusions of unpleasant memories and diminishes their affective tone, outcomes resembling those achieved by the extinction of conditioned emotional responses. Despite this resemblance, the role of inhibitory fronto-hippocampal interactions and retrieval stopping broadly in extinction has received little attention. Here we integrate human and animal research on extinction and retrieval stopping. We argue that reconceptualising extinction to integrate mnemonic inhibitory control with learning would yield a greater understanding of extinction's relevance to mental health. We hypothesize that fear extinction spontaneously engages retrieval stopping across species, and that controlled suppression of hippocampal and amygdala activity by the prefrontal cortex reduces fearful thoughts. Moreover, we argue that retrieval stopping recruits extinction circuitry to achieve affect regulation, linking extinction to how humans cope with intrusive thoughts. We discuss novel hypotheses derived from this theoretical synthesis., (© 2021. The Author(s).)

Suppression-induced forgetting (SIF) refers to a memory impairment resulting from repeated attempts to stop the retrieval of unwanted memory associates. SIF has become established in the literature through a growing number of reports built upon the Think/No-Think (TNT) paradigm. Not all individuals and not all reported experiments yield reliable forgetting, however. Given the reliance on task instructions to motivate participants to suppress target memories, such inconsistencies in SIF may reasonably owe to differences in compliance or expectations as to whether they will again need to retrieve those items (on, say, a final test). We tested these possibilities on a large (N = 497) sample of TNT participants. In addition to successfully replicating SIF, we found that the magnitude of the effect was significantly and negatively correlated with participants' reported compliance during the No-Think trials. This pattern held true on both same- and independent-probe measures of forgetting, as well as when the analysis was conditionalized on initial learning. In contrast, test expectancy was not associated with SIF. Supporting previous intuition and more limited post-hoc examinations, this study provides robust evidence that a lack of compliance with No-Think instructions significantly compromises SIF. As such, it suggests that diminished effects in some studies may owe, at least in part, to non-compliance-a factor that should be carefully tracked and/or controlled. Motivated forgetting is possible, provided that one is sufficiently motivated and capable of following the task instructions., (© 2021. The Author(s).)

People experiencing homelessness (PEH) face extreme weather exposure and limited social support. However, few studies have empirically assessed biophysical and social drivers of health outcomes among unsheltered PEH. Social network, health, and outdoor exposure data were collected from a convenience sample of unsheltered PEH ( n = 246) in Nashville, TN, from August 2018-June 2019. Using multivariate fixed-effects linear regression models, we examined associations between biophysical and social environments and self-reported general health and emotional well-being. We found that study participants reported the lowest general health scores during winter months-Nashville's coldest season. We also found a positive association between the number of nights participants spent indoors during the previous week and general health. Participants who spent even one night indoors during the past week had 1.8-point higher general health scores than participants who spent zero nights indoors ( p < 0.01). Additionally, participants who experienced a conflict with a social contact in the past 30 days had lower emotional well-being scores than participants who experienced no conflict. Finally, women had worse general health and emotional well-being than men. Ecologically framed research about health and well-being among PEH is critically needed, especially as climate change threatens to increase the danger of many homeless environments.

Dynamin-related protein-1 (Drp1) is a key regulator in mitochondrial fission. Excessive Drp1-mediated mitochondrial fission in skeletal muscle under the obese condition is associated with impaired insulin action. However, it remains unknown whether pharmacological inhibition of Drp1, using the Drp1-specific inhibitor Mitochondrial Division Inhibitor 1 (Mdivi-1), is effective in alleviating skeletal muscle insulin resistance and improving whole-body metabolic health under the obese and insulin-resistant condition. We subjected C57BL/6J mice to a high-fat diet (HFD) or low-fat diet (LFD) for 5-weeks. HFD-fed mice received Mdivi-1 or saline injections for the last week of the diet intervention. Additionally, myotubes derived from obese insulin-resistant humans were treated with Mdivi-1 or saline for 12 h. We measured glucose area under the curve (AUC) from a glucose tolerance test (GTT), skeletal muscle insulin action, mitochondrial dynamics, respiration, and H 2 O 2 content. We found that Mdivi-1 attenuated impairments in skeletal muscle insulin signaling and blood glucose AUC from a GTT induced by HFD feeding (p < 0.05). H 2 O 2 content was elevated in skeletal muscle from the HFD group (vs. LFD, p < 0.05), but was reduced with Mdivi-1 treatment, which may partially explain the improvement in skeletal muscle insulin action. Similarly, Mdivi-1 enhanced the mitochondrial network structure, reduced reactive oxygen species, and improved insulin action in myotubes from obese humans (vs. saline, p < 0.05). In conclusion, inhibiting Drp1 with short-term Mdivi-1 administration attenuates the impairment in skeletal muscle insulin signaling and improves whole-body glucose tolerance in the setting of obesity-induced insulin resistance. Targeting Drp1 may be a viable approach to treat obesity-induced insulin resistance., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Sleep's role in memory consolidation is widely acknowledged, but its role in weakening memories is still debated. Memory weakening is evolutionary beneficial and makes an integral contribution to cognition. We sought evidence on whether sleep-based memory reactivation can facilitate memory suppression. Participants learned pairs of associable words (e.g., DIET-CREAM) and were then exposed to hint words (e.g., DIET) and instructed to either recall ("think") or suppress ("no-think") the corresponding target words (e.g., CREAM). As expected, suppression impaired retention when tested immediately after a 90-min nap. To test if reactivation could selectively enhance memory suppression during sleep, we unobtrusively presented one of two sounds conveying suppression instructions during sleep, followed by hint words. Results showed that targeted memory reactivation did not enhance suppression-induced forgetting. Although not predicted, post-hoc analyses revealed that sleep cues strengthened memory, but only for suppressed pairs that were weakly encoded before sleep. The results leave open the question of whether memory suppression can be augmented during sleep, but suggest strategies for future studies manipulating memory suppression during sleep. Additionally, our findings support the notion that sleep reactivation is particularly beneficial for weakly encoded information, which may be prioritized for consolidation.

Purpose: To explore how instructional designers (IDs) view their work and give insight to organizations intending to hire for this role., Method: In 2018, a 28-question survey was utilized to examine the role of instructional designers in medical education and their contributions as educational professionals. The survey was sent to members of the DR-ED listserv, the Instructional Designer listserv through AAMC, relevant EDUCAUSE listservs, and via Twitter in April 2018. Quantitative and qualitative results were analyzed. The target population was determined as those who self-identify as working in instructional design in medical education, understanding that titles of IDs may vary widely in academic medicine., Results: Participants in this study (72) were self-identified as 45 (63%) females and 23 (32%) males. Among the degrees held by participants, 33 (46%) hold a terminal degree, 37 (51%) a master's degree, and 2 (3%) a bachelor's degree. Seven (9%) of institutions employ one ID and 27 (36%) employ two to five IDs, and 19 (25%) of the participants did not know how many instructional designers were employed by their organization. Participants reported that 22 (40%) specialize in more than one type of work such as database development, classroom technology, faculty development, and assessment/evaluation., Conclusion: There is a wide variety of work environments for IDs in academic medicine; these range from large academic research institutions to consultant companies. A significant portion of IDs advise faculty on pedagogy and teaching best practices and develop professional development training. Job titles for IDs are also varied, representative of a wide range of influence within academic medicine organizations. ID expertise that was considered most commonly needed in academic medicine includes familiarity with learning management systems, multimedia literacy, and pedagogy., (© International Association of Medical Science Educators 2019.)

Forgetting is a ubiquitous phenomenon that is actively promoted in many species. How and whether organisms' behavioral goals drive which memories are actively forgotten is unknown. Here we show that processes essential to controlling goal-directed behavior trigger active forgetting of distracting memories that interfere with behavioral goals. When rats need to retrieve particular memories to guide exploration, it reduces later retention of other memories encoded in that environment. As with humans, this retrieval-induced forgetting is competition-dependent, cue-independent and reliant on prefrontal control: Silencing the medial prefrontal cortex with muscimol abolishes the effect. cFos imaging reveals that prefrontal control demands decline over repeated retrievals as competing memories are forgotten successfully, revealing a key adaptive benefit of forgetting. Occurring in 88% of the rats studied, this finding establishes a robust model of how adaptive forgetting harmonizes memory with behavioral demands, permitting isolation of its circuit, cellular and molecular mechanisms.

A 46-year-old female presented after 3 years of steadily increasing numbness in her hands bilaterally with worse symptoms in her right hand. She reported nighttime paresthesia and exacerbation of her symptoms while writing, typing, and driving. Tinel's and carpal tunnel compression test were positive bilaterally. During the right hand carpal tunnel release, a layer of synovium was present deep to the carpal ligament with a tendinous portion running midline longitudinally along the median nerve. This layer was an anomalous palmaris profundus (PP) tendon within the carpal tunnel, which inserted distally in the palmar fascia. The PP tendon was freed and released. The PP is a rare muscle variation of the forearm and wrist, and although it has no function, it has been reported as a cause of median nerve compression at the wrist. More commonly, it is an incidental finding during carpal tunnel surgery. Because of its close association with the median nerve, it can cause confusion when encountered during carpal tunnel surgery. Clinicians should be aware of this rare finding, which may be present during carpal tunnel surgery. We present a case, with intraoperative photographs, of a PP tendon that was encountered during a carpal tunnel release.

Background: Wide-awake local anesthesia and no tourniquet (WALANT) has become more popular in hand surgery. Without a tourniquet, there is no need for preoperative testing or sedation. The use of lidocaine with epinephrine has allowed a larger variety of cases to be done safely in an outpatient setting instead of the hospital. "Minor field sterility," which uses fewer drapes and tools to accomplish the same procedures, is a concept that is also gaining recognition., Methods: Investigation of hand surgeons performing a majority of cases using WALANT and minor field sterility was the beginning of seeing its potential at our institution. Administration was concerned about patient safety, cost-effectiveness, and patient satisfaction of the proposed changes. Analysis of our institution to determine location of these procedures was also imperative to using WALANT., Results: An in-office procedure room was built to allow for WALANT and minor field sterility. The requirements and logistics of developing an in-office procedure room for wide-awake surgery are reviewed in this article., Conclusions: The concurrent use of WALANT and minor field sterility has created a hand surgery practice that is cost-effective for the patient and the facility and resulted in excellent patient outcomes and satisfaction.

Neutrophils represent the most abundant immune cells recruited to inflamed tissues. A lack of dedicated tools has hampered their detection and study. We show that a synthesized peptide, MUB 40 , binds to lactoferrin, the most abundant protein stored in neutrophil-specific and tertiary granules. Lactoferrin is specifically produced by neutrophils among other leukocytes, making MUB 40 a specific neutrophil marker. Naive mammalian neutrophils (human, guinea pig, mouse, rabbit) were labeled by fluorescent MUB 40 conjugates (-Cy5, Dylight405). A peptidase-resistant retro-inverso MUB 40 (RI-MUB 40 ) was synthesized and its lactoferrin-binding property validated. Neutrophil lactoferrin secretion during in vitro Shigella infection was assessed with RI-MUB 40 -Cy5 using live cell microscopy. Systemically administered RI-MUB 40 -Cy5 accumulated at sites of inflammation in a mouse arthritis inflammation model in vivo and showed usefulness as a potential tool for inflammation detection using non-invasive imaging. Improving neutrophil detection with the universal and specific MUB 40 marker will aid the study of broad ranges of inflammatory diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A newly developed microwave (MW) land surface temperature (LST) product is used to substitute thermal infrared (TIR) based LST in the Atmosphere Land Exchange Inverse (ALEXI) modelling framework for estimating ET from space. ALEXI implements a two-source energy balance (TSEB) land surface scheme in a time-differential approach, designed to minimize sensitivity to absolute biases in input records of LST through the analysis of the rate of temperature change in the morning. Thermal infrared (TIR) retrievals of the diurnal LST curve, traditionally from geostationary platforms, are hindered by cloud cover, reducing model coverage on any given day. This study tests the utility of diurnal temperature information retrieved from a constellation of satellites with microwave radiometers that together provide 6-8 observations of Ka-band brightness temperature per location per day. This represents the first ever attempt at a global implementation of ALEXI with MW-based LST and is intended as the first step towards providing all-weather capability to the ALEXI framework. The analysis is based on 9-year long, global records of ALEXI ET generated using both MW and TIR based diurnal LST information as input. In this study, the MW-LST sampling is restricted to the same clear sky days as in the IR-based implementation to be able to analyse the impact of changing the LST dataset separately from the impact of sampling all-sky conditions. The results show that long-term bulk ET estimates from both LST sources agree well, with a spatial correlation of 92% for total ET in the Europe/Africa domain and agreement in seasonal (3-month) totals of 83-97 % depending on the time of year. Most importantly, the ALEXI-MW also matches ALEXI-IR very closely in terms of 3-month inter-annual anomalies, demonstrating its ability to capture the development and extent of drought conditions. Weekly ET output from the two parallel ALEXI implementations is further compared to a common ground measured reference provided by the FLUXNET consortium. Overall, the two model implementations generate similar performance metrics (correlation and RMSE) for all but the most challenging sites in terms of spatial heterogeneity and level of aridity. It is concluded that a constellation of MW satellites can effectively be used to provide LST for estimating ET through ALEXI, which is an important step towards all-sky satellite-based retrieval of ET using an energy balance framework.

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown. Here we show that GABAergic inhibition of hippocampal retrieval activity forms a key link in a fronto-hippocampal inhibitory control pathway underlying thought suppression. Subjects viewed reminders of unwanted thoughts and tried to suppress retrieval while being scanned with functional magnetic resonance imaging. Suppression reduced hippocampal activity and memory for suppressed content. 1 H magnetic resonance spectroscopy revealed that greater resting concentrations of hippocampal GABA predicted better mnemonic control. Higher hippocampal, but not prefrontal GABA, predicted stronger fronto-hippocampal coupling during suppression, suggesting that interneurons local to the hippocampus implement control over intrusive thoughts. Stopping actions did not engage this pathway. These findings specify a multi-level mechanistic model of how the content of awareness is voluntarily controlled.

Observations of land surface temperature (LST) are crucial for the monitoring of surface energy fluxes from satellite. Methods that require high temporal resolution LST observations (e.g., from geostationary orbit) can be difficult to apply globally because several geostationary sensors are required to attain near-global coverage (60°N to 60°S). While these LST observations are available from polar-orbiting sensors, providing global coverage at higher spatial resolutions, the temporal sampling (twice daily observations) can pose significant limitations. For example, the Atmosphere Land Exchange Inverse (ALEXI) surface energy balance model, used for monitoring evapotranspiration and drought, requires an observation of the morning change in LST - a quantity not directly observable from polar-orbiting sensors. Therefore, we have developed and evaluated a data-mining approach to estimate the mid-morning rise in LST from a single sensor (2 observations per day) of LST from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor on the Aqua platform. In general, the data-mining approach produced estimates with low relative error (5 to 10%) and statistically significant correlations when compared against geostationary observations. This approach will facilitate global, near real-time applications of ALEXI at higher spatial and temporal coverage from a single sensor than currently achievable with current geostationary datasets.

Intrusive memories often take the form of distressing images that emerge into a person's awareness, unbidden. A fundamental goal of clinical neuroscience is to understand the mechanisms allowing people to control these memory intrusions and reduce their emotional impact. Mnemonic control engages a right frontoparietal network that interrupts episodic retrieval by modulating hippocampal activity; less is known, however, about how this mechanism contributes to affect regulation. Here we report evidence in humans (males and females) that stopping episodic retrieval to suppress an unpleasant image triggers parallel inhibition of mnemonic and emotional content. Using fMRI, we found that regulation of both mnemonic and emotional content was driven by a shared frontoparietal inhibitory network and was predicted by a common profile of medial temporal lobe downregulation involving the anterior hippocampus and the amygdala. Critically, effective connectivity analysis confirmed that reduced amygdala activity was not merely an indirect consequence of hippocampal suppression; rather, both the hippocampus and the amygdala were targeted by a top-down inhibitory control signal originating from the dorsolateral prefrontal cortex. This negative coupling was greater when unwanted memories intruded into awareness and needed to be purged. Together, these findings support the broad principle that retrieval suppression is achieved by regulating hippocampal processes in tandem with domain-specific brain regions involved in reinstating specific content, in an activity-dependent fashion. SIGNIFICANCE STATEMENT Upsetting events sometimes trigger intrusive images that cause distress and that may contribute to psychiatric disorders. People often respond to intrusions by suppressing their retrieval, excluding them from awareness. Here we examined whether suppressing aversive images might also alter emotional responses to them, and the mechanisms underlying such changes. We found that the better people were at suppressing intrusions, the more it reduced their emotional responses to suppressed images. These dual effects on memory and emotion originated from a common right prefrontal cortical mechanism that downregulated the hippocampus and amygdala in parallel. Thus, suppressing intrusions affected emotional content. Importantly, participants who did not suppress intrusions well showed increased negative affect, suggesting that suppression deficits render people vulnerable to psychiatric disorders., (Copyright © 2017 Gagnepain et al.)

Shigella is a leading cause of dysentery worldwide, with the majority of infections caused by two subgroups, S. flexneri and S. sonnei. Although S. flexneri has been highly prevalent in low-income countries, global development has brought an increase in S. sonnei at the expense of S. flexneri. However, the mechanisms behind this shift are not understood. Here we report that S. sonnei, but not S. flexneri, encodes a type VI secretion system (T6SS) that provides a competitive advantage in the gut. S. sonnei competes against E. coli and S. flexneri in mixed cultures, but this advantage is reduced in T6SS mutant strains. In addition, S. sonnei can persist as well as outcompete E. coli and S. flexneri in mice in a T6SS-dependent manner. These findings suggest that S. sonnei has a competitive advantage over S. flexneri and potentially explain the increasing global prevalence of S. sonnei., (Copyright © 2017 Elsevier Inc. All rights reserved.)