Open-field exploration immediately before the retention test impairs retrieval and spaced fear extinction of contextual fear memory.

According to the behavioral tagging theory, various stages of fear memory, such as contextual fear conditioning, memory retrieval, and fear extinction, can be facilitated by the exploration of a novel open field (OF). A critical time window of efficacy exists for this process. Novel exploration closely adjacent to weak learning may interfere with the setting of the learning tag, leading to a negative effect. In this mouse study, we consistently showed that exposure to a novel or familiar OF immediately prior to the retention test impaired the retrieval of long-term contextual fear memory. However, OF exposure had no effect on the retrieval of recent or remote cued fear memory or short-term contextual fear memory or the reconsolidation of contextual fear memory. In addition, OF exposure impaired spaced but not massed extinction of contextual fear memory. These results suggest that interfering stimulus may result in the transient forgetting of fear memory; however, temporary loss of fear may lead to retention failure of fear extinction. The results of this study are an important complement to the behavioral tagging theory and may provide new guidance for the treatment of post-traumatic stress disorder.

The effect of individual differences on Pavlovian conditioning in specific Internet-use disorders.

The I-PACE model suggests that Internet-use disorders result from the interplay of individual vulnerabilities and cognitive and affective processes. As in substance use disorders, Pavlovian conditioning processes are attributed a key role. However, and despite progress in identifying individual vulnerabilities, factors influencing appetitive conditioning remain poorly understood. We therefore conducted a Pavlovian conditioning experiment in which individuals with risky as well as non-problematic use of either gaming or buying-shopping applications learned to associate different abstract stimuli with either gaming or buying-shopping. Regression analyses were used to identify individual characteristics influencing awareness of the experimental contingencies, speed of acquisition of awareness and the magnitude of the conditioned emotional responses regarding pleasantness and arousal ratings of the stimuli. Results demonstrated successful Pavlovian conditioning and an attentional bias towards reward-predicting cues. Awareness of the experimental contingencies was linked solely to cognitive abilities, while the speed of acquisition of awareness and the magnitude of conditioned responses was influenced by specific personality characteristics, experiences of compensation from using the application and severity of problematic use. Importantly, certain characteristics specifically predicted the magnitude of the conditioned response towards gaming, while others specifically predicted the response towards buying-shopping, highlighting differing vulnerabilities. These findings underscore the importance of targeted interventions and prevention strategies tailored to these specific vulnerability factors. Further implications and limitations are discussed.

A review of functions and mechanisms of clay soil conditioners and catalysts in thermal remediation compared to emerging photo-thermal catalysis.

High temperatures and providing sufficient time for the thermal desorption of persistent organic pollutants (POPs) from contaminated clay soils can lead to intensive energy consumption. Therefore, this article provides a critical review of the potential additives which can improve soil texture and increase the volatility of POPs, and then discusses their enhanced mechanisms for contributing to a green economy. Ca-based additives have been used to reduce plasticity of bentonite clay, absorb water and replenish system heat. In contrast, non-Ca-based additives have been used to decrease the plasticity of kaolin clay. The soil structure and soil plasticity can be changed through cation exchange and flocculation processes. The transition metal oxides and alkali metal oxides can be applied to catalyze and oxidize polycyclic aromatic hydrocarbons, petroleum and emerging contaminants. In this system, reactive oxygen species (•O2- and •OH) are generated from thermal excitation without strong chemical oxidants. Moreover, multiple active ingredients in recycled solid wastes can be controlled to reduce soil plasticity and enhance thermal catalysis. Alternatively, the alkali, nano zero-valent iron and nano-TiN can catalyze hydrodechlorination of POPs under reductive conditions. Especially, photo and photo-thermal catalysis are discussed to accelerate replacement of fossil fuels by renewable energy in thermal remediation.

Evaluation of the Color of Zirconia in Different Substrates of Osseointegrated Implants, Thickness of Materials and Types of Resin Cements.

Objectives: To evaluate the impact of surface conditioning of titanium, zirconia thickness, and cement type on the final color of zirconia luted to the titanium. Methods: A total of 192 grade 5 titanium specimens with the final dimensions 10 mm × 10 mm × 2 mm were fabricated and subjected to four different surface conditioning including, that is, sandblasting, etching, and anodization. In addition, 192 zirconia specimens with the same dimensions as the titanium specimens but altered thicknesses of 0.7 (n = 96) and 1.0 (n = 96) mm were fabricated using 5Y-TZP zirconia. Color as expressed by L ∗ (lightness), a ∗ (red-green axis), and b ∗ (blue-yellow axis) of titanium and zirconia specimens as well as the joined titanium-zirconia complex, total assembly (Panavia V5 clear, PC; opaque, PO, each n = 96) were determined under standardized conditions using a spectroradiometer (SpectraScan P-650). Color differences were calculated using the ΔE 00 formula. ANOVA supplemented with post hoc Tukey test for group comparisons was compiled to estimate possible effects of titanium conditioning, zirconia thickness, and type of cement used on the final zirconia color (SPSS Ver. 28; α = 0.05). Results: All investigated factors affected the zirconia color of the total assembly (p < 0.001). Using PO mean values of all groups were still close to baseline colors (ΔE 00 between 5.5 and 6.2). When using PC, the final color was significantly altered, irrespective of the other parameters. Specimens luted with PO appeared lighter, less reddish (a ∗ was affected predominately by sample thickness), and more bluish, while luting with PC resulted in reduced lightness combined with large shifts along the red and yellow axes. Significance: Color changes of zirconia luted to titanium are primarily affected by the color of the substrate if a translucent cement was used. Vice versa, the application of an opaque cement effectively masked the dark substrate color. Substrate color and choice of cement have to be taken into consideration when performing shade selection.

Examining conceptual generalisation after acquisition, extinction, and reinstatement in evaluative conditioning.

In evaluative conditioning, a neutral conditional stimulus (CS) acquires the valence of a pleasant or unpleasant unconditional stimulus (US) after the CS and US are paired (acquisition). Valence acquired by the CS can generalise to other stimuli from the same category. Presenting the CS alone can reduce evaluative conditioning (extinction), but evaluations can return after the US is presented alone (reinstatement). The current research investigated whether extinction and reinstatement generalise to other category members (generalisation stimuli, GS). In Experiment 1, evaluations generalised in acquisition after conditioning with one category exemplar, but GS evaluations were unaffected by extinction and reinstatement. In Experiment 2, we aimed to enhance generalisation by presenting multiple category exemplars during conditioning. This strengthened the generalisation of evaluations in extinction but not reinstatement. In Experiment 3, conditioning with multiple exemplars caused explicit and implicit evaluations (measured using an affective priming task) to generalise in acquisition but not in extinction or reinstatement. The acquisition and extinction of US expectancy generalised in all experiments, but the reinstatement generalised in Experiment 3 only. Overall, we found partial evidence of evaluative generalisation during extinction (but not reinstatement) and demonstrated that the extinction and reinstatement of US expectancy generalises in evaluative conditioning.

Reduced Intensity Conditioning Prior Autologous Stem Cell Transplantation in Elderly DLBCL Patients.

High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B-cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high-dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow-up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, p = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression-free survival (PFS) (HR 1.80 CI 1.11-2.92, p = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86-2.56, p = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40-1.38, p = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22-0.94, p = 0.032). Age 60-69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60-69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders.

Fear, learning, and the amygdala: a personal reflection in honor of Joseph LeDoux.

In honor of Joseph LeDoux's retirement from an illustrious career in science, I offer a personal reflection on how my graduate training experiences in his lab shaped my subsequent career trajectory and the development of my views on human amygdala function and the scientific enterprise. I discuss the values of openness to scientific exploration and of multi-methodological integration, both of which distinguished his laboratory over the years. I highlight the unique historical context in which the lab's foundational discoveries on the emotional brain occurred and the importance of embracing new technologies to advance an understanding of brain-behavior relationships in affective neuroscience.

Cardioprotection by Preconditioning with Intralipid Is Sustained in a Model of Endothelial Dysfunction for Isolated-Perfused Hearts.

Endothelial dysfunction (ED) is closely associated with most cardiovascular diseases. Experimental models are needed to analyze the potential impact of ED on cardioprotection in constant pressure Langendorff systems (CPLS). One cardioprotective strategy against ischemia/reperfusion injury (I/RI) is conditioning with the lipid emulsion Intralipid (IL). Whether ED modulates the cardioprotective effect of IL remains unknown. The aim of the study was to transfer a protocol using a constant flow Langendorff system for the induction of ED into a CPLS, without the loss of smooth muscle cell functionality, and to analyze the cardioprotective effect of IL against I/RI under ED. In isolated hearts of male Wistar rats, ED was induced by 10 min perfusion of a Krebs-Henseleit buffer containing 60 mM KCl (K+), and the vasodilatory response to the vasodilators histamine (endothelial-dependent) and sodium-nitroprusside (SNP, endothelial-independent) was measured. A CPLS was employed to determine cardioprotection of pre- or postconditioning with 1% IL against I/RI. The constant flow perfusion of K+ reduced endothelial response to histamine but not to SNP, indicating reduced vasodilatory functionality of endothelial cells but not smooth muscle cells. Preconditioning with IL reduced infarct size and improved cardiac function while postconditioning with IL had no effect. The induction of ED neither influenced infarct size nor affected the cardioprotective effect by preconditioning with IL. This protocol allows for studies of cardioprotective strategies under ED in CLPS. The protection by preconditioning with IL seems to be mediated independently of a functional endothelium.

Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study.

RATIONALE: Prior work from our lab and others demonstrates that the endocannabinoid system is a promising avenue for improving fear memory deficits in posttraumatic stress disorder (PTSD). Specifically, 7.5 mg of delta-9-tetrahydrocannabinol (THC) decreases fear responding in healthy adults and increases prefrontal cortex activation during extinction learning and fear renewal in adults with PTSD. OBJECTIVES: The present study will determine whether there is a dose-dependent effect of THC on short-term (24 h) and long-term (one week) fear learning and memory in adults with PTSD. METHODS: Using a randomized, double-blind, placebo-controlled design, N = 36 adults with PTSD completed the study and were randomized to receive placebo (PBO, n = 11), 5 mg of THC (n = 11), or 10 mg of THC (n = 14) prior to fear extinction learning. Participants completed a Pavlovian conditioning paradigm with extinction recall and fear renewal occurring 24 h and one week later, where we measured concurrent functional imaging and behavioral responses. RESULTS: Twenty-four hours after drug administration, individuals with PTSD given 5 mg of THC exhibited greater anterior cingulate cortex and prefrontal cortex activation during early fear renewal. One week later, individuals given 10 mg of THC exhibited greater hippocampus activation during extinction recall and prefrontal cortex activation during fear renewal. CONCLUSIONS: These data suggest that dosing and timing are critical for facilitating fear memory processes in PTSD, and that low-dose oral THC prior to extinction learning can affect brain indices of fear learning and memory both acutely and one week after administration.

Response-independent outcome presentations dissociate stimulus and value based choice.

A stimulus that predicts the delivery of a specific food outcome can bias performance towards instrumental actions that earn that same outcome in a phenomenon known as specific Pavlovian-instrumental transfer (PIT). The precise mechanism by which the specific instrumental action is selected under these circumstances has remained elusive. The present set of experiments explored whether treatments that undermine the response-outcome (R-O) association also affect the expression of specific PIT. Consistent with previous work, in Experiment 1 we showed that specific PIT remains intact after an instrumental degradation treatment that attempted to undermine R-O associations. However, we additionally demonstrated that outcome-devaluation sensitivity also persisted after degradation, suggesting that R-O associations were impervious to the degradation treatment, and precluding any conclusions about the necessity of R-O associations for specific PIT expression. Nevertheless, given the two-lever two-outcome design of this experiment it is possible that R-O associations were indeed undermined by degradation and that the devaluation effect was driven by distinct, incidental Pavlovian lever-outcome associations. To nullify the obscuring effects of these incidental Pavlovian associations, we used a bidirectional lever for instrumental conditioning that could be pushed to the left or the right for distinct outcomes. In Experiment 2 we demonstrated that specific PIT could be observed on this bidirectional manipulandum whether the subjects were hungry or sated, consistent with the literature. The critical third Experiment used an identical design to Experiment 1 except that the two instrumental responses were made on the single bidirectional manipulanda. Here, specific PIT was intact after instrumental degradation and, crucially, we saw no evidence of outcome devaluation sensitivity in these same subjects, suggesting that the R-O associations were weakened or undermined by this treatment. We conclude that the expression of specific PIT is resistant to treatments that undermine R-O associations and disrupt value based choice, and discuss how these findings contribute to our understanding of the associative framework supporting behavioral control.

Ascending Vagal Sensory and Central Noradrenergic Pathways Modulate Retrieval of Passive Avoidance Memory in Male Rats.

Visceral feedback from the body is often subconscious, but plays an important role in guiding motivated behaviors. Vagal sensory neurons relay "gut feelings" to noradrenergic (NA) neurons in the caudal nucleus of the solitary tract (cNTS), which in turn project to the anterior ventrolateral bed nucleus of the stria terminalis (vlBNST) and other hypothalamic-limbic forebrain regions. Prior work supports a role for these circuits in modulating memory consolidation and extinction, but a potential role in retrieval of conditioned avoidance remains untested. To examine this, adult male rats underwent passive avoidance conditioning. We then lesioned gut-sensing vagal afferents by injecting cholecystokinin-conjugated saporin toxin (CSAP) into the vagal nodose ganglia (Experiment 1), or lesioned NA inputs to the vlBNST by injecting saporin toxin conjugated to an antibody against dopamine-beta hydroxylase (DSAP) into the vlBNST (Experiment 2). When avoidance behavior was later assessed, rats with vagal CSAP lesions or NA DSAP lesions displayed significantly increased conditioned passive avoidance. These new findings support the view that gut vagal afferents and the cNTSNA-to-vlBNST circuit play a role in modulating the expression/retrieval of learned passive avoidance. Overall, our data suggest a dynamic modulatory role of vagal sensory feedback to the limbic forebrain in integrating interoceptive signals with contextual cues that elicit conditioned avoidance behavior.

Safety evaluations for transtympanic laser stimulation of the cochlea in Mongolian gerbils (Meriones unguiculatus).

Infrared laser stimulation of the cochlea has been proposed as a possible alternative to conventional auditory prostheses. Whereas previous studies have focused primarily on the short-term effects of laser stimulation, the practical application of this technics requires an investigation into whether prolonged laser exposure can induce neural responses and safely. This study assessed the effect of laser-induced damage to the cochlea on auditory perception using Mongolian gerbils (Meriones unguiculatus) trained with a classical conditioning task. The broadband noise was presented as a conditioned stimulus, and reward licking was recorded as a conditioned response. After training, the subject's cochlea was exposed to a continuous pulsed laser for 15h. Broadband noise of various intensities was presented without pairing it with water before and after laser exposure to assess the decrease in auditory perception due to laser-induced injury. The licking rate did not change after laser exposure of 6.6W/cm2 or weaker but drastically decreased after 26.4W/cm2 or higher. These findings showed, for the first time, that the safety margin of long-term, at least several hours, cochlear laser stimulation exists and will contribute to the appropriate delimitation of the safe and effective laser stimulation parameters in future research.

State of the Science: Disgust and the Anxiety Disorders.

Anxiety disorders have long been conceptualized as disorders of fear, while other emotions have largely been overlooked. However, an emerging literature has increasingly implicated disgust in certain anxiety-related disorders, including obsessive-compulsive disorder, specific phobias (e.g., spider phobia), health anxiety, and posttraumatic stress disorder. Roughly two decades of research has accumulated evidence identifying various mechanisms linking disgust-related phenomena to these disorders. In the present "State of the Science" review, we sought to summarize the current state of the literature with respect to disgust-related mechanisms in anxiety disorders, including trait-level vulnerabilities (e.g., disgust proneness), cognitive processes (e.g., biases of attention and memory), and associated learning mechanisms (e.g., evaluative conditioning). Research in these areas has revealed important ways in which disgust differs from fear-related phenomena, which have important treatment implications. From there, we sought to summarize research on laboratory interventions that attempt to target and attenuate disgust, as well as the early research on formal cognitive-behavioral treatments that integrate disgust-related interventions for anxiety disorders. Although the past two decades of research have revealed important insights related to the role of disgust in psychopathology, much remains to be learned in this area. We propose some future directions, emphasizing the importance of a guiding framework that highlights studying disgust-related mechanisms across different levels of analysis.

Sequential Conditioning With FLAMSA Does Not Improve Outcomes of Allogeneic Stem Cell Transplantation in Chronic Myelomonocytic Leukemia Patients.

As with myelodysplastic syndromes (MDS), effective treatment options for chronic myelomonocytic leukemia (CMML) are limited, and the optimal treatment approach remains undefined. Allogeneic stem cell transplantation (allo-SCT) is potentially curative therapy for patients with CMML. Sequential conditioning with FLAMSA was initially developed for refractory acute myeloid leukemia and has since been applied in the treatment of MDS and CMML. Data on optimal allo-SCT conditioning in CMML Patients is scarce. This retrospective study from the Department of Stem Cell Transplantation at the University Medical Center Hamburg, Germany, compared allo-SCT outcomes in CMML patients across three conditioning regimes: Thiotepa-busulfan (TB), sequential FLAMSA-busulfan fludarabine (FLAMSA-FB), and treosulfan-fludarabine (Treo-Flu). Sixty-nine consecutive patients with CMML who underwent allo-SCT between the years 2006 and 2022 were included in the study. Twenty-two received TB, 27 received FLAMSA-FB, and 20 received Treo-Flu conditioning. Transplant sources included matched related donors (8 patients), mismatched related donors (8 all in the TB group), matched unrelated donors (31), and mismatched unrelated donors (22) with significant group variations (P < .001). Most patients received anti-T lymphocyte Globulin for graft versus host disease (GVHD) prophylaxis (TB 68%, FLAMSA-FB 93%, Treo-Flu 85%, P = .08). CPSS-Molecular score was comparable between the groups. One TB patient experienced primary graft failure, but engraftment times were comparable across the groups. Although not statistically significant, the TB group showed a trend toward improved 3-year overall survival (OS) rates (80%) compared to FLAMSA-FB (37%) and Treo-Flu (55%) (P = .05). The TB group also displayed significantly higher 3-year progression-free survival (PFS) rates (80%) compared to FLAMSA-FB (33%) and Treo-Flu (both 39%), (P = .02). No significant differences were observed in 3-year non-relapse mortality across the TB (20%), FLAMSA-FB (30%), and Treo-Flu (26%) groups (P = .8). Interestingly, no TB patients relapsed at 3 years, contrasting with the FLAMSA-FB (41%) and Treo-Flu groups (30%, P = .02). Lastly, cumulative incidences of acute and chronic GVHD were similar across groups. Our analysis suggests FLAMSA-FB does not improve transplant outcomes, however, TB represents the preferred conditioning regimen for CMML patients undergoing allo-SCT. It demonstrates notable advantages in relapse prevention and leads to improved OS and PFS compared to FLAMSA-FB and Treo-Flu protocols.

A systematic approach to identify gaps in neuroimmunology: TNF-α and fear learning deficits, a worked example.

BACKGROUND: The pathophysiology of several neurodegenerative and neuropsychiatric disorders is linked to an altered immune system. However, it is often unclear how the immune system specifically affects these disorders since neuroimmune interactions are very complex. In this paper, we introduce an adjusted version of the adverse outcome pathway (AOP) approach from toxicology to the field of neuroimmunology. A review of the effect of TNF-α on fear learning deficits is used as a worked example to demonstrate how an AOP approach can help identify gaps of knowledge and crucial steps in the pathophysiology of neuroimmunological disorders. METHODS: The AOP was constructed in five steps. First, the adverse outcome was formulated clearly and specifically. Second, the link between the molecular initiating event and the adverse outcome was established with a preliminary literature search in the Medline database. Third, a systematic literature search was performed in which we identified 95 relevant articles. Fourth, the main biological processes and relevant key events were identified. Fifth, the links between key events were determined and an AOP network was constructed. RESULTS: We identified three pathways through which TNF-α may affect fear learning. First, TNF-α receptor activation increases NF-κB levels which increases oxidative stress levels and reduces the activity of glutamate transporters. This alters the synaptic plasticity which is associated with impaired fear acquisition, consolidation, and fear extinction. Second, activation of TNF-α receptors increases the expression and capacity of the serotonin transporter which is linked to impaired fear acquisition, expression, and extinction. Third, TNF-α receptor 1 activation can induce necroptosis, leading to neuroinflammation which is linked to fear learning deficits. CONCLUSION: To successfully apply the AOP approach in neuroimmunology we recommend defining adverse outcomes more precisely, establishing stronger connections between key events from various biological processes, incorporating feedforward and feedback loops, and identifying more mechanistic knowledge in later key events. These adjustments are needed to map the complex processes within the field of neuroimmunology and to identify gaps of knowledge.

Assessment of land degradation susceptibility within the Shaqlawa subregion of Northern Iraq-Kurdistan Region via synergistic application of remotely acquired datasets and advanced predictive models.

Land degradation (LD) is the decline in a land's functional capacity and productive potential, which includes various anthropogenic and natural drivers. This study focuses on three primary manifestations of LD including soil erosion, landslides, and rockfalls, which are the most prevalent in the Shaqlawa district. A set of 22 LD conditioning factors, encompassing curvature, lithology, aspect, river density, soil type, lineament density, river distance, elevation, road distance, length slope (LS), land use land cover (LULC), stream power index (SPI), valley depth, profile curvature, slope, solar radiation, road density, lineament distance, rainfall, topographic wetness index (TWI), plan curvature, and normalized difference vegetation index (NDVI), were integrated into the analysis. Variance inflation factors (VIF) and tolerance (TOL) values from linear regression indicate that most LD factors have acceptable levels of multicollinearity. The Information Gain Ratio (IGR) identified key variables TWI, NDVI, and lithology-as pivotal factors for predicting LD. Additionally, the study evaluated degradation factors using various machine learning (ML) algorithms, including random forest (RF), Naive Bayes, logistic regression, rotation forest, forest penalized attributes (FPA), and Fisher's Linear discriminant analysis (FLDA). This facilitated categorizing the study area into five susceptibility categories. The FLDA model categorized the highest area under very high degradation risk at 26.72%, emphasizing the varied insights each algorithm brought to characterizing the degradation risk. Additionally, the receiver operating characteristic curves (ROC) were employed for model validation, identifying RF as the most successful model in the training dataset with an area under the curve (AUC) of 0.882, while FLDA outperformed in the testing dataset with an AUC of 0.883. The identified LD-prone areas will help land-use planners and emergency management officials apply effective mitigation strategies for similar terrains.

P2X7 receptors modulate acquisition of cue fear extinction and contextual background memory generalization in male mice.

The purinergic P2X7 receptors (P2X7R) are activated by adenosine triphosphate (ATP) in several brain regions, particularly those involved with emotional control and the regulation of fear-related memories. Here, we investigate the role of P2X7R in fear learning memory, specifically in the acquisition and consolidation phases of the cued fear conditioning paradigm. C57Bl/6 wildtype (WT) male mice that received a single i.p. injection of the selective P2X7R antagonist A438079 prior the conditioning session showed generalization of cued fear memory and impaired fear extinction recall in the test session, while those treated prior the extinction session exhibited a similar behavior profile accompanied by resistance in the extinction learning. However, no effects were observed when this drug was administered immediately after the conditioning, extinction, or before the test session. Our results with P2X7R knockout (P2X7 KO) mice showed a behavioral profile that mirrored the collective effects observed across all pharmacological treatment conditions. This suggests that the P2X7R KO model effectively replicates the behavioral changes induced by the pharmacological interventions, demonstrating that we have successfully isolated the role of P2X7R in the fear and extinction phases of memory. These findings highlight the role of P2X7R in the acquisition and recall of extinction memory and supports P2X7R as a promising candidate for controlling abnormal fear processing, with potential applications for stress exposure-related disorders such as post-traumatic stress disorder (PTSD).

Persistence evaluation of fecal pollution indicators in dewatered sludge and dewatering filtrate of municipal sewage sludge: The impacts of ambient temperature and conditioning treatments.

Sludge resource utilization is one of the important routines for transmitting fecal pollution to water and soil, and sludge dewatering is a crucial step for sludge resource utilization. However, it remains unclear the decay characteristics and persistence of fecal pollution indicators after sludge dewatering. In this study, the persistence of six fecal pollution indicators, namely E. coli (EC), human-specific HF183 Bacteroides (HF183), human adenovirus (HAdV), human JC and BK polyomavirus (JCPyV and BKPyV), and crAssphage, in dewatered sludge cake and dewatering filtrate deriving from raw sewage sludge, as well as three types of sludge conditioned with polyacrylamide (PAM), Fenton's reagent, or Fe[III] and CaO were analyzed. The quantitative polymerase chain reaction (qPCR) and viability-qPCR methods were used to analyze the variation in abundances and infectivity of fecal pollution indicators in dewatered sludge cake or dewatering filtrate over the storage time, respectively. Decay predications of fecal pollution indicators over time were modeled using either the first-order or the biphasic decay model. The qPCR results revealed that fecal pollution indicators in dewatered sludge cake persisted longer than those in dewatering filtrate at the same temperature. Increasing temperature can accelerate the decay of fecal pollution indicators in both dewatered sludge cake and dewatering filtrate. Notably, sludge conditioning treatment may prolong the persistence of fecal pollution indicators in both dewatered sludge cake and dewatering filtrate. Viability-qPCR results indicated that the fecal pollution indicators (except HAdV) in dewatered sludge cakes deriving from both raw sewage sludge and conditioned sludges remained infectious for up to 30 days. After a storage period of 40 days, the abundances of fecal pollution indicators (except for EC) in sludge conditioned with Fenton's reagent were effectively decreased and meanwhile the infectivity of EC was reduced, exhibiting the lowest levels of fecal pollution. Therefore, both ambient temperature and conditioning treatment greatly impacted the decay characteristics and persistence of fecal pollution indicators in dewatered sludge cake and dewatering filtrate, and selecting suitable conditioning method can minimize environmental risks associated with fecal pollution in sewage sludge.

Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation.

Neurofeedback (NF) is endogenous neuromodulation of circumscribed brain circuitry. While its use of real-time brain activity in a closed-loop system is similar to brain-computer interfaces, instead of controlling an external device like the latter, the goal of NF is to change a targeted brain function. In this special issue on NF, we present current and future methods for extracting and manipulating neural function, how these methods may reveal new insights about brain function, applications, and rarely discussed ethical considerations of guiding and interpreting the brain activity of others. Together, the articles in this issue outline the possibilities of NF use and impact in the real world, poising to influence the development of more effective and personalized NF protocols, improving the understanding of underlying psychological and neurological mechanisms and enhancing treatment precision for various neurological and psychiatric conditions.This article is part of the theme issue 'Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation'.

Effect of Alpha Hydroxy Acids as Dentin Conditioning Agents on Growth Factor Release: An In Vitro Study.

AIM: The study aimed to evaluate the effects of alpha hydroxy acids and chelating agents on dentin conditioning for the release of growth factors. METHODS: The agents used for dentin conditioning included 17% ethylenediaminetetraacetic acid (EDTA), 10% glycolic acid (GA), 10% citric acid (CA), and 5% maleic acid (MA). Forty horizontally sectioned (SV1) human dentine slices were conditioned for 5 and 10 minutes so that the growth factor liberation reached quantifiable levels. Transforming growth factor beta-1 (TGF-ß1) release and surface exposure were quantified by enzyme-linked immunosorbent assay (ELISA). Growth factor measurement required immediately removing the solutions from each of the 48-well plates (with consistent dentine surface area and weight) and freezing at -20°C so that ELISA measured the growth factors. RESULTS: After 5-min conditioning of dentine slices, CA was the most effective agent for growth factor release into the aqueous environment as measured by ELISA (post hoc Tukey's test p<0.05). Furthermore, dentine slices subjected to GA treatment for the same duration of time showed noticeably lower surface levels of TGF-ß1 in comparison to the other agents employed. CONCLUSIONS: Based on the findings of this in vitro study, a desirable biological growth factor-mediated effect may be gained when conditioning dentin with milder acidic or chelating agents such as CA, MA, and EDTA.