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Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.
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BACKGROUND: Full pulpotomy has been proposed as an alternative to root canal treatment in teeth with signs and symptoms indicative of irreversible pulpitis (IRP), but the evidence is limited, relying on underpowered studies with a high risk of bias. The aim of this study is to conduct a prospective meta-analysis (PMA) of individual participant data of a series of individual randomised trials to provide robust evidence on the clinical and cost-effectiveness of pulpotomy compared with root canal treatment. METHODS: Individual participant data will be obtained from a series of randomised trials designed and conducted by a consortium of multi-national investigators with an interest in vital pulp treatment. These individualised trials will be conducted using a specified protocol, defined outcomes, and outcome measures. Ten parallel-group randomised trials currently being conducted in 10 countries will provide data from more than 500 participants. The primary outcome is a composite measure defined as (1) the absence of pain indicative of IRP, (2) the absence of signs and symptoms indicative of acute or chronic apical periodontitis, and (3) the absence of radiographic evidence of failure including radiolucency or resorption. Individual participant data will be obtained, assessed, and checked for quality by two independent reviewers prior to the PMA. Pooled estimates on treatment effects will be generated using a 2-stage meta-analysis approach. The first stage involves a standard regression analysis in each trial to produce aggregate data on treatment effect estimates followed by an inverse variance weighted meta-analysis to combine these aggregate data and produce summary statistics and forest plots. Cost-effectiveness analysis based on the composite outcome will be undertaken as a process evaluation to evaluate treatment fidelity and acceptability by patients and dentists. RESULTS: The research question and trial protocol were developed and approved by investigators in all 10 sites. All sites use shared resources including study protocols, data collection forms, participant information leaflets, and consent forms in order to improve flow, consistency, and reproducibility. Each site obtained its own Institutional Review Board approval, and trials were registered in appropriate open access platforms. Patient recruitment has started in most sites, as of July 2023. DISCUSSION: PMA offers a rigorous, flexible, and efficient methodology to answer this important research question and provide results with improved generalisability and external validity compared with traditional trials and retrospective meta-analyses. The results of this study will have implications for both the delivery of clinical practice and structured clinical guidelines' development. TRIAL REGISTRATION: PROSPERO CRD42023446809. Registered on 08 February 2023.
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Pulpite , Humanos , Cavidade Pulpar , Metanálise como Assunto , Estudos Prospectivos , Pulpite/diagnóstico , Pulpite/terapia , Pulpotomia , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Robot-actuated mechanical loading (ML)-based therapies ("mechanotherapies") can promote regeneration after severe skeletal muscle injury, but the effectiveness of such approaches during aging is unknown and may be influenced by age-associated decline in the healing capacity of skeletal muscle. To address this knowledge gap, this work used a noninvasive, load-controlled robotic device to impose highly defined tissue stresses to evaluate the age dependence of ML on muscle repair after injury. The response of injured muscle to robot-actuated cyclic compressive loading was found to be age sensitive, revealing not only a lack of reparative benefit of ML on injured aged muscles but also exacerbation of tissue inflammation. ML alone also disrupted the normal regenerative processes of aged muscle stem cells. However, these negative effects could be reversed by introducing anti-inflammatory therapy alongside ML application, leading to enhanced skeletal muscle regeneration even in aged mice.
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Regeneração , Robótica , Animais , Camundongos , Regeneração/fisiologia , Músculo Esquelético/fisiologia , Anti-InflamatóriosRESUMO
Systems of correlated particles appear in many fields of modern science and represent some of the most intractable computational problems in nature. The computational challenge in these systems arises when interactions become comparable to other energy scales, which makes the state of each particle depend on all other particles1. The lack of general solutions for the three-body problem and acceptable theory for strongly correlated electrons shows that our understanding of correlated systems fades when the particle number or the interaction strength increases. One of the hallmarks of interacting systems is the formation of multiparticle bound states2-9. Here we develop a high-fidelity parameterizable fSim gate and implement the periodic quantum circuit of the spin-½ XXZ model in a ring of 24 superconducting qubits. We study the propagation of these excitations and observe their bound nature for up to five photons. We devise a phase-sensitive method for constructing the few-body spectrum of the bound states and extract their pseudo-charge by introducing a synthetic flux. By introducing interactions between the ring and additional qubits, we observe an unexpected resilience of the bound states to integrability breaking. This finding goes against the idea that bound states in non-integrable systems are unstable when their energies overlap with the continuum spectrum. Our work provides experimental evidence for bound states of interacting photons and discovers their stability beyond the integrability limit.
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The purpose of this study was to determine whether six weeks of high intensity interval training (HIIT) would lead to greater changes in resting concentrations of salivary IL-8 and IL-1ra than moderate intensity continuous training (MICT) in young, healthy adults, and to determine whether changes in IL-8 and IL-1ra after six weeks of either HIIT or MICT were associated with changes in maximal exercise capacity (VO2max). Participants were randomly assigned to 6 weeks of HIIT (n = 12) or MICT (n = 11), matched for workload. Saliva samples were collected at the beginning (T1) and end (T2) of the intervention, and analyzed for IL-8 and IL-1ra. Participants in both groups had significant improvements in VO2max; there were no group differences in improvements. A greater reduction in IL-8 was observed in the MICT group when compared to the HIIT group (HIIT median: -9.5; MICT median: -82.3 pg/µg of protein; U = 11.5, p < 0.001). When combining the HIIT and MICT group, there were significant reductions in IL-8 from T1 to T2. There was no correlation between changes in IL-8 (r < 0.00) or IL-1ra (r = -0.013) with changes in VO2max. In conclusion, 6 weeks of exercise training leads to a reduction in IL-8; MICT may lead to greater reductions when compared to HIIT. Future research examining longer intervention periods is needed to further elucidate the effects of HIIT and MICT on different pro and anti-inflammatory cytokines.
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Treinamento Intervalado de Alta Intensidade , Adulto , Exercício Físico , Humanos , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-8 , Consumo de OxigênioRESUMO
BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Normal tension glaucoma (NTG) is a subset of open-angle glaucoma, demonstrating glaucomatous optic nerve damage in the absence of raised intraocular pressure (IOP). NTG is more prevalent in Asian populations. While generally slow-progressing, NTG may be associated with significant central visual field loss. In recent years, minimally invasive glaucoma surgery has been added to the armamentarium of glaucoma surgery. This prospective study aims to evaluate 12-month surgical outcomes of combined iStent inject (Glaukos Corporation, Laguna Hills, CA) implantation and phacoemulsification in Asian eyes with NTG. METHODS: This is a prospective, single-centre case series of 30 eyes followed up until 12 months after surgery. Outcome measures included IOP, number of glaucoma medications, best-corrected visual acuity (BCVA) and intra and postoperative complications. RESULTS: Mean age of subjects was 73.1 ± 6.3 years. Majority were ethnic Chinese (n = 27, 90%). Baseline medicated mean IOP was 13.8 ± 2.4 mmHg and mean number of glaucoma medications was 1.3 ± 0.7. Mean Humphrey visual field mean deviation was - 13.7 ± 7.6. The mean IOP reduction at all timepoints from postoperative month (POM) 3 onwards was statistically significant (all P < 0.05), with mean reduction of 1.2 mmHg (95% CI: 0.1-2.2, P = 0.037) by POM12. There was statistically significant reduction in mean number of medications from postoperative day (POD) 1 onwards (all P < 0.05), with mean decrease of 1.0 medication (95% CI: 0.9-1.1, P < 0.001) by POM12. By POM12, 25 (83.3%) eyes were medication-free. Three (10%) eyes had stent occlusion by iris requiring laser iridoplasty. One eye had gross hyphema which resolved on conservative management before POM1. Mean BCVA improved from the baseline 0.3 ± 0.3 logMAR to 0.1 ± 0.1 logMAR postoperatively (P < 0.001). There were no major adverse or sight-threatening events. No eyes required further glaucoma surgery during the 12-month follow-up period. CONCLUSION: Asian eyes with NTG which underwent combined iStent inject implantation and phacoemulsification demonstrated a significant and sustained reduction in IOP and glaucoma medications, up to 12 months postoperatively.
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The mid-Proterozoic or "boring billion" exhibited extremely stable environmental conditions, with little change in atmospheric oxygen levels, and mildly oxygenated shallow oceans. A limited number of passive margins with extremely long lifespans are observed from this time, suggesting that subdued tectonic activity-a plate slowdown-was the underlying reason for the environmental stability. However, the Proterozoic also has a unique magmatic and metamorphic record; massif-type anorthosites and anorogenic Rapakivi granites are largely confined to this period and the temperature/pressure (thermobaric ratio) of granulite facies metamorphism peaked at over 1500 °C/GPa during the Mesoproterozoic. Here, we develop a method of calculating plate velocities from the passive margin record, benchmarked against Phanerozoic tectonic velocities. We then extend this approach to geological observations from the Proterozoic, and provide the first quantitative constraints on Proterozoic plate velocities that substantiate the postulated slowdown. Using mantle evolution models, we calculate the consequences of this slowdown for mantle temperatures, magmatic regimes and metamorphic conditions in the crust. We show that higher mantle temperatures in the Proterozoic would have resulted in a larger proportion of intrusive magmatism, with mantle-derived melts emplaced at the Moho or into the lower crust, enabling the production of anorthosites and Rapakivi granites, and giving rise to extreme thermobaric ratios of crustal metamorphism when plate velocities were slowest.
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PURPOSE: To evaluate the safety and efficacy of the iStent inject device combined with phacoemulsification in Asian eyes with primary open angle glaucoma. METHODS: A retrospective study of combined phacoemulsification and iStent inject surgeries performed in a single institution from July 2017 to August 2019 on patients with co-existing cataracts and primary open angle glaucoma (POAG). Outcome measures included best-corrected visual acuity, intraocular pressure (IOP), number of glaucoma eyedrop medications, and surgical complications. RESULTS: A total of 95 eyes were included. Majority of subjects were male (59, 62.1%) and Chinese (83, 87.4%). Mean age was 74.7 ± 8.7 years. Pre-operatively, mean IOP was 16.2 ± 4.3 mmHg and number of medications was 1.9 ± 0.9. Significant post-operative reduction in mean IOP was observed at all timepoints - post-operative month (POM)1: 3.0 ± 5.6 mmHg reduction (n = 95, p < 0.05); POM3: 1.6 ± 3.8 mmHg (n = 66, p < 0.05); POM6: 1.8 ± 4.7 mmHg (n = 55, p < 0.05); POM12: 1.3 ± 4.2 mmHg (n = 48) (p < 0.05). The number of glaucoma medications was also reduced from a mean of 1.9 ± 0.8 to 0.6 ± 1.0 at POM12 (p < 0.05). Intraoperatively, one case of malignant glaucoma occurred. Post operatively, implant obstruction by iris was observed in two eyes post-operatively requiring iridoplasty. One case of cystoid macular edema and one case of drop in visual acuity due to glaucoma progression was/were also observed. CONCLUSION: Asian eyes undergoing combined phacoemulsification and iStent inject surgery demonstrate a significant and sustained reduction in both IOP and number of glaucoma medications. Overall, there is a good safety profile for iStent inject.
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Glaucoma de Ângulo Aberto , Facoemulsificação , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Masculino , Estudos Retrospectivos , Stents , Malha TrabecularRESUMO
Approximately one quarter of UK adults are currently diagnosed with two or more chronic conditions, often referred to as multimorbidity. Chronic stress has been implicated in the development of many diseases common to multimorbidity. Policymakers and clinicians have acknowledged the need for more preventative approaches to deal with the rise of multimorbidity and "early ageing". However divergence may occur between an individual's self-rated health and objectively measured health that may preclude preventative action. The use of biomarkers which look 'under the skin' provide crucial information on an individual's underlying health to facilitate lifestyle change or healthcare utilisation. The UK's Understanding Society dataset, was used to examine whether baseline variation in biomarkers measuring stress-related "wear and tear" - Allostatic Load (AL) - predict changes in future self-rated health (SRH) while adjusting for baseline SRH, socioeconomic and lifestyle factors, and healthcare inputs. An interaction between baseline AL and baseline SRH was included to test for differential rates of SRH change. We examined SRH using the SF6D instrument, measuring health-related-quality of life (HRQoL), as well as its physical and mental health components separately. We found that HRQoL and physical health decline faster for those with higher baseline AL (indicating greater "wear and tear") however the same pattern was not observed for mental health. These findings provide novel insights for clinicians and policymakers on the usefulness of AL in capturing health trajectories of which individual's may not be aware and its importance in targeting resilience enhancing measures earlier in the lifecourse to delay physical health decline.
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Alostase , Adulto , Depreciação , Humanos , Multimorbidade , Qualidade de VidaRESUMO
A promising approach to study condensed-matter systems is to simulate them on an engineered quantum platform1-4. However, the accuracy needed to outperform classical methods has not been achieved so far. Here, using 18 superconducting qubits, we provide an experimental blueprint for an accurate condensed-matter simulator and demonstrate how to investigate fundamental electronic properties. We benchmark the underlying method by reconstructing the single-particle band structure of a one-dimensional wire. We demonstrate nearly complete mitigation of decoherence and readout errors, and measure the energy eigenvalues of this wire with an error of approximately 0.01 rad, whereas typical energy scales are of the order of 1 rad. Insight into the fidelity of this algorithm is gained by highlighting the robust properties of a Fourier transform, including the ability to resolve eigenenergies with a statistical uncertainty of 10-4 rad. We also synthesize magnetic flux and disordered local potentials, which are two key tenets of a condensed-matter system. When sweeping the magnetic flux we observe avoided level crossings in the spectrum, providing a detailed fingerprint of the spatial distribution of local disorder. By combining these methods we reconstruct electronic properties of the eigenstates, observing persistent currents and a strong suppression of conductance with added disorder. Our work describes an accurate method for quantum simulation5,6 and paves the way to study new quantum materials with superconducting qubits.
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Passive acoustic recorders were deployed over two years (February 2018-March 2020) in the Salish Sea to monitor the underwater soundscape. Seasonal cycles and differences between the open Strait of Juan de Fuca and protected inner waterways were pervasive during this period. A comparison between natural and human-derived noise demonstrated the impact of anthropogenic activities on the sound field. Elevated ambient noise levels during winter resulted predominantly from greater sea states and storm events. Abiotic additions were defined through correlations to wind speed, wave and precipitation measures. Vessel noise was a pervasive anthropogenic addition; commercial vessel noise was consistently present, whereas smaller vessels showed weekly and diurnal patterns, especially during the summer when their presence increased. A better understanding of the different soundscape constituents, and when each dominates, is crucial to understanding the human impact on underwater ecosystems and the organisms within them, leading to more effective mitigation measures.
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Ecossistema , Som , Acústica , Colúmbia Britânica , Humanos , RuídoRESUMO
We compute continuum and infinite volume limit extrapolations of the structure factors of neutron matter at finite temperature and density. Using a lattice formulation of leading-order pionless effective field theory, we compute the momentum dependence of the structure factors at finite temperature and at densities beyond the reach of the virial expansion. The Tan contact parameter is computed and the result agrees with the high momentum tail of the vector structure factor. All errors, statistical and systematic, are controlled for. This calculation is a first step towards a model-independent understanding of the linear response of neutron matter at finite temperature.
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The coronavirus disease (COVID-19) pandemic disproportionately affects those with pre-existing conditions and has exacerbated gender inequalities. Cardiovascular disease (CVD) is the leading cause of death among Canadian women. Exercise improves physical and mental health and CVD management. Amid the pandemic, women are experiencing an increase in caregiving responsibilities, job insecurities, and domestic violence creating competing demands for prioritizing their health. Recommendations on how to meet the unique needs of Canadian women with CVD through exercise are provided. Novelty: Exercise recommendations amid the pandemic for women with CVD need to be flexible, feasible, and fun.
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COVID-19 , Doenças Cardiovasculares/terapia , Exercício Físico , Disparidades nos Níveis de Saúde , Saúde Mental , Saúde da Mulher , Canadá , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Guias de Prática Clínica como Assunto , Fatores de RiscoRESUMO
Quantum computing can become scalable through error correction, but logical error rates only decrease with system size when physical errors are sufficiently uncorrelated. During computation, unused high energy levels of the qubits can become excited, creating leakage states that are long-lived and mobile. Particularly for superconducting transmon qubits, this leakage opens a path to errors that are correlated in space and time. Here, we report a reset protocol that returns a qubit to the ground state from all relevant higher level states. We test its performance with the bit-flip stabilizer code, a simplified version of the surface code for quantum error correction. We investigate the accumulation and dynamics of leakage during error correction. Using this protocol, we find lower rates of logical errors and an improved scaling and stability of error suppression with increasing qubit number. This demonstration provides a key step on the path towards scalable quantum computing.
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AIMS: There is renewed interest in the inverse association between psychiatric hospital and prison places, with reciprocal time trends shown in more than one country. We hypothesised that the numbers of admissions to psychiatric hospitals and committals to prisons in Ireland would also correlate inversely over time (i.e. dynamic measures of admission and committal rather than static, cross-sectional numbers of places). METHOD: Publicly available activity statistics for psychiatric hospitals and prisons in Ireland were collated from 1986 to 2010. RESULTS: There was a reciprocal association between psychiatric admissions and prison committals (Pearson r=-0.788, p<0.001), an increase of 91 prison committals for every 100 psychiatric hospital admissions foregone. CONCLUSION: Penrose's hypothesis applies to admissions to psychiatric hospitals and prisons in Ireland over time (dynamic measures), just as it does to the numbers of places in psychiatric hospitals and prisons in Ireland and elsewhere (static, cross-sectional measures). Although no causal connection can be definitively established yet, mentally disordered prisoners are usually known to community mental health services. Psychiatric services for prisons and the community should be linked to ensure that the needs of those currently accessing care through prisons can also be met in the community.
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Serviços Comunitários de Saúde Mental , Prisioneiros , Estudos Transversais , Hospitais Psiquiátricos , Humanos , PrisõesRESUMO
BACKGROUND: The epidermal barrier is important for water conservation, failure of which is evident in dry-skin conditions. Barrier function is fulfilled by the stratum corneum, tight junctions (TJs, which control extracellular water) and keratinocyte mechanisms, such as organic osmolyte transport, which regulate intracellular water homeostasis. Organic osmolyte transport by keratinocytes is largely unexplored and nothing is known regarding how cellular and extracellular mechanisms of water conservation may interact. OBJECTIVES: We aimed to characterize osmolyte transporters in skin and keratinocytes, and, using transporter inhibitors, to investigate whether osmolytes can modify TJs. Such modification would suggest a possible link between intracellular and extracellular mechanisms of water regulation in skin. METHODS: Immunostaining and quantitative polymerase chain reaction of organic osmolyte-treated organ-cultured skin were used to identify changes to organic osmolyte transporters, and TJ protein and gene expression. TJ functional assays were performed on organic osmolyte-treated primary human keratinocytes in culture. RESULTS: Immunostaining demonstrated the expression of transporters for betaine, taurine and myo-inositol in transporter-specific patterns. Treatment of human skin with either betaine or taurine increased the expression of claudin-1, claudin-4 and occludin. Osmolyte transporter inhibition abolished this response. Betaine and taurine increased TJ function in primary human keratinocytes in vitro. CONCLUSIONS: Treatment of skin with organic osmolytes modulates TJ structure and function, which could contribute to the epidermal barrier. This emphasizes a role for organic osmolytes beyond the maintenance of intracellular osmolarity. This could be harnessed to enhance topical therapies for diseases characterized by skin barrier dysfunction.
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Queratinócitos , Proteínas de Junções Íntimas , Epiderme , Humanos , Proteínas de Membrana Transportadoras , Pele , Junções ÍntimasRESUMO
Beneficial bacteria represent an emerging tool against topical diseases, including infection caused by Staphylococcus aureus. Here, we investigated several anti-pathogenic mechanisms of the model probiotic Lacticaseibacillus rhamnosus GG against a clinical S. aureus isolate by implementing various mutants lacking important cell surface molecules. We analysed adhesion of L. rhamnosus and competitive adhesion with S. aureus to primary human keratinocytes, L. rhamnosus and S. aureus auto- and co-aggregation, S. aureus growth inhibition, keratinocyte viability increase, and monocyte Toll-like receptor (TLR) activation by L. rhamnosus as such, or with S. aureus. L. rhamnosus mutated in SpaCBA pili exhibited reduced adhesion to keratinocytes, reduced ability to prevent S. aureus adhesion to keratinocytes and reduced co-aggregation with S. aureus. Mutants in cell wall exopolysaccharides showed enhanced adhesion to keratinocytes and TLR activation in monocytes, suggesting involvement of additional cell surface molecules masked by exopolysaccharides. All L. rhamnosus strains inhibited S. aureus growth, likely due to acidification of the medium. Live (but not UV-inactivated) L. rhamnosus significantly reduced inflammatory TLR activation in monocytes by S. aureus. These data suggest the key role of SpaCBA pili and additional contribution of other cell surface molecules as well as secreted components of L. rhamnosus GG in the multifactorial inhibition of S. aureus adhesion and toxicity in the skin niche.
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Proteínas da Membrana Bacteriana Externa/metabolismo , Queratinócitos/microbiologia , Lacticaseibacillus rhamnosus/fisiologia , Probióticos/farmacologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Aderência Bacteriana , Proteínas da Membrana Bacteriana Externa/genética , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Fímbrias Bacterianas/genética , Fímbrias Bacterianas/metabolismo , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Queratinócitos/efeitos dos fármacos , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/metabolismo , Viabilidade Microbiana/efeitos dos fármacos , Mutação , Probióticos/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificação , Células THP-1 , Receptores Toll-Like/metabolismoRESUMO
Quantum algorithms offer a dramatic speedup for computational problems in material science and chemistry. However, any near-term realizations of these algorithms will need to be optimized to fit within the finite resources offered by existing noisy hardware. Here, taking advantage of the adjustable coupling of gmon qubits, we demonstrate a continuous two-qubit gate set that can provide a threefold reduction in circuit depth as compared to a standard decomposition. We implement two gate families: an imaginary swap-like (iSWAP-like) gate to attain an arbitrary swap angle, θ, and a controlled-phase gate that generates an arbitrary conditional phase, Ï. Using one of each of these gates, we can perform an arbitrary two-qubit gate within the excitation-preserving subspace allowing for a complete implementation of the so-called Fermionic simulation (fSim) gate set. We benchmark the fidelity of the iSWAP-like and controlled-phase gate families as well as 525 other fSim gates spread evenly across the entire fSim(θ,Ï) parameter space, achieving a purity-limited average two-qubit Pauli error of 3.8×10^{-3} per fSim gate.
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Endogenous cannabinoids (endocannabinoids, eCB) are expressed throughout the body and contribute to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and general stress reactivity. This study assessed the contributions of CB1 receptors (CB1R) in the modulation of basal and stress-induced neural and HPA axis activities. Catheterized adult male rats were placed in chambers to acclimate overnight, with their catheters connected and exteriorized from the chambers for relatively stress-free remote injections. The next morning, the CB1R antagonist AM251 (1 or 2 mg/kg) or vehicle was administered, and 30 min later, rats were exposed to loud noise stress (30 min) or no noise (basal condition). Blood, brains, pituitary and adrenal glands were collected immediately after the procedures for analysis of c-fos and CB1R mRNAs, corticosterone (CORT) and adrenocorticotropin hormone (ACTH) plasma levels. Basally, CB1R antagonism induced c-fos mRNA in the basolateral amygdala (BLA) and auditory cortex (AUD) and elevated plasma CORT, indicating disruption of eCB-mediated constitutive inhibition of activity. CB1R blockade also potentiated stress-induced hormone levels and c-fos mRNA in several regions such as the bed nucleus of the stria terminalis (BST), lateral septum (LS), and basolateral amygdala (BLA) and the paraventricular nucleus of the hypothalamus (PVN). CB1R mRNA was detected in all central tissues investigated, and the adrenal cortex, but at very low levels in the anterior pituitary gland. Interestingly, CB1R mRNA was rapidly and bidirectionally regulated in response to stress and/or antagonist treatment in some regions. eCBs therefore modulate the HPA axis by regulating both constitutive and activity-dependent inhibition at multiple levels.