Factors Associated with Owner-Reported Euthanasia in Equids in France.

There is limited evidence regarding the proportion of dead equids in France that were euthanized and the factors influencing the decision-making of euthanasia. The better understanding of which could facilitate research on improvement of welfare, especially on end of life issues. The aim of this study was to estimate the proportion of euthanasia and identify associated factors in equids in France. A web-based survey was created and distributed by the French horse and riding institute to owners who reported an equine death between April 2017 and April 2018 (n = 5 158). Factors associated with euthanasia were identified using a multivariable logistic regression model. The percentage of responses was 10.6% (n = 548/5 158; 95% CI 9.8% to 11.5%). The proportion of euthanasia was 71.0% (n = 389/548; 95% CI 67.2% to 74.8%). The factors "age category", "cause of natural death or reason for euthanasia" and "the length of time during which the animal was reported to be ill by the owner" were significantly associated with euthanasia (P <0.001). The results highlighted that a large majority of owners faced euthanasia decisions and our findings could support veterinarians and owners to better prepare for such an eventuality.

Developing an Optical Interferometric Detection Method based biosensor for detecting specific SARS-CoV-2 immunoglobulins in Serum and Saliva, and their corresponding ELISA correlation.

The standard rapid approach for the diagnosis of coronavirus disease 2019 (COVID-19) is the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. The detection of specific anti-SARS-CoV-2 immunoglobulins is crucial for screening people who have been exposed to the virus, whether or not they presented symptoms. Recent publications report different methods for the detection of specific IgGs, IgMs, and IgAs against SARS-CoV-2; these methods mainly detect immunoglobulins in the serum using conventional techniques such as rapid lateral flow tests or enzyme-linked immunosorbent assay (ELISA). In this article, we report the production of recombinant SARS-CoV-2 spike protein and the development of a rapid, reliable, cost-effective test, capable of detecting immunoglobulins in serum and saliva samples. This method is based on interferometric optical detection. The results obtained using this method and those obtained using ELISA were compared. Owing to its low cost and simplicity, this test can be used periodically for the early detection, surveillance, detection of immunity, and control of the spread of COVID-19.

OASIS evaluation of the French surveillance network for antimicrobial resistance in diseased animals (RESAPATH): success factors underpinning a well-performing voluntary system.

Antimicrobial resistance is a One Health issue requiring the development of surveillance systems in the human, environmental and animal sectors. In the European Economic Area, the surveillance of antimicrobial resistance in zoonotic pathogens and indicator bacteria in healthy food-producing animals is required legally, while countries are also expected to extend their surveillance to diseased animals in the frame of national action plans. In this context, evaluating existing antimicrobial resistance surveillance systems in animal health is important to improve systems in place, but also to help other countries learn from these experiences, understand success factors and anticipate challenges. With this aim, the French surveillance network for antimicrobial resistance in bacteria from diseased animals (RESAPATH) was evaluated using the Outil d'Analyse des Systèmes d'Information en Santé (OASIS) assessment tool. Key performance factors included (i) a strong and inclusive central institutional organisation defining clear and well-accepted surveillance objectives, scope and procedures, (ii) strong skills in epidemiology and microbiology and (iii) a win-win approach enabling the voluntary participation of 71 field laboratories and where free annual proficiency testing plays a pivotal role. The main area for improvement of RESAPATH was its time-consuming data management system.

Identification of levers for improving dead equine traceability: A survey of French equine owners' perception of regulatory procedures following their animal's death.

The core of the French equine traceability system is the census database (SIRE) managed by the French horse and riding institute (IFCE). Following the death of an equine, owners are legally obliged to take charge of cadaver removal by contacting a rendering company directly or after registration on the national ATM-équidés ANGEE association (ATM) website, which proposes negotiated prices for removal and recording of the death in the SIRE database. Despite these offers, ATM notes few users. Owners are also legally obliged to return the equine's passport to the IFCE, but only 30-40 % of owners comply with the regulation. Rendering companies register data on equine mortality in the fallen stock data interchange database (FSDI), but it is difficult to cross-reference these data with SIRE data. Consequently, the death of equines is not well registered in the SIRE database. The objective of the present study was to identify levers that could be used to improve dead equine traceability by i) investigating the level of satisfaction of equine owners with ATM and rendering company services; and ii) investigating the drawbacks of owners having to return the passport to the IFCE. An online survey was designed and distributed by email to the 5 158 owners who used ATM services between April 2017 and April 2018. The response rate was 16.4 %. Most owners were satisfied by ATM and rendering company services. The lack of simple and quick removal procedures and the lack of any connection between ATM and the rendering companies were among the main drawbacks identified. Regarding the return of the passport to the IFCE, most responding owners returned it through the rendering company (65 %) or directly (2 %). The passport was returned significantly more frequently when requested by the renderers. The main reason for not providing the passport was the owner wanted to keep it as a souvenir. These results suggest that ATM and the rendering companies are key players in dead equine traceability. ATM services should be developed through the establishment of a direct connection with rendering companies to accelerate the cadaver removal request and to allow the cross-referencing of data between the ATM, FSDI and SIRE databases for a better dead equine traceability. Rendering companies need regulatory support to help them ask owners for the equine's passport, formalizing their contribution to equine traceability. Finally, effective communication has to be established to inform owners about the removal procedures and the regulations.

Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant.

BACKGROUND: We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. METHODS: The study was performed in 43 centers during October-November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. RESULTS: The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%, and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002, 2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared HCV after anti-HCV therapy. CONCLUSIONS: Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.

Estimating the incidence of equine viral arteritis and the sensitivity of its surveillance in the French breeding stock.

Equine viral arteritis (EVA) may have serious economic impact on the equine industry. For this reason, it is monitored in many countries, especially in breeding stock, to avoid its spread during breeding activities. In France, surveillance is mainly based on serological tests, since mares are not vaccinated, but difficulties in interpreting certain series of results may impair the estimation of the number of outbreaks. In this study, we propose specific rules for identifying seroconversion in order to estimate the number of outbreaks that were detected by the breeding stock surveillance component (BSSC) in France between 2006 and 2013. A consensus among multidisciplinary experts was reached to consider seroconversion as a change in antibody titer from negative to at least 32, or as an eight-fold or greater increase in antibody level. Using these rules, 239 cases and 177 outbreaks were identified. Subsequently, we calculated the BSSC's sensitivity as the ratio of the number of detected outbreaks to the total number of outbreaks that occurred in breeding stock (including unreported outbreaks) estimated using a capture-recapture model. The total number of outbreaks was estimated at 215 (95% credible interval 195-249) and the surveillance sensitivity at 82% (CrI95% 71-91). Our results confirm EVA circulation in French breeding stock, show that neutralizing antibodies can persist up to eight years in naturally infected mares and suggest that certain mares have been reinfected. This study shows that the sensitivity of the BSSC is relatively high and supports its relevance to prevent the disease spreading through mating.

Comparative evaluation of three surveillance systems for infectious equine diseases in France and implications for future synergies.

It is necessary to assess surveillance systems for infectious animal diseases to ensure they meet their objectives and provide high-quality health information. Each system is generally dedicated to one disease and often comprises various components. In many animal industries, several surveillance systems are implemented separately even if they are based on similar components. This lack of synergy may prevent optimal surveillance. The purpose of this study was to assess several surveillance systems within the same industry using the semi-quantitative OASIS method and to compare the results of the assessments in order to propose improvements, including future synergies. We have focused on the surveillance of three major equine diseases in France. We have identified the mutual and specific strengths and weaknesses of each surveillance system. Furthermore, the comparative assessment has highlighted many possible synergies that could improve the effectiveness and efficiency of surveillance as a whole, including the implementation of new joint tools or the pooling of existing teams, tools or skills. Our approach is an original application of the OASIS method, which requires minimal financial resources and is not very time-consuming. Such a comparative evaluation could conceivably be applied to other surveillance systems, other industries and other countries. This approach would be especially relevant to enhance the efficiency of surveillance activities when resources are limited.

DAT isn't all that: cocaine reward and reinforcement require Toll-like receptor 4 signaling.

The initial reinforcing properties of drugs of abuse, such as cocaine, are largely attributed to their ability to activate the mesolimbic dopamine system. Resulting increases in extracellular dopamine in the nucleus accumbens (NAc) are traditionally thought to result from cocaine's ability to block dopamine transporters (DATs). Here we demonstrate that cocaine also interacts with the immunosurveillance receptor complex, Toll-like receptor 4 (TLR4), on microglial cells to initiate central innate immune signaling. Disruption of cocaine signaling at TLR4 suppresses cocaine-induced extracellular dopamine in the NAc, as well as cocaine conditioned place preference and cocaine self-administration. These results provide a novel understanding of the neurobiological mechanisms underlying cocaine reward/reinforcement that includes a critical role for central immune signaling, and offer a new target for medication development for cocaine abuse treatment.

Risk of early breastfeeding cessation among symmetrical, small for gestational age infants.

BACKGROUND: Many studies have shown that children born small for gestational age are at a metabolic disadvantage. Breastfeeding is associated with reduced risk of developing metabolic syndrome. OBJECTIVE: To determine whether ponderal index, weight, length or head circumference at birth affect early exclusive breastfeeding discontinuation. DESIGN: Information from medical records of full-term infants attending the same paediatric clinic was used to examine the relationship between birth size and failure to breastfeed within 28 days after birth. Details of demographics and diagnoses were prospectively recorded. Feeding method was assessed at each child visit by their healthcare provider. Feeding practices were compared between infants of high, normal and low ponderal index at birth. RESULTS: Multivariate models (p's ≤ 0.02) confirmed that the chance of exclusive breastfeeding continuation within 4 weeks of life was less in infants whose birth weight was below 2780 g or whose neonatal head circumference was < 33 cm. Birth length did not account for this effect. Ponderal index was not associated with a higher risk of early discontinuation of exclusive breastfeeding. CONCLUSIONS: This study reports that birth weight ≥ 2780 g and head circumference at birth ≥ 33 cm are independent predictors of breastfeeding onset success.

Opioid activation of toll-like receptor 4 contributes to drug reinforcement.

Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here, we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the nonopioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knock-outs of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4(-/-) mice had reduced oxycodone-induced p38 and JNK phosphorylation, while displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system that amplifies opioid-induced elevations in extracellular dopamine levels, therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward.

5-hydroxytryptamine 2C receptors in the dorsal striatum mediate stress-induced interference with negatively reinforced instrumental escape behavior.

Uncontrollable stress can interfere with instrumental learning and induce anxiety in humans and rodents. While evidence supports a role for serotonin (5-HT) and serotonin 2C receptors (5-HT(2C)R) in the behavioral consequences of uncontrollable stress, the specific sites of action are unknown. These experiments sought to delineate the role of 5-HT and 5-HT(2C)R in the dorsal striatum (DS) and the lateral/basolateral amygdala (BLA) in the expression of stress-induced instrumental escape deficits and exaggerated fear, as these structures are critical to instrumental learning and fear behaviors. Using in vivo microdialysis, we first demonstrated that prior uncontrollable, but not controllable, stress sensitizes extracellular 5-HT in the dorsal striatum, a result that parallels prior work in the BLA. Additionally, rats were implanted with bi-lateral cannula in either the DS or the BLA and exposed to uncontrollable tail shock stress. One day later, rats were injected with 5-HT(2C)R antagonist (SB242084) and fear and instrumental learning behaviors were assessed in a shuttle box. Separately, groups of non-stressed rats received an intra-DS or an intra-BLA injection of the 5-HT(2C)R agonist (CP809101) and behavior was observed. Intra-DS injections of the 5-HT(2C)R antagonist prior to fear/escape tests completely blocked the stress-induced interference with instrumental escape learning; a partial block was observed when injections were in the BLA. Antagonist administration in either region did not influence stress-induced fear behavior. In the absence of prior stress, intra-DS administration of the 5-HT(2C)R agonist was sufficient to interfere with escape behavior without enhancing fear, while intra-BLA administration of the 5-HT(2C)R agonist increased fear behavior but had no effect on escape learning. Results reveal a novel role of the 5-HT(2C)R in the DS in the expression of instrumental escape deficits produced by uncontrollable stress and demonstrate that the involvement of 5-HT(2C)R activation in stress-induced behaviors is regionally specific.

Prognostic value of serum CA125 levels in diffuse large B-cell lymphoma: potential role of a new sex- and age-adjusted reference value.

CA125, a tumor marker normally used to follow the clinical course of ovarian cancer, also may have a role in lymphoma. All available series were analyzed using the standard reference value 35 U/ml, but age and sex may influence serum CA125 (sCA125) levels. We aim to study the prognostic value of serum CA125 (sCA125) levels in diffuse large B-cell lymphoma (DLBCL), considering the influence of age and sex on sCA125 levels. We investigated the relationship between sCA125 and clinical outcome after treatment in 42 patients with DLBCL, comparing both the standard (35 U/ml) and a new age and sex adjusted (sex/age-adjusted) reference value proposed by our group. We found that patients with elevated sCA125 levels had significantly more adverse prognostic factors at diagnosis, lower CR rates, higher relapse rates and worse survival. In the low-risk IPI categories, the presence of elevated sCA125 defined a particularly high-risk subgroup with poorer 3-year PFS when compared with patients with normal sCA125 levels. The use of a sex/age-adjusted reference value for sCA125 may increase the sensitivity to identify those patients with elevated sCA125 levels truly related to DLBCL activity.

Behavioral control over shock blocks behavioral and neurochemical effects of later social defeat.

Experience with behavioral control over tailshock (escapable shock, ES) has been shown to block the behavioral and neurochemical changes produced by later uncontrollable tail shock (inescapable shock, IS). The present experiments tested, in rats, whether the protective effect of control over tailshock extends beyond reducing the behavioral and neurochemical impact of a subsequent tailshock experience to stressors that are quite different. Social defeat (SD) was chosen as the second stress experience because it has few if any cues in common with tailshock. SD produced shuttlebox escape learning deficits ("learned helplessness") and reduced juvenile social investigation 24 h later, as does IS. IS is notable for inducing a large increase in dorsal raphe nucleus (DRN) serotonergic (5-HT) activity as measured by extracellular levels of 5-HT within the DRN, and SD did so as well. ES occurring 7 days before SD blocked this SD-induced DRN activation, as well as the SD-induced interference with shuttlebox escape and reduction in social investigation. Prior exposure to yoked IS did not reduce the DRN 5-HT activation or later behavioral effects produced by SD, and thus the proactive stress-blunting effects of ES can be attributed to it's controllability. Thus, ES confers a very general protection to the impact of a subsequent stress experience.

Allotransplant of microencapsulated parathyroid tissue in severe postsurgical hypoparathyroidism: a case report.

The last therapeutic alternative in severe postsurgical hypoparathyroidism is allotransplantation of microencapsulated parathyroid cells. With this technique, it is possible to implant cells or tissue of parathyroid origin to replace them in such patients, without immusupression. We report an allotransplant of parathyroid tissue in a patient with continous endovenous requirement of calcium to survive. The microencapsulation was carried out with a commercial sodium alginate. We implant 23 microspheres in the nondominant forearm and 40 microspheres in the leg in a second attempt. In this article, we show functionality of the graft for at least 20 months without requirement of endovenous calcium. We report this procedure as a therapeutical alternative in severe hypoparathyroidism.

New real-time PCR-based method for the joint genotyping of JAK2 (V617F) with inherited thrombophilic F5 and F2 mutations.

BACKGROUND: During the last years the appearance of the acquired V617F mutation of the Janus Kinase 2 gene (JAK2) in patients suffering different thrombotic events has been described. We decided to develop a new and rapid multiplex real-time Polymerase Chain Reaction (PCR) in order to detect the V617F mutation together with the inherited prothrombotic mutations of factors F5 and F2. DESIGN AND METHODS: The method was carried out on the LightCycler 2.0 (Roche Diagnostics, Mannheim, Germany) and consisted in a first step of simultaneous amplification by real-time PCR of the three genes to be genotyped, in a 20microl closed tube, using a primer pair together with the correspondent FRET-hybridization probes for each gene. RESULTS: We assayed 41 samples in the multiplex PCR reaction, 19 were positive (46.34%) for V617F mutation. From the V617F positive samples we found 1 sample heterozygous for F2 (5.26%) and 1 sample heterozygous for F5 (5.26%), so a 10.52% of the samples tested combine V617F mutation with inherited thrombophilic mutations. Results were clear, rapid and reliable allowing a significant time saving. CONCLUSIONS: The technique presented in this manuscript is a new achievement in the field of the molecular diagnosis that combines the genotyping of F5 and F2 with the assessment of the JAK2 (V617F) mutation load.

Rapid triplex asymmetric real-time PCR hybridization probe assay for the joint genotyping of F2, F5 and F12.

INTRODUCTION: The Factor 5 Leiden mutation and the G20210A variant of Factor 2 are two important risk factors for hereditary thromboembolism. Several reports have demonstrated that homozygous carriers for C46T mutation of the Factor 12 gene is associated with a significant increased risk for the development of coronary disease as well as cerebral and peripheral venous thrombosis. DESIGN AND METHODS: We develop a rapid and feasible asymmetric multiplex real-time PCR-based method using fluorescence resonance emission transfer (FRET) probes followed by a melting temperature (T(m)) curve assay for the simultaneous clinical diagnosis of F2, F5 and F12 mutations in a 10 microl closed tube. This new tool uses three different fluorescence channels in a LightCycler 2.0 for the robust genotyping of each one of the mutations included in the reaction. RESULTS: Assay evaluation performed on 67 DNA samples previously genotyped with reference methods resulted in full concordance of results for the three mutations tested. Higher asymmetric ratio of primer pair concentration significantly increased the efficiency of the melting peak assay used for the mutation genotyping without modifying the Crossing Point (CP) obtained from the amplification curves. CONCLUSIONS: To our knowledge this is the first triplex real-time PCR FRET-based assay reported in bibliography that allows a rapid and simultaneous genotyping of these three thrombosis risk factors. This new and rapid tool may contribute to the better understanding of the interrelations or contributions of these gene mutations to different thrombotic or coronary disease-related events.

[Registry of mild craniocerebral trauma: multicentre study from the Spanish Association of Pediatric emergencies]. / Registro de traumatismos craneoencefálicos leves: estudio multicéntrico de la Sociedad Española de Urgencias Pediátricas.

OBJECTIVE: To determine management practices of minor head trauma in children evaluated at Spanish Hospital Emergency Departments and to determine patient variables associated with intracranial injury. METHODS: Multicenter and prospective study during 18 months in 9 hospitals in Spain. Patients up to the age of 18 years with minor head trauma (Glasgow Coma Scale score higher than or equal to 13 on admission), treated in Emergency Departments and with a maximum onset of 72h since the traumatism, were included in the study. RESULTS: A total of 1070 patients were studied with a median age of 2.4 years (p25-75 0.9-6.4 years); 61.2% were male. The median time between head trauma and medical consultation was 1 hour (p25-75 0.6-2.5h). Skull X-rays were performed on 64.5% of the children and a head CT scan on 9%; 91.4% of X-ray and 84.4% of CT were normal. The prevalence of intracranial injury was 1.4% (95% CI: 0.8-2.3). Twenty-five point three percent of the patients were admitted; 4 (3.7%) required neurosurgical intervention during admission. None of the patients died. Multiple logistic regression analysis identified loss of consciousness (OR 4.2, 95% CI: 1.1-17; P=0.045), neurological deterioration (OR 8.8, 95% CI: 2.1-37.6; P=0.003) and cephalhaematoma (OR 14.6, 95% CI: 4.9-44; P <0.001) as independent predictors of intracranial injury. CONCLUSIONS: The combination of clinical parameters allows selection of patients with minor head trauma who need complementary explorations. In consequence, the routine use of skull X-ray in their initial evaluation is unnecessary.

Activation of the ventral medial prefrontal cortex during an uncontrollable stressor reproduces both the immediate and long-term protective effects of behavioral control.

The degree of behavioral control that an organism has over a stressor determines the behavioral and neurochemical sequelae of the stressor, with the presence of control preventing the typical outcomes that occur when the stressor is uncontrollable (e.g. failure to learn, exaggerated fear, dorsal raphe nucleus (DRN) 5-HT activation). Furthermore, an experience with a controllable stressor blocks the consequences of later uncontrollable stressors ("immunization"). These effects of control have been argued to be mediated by control-induced activation of ventral medial prefrontal cortex (mPFCv) output to the DRN. The experiments that have led to this interpretation have all involved the inactivation of the mPFCv with muscimol, showing that inactivation during the stressor eliminates the stressor-resistance produced by control, with the controllable stressor now acting as if it were uncontrollable. The present experiments in rats employed the opposite strategy, activating the mPFCv during the stressor. mPFCv microinjection of picrotoxin during the stressor eliminated the DRN 5-HT activation that normally occurs during the uncontrollable stressor, as well as the escape learning deficit and exaggerated fear that normally follows uncontrollable stress. Furthermore, mPFCv activation during an initial exposure to an uncontrollable stressor led the uncontrollable stressor to produce behavioral and neurochemical immunization when the subjects were later exposed to an uncontrollable stressor. That is, the conjoint activation of the mPFCv and exposure to an uncontrollable stressor led the uncontrollable stressor to act as if it were controllable. These results provide strong support for the argument that behavioral control produced stress-resistance by activating the mPFCv.

Controllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear.

Fear conditioning and fear extinction play key roles in the development and treatment of anxiety-related disorders, yet there is little information concerning experiential variables that modulate these processes. Here we examined the impact of exposure to a stressor in a different environment on subsequent fear conditioning and extinction, and whether the degree of behavioral control that the subject has over the stressor is of importance. Rats received a session of either escapable (controllable) tail shock (ES), yoked inescapable (uncontrollable) tail shock (IS), or control treatment (home cage, HC) 7 days before fear conditioning in which a tone and foot shock were paired. Conditioning was measured 24 h later. In a second experiment rats received ES, IS or HC 24 h after contextual fear conditioning. Extinction then occurred every day beginning 7 days later until a criterion was reached. Spontaneous recovery of fear was assessed 14 days after extinction. IS potentiated fear conditioning when given before fear conditioning, and potentiated fear responding during extinction when given after conditioning. Importantly, ES potently interfered with later fear conditioning, decreased fear responding during fear extinction, and prevented spontaneous recovery of fear. Additionally, we examined if the activation of the ventral medial prefrontal cortex (mPFCv) by ES is critical for the protective effects of ES on later fear conditioning. Inactivation of the mPFCv with muscimol at the time of the initial experience with control prevented ES-induced reductions in later contextual and auditory fear conditioning. Finally, we explored if the protective effects of ES extended to an unconditioned fear stimulus, ferret odor. Unlike conditioned fear, prior ES increased the fear response to ferret odor to the same degree as did IS.