Dissecting the brain's fear systems responding to snake threats.

We examined the behavioural responses and Fos expression pattern of rats that were exposed to snake threats from shed snakeskin and a live snake. We differentiated the behavioural responses and the pattern of Fos expression in response to the odour cues and mild threat from a live snake. Animals exposed to the snake odour alone or to the confined snake showed a great deal of risk assessment. Conversely, the intensification of odour during exposure to the live snake decreased the threat ambiguity, and the animals froze for a significantly longer period. Our Fos analysis showed that a pathway formed by the posteroventral part of the medial amygdalar nucleus to the central part of the ventromedial hypothalamic nucleus appeared to be solely responsive to odour cues. In addition, we showed increased Fos expression in a parallel circuit comprising the lateral amygdalar nucleus, ventral subiculum, lateral septum, and juxtadorsomedial region of the lateral hypothalamic area that is responsive to both the odour and mild threat from a live snake. This path is likely to process the environmental boundaries of the threat to be avoided. Both paths merge into the dorsal premammillary nucleus and periaqueductal grey sites, which all increase Fos expression in response to the snake threats and are likely to organize the defensive responses. Moreover, we found that the snake threat mobilized the Edinger-Westphal and supraoculomotor nuclei, which are involved in stress adaptation and attentional mechanisms.

Uncertainty and anxiety: Evolution and neurobiology.

Anxiety is a complex phenomenon: Its eliciting stimuli and circumstances, component behaviors, and functional consequences are only slowly coming to be understood. Here, we examine defense systems from field studies; laboratory studies focusing on experimental analyses of behavior; and, the fear conditioning literature, with a focus on the role of uncertainty in promoting an anxiety pattern that involves high rates of stimulus generalization and resistance to extinction. Respectively, these different areas provide information on evolved elicitors of defense (field studies); outline a defense system focused on obtaining information about uncertain threat (ethoexperimental analyses); and, provide a simple, well-researched, easily measured paradigm for analysis of nonassociative stress-enhanced fear conditioning (the SEFL). Results suggest that all of these-each of which is responsive to uncertainty-play multiple and interactive roles in anxiety. Brain system findings for some relevant models are reviewed, with suggestions that further analyses of current models may be capable of providing a great deal of additional information about these complex interactions and their underlying biology.

Cortagine infused into the medial prefrontal cortex attenuates predator-induced defensive behaviors and Fos protein production in selective nuclei of the amygdala in male CD1 mice.

Corticotropin-releasing factor (CRF) plays an essential role in coordinating the autonomic, endocrine and behavioral responses to stressors. In this study, we investigated the role of CRF within the medial prefrontal cortex (mPFC) in modulating unconditioned defensive behaviors, by examining the effects of microinfusing cortagine a selective type-1 CRF receptor (CRF1) agonist, or acidic-astressin a preferential CRF1 antagonist, into the mPFC in male CD-1 mice exposed to a live predator (rat exposure test--RET). Cortagine microinfusions significantly reduced several indices of defense, including avoidance and freezing, suggesting a specific role for CRF1 within the infralimbic and prelimbic regions of the mPFC in modulating unconditioned behavioral responsivity to a predator. In contrast, microinfusions of acidic-astressin failed to alter defensive behaviors during predator exposure in the RET. Cortagine microinfusions also reduced Fos protein production in the medial, central and basomedial, but not basolateral subnuclei of the amygdala in mice exposed to the rat predatory threat stimulus. These results suggest that CRF1 activation within the mPFC attenuates predator-induced unconditioned anxiety-like defensive behaviors, likely via inhibition of specific amygdalar nuclei. Furthermore, the present findings suggest that the mPFC represents a unique neural region whereby activation of CRF1 produces behavioral effects that contrast with those elicited following systemic administration of CRF1 agonists.

Sex, defense, and risk assessment: Who could ask for anything more?

Over the 30 years since IBNS was founded, a central theme of "Translation" has emerged. This reflects increasing realization that mental disorders such as anxiety and depression are extremely widespread, expensive and painful to societies and individuals across the world. The Blanchard lab has been particularly involved in attempts to understand the evolutionary and functional mechanisms underlying defensive behaviors as a focal component of these disorders. This involved analysis of the relationships between threatening situations/stimuli, and the behaviors (flight, freezing, fight, and risk assessment) that respond to them, for rodents; and also attempts to link these relationships to human responsivity to similar threatening events: Linkages that are complicated by factors such as domestication and sex. In particular it is important to describe and characterize the organization of defensive patterns in people as well as nonhuman animals, and to understand how these patterns can become nonfunctional and pathological.

Are cognitive aspects of defense a core feature of anxiety and depression?

Anxiety and depression are highly prevalent behavior disorders, particularly in women. Recent preclinical work using animal models has been suboptimal in predicting the efficacy of drugs targeted at these conditions, suggesting a potential discrepancy between such models and the human disorders. Notably female animals tend to be equal to, or less responsive than, males in these tasks. A number of analyses suggest that mammalian defense patterns are complex: In addition to relatively discrete and immediate fight, flight, and freezing responses, a risk assessment pattern may occur in response to threat stimuli or situations with ambiguous elements. This pattern combines defensiveness with a number of cognition-linked behaviors such as sensory attention and orientation, approach, contact, and investigation of the potential threat. Studies measuring elements of this pattern suggest that female rats, and perhaps female mice, show higher levels than equivalent males. Higher female involvement may also occur in tasks involving learning/generalization/extinction of defensiveness to conditioned stimuli. Such findings are consonant with recent analyses of "female survival strategies" based on differential adaptiveness of cognitive components of defensiveness in females, due to the necessity of female care of offspring until they are independent. These data suggest the value of additional behavioral and functional analyses of cognitive aspects of defensive behavior; contributing to both an understanding of their underlying mechanisms, and providing more sensitive measures of drug responsivity for use with animal models.

Mecp2 truncation in male mice promotes affiliative social behavior.

Mouse models of Rett syndrome, with targeted mutations in the Mecp2 gene, show a high degree of phenotypic consistency with the clinical syndrome. In addition to severe and age-specific regression in motor and cognitive abilities, a variety of studies have demonstrated that Mecp2 mutant mice display impaired social behavior. Conversely, other studies indicate complex enhancements of social behavior in Mecp2 mutant mice. Since social behavior is a complicated accumulation of constructs, we performed a series of classic and refined social behavior tasks and revealed a relatively consistent pattern of enhanced pro-social behavior in hypomorphic Mecp2 (308/Y) mutant mice. Analyses of repetitive motor acts, and cognitive stereotypy did not reveal any profound differences due to genotype. Taken together, these results suggest that the mutations associated with Rett syndrome are not necessarily associated with autism-relevant social impairment in mice. However, this gene may be a valuable candidate for revealing basic mechanisms of affiliative behavior.

Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors.

A wealth of studies has implicated oxytocin (Oxt) and its receptors (Oxtr) in the mediation of social behaviors and social memory in rodents. It has been suggested that failures in this system contribute to deficits in social interaction that characterize autism spectrum disorders (ASD). In the current analyses, we investigated the expression of autism-related behaviors in mice that lack the ability to synthesize the oxytocin receptor itself, Oxtr knockout (KO) mice, as compared to their wild-type (WT) littermates. In the visible burrow system, Oxtr KO mice showed robust reductions in frontal approach, huddling, allo-grooming, and flight, with more time spent alone, and in self-grooming, as compared to WT. These results were corroborated in the three-chambered test: unlike WT, Oxtr KO mice failed to spend more time in the side of the test box containing an unfamiliar CD-1 mouse. In the social proximity test, Oxtr KO mice showed clear reductions in nose to nose and anogenital sniff behaviors oriented to an unfamiliar C57BL/6J (B6) mouse. In addition, our study revealed no differences between Oxtr WT and KO genotypes in the occurrence of motor and cognitive stereotyped behaviors. A significant genotype effect was found in the scent marking analysis, with Oxtr KO mice showing a decreased number of scent marks, as compared to WT. Overall, the present data indicate that the profile for Oxtr KO mice, including consistent social deficits, and reduced levels of communication, models multiple components of the ASD phenotype. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

[Computerized prescription for medical devices: examples, interest and limits]. / Vers la prescription informatisée des dispositifs médicaux : exemples d'application, intérêts et limites.

INTRODUCTION: Related to the good practice contract implemented in hospitals, the prescription dedicated to medical devices, such as pharmaceuticals, could promote safety and good practice. MATERIAL AND METHOD: We attempted to implement a computerized prescription for medical devices. In order to illustrate the method, two examples were selected: the Negative Pressure Wound Therapy (NPWT) and the Drug Eluting Stents (DES). RESULTS: In partnership with the medical teams was elaborated a computerized protocol which included all the needed items for the good use of NPWT. For DES, a pre-existing questionnaire was used. We updated it in order to integrate new items such as the prescriber's name, the patient's name, the characteristics of the wound, the DES references and the indications. DISCUSSION AND CONCLUSION: Computerized prescriptions for high-risk and expensive medical devices seem to be an interesting approach to guarantee the patient care safety and to reduce the budget impacts. In order to monitor the indications funded as fee-for-service medical devices, a prescription will emerge as a gold standard in the future in France. Eventually, this study highlights a new activity of clinical pharmacy for hospital pharmacists dealing with medical devices.

[Esophageal foreign body: dental plate]. / Corps étranger esophagien: prothèse dentaire.

OBJECTIVE: Describe clinical characteristics and management of dental esophageal foreign body. PATIENT AND METHODS: Observation of a denture wedged in the esophagus in a 55 year man and literature review of cases reported in the literature. RESULTS: Enclosing risk factors for esophageal foreign body of dental origin are the altered consciousness, old persons, and local factors. The diagnosis is suspected with chest radiography and confirm by endoscopy. The therapeutic management with extraction of the foreign body is endoscopic and / or surgery. Complications a e related to time taken and can be sometimes serious. CONCLUSION: The diagnosis of esophageal dental foreign body should be considered in any dysphagia in predisposing persons. The diagnosis may require endoscopy. Prevention go through information of actors in specialized institutes.

[Thyroid differenciated carcinoma in children. Study from Normandy]. / Cancers thyroïdiens différenciés de l'enfant. l'expérience normande.

OBJECTIVE: Definition of a strategy for the management of thyroid differenciated carcinoma in children. DESIGN AND SETTING: Retrospective cohort study from the Normandy area in France. METHOD: Analysis of the medical records of 13 children and adolescents (age > 15 years), presenting with thyroid differenciated carcinoma in three Normandy French hospitals from 1994 to 2006, to determine the clinical features and treatment of the disease. RESULTS: X of the patients were male and y were female, with a mean age at presentation of 11 years. Most frequently symptom was solitary nodes in the thyroid gland (69%). Most frequent histological type was papillary cancer (92%). Size of tumor was > 4 cm in 23% of cases. Children had undergone surgery with total thyroidectomy, radio-iodine treatment and suppressive hormonotherapy. We observed 46% post surgery complications. All patients were alive and none developed a recurrence. CONCLUSION: Thyroid differenciated carcinoma in children and adolescents were more agressif with most frequently metastasis and recurrence than thyroid differenciated carcinoma of adults. Pronostic is good with 90% of survival at 20 years. We propose a coherent plan of treatment: 1. Thyroidectomy with cervical central lymph node dissection (group VI) completed bilateral selected head neck dissection compartments (groups IIa, III, IV) if macroscopic lymph node metastases in lateral cervical compartment. 2. Postoperative radioiodine is done in all tumor > T1N0 and completed with hormonotherapy.

The low-affinity receptor for IgE (CD23) on B lymphocytes is spatially associated with HLA-DR antigens.

Two hybridomas that produce the mAbs 135 and 449 B4 were obtained that inhibited the binding of IgE to the Fc epsilon RL/CD23 on the EBV-transformed B cell line RPMI 8866. mAb 135 was obtained from a mouse immunized with RPMI 8866 cells, whereas mAb 449B4 was obtained from a mouse immunized with a partially purified preparation of Fc epsilon RL/CD23 obtained as the eluate of an IgE immunoabsorbent loaded with a soluble extract of RPMI 8866 cells. These two mAbs bound to Fc epsilon RL/CD23- cell lines and precipitated two polypeptides with 36,000 Mr and 28,000 Mr, which were the HLA-DR alpha and beta chains, respectively. Immunoprecipitation with mAb 135 of NP-40 lysates from dithio-bis(succinimidyl propionate) (DSP) crosslinked 125I-labeled RPMI 8866 or normal B cells incubated with rIL-4 showed three polypeptides with 42,000, 36,000, and 28,000 Mr. The 42,000 Mr polypeptide is identical to the Fc epsilon RL/CD23 since it could be precipitated by the anti-Fc epsilon RL/CD23 mAb 25 after resolubilization from the SDS-PAGE gel. Immunoprecipitations of the crosslinked cell extracts carried out with the anti-Fc epsilon RL/CD23 mAb 25 yielded the same three polypeptides. Furthermore, when RPMI 8866 or rIL-4 preincubated normal B cells were solubilized with a digitonin buffer, which prevents the dissociation of noncovalently linked polypeptide complexes, mAb 135 and mAb 25 precipitated complexes composed of three molecules with 42,000, 36,000, and 28,000 Mr. The well-characterized anti-HLA-DR mAb L243 was unable to block the binding of either IgE or mAb 135 to RPMI 8866 cells, although it could immunoprecipitate the complex (HLA-DR-Fc epsilon RL/CD23) from crosslinked cell lysates. Since mAb 135 and L243 were able to both bind the RPMI 8866 cells, it demonstrates that they bind to different epitopes of the HLA-DR complex, the mAb 135 epitope of the HLA-DR molecule being close to the IgE binding site of the Fc epsilon RL/CD23. These data demonstrated that the Fc epsilon RL/CD23 and HLA-DR antigens are spatially associated on the B cell membrane.

T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines.

Analysis of the cDNA encoding murine interleukin (IL) 17 (cytotoxic T lymphocyte associated antigen 8) predicted a secreted protein sharing 57% amino acid identity with the protein predicted from ORF13, an open reading frame of Herpesvirus saimiri. Here we report on the cloning of human IL-17 (hIL-17), the human counterpart of murine IL-17. hIL-17 is a glycoprotein of 155 amino acids secreted as an homodimer by activated memory CD4+ T cells. Although devoid of direct effects on cells of hematopoietic origin, hIL-17 and the product of its viral counterpart, ORF13, stimulate epithelial, endothelial, and fibroblastic cells to secrete cytokines such as IL-6, IL-8, and granulocyte-colony-stimulating factor, as well as prostaglandin E2. Furthermore, when cultured in the presence of hIL-17, fibroblasts could sustain the proliferation of CD34+ hematopoietic progenitors and their preferential maturation into neutrophils. These observations suggest that hIL-17 may constitute (a) an early initiator of the T cell-dependent inflammmatory reaction; and (b) an element of the cytokine network that bridges the immune system to hematopoiesis.

Maternal separation modulates short-term behavioral and physiological indices of the stress response.

Early-life stress produces an anxiogenic profile in adulthood, presumably by activating the otherwise quiescent hypothalamic-pituitary-adrenal (HPA) axis during the vulnerable 'stress hyporesponsive period'. While the long-term effects of such early-life manipulations have been extensively characterized, little is known of the short-term effects. Here, we compared the short-term effects of two durations of maternal separation stress and one unseparated group (US) on behavioral and physiological indices of the stress response in rat pups. Separations included 3h on each of 12days, from postnatal day (PND) 2 to 13 (MS2-13) and 3days of daily, 6-h separation from PND11-13 (MS11-13). On PND14 (Experiment 1), both MS2-13 and MS11-13 produced marked reductions in freezing toward an adult male conspecific along with reduced levels of glucocorticoid type 2 (GR) and CRF type-1 (CRF(1)) receptor mRNA in the hippocampus. Group MS2-13 but not MS11-13 produced deficits in stressor-induced corticosterone secretion, accompanied by reductions in body weight. Our results suggest that GR and/or CRF(1) levels, not solely the magnitude of corticosterone secretion, may be involved in the modulation of freezing. In a second experiment, we aimed to extend these findings by testing male and female separated and unseparated pups' unconditioned defensive behaviors to cat odor on PND26, and subsequent cue+context conditioning and extinction throughout postnatal days 27-32. Our results show that maternal separation produced reductions in unconditioned freezing on PND26, with MS2-13 showing stronger deficits than MS11-13. However, separation did not affect any other defensive behaviors. Furthermore, separated rats failed to show conditioned freezing, although they did avoid the no-odor block conditioned cue. There were no sex differences other than weight. We suggest that maternal separation may have produced these changes by disrupting normal development of hippocampal regions involved in olfactory-mediated freezing, not in mechanisms of learning and memory per se. These findings may have direct relevance for understanding the mechanisms by which early-life adverse experiences produce short-term and lasting psychopathologies.

[Cranial fasciitis of childhood]. / Fasciite crâniale.

OBJECTIVE: To describe the clinical and pathological features of cranial fasciitis of childhood, and to review and compare this case with those of international literature. METHODS: We report a case of cranial fasciitis of childhood located on the face of a 13-month-old boy. A complete review was performed from the database "Pub Med", looking for the key words "head and neck inflammatory myofibroblastic tumour", "nodular fasciitis", "cranial fasciitis of childhood". RESULTS: Cranial fasciitis is benign rapidly growing fibroblastic tumour, belonging to the group of nodular fasciitis, and has a predilection for the head and neck region of young children. This tumour is highly cellular and often show striking erosion of bone often misdiagnosed as a sarcoma. Surgery with adequate resection margin is the best treatment. There is no tendency for local recurrence. CONCLUSION: Positive pathological diagnosis of cranial fasciitis is uncommon and may be difficult.

Function evaluation of laryngeal reconstruction using infrahyoid muscle after partial laryngectomy in 37patients.

Treatment of small laryngeal cancerous lesions (T1 and T2) is based on partial endoscopic or open surgery and radiotherapy. In addition to the oncological imperative, these techniques must optimally preserve the functions of breathing, swallowing and phonation. OBJECTIVE: To analyze the above functions in patients treated with supracricoid laryngectomy and reconstruction using infrahyoid muscle. MATERIALS AND METHODS: Breathing, swallowing and phonation were analyzed in 37patients treated in two institutes between 2005 and 2015. All patients undergoing the above type of reconstruction with a minimum 1year's follow-up were included. Respiratory study noted any tracheotomy and measured peak inspiratory flow. Preservation of cricoarytenoid units and nasogastric intubation time, and DHI-30 self-administered questionnaire results were collected to analyze swallowing function. Phonation was assessed on the VHI-30 self-administered questionnaire. RESULTS: The rate of primary surgery without tracheotomy was 64.9% (13patients), with rapid resumption of oral feeding (mean intubation time, 13days). Mean VHI score was 28.3 and mean DHI 30score 2.7. Mean peak inspiratory flow was 203.3mL/min. CONCLUSION: Supracricoid laryngectomy with reconstruction using subhyoid muscle is an alternative technique for the treatment of small laryngeal cancerous lesions, providing uncomplicated functional outcome.

Repeated exposure of naïve and peripheral nerve-injured mice to a snake as an experimental model of post-traumatic stress disorder and its co-morbidity with neuropathic pain.

Confrontation of rodents by natural predators provides a number of advantages as a model for traumatic or stressful experience. Using this approach, one of the aims of this study was to investigate a model for the study of post-traumatic stress disorder (PTSD)-related behaviour in mice. Moreover, because PTSD can facilitate the establishment of chronic pain (CP), and in the same way, patients with CP have an increased tendency to develop PTSD when exposed to a traumatic event, our second aim was to analyse whether this comorbidity can be verified in the new paradigm. C57BL/6 male mice underwent chronic constriction injury of the sciatic nerve (CCI), a model of neuropathic CP, or not (sham groups) and were submitted to different threatening situations. Threatened mice exhibited enhanced defensive behaviours, as well as significantly enhanced risk assessment and escape behaviours during context reexposure. Previous snake exposure reduced open-arm time in the elevated plus-maze test, suggesting an increase in anxiety levels. Sham mice showed fear-induced antinociception immediately after a second exposure to the snake, but 1 week later, they exhibited allodynia, suggesting that multiple exposures to the snake led to increased nociceptive responses. Moreover, after reexposure to the aversive environment, allodynia was maintained. CCI alone produced intense allodynia, which was unaltered by exposure to either the snake stimuli or reexposure to the experimental context. Together, these results specifically parallel the behavioural symptoms of PTSD, suggesting that the snake/exuvia/reexposure procedure may constitute a useful animal model to study PTSD.

Defensive behaviors and brain regional activation changes in rats confronting a snake.

In the present study, we examined behavioral and brain regional activation changes of rats). To a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

Mechanism for the water-to-air transfer and concentration of bacteria.

Air bubbles breaking at the air-water interface can remove bacteria that concentrate in the surface microlayer and eject the bacteria into the atmosphere. The bacterial concentrations (numbers per milliliter) in the drops ejected from the bubbles may, depending on drop size, be from 10 to 1000 times that of the water in which the bubbles burst.

Virus transfer from surf to wind.

Bubbles in the sea surf adsorb and carry viruses to the surface where they are propelled into the air on tiny jets of seawater when the bubble bursts. The ejected jets become tiny drops of aerosol. The buble adsorption and virus concentration in the surf is analagous to industrial bubble levitation processes that concentrate metallic ores, enzymes, and finely divided organic crystals. Bubble levitation of viruses delibrately injected into the surf produced 200 times more virus per milliliter in the aerosol than were present in samples from the surf. Some aerosol drops created by the surf and carried by the wind fall out on the beach. The frequency of virus-bearing drops, that is, the number of plaques on seeded plates exposed on the beach, decreased exponentially with the distance downwind from the surf.

Effects of acidic-astressin and ovine-CRF microinfusions into the ventral hippocampus on defensive behaviors in rats.

This study investigated a possible role for ventral hippocampal corticotropin-releasing factor (CRF) in modulating both unconditioned and conditioned defensive behaviors by examining the effects of pre-training ventral hippocampal ovine-CRF (oCRF) or acidic-astressin ([Glu(11,16)]Ast) microinfusions in male Long-Evans hooded rats exposed to various threat stimuli including the elevated plus-maze (EPM) (oCRF), cat odor (oCRF and [Glu(11,16)]Ast) and a live cat ([Glu(11,16)]Ast). Unconditioned defensive behaviors were assessed during threat exposure, while conditioned defensive behaviors were assessed in each predator context 24 h after the initial threat encounter. Pre-training infusions of the CRF(1) and CRF(2) receptor agonist oCRF significantly increased defensive behaviors during both the unconditioned and conditioned components of the cat odor test, as well as exposure to the EPM. In contrast to the behavioral effects of oCRF microinfusions, the CRF(1) and CRF(2) receptor antagonist [Glu(11,16)]Ast significantly decreased defensive behaviors during exposure to cat odor, while producing no discernible effects following a second injection in the cat exposure test. During conditioned test trials, pre-training infusions of [Glu(11,16)]Ast also significantly reduced defensive behaviors during re-exposure to both predator contexts. These results suggest a specific role for ventral hippocampal CRF receptors in modulating anxiety-like behaviors in several ethologically relevant animal models of defense.