Associations between healthcare use and disordered eating among female veterans.

OBJECTIVE: Individuals with eating disorders (EDs) have considerable medical and psychiatric comorbidity as well as increased healthcare use and associated costs. However, EDs remain largely undetected and understudied among veteran populations, and EDs are not routinely screened for or treated in Veterans Affairs (VA) medical settings. Research elucidating the links between disordered eating and VA and non-VA healthcare use is needed to inform policy and practice for ED screening and treatment. METHOD: Data regarding probable EDs and VA and non-VA healthcare use was obtained through a mail survey of 198 female veterans receiving care from VA. RESULTS: A total of 21 participants (10.6%) met probable criteria for subthreshold anorexia nervosa, bulimia nervosa, or binge-eating disorder. Negative binomial regression models revealed that female veterans with EDs reported higher frequency of VA mental healthcare use and substance use disorder treatment, above and beyond the association of comorbid PTSD and depression symptoms. DISCUSSION: These findings confirm the high probability that female veterans with EDs are utilizing significant VA mental health resources. Screening for EDs may be particularly important in VA medical and mental health settings.

Safety and feasibility of robotic-assisted Ivor-Lewis esophagectomy.

Esophagectomy is associated with substantial morbidity. Robotic surgery allows complex resections to be performed with potential benefits over conventional techniques. We applied this technology to transthoracic esophagectomy to assess safety, feasibility, and reliability of this technology. A retrospective cohort study of all patients undergoing robotic-assisted Ivor-Lewis esophagectomy (RAIL) from 2009 to 2014 was conducted. Clinicopathologic factors and surgical outcomes were recorded and compared. All statistical tests were two-sided and a P-value of <0.05 was considered statistically significant. We identified 147 patients with an average age 66 ± 10 years. Neoadjuvant therapy was administered to 114 (77.6%) patients, and all patients underwent a R0 resection. The mean operating room (OR) time was 415 ± 84.6 minutes with a median estimated blood loss (EBL) of 150 (25-600) mL. Mean intensive care unit (ICU) stay was 2.00 ± 4.5 days, median length of hospitalization (LOH) was 9 (4-38) days, and readmissions within 90 days were low at 8 (5.5%). OR time decreased from 471 minutes to 389 minutes after 20 cases and a further decrease to mean of 346 minutes was observed after 120 cases. Complications occurred in 37 patients (25.2%). There were 4 anastomotic (2.7%) leaks. Thirty and 90-day mortality was 0.68% and 1.4%, respectively. This represents to our knowledge the largest series of robotic esophagectomies. RAIL is a safe surgical technique that provides an alternative to standard minimally invasive and open techniques. In our series, there was no increased risk of LOH, complications, or death and re-admission rates were low despite earlier discharge.

Misassembly of full-length Disrupted-in-Schizophrenia 1 protein is linked to altered dopamine homeostasis and behavioral deficits.

Disrupted-in-schizophrenia 1 (DISC1) is a mental illness gene first identified in a Scottish pedigree. So far, DISC1-dependent phenotypes in animal models have been confined to expressing mutant DISC1. Here we investigated how pathology of full-length DISC1 protein could be a major mechanism in sporadic mental illness. We demonstrate that a novel transgenic rat model, modestly overexpressing the full-length DISC1 transgene, showed phenotypes consistent with a significant role of DISC1 misassembly in mental illness. The tgDISC1 rat displayed mainly perinuclear DISC1 aggregates in neurons. Furthermore, the tgDISC1 rat showed a robust signature of behavioral phenotypes that includes amphetamine supersensitivity, hyperexploratory behavior and rotarod deficits, all pointing to changes in dopamine (DA) neurotransmission. To understand the etiology of the behavioral deficits, we undertook a series of molecular studies in the dorsal striatum of tgDISC1 rats. We observed an 80% increase in high-affinity DA D2 receptors, an increased translocation of the dopamine transporter to the plasma membrane and a corresponding increase in DA inflow as observed by cyclic voltammetry. A reciprocal relationship between DISC1 protein assembly and DA homeostasis was corroborated by in vitro studies. Elevated cytosolic dopamine caused an increase in DISC1 multimerization, insolubility and complexing with the dopamine transporter, suggesting a physiological mechanism linking DISC1 assembly and dopamine homeostasis. DISC1 protein pathology and its interaction with dopamine homeostasis is a novel cellular mechanism that is relevant for behavioral control and may have a role in mental illness.

Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

UNLABELLED: Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. CONCLUSIONS: (a) These results confirm the importance of DA release in the NAc for reward-related states, with DA increasing in the core, but not shell subregion. (b) They provide first evidence that during the withholding of expected reward, DA decreases in the NAc core, but not shell region. (c) This decrease in DA appears only after a delay between delivery of reward and extinction likely due to it being masked by persisting DA release. We hypothesize the decrease in extinction-induced release of DA in the NAc core to be a marker for the despair/depression that is known to accompany the failure to obtain expected rewards/reinforcers.

Immunization with DISC1 protein in an animal model of ADHD influences behavior and excitatory amino acids in prefrontal cortex and striatum.

The Disrupted-in-schizophrenia 1 (DISC1) gene is involved in vulnerability to neuropsychiatric disorders. Naples high-excitability (NHE) rat model neuropsychiatric problems characterized by an unbalanced mesocortical dopamine system. Here, we assessed behavioral and neurochemical effects of immunization against multimeric rat DISC1 protein in adult NHE rats, an animal model of attention-deficit hyperactivity disorder and their Random-Bred (NRB) controls. Males of both lines received subcutaneous injections of vehicle (PB), adjuvant only (AD) or recombinant rat DISC1 protein purified from E. coli, suspended in AD (anti-DISC1) at age of 30, 45 and 60 postnatal days (pnd). At 75 pnd, the rats were exposed to a Làt maze and 2 days later to an Olton eight-arm radial maze, and horizontal (HA) and vertical activities (VA) were monitored. Non-selective (NSA) and selective spatial attention (SSA) were monitored in the Làt and in the Olton maze by duration of rearings and working memory, respectively. Post mortem neurochemistry in the prefrontal cortex (PFc), dorsal (DS) and ventral (VS) striatum of L-Glutamate, L-Aspartate and L-Leucine was performed. All immunized rats showed a clear humoral IgM (but not IgG) immune response against the immunogen, indicating that immunological self-tolerance to DISC1 can be overcome by immunization. NHE rats exhibited a higher unspecific IgM response to adjuvant, indicating an immunological abnormality. The sole anti-DISC1 immunization-specific behavioral in the NHE rats was an increased horizontal activity in the Làt maze. Adjuvant treatment increased vertical activity in both lines, but in the NRB controls it increased rearing and decreased horizontal activity. Liquid chromatography/tandem mass spectrometry analysis of soluble or membrane-trapped neurotransmitters aspartate, glutamate and leucine revealed increased soluble aspartate levels in the ventral striatum of NRB controls after anti-DISC1 immunization. Immune activation by adjuvant independent of simultaneous DISC1 immunization led to other specific changes in NHE and control NRB rats. In DISC1-immunized NHE rats, horizontal activity in Lat maze correlated with membrane-trapped glutamate in PFc and in the NRB rats, duration of rearing in Olton maze correlated with membrane-trapped glutamate in PFc and aspartate in dorsal striatum. In addition to non-specific immune activation (by AD), the postnatal anti-DISC1 immune treatment led to behavioral changes related to mechanisms of activity and attention and had influenced amino acids and synaptic markers in striatum and neocortex in the adult NHE as well as control animals.

Intranasal dopamine treatment reinstates object-place memory in aged rats.

Following oral or IV administration, dopamine (DA) cannot cross the blood-brain barrier to a significant extent, but can enter the brain when administered via the nasal passages. Intranasal administration of DA was shown to increase extracellular DA in the striatum, to have antidepressant action and to improve attention and working memory in rats. Here we show that aged (22-24 months old) rats are deficient in an object-place learning task, but that this learning/memory is intact and comparable with that of adult rats upon pre-trial administration of 0.3 mg/kg DA gel into the nasal passages. This result raises the possibility of the therapeutic application of intranasal DA treatment for age-related cognitive disorders.

Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum.

Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of the Naples high-excitability (NHE) line, an animal model for attention-deficit hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal days 28-42 and subsequently tested in the Làt maze and in the Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EAAs were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between lines. Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2) prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA hyperactivty. IN-DA had ameliorative effects on activity level, attention, and working memory, which are likely to be associated with DA action at inhibitory D2 autoreceptors, leading to a reduction in striatal DA hyperactivity and, possibly, DA action on striatal EAA levels, resulting in a decrease of striatal EAA hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic and anti-parkinsonian effects in relation to enhanced central DAergic activity. Our present results strengthen the prospects of potential therapeutic applications of intranasal  DA by indicating an enhancement of selective attention and working memory in a deficit model.

British Dietetic Association evidence-based guidelines for the dietary management of Crohn's disease in adults.

BACKGROUND: Crohn's disease is a debilitating chronic inflammatory bowel disease. Appropriate use of diet and nutritional therapy is integral to the overall management strategy of Crohn's disease. The aim was to develop evidence-based guidelines on the dietary management of Crohn's disease in adults. METHODS: Questions relating to the dietary management of Crohn's disease were developed. These included the roles of enteral nutrition to induce remission, food re-introduction diets to structure food re-introduction and maintain remission, and dietary management of stricturing disease, as well as whether probiotics or prebiotics induce or maintain remission. A comprehensive literature search was conducted and relevant studies from January 1985 to November 2009 were identified using the electronic database search engines CINAHL, Cochrane Library, EMBASE, MEDLINE, Scopus and Web of Science. Evidence statements, recommendations, practical considerations and research recommendations were developed. RESULTS: Fifteen research papers were critically appraised and the evidence formed the basis of these guidelines. Although corticosteroids appear to be more effective, enteral nutrition (elemental or non-elemental) can be offered as an alternative option to induce disease remission. After a course of enteral nutrition, food re-introduction diets may be useful to structure food re-introduction and help maintain disease remission. Dietary fibre is contraindicated in the presence of strictures as a result of the risk of mechanical obstruction. The use of probiotics and prebiotics is not currently supported. CONCLUSIONS: As an alternative to corticosteroids, evidence supports enteral nutrition to induce disease remission. Food re-introduction diets provide structure to food re-introduction and help maintain disease remission. These guidelines aim to reduce variation in clinical practice.

Surgical timing and complications, with body image, quality of life, sexual function and genital sensation in patients with congenital adrenal hyperplasia.

INTRODUCTION: The aim of this project was to document the long-term outcomes relating to sexual function, genital sensation, body image and quality of life, in an Australian cohort of adolescent and adult women with congenital adrenal hyperplasia (CAH) who have undergone feminising genitoplasty in infancy, childhood or adolescence. MATERIALS AND METHODS: Identification and follow-up of women with CAH aged 12-40 years who had their first feminising genitoplasty or ongoing management at a single tertiary referral center with multidisciplinary care (n = 80). Medical records were reviewed for Prader stage, and operative outcomes. The prospective component of the study included tracing indivudals aged 12-40 years (n = 69), of whom 34 were contactable. Twenty-one responded to the invitation to participate in the study, completing some or all of a series of validated standardized questionnaires and/or participation in examination of external genital with sensation testing. Results were compared to a control population of similar age distribution (n = 23). RESULTS: The median Prader stage was 3, median age at surgery was four months, median hospital stay of three days with 80 % of surgery undertaken by one surgeon. There was one major and eight minor complications. Re-operation rates were low. There was no difference between participants and controls in terms of sexual function, quality of life, or body image outcomes including genital appearance. Participants had increased sensitivity to soft touch on genital sensation testing compared to controls. Most participants (71 %) reported that early timing of surgery was 'good', four (19 %) felt their surgery was too late, one felt their surgery was too early, and one was unsure. Most were happy with the outcome of their surgery. DISCUSSION: Outcomes after feminising genitoplasty are mixed and influenced not only by the surgery itself, but also the ongoing management of the condition alongside each patient's own cultural and social context. At present there is no comparative data available on the sexual, mental, body image and quality of life outcomes of young females with CAH who have had their operation delayed until adulthood. Our study is limited by low participant response rate, and difficulty recruiting 1:1 control population for all participants, but nevertheless provides some insight into the outcomes of these patients for which limited data is available. CONCLUSION: In the population studied feminising genitoplasty in infancy and childhood had overall positive outcomes. This occurred in a tertiary center with expert multidisciplinary individualised care.

Nonstenotic Carotid Plaques and Embolic Stroke of Undetermined Source: A Multimodality Review.

Symptomatic nonstenotic carotid artery disease has been increasingly recognized as a thromboembolic source in patients who would otherwise be classified as having embolic stroke of undetermined source. Evidence suggests that certain plaque features seen on sonography, CT, and MR imaging in nonstenotic carotid artery disease may predispose to recurrent stroke in patients with embolic stroke of undetermined source. We performed a focused literature review to further study plaque features in the context of embolic stroke of undetermined source and to determine which plaque features may be associated with ipsilateral ischemic events in such patients. Plaque thickness as seen on both ultrasound and CT appears to have a consistent association with ipsilateral stroke in patients with embolic stroke of undetermined source across multiple studies. Intraplaque hemorrhage as seen on MR imaging is now understood to have a strong association with ipsilateral stroke in patients with embolic stroke of undetermined source. Continued study of various plaque features as seen on different modalities is warranted to uncover other potential associations.

Average SAR prediction, validation, and evaluation for a compact MR scanner head-sized RF coil.

A recently developed compact 3 T (C3T) MRI scanner with high performance gradients [1, 2] has a dedicated radiofrequency (RF) transmit coil that exposes only the head, neck and a small portion of the upper body region during head-first scanning. Due to the unique coil geometry and patient positioning, the established SAR model used for a conventional whole-body scanner cannot be directly translated to the C3T. Here a specific absorption rate (SAR) estimation and validation framework was developed and used to implement a dedicated and accurate SAR prediction model for the C3T. Two different SAR prediction models for the C3T were defined and evaluated: one based on an anatomically derived exposed mass, and one using a fixed anatomical position located caudally to the RF coil to determine the exposed mass. After coil modeling and virtual human body simulation, the designed SAR prediction model was implemented on the C3T and verified with calorimetry and in vivo scan power monitoring. The fixed-demarcation exposed mass model was selected as appropriate exposed mass region to accurately estimate the SAR deposition in the patient on the C3T.

The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy.

Biological therapeutics targeting TNF, IL-1 and IL-6 are widely used for treatment of rheumatoid arthritis, inflammatory bowel disease and a growing list of other syndromes, often with remarkable success. Now advances in neuroscience have collided with this therapeutic approach, perhaps rendering possible the development of nerve stimulators to inhibit cytokines. Action potentials transmitted in the vagus nerve culminate in the release of acetylcholine that blocks cytokine production by cells expressing acetylcholine receptors. The molecular mechanism of this cholinergic anti-inflammatory pathway is attributable to signal transduction by the nicotinic alpha 7 acetylcholine receptor subunit, a regulator of the intracellular signals that control cytokine transcription and translation. Favourable preclinical data support the possibility that nerve stimulators may be added to the future therapeutic armamentarium, possibly replacing some drugs to inhibit cytokines.

Idiopathic Intracranial Hypertension is Associated with a Higher Burden of Visible Cerebral Perivascular Spaces: The Glymphatic Connection.

BACKGROUND AND PURPOSE: Research suggests a connection between idiopathic intracranial hypertension and the cerebral glymphatic system. We hypothesized that visible dilated perivascular spaces, possible glymphatic pathways, would be more prevalent in patients with idiopathic intracranial hypertension. This prevalence could provide a biomarker and add evidence to the glymphatic connection in the pathogenesis of idiopathic intracranial hypertension. MATERIALS AND METHODS: We evaluated 36 adult (older than 21 years of age) patients with idiopathic intracranial hypertension and 19 controls, 21-69 years of age, who underwent a standardized MR imaging protocol that included high-resolution precontrast T2- and T1-weighted images. All patients had complete neuro-ophthalmic examinations for papilledema. The number of visible perivascular spaces was evaluated using a comprehensive 4-point qualitative rating scale, which graded the number of visible perivascular spaces in the centrum semiovale and basal ganglia; a 2-point scale was used for the midbrain. Readers were blinded to patient diagnoses. Continuous variables were compared using a Student t test. RESULTS: The mean number of visible perivascular spaces overall was greater in the idiopathic intracranial hypertension group than in controls (4.5 [SD, 1.9] versus 2.9 [SD, 1.9], respectively; P = .004). This finding was significant for centrum semiovale idiopathic intracranial hypertension (2.3 [SD, 1.4] versus controls, 1.3 [SD, 1.1], P = .003) and basal ganglia idiopathic intracranial hypertension (1.7 [SD, 0.6] versus controls, 1.2 [SD, 0.7], P = .009). There was no significant difference in midbrain idiopathic intracranial hypertension (0.5 [SD, 0.5] versus controls, 0.4 [SD, 0.5], P = .47). CONCLUSIONS: Idiopathic intracranial hypertension is associated with an increased number of visible intracranial perivascular spaces. This finding provides insight into the pathophysiology of idiopathic intracranial hypertension, suggesting a possible relationship between idiopathic intracranial hypertension and glymphatic dysfunction and providing another useful biomarker for the disease.

Carotid Intraplaque Hemorrhage and Stenosis: At What Stage of Plaque Progression Does Intraplaque Hemorrhage Occur, and When is It Most Likely to Be Associated with Symptoms?

BACKGROUND AND PURPOSE: The relationship between carotid intraplaque hemorrhage and luminal stenosis severity is not well-established. We sought to determine whether intraplaque hemorrhage is related to carotid stenosis and at what degree of stenosis intraplaque hemorrhage most likely contributes to ischemic symptoms. MATERIALS AND METHODS: Consecutive patients who underwent MR carotid plaque imaging with MPRAGE sequences to identify intraplaque hemorrhage were retrospectively reviewed. Degrees of stenoses were categorized as minimal (<30%), moderate (30%-69%), and severe (>70%). Arteries were categorized into 2 groups: symptomatic (ipsilateral to a cerebral ischemic event) and asymptomatic (from a patient without an ischemic event). Multiple regression analyses were used to determine independent associations between the degree of stenosis and intraplaque hemorrhage and the presence of intraplaque hemorrhage with symptoms among categories of stenosis. RESULTS: We included 449 patients with 449 carotid arteries: Two hundred twenty-five (50.1%) were symptomatic, and 224 (49.9%) were asymptomatic. An increasing degree of stenosis was independently associated with the presence of intraplaque hemorrhage (OR = 1.02; 95% confidence interval, 1.01-1.03). Intraplaque hemorrhage was independently associated with ischemic events in arteries with <30% stenosis (OR = 5.68; 95% CI, 1.49-21.69). No such association was observed in arteries with >30% stenosis. Of symptomatic arteries with minimal stenosis, 8.7% had intraplaque hemorrhage versus 1.7% of asymptomatic arteries (P = .02). No differences in intraplaque hemorrhage prevalence were found between symptomatic and asymptomatic groups with moderate (P = .18) and severe stenoses (P = .99). CONCLUSIONS: The presence of intraplaque hemorrhage on high-resolution plaque imaging is likely most useful in identifying symptomatic plaques in cases of minimal stenosis.

Changes in Ventricular and Cortical Volumes following Shunt Placement in Patients with Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: While changes in ventricular and extraventricular CSF spaces have been studied following shunt placement in patients with idiopathic normal pressure hydrocephalus, regional changes in cortical volumes have not. These changes are important to better inform disease pathophysiology and evaluation for copathology. The purpose of this work is to investigate changes in ventricular and cortical volumes in patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement. MATERIALS AND METHODS: This is a retrospective cohort study of patients with idiopathic normal pressure hydrocephalus who underwent 3D T1-weighted MR imaging before and after ventriculoperitoneal shunt placement. Images were analyzed using tensor-based morphometry with symmetric normalization to determine the percentage change in ventricular and regional cortical volumes. Ventricular volume changes were assessed using the Wilcoxon signed rank test, and cortical volume changes, using a linear mixed-effects model (P < .05). RESULTS: The study included 22 patients (5 women/17 men; mean age, 73 [SD, 6] years). Ventricular volume decreased after shunt placement with a mean change of -15.4% (P < .001). Measured cortical volume across all participants and cortical ROIs showed a mean percentage increase of 1.4% (P < .001). ROIs near the vertex showed the greatest percentage increase in volume after shunt placement, with smaller decreases in volume in the medial temporal lobes. CONCLUSIONS: Overall, cortical volumes mildly increased after shunt placement in patients with idiopathic normal pressure hydrocephalus with the greatest increases in regions near the vertex, indicating postshunt decompression of the cortex and sulci. Ventricular volumes showed an expected decrease after shunt placement.

The role of cortical serotonin in anxiety and locomotor activity in Wistar rats.

The brain's serotonergic system is known to play an important role in the modulation of anxiety. While the role of serotonin (5-HT) in subcortical structures is well investigated, little is known about the function of cortical 5-HT. The present series of studies used local injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the medial prefrontal cortex (mPFC), entorhinal cortex (EC), or occipital cortex (OccC) of rats to chronically reduce 5-HT neurotransmission in these brain areas. The animals were tested for anxiety-like behavior on the elevated plus-maze and open field. An 82% depletion of 5-HT from the mPFC increased anxiety-like behavior, while no general motor effects were evident. In contrast, a 63% 5-HT-depletion of the EC or a 78% 5-HT-depletion of the OccC did not have any effects on emotional or exploratory behaviors. These findings are in line with a proposed role of 5-HT in the mPFC in the modulation of anxiety- and stress-mediated behavior and demonstrate a functional differentiation between different cortical 5-HT projections.

Reinforcement reduction: a method for training ratio behavior.

By use of intracranial stimulation as reinforcement, fixed-ratio performance could be established directly from continuous reinforcement by gradual reduction of the train duration of the stimuli contingent on all but the terminal response in the desired ratio. Furthermore, stimuli of subreinforcement strength enhanced ratio performance when introduced after training by the conventional method.

Drinking and eating elicited by cortical spreading depression.

Single waves of unilateral and bilateral cortical spreading depression were administered to rats by electrophoretic injection of potassium ions into the occipital cortices. Aggressive and stereotyped eating, drinking, and exploratory behavior were elicited by unilateral and bilateral spreading depression. Onset of the elicited behaviors varied among rats from 4 to 8 minutes after injection of the ions. Direct activation of, or rebound from, inhibition of subcortical motivational mechanisms may be responsible for the effects.

Light-induced activity in the activity box is not aversively motivated and does not show between-trial habituation.

The induction of behaviour by sensory stimuli, i.e. sensorimotor stimulation, is a fundamental aspect of behaviour. Recently, it was found that the presentation of white-light stimuli to a rat in an activity box reliably induces locomotor activity, and, thus, may be able to serve as a paradigm to measure basal, non-aversively motivated sensorimotor processing. However, light can be an aversive stimulus to a rat. In order to test if there is a stressful component in light-induced activity, a retreat-box was introduced into the test-apparatus in experiment 1, so that the animals had the opportunity to escape the light stimuli. It was found, that light-induced activity was also shown, when a retreat-box was available in the activity box, and that light-stimulation did not lead to an increase of entries into or the time spent in the retreat box. Experiment 2 examines the stability of the response to light over trials. Three light-induced activity test-trials were conducted with one day between each test. There was no effect of repeated testing on light-induced activity, which was evident during each of the three test-sessions. It is concluded that stress/anxiety does not significantly contribute to the increase of locomotor behaviour induced by light stimulation under the present conditions. Thus, the paradigm appears to involve a non-aversively motivated behavioural response. Furthermore, light-induced activity did not habituate over at least three test trials, and may, therefore, serve for repeated testing.

Treatment of Strongyloides stercoralis hyperinfection-associated septic shock and acute respiratory distress syndrome with drotrecogin alfa (activated) in a renal transplant recipient.

We report a case of Strongyloides stercoralis hyperinfection syndrome in a renal transplant recipient complicated by septic shock, acute respiratory distress syndrome, and Klebsiella pneumoniae superinfection. The patient was treated successfully with drotrecogin alfa (activated), parenteral ivermectin, albendazole, and piperacillin/tazobactam. This outcome suggests that drotrecogin alfa (activated) may be useful therapy for transplant recipients who develop severe sepsis or septic shock secondary to potentially lethal opportunistic infections.