Pilot Implementation of Guiando Buenas Decisiones, an Evidence-Based Parenting Program for Spanish-Speaking Families, in Pediatric Primary Care in a Large, U.S. Health System: A Qualitative Interview Study.

Adolescent substance use is a significant public health problem in the United States and Hispanic youth engage in substance use services at lower rates than other groups. For this under-served group, prevention services delivered in non-stigmatized, non-specialty care settings may increase access to the services. We describe findings from a feasibility pilot of the implementation of a virtual version of Guiando Buenas Decisiones (GBD), a universal, group-based substance use prevention program for parents. It was conducted with Spanish-speaking families and delivered, virtually, in pediatric primary care in a large healthcare system in the U.S. Through qualitative interviews with pediatricians (n =7) and parents (n = 26), we explored potential barriers and facilitators of GBD enrollment and engagement. Parents and pediatricians alike noted the dearth of universal prevention programming in Spanish and that GBD could help address the need for linguistically appropriate programming. Parents liked the curriculum content, materials and videos; they felt the focus on strengthening family bonds, setting clear expectations and guidelines, the use of family meetings, and the positive tools provided for navigating family conflict were well-aligned with their cultural and family values. Feedback from parents was helpful for informing more personalized and attentive approaches to program outreach and recruitment methods, and for adaptation of recruitment fliers and letters. In this pediatric primary care context serving an underserved population, we found virtual GBD feasible to implement, acceptable and appealing to parents, and judged by pediatricians as a promising, much-needed addition to their prevention armamentarium.

Free-Roaming Dog Surveys in Quito, Ecuador: Experiences, Lessons Learned, and Future Work.

The selection of a survey method of free-roaming dog populations should be based on analyses of local capacities and management priorities. Here, we compare the results of surveys of the stray dog population in Quito, Ecuador, using two different methodologies and propose an alternative method for future surveys in the city. We carried out all surveys in ~5 km-transects in a sample of eight urban and eight rural parishes (16 transects total). In 2018, we used the capture-recapture method to estimate absolute population size and 95% CI. We began transect surveys at 04 h 00 (local time) and identified individuals with photographs. The main limitations of this method were errors in identifying individuals, since photographs were not always clear, partly due to low light conditions during the surveys. This method also required more time and more complex logistics. In 2019, we used distance sampling to estimate population density and began the surveys at 08 h 00 (local time). Errors in the estimation of animal-observer distances and angles were our main concern when using this method. For future surveys, we propose to carry out direct observations of dog abundance (number of free-roaming dogs/km) during street counts, complemented with capture-recapture surveys every 5 years. This alternative method albeit simple, is sensitive enough to (1) provide local authorities with objective assessments of management interventions, (2) better understanding the dynamics of free-roaming dog populations and (3) increasing public awareness about the problem of pet abandonment through citizen participation in the surveys.

Prevalence and risk factors for the presence of serum antibodies against canine distemper, canine parvovirus, and canine adenovirus in communities in mainland Ecuador.

The purpose of this study was to estimate the apparent prevalence and identify risk factors for antibody levels (AL) against canine distemper virus (CDV), canine parvovirus (CPV), and canine adenovirus (CAV) in three communities in the metropolitan area of Quito, Ecuador that have limited access to regular veterinary care. Whole blood samples were collected from 154 dogs presenting to three veterinary field clinics in mainland Ecuador and tested for AL against CDV, CPV, and CAV by a commercially available point-of-care ELISA. Potential risk factors for the presence of AL were analyzed. A majority of dogs had AL against CDV (66%, 95% CI = 58-73%), CPV (95%, 95% CI = 91-98%) and CAV (60%, 95% CI = 52-67%). Dogs had significantly greater odds of AL against CDV if they were >2 years of age, from an urban community, and had previously received veterinary care. Dogs had significantly greater odds of AL against CAV if they were male, >2 years of age, and had previously received veterinary care. Results provide baseline estimates of AL within each community and allow for the targeting of future veterinary services to communities and dogs most at risk.

Recent metformin adherence and the risk of hypoglycaemia in the year following intensification with a sulfonylurea.

AIM: To evaluate whether recent low adherence to metformin monotherapy is associated with hypoglycaemia after addition of a sulfonylurea. METHODS: We assembled a retrospective cohort of veterans who filled a new prescription for metformin between 2001 and 2011 and intensified treatment with a sulfonylurea after ≥1 year of metformin use. We calculated metformin adherence from pharmacy data using the proportion of days covered in the 180-day period before intensification. The primary outcome was hypoglycaemia, defined as a hospitalization or emergency department visit for hypoglycaemia or an outpatient blood glucose measurement <3.3 mmol/l in the year following intensification. Cox proportional hazards models were used to compare the risk of hypoglycaemia between participants with low (<80%) and high (≥80%) adherence. Adherence was also modelled as a continuous variable using restricted cubic splines. RESULTS: Of 187 267 participants who initiated metformin monotherapy, 49 424 added a sulfonylurea after ≥1 year. The median (interquartile range) rate of treatment adherence was 87 (50-100)% and 43% had adherence <80%. Hypoglycaemia rates per 1000 person-years were 23.1 (95% CI 21.1-25.4) and 24.5 (95% CI 22.7-26.4) in participants with low and high adherence, respectively (adjusted hazard ratio 0.95, 95% CI 0.84-1.08). The risk of hypoglycaemia was similar across all levels of adherence when adherence was modelled as a continuous variable. CONCLUSIONS: We found no evidence that past low adherence to metformin monotherapy was associated with hypoglycaemia after intensification with a sulfonylurea.

Dog overpopulation and burden of exposure to canine distemper virus and other pathogens on Santa Cruz Island, Galapagos.

Dog overpopulation and diseases are hazards to native island species and humans on the Galapagos. Vaccination and importation of dogs are prohibited on the Galapagos. Risk management of these hazards requires the use of science-based risk assessment and risk communication. The objectives of the study reported here were (i) to estimate the human:dog ratio and (ii) the prevalence of and identify exposure factors associated with positive antibody titers to canine distemper virus (CDV) and other pathogens, as well as infection with intestinal parasites in owned dogs on Santa Cruz Island, Galapagos in September 2014. The observed human:dog ratio was 6.148:1 which extrapolates to 2503 dogs (two times more than a recent dog count conducted by Galapagos Biosecurity Agency in March 2014). The proportion of spayed female dogs (50%) was higher, compared to neutered male dogs (30%) (p=0.04). Prevalence of dogs with positive antibody titers to CDV was 36% (95% CI=26, 46%), to canine parvovirus was 89% (95% CI=82, 95%), and to canine adenovirus was 40% (95% CI=30, 51%). The frequency of seropositive dogs to CDV was lower in urban dogs (26%), compared to rural dogs (53%) (p<0.05). A positive interaction effect between rural residence and spay/neuter status on seropositivity to CDV was observed, which we discuss in this report. Because vaccination is prohibited, the dog population on Santa Cruz is susceptible to an outbreak of CDV (particularly among urban dogs) with potential spill over to marine mammals. Dog's age (1-2 or 3-14 years old, compared to younger dogs), and residence (rural, urban) were associated with positive antibody titers to parvovirus, adenovirus, Ehrlichia spp., or Anaplasma spp., as well as infection with Ancylostoma spp., an intestinal parasite in dogs that can be transmitted to humans, particularly children. These results provide the most comprehensive assessment of dog overpopulation and exposure to CDV and other pathogens on the Galapagos to date.

Early discontinuation of treatment in patients with orthostatic hypotension.

BACKGROUND: Midodrine and fludrocortisone are considered the first-line pharmacologic treatments for orthostatic hypotension (OH). Although OH is thought to require long-term therapy, it is unknown how long patients remain on treatment ("persistence"). METHODS: We assembled a retrospective cohort of patients with OH aged ≥ 50 years enrolled in Tennessee Medicaid (1996-2008), and identified new episodes of midodrine and fludrocortisone use. Follow-up continued from the first medication fill through treatment discontinuation (90 days without medication), change in treatment, death, hospitalization, and loss of enrollment or study end. We compared persistence on treatment using Cox regression models and fludrocortisone as reference. Covariates included demographics, healthcare utilization measurements and co-morbidities. RESULTS: We identified 1704 OH patients, who initiated 1767 episodes of fludrocortisone (1103) or midodrine (664) use. The median age was 69 years, 53% were female and 80% were white. During 738 person years of follow-up, episodes of use ended because of treatment discontinuation in 467 (27% fludrocortisone, 25% midodrine); treatment change in 72 (3% fludrocortisone, 6% midodrine) and death in 53 (3% fludrocortisone, 2% midodrine). Overall median persistence on fludrocortisone and midodrine was 254 (IQR: 119-783) and 259 (IQR: 119-807) days, respectively. The adjusted hazard ratio (aHR) for overall non-persistence on midodrine compared to fludrocortisone was 1.07 (95% CI: 0.90-1.28). CONCLUSIONS: Overall duration of OH treatment with first-line medications was short, and similar for fludrocortisone and midodrine. Further research is warranted to determine the causes of this low persistence. (Words#234).

Incidence and risk factors for progressive multifocal leukoencephalopathy among patients with selected rheumatic diseases.

OBJECTIVE: To ascertain the incidence of progressive multifocal leukoencephalopathy (PML) in patients with selected rheumatic diseases, to describe the characteristics of PML cases occurring in this setting, and to evaluate the extent to which such cases occurred in the context of biologic therapies such as rituximab or tumor necrosis factor antagonists. METHODS: We conducted a large population-based study to describe the incidence and risk factors for PML among patients with rheumatoid arthritis, psoriatic arthritis, psoriasis, juvenile idiopathic arthritis, inflammatory bowel disease, and ankylosing spondylitis using national inpatient and outpatient administrative data from the entire Center for Medicare and Medicaid Services from 2000-2009. Suspected PML cases were identified using hospital discharge diagnosis codes. Risk factors for PML were evaluated using outpatient data ≥6 months prior to PML diagnosis. RESULTS: Among 2,030,578 patients with autoimmune diseases of interest, a total of 53 PML cases were identified (2.6 per 100,000 patients). Most PML cases had human immunodeficiency virus (HIV) and/or cancer. Nine PML cases had evidence for biologic use prior to PML hospitalization, of which 3 had neither HIV nor malignancy and were exposed to biologics within 12 (rituximab) or 6 months (all other biologics) prior to PML diagnosis. PML occurred at an estimated incidence of 0.2 per 100,000 patients with autoimmune diseases who did not have HIV or malignancy. CONCLUSION: PML occurs at a very low incidence among patients with rheumatic diseases but can occur even in the absence of HIV or malignancy.

Comparisons of persistence and durability among three oral antidiabetic therapies using electronic prescription-fill data: the impact of adherence requirements and stockpiling.

Two important challenges are inherent in the design of studies using prescription data from electronic health records: how to define the minimum level of adherence that would qualify as "continuous drug use" and how to handle stockpiling of medications. Generally, the sensitivity of a study's conclusions to these design choices is not analyzed. In our study, covariate adjusted Cox models were used to compare persistence and durability with respect to three common oral antidiabetic therapies in a cohort of 12,697 incident users. Assuming 50% stockpiling, sulfonylurea therapy, as compared with metformin, showed a significantly lower risk of nonpersistence (changing or stopping therapy) when no gap days were allowed (HR 0.95, P = 0.032), no significant difference when 14 gap days were allowed (HR 0.99, P = 0.536), and significantly greater risk of nonpersistence when 30 gap days were allowed (HR 1.05, P = 0.046). All the drug comparisons showed statistically significant effects in both directions, the risk of nonpersistence increasing or decreasing depending on the design parameters.

Changing patterns of medication use in patients with rheumatoid arthritis in a Medicaid population.

OBJECTIVE: To examine changes in patterns of medication utilization in patients with RA. METHODS: Data from Tennessee Medicaid (TennCare) databases (1995-2004) were used to identify adults with both a diagnosis of RA and at least one DMARD prescription each year. Annual age-specific utilization of DMARDs, glucocorticoids, NSAIDs and narcotics was measured on the last day of each year to determine the point prevalence of use of these agents. RESULTS: Records from 23 342 patients with treated RA were analysed. Most patients were females (78%) and white (74%). The median age was 57 yrs (interquartile range: 48-65). The proportion of patients who had a current DMARD prescription on the index date increased from 62% in 1995 to 71% in 2004 (P < 0.001). MTX was the most commonly used DMARD. By the end of 2004, 22% of patients had a current prescription for a biologic, and etanercept represented 51% of all biologic therapies. During the study period, the overall utilization of glucocorticoids decreased from 46% to 38% (P < 0.001), whereas NSAID utilization increased from 33% to 38% (P < 0.001), and use of narcotics increased from 38% to 55% (P < 0.001). A secondary analysis that identified RA patients based on diagnosis codes alone, showed similar patterns, but lower DMARD utilization which increased from 33% to 52% overall and from 0% to 16% for biologics. CONCLUSIONS: The utilization of DMARDs increased in TennCare patients with RA, and by 2004, use of biologics was substantial. Although glucocorticoid utilization decreased, use of both NSAIDs and narcotics increased.

Estimating the undetected burden of influenza hospitalizations in children.

During the 2004-2005 influenza season two independent influenza surveillance systems operated simultaneously in three United States counties. The New Vaccine Surveillance Network (NVSN) prospectively enrolled children hospitalized for respiratory symptoms/fever and tested them using culture and RT-PCR. The Emerging Infections Program (EIP) and a similar clinical-laboratory surveillance system identified hospitalized children who had positive influenza tests obtained as part of their usual medical care. Using data from these systems, we applied capture-recapture analyses to estimate the burden of influenza related-hospitalizations in children aged<5 years. During the 2004-2005 influenza season the influenza-related hospitalization rate estimated by capture-recapture analysis was 8.6/10,000 children aged<5 years. When compared to this estimate, the sensitivity of the prospective surveillance system was 69% and the sensitivity of the clinical-laboratory based system was 39%. In the face of limited resources and an increasing need for influenza surveillance, capture-recapture analysis provides better estimates than either system alone.

Infusion of neurotoxic doses of N-methyl-D-aspartate into the lateral hypothalamus in rats produces stomach erosions, hyperthermia, and a disruption in eating behavior.

The present study examined whether damage to intrinsic lateral hypothalamic (LH) neurons induced by microinfusions of N-methyl-D-aspartate (NMDA) would produce effects similar to those seen after electrolytic LH lesions. In Experiment 1, rats receiving electrolytic (1.2 mA anodal current, 10 s) LH lesions displayed motor impairments, whereas those receiving NMDA (20 microg/microl) infusions did not. Both electrolytic lesions and NMDA infusions were associated with eating deficits, hyperthermia, and gastric erosion formation 24 hr after surgery. In Experiment 2, either 20 microg/microl or 10 microg/microl NMDA destroyed LH cells and produced dose-dependent gastric mucosal erosions as well as similar increases in body temperature. These results indicate that an alteration in the acute activity of intrinsic LH neurons plays a role in the production of gastric mucosal injury and hyperthermia and lend support to other studies implicating a role of LH neurons in eating behavior.

Gastric mucosal erosion produced by NMDA microinfusions in the lateral hypothalamus: effect of selective knife cuts.

Bilateral infusions of N-methyl-D-aspartate (NMDA) into the lateral hypothalamus (LH) produce gastric erosions in rats. The present study attempted to determine the neural pathways that mediate this effect. In order to interrupt axonal transmission, knife cuts (KC) were made in different planes adjacent to the LH. In separate groups of rats, KC were made anterior, posterior or lateral to the LH just prior to bilateral NMDA infusions (20 micrograms/microliter). The incidence of gastric erosions was measured 24 h after NMDA infusions. Animals receiving sham KC and infused with NMDA exhibited significantly more gastric erosions than those infused with vehicle. Lateral parasagittal KC blocked the occurrence of gastric erosions produced by NMDA, whereas anterior coronal KC significantly increased the incidence of erosions produced by NMDA. Posterior coronal KC did not alter the incidence of gastric erosions produced by NMDA infusions into the LH. These results suggest that intrinsic LH neurons with gastric function project axons laterally and probably descend through the internal capsule to brainstem medullary nuclei. The results of the anterior KC suggest that the LH sends and/or receives inhibitory projections from neural structures (possibly the amygdaloid complex) anterior to the plane of the KC.

Body temperature and wheel running predict survival times in rats exposed to activity-stress.

The relationship between restricted feeding, core body temperature (Tb), wheel running, survival, and gastric erosion formation was examined in female rats exposed to activity-stress. Core body temperature and gross motor activity were telemetrically monitored in four groups of rats that had free access to running wheels and in one group that was not allowed to run on the wheels. Twenty-four hours prior to the onset of hypothermia and predicted mortality, different groups were left undisturbed, warmed with a heat lamp, denied access to running wheels, or euthanized. Length of survival in wheel-running rats varied from 2 to 12 days. During the first day of food deprivation, premorbid changes in the variability of Tb during the diurnal period and the mean number of wheel revolutions during the nocturnal period were strongly predictive of length of survival. Warming rats with a heat lamp or preventing rats from ever running on the wheel increased the length of survival and attenuated gastric erosion formation. Only rats that were warmed had a greater likelihood of survival. Gastric pathology was also reduced in rats that were euthanized prior to becoming moribund. Rats that were left undisturbed or locked from the running wheel over the last 24 h of testing became moribund and had extensive gastric mucosal damage. These results indicate that thermoregulatory disturbances induced by restricted feeding and not wheel running alone are critical in determining survival and the degree of gastric mucosal injury in rats exposed to activity-stress. Results further suggest that predisposing factors may put some rats at risk for the development of activity-stress-induced mortality.

Lateral hypothalamic lesions cause gastric injury by stimulating gastric contractility.

Changes in gastric contractility following lateral hypothalamic (LH) lesions with and without bilateral cervical vagotomy were measured in urethan-anesthetized rats. LH lesions were induced with direct current passed through stereotaxically placed electrodes. Gastric contractility was recorded continuously for 4 h with acutely implanted strain gauge force transducers and analyzed by computer. LH lesions consistently stimulated gastric contractility and caused more gastric mucosal injury than control conditions. Vagotomy blocked both gastric mucosal injury and high-amplitude gastric contractions. In rats with LH lesions and exogenously infused intragastric hydrochloric acid, atropine methyl nitrate inhibited high-amplitude gastric contractions and gastric erosions. These findings indicate that LH lesions stimulate vagally mediated high-amplitude gastric contractions, which, in the presence of hydrochloric acid, cause gastric mucosal erosions.

Effects of amygdaloid lesions on gastric erosion formation during exposure to activity-stress.

To examine the role of the amygdala in the production of gastric ulcers induced by activity-stress, electrolytic lesions were placed in the centromedial (CENT) and medial (MED) amygdaloid nuclei, as well as in the intra-amygdaloid division of the bed nucleus of the stria terminalis (BNST). As compared to sham-operated controls (CONT), gastric ulceration was attenuated in rats with CENT lesions and exacerbated in rats with lesions located in the BNST or MED. Wheel running did not differ significantly between control animals and lesioned rats, but did differ within lesioned groups. Rats with MED lesions ran more than rats with CENT or BNST lesions. Results support the view that the integrity of the centromedial amygdala is critical for the maintenance of the viscera and demonstrate that neurogenic factors contribute to the development of gastric erosions during exposure to activity-stress.

Gastric mucosal erosions induced by lateral hypothalamic damage: neuronal and dopaminergic mechanisms.

Electrolytic lateral hypothalamic (LH) lesions produce numerous disorders including aphagia, gastric mucosal erosions and autonomic and sensorimotor dysfunctions. This series of experiments examined whether damage to LH neurons or dopaminergic fibers of passage produce similar forms and severity of gastric erosions, as well as other disorders. In Experiment 1, LH neurons were destroyed by the excitatory neurotoxin, kainic acid, that presumably leaves axonal fibers of passage intact. Relatively selective damage to LH neurons with kainic acid produced glandular gastric erosions, as well as sensorimotor and autonomic dysfunctions similar to those seen following electrolytic LH lesions. This suggests that direct damage to LH cell bodies may be a primary cause of many of the disorders observed following LH lesions. In Experiments 2 and 3, electrolytic lesions were used to destroy cell bodies in the substantia nigra and their dopaminergic fibers (some of which pass through the LH area). This resulted in the production of gastric erosions in the absence of significant autonomic dysfunctions. Furthermore, atropine methylnitrate prevented the occurrence of gastric erosions following substantia nigra lesions, suggesting that the erosion formation is mediated via parasympathetic-vagal activity. In contrast, destruction of the ventral tegmental area (and its associated dopaminergic fibers) had no significant effect on gastric erosion formation. Experiment 4 showed that apomorphine, a central and peripheral dopamine agonist, provided protection against LH lesion-induced gastric erosion formation, whereas domperidone, a peripheral dopamine antagonist, had no effect. Taken together, this study suggests that (a) both LH neurons and fibers of passage provide a potential anatomical basis for the development of gastric mucosal erosions, (b) that an alteration in dopamine levels, either centrally or peripherally, may represent an important neurochemical mechanism for the development of erosions, and (c) that the occurrence of gastric erosion can be dissociated from other symptoms of the LH syndrome.

Destruction of different fiber tracts underlies development of lateral hypothalamic lesion-induced hyperthermia and loss of bombesin-induced hypothermia.

The relative roles of lateral hypothalamic cell bodies and fibers of passage were assessed in the development of lesion-induced hyperthermia and bombesin-induced hypothermia. Electrolytic lesions or discrete fiber transections were combined with intracisternal bombesin injection to show that each of these two thermoregulatory effects involves fibers crossing the borders of the lateral hypothalamus; however, the two effects primarily involve fibers crossing different borders. Thus, the hyperthermia and the abolition of bombesin-induced hypothermia which follow lateral hypothalamic damage appear to result from disruption of separate thermoregulatory pathways.

Gastric mucosal damage induced by lateral hypothalamic lesions in female rats: influence of age and ovariectomy.

Male rats given lateral hypothalamic (LH) lesions exhibit an acute increase in gastric acid secretion and develop erosions of the glandular portion of the stomach within 24 h. Since this process has been examined predominantly in male rats, the present experiments were devised to study the effects of LH lesions on the gastric mucosa of female rats. In Experiment 1, 1-year-old Sprague-Dawley female rats given LH lesions exhibited erosions in the rumenal portion of the stomach, a pattern unlike that found in both young and old male rats. Although the glandular mucosa lacked evidence of gross defects, the mucosa appeared blanched and covered with a mucus-like secretion. Experiment 2 demonstrated that, like male rats, LH lesions produced gastric hypersecretion in 1-year-old females. The results of the first two experiments indicate that the dissimilar patterns of gastric mucosal injury between males and older females cannot be accounted for on the basis of differences in gastric acid secretion. Experiment 3 demonstrated that, unlike older females but like males, 4-month-old female rats given LH lesions developed gastric erosions in the glandular mucosa only. Additionally, ovariectomy had no significant effect in altering the extent of gastric pathology. Taken together, these results suggests that (1) age and gender are important variables in neurogenic gastric mucosal injury, (2) differences in the type of gastric ulceration cannot be accounted for by differences in acid secretion, (3) ovarian hormones do not appear to play a significant role in gastric ulceration following brain damage.

Contrasting effects of centromedial and basolateral amygdaloid lesions on stress-related responses in the rat.

The effects of lesions in the centromedial and basolateral amygdala were examined using three different tests sensitive to the following stress-related responses: exploratory behavior, pain reactivity, and immune responses. The most clear-cut results were found with exploratory behavior. Rats with lesions of the centromedial amygdala tended to explore a radial-arm maze more quickly and entered more novel arms of the maze than controls. Those with lesions of the basolateral amygdala were generally too hesitant to explore at all. No significant differences were found between groups on measurements of natural killer cell activity. In tests of pain perception, rats in the control group displayed an analgesic response on the hot plate following an injection of the anxiogenic drug, RO 15-1788, whereas rats with centromedial lesions tended to exhibit a blunted response. These findings provide modest support for the view that the central and lateral regions of the amygdala play complementary roles in aversively motivated behaviors and in stress-related response patterns.

The role of the hypothalamus and dorsal vagal complex in gastrointestinal function and pathophysiology.

A foregone conclusion is that central neural and endocrine control of gastrointestinal functions is based on a complex array of interconnecting brain structures, neurochemical systems, and hormonal modulators. As might be expected, a considerable degree of redundancy is seen not only in the manner in which certain brain structures appear to participate in the regulation of GI functions, but also in the extent to which certain neurotransmitters or brain-gut peptides, when injected centrally, alter these functions. Despite the seemingly ambiguous nature of brain-gut interactions, a picture is beginning to unfold that suggests that GI properties are based on certain reflexes (e.g., vago-vagal). These reflexes, in turn, appear to be influenced by brain structures in a hierarchical manner, not all that dissimilar to the system described by Papez and expanded on by MacLean several years ago. For example, the perceptual or cognitive aspects of both external and internal stimuli are monitored at various brain levels, but obviously higher cortical processes are intimately involved. Aversive events provide sensory information, which is integrated primarily by the limbic system (e.g., amygdala) and translated into the expression of emotional behavior and associated autonomic response patterns. Various hypothalamic structures, in turn, appear most strongly to influence physiological changes associated with aversive events by virtue of the direct connections to the autonomic and endocrine systems. Ultimately, the visceral outcome can be seen as being based on the integrated convergence of information from cortical, limbic, and hypothalamic structures onto medullary nerve nuclei as well as other efferent systems. With respect to animal models of neurogenic or stress ulcer, activity of the dorsal vagal complex and vagal efferents appears to be the final common pathway for pathologic changes in the gut.