Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse.

Equine obesity can cause life-threatening secondary chronic conditions, similar to those in humans and other animal species. Equine metabolic syndrome (EMS), primarily characterized by hyperinsulinemia, is often present in obese horses and ponies. Due to clinical similarities to conditions such as pituitary pars intermedia dysfunction (formerly equine Cushing's disease), conclusive diagnosis of EMS often proves challenging. Aside from changes in diet and exercise, few targeted treatments are available for EMS, emphasizing the need for early identification of at-risk individuals to enable implementation of preventative measures. A genomewide association study (GWAS) using Arabian horses with a history of severe laminitis secondary to EMS revealed significant genetic markers near a single candidate gene () that may play a role in cholesterol homeostasis. The best marker, BIEC2-263524 (chr14:69276814 T > C), was correlated with elevated insulin values and increased frequency of laminitis ( = 0.0024 and = 9.663 × 10, respectively). In a second population of Arabian horses, the BIEC2-263524 marker maintained its associations with higher modified insulin-to-glucose ratio (MIRG) values ( = 0.0056) and BCS ( = 0.0063). Screening of the predicted coding regions by sequencing identified a polymorphic guanine homopolymer and 5 haplotypes in the 3' untranslated region (UTR). An 11 guanine (11-G) allele at was correlated with elevated insulin values in the GWAS population ( = 0.0008) and, in the second population, elevated MIRG and increased BCS > 6.5 ( = 0.0055 and = 0.0162, respectively). The BIEC2-263524-C and the 3' UTR -11(G) polymorphisms were correlated at a 98% frequency, indicating strong linkage disequilibrium across this 150-kb haplotype. Assays for these markers could diagnose horses with a genetic predisposition to develop obesity. Additionally, discovery of FAM174A function may improve our understanding of the etiology of this troubling illness in the horse and warrants investigation of this locus for a role in metabolic- and obesity-related disorders of other species.

Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder.

A theory is proposed to explain the benefits of yoga practices in diverse, frequently comorbid medical conditions based on the concept that yoga practices reduce allostatic load in stress response systems such that optimal homeostasis is restored. It is hypothesized that stress induces (1) imbalance of the autonomic nervous system (ANS) with decreased parasympathetic nervous system (PNS) and increased sympathetic nervous system (SNS) activity, (2) underactivity of the gamma amino-butyric acid (GABA) system, the primary inhibitory neurotransmitter system, and (3) increased allostatic load. It is further hypothesized that yoga-based practices (4) correct underactivity of the PNS and GABA systems in part through stimulation of the vagus nerves, the main peripheral pathway of the PNS, and (5) reduce allostatic load. Depression, epilepsy, post traumatic stress disorder (PTSD), and chronic pain exemplify medical conditions that are exacerbated by stress, have low heart rate variability (HRV) and low GABAergic activity, respond to pharmacologic agents that increase activity of the GABA system, and show symptom improvement in response to yoga-based interventions. The observation that treatment resistant cases of epilepsy and depression respond to vagal nerve stimulation corroborates the need to correct PNS underactivity as part of a successful treatment plan in some cases. According to the proposed theory, the decreased PNS and GABAergic activity that underlies stress-related disorders can be corrected by yoga practices resulting in amelioration of disease symptoms. This has far-reaching implications for the integration of yoga-based practices in the treatment of a broad array of disorders exacerbated by stress.

Theatrical entertainments and kind words: nursing the insane in Western North Carolina, 1882-1907.

This paper argues that at the turn of the 19th century, nurses at the State Hospital in Morganton, North Carolina (now called Broughton Hospital) played critical roles in successfully implementing the best-known therapeutic methods of the time. They were also instrumental in developing the hospital's visibility and acceptance in rural western North Carolina. When the Hospital established its first nurse training school in 1895, this corps of first-generation western North Carolinians practising institutional nursing was highly esteemed in their field. Their skills not only served the community outside of the Hospital's walls, but were also sought out by other private and state asylums.

Morphological variation in the horse: defining complex traits of body size and shape.

Horses, like many domesticated species, have been selected for broad variation in skeletal size. This variation is not only an interesting model of rapid evolutionary change during domestication, but is also directly applicable to the horse industry. Breeders select for complex traits like body size and skeletal conformation to improve marketability, function, soundness and performance in the show ring. Using a well-defined set of 35 measurements, we have identified and quantified skeletal variation in the horse species. We collected measurements from 1215 horses representing 65 breeds of diverse conformation such as the American Miniature, Shetland Pony, Arabian Horse, Thoroughbred, Shire and Clydesdale. Principal components analysis has identified two key dimensions of skeletal variation in the horse. Principal component 1 is positively correlated with every measurement and quantifies overall body size. Principal component 2 captures a pattern of bone widths vs. lengths and thus quantifies variation in overall bone thickness. By defining these complex skeletal traits, we have created a framework for whole genome association studies to identify quantitative trait loci that contribute to this variation.

Hypoperfusion of inferior frontal brain regions in abstinent alcoholics: a pilot SPECT study.

OBJECTIVE: This pilot study evaluated hypotheses concerning the relationship between cerebral hypoperfusion and residual deficits in the functioning of frontal brain systems in abstinent long-term alcoholics. METHOD: The participants (N = 22) were 10 healthy, abstinent alcoholics (9 men) and 12 age-equivalent nonalcoholic controls (10 men). Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Measures of alcohol use, abstinence and neuropsychological functioning were also obtained to relate to SPECT findings. RESULTS: A positive relationship was observed between perfusion levels in the left inferior frontal brain region and years of sobriety. Alcoholics with less than 4 years of sobriety had significantly reduced left inferior frontal perfusion compared with both nonalcoholic controls and alcoholics having longer periods of sobriety. CONCLUSIONS: The findings support the hypothesis that frontal brain abnormalities in alcoholics may subside with extended abstinence.

Hypoperfusion of the cerebellum and aging effects on cerebral cortex blood flow in abstinent alcoholics: a SPECT study.

BACKGROUND: This study evaluated hypotheses concerning alcoholism, aging, and the relationship between cerebral hypoperfusion and residual deficits in the functioning of cerebellar and neocortical brain systems. METHODS: The participants were 10 healthy abstinent alcoholics (9 men, 1 woman) and 12 nonalcoholic controls (10 men, 2 women) ranging in age from 35 to 67 years. Cerebral blood flow was observed through the use of regionally specific computer-derived quantitative analysis of single photon emission computed tomography (SPECT) perfusion images. Cerebellar perfusion was measured and compared with cerebral cortex perfusion in age-equivalent subgroups of alcoholics and controls (under 55 years; 55 years and over). RESULTS: In abstinent alcoholics under age 55, cerebellar perfusion ratios were significantly reduced compared with the controls. In alcoholics and nonalcoholic controls 55 years old and older, this relationship was reversed, probably as a result of diminished cortical perfusion with aging in the alcoholics and of cerebellar decline in the controls. CONCLUSIONS: The findings support hypotheses that the residual effects of alcoholism include cerebellar brain abnormalities and that aging combined with long-term alcoholism leads to cerebral cortical decline.

Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism.

This study sought to identify whether subjects with a family history (FH + ) of alcoholism had changes in regional cerebral blood volume (rCBV) after an alprazolam challenge which distinguished them from subjects without a family history (FH -) of alcoholism using functional MRI (fMRI). Twelve FH + and eight FH - subjects were challenged with 1 mg of alprazolam or placebo in a double-blind crossover design. FMRI scans were obtained at baseline, 1 and 2 h after the challenge using the dynamic susceptibility contrast method with gadolinium. Mood scales, the Tufts Addiction Research Center Inventory-Morphine Benzedrine Group Scale and the drug liking scale, were administered every 30 min to assess drug effects. Global analysis of CBV showed a treatment by time decrease on alprazolam relative to placebo, but no effect by family history. The FH + group showed rCBV decreases at 1 h in the left caudate and left inferior prefrontal region, while the FH - group showed rCBV decreases at 2 h in the right inferior prefrontal region and anterior cingulate in response to alprazolam relative to placebo. FH + subjects reported more mood enhancement with alprazolam. This fMRI technique detected global and regional CBV changes induced by alprazolam. The location and rate of alprazolam-induced rCBV changes differed between FH + and FH - subjects. These changes may be related to the increased mood enhancement found in subjects genetically predisposed to alcoholism.

Prior head injury in male veterans with borderline personality disorder.

This study evaluated the relationship between traumatic brain injury (TBI) and borderline personality disorder (BPD). Forty-three males with BPD were compared with 49 age- and sex-matched controls with other psychiatric diagnoses. The occurrence of TBI was identified by chart review. Head injury was identified in 42% of patients meeting criteria for BPD but in only 4% of controls (p < .001). All patients but one had sustained a TBI prior to the diagnosis of BPD. The prevalence of TBI is higher in subjects with BPD than in controls. Since TBI occurred prior to the full expression of the BPD clinical syndrome, TBI appears to be a cause rather than the result of BPD.

Mapping of SPECT regional cerebral perfusion abnormalities in obsessive-compulsive disorder.

Locations of cerebral perfusion abnormalities in obsessive-compulsive disorder (OCD) were mapped with single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). This report is a new, more thorough analysis of a previous study of these subjects that used region-of-interest methods. Ten obsessive-compulsive patients and seven age- and sex-matched control subjects were studied. Image sets were converted into stereotaxic space, normalized to each subject's mean cerebral value, then group averaged. Difference images were calculated and searched for regions with significant between-group cerebral perfusion differences. Obsessive-compulsive patients had significantly higher relative cerebral perfusion in medial-frontal and right frontal cortex and in cerebellum, and significantly reduced perfusion in right visual association cortex. Increased frontal Perfusion agrees with several prior reports. The caudate nucleus, which has been controversial in neuroimaging studies of OCD, did not display a difference between groups. The results of this study provide information about the locations and extents of cerebral perfusion abnormalities in OCD. Regional abnormalities were compared with those reported in prior functional neuroimaging studies. Issues related to OCD hyperfrontality and frontal lateralization of psychopathology are discussed. Normal caudate nucleus findings are considered in relation to prior functional imaging studies and hypotheses of OCD pathology. © 1994 Wiley-Liss, Inc.

1,3-dichloropropene: two-generation inhalation reproduction study in Fischer 344 rats.

This study evaluated the effects of inhaled technical-grade 1,3-dichloropropene (DCPT) on reproduction and neonatal growth and survival. Groups of 30 male and 30 female Fischer 344 rats, approximately 6 weeks of age, were exposed via inhalation to 0, 10, 30 or 90 ppm DCPT for 6 hr/day, 5 days/week, for two generations. The parental f0 and f1 generations were each bred twice. Reproductive and neonatal parameters evaluated included indices of fertility and pup survival, gestation length, litter size, pup body weight, and pup sex ratio. Gross and histologic examinations were concluded on all f0 and f1 adults. In addition, randomly selected f1b and f2b weanlings were given gross examinations. Parental effects were limited to rats exposed to 90 ppm DCPT and included decreased body weights and histopathologic effects on the nasal mucosa of adult male and female rats. The histopathologic effects consisted of slight, focal hyperplasia of the respiratory epithelium and/or focal degenerative changes in the olfactory epithelium. No adverse effects on reproductive parameters or neonatal growth or survival were observed in the f1a, f1b, f2a, or f2b litters even at an exposure concentration which produced effects in adult animals. Based on these results, it is concluded that inhalation exposure of rats up to 90 ppm DCPT for two successive generations did not adversely affect the reproductive and neonatal parameters evaluated.