Nest -Building Behavior In House Mice (Mus Musculus), A Potential Model Of Obsessive -Compulsive Disorder In Humans

Thesis (Ph.D.) University of Alaska Fairbanks, 2007OCD (obsessive-compulsive disorder) is a chronic and debilitating psychiatric condition characterized by intrusive and persistent thoughts (obsessions) and repetitive behaviors (compulsions) that become ritualistic in an attempt to escape the obsessions. Currently there is a paucity of animal models with robust and spontaneous (non-drug or non-behaviorally induced) compulsive-like behaviors. This study is aimed at validating a novel robust and spontaneous genetic mouse model of OCD. The compulsive-like nest-building behavior in mice selected for high levels of nest-building behavior (BIG) has good face validity, with a behavioral phenotype that resembles hoarding behavior characteristic of OCD. In addition, male and female BIG mice displayed compulsivelike digging behavior relative to mice selected for low levels of nest-building behavior (SMALL), as assessed by the marble-burying test. Both chronic oral fluoxetine and clomipramine treatment reduced compulsive-like nest-building behavior in male BIG mice. Furthermore, chronic oral fluoxetine administration decreased nest-building behavior of BIG mice in a dose-dependent manner, while desipramine, an antidepressant not effective for treating OCD, did not significantly alter this behavior. The administration of fluoxetine did not cause a decrease in general locomotor behavior. These findings suggest that the nest-building phenotype has predictive validity. In addition, chronic oral fluoxetine treatment reduced compulsive-like digging behavior in male and female BIG mice as compared to SMALL mice. Gender effects were also found in treatment response. Clomipramine did not reduce nest-building in female BIG mice in a dose-dependent manner, which is consistent with previous studies. These data are in contrast to previous studies using BIG male mice which had a significant decrease in nest-building behavior with oral clomipramine. These results are consistent with studies on humans, which have found gender differences in the treatment effects of antidepressants. Additional construct validity is implicated by the results of targeted serotonergic lesions of the raphe nuclei in male BIG mice, which reduced repetitive nest-building behavior. More research is necessary to confirm the appropriateness of this model for human OCD; however, this model is promising based on the data that support good face, predictive and construct validity

Acetylcholinesterase inhibition ameliorates deficits in motivational drive

<p>Abstract</p> <p>Background</p> <p>Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes.</p> <p>Methods</p> <p>We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes.</p> <p>Results</p> <p>CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens.</p> <p>Conclusions</p> <p>Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.</p

Dispersed Crude Oil Induces Dysbiosis In the Red Snapper \u3ci\u3eLutjanus campechanus\u3c/i\u3e External Microbiota

The fish external microbiota competitively excludes primary pathogens and prevents the proliferation of opportunists. A shift from healthy microbiota composition, known as dysbiosis, may be triggered by environmental stressors and increases host susceptibility to disease. The Deepwater Horizon (DWH) oil spill was a significant stressor event in the Gulf of Mexico. Despite anecdotal reports of skin lesions on fishes following the oil spill, little information is available on the impact of dispersed oil on the fish external microbiota. In this study, juvenile red snapper (Lutjanus campechanus) were exposed to a chemically enhanced water-accommodated fraction (CEWAF) of Corexit 9500/DWH oil (CEWAF) and/or the bacterial pathogen Vibrio anguillarum in treatments designed to detect changes in and recovery of the external microbiota. In fish chronically exposed to CEWAF, immunoglobulin M (IgM) expression significantly decreased between 2 and 4 weeks of exposure, coinciding with elevated liver total polycyclic aromatic hydrocarbons (PAHs). Dysbiosis was detected on fish chronically exposed to CEWAF compared to seawater controls, and addition of a pathogen challenge altered the final microbiota composition. Dysbiosis was prevented by returning fish to clean seawater for 21 days after 1 week of CEWAF exposure. Four fish exhibited lesions during the trial, all of which were exposed to CEWAF but not all of which were exposed to V. anguillarum. This study indicates that month-long exposure to dispersed oil leads to dysbiosis in the external microbiota. As the microbiota is vital to host health, these effects should be considered when determining the total impacts of pollutants in aquatic ecosystems

Manifestation of the Hofstadter butterfly in far-infrared absorption

The far-infrared absorption of a two-dimensional electron gas with a square-lattice modulation in a perpendicular constant magnetic field is calculated self-consistently within the Hartree approximation. For strong modulation and short period we obtain intra- and intersubband magnetoplasmon modes reflecting the subbands of the Hofstadter butterfly in two or more Landau bands. The character of the absorption and the correlation of the peaks to the number of flux quanta through each unit cell of the periodic potential depends strongly on the location of the chemical potential with respect to the subbands, or what is the same, on the density of electrons in the system.Comment: RevTeX file + 4 postscript figures, to be published Phys. Rev. B Rapid Com

Commissioning of the vacuum system of the KATRIN Main Spectrometer

The KATRIN experiment will probe the neutrino mass by measuring the beta-electron energy spectrum near the endpoint of tritium beta-decay. An integral energy analysis will be performed by an electro-static spectrometer (Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240 m^3, and a complex inner electrode system with about 120000 individual parts. The strong magnetic field that guides the beta-electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300{\deg}C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure

Pancytopenia due to iron deficiency worsened by iron infusion: a case report

<p>Abstract</p> <p>Introduction</p> <p>Iron deficiency anemia is commonly associated with thrombocytosis, although thrombocytopenia has been reported in occasional patients with iron-deficiency anemia. Much less common is the development of thrombocytopenia following replenishment of iron stores.</p> <p>Case Presentation</p> <p>We present the unusual case of a 39 year old African American female Jehovah's Witness who presented with a 10 month history of menorrhagia and pancytopenia. Laboratory investigations confirmed a severe iron deficiency. Since blood transfusion was unacceptable to her, she was started on intravenous iron replacement therapy. This precipitated a sudden drop in both her platelet and white blood cell counts. Histopathological examination of the bone marrow revealed a hypercellular marrow with orderly trilineage hematopoiesis, iron deficiency anemia, granulocytic hyperplasia, and mild megakaryocytic hypoplasia. Both her white blood cell and platelet counts recovered uneventfully with continuing iron supplementation. The possible mechanism for this phenomenon is discussed in this report.</p> <p>Conclusion</p> <p>This case illustrates two rather uncommon associations of a very common problem. Severe iron deficiency anemia may be associated with pancytopenia and iron replacement may cause a transient decline in megakaryopoiesis and leukopoiesis. Severe iron deficiency should be added to the list of conditions leading to thrombocytopenia.</p

Condition Indices as Surrogates of Energy Density and Lipid Content in Juveniles of Three Fish Species

To guide the selection of condition indices for juvenile fishes, we compared the ability of several indirect condition indices (those based on length-mass relationships, the hepatosomatic index, and relative lipid estimates from the Distell fish fatmeter) to assess energy density and lipid content of Summer Flounder Paralichthys dentatus, Striped BassMorone saxatilis, and Atlantic Croakers Micropogonias undulatus. These species use estuarine areas as nurseries, but they have different life history strategies and ecological niches that affect their energy storage strategies. We tested hypotheses that differences in the distribution and role of lipids as energy stores among species would influence the suitability of condition indices for estimating energy and lipid content. Length-based indices were most suitable for estimating energy and lipid content of juvenile Summer Flounder and Striped Bass, suggesting that length-based indices may be appropriate for juveniles that store energy as proteins (i.e., juveniles with low lipid content). The fatmeter suitably predicted energy and lipid content of Atlantic Croakers, indicating its potential for assessing condition of juveniles that store lipids for migration and that display a high range of observed lipid content. Even though a small size range was examined, fish length improved predictions of energy and lipid content for some of the indirect condition indices for Atlantic Croakers and Summer Flounder, suggesting that fish length should be considered when developing relationships among measures of condition. The selection of condition indices should be tailored to the life stage and species of interest based on the energy and lipid storage strategies used by the fish

Impact of Dreissena fouling on the physiological condition of native and invasive bivalves : interspecific and temporal variations

The impact of Dreissena fouling on unionids has hardly been studied in Europe, despite the fact that in some ecosystems (e.g. Lake Balaton, Hungary) infestations of several hundreds to a thousand individuals per unionid have been observed. At present, the zebra mussel Dreissena polymorpha is a dominant species in Lake Balaton and in the last decade three other invasive bivalves were introduced, potentially increasing the pressure on native unionid survival. We examined whether the fouling of dreissenids (zebra and quagga (D. rostriformis bugensis) mussels) has a negative impact on native (Anodonta anatina, Unio pictorum and U. tumidus) and invasive (Corbicula fluminea and Sinanodonta woodiana) bivalves and whether there are any interspecific and temporal variations in fouling intensity and physiological condition measured by standard condition index and glycogen content. A significant negative impact was detected on native unionids only in July and September (no impact was detected in May), when the fouling rate was high. For invasive species, a significant negative impact was detected on S. woodiana with a high level of dressenid infestation; whereas no significant impact was detected on C. fluminea. Overall, this study confirms that Dreissena may threaten unionid species including the invasive S. woodiana, although high interspecific and temporal variations were observed. This situation should be taken into account in future ecological and conservational assessments because species respond differently to Dreissena fouling and effects seem to be more pronounced in late summer/early autumn. In addition, this study provides the first evidence that the invasive C. fluminea appear to be less vulnerable to dressenid fouling.The study was supported by the Hungarian Scientific Fund (KTIA-OTKA) under the contract No. CNK80140

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA &lt; 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged &gt; 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p &lt; 0.001]. By multivariate analysis, females (p &lt; 0.01) and PWID (p &lt; 0.001), presented a longer time to ART initiation, while older people (p &lt; 0.001), people with higher educational levels (p &lt; 0.001), unemployed (p = 0.02) and students (p &lt; 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability