Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF in mouse ovaries: relationship to oocytes developmental potential.

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Li-Min Wu

Full Text Available BACKGROUND: Brain-derived neurotropic factor (BDNF was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. METHODS: Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. RESULTS: Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn't affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. CONCLUSION: BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.

Paecilomyces tenuipes extract prevents depression-like behaviors in chronic unpredictable mild stress-induced rat model via modulation of neurotransmitters.

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Liu, Chungang; Wang, Juan; Xu, Shiqi; An, Shengshu; Tang, Siying; He, Jian; Liu, Yang; Lee, Robert J; Wang, Di

2017-08-01

The medicinal fungus Paecilomyces tenuipes exhibits a variety of pharmacological effects, including antidepressive effects. The chronic unpredictable mild stress (CUMS)‑induced rat model has served an important role in studies involving antidepressants screening. The aim of the present study was to evaluate the antidepressant‑like activity of P. tenuipes N45 aqueous extract (PTNE) in a CUMS‑induced rat model of behavioral despair depression. Following 4 weeks of PTNE treatment, behavioral tests were conducted to investigate the antidepressant‑like activities, and the levels of neurotransmitters and hormones in blood and hypothalamus were measured. The results demonstrated that PTNE treatment significantly increased movement in the forced running test, whereas the immobility time was reduced in the hotplate test and the forced swim test in depression‑model rats. PTNE treatment was able to normalize the levels of hormones and neurotransmitters in serum and hypothalamus of CUMS rats. The data demonstrated that PTNE treatment may be a potential pharmaceutical agent in treatment‑resistant depression, and the effects of PTNE may be partly mediated through normalizing the levels of neurotransmitters.

Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

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Ru-Peng Liu

2013-01-01

Full Text Available To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA at the auricular concha region (ACR of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once daily for 14 days. The results showed that blood pressure and heart rate were significantly reduced in the EA-ACR group than in the UCMS alone group or the EA-ear-tip group. The open-field test scores significantly decreased in the UCMS alone and EA-ear-tip groups but not in the EA-ACR group. Both EA treatments downregulated levels of plasma cortisol and ACTH in UCMS rats back to normal levels. The present study suggested that EA-ACR can elicit similar cardioinhibitory effects as vagus nerve stimulation (VNS, and EA-ACR significantly antagonized UCMS-induced depressive status in UCMS rats. The antidepressant effect of EA-ACR is possibly mediated via the normalization of the hypothalamic-pituitary-adrenal (HPA axis hyperactivity.

Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway.

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Gawali, Nitin B; Bulani, Vipin D; Gursahani, Malvika S; Deshpande, Padmini S; Kothavade, Pankaj S; Juvekar, Archana R

2017-05-15

Agmatine, a neurotransmitter/neuromodulator, has shown to exert numerous effects on the CNS. Chronic stress is a risk factor for development of depression, anxiety and deterioration of cognitive performance. Compelling evidences indicate an involvement of nitric oxide (NO) pathway in these disorders. Hence, investigation of the beneficial effects of agmatine on chronic unpredictable mild stress (CUMS)-induced depression, anxiety and cognitive performance with the involvement of nitrergic pathway was undertaken. Mice were subjected to a battery of stressors for 28days. Agmatine (20 and 40mg/kg, i.p.) alone and in combination with NO modulators like L-NAME (15mg/kg, i.p.) and l-arginine (400mg/kg i.p.) were administered daily. The results showed that 4-weeks CUMS produces significant depression and anxiety-like behaviour. Stressed mice have also shown a significant high serum corticosterone (CORT) and low BDNF level. Chronic treatment with agmatine produced significant antidepressant-like behaviour in forced swim test (FST) and sucrose preference test, whereas, anxiolytic-like behaviour in elevated plus maze (EPM) and open field test (OFT) with improved cognitive impairment in Morris water maze (MWM). Furthermore, agmatine administration reduced the levels of acetylcholinesterase and oxidative stress markers. In addition, agmatine treatment significantly increased the BDNF level and inhibited serum CORT level in stressed mice. Treatment with L-NAME (15mg/kg) potentiated the effect of agmatine whereas l-arginine abolished the anxiolytic, antidepressant and neuroprotective effects of agmatine. Agmatine showed marked effect on depression and anxiety-like behaviour in mice through nitrergic pathway, which may be related to modulation of oxidative-nitrergic stress, CORT and BDNF levels. Copyright © 2017 Elsevier B.V. All rights reserved.

The Impacts of Swimming Exercise on Hippocampal Expression of Neurotrophic Factors in Rats Exposed to Chronic Unpredictable Mild Stress

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Pei Jiang

2014-01-01

Full Text Available Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1 and peptides (VGF and NPY in rats exposed to chronic unpredictable mild stress (CUMS. Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS.

Ondansetron attenuates depression co-morbid with obesity in obese mice subjected to chronic unpredictable mild stress; an approach using behavioral battery tests.

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Kurhe, Yeshwant; Radhakrishnan, Mahesh; Gupta, Deepali

2014-09-01

The aim of the present work was to investigate the role of ondansetron on the high fat diet (HFD) induced obese mice for behavioral and biochemical alterations using chronic unpredictable mild stress (CUMS) model of depression. Animals were fed with high fat diet for 14 weeks and subjected to different stress procedures for 4 weeks. Treatment with ondansetron was started on day 15. After day 28 behavioral assays and biochemical estimations were performed. Behavioral paradigms viz. sucrose preference test, locomotor score, forced swim test (FST) and elevated plus maze (EPM), whereas biochemical parameters like plasma glucose, total cholesterol, triglycerides and total proteins were estimated. Results examines that in behavioral assays, ondansetron significantly (P glucose, total cholesterol, triglycerides and total proteins were significantly (P glucose level indicates that, it could be "altered glucose level" playing an important role in depression co-morbid with obesity. Ondansetron through allosteric modulation of serotonergic system elevates the serotonin level and thereby regulates the insulin secretion and hence, reversing the "altered glucose level", could be the possible antidepressive-like mechanism against depression co-morbid with obesity.

Chronic unpredictable mild stress alters an anxiety-related defensive response, Fos immunoreactivity and hippocampal adult neurogenesis.

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de Andrade, J S; Céspedes, I C; Abrão, R O; Dos Santos, T B; Diniz, L; Britto, L R G; Spadari-Bratfisch, R C; Ortolani, D; Melo-Thomas, L; da Silva, R C B; Viana, M B

2013-08-01

Previous results show that elevated T-maze (ETM) avoidance responses are facilitated by acute restraint. Escape, on the other hand, was unaltered. To examine if the magnitude of the stressor is an important factor influencing these results, we investigated the effects of unpredictable chronic mild stress (UCMS) on ETM avoidance and escape measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to map areas activated by stress exposure in response to ETM avoidance and escape performance. Additionally, the effects of the UCMS protocol on the number of cells expressing the marker of migrating neuroblasts doublecortin (DCX) in the hippocampus were investigated. Corticosterone serum levels were also measured. Results showed that UCMS facilitates ETM avoidance, not altering escape. In unstressed animals, avoidance performance increases Fos-ir in the cingulate cortex, hippocampus (dentate gyrus) and basomedial amygdala, and escape increases Fos-ir in the dorsolateral periaqueductal gray and locus ceruleus. In stressed animals submitted to ETM avoidance, increases in Fos-ir were observed in the cingulate cortex, ventrolateral septum, hippocampus, hypothalamus, amygdala, dorsal and median raphe nuclei. In stressed animals submitted to ETM escape, increases in Fos-ir were observed in the cingulate cortex, periaqueductal gray and locus ceruleus. Also, UCMS exposure decreased the number of DCX-positive cells in the dorsal and ventral hippocampus and increased corticosterone serum levels. These data suggest that the anxiogenic effects of UCMS are related to the activation of specific neurobiological circuits that modulate anxiety and confirm that this stress protocol activates the hypothalamus-pituitary-adrenal axis and decreases hippocampal adult neurogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress (UCMS-Exposed Mice

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Esen Gumuslu

2014-01-01

Full Text Available Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT 1 and MT 2 receptors and as an antagonist of 5-HT 2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS-induced cognitive deterioration in mice in passive avoidance (PA, modified elevated plus maze (mEPM, novel object recognition (NOR, and Morris water maze (MWM tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF and cyclic adenosine monophosphate (cAMP response element binding protein (CREB messenger ribonucleic acid (mRNA levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR. Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p., melatonin (10 mg/kg, or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience.

Antidepressant-Like Effect of Lipid Extract of Channa striatus in Chronic Unpredictable Mild Stress Model of Depression in Rats

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Mohamed Saleem Abdul Shukkoor

2016-01-01

Full Text Available This study evaluated the antidepressant-like effect of lipid extract of C. striatus in chronic unpredictable mild stress (CUMS model of depression in male rats and its mechanism of action. The animals were subjected to CUMS for six weeks by using variety of stressors. At the end of CUMS protocol, animals were subjected to forced swimming test (FST and open field test followed by biochemical assay. The CUMS protocol produced depressive-like behavior in rats by decreasing the body weight, decreasing the sucrose preference, and increasing the duration of immobility in FST. The CUMS protocol increased plasma corticosterone and decreased hippocampal and prefrontal cortex levels of monoamines (serotonin, noradrenaline, and dopamine and brain-derived neurotrophic factor. Further, the CUMS protocol increased interleukin-6 (in hippocampus and prefrontal cortex and nuclear factor-kappa B (in prefrontal cortex but not in hippocampus. The lipid extract of C. striatus (125, 250, and 500 mg/kg significantly (p<0.05 reversed all the above parameters in rats subjected to CUMS, thus exhibiting antidepressant-like effect. The mechanism was found to be mediated through decrease in plasma corticosterone, increase in serotonin levels in prefrontal cortex, increase in dopamine and noradrenaline levels in hippocampus and prefrontal cortex, increase in BDNF in hippocampus and prefrontal cortex, and decrease in IL-6 and NF-κB in prefrontal cortex.

Exacerbation of N-nitrosodiethylamine Induced Hepatotoxicity and DNA Damage in Mice Exposed to Chronic Unpredictable Stress

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Nayeem Bilal

2017-06-01

Full Text Available Psychological stress contributes to increased susceptibility to a number of diseases including cancer. The present study was designed to assess the effect of chronic unpredictable stress on N-nitrosodiethylamine induced liver toxicity in terms of in vivo antioxidant status and DNA damage in Swiss albino mice. The animals used in this study were randomized into different groups based on the treatment with N-nitrosodiethylamine or chronic unpredictable stress alone and post-stress administration of N-nitrosodiethylamine. The mice were sacrificed after 12 weeks of treatment, and the status of major enzymatic and non-enzymatic antioxidants, liver function markers, lipid peroxidation and the extent of DNA damage were determined in circulation and liver tissues of all the groups. The N-nitrosodiethylamine treated group showed significantly compromised levels of the antioxidant enzymes, lipid peroxidation, and the liver function markers with enhanced DNA damage as compared to chronic unpredictable stress or control groups. A similar but less typical pattern observed in the chronic unpredictable stress treated mice. All the measured biochemical parameters were significantly altered in the group treated with the combination of chronic unpredictable stress and N-nitrosodiethylamine when compared to controls, or chronic unpredictable stress alone and/or N-nitrosodiethylamine alone treated groups. Thus, exposure to continuous, unpredictable stress conditions even in general life may significantly enhance the hepatotoxic potential of N-nitrosodiethylamine through an increase in the oxidative stress and DNA damage.

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

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Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

2017-11-01

Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress.

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Culig, Luka; Surget, Alexandre; Bourdey, Marlene; Khemissi, Wahid; Le Guisquet, Anne-Marie; Vogel, Elise; Sahay, Amar; Hen, René; Belzung, Catherine

2017-11-01

Major depression is hypothesized to be associated with dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery. We investigated this question by using a 10-week unpredictable chronic mild stress (UCMS) model on a transgenic mouse line (iBax mice), in which the pro-apoptotic gene Bax can be inducibly ablated in neural stem cells following Tamoxifen injection, therefore enhancing the survival of newborn neurons in the adult brain. We did not observe any effect of our treatment in non-stress conditions, but we did find that increasing AHN after 2 weeks of UCMS is sufficient to counteract the effects of UCMS on certain behaviors (splash test and changes in coat state) and endocrine levels and thus to display some antidepressant-like effects. We observed that increasing AHN lowered the elevated basal corticosterone levels in mice exposed to UCMS. This was accompanied by a tamoxifen-induced reversal of the lack of stress-induced decrease in neuronal activation in the anteromedial division of the bed nucleus of the stria terminalis (BSTMA) after intrahippocampal dexamethasone infusion, pointing to a possible mechanism through which adult-born neurons might have exerted their effects. Our results contribute to the neurogenesis hypothesis of depression by suggesting that increasing AHN may be beneficial not just before, but also after exposure to stress by counteracting several of its effects, in part through regulating the HPA axis. Copyright © 2017 Elsevier Ltd. All rights

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats

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Yang X

2017-10-01

Full Text Available Xin-Hua Yang,1 Su-Qi Song,2 Yun Xu3 1Department of Pharmacy, Hefei Eighth People’s Hospital, Hefei, 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 3Faculty of Pharmacy, Anhui Medical University, Hefei, China Abstract: Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES, a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS, after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively. The sucrose preference test, open field test, and forced swimming test were used to explore the antidepressant-like effects of RES. The activity of the hypothalamic–pituitary–adrenal (HPA axis was evaluated by detecting the plasma corticosterone concentration and hypothalamic mRNA expression of corticotrophin-releasing hormone. The plasma interleukin-6 (IL-6, C-reactive protein (CRP, and tumor necrosis factor-α (TNF-α concentrations were measured by enzyme-linked immunosorbent assay. Hippocampal protein expression of brain-derived neurotrophic factor (BDNF and the Wnt/β-catenin pathway were analyzed by western blot. The results showed that RES relieved depression-like behavior of CUMS rats, as indicated by the increased sucrose preference and the decreased immobile time. Rats that received RES treatment exhibited reduced plasma corticosterone levels and corticotrophin-releasing hormone mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by RES. Moreover, after RES treatment, the rats exhibited increased

The chronic mild stress (CMS) model of depression: History, evaluation and usage.

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Willner, Paul

2017-02-01

Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.

BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.

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Wang, Jun-Ming; Yang, Lian-He; Zhang, Yue-Yue; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

2015-11-01

Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice

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Yeshwant Kurhe

2016-06-01

Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

The Antidepressant Effect of Angelica sinensis Extracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

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Jun Shen

2016-01-01

Full Text Available Angelica sinensis (AS, a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS- induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF and the phosphorylation of cAMP-response element binding protein (CREB and extracellular signal-regulated protein kinase (ERK 1/2 were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB were upregulated in the hippocampus.

Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats Based on Serum Metabolic Profiles

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Xiaoxia Gao

2018-01-01

Full Text Available The petroleum ether fraction of Bupleuri Radix which is contained in the traditional Chinese medicine prescription of Xiaoyaosan (XYS may have a therapeutic effect in depressed subjects based on the results of our previous study. It has been reported that Bupleuri Radix can cause liver toxicity following overdosing or long-term use. Therefore, this study aimed to decipher the differential effective and toxic responses of Bupleuri Radix in chronic unpredictable mild stress (CUMS (with depression and healthy rats based on serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC- Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum ether fraction of Bupleuri Radix (PBR produces an antidepressant effect through regulating glycometabolism, amino acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. It also induces more severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats, which exhibited a comparatively mild drug-induced toxic reaction. The altered lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid metabolism, and bile acid metabolism could be at least partly responsible for the PBR toxic responses in healthy rats. The differential effective and toxic response of PBR in CUMS rats and healthy rats provide a new standard for the more rational and safer application of clinical drugs in the future.

Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress.

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Xian-cang Ma

Full Text Available Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS, an animal model of depression.C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST and forced swimming test (FST, the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice.These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.

Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

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Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

2014-05-01

Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain.

Ethanol extract of Rehmannia glutinosa exerts antidepressant-like effects on a rat chronic unpredictable mild stress model by involving monoamines and BDNF.

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Wang, Jun-Ming; Pei, Li-Xin; Zhang, Yue-Yue; Cheng, Yong-Xian; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

2018-06-01

The dried roots of Rehmannia glutinosa Libosch. (Scrophulariaceae) are of both medicinal and nutritional importance. Our previous study has found that the 80% ethanol extract of R. glutinosa (RGEE) produced antidepressant-like activities in mouse behavioral despair depression models. However, its mechanisms are still unclear. The present study aimed to observe the antidepressant-like mechanisms of RGEE on a rat chronic unpredictable mild stress (CUMS) model by involving monoaminergic neurotransmitters and brain-derived neurotrophic factor (BDNF). CUMS-stressed rats were orally given RGEE daily (150, 300, and 600 mg/kg) or fluoxetine hydrochloride (FH) for 3 weeks after starting the CUMS procedure. Sucrose preference test was carried out to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. Results demonstrated that CUMS induced depression-like behavior, whereas RGEE and FH administration inhibited this symptom. Furthermore, CUMS caused excessively elevated levels of serum corticosterone (CORT), an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, in a manner attenuated by RGEE and FH administration. RGEE administration also further elevated monoamine neurotransmitters and BDNF levels, up-regulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB) in hippocampus of rats suffering CUMS. Together, our findings suggest that RGEE can improve CUMS-evoked depression-like behavior, and indicate its mechanisms may partially be associated with restoring HPA axis dysfunctions, enhancing monoamineergic nervous systems, and up-regulating BDNF and TrkB expression.

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

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Yang Yang

2017-07-01

Full Text Available In the clinic selective serotonin reuptake inhibitors (SSRIs, like Fluoxetine, remain the primary treatment for major depression. It has been suggested that miR-16 regulates serotonin transporters (SERT via raphe nuclei and hippocampal responses to antidepressants. However, the underlying mechanism and regulatory pathways are still obtuse. Here, a chronic unpredicted mild stress (CUMS depression model in rats was established, and then raphe nuclei miR-16 and intragastric Fluoxetine injections were administered for a duration of 3 weeks. An open field test and sucrose preference quantification displayed a significant decrease in the CUMS groups when compare to the control groups, however these changes were attenuated by both miR-16 and Fluoxetine treatments. A dual-luciferase reporter assay system verified that hsa-miR-16 inhibitory effects involve the targeting of 3′UTR on the 5-HTT gene. Expression levels of miR-16 and BDNF in the hippocampus were examined with RT-PCR, and it was found that increased 5-HT2a receptor expression induced by CUMS can be decreased by miR-16 and Fluoxetine administration. Immunofluorescence showed that expression levels of neuron NeuN and MAP-2 in CUMS rats were lower. Apoptosis and autophagy levels were evaluated separately through relative expression of Bcl-2, Caspase-3, Beclin-1, and LC3II. Furthermore, CUMS was found to decrease levels of hippocampal mTOR, PI3K, and AKT. These findings indicate that apoptosis and autophagy related pathways could be involved in the effectiveness of antidepressants, in which miR-16 participates in the regulation of, and is likely to help integrate rapid therapeutic strategies to alleviate depression clinically. These findings indicate that miR-16 participates in the regulation of apoptosis and autophagy and could account for some part of the therapeutic effect of SSRIs. This discovery has the potential to further the understanding of SSRIs and accelerate the development of new

Evaluation of behavioural and antioxidant activity of Cytisus scoparius Link in rats exposed to chronic unpredictable mild stress

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Harisudhan Thanukrishnan

2008-04-01

Full Text Available Abstract Background Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. Cytisus scoparius (CS Link, (Family: Leguminosae, also called Sarothamnus scoparius, has been shown in invitro experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats. Methods 60% methanolic extract of CS was quantified for phenolic content by Folin-Ciocalteau's method. Chronic unpredictable mild stress (CMS was employed to induce stress in rats. CS (125 and 250 mg/kg, p.o and diazepam (DZM (2 mg/kg, p.o was administered during the 21 day stress exposure period. Anxiolytic and antidepressant activities of CS were assessed in open field exploratory and behavioural despair paradigms, respectively. Plasma glucose and total lipids; endogenous antioxidant enzymes such as superoxide dismutase (SOD, catalase (CAT; non-enzymic-ascorbic acid and thiobarbituric acid reactive substances (TBARS levels were measured in brain, kidneys and adrenals using standard protocols to assess the effect of CS. Results Total phenolic content of CS was found to be 8.54 ± 0.16% w/w. CMS produced anxiogenic and depressive behaviour in experimental rats with metabolic disturbance. Significant decrease in SOD, CAT levels and increase in lipid peroxidation level was observed in stressed rats. CS administration for 21 days during stress exposure significantly increased the ambulatory behaviour and decreased the freezing time in open field behaviour. In behavioural despair test no significant alteration in the immobility period was observed. CS also improved SOD, CAT, and ascorbic acid level and controlled the lipid peroxidation in different tissues

Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway.

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Tao, Weiwei; Dong, Yu; Su, Qiang; Wang, Hanqing; Chen, Yanyan; Xue, Wenda; Chen, Chang; Xia, Baomei; Duan, Jinao; Chen, Gang

2016-07-15

Major depression is a common long-lasting or recurrent psychiatric disease with high lifetime prevalence and high incidence of suicide. The main purpose of the current study was to verify whether liquiritigenin conferred an antidepressant-like effect on the depressive mouse model established by unpredictable chronic mild stress (UCMS) and explore its possible mechanism. The results of depression-related behaviors including sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) indicated that both liquiritigenin (7.5mg/kg, 15mg/kg) and fluoxetine (20mg/kg) dramatically improved the depression symptoms. Enzyme-linked immunosorbent assay (ELISA) revealed that treatment with liquiritigenin significantly reduced the concentrations of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in serum and hippocampus. Compared with the UCMS group, the administrations of liquiritigenin, increased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and decreased Malondialdehyde (MDA) content. Meanwhile, glucocorticoids (GC) content was reduced in the liquiritigenin group, which suggested that liquiritigenin exhibiting the ameliorative effect on activated hypothalamic-pituitary-adrenal (HPA) axis stimulated with UCMS. Mice treated with liquiritigenin showed restored levels of neurotransmitter norepinephrine (NE) and serotonin (5-HT). Western blot analysis displayed up-regulated expressions of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p- mammalian target of rapamycin (mTOR), p-tropomyosin-related kinase B (TrkB), brain-derived neurotrophic factor (BDNF). Thus, it was supposed that liquiritigenin might be useful for the treatment of chronic depression possibly through PI3K/Akt/mTOR mediated BDNF/TrkB pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Antidepressant-like effect of essential oil of Perilla frutescens in a chronic, unpredictable, mild stress-induced depression model mice.

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Ji, Wei-Wei; Li, Rui-Peng; Li, Meng; Wang, Shu-Yuan; Zhang, Xian; Niu, Xing-Xing; Li, Wei; Yan, Lu; Wang, Yang; Fu, Qiang; Ma, Shi-Ping

2014-10-01

Perilla frutescens (Perilla leaf), a garnishing vegetable in East Asian countries, as well as a plant-based medicine, has been used for centuries to treat various conditions, including depression. Several studies have demonstrated that the essential oil of P. frutescens (EOPF) attenuated the depressive-like behavior in mice. The present study was designed to test the anti-depressant effects of EOPF and the possible mechanisms in an chronic, unpredictable, mild stress (CUMS)-induced mouse model. With the exposure to stressor once daily for five consecutive weeks, EOPF (3, 6, and 9 mg·kg(-1)) and a positive control drug fluoxetine (20 mg·kg(-1)) were administered through gastric intubation to mice once daily for three consecutive weeks from the 3(rd) week. Open-field test, sucrose consumption test, tail suspension test (TST), and forced swimming test (FST) were used to evaluate the behavioral activity. The contents of 5-hydroxytryptamine (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in mouse hippocampus were determined by HPLC-ECD. Serum interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α levels were evaluated by enzyme-linked immunosorbent assay (ELISA). The results showed that CUMS significantly decreased the levels of 5-HT and 5-HIAA in the hippocampus, with an increase in plasma IL-6, IL-1β, and TNF-α levels. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. EOPF administration could effectively reverse the alterations in the concentrations of 5-HT and 5-HIAA; reduce the IL-6, IL-1β, and TNF-α levels. Moreover, EOPF could effectively reverse alterations in immobility duration, sucrose consumption, and open-field activity. However, the effect was not dose-dependent. In conclusion, EOPF administration exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of EOPF might be related to the relation between

Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

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Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders

2010-01-01

Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core ...

Decreased hedonic responsiveness following chronic mild stress is not secondary to loss of body weight.

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Willner, P; Moreau, J L; Nielsen, C K; Papp, M; Sluzewska, A

1996-07-01

Chronic exposure to mild unpredictable stress (CMS) has previously been found to decrease hedonic responsiveness, as measured by the consumption of palatable sweet solutions or sensitivity to brain stimulation reward. These effects are reversed by chronic treatment with antidepressant drugs, and the CMS procedure has been proposed as a relatively valid animal model of depression. It has recently been suggested that the behavioural effects of CMS may be secondary to loss of body weight. This article collates data from five laboratories using the CMS procedure. Data are presented from seven studies using five different rat strains, as well as CD1 mice. Three-week exposure to CMS significantly decreased sucrose consumption by Lister hooded, PVG hooded, Wistar, and Wistar WU rats, and by CD1 mice, and sensitivity to brain stimulation reward in Ibm:Ro Ro rats. Weight loss in different experiments varied between 0 and 10%. Hedonic sensitivity relative to body weight (e.g., mg sucrose/g body weight) decreased significantly in all experiments. Animals maintained on a restricted feeding regime lost weight but did not show decreases in sucrose intake. It is concluded that decreased hedonic sensitivity following chronic mild stress cannot be attributed to loss of body weight.

Effects of chronic stress on the brain – the evidence from morphological examinations of hippocampus in a chronic unpredictable stress (CUS model in rats

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Joanna Sekita-Krzak

2016-12-01

    Abstract Background. Chronic stress exposure deteriorates memory and increases the risk of psychiatric disorders, including depression. Objectives. The objective of this study was to perform morphological studies in experimental model of neuropsychiatric disorder and to assess histologically the effect of chronic unpredictable stress procedure (CUS influence on hippocampus. Material and methods. Chronic unpredictable stress procedure (CUS was applied for 8 weeks in rats by the modified method described by Katz et al. Experimental model of neuropsychiatric disorder was used based on morphological studies of hippocampal formation. Results. Stress-induced alterations were observed in the hippocampus. Nerve cell changes included  neuron shrinkage and dendritic remodeling. The most vulnerable hippocampal cells to chronic stress were CA3 and CA4 pyramidal neurons. In dentate gyrus chronic stress led to granule neuron shrinkage and slight exacerbation of apoptosis in the polygonal cell layer. CUS led to statistically significant changes in quantitative characteristics of the CA3 and CA4 neuron size and nuclei diameter. Conclusions. Chronic stress induces degeneration of hippocampal neurons. The observed neuronal changes indicate the damage of the neurons did not involve neither apoptosis nor necrosis Similarity between histological changes obtained in 8-week long CUS procedure applied in our research and morphological changes described in depressed patients confirms the usefulness of the applied stress procedure as the experimental model of depression.   Key words: stress, depression, hippocampus, chronic unpredictable stress procedure (CUS, animal model, morphology.

L-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters.

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Xue, Jinsong; Li, Hongyan; Deng, Xueyang; Ma, Zhanqiang; Fu, Qiang; Ma, Shiping

2015-07-01

L-Menthone (MTN) is a Chinese old remedy extracted from the genus Mentha. It has been widely used as a cooling agent and a counterirritant for pain relief, although its antidepressant-like effects have not yet been reported. The present study was designed to investigate whether MTN confers an antidepressant-like effect in mice exposed to unpredictable chronic mild stress (UCMS) and to explore its potential mechanisms. The effects of MTN on mouse behavioral changes were investigated in our study. We determined the levels of the nucleotide binding, oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, inflammatory cytokines and neurotransmitters in the hippocampus of mice. Behavioral tests, including the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) revealed that MTN (15 and 30mg/kg) treatments for 3weeks alleviated the depression symptoms of UCMS in mice. Mice receiving MTN treatments exhibited reduced levels of NLRP3 and caspase-1. Moreover, MTN treatments reversed the UCMS-induced alterations in the concentrations of neurotransmitter norepinephrine (NE) and serotonin (5-HT) and inhibited the expression of pro-inflammatory cytokines (PIC) interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the hippocampus of mice. Taken together, our findings suggested that MTN may play a potential antidepressant-like role in the UCMS mouse model by regulating the NLRP3 inflammasome and mediating inflammatory cytokines and central neurotransmitters, which together provide insight towards the development of novel therapeutic treatments for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term treatment with peony glycosides reverses chronic unpredictable mild stress-induced depressive-like behavior via increasing expression of neurotrophins in rat brain.

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Mao, Qing-Qiu; Xian, Yan-Fang; Ip, Siu-Po; Tsai, Sam-Hip; Che, Chun-Tao

2010-07-11

The root part of Paeonia lactiflora Pall., commonly known as peony, is a commonly used Chinese herb for the treatment of depression-like disorders. Previous studies in our laboratory have showed that total glycosides of peony (TGP) produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to investigate the mechanism(s) underlying the antidepressant-like action of TGP by measuring neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in non-stressed and chronic unpredictable mild stress (CUMS)-treated rats. TGP (80 or 160 mg/kg/day) was administered by oral gavage to the animals for 5 weeks. The results showed that CUMS caused depression-like behavior in rats, as indicated by the significant decreases in sucrose consumption and locomotor activity (assessed by open-field test). In addition, it was found that BDNF contents in the hippocampus and frontal cortex were significantly decreased in CUMS-treated rats. CUMS treatment also significantly decreased the level of NGF in the frontal cortex of the animals. Daily intragastric administration of TGP (80 or 160 mg/kg/day) during the five weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. Treating non-stressed animals with TGP (160 mg/kg) for 5 weeks also significantly increased BDNF contents in the hippocampus and frontal cortex, and NGF contents in the frontal cortex. The results suggest that the antidepressant-like action of TGP is mediated, at least in part, by increasing the expression of BDNF and NGF in selective brain tissues. Copyright 2010 Elsevier B.V. All rights reserved.

Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence.

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Chaby, Lauren E; Cavigelli, Sonia A; White, Amanda; Wang, Kayllie; Braithwaite, Victoria A

2013-01-01

Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid "stress" hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision-making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g., isolation, crowding, cage tilt) were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias [F (1, 12) = 5.000, P chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object [T (1, 14) = 2.240, P = 0.04; T (1, 14) = 2.419, P = 0.03, respectively]. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions.

Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level.

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Jindal, Ankur; Mahesh, Radhakrishnan; Bhatt, Shvetank

2013-11-01

Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21 days (8-28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (pBDNF level and inhibited the hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any

cAMP/PKA-CREB-BDNF signaling pathway in hippocampus mediates cyclooxygenase 2-induced learning/memory deficits of rats subjected to chronic unpredictable mild stress.

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Luo, Ying; Kuang, Shengnan; Li, Huan; Ran, Dongzhi; Yang, Junqing

2017-05-30

To investigate the mechanism of cyclooxygenase 2 (COX2) in learning and memory impairments in rats subjected to chronic unpredictable mild stress (CUMS), meloxicam was used intragastrically to inhibit the activity of cyclooxygenase 2. Moreover, cyclooxygenase 2 over-expressing or RNA interfere lentivirus was injected intraventricularly to increase or decrease the enzyme's expression, respectively. The body weights and sucrose consumption were used to analyze depressive behaviors, while the Morris water maze and step-down-type passive avoidance tests were carried out to evaluate the learning-memory functions. The levels of inflammatory cytokines were measured to estimate inflammation and the contents of cyclic adenosine monophosphate (cAMP) were used to measure the levels of the second messenger. Changes in cyclooxygenase 2 mRNA levels were analyzed using reverse transcription polymerase chain reaction. Moreover, the expression of cyclooxygenase 2, brain-derived neurotrophic factor (BDNF), prostaglandins receptor 3 (EP3), protein kinase A (PKA), cAMP response element binding protein (CREB), and phosphorylated CREB were estimated using immunohistochemical staining or western blotting. The results showed that CUMS led to significant depressive-like behaviors and learning and memory dysfunctions. Also, the cAMP levels decreased significantly, while levels of inflammatory cytokines and prostaglandins E2 increased significantly. The expressions of PKA, BDNF, phosphorylated CREB/CREB declined and cyclooxygenase 2 was increased. Meloxicam and cyclooxygenase 2 RNA interfere lentivirus reversed the changes caused by CUMS while cyclooxygenase 2-overexpressing lentivirus worsened these abnormalities. The findings also showed that CUMS increased cyclooxygenase 2 expression, which can cause learning and memory impairments, mainly through activating the hippocampal neuronal cAMP/PKA-CREB-BDNF signaling pathways.

Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic Unpredictable Mild Stress by Modulating the Hypothalamic-Pituitary-Adrenal Axis Function and Activating BDNF Signaling Pathway.

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Zu, Xianpeng; Zhang, Mingjian; Li, Wencai; Xie, Haisheng; Lin, Zhang; Yang, Niao; Liu, Xinru; Zhang, Weidong

2017-11-01

Preliminary studies conducted in our laboratory have confirmed that Bacopaside I (BS-I), a saponin compound isolated from Bacopa monnieri, displayed antidepressant-like activity in the mouse behavioral despair model. The present investigation aimed to verify the antidepressant-like action of BS-I using a mouse model of behavioral deficits induced by chronic unpredictable mild stress (CUMS) and further probe its underlying mechanism of action. Mice were exposed to CUMS for a period of 5 consecutive weeks to induce depression-like behavior. Then, oral gavage administrations with vehicle (model group), fluoxetine (12 mg/kg, positive group) or BS-I (5, 15, 45 mg/kg, treated group) once daily were started during the last two weeks of CUMS procedure. The results showed that BS-I significantly ameliorated CUMS-induced depression-like behaviors in mice, as characterized by an elevated sucrose consumption in the sucrose preference test and reduced immobility time without affecting spontaneous locomotor activity in the forced swimming test, tail suspension test and open field test. It was also found that BS-I treatment reversed the increased level of plasma corticosterone and decreased mRNA and protein expressions of glucocorticoid receptor induced by CUMS exposure, indicating that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity of CUMS-exposed mice was restored by BS-I treatment. Furthermore, chronic administration of BS-I elevated expression levels of brain-derived neurotrophic factor (BDNF) (mRNA and protein) and activated the phosphorylation of extracellular signal-regulated kinase and cAMP response element-binding protein in the hippocampus and prefrontal cortex in mice subjected to CUMS procedure. Taken together, these results indicated that BS-I exhibited an obvious antidepressant-like effect in mouse model of CUMS-induced depression that was mediated, at least in part, by modulating HPA hyperactivity and activating BDNF signaling pathway.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice

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Susana eMonteiro

2015-02-01

Full Text Available Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight and an overactive hypothalamic-pituitary-adrenal (HPA axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen.The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to chronic unpredictable stress.

Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence

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Lauren eChaby

2013-07-01

Full Text Available Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid stress hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g. isolation, crowding, cage tilt were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias (F1,12 = 5.000, P < 0.05, altered coping response (T1,14 = 2.216, P = 0.04, and accelerated decision making (T1,14 = 3.245, P = 0.01. Exposure to chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object (T1,14 = 2.240, P = 0.04; T1,14 = 2.419, P = 0.03, respectively. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions. Stress during adolescence also induced short-term changes in the way animals moved around a novel environment.

Effects of Refined Xiaoyaosan on Depressive-Like Behaviors in Rats with Chronic Unpredictable Mild Stress through Neurosteroids, Their Synthesis and Metabolic Enzymes

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Xiaoling Guo

2017-08-01

Full Text Available Abstract: To observe the effects of refined Xiaoyaosan (XYS on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS, and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model. Rats in the XYS group, and fluoxetine group were given intragastric administration with refined XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. The contents of pregnenolone (PREG, progesterone (PROG and alloprognanolone (ALLO in the plasma of rats were measured by ELISA. The levels of PREG, PROG and ALLO in the hippocampus and amygdala tissues were measured by LC-MS/MS. The mRNA expressions of 3α-hydroxysteroid dehydrogenase (3α-HSD, 3β-hydroxysteroid dehydrogenase (3β-HSD, cholesterol side-chain cleavage enzyme (P450scc and 5α-reductase (5a-R in the hippocampus and amygdala were detected by RT-qPCR methods. Results: There were changes in the model rats. The contents of PREG, PROG and ALLO changed similarly, which reflected in the decrease of PROG and ALLO, and the increase of PREG. The mRNA expression of P450scc was increased, and the mRNA expressions of 3α-HSD, 3β-HSD and 5a-R were decreased. Refined XYS could improve the behaviors of rats and the biological indicators. Conclusions: There is a neurosteroid dysfunction in the brain region of depression rat model animals, and the mechanism of refined XYS depression treatment may be related to the regulation of the control of mRNA expression of related synthesis and metabolic enzymes in the hippocampus and amygdala, further affecting the contents of neurosteroids.

Antidepressant-like effect of the water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress.

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Xing, Hang; Zhang, Kuo; Zhang, Ruowen; Shi, Huiyan; Bi, Kaishun; Chen, Xiaohui

2015-12-01

Water extract of the fixed combination of Gardenia jasminoides Ellis fruit, Citrus aurantium L. fruit and Magnolia officinalis Rehd. et Wils. bark, traditional name - Zhi-Zi-Hou-Po (ZZHPD) is used for treatment of depressive-like symptoms in traditional Chinese medicine for centuries. The present study aimed to explore antidepressant-like effects and potential mechanisms of ZZHPD in a rat model of chronic unpredictable mild stress (CUMS). Antidepressant-like effects of ZZHPD were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system, neurotrophin and hippocampal neurogenesis. Antidepressant-like effects of ZZHPD (3.66, 7.32 and 14.64 g/kg/day) were estimated through coat state test, sucrose preference test, forced swimming test and open-field test. Effects of ZZHPD on hypothalamic-pituitary-adrenal (HPA) axis were evaluated by hormones measurement and dexamethasone suppression test. In addition, the expression of brain-derived neurotrophic factor (BDNF) in hippocampus was measured, as well as hippocampal neurogenesis was investigated by doublecortin (DCX) and 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN). The results demonstrated that ZZHPD significantly reversed the depressive-like behaviors, normalized the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT), restored the negative feedback loop of HPA axis and improved the levels of BDNF, DCX and BrdU/NeuN compared with those in CUMS-induced rats. The above results revealed that ZZHPD exerted antidepressant-like effects possibly by normalizing HPA axis function, increasing expression of BDNF in hippocampus and promoting hippocampal neurogenesis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats.

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Yang, Xin-Hua; Song, Su-Qi; Xu, Yun

2017-01-01

Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS), after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively. The sucrose preference test, open field test, and forced swimming test were used to explore the antidepressant-like effects of RES. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the plasma corticosterone concentration and hypothalamic mRNA expression of corticotrophin-releasing hormone. The plasma interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) concentrations were measured by enzyme-linked immunosorbent assay. Hippocampal protein expression of brain-derived neurotrophic factor (BDNF) and the Wnt/β-catenin pathway were analyzed by western blot. The results showed that RES relieved depression-like behavior of CUMS rats, as indicated by the increased sucrose preference and the decreased immobile time. Rats that received RES treatment exhibited reduced plasma corticosterone levels and corticotrophin-releasing hormone mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by RES. Moreover, after RES treatment, the rats exhibited increased plasma IL-6, CRP, and TNF-α concentrations. Furthermore, RES treatment upregulated the hippocampal protein levels of BDNF and the relative ratio of p-β-catenin/β-catenin while downregulating the relative ratio of p-GSK-3β/GSK-3β. Our findings suggest that RES improved

Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

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Wang, Zhe; Zhang, Dongdong; Hui, Shan; Zhang, Yingjin; Hu, Suiyu

2013-04-01

To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

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Ortiz, J Bryce; Taylor, Sara B; Hoffman, Ann N; Campbell, Alyssa N; Lucas, Louis R; Conrad, Cheryl D

2015-04-01

Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for 2 days and given one retention trial on the third day, with brains removed 30min later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice.

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Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

2015-01-01

Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamic-pituitary-adrenal axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen. The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to CUS.

Anhedonia but not passive floating is an indicator of depressive-like behavior in two chronic stress paradigms.

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Stepanichev, Mikhail Yu; Tishkina, Anna O; Novikova, Margarita R; Levshina, Irina P; Freiman, Sofiya V; Onufriev, Mikhail V; Levchenko, Olga A; Lazareva, Natalia A; Gulyaeva, Natalia V

2016-01-01

Depression is the most common form of mental disability in the world. Depressive episodes may be precipitated by severe acute stressful events or by mild chronic stressors. Studies on the mechanisms of depression require both appropriate experimental models (most of them based on the exposure of animals to chronic stressors), and appropriate tests for assessment of depressive states. In this study male Wistar rats were exposed to two different chronic stress paradigms: an eight-week chronic unpredictable mild stress or a two-week combined chronic stress. The behavioral effects of stress were evaluated using sucrose preference, forced swim and open field tests. After the exposure to chronic unpredictable mild stress, anhedonia was developed, activity in the open field increased, while no changes in the duration of passive floating could be detected. After chronic combined stress, anhedonia was also evident, whereas behavior in the open field and forced swim test did not change. The levels of corticosterone in the blood and brain structures involved in stress-response did not differ from control in both experiments. The absence of significant changes in corticosterone levels and passive floating may be indicative of the adaptation of animals to chronic stress. Anhedonia appears to be a more sensitive indicator of depressive-like behavioral effects of chronic stress as compared to behavior in the forced swim or open field tests.

Mitigation of chronic unpredictable stress–induced cognitive deficits ...

African Journals Online (AJOL)

Methods: The mice were subjected to different unpredictable stressors for a period of 4 weeks. Behavioral tests, including open field (OFT) and Morris water maze (MWMT) tests were used to evaluate pharmacological effects. Serum corticosterone levels, protein expression level of BDNF and pCREB/CREB in hippocampus ...

Integration of ¹H NMR and UPLC-Q-TOF/MS for a comprehensive urinary metabonomics study on a rat model of depression induced by chronic unpredictable mild stress.

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Hong-Mei Jia

Full Text Available Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing (1H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11, 16, 17, 21-25, and 27-36 were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1-2, 4-6, 15, 18, 20-23, 27, 32, 35-36 involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC and indoleamine 2, 3-dioxygenase (IDO in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of (1H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify

Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

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Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

2017-03-15

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Suyusan's effect on cytokine in the chronic mild unpredictable stressors depression rats

International Nuclear Information System (INIS)

Chen Liping; Wang Fawei; Lin Mingxiong; Dong Xiaojun; Zhang Yuanyuan

2008-01-01

To explore the serum levels of interleukin 2 (IL-2), interleukin 6 (IL-6) and tumor necrosis factor a (TNF-α) on chronic stress depression rat model treated with traditional chinese herbs. 40 wistar rats were randomly allocated to 5 groups as follows: control group, depression model group, lower dosage Suyusan group, higher dosage Suyusan group and amitriptyline group. Each group had 8 rats. Each rat was raised in one cage except the control group, in which 4 rats were raised in one cage. The levels of serum IL-2, IL-6 and TNF-α were observed by radioimmunoassay. The results showed that compared with control group, the serum IL-2, IL-6 and TNF-α levels in depression model group increased significantly (P<0.05); the serum IL-2, IL-6 levels in Suyusan group and amitriptyline group decreased, which had significant difference compared with those in depression model group (P<0.05). There was no significant difference between treatment group and control group. Conclusion: Suyusan decoction may regulate cytokine in the stressors induced depression rats, and maybe useful in depression treatment by decreasing cytokine which is high. (authors)

Diagnosis of mild chronic pancreatitis (Cambridge classification): comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography.

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Sai, Jin-Kan; Suyama, Masafumi; Kubokawa, Yoshihiro; Watanabe, Sumio

2008-02-28

To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis. Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement (kappa statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

Protective effects of chronic mild stress during adolescence in the low-novelty responder rat.

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Rana, Samir; Nam, Hyungwoo; Glover, Matthew E; Akil, Huda; Watson, Stanley J; Clinton, Sarah M; Kerman, Ilan A

2016-01-01

Stress-elicited behavioral and physiologic responses vary widely across individuals and depend on a combination of environmental and genetic factors. Adolescence is an important developmental period when neural circuits that guide emotional behavior and stress reactivity are still maturing. A critical question is whether stress exposure elicits contrasting effects when it occurs during adolescence versus adulthood. We previously found that Sprague-Dawley rats selectively bred for low-behavioral response to novelty (bred Low Responders; bLRs) are particularly sensitive to chronic unpredictable mild stress (CMS) exposure in adulthood, which exacerbates their typically high levels of spontaneous depressive- and anxiety-like behavior. Given developmental processes known to occur during adolescence, we sought to determine whether the impact of CMS on bLR rats is equivalent when they are exposed to it during adolescence as compared with adulthood. Young bLR rats were either exposed to CMS or control condition from postnatal days 35-60. As adults, we found that CMS-exposed bLRs maintained high levels of sucrose preference and exhibited increased social exploration along with decreased immobility on the forced swim test compared with bLR controls. These data indicate a protective effect of CMS exposure during adolescence in bLR rats.

Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression

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Zhao, Jing; Jung, Yang-Hee; Jang, Choon-Gon; Chun, Kwang-Hoon; Kwon, Sung Won; Lee, Jeongmi

2015-03-01

Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. Body weight measurement and behavior tests including an open field test and the forced swimming test were completed with the mice as a measure of the phenotypes of depression and antidepressive effects. As a result, 23 metabolites that had been differentially expressed among the control, CMS, and antidepressant-treated groups demonstrated that amino acid metabolism, energy metabolism, adenosine receptors, and neurotransmitters are commonly perturbed by drug treatment. Potential predictive markers for treatment effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for imipramine. Collectively, the current study provides insights into the molecular mechanisms of the antidepressant effects of two widely used medications.

Chronic mild stress influences nerve growth factor through a matrix metalloproteinase-dependent mechanism.

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Kucharczyk, Mateusz; Kurek, Anna; Detka, Jan; Slusarczyk, Joanna; Papp, Mariusz; Tota, Katarzyna; Basta-Kaim, Agnieszka; Kubera, Marta; Lason, Wladyslaw; Budziszewska, Bogusława

2016-04-01

Stress is generally a beneficial experience that motivates an organism to action to overcome the stressful challenge. In particular situations, when stress becomes chronic might be harmful and devastating. The hypothalamus is a critical coordinator of stress and the metabolic response; therefore, disruptions in this structure may be a significant cause of the hormonal and metabolic disturbances observed in depression. Chronic stress induces adverse changes in the morphology of neural cells that are often associated with a deficiency of neurotrophic factors (NTFs); additionally, many studies indicate that insufficient NTF synthesis may participate in the pathogenesis of depression. The aim of the present study was to determine the expression of the nerve growth factor (NGF) in the hypothalamus of male rats subjected to chronic mild stress (CMS) or to prenatal stress (PS) and to PS in combination with an acute stress event (AS). It has been found that chronic mild stress, but not prenatal stress, acute stress or a combination of PS with AS, decreased the concentration of the mature form of NGF (m-NGF) in the rat hypothalamus. A discrepancy between an increase in the Ngf mRNA and a decrease in the m-NGF levels suggested that chronic mild stress inhibited NGF maturation or enhanced the degradation of this factor. We have shown that NGF degradation in the hypothalamus of rats subjected to chronic mild stress is matrix metalloproteinase-dependent and related to an increase in the active forms of some metalloproteinases (MMP), including MMP2, MMP3, MMP9 and MMP13, while the NGF maturation process does not seem to be changed. We suggested that activated MMP2 and MMP9 potently cleave the mature but not the pro- form of NGF into biologically inactive products, which is the reason for m-NGF decomposition. In turn, the enhanced expression of Ngf in the hypothalamus of these rats is an attempt to overcome the reduced levels of m-NGF. Additionally, the decreased level of m

Does Chronic Unpredictable Stress during Adolescence Affect Spatial Cognition in Adulthood?

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Chaby, Lauren E; Sheriff, Michael J; Hirrlinger, Amy M; Lim, James; Fetherston, Thomas B; Braithwaite, Victoria A

2015-01-01

Spatial abilities allow animals to retain and cognitively manipulate information about their spatial environment and are dependent upon neural structures that mature during adolescence. Exposure to stress in adolescence is thought to disrupt neural maturation, possibly compromising cognitive processes later in life. We examined whether exposure to chronic unpredictable stress in adolescence affects spatial ability in late adulthood. We evaluated spatial learning, reference and working memory, as well as long-term retention of visuospatial cues using a radial arm water maze. We found that stress in adolescence decreased the rate of improvement in spatial learning in adulthood. However, we found no overall performance impairments in adult reference memory, working memory, or retention caused by adolescent-stress. Together, these findings suggest that adolescent-stress may alter the strategy used to solve spatial challenges, resulting in performance that is more consistent but is not refined by incorporating available spatial information. Interestingly, we also found that adolescent-stressed rats showed a shorter latency to begin the water maze task when re-exposed to the maze after an overnight delay compared with control rats. This suggests that adolescent exposure to reoccurring stressors may prepare animals for subsequent reoccurring challenges. Overall, our results show that stress in adolescence does not affect all cognitive processes, but may affect cognition in a context-dependent manner.

Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

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Hasan, Shirin; Suhail, Nida; Bilal, Nayeem; Ashraf, Ghulam Md; Zaidi, Syed Kashif; AlNohair, Sultan; Banu, Naheed

2016-05-01

Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention.

Association between endothelial dysfunction and depression-like symptoms in chronic mild stress model of depression

DEFF Research Database (Denmark)

Bouzinova, Elena; Bødtkjer, Donna Marie Briggs; Kudryavtseva, Olga

2014-01-01

OBJECTIVE: Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it in vitro. In the chronic mild stress model, some rats develop depression-like symptoms (including...... "anhedonia"), whereas others are stress resilient. METHODS: After 8 weeks of chronic mild stress, anhedonic rats reduced their sucrose intake by 55% (7%), whereas resilient rats did not. Acetylcholine-induced endothelium-dependent relaxation of norepinephrine-preconstricted mesenteric arteries was analyzed......-like response) was reduced in anhedonic rats (p depression-like symptoms are associated with reduced endothelium-dependent relaxation due to suppressed...

Cognitive deficits in the rat chronic mild stress model for depression: relation to anhedonic-like responses

DEFF Research Database (Denmark)

Henningsen, Kim; Andreasen T., Jesper; Bouzinova, Elena V.

2009-01-01

in the spontaneous alternation test, possibly reflecting a deficit in working memory. This effect was independent of whether the stressed rats were anhedonic-like or stress-resilient as measured by their sucrose intake. CMS did not influence performance in passive avoidance and auditory cued fear conditioning......The chronic mild stress (CMS) protocol is widely used to evoke depressive-like behaviours in laboratory rats. The aim of the present study was to examine the effects of chronic stress on cognitive performance. About 70% of rats exposed to 7 weeks of chronic mild stress showed a gradual reduction...... in consumption of a sucrose solution, indicating an anhedonic-like state. The remaining rats did not reduce their sucrose intake, but appeared resilient to the stress-induced effects on sucrose intake. Cognitive profiling of the CMS rats revealed that chronic stress had a negative effect on performance...

Mild Traumatic Brain Injury Chronically Impairs Sleep- and Wake-Dependent Emotional Processing.

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Mantua, Janna; Henry, Owen S; Garskovas, Nolan F; Spencer, Rebecca M C

2017-06-01

A single traumatic brain injury (TBI), even when mild (ie, concussion), can cause lasting consequences. Individuals with a history of chronic (>1-year prior) mild TBI have an increased risk of mood disturbances (eg, depression, suicide). This population also has lingering sleep alterations, including poor sleep quality and changes in sleep stage proportions. Given these sleep deficits, we aimed to test whether sleep-dependent emotional memory consolidation is reduced in this population. We utilized a mild TBI group (3.7 ± 2.9 years post injury) and an uninjured (non-TBI) population. Participants viewed negative and neutral images both before and after a 12-hour period containing sleep ("Sleep" group) or an equivalent period of time spent awake ("Wake" group). Participants rated images for valence/arousal at both sessions, and memory recognition was tested at session two. The TBI group had less rapid eye movement (REM), longer REM latency, and more sleep complaints. Sleep-dependent memory consolidation of nonemotional images was present in all participants. However, consolidation of negative images was only present in the non-TBI group. A lack of differentiation between the TBI Sleep and Wake groups was due to poor performance in the sleep group and, unexpectedly, enhanced performance in the wake group. Additionally, although the non-TBI participants habituated to negative images over a waking period, the TBI participants did not. We propose disrupted sleep- and wake-dependent emotional processing contributes to poor emotional outcomes following chronic, mild TBI. This work has broad implications, as roughly one-third of the US population will sustain a mild TBI during their lifetime. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Poincaré chaos and unpredictable functions

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Akhmet, Marat; Fen, Mehmet Onur

2017-07-01

The results of this study are continuation of the research of Poincaré chaos initiated in the papers (M. Akhmet and M.O. Fen, Commun Nonlinear Sci Numer Simulat 40 (2016) 1-5; M. Akhmet and M.O. Fen, Turk J Math, doi:10.3906/mat-1603-51, in press). We focus on the construction of an unpredictable function, continuous on the real axis. As auxiliary results, unpredictable orbits for the symbolic dynamics and the logistic map are obtained. By shaping the unpredictable function as well as Poisson function we have performed the first step in the development of the theory of unpredictable solutions for differential and discrete equations. The results are preliminary ones for deep analysis of chaos existence in differential and hybrid systems. Illustrative examples concerning unpredictable solutions of differential equations are provided.

Non-autonomous equations with unpredictable solutions

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Akhmet, Marat; Fen, Mehmet Onur

2018-06-01

To make research of chaos more amenable to investigating differential and discrete equations, we introduce the concepts of an unpredictable function and sequence. The topology of uniform convergence on compact sets is applied to define unpredictable functions [1,2]. The unpredictable sequence is defined as a specific unpredictable function on the set of integers. The definitions are convenient to be verified as solutions of differential and discrete equations. The topology is metrizable and easy for applications with integral operators. To demonstrate the effectiveness of the approach, the existence and uniqueness of the unpredictable solution for a delay differential equation are proved as well as for quasilinear discrete systems. As a corollary of the theorem, a similar assertion for a quasilinear ordinary differential equation is formulated. The results are demonstrated numerically, and an application to Hopfield neural networks is provided. In particular, Poincaré chaos near periodic orbits is observed. The completed research contributes to the theory of chaos as well as to the theory of differential and discrete equations, considering unpredictable solutions.

Changed Synaptic Plasticity in Neural Circuits of Depressive-Like and Escitalopram-Treated Rats

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Li, Xiao-Li; Yuan, Yong-Gui; Xu, Hua; Wu, Di; Gong, Wei-Gang; Geng, Lei-Yu; Wu, Fang-Fang; Tang, Hao; Xu, Lin

2015-01-01

Background: Although progress has been made in the detection and characterization of neural plasticity in depression, it has not been fully understood in individual synaptic changes in the neural circuits under chronic stress and antidepressant treatment. Methods: Using electron microscopy and Western-blot analyses, the present study quantitatively examined the changes in the Gray’s Type I synaptic ultrastructures and the expression of synapse-associated proteins in the key brain regions of rats’ depressive-related neural circuit after chronic unpredicted mild stress and/or escitalopram administration. Meanwhile, their depressive behaviors were also determined by several tests. Results: The Type I synapses underwent considerable remodeling after chronic unpredicted mild stress, which resulted in the changed width of the synaptic cleft, length of the active zone, postsynaptic density thickness, and/or synaptic curvature in the subregions of medial prefrontal cortex and hippocampus, as well as the basolateral amygdaloid nucleus of the amygdala, accompanied by changed expression of several synapse-associated proteins. Chronic escitalopram administration significantly changed the above alternations in the chronic unpredicted mild stress rats but had little effect on normal controls. Also, there was a positive correlation between the locomotor activity and the maximal synaptic postsynaptic density thickness in the stratum radiatum of the Cornu Ammonis 1 region and a negative correlation between the sucrose preference and the length of the active zone in the basolateral amygdaloid nucleus region in chronic unpredicted mild stress rats. Conclusion: These findings strongly indicate that chronic stress and escitalopram can alter synaptic plasticity in the neural circuits, and the remodeled synaptic ultrastructure was correlated with the rats’ depressive behaviors, suggesting a therapeutic target for further exploration. PMID:25899067

THE UNPREDICTABILITY THEORY AND THE CONTRACTUAL LIABILITY

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CRISTINA ZAMSA

2011-04-01

Full Text Available The purpose of the present study is to establish a relationship between the unpredictability theory and the contractual liability, from both theoretical and practical point of view. Usually, the unpredictability is invoked by way of defense by the debtor, refusing to perform the excessively onerous obligation. However the unpredictability theory shall apply also to the hypothesis of a performed obligation, by way of main action, depending on more factors: the nature of the agreement, investigating the attitude of the party affected by the unpredictability. Observing the conditions and the effects of these two ways of invoking the unpredictability will form the objectives of the present study.The debtor of the excessively onerous, in order to avoid the contractual liability, shall nevertheless perform such obligation, by carrying along some additional costs. If subsequently, the creditor shall refuse to revise the agreement and implicitly, to reimburse the exorbitant costs, the debtor will have to raise the unpredictability by way of action, in order to recover the exorbitant costs in performing the obligation. In such case, the unpredictability is accompanied by another legal issue: the contractual liability of the co-contractor of the party affected by unpredictability.

Exposure to chronic mild stress prevents kappa opioid-mediated reinstatement of cocaine and nicotine place preference

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Ream eAl-Hasani

2013-08-01

Full Text Available Stress increases the risk of drug abuse, causes relapse to drug seeking, and potentiates the rewarding properties of both nicotine and cocaine. Understanding the mechanisms by which stress regulates the rewarding properties of drugs of abuse provides valuable insight into potential treatments for drug abuse. Prior reports have demonstrated that stress causes dynorphin release, activating kappa-opioid receptors (KOR in monoamine circuits resulting in both potentiation and reinstatement of cocaine and nicotine conditioned place preference. Here we report that kappa-opioid dependent reinstatement of cocaine and nicotine place preference is reduced when the mice are exposed to a randomized chronic mild stress regime prior to training in a conditioned place preference-reinstatement paradigm. The chronic mild stress schedule involves seven different stressors (removal of nesting for 24hr, 5min forced swim stress at 15°C, 8hr food and water deprivation, damp bedding overnight, white noise, cage tilt and disrupted home cage lighting rotated over a three-week period. This response is KOR-selective, because chronic mild stress does not protect against cocaine or nicotine drug-primed reinstatement. This protection from reinstatement is also observed following sub-chronic social defeat stress, where each mouse is placed in an aggressor mouse home cage for a period of 20 min over five days. In contrast, a single acute stressor resulted in a potentiation of KOR-induced reinstatement, similarly to previously reported. Prior studies have shown that stress alters sensitivity to opioids and prior stress can influence the pharmacodynamics of the opioid receptor system. Together, these findings suggest that exposure to different forms of stress may cause a dysregulation of kappa opioid circuitry and that changes resulting from mild stress can have protective and adaptive effects against drug relapse.

5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels

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Wei Yang

2018-02-01

Full Text Available The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg. 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

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Yang, Wei; Wang, Huanlin

2018-02-01

The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg). 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

3, 4-methylenedioximethamphetamin reverses anxiety induced by chronic mild stress

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Laura Andrea León A

2013-01-01

Full Text Available Here we report the effects of subchronic 3, 4 methylenedioximethamphetamine (MDMA on the elevated plusmaze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI – fluoxetine (2.0 ug/ul or MDMA, (2.0 ug/ul for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub chronic MDMA interacted with MCS leading to a decrease in anxiety related behaviors including: percentage of open arms entries (F [2, 26] = 4.00; p = 0.031, time spent in the open arms (F [2, 26] = 3.656; p = 0.040 and time spent in the open arms extremities (F [2, 26] = 5.842; p = 0.008. These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence.

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Kaye, Jesse T; Bradford, Daniel E; Magruder, Katherine P; Curtin, John J

2017-05-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction.

Probing for Neuroadaptations to Unpredictable Stressors in Addiction: Translational Methods and Emerging Evidence

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Kaye, Jesse T.; Bradford, Daniel E.; Magruder, Katherine P.; Curtin, John J.

2017-01-01

Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction. This research rests on a solid foundation provided by three separate pillars of evidence from (a) rodent behavioral neuroscience on stress neuroadaptations in addiction, (b) rodent affective neuroscience on startle potentiation, and (c) human addiction and affective science with startle potentiation. Rodent stress neuroadaptation models implicate adaptations in corticotropin-releasing factor and norepinephrine circuits within the central extended amygdala following chronic alcohol and other drug use that mediate anxious behaviors and stress-induced reinstatement among drug-dependent rodents. Basic affective neuroscience indicates that these same neural mechanisms are involved in startle potentiation to unpredictable stressors in particular (vs. predictable stressors). We believe that synthesis of these evidence bases should focus us on the role of unpredictable stressors in addiction etiology and relapse. Startle potentiation in unpredictable stressor tasks is proposed to provide an attractive and flexible test bed to encourage tight translation and reverse translation between animal models and human clinical research on stress neuroadaptations. Experimental therapeutics approaches focused on unpredictable stressors hold high promise to identify, repurpose, or refine pharmacological and psychosocial interventions for addiction. PMID:28499100

Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

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Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

2015-01-01

It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction. PMID:26630275

Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

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Henningsen, Kim; Johannesen, Mads Dyrvig; Bouzinova, Elena

2012-01-01

In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

Prior exposure to repeated immobilization or chronic unpredictable stress protects from some negative sequels of an acute immobilization.

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Pastor-Ciurana, Jordi; Rabasa, Cristina; Ortega-Sánchez, Juan A; Sanchís-Ollè, Maria; Gabriel-Salazar, Marina; Ginesta, Marta; Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

2014-05-15

Exposure to chronic unpredictable stress (CUS) is gaining acceptance as a putative animal model of depression. However, there is evidence that chronic exposure to stress can offer non-specific stress protection from some effects of acute superimposed stressors. We then compared in adult male rats the protection afforded by prior exposure to CUS with the one offered by repeated immobilization on boards (IMO) regarding some of the negative consequences of an acute exposure to IMO. Repeated exposure to IMO protected from the negative consequences of an acute IMO on activity in an open-field, saccharin intake and body weight gain. Active coping during IMO (struggling) was markedly reduced by repeated exposure to the same stressor, but it was not affected by a prior history of CUS, suggesting that our CUS protocol does not appear to impair active coping responses. CUS exposure itself caused a strong reduction of activity in the open-field but appeared to protect from the hypo-activity induced by acute IMO. Moreover, prior CUS offered partial protection from acute IMO-induced reduction of saccharin intake and body weight gain. It can be concluded that a prior history of CUS protects from some of the negative consequences of exposure to a novel severe stressor, suggesting the development of partial cross-adaptation whose precise mechanisms remain to be studied. Copyright © 2014 Elsevier B.V. All rights reserved.

Unpredictability and the transmission of numbers

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Myers, John M.; Madjid, F. Hadi

2016-03-01

Curiously overlooked in physics is its dependence on the transmission of numbers. For example, the transmission of numerical clock readings is implicit in the concept of a coordinate system. The transmission of numbers and other logical distinctions is often achieved over a computer-mediated communications network in the face of an unpredictable environment. By unpredictable we mean something stronger than the spread of probabilities over given possible outcomes, namely an opening to unforeseeable possibilities. Unpredictability, until now overlooked in theoretical physics, makes the transmission of numbers interesting. Based on recent proofs within quantum theory that provide a theoretical foundation to unpredictability, here we show how regularities in physics rest on a background of channels over which numbers are transmitted. As is known to engineers of digital communications, numerical transmissions depend on coordination reminiscent of the cycle of throwing and catching by players tossing a ball back and forth. In digital communications, the players are computers, and the required coordination involves unpredictably adjusting "live clocks" that step these computers through phases of a cycle. We show how this phasing, which we call logical synchronization, constrains number-carrying networks, and, if a spacetime manifold in invoked, put "stripes" on spacetime. Via its logically synchronized channels, a network of live clocks serves as a reference against which to locate events. Such a network in any case underpins a coordinate frame, and in some cases the direct use of a network can be tailored to investigate an unpredictable environment. Examples include explorations of gravitational variations near Earth.

Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats.

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Li, Ying; Ji, Yong-juan; Jiang, Hong; Liu, De-xiang; Zhang, Qian; Fan, Shu-jian; Pan, Fang

2009-07-05

Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Age and stress had different effects on the behavior of different aged animals (age: F = 6.173, P BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress in both age groups (P BDNF (F = 9.408, P BDNF expression compared to the young stressed group at every testing time point. Stress has age-dependent effects on behavioral responses and hippocampal BDNF expression in rats.

The effects of stress on alcohol consumption: mild acute and sub-chronic stressors differentially affect apomorphine susceptible and unsusceptible rats.

NARCIS (Netherlands)

Kam, E.L. van der; Coolen, J.C.; Ellenbroek, B.A.; Cools, A.R.

2005-01-01

The aim of this study was to investigate the effects of mild acute and mild sub-chronic challenges on alcohol intake and preference in the genetically selected ratlines of apomorphine susceptible (APO-SUS) and apomorphine unsusceptible (APO-UNSUS) animals. Animals from both lines were subjected to

Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury.

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Hattori, Naoya; Swan, Megan; Stobbe, Gary A; Uomoto, Jay M; Minoshima, Satoshi; Djang, David; Krishnananthan, Ruben; Lewis, David H

2009-07-01

Patients with mild traumatic brain injury (TBI) often complain of cognitive fatigue during the chronic recovery phase. The Paced Auditory Serial Addition Test (PASAT) is a complex psychologic measure that may demonstrate subtle deficiencies in higher cognitive functions. The purpose of this study was to investigate the brain activation of regional cerebral blood flow (rCBF) with PASAT in patients with mild TBI to explore mechanisms for the cognitive fatigue. Two groups consisting of 15 patients with mild TBI and 15 healthy control subjects underwent (99m)Tc-ethylene cysteine dimer SPECT at rest and during PASAT on a separate day. Cortical rCBF was extracted using a 3-dimensional stereotactic surface projection and statistically analyzed to identify areas of activation, which were compared with PASAT performance scores. Image analysis demonstrated a difference in the pattern of activation between patients with mild TBI and healthy control subjects. Healthy control subjects activated the superior temporal cortex (Brodmann area [BA] 22) bilaterally, the precentral gyrus (BA 9) on the left, and the precentral gyrus (BA 6) and cerebellum bilaterally. Patients with mild TBI demonstrated a larger area of supratentorial activation (BAs 9, 10, 13, and 46) but a smaller area of activation in the cerebellum, indicating frontocerebellar dissociation. Patients with mild TBI and cognitive fatigue demonstrated a different pattern of activation during PASAT. Frontocerebellar dissociation may explain cognitive impairment and cognitive fatigue in the chronic recovery phase of mild traumatic brain injury.

A feasibility study of predictable and unpredictable surf-like sounds for tinnitus therapy using personal music players.

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Durai, Mithila; Kobayashi, Kei; Searchfield, Grant D

2018-05-28

To evaluate the feasibility of predictable or unpredictable amplitude-modulated sounds for tinnitus therapy. The study consisted of two parts. (1) An adaptation experiment. Loudness level matches and rating scales (10-point) for loudness and distress were obtained at a silent baseline and at the end of three counterbalanced 30-min exposures (silence, predictable and unpredictable). (2) A qualitative 2-week sound therapy feasibility trial. Participants took home a personal music player (PMP). Part 1: 23 individuals with chronic tinnitus and part 2: seven individuals randomly selected from Part 1. Self-reported tinnitus loudness and annoyance were significantly lower than baseline ratings after acute unpredictable sound exposure. Tinnitus annoyance ratings were also significantly lower than the baseline but the effect was small. The feasibility trial identified that participant preferences for sounds varied. Three participants did not obtain any benefit from either sound. Three participants preferred unpredictable compared to predictable sounds. Some participants had difficulty using the PMP, the average self-report hours of use were low (less <1 h/day). Unpredictable surf-like sounds played using a PMP is a feasible tinnitus treatment. Further work is required to improve the acceptance of the sound and ease of PMP use.

Chronic nailbiting: a controlled comparison of competing response and mild aversion treatments.

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Allen, K W

1996-03-01

Recent studies have suggested that competing response, an abridged version of Azrin and Nunn's (1973) habit reversal method (Behaviour Research and Therapy, 11, 619-628), is a key component in the treatment of chronic nailbiting (Horne & Wilkinson, 1980, Behaviour Research and Therapy, 18, 287-291; Silber & Haynes, 1992, Behaviour Research and Therapy, 30, 15-22). This study replicated and extended the latter by adding an 8 week follow-up period and by using a non-student sample. Forty-five chronic nailbiter Ss were divided into three experimental groups. One method involved the use of mild aversion in which Ss painted a bitter substance on their nails. A second method required the subject to perform a competing response whenever they had the urge to nailbite or found themselves biting their nails. Both methods included self-monitoring of the behaviour and a third group of Ss performed self-monitoring alone as a control condition. The study lasted 12 weeks. Mild aversion resulted in significant improvements in nail length, with the competing response method just failing to show significance in this regard. There was no significant improvement for the control group. The implications for further study and the benefits of competing response in the light of these findings are discussed in terms of treatment success and use of therapist time.

Hereditary chronic pancreatitis

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Mössner Joachim

2007-01-01

Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

Mild Cognitive Impairment

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... more: Key Types of Dementia , What Is Alzheimer's? , Alzheimer's Risk Factors Symptoms back to top Experts classify Mild cognitive ... in Chronic Traumatic Encephalopathy 2014 Thor Stein Genetic Risk Factors Underlying Chronic Trauma and Alzheimer's Disease Pathology 2014 Kun Ping Lu Validation of ...

Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

DEFF Research Database (Denmark)

Eidemak, I; Feldt-Rasmussen, B; Kanstrup, I L

1995-01-01

Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twenty-nine non-diabetic patients with a glomerular filtration rate of 25 ml.min-1.1.73 m-2 (11-43) (median, range) and 15 sex, age, and body mass index matched.......02) (M/I ratio 1.77 +/- 0.71 vs 2.57 +/- 0.70 (mg/(kgBW.min) per pmol/l.100, p aerobic work capacity was significantly lower in the patients than in the control subjects (24 +/- 8 vs 32 +/- 11 ml O2/(kg body weight.min), p .../I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting...

Muscle magnetic resonance imaging sensitivity does not decrease in chronic, mild, or proximal lower limb neuropathies.

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Deroide, Nicolas; Bousson, Valérie; Daguet, Edouard; Dumurgier, Julien; Tin, Sophie Ng Wing; Hannouche, Didier; Richette, Pascal; Beaudreuil, Johann; Lioté, Frédéric; Lévy, Bernard; Vicaut, Eric; Laredo, Jean Denis; Kubis, Nathalie

2012-05-01

Muscle magnetic resonance imaging (MRI) is an innovative tool for exploring focal neuropathies. However, its usefulness in mild, proximal, or chronic lesions, when electromyography (EMG), the current "gold standard" sensitivity is inadequate, has yet to be studied. Clinical, MRI, and EMG examinations were performed in 113 muscles of 17 consecutive patients with clinically diagnosed lower limb focal neuropathies. The sensitivity and specificity of MRI and EMG were evaluated in relation to disease duration, severity, and anatomical location. Muscle MRI was highly sensitive for the detection of denervated muscle, and, unlike EMG, its sensitivity did not decrease regardless of the anatomical location, duration, or severity of the neuropathy. Five MRI false positives were noted, including three in the thigh muscles. Muscle MRI is an alternative tool to EMG in proximal, mild, or chronic clinical diagnoses of lower limb focal neuropathies. However, it also seems prone to false-positive results, particularly in proximal muscles. Copyright © 2012 Wiley Periodicals, Inc.

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

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Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A; Austin, John H M; Bluemke, David A; Carr, James; Choi, Jiwoong; Goldstein, Thomas A; Gomes, Antoinette S; Hoffman, Eric A; Kawut, Steven M; Lima, Joao; Michos, Erin D; Post, Wendy S; Po, Ming Jack; Prince, Martin R; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M; Barr, R Graham

2015-09-01

Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

Effects of prenatal exposure to chronic mild stress and toluene in rats

DEFF Research Database (Denmark)

Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M

2005-01-01

The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated...... in female offspring of pregnant rats (Mol:WIST) exposed to chronic mild stress (CMS) during gestational days (GD) 9-20, or 1500 ppm toluene, 6 h/day during gestational days 7-20, or a combination of the two. Prenatal CMS was associated with decreased thymic weight and increased auditory startle response....... The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of improved...

Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

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Ayuob, Nasra Naeim; El Wahab, Manal Galal Abd; Ali, Soad Shaker; Abdel-Tawab, Hanem Saad

2018-01-22

Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

Changes in proinflammatory cytokines and white matter in chronically stressed rats

Directory of Open Access Journals (Sweden)

Yang P

2015-03-01

Full Text Available Ping Yang,1 Zhenyong Gao,1 Handi Zhang,1 Zeman Fang,1 Cairu Wu,1 Haiyun Xu,1,2 Qing-Jun Huang1 1Mental Health Center, 2Department of Anatomy, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies. Keywords: cytokines, depression, myelination, oligodendrocytes, stress 

Antidepressant-like effect of Butea superba in mice exposed to chronic mild stress and its possible mechanism of action.

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Mizuki, Daishu; Matsumoto, Kinzo; Tanaka, Ken; Thi Le, Xoan; Fujiwara, Hironori; Ishikawa, Tsutomu; Higuchi, Yoshihiro

2014-10-28

Butea superba (BS) is a Thai medicinal plant that has been used as a folk medicine to improve physical and mental conditions and to prevent impaired sexual performance in middle-aged or elderly males. We have previously reported that this plant extract could improve cognitive deficits and depression-like behavior in olfactory bulbectomized mice, an animal model of dementia and depression. In this study we examined the effect of BS on depression-like behavior in mice subjected to unpredictable chronic mild stress (UCMS) to clarify the antidepressant-like activity of BS and the molecular mechanism underlying this effect. UCMS mice were administered BS daily (300 mg of dried herb weight/kg, p.o.) or a reference drug, imipramine (IMP, 10 mg/kg, i.p.), 1 week after starting the UCMS procedure. We employed the sucrose preference test and the tail suspension test to analyze anhedonia and depression-like behavior of mice, respectively. Serum and brain tissues of mice were used for neurochemical and immunohistochemical studies. The UCMS procedure induced anhedonia and depression-like behavior, and BS treatment, as well as IMP treatment, attenuated these symptoms. UCMS caused an elevation of serum corticosterone level, an index of hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis, in a manner attenuated by BS and IMP treatment. BS treatment also attenuated UCMS-induced decrease in the expression levels of brain-derived neurotrophic factor (BDNF) mRNA, cyclic AMP-responsive element binding protein (CREB) and a phosphorylated form of N-methyl-d-aspartate receptor subunit NR1, synaptic plasticity-related signaling proteins. Moreover, the UCMS procedure reduced doublecortin-positive cells in the dentate gyrus region of the hippocampus. BS administration reversed these UCMS-induced neurochemical and histological abnormalities. These results suggest that BS can ameliorate chronic stress-induced depression-like symptoms and that the effects of BS are mediated by

Quercetin ameliorates chronic unpredicted stress-induced behavioral dysfunction in male Swiss albino mice by modulating hippocampal insulin signaling pathway.

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Mehta, Vineet; Singh, Tiratha Raj; Udayabanu, Malairaman

2017-12-01

Chronic stress is associated with impaired neurogenesis, neurodegeneration and behavioral dysfunction, whereas the mechanism underlying stress-mediated neurological complications is still not clear. In the present study, we aimed to investigate whether chronic unpredicted stress (CUS) mediated neurological alterations are associated with impaired hippocampal insulin signaling or not, and studied the effect of quercetin in this scenario. Male Swiss albino mice were subjected to 21day CUS, during which 30mg/kg quercetin treatment was given orally. After 21days, behavioral functions were evaluated in terms of locomotor activity (Actophotometer), muscle coordination (Rota-rod), depression (Tail Suspension Test (TST), Forced Swim Test (FST)) and memory performance (Passive-avoidance step-down task (PASD)). Further, hippocampal insulin signaling was evaluated in terms of protein expression of insulin, insulin receptor (IR) and glucose transporter 4 (GLUT-4) and neurogenesis was evaluated in terms of doublecortin (DCX) expression. 21day CUS significantly impaired locomotion and had no effect on muscle coordination. Stressed animals were depressed and showed markedly impaired memory functions. Quercetin treatment significantly improvement stress-mediated behavior dysfunction as indicated by improved locomotion, lesser immobility time and greater frequency of upward turning in TST and FST and increased transfer latency on the day 2 (short-term memory) and day 5 (long-term memory) in PASD test. We observed significantly higher IR expression and significantly lower GLUT-4 expression in the hippocampus of stressed animals, despite of nonsignificant difference in insulin levels. Further, chronic stress impaired hippocampal neurogenesis, as indicated by the significantly reduced levels of hippocampal DCX expression. Quercetin treatment significantly lowered insulin and IR expression and significantly enhanced GLUT-4 and DCX expression in the hippocampus, when compared to CUS. In

Stressful Presentations: Mild Chronic Cold Stress in Mice Influences Baseline Properties of Dendritic Cells

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Kathleen Marie Kokolus

2014-02-01

Full Text Available The ability of dendritic cells to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to study immune responses. Physiological stress is well recognized to impair several arms of immune protection. The goals of this report are to briefly summarize previous work revealing how DCs respond to various forms of physiologically relevant stress and to present new data highlighting the potential for chronic mild cold stress inherent in mice housed at standard ambient temperatures required for laboratory mice to influence baseline DCs properties. Since recent data from our group shows that CD8+ T cell function is altered by mild chronic cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether mild cold stress may also be influencing DC properties. We found increased numbers of splenic DCs (CD11c+ in cold stressed mice compared to mice housed at a thermoneutral temperature, which significantly reduces cold stress. However, many of the DCs which are expanded in cold stressed mice express an immature phenotype. We also found that antigen presentation and ability of splenocytes to activate T cells were impaired compared to that seen in DCs isolated from mice at thermoneutrality. The new data presented here strongly suggest that the housing temperature of mice can affect fundamental properties of DC function which in turn could be influencing the response of DCs to added experimental stressors or other treatments.

Nicotine reverses anhedonic-like response and cognitive impairment in the rat chronic mild stress model of depression

DEFF Research Database (Denmark)

Andreasen T., Jesper; Henningsen, Kim; Bate, Simon

2011-01-01

Smoking rates among depressed individuals are higher than is observed in the background population, and nicotine alleviates depressive symptoms. In rodents, nicotine shows antidepressant-like effects in the forced swim and learned helplessness paradigms. Clinical depression is associated with both...... anhedonia and cognitive impairments. In rats, chronic mild stress (CMS) decreases voluntary sucrose intake, reflecting an anhedonic-like state, and impairs performance in the spontaneous alternation behaviour (SAB) test, suggesting impaired cognitive function. Here, we examine the effect of chronic...... with depression....

Acute agmatine administration, similar to ketamine, reverses depressive-like behavior induced by chronic unpredictable stress in mice.

Science.gov (United States)

Neis, Vivian B; Bettio, Luis E B; Moretti, Morgana; Rosa, Priscila B; Ribeiro, Camille M; Freitas, Andiara E; Gonçalves, Filipe M; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

Agmatine is an endogenous neuromodulator that has been shown to have antidepressant-like properties. We have previously demonstrated that it can induce a rapid increase in BDNF levels after acute administration, suggesting that agmatine may be a fast-acting antidepressant. To investigate this hypothesis, the present study evaluated the effects of a single administration of agmatine in mice subjected to chronic unpredictable stress (CUS), a model of depression responsive only to chronic treatment with conventional antidepressants. The ability of agmatine to reverse CUS-induced behavioral and biochemical alterations was evaluated and compared with those elicited by the fast-acting antidepressant (ketamine) and the conventional antidepressant (fluoxetine). After exposed to CUS for 14days, mice received a single oral dose of agmatine (0.1mg/kg), ketamine (1mg/kg) or fluoxetine (10mg/kg), and were submitted to behavioral evaluation after 24h. The exposure to CUS caused an increased immobility time in the tail suspension test (TST) but did not change anhedonic-related parameters in the splash test. Our findings provided evidence that, similarly to ketamine, agmatine is able to reverse CUS-induced depressive-like behavior in the TST. Western blot analyses of prefrontal cortex (PFC) demonstrated that mice exposed to CUS and/or treated with agmatine, fluoxetine or ketamine did not present alterations in the immunocontent of synaptic proteins [i.e. GluA1, postsynaptic density protein 95 (PSD-95) and synapsin]. Altogether, our findings indicate that a single administration of agmatine is able to reverse behavioral alterations induced by CUS in the TST, suggesting that this compound may have fast-acting antidepressant-like properties. However, there was no alteration in the levels of synaptic proteins in the PFC, a result that need to be further investigated in other time points. Copyright © 2016 Elsevier Inc. All rights reserved.

The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment

DEFF Research Database (Denmark)

Jayatissa, Magdalena N; Bisgaard, Christina; West, Mark J

2008-01-01

mild stress and chronic escitalopram treatment. Furthermore, we investigated which classes of immature granule cells are affected by stress and targeted by escitalopram. Rats were initially exposed to 2weeks of CMS and 4weeks of escitalopram treatment with concurrent exposure to stress. The behavioral...... changes, indicating a decrease in sensitivity to a reward, were assessed in terms of sucrose consumption. We found a significant 22.4% decrease in the total number of granule cells in the stressed rats. This decrease was reversed in the stressed escitalopram treated rats that responded to the treatment......, but not in the rats that did not respond to escitalopram treatment. These changes were not followed by alterations in the volume of the granule cell layer. We also showed a differential regulation of dentate neurons, in different stages of development, by chronic stress and chronic escitalopram treatment. Our study...

Unpredictable visual changes cause temporal memory averaging.

Science.gov (United States)

Ohyama, Junji; Watanabe, Katsumi

2007-09-01

Various factors influence the perceived timing of visual events. Yet, little is known about the ways in which transient visual stimuli affect the estimation of the timing of other visual events. In the present study, we examined how a sudden color change of an object would influence the remembered timing of another transient event. In each trial, subjects saw a green or red disk travel in circular motion. A visual flash (white frame) occurred at random times during the motion sequence. The color of the disk changed either at random times (unpredictable condition), at a fixed time relative to the motion sequence (predictable condition), or it did not change (no-change condition). The subjects' temporal memory of the visual flash in the predictable condition was as veridical as that in the no-change condition. In the unpredictable condition, however, the flash was reported to occur closer to the timing of the color change than actual timing. Thus, an unpredictable visual change distorts the temporal memory of another visual event such that the remembered moment of the event is closer to the timing of the unpredictable visual change.

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.

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Thakur, Tarun; Gulati, Kavita; Rai, Nishant; Ray, Arunabha

2017-09-01

The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses. Copyright © 2017. Published by Elsevier B.V.

Timing matters: the interval between acute stressors within chronic mild stress modifies behavioral and physiologic stress responses in male rats.

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Cavigelli, Sonia A; Bao, Alexander D; Bourne, Rebecca A; Caruso, Michael J; Caulfield, Jasmine I; Chen, Mary; Smyth, Joshua M

2018-04-12

Chronic mild stress can lead to negative health outcomes. Frequency, duration, and intensity of acute stressors can affect health-related processes. We tested whether the temporal pattern of daily acute stressors (clustered or dispersed across the day) affects depression-related physiology. We used a rodent model to keep stressor frequency, duration, and intensity constant, and experimentally manipulated the temporal pattern of acute stressors delivered during the active phase of the day. Adult male Sprague-Dawley rats were exposed to one of three chronic mild stress groups: Clustered: stressors that occurred within 1 hour of each other (n = 21), Dispersed: stressors that were spread out across the active phase (n = 21), and Control: no stressors presented (n = 21). Acute mild stressors included noise, strobe lights, novel cage, cage tilt, wet bedding, and water immersion. Depression-related outcomes included: sucrose preference, body weight, circulating glucocorticoid (corticosterone) concentration after a novel acute stressor and during basal morning and evening times, and endotoxin-induced circulating interleukin-6 concentrations. Compared to control rats, those in the Clustered group gained less weight, consumed less sucrose, had a blunted acute corticosterone response, and an accentuated acute interleukin-6 response. Rats in the Dispersed group had an attenuated corticosterone decline during the active period and after an acute stressor compared to the Control group. During a chronic mild stress experience, the temporal distribution of daily acute stressors affected health-related physiologic processes. Regular exposure to daily stressors in rapid succession may predict more depression-related symptoms, whereas exposure to stressors dispersed throughout the day may predict diminished glucocorticoid negative feedback.

Clinical Comparison of 99mTc Exametazime and 123I Ioflupane SPECT in Patients with Chronic Mild Traumatic Brain Injury

OpenAIRE

Newberg, Andrew B.; Serruya, Mijail; Gepty, Andrew; Intenzo, Charles; Lewis, Todd; Amen, Daniel; Russell, David S.; Wintering, Nancy

2014-01-01

BACKGROUND: This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population. METHODS AND FINDINGS: Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both (99m)Tc exametazime to m...

A giant adrenal lipoma presenting in a woman with chronic mild postprandial abdominal pain: a case report.

Science.gov (United States)

Kapetanakis, Stylianos; Drygiannakis, Ioannis; Tzortzinis, Anastasios; Papanas, Nikolaos; Fiska, Aliki

2011-04-05

Adrenal lipomas are rare, small, benign, non-functioning tumors, which must be histopathologically differentiated from other tumors such as myelolipomas or liposarcomas. They are usually identified incidentally during autopsy, imaging, or laparotomy. Occasionally, they may present acutely due to complications such as abdominal pain from retroperitoneal bleeding, or systemic symptoms of infection. We report a giant adrenal lipoma (to the best of our knowledge, the second largest in the literature) clinically presenting with chronic mild postprandial pain. A 54-year-old Caucasian woman presented several times over a period of 10 years to various emergency departments complaining of long-term mild postprandial abdominal pain. Although clinical examinations were unrevealing, an abdominal computed tomography scan performed at her most recent presentation led to the identification of a large lipoma of the left adrenal gland, which occupied most of the retroperitoneal space. Myelolipoma was ruled out due to the absence of megakaryocytes, immature leukocytes, or erythrocytes. Liposarcoma was ruled out due to the absence of lipoblasts. The size of the lipoma (16 × 14 × 7 cm) is, to the best of our knowledge, the second largest reported to date. After surgical resection, our patient was relieved of her symptoms and remains healthy six years postoperatively. Physicians should be aware that differential diagnosis of mild chronic abdominal pain in patients presenting in emergency rooms may include large adrenal lipomas. When initial diagnostic investigation is not revealing, out-patient specialist evaluation should be planned to enable appropriate further investigations.

The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

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Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

2018-06-01

This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

[Lung dysfunction in patients with mild chronic obstructive bronchitis].

Science.gov (United States)

Nefedov, V B; Popova, L A; Shergina, E A

2004-01-01

VC, FVC, FEV1, FEV1/VC%, PEF, MEF25, MEF50, MEF75, TCL, TGV, RV, Ravt, Riin, Rex, DLCO-SS, PaO2, and PaO2 were determined in 33 patients with mild chronic obstructive lung disease (FEV1 > 70% of the normal value). All the patients were found to have impaired bronchial patency; most (63.6%) patients had lung volume and capacity changes, almost half (45.5%) the patients had pulmonary gas exchange dysfunction. Impaired bronchial patency mainly appeared as decreased MEF50, MEF15, and FEV1/VC%; altered lung volumes and capacities manifested chiefly by increased RV and decreased VC; pulmonary gas exchange dysfunction showed up primarily as lowered PaO2. The magnitude of the observed functional changes was generally slight. MEF50, MEF75, FEV1/VC%, and VC dropped to 59-20 and 79-70% of the normal value, respectively. RV increased up to 142-196% of the normal value; PaO2 reduced up to 79-60% mm Hg.

Hyperoside protects against chronic mild stress-induced learning and memory deficits.

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Gong, Yeli; Yang, Youhua; Chen, Xiaoqing; Yang, Min; Huang, Dan; Yang, Rong; Zhou, Lianying; Li, Changlei; Xiong, Qiuju; Xiong, Zhe

2017-07-01

Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid mainly found in fruits, fruit juices (most notably flavanols, flavanones, and anthocyanins) and Chinese traditional medicines. It has been applied to relieve pain and improve cardiovascular functions in clinic. However, the effects of hyperoside on cognitive impairment induced by chronic stress and the underlying molecular mechanisms remain unclear. In the current study, we used chronic mild stress (CMS) rats to investigate the effects of hyperoside on learning and memory and further explore the possible mechanisms. Our results demonstrated that hyperoside reduced the escape latency and the swimming distance of CMS rats in Morris water maze test and reversed depressive symptoms in forced swim test (FST) and sucrose preference test. In addition, hyperoside increased the expression of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a, an inhibitor of the BDNF receptor TrkB, prevented the protective effects of hyperoside on learning and memory in CMS rats. Taken together, these results indicate that hyperoside reverses the cognitive impairment induced by CMS, which is associated with the regulation of BDNF signaling pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dendritic Spines in Depression: What We Learned from Animal Models

OpenAIRE

Qiao, Hui; Li, Ming-Xing; Xu, Chang; Chen, Hui-Bin; An, Shu-Cheng; Ma, Xin-Ming

2016-01-01

Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have ...

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

Science.gov (United States)

Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

2014-09-01

The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression. Copyright © 2014 Elsevier Ltd. All rights reserved.

Short- and long-term antidepressant effects of ketamine in a rat chronic unpredictable stress model.

Science.gov (United States)

Jiang, Yinghong; Wang, Yiqiang; Sun, Xiaoran; Lian, Bo; Sun, Hongwei; Wang, Gang; Du, Zhongde; Li, Qi; Sun, Lin

2017-08-01

This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory. After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75). The influence of ketamine on behavioral reactivity was assessed 24 hr (short-term) or 7 weeks after ketamine treatment (long-term). Behavioral tests used to assess the effects of these treatments included the sucrose preference (SP), open field (OF), elevated plus maze (EPM), forced swimming (FS), and water maze (WM) to detect anxiety-like behavior (OF and EPM), forced swimming (FS), and water maze (WM). Results: Short-term ketamine administration resulted in increases of body weight gain, higher sensitivity to sucrose, augmented locomotor activity in the OF, more entries into the open arms of the EPM, along increased activity in the FS test; all responses indicative of reductions in depression/despair in anxiety-eliciting situations. No significant differences in these behaviors were obtained under conditions of long-term ketamine administration ( p  > .05). The CUS + Ketamine group showed significantly increased activity as compared with the CUS + Vehicle group for analysis of the long-term effects of ketamine (* p   .05). Taken together these findings demonstrate that a short-term administration of ketamine induced rapid antidepressant-like effects in adult male rats exposed to CUS conditions, effects that were not observed in response to the long-term treatment regime.

A giant adrenal lipoma presenting in a woman with chronic mild postprandial abdominal pain: a case report

Directory of Open Access Journals (Sweden)

Tzortzinis Anastasios

2011-04-01

Full Text Available Abstract Introduction Adrenal lipomas are rare, small, benign, non-functioning tumors, which must be histopathologically differentiated from other tumors such as myelolipomas or liposarcomas. They are usually identified incidentally during autopsy, imaging, or laparotomy. Occasionally, they may present acutely due to complications such as abdominal pain from retroperitoneal bleeding, or systemic symptoms of infection. We report a giant adrenal lipoma (to the best of our knowledge, the second largest in the literature clinically presenting with chronic mild postprandial pain. Case presentation A 54-year-old Caucasian woman presented several times over a period of 10 years to various emergency departments complaining of long-term mild postprandial abdominal pain. Although clinical examinations were unrevealing, an abdominal computed tomography scan performed at her most recent presentation led to the identification of a large lipoma of the left adrenal gland, which occupied most of the retroperitoneal space. Myelolipoma was ruled out due to the absence of megakaryocytes, immature leukocytes, or erythrocytes. Liposarcoma was ruled out due to the absence of lipoblasts. The size of the lipoma (16 × 14 × 7 cm is, to the best of our knowledge, the second largest reported to date. After surgical resection, our patient was relieved of her symptoms and remains healthy six years postoperatively. Conclusion Physicians should be aware that differential diagnosis of mild chronic abdominal pain in patients presenting in emergency rooms may include large adrenal lipomas. When initial diagnostic investigation is not revealing, out-patient specialist evaluation should be planned to enable appropriate further investigations.

Study of gastro-oesophageal reflux disease in patients with mild-to-moderate chronic obstructive pulmonary disease in India.

Science.gov (United States)

Kamble, Nitish L; Khan, Naushad A; Kumar, Naresh; Nayak, Hemanta K; Daga, Mradul K

2013-04-01

To study the incidence and pattern of gastro-oesophageal reflux disease (GORD) in patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) using dual-probe 24-h oesophageal pH recording. This was a prospective study of 50 patients with mild-to-moderate stage COPD based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. A detailed history of illness along with spirometry was done in all patients. In the study group, reflux symptoms were measured using a validated scoring system. All the patients underwent oesophageal manometry and dual-probe 24-h oesophageal pH recording. Symptoms of gastro-oesophageal reflux were present in 38 patients. Twenty-four-hour oesophageal pH monitoring revealed pathological reflux in 31 out of 38 symptomatic and 8 out of 12 asymptomatic patients. The overall rate of GORD was 78% in our study. Only distal GORD was observed in 11 (28.9%), and both distal and proximal GORD was observed in 20 (52.6%) out of the 38 symptomatic subjects. In the remaining 12 asymptomatic patients, eight had GORD. Distal GORD was present in six (50%) patients, and two (16.6%) had both distal and proximal GORD in this group. Isolated proximal GORD was not observed in any patient. There is an increased occurrence of GORD in patients with even mild-to-moderate COPD. © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.

Browse Title Index

African Journals Online (AJOL)

Items 401 - 450 of 1323 ... ... of chronic unpredictable mild stress on the mice salivary glands? ... vitro antifungal activities on six human pathogenic fungi, Abstract PDF ... of a traditional herbal medicine containing garlic and black cumin, Abstract.

Influence of chronic back pain on kinematic reactions to unpredictable arm pulls.

Science.gov (United States)

Götze, Martin; Ernst, Michael; Koch, Markus; Blickhan, Reinhard

2015-03-01

There is evidence that muscle reflexes are delayed in patients with chronic low back pain in response to perturbations. It is still unrevealed whether these delays accompanied by an altered kinematic or compensated by adaption of other muscle parameters. The aim of this study was to investigate whether chronic low back pain patients show an altered kinematic reaction and if such data are reliable for the classification of chronic low back pain. In an experiment involving 30 females, sudden lateral perturbations were applied to the arm of a subject in an upright, standing position. Kinematics was used to distinguish between chronic low back pain patients and healthy controls. A calculated model of a stepwise discriminant function analysis correctly predicted 100% of patients and 80% of healthy controls. The estimation of the classification error revealed a constant rate for the classification of the healthy controls and a slightly decreased rate for the patients. Observed reflex delays and identified kinematic differences inside and outside the region of pain during impaired movement indicated that chronic low back pain patients have an altered motor control that is not restricted to the lumbo-pelvic region. This applied paradigm of external perturbations can be used to detect chronic low back pain patients and also persons without chronic low back pain but with an altered motor control. Further investigations are essential to reveal whether healthy persons with changes in motor function have an increased potential to develop chronic back pain. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chronic stress induced cognitive impairment in APP/PS-1 double transgenic mouse model of Alzheimer's disease

Directory of Open Access Journals (Sweden)

Bing HAN

2015-08-01

Full Text Available Objective  To observe the effect of chronic unpredictable mild stress (CUMS on the cognitive function and brain morphological changes in APP/PS-1 mice, one of the genetic mouse models of Alzheimer's disease (AD, and to investigate the possible role of environmental factors in genetic mouse model of AD. Methods  There were 22-week-old wild-type C57BL/6 male mice (control group, N = 15 and APP/PS-1 double transgenic male mice [N = 27: AD group (N = 13 and AD + CUMS group (N = 14] tested in this study. Morris water maze test was used to evaluate spatial learning and memory of the mice. Amyloid deposition in the hippocampus was determined by Congo red staining. The ultrastructure of neurons in hippocampal CA1 region was observed by transmission electron microscope (TEM.  Results  Compared with control group, AD + CUMS group had significantly longer fifth-day escape latency [(33.14 ± 14.37 s vs (21.22 ± 12.16 s; t = -2.701, P = 0.045], and significantly shortened time spent in platform quadrant [(9.74±1.35 s vs (15.02 ± 1.33 s; t = 2.639, P = 0.012] in Morris water maze test. Compared with AD group, the percentage of amyloid plaque area in hippocampal area was increased in AD + CUMS group [(0.59 ± 0.03% vs (0.04 ± 0.03%; t = -2.900, P = 0.005]. The ultrastructure of hippocampal neurons in AD group was slightly damaged: cellular membrane was intact; cell matrix was uniform; intracelluar lipofuscin could be seen; the structure of nucleus and nuclear membrane had no obvious changes; mild fusion of cristae and membrane was seen in mitochondria; Golgi apparatus was partially indistinct; endoplasmic reticulum was mildly expanded. The ultrastructure of hippocampal neurons in AD + CUMS group was obviously damaged, including blurred cell membrane, reduced low-density and high-density granules in cytoplasm, uneven cell matrix, reduced number of organelles, lipofuscin and autophagosome deposition, obvious condensation of chromatin distributing over

Quantum randomness and unpredictability

Energy Technology Data Exchange (ETDEWEB)

Jaeger, Gregg [Quantum Communication and Measurement Laboratory, Department of Electrical and Computer Engineering and Division of Natural Science and Mathematics, Boston University, Boston, MA (United States)

2017-06-15

Quantum mechanics is a physical theory supplying probabilities corresponding to expectation values for measurement outcomes. Indeed, its formalism can be constructed with measurement as a fundamental process, as was done by Schwinger, provided that individual measurements outcomes occur in a random way. The randomness appearing in quantum mechanics, as with other forms of randomness, has often been considered equivalent to a form of indeterminism. Here, it is argued that quantum randomness should instead be understood as a form of unpredictability because, amongst other things, indeterminism is not a necessary condition for randomness. For concreteness, an explication of the randomness of quantum mechanics as the unpredictability of quantum measurement outcomes is provided. Finally, it is shown how this view can be combined with the recently introduced view that the very appearance of individual quantum measurement outcomes can be grounded in the Plenitude principle of Leibniz, a principle variants of which have been utilized in physics by Dirac and Gell-Mann in relation to the fundamental processes. This move provides further support to Schwinger's ''symbolic'' derivation of quantum mechanics from measurement. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Examination of the interaction of different lighting conditions and chronic mild stress in animal model.

Science.gov (United States)

Muller, A; Gal, N; Betlehem, J; Fuller, N; Acs, P; Kovacs, G L; Fusz, K; Jozsa, R; Olah, A

2015-09-01

We examined the effects of different shift work schedules and chronic mild stress (CMS) on mood using animal model. The most common international shift work schedules in nursing were applied by three groups of Wistar-rats and a control group with normal light-dark cycle. One subgroup from each group was subjected to CMS. Levels of anxiety and emotional life were evaluated in light-dark box. Differences between the groups according to independent and dependent variables were examined with one- and two-way analysis of variance, with a significance level defined at p animals.

Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: A pilot study.

Science.gov (United States)

Choi, Gyu-Sik; Kwak, Sang Gyu; Lee, Han Do; Chang, Min Cheol

2018-02-28

Central pain can occur following traumatic brain injury, leading to poor functional recovery, limitation of activities of daily living, and decreased quality of life. The aim of this study was to determine whether high-frequency (10 Hz) repetitive transcranial magnetic stimulation, applied over the primary motor cortex of the affected hemisphere, can be used to manage chronic central pain after mild traumatic brain injury. Prospective randomized feasibility study. Twelve patients with mild traumatic brain injury and chronic central pain were randomly assigned to transcranial magnetic stimulation (high-frequency stimulation, 10 sessions) or sham groups. Diffuse tensor tractography revealed partially injured spinothalamocortical tracts in all recruited patients. A numerical rating scale (NRS) was used to evaluate pain intensity during pre-treatment and immediately after the 5th transcranial magnetic stimulation session (post1), 10th transcranial magnetic stimulation session (post2), and 1 (post3), 2 (post4), and 4 weeks (post 5) after finishing treatment. Physical and mental health status were evaluated using the Short Form 36 Health Survey (SF-36), including physical and mental component scores (PCS, MCS). The NRS score of the repetitive transcranial magnetic stimulation group was significantly lower than the sham group score at all clinical evaluation time-points during and after transcranial magnetic stimulation sessions. The transcranial magnetic stimulation group's SF-36 PCS score was significantly higher at post2, post3, post4, and post5 compared with the sham group. High-frequency transcranial magnetic stimulation may be used to manage chronic central pain and improve quality of life in patients with mild traumatic brain injury. However, this is a pilot study and further research is needed.

The protective effects of social bonding on behavioral and pituitary-adrenal axis reactivity to chronic mild stress in prairie voles.

Science.gov (United States)

McNeal, Neal; Appleton, Katherine M; Johnson, Alan Kim; Scotti, Melissa-Ann L; Wardwell, Joshua; Murphy, Rachel; Bishop, Christina; Knecht, Alison; Grippo, Angela J

2017-03-01

Positive social interactions may protect against stress. This study investigated the beneficial effects of pairing with a social partner on behaviors and neuroendocrine function in response to chronic mild stress (CMS) in 13 prairie vole pairs. Following 5 days of social bonding, male and female prairie voles were exposed to 10 days of CMS (mild, unpredictable stressors of varying durations, for instance, strobe light, white noise, and damp bedding), housed with either the social partner (paired group) or individually (isolated group). Active and passive behavioral responses to the forced swim test (FST) and tail-suspension test (TST), and plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, were measured in all prairie voles following the CMS period. Both female and male prairie voles housed with a social partner displayed lower durations of passive behavioral responses (immobility, a maladaptive behavioral response) in the FST (mean ± SEM; females: 17.3 ± 5.4 s; males: 9.3 ± 4.6 s) and TST (females: 56.8 ± 16.4 s; males: 40.2 ± 11.3 s), versus both sexes housed individually (females, FST: 98.6 ± 12.9 s; females, TST: 155.1 ± 19.3 s; males, FST: 92.4 ± 14.1 s; males, TST: 158.9 ± 22.0 s). Female (but not male) prairie voles displayed attenuated plasma stress hormones when housed with a male partner (ACTH: 945 ± 24.7 pg/ml; corticosterone: 624 ± 139.5 ng/ml), versus females housed individually (ACTH: 1100 ± 23.2 pg/ml; corticosterone: 1064 ± 121.7 ng/ml). These results may inform understanding of the benefits of social interactions on stress resilience. Lay Summary: Social stress can lead to depression. The study of social bonding and stress using an animal model will inform understanding of the protective effects of social bonds. This study showed that social bonding in a rodent model can protect against behavioral responses to stress, and may

Pulmonary complications after abdominal surgery in patients with mild-to-moderate chronic obstructive pulmonary disease

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Kim TH

2016-11-01

Full Text Available Tae Hoon Kim, Jae Seung Lee, Sei Won Lee, Yeon-Mok Oh Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Abstract: Postoperative pulmonary complications (PPCs are one of the most important causes of postoperative morbidity and mortality after abdominal surgery. Although chronic obstructive pulmonary disease (COPD has been considered a risk factor for PPCs, it remains unclear whether mild-to-moderate COPD is a risk factor. This retrospective cohort study included 387 subjects who underwent abdominal surgery with general anesthesia in a tertiary referral hospital. PPCs included pneumonia, pulmonary edema, pulmonary thromboembolism, atelectasis, and acute exacerbation of COPD. Among the 387 subjects, PPCs developed in 14 (12.0% of 117 patients with mild-to-moderate COPD and in 13 (15.1% of 86 control patients. Multiple logistic regression analysis revealed that mild-to-moderate COPD was not a significant risk factor for PPCs (odds ratio [OR] =0.79; 95% confidence interval [CI] =0.31–2.03; P=0.628. However, previous hospitalization for respiratory problems (OR =4.20; 95% CI =1.52–11.59, emergency surgery (OR =3.93; 95% CI =1.75–8.82, increased amount of red blood cell (RBC transfusion (OR =1.09; 95% CI =1.05–1.14 for one pack increase of RBC transfusion, and laparoscopic surgery (OR =0.41; 95% CI =0.18–0.93 were independent predictors of PPCs. These findings suggested that mild-to-moderate COPD may not be a significant risk factor for PPCs after abdominal surgery.Keywords: postoperative pulmonary complications, spirometry, risk factor, abdominal surgery, postoperative complications, postoperative care

Effects of chronic mild stress on the development of drug dependence in rats.

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Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Litwa, Ewa; Willner, Paul

2014-09-01

There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

Clinical comparison of 99mTc exametazime and 123I Ioflupane SPECT in patients with chronic mild traumatic brain injury.

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Andrew B Newberg

Full Text Available BACKGROUND: This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI. The goal was to determine how these two different scan might be used and compared to each other in this patient population. METHODS AND FINDINGS: Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both (99mTc exametazime to measure cerebral blood flow (CBF and (123I ioflupane to measure dopamine transporter (DAT binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001. Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients. CONCLUSIONS: Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.

Effect of high-frequency repetitive transcranial magnetic stimulation on chronic central pain after mild traumatic brain injury: A pilot study

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Gyu-sik Choi

2018-01-01

Full Text Available Objective: Central pain can occur following traumatic brain injury, leading to poor functional recovery, limitation of activities of daily living, and decreased quality of life. The aim of this study was to determine whether high-frequency (10 Hz repetitive transcranial magnetic stimulation, applied over the primary motor cortex of the affected hemisphere, can be used to manage chronic central pain after mild traumatic brain injury. Design: Prospective randomized feasibility study. Methods: Twelve patients with mild traumatic brain injury and chronic central pain were randomly assigned to transcranial magnetic stimulation (high-frequency stimulation, 10 sessions or sham groups. Diffuse tensor tractography revealed partially injured spinothalamocortical tracts in all recruited patients. A numerical rating scale (NRS was used to evaluate pain intensity during pre-treatment and immediately after the 5th transcranial magnetic stimulation session (post1, 10th transcranial magnetic stimulation session (post2, and 1 (post3, 2 (post4, and 4 weeks (post 5 after finishing treatment. Physical and mental health status were evaluated using the Short Form 36 Health Survey (SF-36, including physical and mental component scores (PCS, MCS. Results: The NRS score of the repetitive transcranial magnetic stimulation group was significantly lower than the sham group score at all clinical evaluation time-points during and after transcranial magnetic stimulation sessions. The transcranial magnetic stimulation group’s SF-36 PCS score was significantly higher at post2, post3, post4, and post5 compared with the sham group. Conclusion: High-frequency transcranial magnetic stimulation may be used to manage chronic central pain and improve quality of life in patients with mild traumatic brain injury. However, this is a pilot study and further research is needed.

Diagnostic Instability and Reversals of Chronic Obstructive Pulmonary Disease Diagnosis in Individuals with Mild to Moderate Airflow Obstruction.

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Aaron, Shawn D; Tan, Wan C; Bourbeau, Jean; Sin, Don D; Loves, Robyn H; MacNeil, Jenna; Whitmore, George A

2017-08-01

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease, and reversal of COPD diagnosis is thought to be uncommon. To determine whether a spirometric diagnosis of mild or moderate COPD is subject to variability and potential error. We examined two prospective cohort studies that enrolled subjects with mild to moderate post-bronchodilator airflow obstruction. The Lung Health Study (n = 5,861 subjects; study duration, 5 yr) and the Canadian Cohort of Obstructive Lung Disease (CanCOLD) study (n = 1,551 subjects; study duration, 4 yr) were examined to determine frequencies of (1) diagnostic instability, represented by how often patients initially met criteria for a spirometric diagnosis of COPD but then crossed the diagnostic threshold to normal and then crossed back to COPD over a series of annual visits, or vice versa; and (2) diagnostic reversals, defined as how often an individual's COPD diagnosis at the study outset reversed to normal by the end of the study. Diagnostic instability was common and occurred in 19.5% of the Lung Health Study subjects and 6.4% of the CanCOLD subjects. Diagnostic reversals of COPD from the beginning to the end of the study period occurred in 12.6% and 27.2% of subjects in the Lung Health Study and CanCOLD study, respectively. The risk of diagnostic instability was greatest for subjects whose baseline FEV 1 /FVC value was closest to the diagnostic threshold, and the risk of diagnostic reversal was greatest for subjects who quit smoking during the study. A single post-bronchodilator spirometric assessment may not be reliable for diagnosing COPD in patients with mild to moderate airflow obstruction at baseline.

Do epigenetic events take place in the vastus lateralis of patients with mild chronic obstructive pulmonary disease?

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Ester Puig-Vilanova

Full Text Available Muscle dysfunction is a major comorbidity in Chronic Obstructive Pulmonary Disease (COPD. Several biological mechanisms including epigenetic events regulate muscle mass and function in models of muscle atrophy. Investigations conducted so far have focused on the elucidation of biological mechanisms involved in muscle dysfunction in advanced COPD. We assessed whether the epigenetic profile may be altered in the vastus lateralis of patients with mild COPD, normal body composition, and mildly impaired muscle function and exercise capacity. In vastus lateralis (VL of mild COPD patients with well-preserved body composition and in healthy age-matched controls, expression of DNA methylation, muscle-enriched microRNAs, histone acetyltransferases (HTAs and deacetylases (HDACs, protein acetylation, small ubiquitin-related modifier (SUMO ligases, and muscle structure were explored. All subjects were clinically evaluated. Compared to healthy controls, in the VL of mild COPD patients, muscle function and exercise capacity were moderately reduced, DNA methylation levels did not differ, miR-1 expression levels were increased and positively correlated with both forced expiratory volume in one second (FEV1 and quadriceps force, HDAC4 protein levels were increased, and muscle fiber types and sizes were not different. Moderate skeletal muscle dysfunction is a relevant feature in patients with mild COPD and preserved body composition. Several epigenetic events are differentially expressed in the limb muscles of these patients, probably as an attempt to counterbalance the underlying mechanisms that alter muscle function and mass. The study of patients at early stages of their disease is of interest as they are a target for timely therapeutic interventions that may slow down the course of the disease and prevent the deleterious effects of major comorbidities.

Developmental Exposure to Mild Variable Stress: Adult ...

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In utero exposure to mild variable stress has been reported to influence learning and memory formation in offspring. Our research aims to examine whether nonchemical environmental stressors will exacerbate effects to chemical exposure. This study utilized a varying stress paradigm to simulate human psychosocial stress incurred during and after pregnancy to identify phenotypic learning changes in adult offspring that are potential stress markers. We additionally wanted to compare these behavioral outcomes to rat performance induced by perinatal exposure to manganese (Mn), a neurotoxic environmental element, at 2 or 5 g/l in drinking water throughout gestation and lactation. Pregnant Long Evans rats were exposed to an unpredictable series of mild stressful events which had previously been shown to increase maternal corticosterone levels. Nonchemical stressors were presented from GD 13 through GD 21 and included varying noise, light, housing, and confinement during both sleep and wake cycles. A subgroup of offspring was also exposed to periods of maternal separation. Starting at PND 97 offspring were trained with a trace fear conditioning protocol whereby rats were exposed to a compound cue (light and tone) followed by 30 seconds (trace period) and a mild foot shock (1mA, 0.5 seconds). Five paired training sessions occurred on the first day. The following day, context and cue learning were assessed by measuring motor activity. Preliminary data suggests adu

Clinical comparison of 99mTc exametazime and 123I Ioflupane SPECT in patients with chronic mild traumatic brain injury.

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Newberg, Andrew B; Serruya, Mijail; Gepty, Andrew; Intenzo, Charles; Lewis, Todd; Amen, Daniel; Russell, David S; Wintering, Nancy

2014-01-01

This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population. Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both (99m)Tc exametazime to measure cerebral blood flow (CBF) and (123)I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (pTBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.

The management of patients with mild hepatitis C

NARCIS (Netherlands)

Verslype, C.; Michielsen, P.; Adler, M.; Orlent, H.; Sprengers, D.; Delwaide, J.; D'Heygere, F.; Langlet, Ph; Brenard, R.; Colle, I.; Reynaert, H.; Stärkel, P.; Henrion, J.

2005-01-01

Infection with the hepatitis C virus (HCV) represents an important public health problem and is a leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is a heterogeneous disease. Many patients have mild disease at presentation but not all of them will

Eliminating Unpredictable Variation through Iterated Learning

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Smith, Kenny; Wonnacott, Elizabeth

2010-01-01

Human languages may be shaped not only by the (individual psychological) processes of language acquisition, but also by population-level processes arising from repeated language learning and use. One prevalent feature of natural languages is that they avoid unpredictable variation. The current work explores whether linguistic predictability might…

Desipramine rescues age-related phenotypes in depression-like rats induced by chronic mild stress.

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Xie, Xiaoxian; Chen, Yangyang; Wang, Qi; Shen, Qichen; Ma, Lingyan; Huang, Liangfeng; Wu, Tao; Fu, Zhengwei

2017-11-01

Our previous finding demonstrates that major depressive disorder can mediate accelerated aging in rats. Desipramine is a typical tricyclic antidepressant, and can provide neuroprotection and counteract depression-like behaviors. However, whether desipramine can rescue age-related phenotypes in depressed individuals is not understood. In the present study, we investigated the physiological function of desipramine on rescuing the age-related phenotypes in these animals. The rats were induced by chronic mild stress paradigm, and the depression-like behaviors of rats were detected by sucrose intake test, open field test (OFT) and forced swimming test (FST). Then the depressed rats were treated by desipramine. Desipramine administration was effective in counteracting depression-like behaviors by increasing the sucrose solution intake, reducing the immobility time in the FST, and increasing total distance travelled and numbers of grid line crossed in the OFT. Moreover, desipramine treatment was able to reduce the oxidative damage to rat liver, and to increase the expression of telomerase reverse transcriptase (TERT), leading to correspondingly restored telomerase activity. Our findings identify that one function of desipramine may partly be to rescue age-related phenotypes in depressed individuals induced by chronic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

5-HT2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

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Minal Jaggar

2017-12-01

Full Text Available Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin2A (5-HT2A receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS on depression-like behavior, serum metabolic measures, and gene expression in stress-associated neurocircuitry of the prefrontal cortex (PFC and hippocampus in 5-HT2A receptor knockout (5-HT2A−/− and wild-type mice of both sexes. While 5-HT2A−/− male and female mice exhibited a baseline reduced anxiety-like state, this did not alter the onset or severity of behavioral despair during and at the cessation of CUS, indicating that these mice can develop stress-evoked depressive behavior. Analysis of metabolic parameters in serum revealed a CUS-evoked dyslipidemia, which was abrogated in 5-HT2A−/− female mice with a hyperlipidemic baseline phenotype. 5-HT2A−/− male mice in contrast did not exhibit such a baseline shift in their serum lipid profile. Specific stress-responsive genes (Crh, Crhr1, Nr3c1, and Nr3c2, trophic factors (Bdnf, Igf1 and immediate early genes (IEGs (Arc, Fos, Fosb, Egr1-4 in the PFC and hippocampus were altered in 5-HT2A−/− mice both under baseline and CUS conditions. Our results support a role for the 5-HT2A receptor in specific metabolic and transcriptional, but not behavioral, consequences of CUS, and highlight that the contribution of the 5-HT2A receptor to stress-evoked changes is sexually dimorphic. Keywords: 5-HT2A−/− mice, Prefrontal cortex, Hippocampus, Gene expression, Sexual dimorphism, Despair

DISTURBANCES OF BIOLOGICAL RHYTHMS IN A RAT CHRONIC MILD STRESS MODEL OF DEPRESSION

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Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena

validated animal model of depression, the chronic mild stress model (CMS). Depression-like and control rats were killed by decapitation within 24 h. Trunk blood, brain and liver tissue were collected. The quantitative amount of plasma corticosterone and melatonin were measured using an ELISA and RIA kit...... that depression-like animals showed an abnormal circadian rhythm in the liver and in subregions of the rat brains related to depression. However, the SCN was partly protected against stress. We found an increased level of corticosteron and melatonin, in the depression-like animals as well as a shifted circadian......Aim: The focus of this project is to identify biomarkers related to circadian disturbances in major depressive disorder. Background: A large body of clinical data from depressed individuals showed that sleep, temperature, hormones, physiological states and moodchanges are consistent...

Spirituality, Illness Unpredictability, and Math Anxiety Effects on Negative Affect and Affect-Management Coping for Individuals Diagnosed with Alpha-1 Antitrypsin Deficiency.

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Worthington, Amber K; Parrott, Roxanne L; Smith, Rachel A

2018-04-01

A growing number of genetic tests are included in diagnostic protocols associated with many common conditions. A positive diagnosis associated with the presence of some gene versions in many instances predicts a range of possible outcomes, and the uncertainty linked to such results contributes to the need to understand varied responses and plan strategic communication. Uncertainty in illness theory (UIT; Mishel, 1988, 1990) guided the investigation of efforts to feel in control and hopeful regarding genetic testing and diagnosis for alpha-1 antitrypsin deficiency (AATD). Participants included 137 individuals with AATD recruited from the Alpha-1 Research Registry who were surveyed about their subjective numeracy, anxiety about math, spirituality, perceptions of illness unpredictability, negative affect regarding genetic testing, and coping strategies about a diagnosis. Results revealed that experiencing more fear and worry contributed both directly and indirectly to affect-management coping strategies, operating through individual perceptions of illness unpredictability. The inability to predict the symptoms and course of events related to a genetic illness and anxiety regarding math heightened fear and worry. Spirituality lessened both illness unpredictability and negative affective responses to a diagnosis. Results affirm the importance of clinician and counselor efforts to incorporate attention to patient spirituality. They also illustrate the complexity associated with strategic efforts to plan communication about the different versions of a gene's effects on well-being, when some versions align with mild health effects and others with severe effects.

Ex-vivo diffusion MRI reveals microstructural alterations in stress-sensitive brain regions: A chronic mild stress recovery study

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Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove

Depression is a leading cause of disability worldwide and causes significant microstructural alterations in stress-sensitive brain regions. However, the potential recovery of these microstructural alterations has not previously been investigated, which we, therefore, set out to do using diffusion...... MRI (d-MRI) in the chronic mild stress (CMS) rat model of depression. This study reveals significant microstructural alterations after 8 weeks of recovery, in the opposite direction to change induced by stress in the acute phase of the experiment. Such findings may be useful in the prognosis...... of depression or for monitoring treatment response....

A representative prescription for emotional disease, Ding-Zhi-Xiao-Wan restores 5-HT system deficit through interfering the synthesis and transshipment in chronic mild stress-induced depressive rats.

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Dong, Xian-Zhe; Li, Zhao-Liang; Zheng, Xiao-Li; Mu, Li-Hua; Zhang, Gang-qiang; Liu, Ping

2013-12-12

Ding-Zhi-Xiao-Wan (DZ, also known as Kai-Xin-San) is a famous traditional Chinese medicine used for the treatment of emotional disease. Previously, we have found that in a variety of animal models of depression (such as tail suspension model, model of chronic fatigue and forced swimming model) DZ demonstrated significant antidepressant behavior and promoted the production of 5-hydroxytryptamine (5-HT). However, the mechanisms of 5-HT regulation are still unclear. Therefore, the current study is designed to further investigate the antidepressant effect of DZ by observing its influence on 5-HT synthesis, metabolism, transport and other key links, so as to clarify the molecular mechanism of its 5-HT regulation. Solitary rising combined with the chronic unpredictable mild stress (CMS) was used to establish the rat model of depression. The rats were given DZ for 3 weeks, the behavior change and the following items in hippocampus and prefrontal cortex were detected simultaneously: 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC), monoamine oxidase (MAO) and 5-HT transporter (5-HTT) were observed. Our results showed that treatment with the DZ significantly improved the behavior and simultaneously increased the 5-HT level in the hippocampus, prefrontal cortex tissues and hippocampus extracellular of depressive rats. In future studies revealed that DZ could significantly increase the protein and mRNA expression of the key enzymes TPH during the 5-HT synthesis process in the hippocampus and prefrontal cortex of the depressed rats, and suppress the expression of 5-HTT protein and mRNA at the same time. But it had no effects on MAO-A and MAO-B activities. We believe that antidepressant effect of DZ is caused by the increase of 5-HT synthesis and reduction of 5-HT re-uptake, and eventually increase the content of 5-HT in the brain and the synaptic gaps. © 2013 Published by Elsevier Ireland Ltd.

Increase of mild disability in Japanese elders: A seven year follow-up cohort study

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Okochi Jiro

2005-05-01

Full Text Available Abstract Background Japan has the highest life expectancy in the world. In a 2002 census government report, 18.5% of Japanese were 65 years old and over and 7.9% were over 75 years old. In this ageing population, the increase in the number of dependent older persons, especially those with mild levels of disability, has had a significant impact on the insurance budget. This study examines the increase of mild disability and its related factors. Methods All community-dwelling residents aged 65 and over and without functional decline (n = 1560, of Omishima town, Japan, were assessed in 1996 using a simple illustrative measure, "the Typology of the Aged with Illustrations" to establish a baseline level of function and were followed annually until 2002. The prevalence and incidence of low to severe disability, and their association with chronic conditions present at the commencement of the study, was analyzed. A polychotomous logistic regression model was constructed to estimate the association of each chronic condition with two levels of disability. Results An increase in mild functional decline was more prevalent than severe functional decline. The accumulation of mild disability was more prominent in women. The major chronic conditions associated with mild disability were chronic arthritis and diabetes in women, and cerebrovascular accident and malignancy in men. Conclusion This study showed a tendency for mild disability prevalence to increase in Japanese elders, and some risk factors were identified. As mild disability increasingly prevalent, these findings will help determine priorities for its prevention in Japanese elders.

Some remarks on the compatibility between determinism and unpredictability.

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Franceschelli, Sara

2012-09-01

Determinism and unpredictability are compatible since deterministic flows can produce, if sensitive to initial conditions, unpredictable behaviors. Within this perspective, the notion of scenario to chaos transition offers a new form of predictability for the behavior of sensitive to initial condition systems under the variation of a control parameter. In this paper I first shed light on the genesis of this notion, based on a dynamical systems approach and on considerations of structural stability. I then suggest a link to the figure of epigenetic landscape, partially inspired by a dynamical systems perspective, and offering a theoretical framework to apprehend developmental noise. Copyright © 2012 Elsevier Ltd. All rights reserved.

Living with advanced Parkinson's disease: a constant struggle with unpredictability.

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Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen

2011-02-01

This paper is a report of an exploration of patients' lifeworld and way of managing life with advanced Parkinson's disease prior to Deep Brain Stimulation and what they expect from life following this treatment. Parkinson's disease is a progressive neurodegenerative disease, which is initially well-treated with L-dopa. Living with Parkinson's disease means living with the experience of continuous loss of independence and self-esteem and unpredictable ON/OFF phenomena. Thus, in the advanced stage of the disease, treatment with Deep Brain Stimulation may become relevant. Eleven patients eligible for Deep Brain Stimulation were interviewed prior to treatment. Data were collected in 2007 and analysed according to the hermeneutic phenomenological methodology of van Manen, using the four existentials as analytic tools. Living with advanced Parkinson's disease can be described as the experience of living with and managing unpredictability. The disease gradually took over, and participants had to struggle with unpredictability on a daily basis. Themes in relation to this were: The body - setting the agenda, Always a struggle to be on time, Living in dependence and compromise - being a burden, and Living with restrained space and changes in social life. Parkinson's disease leads to profound bodily restrictions. Living with an unpredictable body affects all aspects of life, and nurses need to be aware of the impact the disease has on the entire lifeworld, and how this may affect the way treatment is perceived. © 2010 Blackwell Publishing Ltd.

Functional states of rat cortical circuits during the unpredictable availability of a reward-related cue.

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Fernández-Lamo, Iván; Sánchez-Campusano, Raudel; Gruart, Agnès; Delgado-García, José M

2016-11-21

Proper performance of acquired abilities can be disturbed by the unexpected occurrence of external changes. Rats trained with an operant conditioning task (to press a lever in order to obtain a food pellet) using a fixed-ratio (1:1) schedule were subsequently placed in a Skinner box in which the lever could be removed randomly. Field postsynaptic potentials (fPSPs) were chronically evoked in perforant pathway-hippocampal CA1 (PP-CA1), CA1-subiculum (CA1-SUB), CA1-medial prefrontal cortex (CA1-mPFC), mPFC-nucleus accumbens (mPFC-NAc), and mPFC-basolateral amygdala (mPFC-BLA) synapses during lever IN and lever OUT situations. While lever presses were accompanied by a significant increase in fPSP slopes at the five synapses, the unpredictable absence of the lever were accompanied by decreased fPSP slopes in all, except PP-CA1 synapses. Spectral analysis of local field potentials (LFPs) recorded when the animal approached the corresponding area in the lever OUT situation presented lower spectral powers than during lever IN occasions for all recording sites, apart from CA1. Thus, the unpredictable availability of a reward-related cue modified the activity of cortical and subcortical areas related with the acquisition of operant learning tasks, suggesting an immediate functional reorganization of these neural circuits to address the changed situation and to modify ongoing behaviors accordingly.

Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

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Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

2010-12-17

Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Unpredictable Variable Prenatal Stress Programs Expression of Genes Involved in Appetite Control and Energy Expenditure

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Moyer, E. L.; Al-Shayeb, B.; Baer, L. A.; Ronca, A. E.

2016-01-01

Exposure to stress in the womb shapes neurobiological and physiological outcomes of offspring in later life, including body weight regulation and metabolic profiles. Our previous work utilizing a centrifugation-induced hyper-gravity demonstrated significantly increased (8-15%) body mass in male, but not female, rats exposed throughout gestation to chronic 2-g from conception to birth. We reported a similar outcome in adult offspring exposed throughout gestation to Unpredictable Variable Prenatal Stress (UVPS). Here we examine gene expression changes and the plasma of animals treated with our UVPS model to identify a potential role for prenatal stress in this hypergravity programming effect. Specifically we focused on appetite control and energy expenditure pathways in prenatally stressed adult (90-day-old) male Sprague-Dawley rats.

Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats.

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Firoozmand, Lília Taddeo; Sanches, Andrea; Damaceno-Rodrigues, Nilsa Regina; Perez, Juliana Dinéia; Aragão, Danielle Sanches; Rosa, Rodolfo Mattar; Marcondes, Fernanda Klein; Casarini, Dulce Elena; Caldini, Elia Garcia; Cunha, Tatiana Sousa

2018-04-20

To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade.

ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress.

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Bai, Yin-Yin; Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Kang, Zhi-Long; Zhou, Li; Liu, Dennis; Zeng, Yue-Qing; Wang, Ting-Hua; Tian, Chang-Fu; Liao, Hong; Bobrovskaya, Larisa; Zhou, Xin-Fu

2016-11-01

Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. Brain-derived neurotropic factor (BDNF) has long been investigated for its positive role in regulation of mood, although the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced upregulation of proBDNF was abolished by chronic administration of fluoxetine. We then established a rat model of UCMS and found that the expression of proBDNF/p75 NTR /sortilin was upregulated, whereas the expression of mature BDNF and TrkB was downregulated in both neocortex and hippocampus of chronically stressed rats. Finally, we found that the injection of anti-proBDNF antibody via intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) approaches into the UCMS rats significantly reversed the stress-induced depression-like behavior and restored the exploratory activity and spine growth. Although intramuscular injection of AAV-proBDNF did not exacerbate the UCMS-elicited rat mood-related behavioral or pathological abnormalities, i.c.v. injection of AAV-proBDNF increased the depression-like behavior in naive rats. Our findings suggest that proBDNF plays a role in the development of chronic stress-induced mood disturbances in rodents. Central (i.c.v.) or peripheral (i.p.) inhibition of proBDNF by injecting specific anti-proBDNF antibodies may provide a novel therapeutic approach for the treatment of stress-related mood disorders.

Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress.

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Chen, Guotao; Yang, Baibing; Chen, Jianhuai; Zhu, Leilei; Jiang, Hesong; Yu, Wen; Zang, Fengchao; Chen, Yun; Dai, Yutian

2018-02-01

Non-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms. To develop a noED animal model based on chronic mild stress and investigate brain activity changes. We used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state. The apomorphine test and sexual behavior test were used to select male rats with ED. Rats with depression and ED were considered to have noED. Blood oxygen level-dependent-based resting-state functional magnetic resonance imaging (fMRI) studies were conducted on these rats, and the amplitude of low-frequency fluctuations and functional connectivity were analyzed to determine brain activity changes. The sexual behavior test and resting-state fMRI were used for outcome measures. The induction of depression was confirmed by the sucrose consumption test. A low intromission ratio and increased mount and intromission latencies were observed in male rats with depression. No erection was observed in male rats with depression during the apomorphine test. Male rats with depression and ED were considered to have noED. The possible central pathologic mechanism shown by fMRI involved the amygdaloid body, dorsal thalamus, hypothalamus, caudate-putamen, cingulate gyrus, insular cortex, visual cortex, sensory cortex, motor cortex, and cerebellum. Similar findings have been found in humans. The present study provided a novel noED rat model for further research on the central mechanism of noED. The present study developed a novel noED rat model and analyzed brain activity changes based at fMRI. The observed brain activity alterations might not extend to humans. The present study developed a novel noED rat model with brain activity alterations related to sexual arousal and erection, which will be helpful for further research involving the central mechanism of noED. Chen

Skin Autofluorescence and Subclinical Atherosclerosis in Mild to Moderate Chronic Kidney Disease: A Case-Control Study.

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Sánchez, Enric; Betriu, Àngels; Arroyo, David; López, Carolina; Hernández, Marta; Rius, Ferran; Fernández, Elvira; Lecube, Albert

2017-01-01

Advanced glycation end-products (AGEs) are increased and predict mortality in patients with chronic kidney disease (CKD) who are undergoing hemodialysis, irrespective of the presence of type 2 diabetes. However, little information exits about the relationship between AGEs and subclinical atherosclerosis at the early stages of CKD. A case-control study was performed including 87 patients with mild-to-moderate stages of CKD (glomerular filtration rate from 89 to 30 ml/min/per 1.73m2) and 87 non-diabetic non-CKD subjects matched by age, gender, body mass index, and waist circumference. Skin autofluorescence (AF), a non-invasive assessment of AGEs, was measured. The presence of atheromatous disease in carotid and femoral arteries was evaluated using vascular ultrasound, and vascular age and SCORE risk were estimated. Patients with mild-to-moderate stages of CKD showed an increase in skin AF compared with control subjects (2.5±0.6 vs. 2.2±0.4 AU, pskin AF value >2.0 AU was accompanied by a 3-fold increased risk of detecting the presence of an atheromathous plaque (OR 3.0, 95% CI 1.4-6.5, p = 0.006). When vascular age was assessed through skin AF, subjects with CKD were almost 12 years older than control subjects (70.3±25.5 vs. 58.5±20.2 years, p = 0.001). Skin AF was negatively correlated with glomerular filtration rate (r = -0.354, pskin AF (R2 = 0.289, pSkin AF is elevated in patients with mild-to-moderate CKD compared with control subjects. This finding may be independently associated with the glomerular filtration rate and the presence of subclinical atheromatous disease. Therefore, the use of skin AF may help to accurately evaluate the real cardiovascular risk at the early stages of CKD.

The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

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Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

2018-01-09

Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that

Steroid-Responsive Chronic Schizophreniform Syndrome in the Context of Mildly Increased Antithyroid Peroxidase Antibodies

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Ludger Tebartz van Elst

2017-04-01

Full Text Available BackgroundSchizophreniform syndromes can be divided into primary forms from polygenic causes or secondary forms due to immunological, epileptiform, monogenic, or degenerative causes. Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT is a secondary immunological form associated with increased thyroid antibodies, such as antithyroid peroxidase antibodies and shows a good response to corticosteroids.Case presentationWe present the case of a 41-year-old woman suffering from a schizophreniform syndrome. Starting at the age of 35, she developed psychotic exacerbations with formal thought disorder, acoustic hallucinations, cenesthopathic experiences, and loss of ego boundaries. At the same time, she began to suffer from chronic sexual delusions and olfactory hallucinations, which did not respond to neuroleptic medication. Her levels of antithyroid peroxidase antibodies were slightly increased, and the blood–brain barrier was disturbed. An electroencephalogram (EEG showed intermittent generalized slowing, and cerebral magnetic resonance imaging (cMRI depicted mild temporolateral atrophy. High-dose corticosteroid treatment led to convincing improvement of attentional performance and the disappearance of delusions and olfactory hallucinations.ConclusionSREAT can mimic typical symptoms of schizophreniform syndromes. The increased titer of antithyroid peroxidase antibodies in combination with the EEG slowing, blood–brain barrier dysfunction, and the cMRI alterations were the basis for suspecting an immunological cause in our patient. Chronic delusions, olfactory hallucinations, and cognitive deficits were successfully treated with corticosteroids. The occurrence of secondary immunological forms of schizophreniform syndromes demonstrates the need for innovative immunosuppressive treatment options.

Expert Statement on the Single-Agent Use of Inhaled Bronchodilator in the Treatment of Stable Mild-Moderate Chronic Obstructive Pulmonary Disease.

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Riesco Miranda, Juan Antonio; Alcázar, Bernardino; Alfageme, Inmaculada; Casanova, Ciro; Celli, Bartolomé; de-Torres, Juan P; Jiménez Ruiz, Carlos A

2017-10-01

To describe the evidence- and experience-based expert consensus on the use of single-agent bronchodilators in patients with stable mild-moderate chronic obstructive pulmonary disease (COPD). Using Delphi methodology, a panel of 7 respiratory medicine experts was established, who, in the first nominal group meeting defined the scope, users, and document sections. The panel drew up 14 questions on the use of single-agent bronchodilators in patients with mild-moderate stable COPD to be answered with a systematic review of the literature. The results of the review were discussed in a second nominal group meeting and 17 statements were generated. Agreement/disagreement with the statements was tested among16 different experts including respiratory medicine experts and primary care physicians. Statements were scored from1 (total disagreement) to10 (total agreement). Agreement was considered if at least 70% voted ≥7. The level of evidence and grade of recommendation of the systematic literature review was assessed using the Oxford Centre for Evidence-based Medicine levels. A total of 12 of the 17 statements were selected. Specific statements were generated on different profiles of patients with stable mild-moderate COPD in whom single-agent bronchodilators could be prescribed. These statements on the use of single-agent bronchodilators might improve the outcomes and prognosis of patients with stable mild-moderate COPD. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice.

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Shang, Xueliang; Shang, Yingchun; Fu, Jingxuan; Zhang, Tao

2017-08-01

The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild stress (CUMS) and isolated feeding. Mice were exposed to CUMS continued for 28 days, while nicotine (0.2 mg/kg) was also administrated for 28 days. Weight and sucrose consumption were measured during model establishing period. The anxiety and behavioral despair were analyzed using the forced swim test (FST) and open-field test (OFT). Spatial cognition was evaluated using Morris water maze (MWM) test. Following behavioral assessment, both long-term potentiation (LTP) and depotentiation (DEP) were recorded in the hippocampal dentate gyrus (DG) region. Both synaptic and Notch1 proteins were measured by Western. Nicotine increased stressed mouse's sucrose consumption. The MWM test showed that spatial learning and reversal learning in stressed animals were remarkably affected relative to controls, whereas nicotine partially rescued cognitive functions. Additionally, nicotine considerably alleviated the level of anxiety and the degree of behavioral despair in stressed mice. It effectively mitigated the depression-induced impairment of hippocampal synaptic plasticity, in which both the LTP and DEP were significantly inhibited in stressed mice. Moreover, nicotine enhanced the expression of synaptic and Notch1 proteins in stressed animals. The results suggest that nicotine ameliorates the depression-like symptoms and improves the hippocampal synaptic plasticity closely associated with activating transmembrane ion channel receptors and Notch signaling components. Graphical Abstract ᅟ.

The Spectrum of Disease in Chronic Traumatic Encephalopathy

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McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

2013-01-01

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…

Unpredictable drug reaction in a child with Cornelia de Lange syndrome.

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Stevic, Marija; Milojevic, Irina; Bokun, Zlatko; Simic, Dusica

2015-02-01

Preoperative use of midazolam sedation is mandatory during induction of anesthesia in noncooperative and hyperactive children to prevent possible obstacles. Unusual drug reactions rarely occur in patients undergoing anesthesia or in intensive care unit. This report describes an unpredictable drug reaction after a routine midazolam premedication in a patient with no history of allergy. There has been no literature data yet to show that midazolam can provoke respiratory problems in patients with Cornelia de Lange Syndrome. In our opinion midazolam should be avoided in patients with Cornelia de Lange Syndrome, which we enforced after first unpredictable reaction.

Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease

DEFF Research Database (Denmark)

Pitt, Bertram; Kober, Lars; Ponikowski, Piotr

2013-01-01

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroida......Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non......-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD)....

The effect of unpredictable early childhood environments on parenting in adulthood.

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Szepsenwol, Ohad; Simpson, Jeffry A; Griskevicius, Vladas; Raby, K Lee

2015-12-01

Life history theory suggests that individual differences in parenting are partially rooted in environmental conditions experienced early in life. Whereas certain conditions should promote increased investment in parenting, unpredictable and/or harsh environments should promote decreased investment in parenting, especially in men. We tested this hypothesis in 3 studies. In Study 1a, we conducted analyses on 112 parents taking part in the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA), all of whom have been continuously studied starting before they were born. Parenting orientations were assessed at age 32 via an interview. Findings showed that experiencing more unpredictability at ages 0-4 (i.e., frequent changes in parental employment status, cohabitation status, and residence) prospectively forecasted more negative parenting orientations among men, but not women. This effect was serially mediated by lower early maternal supportive presence measured at ages 0-4 and insecure attachment assessed at ages 19 and 26. In Study 1b, we replicated these findings on 96 parents from the MLSRA using behavioral observations of their parental supportive presence. In Study 2, we replicated the effect of early-life unpredictability on men's parenting orientations with a sample of 435 parents. This effect was mediated by adult attachment anxiety and avoidance. Across all studies, greater early-life harshness (low socioeconomic status [SES]) did not predict adult parenting outcomes. These findings suggest that greater early-life unpredictability may be conveyed to children through less supportive parenting, which results in insecure attachment representations in adulthood. Among men, this process culminates in less positive adult parenting orientations and less supportive parenting. (c) 2015 APA, all rights reserved).

Major depressive disorder mediates accelerated aging in rats subjected to chronic mild stress.

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Xie, Xiaoxian; Chen, Yangyang; Ma, Lingyan; Shen, Qichen; Huang, Liangfeng; Zhao, Binggong; Wu, Tao; Fu, Zhengwei

2017-06-30

Major depressive disorder (MDD) has a complex etiology and is characterized by a change in mood and psychophysiological state. MDD has been shown to mediate accelerated biological aging in patients, although the underlying mechanism is not well understood. In the present study, we used a chronic mild stress (CMS) paradigm to induce anhedonia, one of the main symptoms of MDD. CMS induced depression-like symptoms in rats, including reduced sucrose preference and increased immobility time in the forced swim test. Moreover, stressed rats travelled a shorter total distance, had fewer grid line crossings, and spent less time in the outer zone in the open field test than controls. CMS altered the levels of 5-hydroxytryptophan, dopamine, and corticosterone in the serum and hippocampus (P<0.05); these rats also exhibited impaired liver function, decreased telomerase activity, and telomere shortening, which was associated with increased oxidative damage along with decreased superoxide dismutase and glutathione reductase activities. Mitochondria in CMS-treated rats showed ultrastructural damage as well as reduced DNA content and integrity. These findings provide physiological and cellular evidence that the MDD can mediate accelerated aging in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

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Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

2016-05-24

Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

Chronic dry cough: Diagnostic and management approaches

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Ashok Mahashur

2015-01-01

Full Text Available Cough is the most common symptom for which medical treatment is sought in the outpatient setting. Chronic dry cough poses a great diagnostic and management challenge due to myriad etiologies. Chronic cough has been commonly considered to be caused by gastroesophageal reflux, post-nasal drip or asthma. However, recent evidences suggest that many patients with these conditions do not have cough, and in those with cough, the response to specific treatments is unpredictable at best. This raises questions about the concept of a triad of treatable causes for chronic cough. This article discusses the mechanism and etiology of cough, along with recent advances in the field of cough, highlighting some of the diagnostic and management challenges.

Efficacy and safety of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis: a randomized, double-blind trial.

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Hordinsky, Maria; Fleischer, Alan; Rivers, Jason K; Poulin, Yves; Belsito, Donald; Hultsch, Thomas

2010-08-01

Chronic hand dermatitis is common and difficult to treat. Our aim was to assess the efficacy of pimecrolimus cream 1% in mild-to-moderate chronic hand dermatitis. Adult patients (n = 652) were randomized to pimecrolimus 1% or vehicle cream twice daily with overnight occlusion for 6 weeks, followed by a 6-week open-label pimecrolimus treatment. Primary efficacy was 5-point Investigators' Global Assessment of prospectively selected 'target hand' as treatment success (Investigators' Global Assessment 0 or 1) and treatment failure. Pruritus relief was also assessed. Following double-blind phase treatment, target hand treatment success was achieved in 29.8 and 23.2% of the patients in the pimecrolimus and vehicle groups, respectively (p = 0.057). The proportion of patients experiencing pruritus relief was significantly higher in the pimecrolimus group compared to the vehicle group at all time points throughout the double-blind phase. The groups were comparable with respect to treating disease signs. Pruritus relief, however, was significantly greater in the pimecrolimus group. Copyright 2010 S. Karger AG, Basel.

Treatment of a mild chronic case of ciguatera fish poisoning with intravenous mannitol, a case study.

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Mitchell, Gary

2005-03-01

This article describes a recent case of ciguatera poisoning treated with intravenous mannitol. Mannitol has been used with good effect in non-controlled studies in acutely severely poisoned patients, but is not described in the treatment of chronic or milder poisoning. Our patient was a 35-year-old Niuean man who had eaten a ciguatoxic fish two weeks previously. His symptoms were not severe but were very unpleasant and restricted his ability to work. He was given a single dose of mannitol (0.66g/kg) as an intravenous infusion over two hours. His symptoms dramatically improved within 24 hours, and within a few days he felt virtually back to his former self. He experienced no side effects to the mannitol. It is suggested that intravenous mannitol may prove to be a useful treatment for mild to moderate ciguatera poisoning, and for patients who present late for treatment.

Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat.

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Lange, M D; Daldrup, T; Remmers, F; Szkudlarek, H J; Lesting, J; Guggenhuber, S; Ruehle, S; Jüngling, K; Seidenbecher, T; Lutz, B; Pape, H C

2017-10-01

The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with unpredictable environmental contingencies. Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the extended amygdala have been suggested keys to the control of phasic and sustained states of fear, although the underlying synaptic pathways and mechanisms remain poorly understood. Here, we show that the endocannabinoid system acting in synaptic circuits of the extended amygdala can explain the fear response profile during exposure to unpredictable threat. Using fear training with predictable or unpredictable cues in mice, combined with local and cell-type-specific deficiency and rescue of cannabinoid type 1 (CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis (BNST) are both necessary and sufficient for the shift from phasic to sustained fear in response to an unpredictable threat. These results thereby identify the causal role of a defined protein in a distinct brain pathway for the temporal development of a sustained state of anxious apprehension during unpredictability of environmental influences, reminiscent of anxiety symptoms in humans.

How does early maternal separation and chronic stress in adult rats affect the immunoreactivity of serotonergic neurons within the dorsal raphe nucleus?

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Pollano, Antonella; Trujillo, Verónica; Suárez, Marta M

2018-01-01

Vulnerability to emotional disorders like depression derives from interactions between early and late environments, including stressful conditions. The serotonin (5HT) system is strongly affected by stress and chronic unpredictable stress can alter the 5HT system. We evaluated the distribution of active serotonergic neurons in the dorsal raphe nucleus (DR) through immunohistochemistry in maternally separated and chronically stressed rats treated with an antidepressant, tianeptine, whose mechanism of action is still under review. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50-74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle. We found an interaction between the effects of MS and chronic unpredictable stress on Fos-5HT immunoreactive cells at mid-caudal level of the DR. MS-chronically stressed rats showed an increase of Fos-5HT immunoreactive cells compared with AFR-chronically stressed rats. The ventrolateral (DRL/VLPAG) and dorsal (DRD) subdivisions of the DR were significantly more active than the ventral part (DRV). At the rostral level of the DR, tianeptine decreased the number of Fos-5HT cells in DR in the AFR groups, both unstressed and stressed. Overall, our results support the idea of a match in phenotype exhibited when the early and the adult environment correspond.

Cut-Off Points for Mild, Moderate, and Severe Pain on the Numeric Rating Scale for Pain in Patients with Chronic Musculoskeletal Pain : Variability and Influence of Sex and Catastrophizing

NARCIS (Netherlands)

Boonstra, Anne M; Stewart, Roy E; Köke, Albère J A; Oosterwijk, René F A; Swaan, Jeannette L; Schreurs, Karlein M G; Schiphorst Preuper, Henrica R

2016-01-01

Objectives: The 0-10 Numeric Rating Scale (NRS) is often used in pain management. The aims of our study were to determine the cut-off points for mild, moderate, and severe pain in terms of pain-related interference with functioning in patients with chronic musculoskeletal pain, to measure the

Opposing Subjective Temporal Experiences in Response to Unpredictable and Predictable Fear-Relevant Stimuli

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Qian Cui

2018-03-01

Full Text Available Previous studies have found that the durations of fear-relevant stimuli were overestimated compared to those of neutral stimuli, even when the fear-relevant stimuli were only anticipated. The current study aimed to investigate the effect of the predictability of fear-relevant stimuli on sub-second temporal estimations. In Experiments 1a and 1b, a randomized design was employed to render the emotional valence of each trial unpredictable. In Experiments 2a and 2b, we incorporated a block design and a cueing paradigm, respectively, to render the emotional stimuli predictable. Compared with the neutral condition, the estimated blank interval was judged as being shorter under the unpredictable fear-relevant condition, while it was judged as being longer under the predictable fear-relevant condition. In other words, the unpredictable and predictable fear-relevant stimuli led to opposing temporal distortions. These results demonstrated that emotions modulate interval perception during different time processing stages.

A starch, glycyrretinic, zinc oxide and bisabolol based cream in the treatment of chronic mild-to-moderate atopic dermatitis in children: a three-center, assessor blinded trial.

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Licari, Amelia; Ruffinazzi, Giulia; DE Filippo, Maria; Castagnoli, Riccardo; Marseglia, Alessia; Agostinis, Fabio; Puviani, Mario; Milani, Massimo; Marseglia, Gian L

2017-12-01

Atopic dermatitis (AD) is a very common chronic inflammatory and eczematous skin condition characterized by flares and remissions. Skin barrier alteration or dysfunction is the most relevant patogenetic factor. Topical corticosteroids are the mainstay treatment of AD, especially during flare periods. The daily use of emollients and moisturizers is also considered a relevant adjunctive strategy to improve skin barrier function and skin appearance in AD patients. Long-term use of topical corticosteroids is associated with important drawbacks and side effects. A corticosteroid-free cream containing starch, glycyrretinic acid, zinc oxide and bisabolol (Dermamid™; Difa Cooper, Caronno Pertusella, Varese, Italy) has been designed for the treatment of acute eczematous conditions like diaper dermatitis. However, this formulation could be particularly suitable also for AD. We evaluated in a three-center, assessor-blinded prospective 6-week treatment trial the efficacy and tolerability of this cream in children with chronic mild-to-moderate atopic dermatitis. A total of 30 children (mean age 5 years, 18 males and 12 females) with chronic mild to moderate AD, affecting face, lower and upper limbs or trunk, were enrolled after parents' written informed consent. Exclusion criteria were a condition of immunosuppression, acute flares or a positive history of allergy to one of the components of the cream. The primary outcome was the evolution total eczema severity score (TESS) calculated as the sum of the single eczema severity score for each body area involved. Single area Eczema Severity Score (ESS) was calculated assessing eczema, infiltration, lichenification and scraching lesions using a 4-point scale grade (with 0=no sign, and 4=severe sign). A secondary endpoint was the percentage of subjects reaching at least 50% of TESS reduction at week 6 in comparison with baseline. The TESS was evaluated at baseline and after 3 and 6 weeks of treatment (twice daily application) in an

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.

Science.gov (United States)

Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; Larochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean; Delabesse, Eric

2013-01-31

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. Mutations of key transcription factor in myeloid malignancies.

Actual Therapeutic Indication of an Old Drug: Urea for Treatment of Severely Symptomatic and Mild Chronic Hyponatremia Related to SIADH

Directory of Open Access Journals (Sweden)

Guy Decaux

2014-09-01

Full Text Available Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done.

Cut-Off Points for Mild, Moderate, and Severe Pain on the Numeric Rating Scale for Pain in Patients with Chronic Musculoskeletal Pain: Variability and Influence of Sex and Catastrophizing

NARCIS (Netherlands)

Boonstra, A.M.; Stewart, R.; Koke, A.J.A.; Oosterwijk, R.F.A.; Swaan, J.L.; Schreurs, Karlein Maria Gertrudis; Schiphorst Preuper, H.R.

2016-01-01

Objectives: The 0–10 Numeric Rating Scale (NRS) is often used in pain management. The aims of our study were to determine the cut-off points for mild, moderate, and severe pain in terms of pain-related interference with functioning in patients with chronic musculoskeletal pain, to measure the

The effects of feeding unpredictability and classical conditioning on pre-release training of white-lipped peccary (Mammalia, Tayassuidae.

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Selene S C Nogueira

Full Text Available Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari, a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3 and unpredictable feeding phases (U1- signaled and U2- non-signaled. The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2 than during the other two predictable phases (C1 and C3. The peccaries also spent less time feeding during the signaled unpredictable phase (U1 and the following control phase (C2 than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2, also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild.

The effects of feeding unpredictability and classical conditioning on pre-release training of white-lipped peccary (Mammalia, Tayassuidae).

Science.gov (United States)

Nogueira, Selene S C; Abreu, Shauana A; Peregrino, Helderes; Nogueira-Filho, Sérgio L G

2014-01-01

Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari), a vulnerable Neotropical species, as a model, we evaluated an unpredictable feeding schedule. Associating this with the effect of classical conditioning on behavioral activities, we assessed the inclusion of this approach in pre-release training protocols. The experimental design comprised predictable feeding phases (control phases: C1, C2 and C3) and unpredictable feeding phases (U1- signaled and U2- non-signaled). The animals explored more during the signaled and non-signaled unpredictable phases and during the second control phase (C2) than during the other two predictable phases (C1 and C3). The peccaries also spent less time feeding during the signaled unpredictable phase (U1) and the following control phase (C2) than during the other phases. Moreover, they spent more time in aggressive encounters during U1 than the other experimental phases. However, the animals did not show differences in the time they spent on affiliative interactions or in the body weight change during the different phases. The signaled unpredictability, besides improving foraging behavior, showing a prolonged effect on the next control phase (C2), also increased the competition for food. The signaled feeding unpredictability schedule, mimicking wild conditions by eliciting the expression of naturalistic behaviors in pre-release training, may be essential to fully prepare them for survival in the wild.

Respiratory Consequences of Mild-to-Moderate Obesity: Impact on Exercise Performance in Health and in Chronic Obstructive Pulmonary Disease

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Denis E. O'Donnell

2012-01-01

Full Text Available In many parts of the world, the prevalence of obesity is increasing at an alarming rate. The association between obesity, multiple comorbidities, and increased mortality is now firmly established in many epidemiological studies. However, the link between obesity and exercise intolerance is less well studied and is the focus of this paper. Although exercise limitation is likely to be multifactorial in obesity, it is widely believed that the respiratory mechanical constraints and the attendant dyspnea are important contributors. In this paper, we examined the evidence that critical ventilatory constraint is a proximate source of exercise limitation in individuals with mild-to-moderate obesity. We first reviewed existing information on exercise performance, including ventilatory and perceptual response patterns, in obese individuals who are otherwise healthy. We then considered the impact of obesity in patients with preexisting respiratory mechanical abnormalities due to chronic obstructive pulmonary disease (COPD, with particular reference to the effect on dyspnea and exercise performance. Our main conclusion, based on the existing and rather sparse literature on the subject, is that abnormalities of dynamic respiratory mechanics are not likely to be the dominant source of dyspnea and exercise intolerance in otherwise healthy individuals or in patients with COPD with mild-to-moderate obesity.

Diffusion MRI and MR spectroscopy reveal microstructural and metabolic brain alterations in chronic mild stress exposed rats: A CMS recovery study.

Science.gov (United States)

Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove; Kroenke, Christopher D; Jespersen, Sune Nørhøj

2018-02-15

Chronic mild stress (CMS) induced depression elicits several debilitating symptoms and causes a significant economic burden on society. High variability in the symptomatology of depression poses substantial impediment to accurate diagnosis and therapy outcome. CMS exposure induces significant metabolic and microstructural alterations in the hippocampus (HP), prefrontal cortex (PFC), caudate-putamen (CP) and amygdala (AM), however, recovery from these maladaptive changes are limited and this may provide negative effects on the therapeutic treatment and management of depression. The present study utilized anhedonic rats from the unpredictable CMS model of depression to study metabolic recovery in the ventral hippocampus (vHP) and microstructural recovery in the HP, AM, CP, and PFC. The study employed 1 H MR spectroscopy ( 1 H MRS) and in-vivo diffusion MRI (d-MRI) at the age of week 18 (week 1 post CMS exposure) week 20 (week 3 post CMS) and week 25 (week 8 post CMS exposure) in the anhedonic group, and at the age of week 18 and week 22 in the control group. The d-MRI data have provided an array of diffusion tensor metrics (FA, MD, AD, and RD), and fast kurtosis metrics (MKT, W L and W T ). CMS exposure induced a significant metabolic alteration in vHP, and significant microstructural alterations were observed in the HP, AM, and PFC in comparison to the age match control and within the anhedonic group. A significantly high level of N-acetylaspartate (NAA) was observed in vHP at the age of week 18 in comparison to age match control and week 20 and week 25 of the anhedonic group. HP and AM showed significant microstructural alterations up to the age of week 22 in the anhedonic group. PFC showed significant microstructural alterations only at the age of week 18, however, most of the metrics showed significantly higher value at the age of week 20 in the anhedonic group. The significantly increased NAA concentration may indicate impaired catabolism due to astrogliosis or

Management of mild to moderate acne vulgaris | Malahlela | South ...

African Journals Online (AJOL)

Acne is a chronic inflammatory disease of the pilosebaceous units. It is the most common diagnosis in dermatology and regularly affects adolescents and young adults. Acne can be mild, moderate or severe. Treatment includes topical keratolytics, topical retinoids, antibiotics, hormonal therapy and systemic retinoids in ...

Proteomics portrait of archival lesions of chronic pancreatitis.

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Sheng Pan

Full Text Available Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The etiology is multi-fold, but all lead to progressive scarring and loss of pancreatic function. Early diagnosis is difficult; and the understanding of the molecular events that underlie this progressive disease is limited. In this study, we investigated differential proteins associated with mild and severe chronic pancreatitis in comparison with normal pancreas and pancreatic cancer. Paraffin-embedded formalin-fixed tissues from five well-characterized specimens each of normal pancreas (NL, mild chronic pancreatitis (MCP, severe chronic pancreatitis (SCP and pancreatic ductal adenocarcinoma (PDAC were subjected to proteomic analysis using a "label-free" comparative approach. Our results show that the numbers of differential proteins increase substantially with the disease severity, from mild to severe chronic pancreatitis, while the number of dysregulated proteins is highest in pancreatic adenocarcinoma. Important functional groups and biological processes associated with chronic pancreatitis and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate cell activation, glycoproteins, and inflammatory proteins. Three differential proteins were selected for verification by immunohistochemistry, including collagen 14A1, lumican and versican. Further canonical pathway analysis revealed that acute phase response signal, prothrombin activation pathway, and pancreatic fibrosis/pancreatic stellate cell activation pathway were the most significant pathways involved in chronic pancreatitis, while pathways relating to metabolism were the most significant pathways in pancreatic adenocarcinoma. Our study reveals a group of differentially expressed proteins and the related pathways that may shed light on the pathogenesis of chronic pancreatitis and the common molecular events associated with chronic pancreatitis and pancreatic adenocarcinoma.

Systemic oxidative stress markers in animal model for depression

DEFF Research Database (Denmark)

Bouzinova, Elena; Kravtsova, Violetta; Aalkjær, Christian

Involvement of oxidative stress (OxS) in development of major depressive disorder has recently become evident, though mechanisms behind this remain elusive. We analyzed therefore OxS pathways in rat Chronic Mild Stress (CMS) model of depression. Rats are exposed to chronic unpredictable mild...... mg/kg/day). Saline injections were done to control the vehicle effect. Escitalopram treated rats were sub-divided into 2 groups: responders and non-responders, according to their hedonic state and compared to non-stressed rats, treated with either saline or Escitalopram. Measurement of total...... glutathione and malondialdehyde (MDA) in lungs, heart, skeletal muscles, liver, saphenous, mesenteric, and tail arteries were used as estimates for OxS. In heart, glutathione was increased in CMS rats in comparison with non-stressed vehicle group. Accordingly, an estimate for free radical activity, MDA...

Novel antidepressant candidate RO-05 modulated glucocorticoid receptors activation and FKBP5 expression in chronic mild stress model in rats.

Science.gov (United States)

Xing, Y; Hou, J; Meng, Q; Yang, M; Kurihara, H; Tian, J

2015-04-02

In this study, a novel TRI (triple reuptake inhibitors) antidepressant candidate RO-05 (4-[1-[1-(benzoyloxy)cyclohexyl]-2-(dimethylamino)ethyl]-phenyl benzoate) was investigated in TST (tail suspension test), FST (forced swimming test) and CMS (chronic mild stress) model. Results showed RO-05 significantly decreased the immobility time in FST and TST at 4.5-, 9-, 18-mg/kg in rats and 9-, 18-, 36-mg/kg in mice. Chronic administration of 18-mg/kg RO-05 improved the behavioral index, anhedonia and normalized the hyperactivity of HPA (hypothalamic-pituitary-adrenal axis) of CMS rats. We further investigated the possible mechanisms of RO-05 in the CMS model. Eighteen milligrams per kilogram of RO-05 chronic administration significantly reversed the increase of mRNA and protein expression of FKBP5 in the CMS rat hippocampus, which facilitated the activation of GR- (glucocorticoid receptor) and GR-responsive gene Foxo1 expression. RO-05 also elevated the expression of BDNF (brain-derived neurotrophic factor) in CMS rat hippocampus. In summary, our results indicated that RO-05 is a promising antidepressant candidate. The possible antidepressant mechanisms of RO-05 were the modulation of FKBP5 expression, GR activation, corresponding inhibition of HPA axis hyperactivity, and the increase of BDNF expression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Molecular pathways associated with stress resilience and drug resistance in the chronic mild stress rat model of depression: a gene expression study

DEFF Research Database (Denmark)

Bergström, Anders; Jayatissa, Magdalena Niepsuj; Andersen, Thomas Thykjær

2007-01-01

The current antidepressant drugs are ineffective in 30 to 40% of the treated patients; hence, the pathophysiology of the disease needs to be further elucidated. We used the chronic mild stress (CMS) paradigm to induce anhedonia, a core symptom of major depression, in rats. A fraction of the animals...... exposed to CMS is resistant to the development of anhedonia; they are CMS resilient. In the CMS-sensitive animals, the induced anhedonic state is reversed in 50% of the animals when treating with escitalopram, whereas the remaining animals are treatment resistant. We used the microarray and the real...

How unpredictable access to food increases the body fat of small passerines: A mechanistic approach.

Science.gov (United States)

Anselme, Patrick; Otto, Tobias; Güntürkün, Onur

2017-11-01

Unpredictable rewards increase the vigor of responses in autoshaping (a Pavlovian conditioning procedure) and are preferred to predictable rewards in free-choice tasks involving fixed- versus variable-delay schedules. The significance those behavioral properties may have in field conditions is currently unknown. However, it is noticeable that when exposed to unpredictable food, small passerines - such as robins, titmice, and starlings - get fatter than when food is abundant. In functional terms, fattening is viewed as an evolutionary strategy acting against the risk of starvation when food is in short supply. But this functional view does not explain the causal mechanisms by which small passerines come to be fatter under food uncertainty. Here, it is suggested that one of these causal mechanisms is that involved in behavioral invigoration and preference for food uncertainty in the laboratory. Based on a psychological theory of motivational changes under food uncertainty, we developed an integrative computational model to test this idea. We show that, for functional (adaptive) reasons, the excitatory property of reward unpredictability can underlie the propensity of wild birds to forage longer and/or more intensively in an unpredictable environment, with the consequence that they can put on more fat reserves. Copyright © 2017 Elsevier B.V. All rights reserved.

Dapoxetine: An Innovative Approach in the Therapeutic Management In Animal Model of Depression

Directory of Open Access Journals (Sweden)

Hira Rafi

2016-01-01

Full Text Available Stress is a complicated condition that effects on person’s mental and physical health, and it is the precursor of other psychological disorders mainly depression. Serotonin (5-Hydroxytryptamine; 5-HT is well known to have hypofunction in unpredictable chronic mild stress whereas, unpredictable chronic mild stress (UCMS has produced the most steady and continuous results of anhedonia and learned helplessness particularly in rats. The stress-induced depressive like behavior can be reversed by many antidepressants such as SSRIs. Selective serotonin [5-hydroxytryptamine (5-HT] reuptake inhibitors (SSRIs is mostly prescribed antidepressant that can deplete neurochemical and behavioral deficits. The present study was designed to investigate whether repeated administration of dapoxetine at dose (1.0 mg/kg could reverse the behavioral deficits induced by UCMS in rat model of depression. UCMS induced behavioral deficits. Locomotor  activity in familiar environment (home cage, novel (open field environment and anxiolytic behavior in light/dark activity box were greater in unstressed group than stressed group. The inhibition of serotonin reuptake at pre-synaptic receptors by repeated dapoxetine administration is mainly the mechanism involved and discussed. This particular study may assist in novel approach for understanding the interaction between stress and behavioral functions and extending the therapeutic use of dapoxetine.

Anxiety and depression in patients suffering from chronic low backache

International Nuclear Information System (INIS)

Bhatti, A.R.; Saleem, B.; Ahsin, S.; Farooqi, A.Z.; Farooqi, A.Z.

2014-01-01

To determine the frequency of anxiety and depression in patients with chronic low backache and to document other co-morbidities among these patients presenting at rheumatology clinic of a tertiary care hospital in Islamabad. Study Design: Cross sectional study. Place and Duration of Study: Study was conducted at Pakistan Institute of Medical Sciences from July 2012 to April 2013. Methodology: A total of 170 chronic low backache patients were administered urdu translated Zung Self-Rating Depression Scale and Zung Self-Rating Anxiety Scales. Scoring was done on Likert-type scale of 1-4 (based on these replies: a little of the time, some of the time, good part of the time, most of the time) with overall assessment by cumulative score ranging from 20 to 80, where 20-44 was normal range, 45-59 mildly depressed/anxious, 60-69 moderately depressed / anxious and 70 and above severely depressed / anxious. Results: Out of 170 patients, 157 patients above 18 years of age with male to female ratio 2:3 completed the study. Among study sample 72.2% had mild depression, 21.6% had mild anxiety, 32% had mixed mild anxiety and depression, 0.8% had severe depression, 1.6% had severe anxiety while 2.4% suffered from severe mixed symptoms. Overall, 125 (79.6%) patients were suffering from mild to severe form of depression and anxiety both alone or mixed. Obesity was present in 34 (21.66%) of patients with chronic backache and out of these 29 (85.3%) had psychological co-morbidity. Conclusion: Two thirds of the chronic backache patients reporting at rheumatology clinic of a tertiary care hospital were suffering from mild to severe degree of depression and anxiety. This worrying situation calls for thorough systematic evaluation of all chronic backache patient arriving at rheumatology clinic for mood disorders and psychological ailment. (author)

How to create a health care organization that can succeed in an unpredictable future.

Science.gov (United States)

Olden, Peter C; Haynos, Jessika

2013-01-01

For those who manage organizations, it has been said that success does not come from predicting the future but instead comes from creating an organization that can succeed in an unpredictable future. Managers are responsible for creating such an organization. To do that, managers can apply management-related principles and methods. This article explains selected principles of organization structure, human resources, culture, decision making, and change management and how to apply them to health care organizations. If done well, that will help such organizations succeed in an unpredictable future.

The contribution of rib fractures to chronic pain and disability.

Science.gov (United States)

Gordy, Stephanie; Fabricant, Loic; Ham, Bruce; Mullins, Richard; Mayberry, John

2014-05-01

The contribution of rib fractures to chronic pain and disability is not well described. Two hundred three patients with rib fractures were followed for 6 months. Chronic pain was assessed using the McGill Pain Questionnaire Pain Rating Index and Present Pain Intensity (PPI) scales. Disability was defined as a decrease in work or functional status. The prevalence of chronic pain was 22% and disability was 53%. Acute PPI predicted chronic pain. Associated injuries, bilateral rib fractures, injury severity score, and number of rib fractures were not predictive of chronic pain. No acute injury characteristics were predictive of disability. Among 89 patients with isolated rib fractures, the prevalence of chronic pain was 28% and of disability was 40%. No injury characteristics predicted chronic pain. Bilateral rib fractures and acute PPI predicted disability. The contribution of rib fractures to chronic pain and disability is significant but unpredictable with conventional injury descriptors. Copyright © 2014 Elsevier Inc. All rights reserved.

Proteomic investigation of the ventral rat hippocampus links DRP-2 to escitalopram treatment resistance and SNAP to stress resilience in the chronic mild stress model of depression

DEFF Research Database (Denmark)

Bisgaard, Christina; Jayatissa, Magdalena N; Enghild, Jan J

2007-01-01

etiology and recovery. Thus two-dimensional differential in-gel electrophoresis was employed to compare the ventral hippocampal proteomes between different treatment groups in the chronic mild stress (CMS) model of depression. The CMS paradigm induces anhedonic behaviour, which is a major symptom......The development of depression as well as recovery from depression is most likely accompanied by a change in protein expression profiles. The purpose of the present study was to quantitatively investigate global protein expression differences independent of any hypothesis describing depression...... of depression, by exposing rats to a series of mild stressors for 7 weeks, with antidepressant treatment during the last 4 weeks. In the CMS model, animals were split into six different groups at the end of treatment; unchallenged control escitalopram (n = 12), unchallenged control vehicle (n = 12), CMS vehicle...

The association between microhaemorrhages and post - traumatic functional outcome in the chronic phase after mild traumatic brain injury

Energy Technology Data Exchange (ETDEWEB)

Haan, S. de; Groot, J.C. de [University Medical Center Groningen, Department of Radiology, University of Groningen, Groningen (Netherlands); Jacobs, B.; Naalt, J. van der [University Medical Center Groningen, Department of Neurology, University of Groningen, Groningen (Netherlands)

2017-10-15

In the chronic phase after mild traumatic brain injury (mTBI), microhaemorrhages are frequently detected on magnetic resonance imaging (MRI). It is however unclear whether microhaemorrhages are associated with functional outcome and which MRI sequence is most appropriate to address this association. We aimed to determine the association between microhaemorrhages and functional outcome in the chronic posttraumatic phase after injury with the most suitable MRI sequence to address this association. One hundred twenty-seven patients classified with mTBI admitted to the outpatient clinic from 2008 to 2015 for persisting posttraumatic complaints were stratified according to the presence of MRI abnormalities (n = 63 (MRI+ group) and n = 64 without abnormalities (MRI- group)). For the detection of microhaemorrhages, susceptibility-weighted imaging (SWI) and T2* gradient recalled echo (T2*GRE) were used. The relation between the functional outcome (dichotomized Glasgow Outcome Scale Extended scores) and the number and localization of microhaemorrhages was analysed using binary logistic regression. SWI detected twice as many microhaemorrhages compared to T2*GRE: 341 vs. 179. Lesions were predominantly present in the frontal and temporal lobes. Unfavourable outcome was present in 67% of the MRI+ group with a significant association of total number of microhaemorrhages in the temporal cortical area on SWI (OR 0.43 (0.21-0.90) p = 0.02), with an explained variance of 44%. The number of microhaemorrhages was not correlated with the number of posttraumatic complaints. An unfavourable outcome in the chronic posttraumatic phase is associated with the presence and number of microhaemorrhages in the temporal cortical area. SWI is preferably used to detect these microhaemorrhages. (orig.)

The association between microhaemorrhages and post - traumatic functional outcome in the chronic phase after mild traumatic brain injury

International Nuclear Information System (INIS)

Haan, S. de; Groot, J.C. de; Jacobs, B.; Naalt, J. van der

2017-01-01

In the chronic phase after mild traumatic brain injury (mTBI), microhaemorrhages are frequently detected on magnetic resonance imaging (MRI). It is however unclear whether microhaemorrhages are associated with functional outcome and which MRI sequence is most appropriate to address this association. We aimed to determine the association between microhaemorrhages and functional outcome in the chronic posttraumatic phase after injury with the most suitable MRI sequence to address this association. One hundred twenty-seven patients classified with mTBI admitted to the outpatient clinic from 2008 to 2015 for persisting posttraumatic complaints were stratified according to the presence of MRI abnormalities (n = 63 (MRI+ group) and n = 64 without abnormalities (MRI- group)). For the detection of microhaemorrhages, susceptibility-weighted imaging (SWI) and T2* gradient recalled echo (T2*GRE) were used. The relation between the functional outcome (dichotomized Glasgow Outcome Scale Extended scores) and the number and localization of microhaemorrhages was analysed using binary logistic regression. SWI detected twice as many microhaemorrhages compared to T2*GRE: 341 vs. 179. Lesions were predominantly present in the frontal and temporal lobes. Unfavourable outcome was present in 67% of the MRI+ group with a significant association of total number of microhaemorrhages in the temporal cortical area on SWI (OR 0.43 (0.21-0.90) p = 0.02), with an explained variance of 44%. The number of microhaemorrhages was not correlated with the number of posttraumatic complaints. An unfavourable outcome in the chronic posttraumatic phase is associated with the presence and number of microhaemorrhages in the temporal cortical area. SWI is preferably used to detect these microhaemorrhages. (orig.)

Unpredictable and Uncontrollable Events: A New Perspective on Experimental Neurosis

Science.gov (United States)

Kihlstrom, John F.; Mineka, Susan

1978-01-01

Recent work has shown that unpredictable and/or uncontrollable events can produce a variety of cognitive, affective, and somatic disturbances to the organism. These disturbances are compared to and found to be quite similar to the symptoms of the classic cases of experimental neurosis described by Pavlov, Gantt, Liddell, Masserman, and Wolpe.…

The boundaries of mild chronic obstructive pulmonary disease (COPD): design of the searching clinical COPD onset (SOON) study.

Science.gov (United States)

Labarca, Gonzalo; Bustamante, Andrea; Valdivia, Gonzalo; Díaz, Rodrigo; Huete, Álvaro; Mac Nab, Paul; Mendoza, Laura; Leppe, Jaime; Lisboa, Carmen; Saldías, Fernando; Díaz, Orlando

2017-08-11

Clinical onset of chronic obstructive pulmonary disease (COPD) is the point at which the disease is first identifiable by physicians. It is a poorly defined stage which seems to include both mild spirometric and non-spirometric disease, and could be described as early grade COPD, for practical purposes. While dyspnoea; chronic bronchitis and CT imaging evidence of emphysema and airway disease may be present very early, the lone significance of dyspnoea, the most relevant symptom in COPD in identifying these individuals, has been scarcely assessed.The Searching Clinical COPD Onset (SOON) Study was designed primarily to detect clinical, physiological and structural differences between dyspnoeic and non-dyspnoeic individuals with early grade COPD. It is hypothesised that presence of dyspnoea in early disease may identify a subtype of individuals with reduced exercise capacity, notwithstanding of their spirometry results. In addition, dyspnoeic individuals will share worse quality of life, lower physical activity, greater lung hyperinflation greater emphysema and airway thickness and reduced peripheral muscle mass than their non-dyspnoeic counterpart. SOON is a monocentric study, with a cross sectional design aimed at obtaining representative samples of current or ex-smoker-adults aged ≥45 and ≤80 years. Two hundred and forty participants will be enrolled into four strata, according to normal spirometry or mild spirometric obstruction and presence or not of dyspnoea modified Medical Research Council score ≥1. The primary outcome will be the difference between dyspnoeic and non-dyspnoeic individuals on the 6-min walk test performance, regardless of their spirometry results. To account for the confounding effect of heart failure on dyspnoea, stress echocardiography will be also performed. Secondary outcomes will include clinical (quality of life, physical activity), physiological (exercise testing) and structural characteristics (emphysema, airway disease and

Chronic effect of ketanserin in mild to moderate essential hypertension.

Science.gov (United States)

Woittiez, A J; Wenting, G J; van den Meiracker, A H; Ritsema van Eck, H J; Man in't Veld, A J; Zantvoort, F A; Schalekamp, M A

1986-02-01

Ketanserin, an antagonist highly selective for 5-hydroxytryptamine (serotonin) type 2 (S2) receptors, was given as monotherapy in a dose of 40 mg b.i.d. to 24 subjects with mild to moderate essential hypertension. Its effects were evaluated in a placebo-controlled double-blind crossover study. The effect on blood pressure in 18 subjects was monitored by 24-hour ambulatory intra-arterial measurements. Systolic and diastolic intra-arterial pressures were significantly lowered by ketanserin both during the day and at night, whereas heart rate was unchanged. Cuff pressure readings (triplicate measurements) with the London School of Hygiene sphygmomanometer and an automatic device (12 measurements in 1 hour) in the outpatient clinic also showed a significant effect on both supine and standing pressures. No postural hypotension was noted. Ketanserin had no effect on endogenous creatinine clearance, serum cholesterol levels, and the plasma levels of norepinephrine, renin, and aldosterone. The only side effect that was significantly more common with ketanserin than with placebo treatment was an increase in body weight. Ketanserin may have a place in the treatment of mild to moderate essential hypertension.

Estimation of the year-on-year volatility and the unpredictability of the United States energy system

Science.gov (United States)

Sherwin, Evan D.; Henrion, Max; Azevedo, Inês M. L.

2018-04-01

Long-term projections of energy consumption, supply and prices heavily influence decisions regarding long-lived energy infrastructure. Predicting the evolution of these quantities over multiple years to decades is a difficult task. Here, we estimate year-on-year volatility and unpredictability over multi-decade time frames for many quantities in the US energy system using historical projections. We determine the distribution over time of the most extreme projection errors (unpredictability) from 1985 to 2014, and the largest year-over-year changes (volatility) in the quantities themselves from 1949 to 2014. Our results show that both volatility and unpredictability have increased in the past decade, compared to the three and two decades before it. These findings may be useful for energy decision-makers to consider as they invest in and regulate long-lived energy infrastructure in a deeply uncertain world.

Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

Directory of Open Access Journals (Sweden)

Amira M. Abo-youssef

2016-06-01

Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

Chronic Hypopituitarism Associated with Increased Postconcussive Symptoms Is Prevalent after Blast-Induced Mild Traumatic Brain Injury

Directory of Open Access Journals (Sweden)

Arundhati Undurti

2018-02-01

Full Text Available The most frequent injury sustained by US service members deployed to Iraq or Afghanistan is mild traumatic brain injuries (mTBI, or concussion, by far most often caused by blast waves from improvised explosive devices or other explosive ordnance. TBI from all causes gives rise to chronic neuroendocrine disorders with an estimated prevalence of 25–50%. The current study expands upon our earlier finding that chronic pituitary gland dysfunction occurs with a similarly high frequency after blast-related concussions. We measured circulating hormone levels and accessed demographic and testing data from two groups of male veterans with hazardous duty experience in Iraq or Afghanistan. Veterans in the mTBI group had experienced one or more blast-related concussion. Members of the deployment control (DC group encountered similar deployment conditions but had no history of blast-related mTBI. 12 of 39 (31% of the mTBI participants and 3 of 20 (15% veterans in the DC group screened positive for one or more neuroendocrine disorders. Positive screens for growth hormone deficiency occurred most often. Analysis of responses on self-report questionnaires revealed main effects of both mTBI and hypopituitarism on postconcussive and posttraumatic stress disorder (PTSD symptoms. Symptoms associated with pituitary dysfunction overlap considerably with those of PTSD. They include cognitive deficiencies, mood and anxiety disorders, sleep problems, diminished quality of life, deleterious changes in metabolism and body composition, and increased cardiovascular mortality. When such symptoms are due to hypopituitarism, they may be alleviated by hormone replacement. These findings suggest consideration of routine post-deployment neuroendocrine screening of service members and veterans who have experienced blast-related mTBI and are reporting postconcussive symptoms.

Chronic Hypopituitarism Associated with Increased Postconcussive Symptoms Is Prevalent after Blast-Induced Mild Traumatic Brain Injury

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Undurti, Arundhati; Colasurdo, Elizabeth A.; Sikkema, Carl L.; Schultz, Jaclyn S.; Peskind, Elaine R.; Pagulayan, Kathleen F.; Wilkinson, Charles W.

2018-01-01

The most frequent injury sustained by US service members deployed to Iraq or Afghanistan is mild traumatic brain injuries (mTBI), or concussion, by far most often caused by blast waves from improvised explosive devices or other explosive ordnance. TBI from all causes gives rise to chronic neuroendocrine disorders with an estimated prevalence of 25–50%. The current study expands upon our earlier finding that chronic pituitary gland dysfunction occurs with a similarly high frequency after blast-related concussions. We measured circulating hormone levels and accessed demographic and testing data from two groups of male veterans with hazardous duty experience in Iraq or Afghanistan. Veterans in the mTBI group had experienced one or more blast-related concussion. Members of the deployment control (DC) group encountered similar deployment conditions but had no history of blast-related mTBI. 12 of 39 (31%) of the mTBI participants and 3 of 20 (15%) veterans in the DC group screened positive for one or more neuroendocrine disorders. Positive screens for growth hormone deficiency occurred most often. Analysis of responses on self-report questionnaires revealed main effects of both mTBI and hypopituitarism on postconcussive and posttraumatic stress disorder (PTSD) symptoms. Symptoms associated with pituitary dysfunction overlap considerably with those of PTSD. They include cognitive deficiencies, mood and anxiety disorders, sleep problems, diminished quality of life, deleterious changes in metabolism and body composition, and increased cardiovascular mortality. When such symptoms are due to hypopituitarism, they may be alleviated by hormone replacement. These findings suggest consideration of routine post-deployment neuroendocrine screening of service members and veterans who have experienced blast-related mTBI and are reporting postconcussive symptoms. PMID:29515515

Complex interactions between the subject factors of biological sex and prior histories of binge-drinking and unpredictable stress influence behavioral sensitivity to alcohol and alcohol intake.

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Quadir, Sema G; Guzelian, Eugenie; Palmer, Mason A; Martin, Douglas L; Kim, Jennifer; Szumlinski, Karen K

2017-08-10

Alcohol use disorders, affective disorders and their comorbidity are sexually dimorphic in humans. However, it is difficult to disentangle the interactions between subject factors influencing alcohol sensitivity in studies of humans. Herein, we combined murine models of unpredictable, chronic, mild stress (UCMS) and voluntary binge-drinking to examine for sex differences in the interactions between prior histories of excessive ethanol-drinking and stress upon ethanol-induced changes in motor behavior and subsequent drinking. In Experiment 1, female mice were insensitive to the UCMS-induced increase in ethanol-induced locomotion and ethanol intake under continuous alcohol-access. Experiment 2 revealed interactions between ethanol dose and sex (females>males), binge-drinking history (water>ethanol), and UCMS history (UCMS>controls), with no additive effect of a sequential prior history of both binge drinking and UCMS observed. We also observed an interaction between UCMS history and sex for righting recovery. UCMS history potentiated subsequent binge-drinking in water controls of both sexes and in male binge-drinking mice. Conversely, a prior binge-drinking history increased subsequent ethanol intake in females only, irrespective of prior UCMS history. In Experiment 3, a concurrent history of binge-drinking and UCMS did not alter ethanol intake, nor did it influence the ethanol dose-locomotor response function, but it did augment alcohol-induced sedation and reduced subsequent alcohol intake over that produced by binge-drinking alone. Thus, the subject factors of biological sex, prior stressor history and prior binge-drinking history interact in complex ways in mice to impact sensitivity to alcohol's motor-stimulating, -incoordinating and intoxicating effects, as well as to influence subsequent heavy drinking. Copyright © 2017 Elsevier Inc. All rights reserved.

Lingmao Formula Combined with Entecavir for HBeAg-Positive Chronic Hepatitis B Patients with Mildly Elevated Alanine Aminotransferase: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

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Xiao-Jun Zhu

2013-01-01

Full Text Available Objective. To determine the efficacy and safety of Lingmao Formula combined with entecavir for HBeAg-positive chronic hepatitis B patients with mildly elevated alanine aminotransferase (ALT. Methods. 301 patients were randomly assigned to receive Lingmao Formula combined with entecavir (treatment group or placebo combined with entecavir (control group for 52 weeks. The outcomes of interest included the reduction of serum HBV DNA level, HBeAg loss, HBeAg seroconversion, ALT normalization, and histological improvement. Results. The mean decrease of serum HBV DNA level from baseline and the percentage of patients who had reduction in serum HBV DNA level ≥2 lg copies/mL in treatment group were significantly greater than that in control group (5.5 versus 5.4 lg copies/mL, P=0.010; 98.5% versus 92.6%, P=0.019. The percentage of HBeAg loss in treatment group was 22.8%, which was much higher than a percentage of 12.6% in control group (P=0.038. There was no significant difference between the two groups in histological improvement. Safety was similar in the two groups. Conclusions. The combination of Lingmao Formula with entecavir could result in significant decrease of serum HBV DNA and increase of HBeAg loss for HBeAg-positive chronic hepatitis B patients with mildly elevated ALT without any serious adverse events. Clinical trial registration number is ChiCTR-TRC-09000594.

Defensive motivation and attention in anticipation of different types of predictable and unpredictable threat: A startle and event-related potential investigation.

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Nelson, Brady D; Hajcak, Greg

2017-08-01

Predictability is an important characteristic of threat that impacts defensive motivation and attentional engagement. Supporting research has primarily focused on actual threat (e.g., shocks), and it is unclear whether the predictability of less intense threat (e.g., unpleasant pictures) similarly affects motivation and attention. The present study utilized a within-subject design and examined defensive motivation (startle reflex and self-reported anxiety) and attention (probe N100 and P300) in anticipation of shocks and unpleasant pictures during a no, predictable, and unpredictable threat task. This study also examined the impact of predictability on the P300 to shocks and late positive potential (LPP) to unpleasant pictures. The startle reflex and self-reported anxiety were increased in anticipation of both types of threat relative to no threat. Furthermore, startle potentiation in anticipation of unpredictable threat was greater for shocks compared to unpleasant pictures, but there was no difference for predictable threat. The probe N100 was enhanced in anticipation of unpredictable threat relative to predictable threat and no threat, and the probe P300 was suppressed in anticipation of predictable and unpredictable threat relative to no threat. These effects did not differ between the shock and unpleasant picture trials. Finally, the P300 and early LPP component were increased in response to unpredictable relative to predictable shocks and unpleasant pictures, respectively. The present study suggests that the unpredictability of unpleasant pictures increases defensive motivation, but to a lesser degree relative to actual threat. Moreover, unpredictability enhances attentional engagement in anticipation of, and in reaction to, both types of threat. © 2017 Society for Psychophysiological Research.

Irreversibility in physics stemming from unpredictable symbol-handling agents

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Myers, John M.; Madjid, F. Hadi

2016-05-01

The basic equations of physics involve a time variable t and are invariant under the transformation t --> -t. This invariance at first sight appears to impose time reversibility as a principle of physics, in conflict with thermodynamics. But equations written on the blackboard are not the whole story in physics. In prior work we sharpened a distinction obscured in today's theoretical physics, the distinction between obtaining evidence from experiments on the laboratory bench and explaining that evidence in mathematical symbols on the blackboard. The sharp distinction rests on a proof within the mathematics of quantum theory that no amount of evidence, represented in quantum theory in terms of probabilities, can uniquely determine its explanation in terms of wave functions and linear operators. Building on the proof we show here a role in physics for unpredictable symbol-handling agents acting both at the blackboard and at the workbench, communicating back and forth by means of transmitted symbols. Because of their unpredictability, symbol-handling agents introduce a heretofore overlooked source of irreversibility into physics, even when the equations they write on the blackboard are invariant under t --> -t. Widening the scope of descriptions admissible to physics to include the agents and the symbols that link theory to experiments opens up a new source of time-irreversibility in physics.

Effects of berberine on a rat model of chronic stress and depression via gastrointestinal tract pathology and gastrointestinal flora profile assays.

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Zhu, Xiaohui; Sun, Yangdong; Zhang, Chenggang; Liu, Haifeng

2017-05-01

Chronic stress and depression are challenging conditions to treat, owing to their complexity and lack of clinically available and effective therapeutic agents. The aim of the present study was to investigate the mechanism by which berberine acts, by examining alterations to gastrointestinal tract histopathology and flora profile in a rat model, following the induction of stress. Research associating gastrointestinal flora and depression has increased, thus, the present study hypothesized that stress induces depression and changes in the gastrointestinal system. The chronic mild stress rat model was previously established based on a set of 10 chronic unpredictable stress methods. In the present study, the measurements of body weight, behavior, gastrointestinal tract histopathology and gastrointestinal flora profile were collected in order to elucidate understanding of chronic stress and depression in this region. In the present study, induced stress and the resulting depression was demonstrated to significantly decrease the body weight and sucrose preference of rats, as well as significantly increasing traverse time, vertical movement time, grooming time and motionless time in an open‑field test. Following modeling and subsequent treatment with low or high doses of berberine, the measurements were significantly different when compared with unstressed rats. Berberine appears to reverse the physical damage brought about by stress within the gastric mucosa and intestinal microvilli of the stomach, ileum, cecum and colon. Using enterobacterial repetitive intergenic consensus sequence‑based polymerase chain reaction analysis, several distinctive bands disappeared following modeling; however, novel distinctive bands appeared in response to the graded berberine treatment. In conclusion, the present study identified that high concentrations of berberine markedly protects rats from various symptoms of chronic stress and depression, with the potential of facilitating

Efficacy and safety of oral ketamine versus diclofenac to alleviate mild to moderate depression in chronic pain patients: A double-blind, randomized, controlled trial.

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Jafarinia, Morteza; Afarideh, Mohsen; Tafakhori, Abbas; Arbabi, Mohammad; Ghajar, Alireza; Noorbala, Ahmad Ali; Saravi, Maryam Alamdar; Agah, Elmira; Akhondzadeh, Shahin

2016-11-01

Ketamine is a glutamate N-methyl-d-aspartate receptor antagonist capable of exerting antidepressive effects in single or repeated intravenous infusions. The objective of this study was to investigate the safety and the efficacy of oral ketamine vs. diclofenac monotherapy in reducing symptoms of mild to moderate depression among patients with chronic pain. This study is a 6-week, randomized, double-blind, controlled, parallel-group trial with two intervention arms (ketamine, fixed daily dosage of 150mg vs. diclofenac, fixed daily dosage of 150mg). Twenty participants in each arm completed the trial program all of whom had two post-baseline measurements at week 3 and week 6. Reduction in depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS) and the hospital anxiety and depression subscale for depression (HADSDepression) scores at baseline and week 3 and week 6 post-intervention. Significantly lower HDRS scores were observed in the ketamine treatment group as early as 6 weeks post-intervention (P=0.008). By comparison, mean (±standard deviation) HADS depression subscale scores were significantly lower for individuals receiving ketamine compared to diclofenac for both post-baseline measures at week 3 (6.95±1.47 vs. 8.40±1.6, P=0.005) and week 6 (6.20±1.15 vs. 7.35±1.18, p=0.003). The limitations of the present study were its small sample size and the short-term follow-up period. Oral ketamine appears to be a safe and effective option in improving depressive symptoms of patients with chronic pain with mild-to-moderate depression. Copyright © 2016 Elsevier B.V. All rights reserved.

Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress.

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Shen, Ji-Duo; Wei, Yu; Li, Yu-Jie; Qiao, Jing-Yi; Li, Yu-Cheng

2017-08-01

Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3β and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.

Sleep deprivation does not affect neuronal susceptibility to mild traumatic brain injury in the rat

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Caron AM

2015-06-01

Full Text Available Aimee M Caron, Richard Stephenson Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada Abstract: Mild and moderate traumatic brain injuries (TBIs (and concussion occur frequently as a result of falls, automobile accidents, and sporting activities, and are a major cause of acute and chronic disability. Fatigue and excessive sleepiness are associated with increased risk of accidents, but it is unknown whether prior sleep debt also affects the pathophysiological outcome of concussive injury. Using the “dark neuron” (DN as a marker of reversible neuronal damage, we tested the hypothesis that acute (48 hours total sleep deprivation (TSD and chronic sleep restriction (CSR; 10 days, 6-hour sleep/day affect DN formation following mild TBI in the rat. TSD and CSR were administered using a walking wheel apparatus. Mild TBI was administered under anesthesia using a weight-drop impact model, and the acute neuronal response was observed without recovery. DNs were detected using standard bright-field microscopy with toluidine blue stain following appropriate tissue fixation. DN density was low under home cage and sleep deprivation control conditions (respective median DN densities, 0.14% and 0.22% of neurons, and this was unaffected by TSD alone (0.1%. Mild TBI caused significantly higher DN densities (0.76%, and this was unchanged by preexisting acute or chronic sleep debt (TSD, 0.23%; CSR, 0.7%. Thus, although sleep debt may be predicted to increase the incidence of concussive injury, the present data suggest that sleep debt does not exacerbate the resulting neuronal damage. Keywords: sleep deprivation, concussion, traumatic brain injury, dark neuron, neurodegeneration, rat cortex

Self-rated health in patients with mild Alzheimer's disease: baseline data from the Danish Alzheimer Intervention Study

DEFF Research Database (Denmark)

Waldorff, Frans Boch; Nielsen, Anni B S; Waldemar, Gunhild

2010-01-01

, but the validity and the influence on other factors on SRH among cognitively impaired persons remain unknown. This study reports how patients with mild Alzheimer's disease (AD) report SRH and which factors influence SRH. The study was based on baseline data from 321 home living patients with mild AD who...... participated in the Danish Alzheimer Intervention Study (DAISY). Analysis using the generalized estimating equation (GEE) models revealed that good/excellent SRH among patients with mild AD were associated with longer education, lack of other chronic conditions, higher scores of quality of life (QOL), lower...

Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA.

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Sarro, E C; Sullivan, R M; Barr, G

2014-01-31

Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpaired odor-shock conditioning for 5 days, which produces deficits in adult behavior and amygdala dysfunction. In adulthood, we used the Light/Dark box test to measure anxiety-related behaviors, measuring the latency to enter the lit area and quantified urination and defecation. The amygdala was then dissected and a microarray analysis was performed to examine changes in gene expression. Animals that had received early unpredictable trauma displayed significantly longer latencies to enter the lit area and more defecation and urination. The microarray analysis revealed over-represented genes related to learning and memory, synaptic transmission and trans-membrane transport. Gene ontology and pathway analysis identified highly represented disease states related to anxiety phenotypes, including social anxiety, obsessive-compulsive disorders, post-traumatic stress disorder and bipolar disorder. Addiction-related genes were also overrepresented in this analysis. Unpredictable shock during early development increased anxiety-like behaviors in adulthood with concomitant changes in genes related to neurotransmission, resulting in gene expression patterns similar to anxiety-related psychiatric disorders. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model.

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Chaloner, Aaron; Greenwood-Van Meerveld, Beverley

2013-03-01

Visceral pain is the hallmark feature of irritable bowel syndrome (IBS), a gastrointestinal disorder, which is more commonly diagnosed in women. Female IBS patients frequently report a history of early life adversity (ELA); however, sex differences in ELA-induced visceral pain and the role of ovarian hormones have yet to be investigated. Therefore, we tested the hypothesis that ELA induces visceral hypersensitivity through a sexually dimorphic mechanism mediated via estradiol. As a model of ELA, neonatal rats were exposed to different pairings of an odor and shock to control for trauma predictability. In adulthood, visceral sensitivity was assessed via a visceromotor response to colorectal distension. Following ovariectomy and estradiol replacement in a separate group of rats, the visceral sensitivity was quantified. We found that females that received unpredictable odor-shock developed visceral hypersensitivity in adulthood. In contrast, visceral sensitivity was not significantly different following ELA in adult males. Ovariectomy reversed visceral hypersensitivity following unpredictable ELA, whereas estradiol replacement reestablished visceral hypersensitivity in the unpredictable group. This study is the first to show sex-related differences in visceral sensitivity following unpredictable ELA. Our data highlight the activational effect of estradiol as a pivotal mechanism in maintaining visceral hypersensitivity. This article directly implicates a critical role for ovarian hormones in maintaining visceral hypersensitivity following ELA, specifically identifying the activational effect of estradiol as a key modulator of visceral sensitivity. These data suggest that ELA induces persistent functional abdominal pain in female IBS patients through an estrogen-dependent mechanism. Copyright © 2013 American Pain Society. All rights reserved.

Grading the intensity of nondental orofacial pain: identification of cutoff points for mild, moderate, and severe pain

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Brailo V

2015-02-01

Full Text Available Vlaho Brailo,1 Joanna M Zakrzewska2 1Department of Oral Medicine, School of Dental Medicine, University of Zagreb, Zagreb, Croatia; 2Facial Pain Unit, Division of Diagnostic, Surgical and Medical Sciences, Eastman Dental Hospital, UCLH NHS Foundation Trust/University College London, London, UK Background: When assessing pain in clinical practice, clinicians often label pain as mild, moderate, and severe. However, these categories are not distinctly defined, and are often used arbitrarily. Instruments for pain assessment use more sophisticated scales, such as a 0–10 numerical rating scale, and apart from pain intensity assess pain-related interference and disability. The aim of the study was to identify cutoff points for mild, moderate, and severe nondental orofacial pain using a numerical rating scale, a pain-related interference scale, and a disability measurement. Materials and methods: A total of 245 patients referred to the Facial Pain Unit in London were included in the study. Intensity and pain-related interference were assessed by the Brief Pain Inventory. Pain-related disability was assessed by the Chronic Graded Pain Scale. Average pain intensity (0–10 was classified into nine schemes with varying cutoff points of mild, moderate, and severe pain. The scheme with the most significant intergroup difference, expressed by multivariate analysis of variance, provided the cutoffs between mild, moderate, and severe pain. Results: The combination that showed the greatest intergroup differences for all patients was scheme 47 (mild 1–4, moderate 5–7, severe 8–10. The same combination provided the greatest intergroup differences in subgroups of patients with temporomandibular disorder and chronic idiopathic facial pain, respectively. Among the trigeminal neuralgia patients alone, the combination with the highest intergroup differences was scheme 48 (mild 1–4, moderate 5–8, severe 9–10. Conclusion: The cutoff points established in

Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid.

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Chen, Jiao; Wang, Zhen-zhen; Zuo, Wei; Zhang, Shuai; Chu, Shi-feng; Chen, Nai-hong

2016-02-01

Major depression is thought to originate from maladaptation to adverse events, particularly when impairments occur in mood-related brain regions. Hypothalamus-pituitary-adrenal (HPA) axis is one of the major systems involved in physiological stress response. HPA axis dysfunction and high glucocorticoid concentrations play an important role in the pathogenesis of depression. In addition, astrocytic disability and dysfunction of neurotrophin brain-derived neurotrophin factor (BDNF) greatly influence the development of depression and anxiety disorders. Therefore, we investigated whether depressive-like and anxiety-like behaviors manifest in the absence of glucocorticoid production and circulation in adrenalectomized (ADX) rats after chronic mild stress (CMS) exposure and its potential molecular mechanisms. The results demonstrate that glucocorticoid-controlled rats showed anxiety-like behaviors but not depression-like behaviors after CMS. Molecular and cellular changes included the decreased BDNF in the hippocampus, astrocytic dysfunction with connexin43 (cx43) decreasing and abnormality in gap junction in prefrontal cortex (PFC). Interestingly, we did not find any changes in glucocorticoid receptor (GR) or its chaperone protein FK506 binding protein 51 (FKBP5) expression in the hippocampus or PFC in ADX rats subjected to CMS. In conclusion, the production and circulation of glucocorticoids are one of the contributing factors in the development of depression-like behaviors in response to CMS. In contrast, the effects of CMS on anxiety-like behaviors are independent of the presence of circulating glucocorticoids. Meanwhile, stress decreased GR expression and enhanced FKBP5 expression via higher glucocorticoid exposure. Gap junction dysfunction and changes in BDNF may be associated with anxiety-like behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

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Yu Ri Kim

2017-02-01

Full Text Available The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ augmentation for cilostazol (CLS-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS. Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects.

Families of Children with Chronic Illness and the Relational Family Model

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Tanja Pate

2016-09-01

Full Text Available Families of children with chronic illness experience persistent stress. Facing the diagnosis and learning how to cope with it is a stressful experience not only for the child but also for the parents and for the whole family. The illness, with its unpredictability and treatment, disturbs their daily routine and threatens the whole family system. Parental involvement in the child’s disease management and their emotional support are crucial for effective coping and adaptation to the child’s chronic illness. The aim of this article is to present the importance of the parental role in these families through theoretical findings of the relational family model.

Anxiety and Depression Symptom Dimensions Demonstrate Unique Relationships with the Startle Reflex in Anticipation of Unpredictable Threat in 8 to 14 Year-Old Girls

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Nelson, Brady D.; Hajcak, Greg

2016-01-01

There is growing evidence that heightened sensitivity to unpredictability is a core mechanism of anxiety disorders. In adults, multiple anxiety disorders have been associated with a heightened startle reflex in anticipation of unpredictable threat. Child and adolescent anxiety has been linked to an increased startle reflex across baseline, safety, and threat conditions. However, it is unclear whether anxiety in youth is related to the startle reflex as a function of threat predictability. In a sample of 90 8 to 14 year-old girls, the present study examined the association between anxiety symptom dimensions and startle potentiation during a no, predictable, and unpredictable threat task. Depression symptom dimensions were also examined given their high comorbidity with anxiety and mixed relationship with the startle reflex and sensitivity to unpredictability. To assess current symptoms, participants completed the self-report Screen for Child Anxiety Related Emotional Disorders and Children’s Depression Inventory. Results indicated that social phobia symptoms were associated with heightened startle potentiation in anticipation of unpredictable threat and attenuated startle potentiation in anticipation of predictable threat. Negative mood and negative self-esteem symptoms were associated with attenuated and heightened startle potentiation in anticipation of unpredictable threat, respectively. All results remained significant after controlling for the other symptom dimensions. The present study provides initial evidence that anxiety and depression symptom dimensions demonstrate unique associations with the startle reflex in anticipation of unpredictable threat in children and adolescents. PMID:27224989

Clinical and Physiological Effects of Exercise Training in Dyspneic Mild COPD Patients: Design of the Study

OpenAIRE

Gonzalo Labarca; Andrea Bustamante; Francisco Rodríguez; Igor Nuñez; Gonzalo Valdivia; Paul Mac Nab; Álvaro Huete; Jaime Leppe; Fernando Saldías; Orlando Díaz

2017-01-01

Introduction: Mild chronic obstructive pulmonary disease (COPD) may be associated with physical inactivity, exercise limitation, and impaired health related quality of life, because of a combination of deconditioning, dyspnea, and reduced peripheral muscle mass. Although the benefits of exercise training (ET) in counteracting these consequences are well established in moderate-to-very-severe COPD, it is unclear if they are also effective in mild disease. The aim of this paper is to describe t...

Old worries and new anxieties: behavioral symptoms and mild cognitive impairment in a population study.

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Andreescu, Carmen; Teverovsky, Esther; Fu, Bo; Hughes, Tiffany F; Chang, Chung-Chou H; Ganguli, Mary

2014-03-01

To disentangle the complex associations of depression and anxiety with mild cognitive impairment (MCI) at the population level. We examined subgroups of anxiety symptoms and depression symptom profiles in relation to MCI, which we defined using both cognitive and functional approaches. We used an epidemiologic, cross-sectional study with an age-stratified, random, population-based sample of 1,982 individuals aged 65 years and over. Three definitions of MCI were used: 1) a purely cognitive classification into amnestic and nonamnestic MCI, 2) a combined cognitive-functional definition by International Working Group (IWG) criteria, and 3) a purely functional definition by the Clinical Dementia Rating (CDR) of 0.5. Three depression profiles were identified by factor analysis of the modified Center for Epidemiological Studies-Depression Scale: core mood, self-esteem/interpersonal, and apathy/neurovegetative profiles. Three anxiety groups, chronic mild worry, chronic severe anxiety, and recent-onset anxiety, were based on screening questions. Recent-onset anxiety was associated with MCI by nonamnestic and IWG criteria, chronic severe anxiety was associated with MCI by all definitions, and chronic mild worry was associated with none. Of the depression profiles, the core mood profile was associated with CDR-defined MCI, the apathy/neurovegetative profile was associated with MCI by amnestic, IWG, and CDR definitions, and the self-esteem/interpersonal profile was associated with none. In this population-based sample, subgroups with different anxiety and depression profiles had different relationships with cognitive and functional definitions of MCI. Anxiety, depression, and MCI are all multidimensional entities, interacting in complex ways that may shed light on underlying neural mechanisms. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Age-related changes in compensatory stepping in response to unpredictable perturbations.

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McIlroy, W E; Maki, B E

1996-11-01

Recent studies highlight the importance of compensatory stepping to preserve stability, and the spatial and temporal demands placed on the control of this reaction. Age-related changes in the control of stepping could greatly influence the risk of falling. The present study compares, in healthy elderly and young adults, the characteristics of compensatory stepping responses to unpredictable postural perturbations. A moving platform was used to unpredictably perturb the upright stance of 14 naive, active and mobile subjects (5 aged 22 to 28 and 9 aged 65 to 81). The first 10 randomized trials (5 forward and 5 backward) were evaluated to allow a focus on reactions to relatively novel perturbations. The behavior of the subjects was not constrained. Forceplate and kinematic measures were used to evaluate the responses evoked by the brief (600 msec) platform translation. Subjects stepped in 98% of the trials. Although the elderly were less likely to execute a lateral anticipatory postural adjustment prior to foot-lift, the onset of swing-leg unloading tended to begin at the same time in the two age groups. There was remarkable similarity between the young and elderly in many other characteristics of the first step of the response. In spite of this similarity, the elderly subjects were twice as likely to take additional steps to regain stability (63% of trials for elderly). Moreover, in elderly subjects, the additional steps were often directed so as to preserve lateral stability, whereas the young rarely showed this tendency. Given the functional significance of base-of-support changes as a strategy for preserving stability and the age-related differences presently revealed, assessment of the capacity to preserve stability against unpredictable perturbation, and specific measures such as the occurrence or placement of multiple steps, may prove to be a significant predictor of falling risk and an important outcome in evaluating or developing intervention strategies to

Undefined and unpredictable responsibility: a focus group study of the experiences of informal caregiver spouses of patients with severe COPD.

Science.gov (United States)

Bove, Dorthe Gaby; Zakrisson, Ann-Britt; Midtgaard, Julie; Lomborg, Kirsten; Overgaard, Dorthe

2016-02-01

To explore how spouses of patients with severe chronic obstructive pulmonary disease experience their role as informal caregiver. Informal caregiver spouses are of pivotal importance in the way that patients with chronic obstructive pulmonary disease cope with their daily life, including their opportunity to stay at home and avoid hospitalisations in the last stages of the disease. However, caregiving is associated with increased morbidity and mortality among caregivers. Further understanding of the role as an informal caregiver spouse of patients with severe chronic obstructive pulmonary disease is needed to develop supportive interventions aimed at reducing the caregiver burden. The study had a qualitative exploratory design. The data collection and analysis were based on framework method. Framework method is a thematic methodology and consists of five key stages: familiarisation, identifying a thematic framework, indexing, charting and mapping & interpretation. Three focus groups were conducted in November 2013 with 22 spouses of patients with severe chronic obstructive pulmonary disease. Undefined and unpredictable responsibility was found to be the overarching theme describing the informal caregiver role. Underlying themes were: being constantly in a state of alertness, social life modified, maintaining normality, ambivalence in the relationship and a willingness to be involved. The informal caregiver spouses experienced ambiguity about expectations from their private and the health professionals' surroundings. The informal caregiver spouses wanted to provide meaningful care for their partners, but sought knowledge and support from the health professionals. We recommend that nurses take on the responsibility for including the informal caregiver spouses in those aspects of decision-making that involve the common life of the patients and their spouses. © 2016 John Wiley & Sons Ltd.

High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

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Charles W. Wilkinson

2012-02-01

Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

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Guo, Lei; Chen, Yi-Xi; Hu, Yu-Ting; Wu, Xue-Yan; He, Yang; Wu, Juan-Li; Huang, Man-Li; Mason, Matthew; Bao, Ai-Min

2018-05-21

Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences. Copyright © 2018 Elsevier Ltd. All rights reserved.

Does hypokalemia contribute to acute kidney injury in chronic laxative abuse?

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Eun-Young Lee

2015-06-01

Full Text Available Prolonged hypokalemia from chronic laxative abuse is recognized as the cause of chronic tubulointerstitial disease, known as “hypokalemic nephropathy,” but it is not clear whether it contributes to acute kidney injury (AKI. A 42-year-old woman with a history of chronic kidney disease as a result of chronic laxative abuse from a purging type of anorexia nervosa (AN-P, developed an anuric AKI requiring hemodialysis and a mild AKI 2 months later. Both episodes of AKI involved severe to moderate hypokalemia (1.2 and 2.7 mmol/L, respectively, volume depletion, and mild rhabdomyolysis. The histologic findings of the first AKI revealed the remnants of acute tubular necrosis with advanced chronic tubulointerstitial nephritis and ischemic glomerular injury. Along with these observations, the intertwined relationship among precipitants of recurrent AKI in AN-P is discussed, and then we postulate a contributory role of hypokalemia involved in the pathophysiology of the renal ischemia-induced AKI.

Chronic mild stress impairs latent inhibition and induces region-specific neural activation in CHL1-deficient mice, a mouse model of schizophrenia.

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Buhusi, Mona; Obray, Daniel; Guercio, Bret; Bartlett, Mitchell J; Buhusi, Catalin V

2017-08-30

Schizophrenia is a neurodevelopmental disorder characterized by abnormal processing of information and attentional deficits. Schizophrenia has a high genetic component but is precipitated by environmental factors, as proposed by the 'two-hit' theory of schizophrenia. Here we compared latent inhibition as a measure of learning and attention, in CHL1-deficient mice, an animal model of schizophrenia, and their wild-type littermates, under no-stress and chronic mild stress conditions. All unstressed mice as well as the stressed wild-type mice showed latent inhibition. In contrast, CHL1-deficient mice did not show latent inhibition after exposure to chronic stress. Differences in neuronal activation (c-Fos-positive cell counts) were noted in brain regions associated with latent inhibition: Neuronal activation in the prelimbic/infralimbic cortices and the nucleus accumbens shell was affected solely by stress. Neuronal activation in basolateral amygdala and ventral hippocampus was affected independently by stress and genotype. Most importantly, neural activation in nucleus accumbens core was affected by the interaction between stress and genotype. These results provide strong support for a 'two-hit' (genes x environment) effect on latent inhibition in CHL1-deficient mice, and identify CHL1-deficient mice as a model of schizophrenia-like learning and attention impairments. Copyright © 2017 Elsevier B.V. All rights reserved.

Anxiety and Depression Symptom Dimensions Demonstrate Unique Relationships with the Startle Reflex in Anticipation of Unpredictable Threat in 8 to 14 Year-Old Girls.

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Nelson, Brady D; Hajcak, Greg

2017-02-01

There is growing evidence that heightened sensitivity to unpredictability is a core mechanism of anxiety disorders. In adults, multiple anxiety disorders have been associated with a heightened startle reflex in anticipation of unpredictable threat. Child and adolescent anxiety has been linked to an increased startle reflex across baseline, safety, and threat conditions. However, it is unclear whether anxiety in youth is related to the startle reflex as a function of threat predictability. In a sample of 90 8 to 14 year-old girls, the present study examined the association between anxiety symptom dimensions and startle potentiation during a no, predictable, and unpredictable threat task. Depression symptom dimensions were also examined given their high comorbidity with anxiety and mixed relationship with the startle reflex and sensitivity to unpredictability. To assess current symptoms, participants completed the self-report Screen for Child Anxiety Related Emotional Disorders and Children's Depression Inventory. Results indicated that social phobia symptoms were associated with heightened startle potentiation in anticipation of unpredictable threat and attenuated startle potentiation in anticipation of predictable threat. Negative mood and negative self-esteem symptoms were associated with attenuated and heightened startle potentiation in anticipation of unpredictable threat, respectively. All results remained significant after controlling for the other symptom dimensions. The present study provides initial evidence that anxiety and depression symptom dimensions demonstrate unique associations with the startle reflex in anticipation of unpredictable threat in children and adolescents.

Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

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Khedr LH

2015-11-01

Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

Non-invasive method distinguishes chronic telogen effluvium from mild female pattern hair loss: clinicopathological correlation.

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Bittencourt, Caroline; Teixeira, Fernanda; Ferraro, Daniela A; Soares, Tania C B; Moraes, Aparecida M; Cintra, Maria L

2016-07-01

The distinction between chronic telogen effluvium (CTE) and female pattern hair loss (FPHL) is important because of their different prognosis and treatment. Non-invasive methods have been described to be useful in differentiating FPHL from CTE. This prospective study investigated the use of the washing method to differentiate CTE from mild FPHL. Twenty patients with CTE and 17 with FPHL were recruited and followed for 18 months. The diagnosis was established through clinical, laboratory, and histological studies. The patients were asked to abstain from washing their hair for 5 days and then shampoo and collect all hair shed in the process. Hair shafts were then counted and divided into two groups: up to 3 cm in length or longer. In the CTE group, the mean hair count was high (438), and in all cases, hairs comprised hairs, the higher was the density of terminal follicles seen histologically. The CTE group presented a greater number of patients with serum iron values <70 μg/dl. Ferritin levels ranged from 6.98 to 128.33, average of 66.65 (CTE), and 16.5-304.8, average of 114.97 ng/ml (FPHL), but no significant differences were found. The washing test can be useful to avoid biopsy procedures. Iron serum levels are possibly an additional parameter that may improve CTE diagnosis if combined with an earlier test. © 2015 The International Society of Dermatology.

Predictors of cognitive and physical fatigue in post-acute mild-moderate traumatic brain injury.

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Schiehser, Dawn M; Delano-Wood, Lisa; Jak, Amy J; Hanson, Karen L; Sorg, Scott F; Orff, Henry; Clark, Alexandra L

2017-10-01

Post-traumatic fatigue (PTF) is a common, disabling, and often chronic symptom following traumatic brain injury (TBI). Yet, the impact of chronic cognitive and physical fatigue and their associations with psychiatric, sleep, cognitive, and psychosocial sequelae in mild-moderate TBI remain poorly understood. Sixty Veterans with a history of mild-moderate TBI and 40 Veteran controls (VC) were administered the Modified Fatigue Impact Scale, a validated measure of TBI-related cognitive and physical fatigue as well as measures of neuropsychiatric, psychosocial, sleep, and objective cognitive functioning. Compared to VC, TBI Veterans endorsed significantly greater levels of cognitive and physical fatigue. In TBI, psychiatric symptoms, sleep disturbance, and post-traumatic amnesia (PTA) were associated with both cognitive and physical fatigue, while loss of consciousness (LOC) and poor attention/processing speed were related to elevations in cognitive fatigue only. In regression analyses, anxiety, sleep disturbance, and LOC significantly predicted cognitive fatigue, while only post-traumatic stress symptoms and PTA contributed to physical fatigue. Cognitive and physical fatigue are problematic symptoms following mild-moderate TBI that are differentially associated with specific injury and psychiatric sequelae. Findings provide potential symptom targets for interventions aimed at ameliorating fatigue, and further underscore the importance of assessing and treating fatigue as a multi-dimensional symptom following TBI.

Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment.

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Spasojevic, Natasa; Jovanovic, Predrag; Dronjak, Sladjana

2015-03-01

We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment

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NATASA SPASOJEVIC

2015-03-01

Full Text Available We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

Metabolic and vascular pattern in medial pterygoid muscle is altered by chronic stress in an animal model of hypodontia.

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Fernández, Rodrigo Alberto Restrepo; Pereira, Yamba Carla Lara; Iyomasa, Daniela Mizusaki; Calzzani, Ricardo Alexandre; Leite-Panissi, Christie Ramos Andrade; Iyomasa, Mamie Mizusaki; Nascimento, Glauce Crivelaro

2018-03-01

Psychological stress is an important perpetuating, worsening and risk factor for temporomandibular disorders of muscular or articular origin. Occlusion instability, by the way, is considered a risk factor of this pathology and can be reproduced in some experimental animal models. The exact physiologic mechanism underlying these relations however, remains unclear. Our purpose was to test the hypothesis that chronic stress and unilateral exodontia induce metabolic and vascular changes in the medial pterygoid muscle of rats. Adult Wistar rats were submitted to chronic unpredictable stress and/or unilateral exodontia and their plasma and medial pterygoid muscle were removed for analysis. The parameters evaluated included plasma levels of corticosterone, metabolic activity by succinate dehydrogenase, oxidative capacity by nicotinamide adenine dinucleotide diaphorase, capillary density by laminin and alfa-CD staining and reactive oxidative species production. Chronic unpredictable stress as an isolated factor, increased oxidative metabolism, capillary density and reactive oxygen species production at medial pterygoid muscle. Conversely, exodontia has a main effect in metabolism, promoting glycolytic transformation of muscle fibers. Association of both factors induced a major glycolytic pattern in muscle and vascular changes. Our findings provide insights into the mechanisms, possibly inducing metabolic and vascular alterations on medial pterygoid muscle of rats, by which chronic stress and occlusal instabilities might be involved as risk factors in the pathophysiology of temporomandibular disorders with muscular components. Copyright © 2017 Elsevier Inc. All rights reserved.

Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum.

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Martin-Soelch, Chantal; Szczepanik, Joanna; Nugent, Allison; Barhaghi, Krystle; Rallis, Denise; Herscovitch, Peter; Carson, Richard E; Drevets, Wayne C

2011-05-01

Electrophysiological studies have shown that mesostriatal dopamine (DA) neurons increase activity in response to unpredicted rewards. With respect to other functions of the mesostriatal dopaminergic system, dopamine's actions show prominent laterality effects. Whether changes in DA transmission elicited by rewards also are lateralized, however, has not been investigated. Using [¹¹C]raclopride-PET to assess the striatal DA response to unpredictable monetary rewards, we hypothesized that such rewards would induce an asymmetric reduction in [¹¹C]raclopride binding in the ventral striatum, reflecting lateralization of endogenous dopamine release. In 24 healthy volunteers, differences in the regional D₂/₃ receptor binding potential (ΔBP) between an unpredictable reward condition and a sensorimotor control condition were measured using the bolus-plus-constant-infusion [¹¹C]raclopride method. During the reward condition subjects randomly received monetary awards while performing a 'slot-machine' task. The ΔBP between conditions was assessed in striatal regions-of-interest and compared between left and right sides. We found a significant condition × lateralization interaction in the ventral striatum. A significant reduction in binding potential (BP(ND) ) in the reward condition vs. the control condition was found only in the right ventral striatum, and the ΔBP was greater in the right than the left ventral striatum. Unexpectedly, these laterality effects appeared to be partly accounted for by gender differences, as our data showed a significant bilateral BP(ND) reduction in women while in men the reduction reached significance only in the right ventral striatum. These data suggest that DA release in response to unpredictable reward is lateralized in the human ventral striatum, particularly in males. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

HMGB1 mediates depressive behavior induced by chronic stress through activating the kynurenine pathway.

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Wang, Bo; Lian, Yong-Jie; Su, Wen-Jun; Peng, Wei; Dong, Xin; Liu, Lin-Lin; Gong, Hong; Zhang, Ting; Jiang, Chun-Lei; Wang, Yun-Xia

2017-11-28

Our previous study has reported that the proactive secretion and role of central high mobility group box 1 (HMGB1) in lipopolysaccharide-induced depressive behavior. Here, the potential mechanism of HMGB1 mediating chronic-stress-induced depression through the kynurenine pathway (KP) was further explored both in vivo and in vitro. Depression model was established with the 4-week chronic unpredictable mild stress (CUMS). Sucrose preference and Barnes maze test were performed to reflect depressive behaviors. The ratio of kynurenine (KYN)/tryptophan (Trp) represented the enzyme activity of indoleamine-2,3-dioxygenase (IDO). Gene transcription and protein expression were assayed by real-time RT-PCR and western-blot or ELISA kit respectively. Along with depressive behaviors, HMGB1 concentrations in the hippocampus and serum substantially increased post 4-week CUMS exposure. Concurrent with the upregulated HMGB1 protein, the regulator of translocation of HMGB1, sirtuin 1 (SIRT1) concentration in the hippocampus remarkably increased. In addition to HMGB1 and SIRT1, IDO, the rate limiting enzyme of KP, was upregulated at the level of mRNA expression and enzyme activity in stressed hippocampi and LPS/HMGB1-treated hippocampal slices. The gene transcription of kynurenine monooxygenase (KMO) and kynureninase (KYNU) in the downstream of KP also increased both in vivo and in vitro. Mice treated with ethyl pyruvate (EP), the inhibitor of HMGB1 releasing, were observed with lower tendency of developing depressive behaviors and reduced activation of enzymes in KP. All of these experiments demonstrate that the role of HMGB1 on the induction of depressive behavior is mediated by KP activation. Copyright © 2017 Elsevier Inc. All rights reserved.

A comparison of individual qualities of resiliency in adolescents with mild intellectual disability and typically developing adolescents

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Pavlović Miroslav V.

2017-01-01

Full Text Available Intellectual disability (ID is a chronic adversity that increases the likelihood of negative developmental outcomes. The aim of this research is to examine differences between adolescents with mild ID and typically developing (TD adolescents in personal qualities which contribute to successful adaptation. The sample consisted of 92 adolescents with mild ID and 772 TD adolescents, 13-19 years of age, of both sexes. Resiliency was assessed using the Resiliency Scales for Children and Adolescents. In comparison to TD adolescents, adolescents with mild ID have significantly lower levels of sense of mastery and sense of relatedness and a higher level of emotional reactivity. In the subsample of adolescents with mild ID there were no age or sex differences for resiliency. Adolescents with mild ID have a lower level of resiliency than TD adolescents, which highlights the need to develop programs focused on personal qualities associated with positive developmental outcomes.

Antidepressant-Like Effects of Shuyusan in Rats Exposed to Chronic Stress: Effects on Hypothalamic-Pituitary-Adrenal Function

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Liping Chen

2012-01-01

Full Text Available This study was to investigate antidepressant activities of Shuyusan (a Chinese herb, using a rats model of depression induced by unpredictable chronic mild stress (UCMS. The administration groups were treated with Shuyusan decoction for 3 weeks and compared with fluoxetine treatment. In order to understand the potential antidepressant-like activities of Shuyusan, tail suspension test (TST and forced swimming test (FST were used as behavioral despair study. The level of corticotropin-releasing factor (CRH, adrenocorticotropic hormone (ACTH, corticosterone (CORT and hippocampus glucocorticoid receptor expression were examined. After modeling, there was a significant prolongation of immobility time in administration groups with the TST and FST. High-dose Shuyusan could reduce the immobility time measured with the TST and FST. The immobility time in high-dose herbs group and fluoxetine group was increased significantly compared with the model group. After 3 weeks herbs fed, the serum contents level of CRH, ACTH, and CORT in high-dose herb group was significantly decreased compared to the model group. The result indicated that Shuyusan had antidepressant activity effects on UCMS model rats. The potential antidepressant effect may be related to decreasing glucocorticoid levels activity, regulating the function of HPA axis, and inhibiting glucocorticoid receptor expression in hippocampus.

Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

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Yang, C.; Guo, X. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wang, G.H. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wuhan University, Institute of Neuropsychiatry, Wuhan, China, Institute of Neuropsychiatry, Wuhan University, Wuhan (China); Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China)

2014-03-03

Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

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Yang, C.; Guo, X.; Wang, G.H.; Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y.

2014-01-01

Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD

Implementing unpredictability in feeding enrichment for Malayan sun bears (Helarctos malayanus).

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Schneider, Marion; Nogge, Gunther; Kolter, Lydia

2014-01-01

Bears in the wild spend large proportions of time in foraging activities. In zoos their time budgets differ markedly from those of their wild counterparts. Feeding enrichment has been documented to increase foraging behavior and to reduce stereotypies. But in general these procedures have no long-term effects and result in habituation. As can be expected by the predictions of the optimal foraging theory, foraging activities are restricted as long as the availability of food is predictable. To quantify the effect of spatial unpredictability, three feeding methods have been designed to stimulate functional foraging behavior in captive Malayan sun bears in the long-term. In order to examine if habituation occurs, the most effective method was tested for 12 consecutive days. Activities of four adult sun bears at the Cologne Zoo were recorded by focal animal recording of foraging behaviors and time sampling of activities for a total of 360 hr. Implementing unpredictability significantly increased the time the bears spent foraging and led to a higher diversity of foraging behaviors. The effects lasted throughout the entire day and no habituation occurred in the course of 12 consecutive days. The study shows how functional species typical behavior in captive Malayan sun bears can be stimulated in the long-term by simulating natural characteristics of food availability. © 2014 Wiley Periodicals, Inc.

User interaction concepts in smart caring homes for elderly with chronic conditions

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Bara, C.-D.; Cabrita, M.; op den Akker, Harm; Hermens, Hermanus J.

2015-01-01

This article addresses the design and implementation of user interaction concepts for smart caring homes. Elderly suffering from age related frailty or chronic diseases, such as chronic obstructive pulmonary disease and mild dementia are the targeted primary users. Their informal and formal

Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress.

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Song, Li; Che, Wang; Min-Wei, Wang; Murakami, Yukihisa; Matsumoto, Kinzo

2006-02-01

Increasing evidences indicate the concurrence and interrelationship of depression and cognitive impairments. The present study was undertaken to investigate the effects of two depressive animal models, learned helplessness (LH) and chronic mild stress (CMS), on the cognitive functions of mice in the Morris water maze task. Our results demonstrated that both LH and CMS significantly decreased the cognitive performance of stressed mice in the water maze task. The escaping latency to the platform was prolonged and the probe test percentage in the platform quadrant was reduced. These two models also increased the plasma corticosterone concentration and decreased the brain derived neurotrophic factor (BDNF) and cAMP-response element-biding protein (CREB) messenger ribonucleic acid (mRNA) levels in hippocampus, which might cause the spatial cognition deficits. Repeated treatment with antidepressant drugs, imipramine (Imi) and fluoxetine (Flu), significantly reduced the plasma corticosterone concentration and enhanced the BDNF and CREB levels. Furthermore, antidepressant treated animals showed an ameliorated cognitive performance compared with the vehicle treated stressed animals. These data suggest that both LH and CMS impair the spatial cognitive function and repeated treatment with antidepressant drugs decreases the prevalence of cognitive impairments induced by these two animal models. Those might in part be attributed to the reduced plasma corticosterone and enhanced hippocampal BDNF and CREB expressions. This study provided a better understanding of molecular mechanisms underlying interactions of depression and cognitive impairments, although animal models used in this study can mimic only some aspects of depression or cognition of human.

Mild perinatal adversities moderate the association between maternal harsh parenting and hair cortisol: Evidence for differential susceptibility.

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Windhorst, Dafna A; Rippe, Ralph C A; Mileva-Seitz, Viara R; Verhulst, Frank C; Jaddoe, Vincent W V; Noppe, Gerard; van Rossum, Elisabeth F C; van den Akker, Erica L T; Tiemeier, Henning; van IJzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

2017-04-01

It has been shown that following exposure to mild perinatal adversity, children have greater susceptibility to both the negative and positive aspects of their subsequent environment. In a large population-based cohort study (N = 1,776), we investigated whether mild perinatal adversity moderated the association between maternal harsh parenting and children's hair cortisol levels, a biomarker of chronic stress. Mild perinatal adversity was defined as late preterm birth (gestational age at birth of 34-37 weeks, 6 days) or small for gestational age (birth weight between the 2.5th and 10th percentile for full term gestational age). Harsh parenting was assessed by maternal self-report at 3 years. Children's hair cortisol concentrations were measured from hair samples collected at age 6. There were no significant bivariate associations between mild perinatal adversities and harsh parenting and hair cortisol. However, mild perinatal adversities moderated the association between maternal harsh parenting and hair cortisol levels. Children with mild perinatal adversity had lower cortisol levels if parented more harshly and higher cortisol levels in the absence of harsh parenting than children who did not experience mild perinatal adversity. These results provide further evidence that mild perinatal adversity is a potential marker of differential susceptibility to environmental influences. © 2017 Wiley Periodicals, Inc.

Current status of fluid biomarkers in mild traumatic brain injury

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Kulbe, Jacqueline R.; Geddes, James W.

2015-01-01

Mild traumatic brain injury (mTBI) affects millions of people annually and is difficult to diagnose. Mild injury is insensitive to conventional imaging techniques and diagnoses are often made using subjective criteria such as self-reported symptoms. Many people who sustain a mTBI develop persistent post-concussive symptoms. Athletes and military personnel are at great risk for repeat injury which can result in second impact syndrome or chronic traumatic encephalopathy. An objective and quantifiable measure, such as a serum biomarker, is needed to aid in mTBI diagnosis, prognosis, return to play/duty assessments, and would further elucidate mTBI pathophysiology. The majority of TBI biomarker research focuses on severe TBI with few studies specific to mild injury. Most studies use a hypothesis-driven approach, screening biofluids for markers known to be associated with TBI pathophysiology. This approach has yielded limited success in identifying markers that can be used clinically, additional candidate biomarkers are needed. Innovative and unbiased methods such as proteomics, microRNA arrays, urinary screens, autoantibody identification and phage display would complement more traditional approaches to aid in the discovery of novel mTBI biomarkers. PMID:25981889

Oral health in patients with chronic kidney disease - emphasis on periodontitis

OpenAIRE

Nylund, Karita

2017-01-01

ORAL HEALTH IN PATIENTS WITH CHRONIC KIDNEY DISEASE - EMPHASIS ON PERIODONTITIS Background: Periodontitis is a common bacteria-induced chronic inflammatory disease with mild symptoms. It leads to destruction of the periodontium and finally to tooth loss in a susceptible patient. Periodontitis is associated with many systemic diseases such as diabetes, atherosclerosis, cardiovascular diseases, and chronic kidney disease (CKD) through low-grade systemic inflammation. However, no causality c...

[Chronic mild inflammation links obesity, metabolic syndrome, atherosclerosis and diabetes].

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Andel, M; Polák, J; Kraml, P; Dlouhý, P; Stich, V

2009-01-01

Chronic low grade inflammation is relatively new concept in metabolic medicine. This concept describes the relations between the inflammation and adipose tissue, insulin resistence, atherosclerosis and type 2 diabetes mellitus. Macrophages and lymphocytes deposed in adipose tissue produce proinflammatory cytokines which directly or through the CRP liver secretion are targeting endothelial cells, hepatocytes and beta cells of Langerhans islets of pancreas. The dysfunction of these cells follows often further disturbances and in case of beta cells - the cell death. The connection between the adipose tissue insulin resistence, atherosclerosis and type 2 diabetes was earlier described with endocrine and metabolic descriptors. The concept of chronic low grade inflammation creates also another description of multilateral connections in metabolic syndome. The salicylates and the drugs related to them seem to have some glucose lowering properties. The recent development in the field ofchronic low grade inflammation represents also certain therapeutic hope for antiinflammatory intervention in type 2 diabetes.

The effect of combining manual therapy with exercise for mild chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

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Engel, Roger M; Wearing, Jaxson; Gonski, Peter; Vemulpad, Subramanyam

2017-06-17

Chronic obstructive pulmonary disease (COPD) is a major cause of disability and hospital admission. Current management strategies have not been successful in altering the loss of lung function typically seen as the disease progresses. A recent systematic review into the use of spinal manipulative therapy (SMT) in the management of COPD concluded that there was low level evidence to support the view that a combination of SMT and exercise had the potential to improve lung function more than exercise alone in people with moderate to severe COPD. The aim of this study is to investigate whether the combination of exercise and manual therapy (MT) that includes SMT produces sustainable improvements in lung function and exercise capacity in people with mild COPD. The study is a randomised controlled trial of 202 people with stable mild COPD. The cohort will be divided into two equal groups matched at baseline. The first group will receive a standardised exercise program. The second group will receive MT that includes SMT plus the same standardised exercise program. Exercise will be administered a total of 36 times over an 18-week period, while MT will be administered in conjunction with exercise a total of 15 times over a 6-week period. The primary outcome measure is lung function (forced expiratory volume in the 1 st second: FEV 1 and forced vital capacity: FVC). The secondary outcome measures are the 6-minute walking test (6MWT), quality of life questionnaire (St George's Respiratory Questionnaire: SGRQ), anxiety and depression levels (Hospital Anxiety and Depression Scale: HADS), frequency of exacerbations, chest wall expansion measurements (tape measurements) and systemic inflammatory biomarker levels. Outcome measurements will be taken by blinded assessors on seven occasions over a 48-week period. Adverse event data will also be gathered at the beginning of each intervention session. This randomised controlled trial is designed to investigate whether the combination

Chronic Diarrhea: A Concern After Gallbladder Removal?

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Chronic diarrhea: A concern after gallbladder removal? I had my gallbladder removed six months ago, and I'm still having diarrhea. Is this ... mild diarrhea after cholecystectomy is not cause for concern, but speak to your doctor if you are ...

MMPI-2 profiles 23 years after paediatric mild traumatic brain injury.

Science.gov (United States)

Hessen, Erik; Anderson, Vicki; Nestvold, Knut

2008-01-01

Research suggest that post-concussive syndrome after mild traumatic brain injury (mTBI) is more common than chronic cognitive impairment. The aim of this study was to investigate very long-term outcome of subjective complaints after paediatric mTBI. The study was a follow-up 23 years after a prospective head injury study at a general hospital in Norway. Forty-one patients were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) 23 years after sustaining mTBI as children. A good overall outcome was found with scores close to the normative mean, average length of education and normal employment rate. However, the children that sustained complicated mTBI showed slightly more pathological scores, typical for mild post-concussive syndrome. The most important predictors of poor outcome were skull fracture and a combination of post-traumatic amnesia > 30 minutes and EEG pathology within 24 hours after TBI. No influence of pre- and post-injury risk factors on current MMPI-2 profiles was evident. The results give support for the notion of potentially differential impact of uncomplicated vs complicated mTBI. The findings suggest that children and adolescents sustaining complicated mTBI may be at risk of developing subtle chronic symptoms typical of post-concussive syndrome.

[Chronic pancreatitis: which is the role of 320-row CT for the staging?].

Science.gov (United States)

Stabile Ianora, Amato Antonio; Rubini, Giuseppe; Lorusso, Filomenamila; Ambriola, Angela; Rella, Leonarda; Di Crescenzo, Vincenzo; Moschetta, Marco

2013-01-01

The purpose of this study was to evaluate the diagnostic potential of multi-planar and volumetric reconstructions obtained from isotropic data by using 16-slice computed tomography (CT) in the diagnosis and staging of chronic pancreatitis. In a group of 42 patients CT images were evaluated searching for alterations in morphology and structure of the pancreas, alterations of the Wirsung duct, dilatation of the bile ducts, fluid collections, and vascular involvement of the digestive tract. The disease was then staged in mild, moderate and severe and correlated with the clinical staging. CT allowed the recognition of chronic pancreatitis in all cases. The staging was correct in 25/42 patients, with an accuracy rate of 59.5%. In the staging of moderate and severe forms, CT correlation with clinical and laboratory data was valid, but in mild forms it appeared less significant. Multi-detector CT is accurate in the recognition of moderate, advanced forms of chronic pancreatitis and in the identification of its complications, while it is poorly correlated with the clinical staging in mild forms of the disease.

Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

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Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

2014-01-01

The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

Institutionalized unpredictability and café routines: The case of young people in Bosnia and Herzegovina

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Čelebičić Vanja

2017-01-01

Full Text Available When life is very unpredictable or uncertain, a routine set of practices may become a very significant element in a person’s daily life, as it may allow a sense of protection from the unknown (Ehn & Löfgren 2010 and encourage feelings of belonging (Rapport & Dawson 1998. In this article I explore how people relate to the immediate future when their presents are filled with unpredictability. More specifically, I explore the everyday practices around café routines of some young people living in Bihać, a town in northwestern Bosnia- Herzegovina (BiH. Popular discourses often link between young people's tendencies to spend time in cafés with apathy and letargy, or alternativley with bad economic conditions. However, these views, whether empathetic or critical, are neither adeqate nor very empowering. Instead, I suggest that we must view café routines within the context of what I call ‘institutionalized unpredictability’. This allows us to distance ourselves from thinking about young people’s practices through dominant paradigms of engagement and disengagement and opens up the possibility to view café routines as ‘radically unpolitical' acts (Farthing 2010. I argue that café routines are both young people’s response to ‘institutionalized unpredictability’, as well as their way to criticize and reproduce it. I further show how institutionalized unpredictability was shaping and shaped by both state and nonstate related practices, relationships, processes and aspirations, suggesting that this is precisely what made it so powerfully pervasive and debilitating.

Unpredictability of nectar nicotine promotes outcrossing by hummingbirds in Nicotiana attenuata.

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Kessler, Danny; Bhattacharya, Samik; Diezel, Celia; Rothe, Eva; Gase, Klaus; Schöttner, Matthias; Baldwin, Ian T

2012-08-01

Many plants use sophisticated strategies to maximize their reproductive success via outcrossing. Nicotiana attenuata flowers produce nectar with nicotine at concentrations that are repellent to hummingbirds, increasing the number of flowers visited per plant. In choice tests using native hummingbirds, we show that these important pollinators learn to tolerate high-nicotine nectar but prefer low-nicotine nectar, and show no signs of nicotine addiction. Nectar nicotine concentrations, unlike those of other vegetative tissues, are unpredictably variable among flowers, not only among populations, but also within populations, and even among flowers within an inflorescence. To evaluate whether variations in nectar nicotine concentrations increase outcrossing, polymorphic microsatellite markers, optimized to evaluate paternity in native N. attenuata populations, were used to compare outcrossing in plants silenced for expression of a biosynthetic gene for nicotine production (Napmt1/2) and in control empty vector plants, which were antherectomized and transplanted into native populations. When only exposed to hummingbird pollinators, seeds produced by flowers with nicotine in their nectar had a greater number of genetically different sires, compared to seeds from nicotine-free flowers. As the variation in nectar nicotine levels among flowers in an inflorescence decreased in N. attenuata plants silenced in various combinations of three Dicer-like (DCL) proteins, small RNAs are probably involved in the unpredictable variation in nectar nicotine levels within a plant. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Reminiscence and adaptation to critical life events in older adults with mild to moderate depressive symptoms

NARCIS (Netherlands)

Korte, J.; Bohlmeijer, Ernst Thomas; Westerhof, Gerben Johan; Pot, Anne Margriet

2011-01-01

Objectives: The role of reminiscence as a way of adapting to critical life events and chronic medical conditions was investigated in older adults with mild to moderate depressive symptoms. Reminiscence is the (non)volitional act or process of recollecting memories of one's self in the past. Method:

Chronic mild stress increases alcohol intake in mice with low dopamine D2 receptor levels.

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Delis, Foteini; Thanos, Panayotis K; Rombola, Christina; Rosko, Lauren; Grandy, David; Wang, Gene-Jack; Volkow, Nora D

2013-02-01

Alcohol use disorders emerge from a complex interaction between environmental and genetic factors. Stress and dopamine D2 receptor levels (DRD2) have been shown to play a central role in alcoholism. To better understand the interactions between DRD2 and stress in ethanol intake behavior, we subjected Drd2 wild-type (+/+), heterozygous (+/-), and knockout (-/-) mice to 4 weeks of chronic mild stress (CMS) and to an ethanol two-bottle choice during CMS weeks 2-4. Prior to and at the end of the experiment, the animals were tested in the forced swim and open field tests. We measured ethanol intake and preference, immobility in the force swim test, and activity in the open field. We show that under no CMS, Drd2+/- and Drd2-/- mice had lower ethanol intake and preference compared with Drd2+/+. Exposure to CMS decreased ethanol intake and preference in Drd2+/+ and increased them in Drd2+/- and Drd2-/- mice. At baseline, Drd2+/- and Drd2-/- mice had significantly lower activity in the open field than Drd2+/+, whereas no genotype differences were observed in the forced swim test. Exposure to CMS increased immobility during the forced swim test in Drd2+/- mice, but not in Drd2+/+ or Drd2-/- mice, and ethanol intake reversed this behavior. No changes were observed in open field test measures. These findings suggest that in the presence of a stressful environment, low DRD2 levels are associated with increased ethanol intake and preference and that under this condition, increased ethanol consumption could be used as a strategy to alleviate negative mood. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Cognitive Disorders, Depressive Status and Chronic Complications of Type 2 Diabetes Mellitus

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Tache Mirela

2014-12-01

Full Text Available Background and aims: Depression and cognitive disorders were reported more frequently in patients with diabetes mellitus (DM. Our aim was to analyze the association of cognitive disorders and depression association with chronic complications of DM in a group of Romanian patients. Materials and methods: The data was analyzed from 181 patients, with a mean age of 58,3 years to whom we applied the MMSE (Mini- Mental State Examination and MADRS (Montgomery-Asberg Depression Rating Scale questionnaires. We also analyzed the presence of chronic DM complications, HbA1c and lipid profile. Results: Most patients with type 2 diabetes mellitus (T2DM had mild cognitive impairment (92%, more common in the age group 50-59 years. Chronic macrovascular complications were present in 74.58%, while chronic microvascular complications were present in 61.87% of patients with T2DM who associated mild and moderate cognitive impairment (p = 0.013. The most common form of depression was mild depression (90.2%, present in most patients with DM, regardless of progression and type of treatment. MADRS depression test scores were statistically significant correlated with the presence of peripheral artery disease - PAD (p <0.001, ischemic heart disease - IHD (p <0.001 and chronic kidney disease - CKD (p =0.05. We did not find a statistically significant correlation with HbA1c and serum lipid values (p˃0,05. Conclusion: Chronic diabetes macrovascular complications (PAD, IHD and CKD were more frequently associated with cognitive disorders and depression in patients with T2DM independent of the degree of metabolic control.

Headache Associated with Myasthenia Gravis: The Impact of Mild Ocular Symptoms

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Yoshinori Nishimoto

2011-01-01

Full Text Available Myasthenia gravis (MG patients visiting outpatient clinics frequently complain of headache. However, there have been few reports on the relation between chronic headache and myasthenia gravis (MG. We aimed to investigate whether MG symptoms affect the development or worsening of chronic headache. Among the 184 MG patients who were followed at the MG clinics, tension-type headache was observed in 71 (38.6% patients and 9 (4.9% complained of migraine. Twenty-five (13.6% complained that headache appeared or was exacerbated after the MG onset. The investigation into differences in the clinical characteristics of the MG patients showed that women tended to suffer from MG-associated headache more often than men. Logistic regression analyses revealed that female gender and mild ocular symptoms were independently predictive of headache associated with MG. Our results suggest that treatment of chronic headache should be required to improve the quality of life in MG patients.

Chronic stress disrupts neural coherence between cortico-limbic structures

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João Filipe Oliveira

2013-02-01

Full Text Available Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP and the medial prefrontal cortex (mPFC in rats subjected to short term (STS and chronic unpredictable stress (CUS. CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

Effects of a chronic stress treatment on vaccinal response in lambs.

Science.gov (United States)

Destrez, A; Boissy, A; Guilloteau, L; Andanson, S; Souriau, A; Laroucau, K; Chaillou, E; Deiss, V

2017-05-01

Farming systems can expose animals to chronic mild stress which is known to induce negative affective state. Affective state in animals, as in humans, can be assessed through behavioral cues. This study aimed to describe the effect of a chronic mild stress, known to induce a negative affective state, on sheep health through their response to vaccination. The study used 15 lambs subjected to a model of chronic mild stress for 15 weeks and 15 lambs reared under conventional farming as a control group. After 7 weeks of stressful treatment, the lambs were individually exposed to a judgment bias test to assess a putative stress-induced 'pessimism.' After 15 weeks of stressful treatment, antibody immune response was measured after an injection of a live vaccine challenge (Chlamydia abortus attenuated vaccine strain 1B). Stressed lambs displayed a pessimistic-like perception in the judgment bias test, revealing a negative affective state. Stressed and control animals showed different immunological reactions to vaccine challenge: stressed sheep had lower hemoglobin concentrations and higher platelet, granulocyte and acute-phase protein concentrations. Antibody response induced by the vaccine strain was not different between stressed and control sheep. Our results suggest that negative affective state induced by chronic stress treatment may induce a stronger inflammatory response to vaccine challenge in sheep. Improvement of animal health may be achieved through consideration of stressors that may affect the emotional and immunological state of sheep.

A putative low-carbohydrate ketogenic diet elicits mild nutritional ketosis but does not impair the acute or chronic hypertrophic responses to resistance exercise in rodents.

Science.gov (United States)

Roberts, Michael D; Holland, A Maleah; Kephart, Wesley C; Mobley, C Brooks; Mumford, Petey W; Lowery, Ryan P; Fox, Carlton D; McCloskey, Anna E; Shake, Joshua J; Mesquita, Paulo; Patel, Romil K; Martin, Jeffrey S; Young, Kaelin C; Kavazis, Andreas N; Wilson, Jacob M

2016-05-15

We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise. Copyright © 2016 the American Physiological Society.

Coping with chaos: unpredictable food supplies intensify torpor use in an arid-zone marsupial, the fat-tailed dunnart ( Sminthopsis crassicaudata)

Science.gov (United States)

Munn, Adam J.; Kern, Pippa; McAllan, Bronwyn M.

2010-06-01

The severity, duration and amplitude of extreme weather events are forecast to intensify with current climate trends, over both long (e.g. seasonal) and short (e.g. daily) time-scales. As such, the predictability of food supplies for many small endotherms is likely to become increasingly important. Numerous small mammals and birds combat food shortages using torpor, a controlled reduction in metabolic rate and body temperature that helps lower their daily energy requirements. As such, torpor often has been cited as a key feature allowing some small endotherms to survive highly unpredictable climates, such as tropics or dry deserts, but mensurative demonstrations of this are lacking. We have shown here that when a small desert marsupial, the fat-tailed dunnart ( Sminthopsis crassicaudata), is offered unpredictable levels of daily food, they increase frequency of daily torpor and length of bouts compared with animals offered ad libitum food, but this was not found for animals offered a 70% food-restricted diet. Our data suggest that simple food restriction may not be sufficient for evaluating the efficacy of torpor as a strategy for managing unpredictable climates.

Predictable and unpredictable modes of seasonal mean precipitation over Northeast China

Science.gov (United States)

Ying, Kairan; Frederiksen, Carsten S.; Zhao, Tianbao; Zheng, Xiaogu; Xiong, Zhe; Yi, Xue; Li, Chunxiang

2018-04-01

This study investigates the patterns of interannual variability that arise from the potentially predictable (slow) and unpredictable (intraseasonal) components of seasonal mean precipitation over Northeast (NE) China, using observations from a network of 162 meteorological stations for the period 1961-2014. A variance decomposition method is applied to identify the sources of predictability, as well as the sources of prediction uncertainty, for January-February-March (JFM), April-May-June (AMJ), July-August-September (JAS) and October-November-December (OND). The averaged potential predictability (ratio of slow to total variance) of NE China precipitation has the highest value of 0.32 during JAS and lowest value of 0.1 in AMJ. Possible sources of seasonal prediction for the leading predictable precipitation EOF modes come from the SST anomalies in the Japan Sea, as well as the North Atlantic during JFM, the Indian Ocean SST in AMJ, and the eastern tropical Pacific SST in JAS and OND. The prolonged linear trend, which is seen in the principal component time series of the leading predictable mode in JFM and OND, may also serve as a source of predictability. The Polar-Eurasia and Northern Annular Mode atmospheric teleconnection patterns are closely connected with the leading and the second predictable mode of JAS, respectively. The Hadley cell circulation is closely related to the leading predictable mode of OND. The leading/second unpredictable precipitation modes for all these four seasons show a similar monopole/dipole structure, and can be largely attributed to the intraseasonal variabilities of the atmosphere.

Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury : Acute versus chronic disturbances?

NARCIS (Netherlands)

Metting, Zwany; Spikman, Jacoba M.; Rodiger, Lars A.; van der Naalt, Joukje

In a subgroup of patients with mild traumatic brain injury (TBI) residual symptoms, interfering with outcome and return to work, are found. With neuropsychological assessment cognitive deficits can be demonstrated although the pathological underpinnings of these cognitive deficits are not fully

Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress

Science.gov (United States)

Wei, Sheng; Ji, Xiao-wei; Wu, Chun-ling; Li, Zi-fa; Sun, Peng; Wang, Jie-qiong; Zhao, Qi-tao; Gao, Jie; Guo, Ying-hui; Sun, Shi-guang; Qiao, Ming-qi

2014-01-01

Background Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. Material/Methods Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. Results In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. Conclusions Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS. PMID:24911067

Young-Adult Male Rats’ Vulnerability to Chronic Mild Stress Is Reflected by Anxious-Like instead of Depressive-Like Behaviors

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Herrera-Pérez José Jaime

2016-01-01

Full Text Available In a previous study, we found that chronic mild stress (CMS paradigm did not induce anhedonia in young-adult male rats but it reduced their body weight gain. These contrasting results encouraged us to explore other indicators of animal’s vulnerability to stress such as anxious-like behaviors, since stress is an etiologic factor also for anxiety. Thus, in this study, we evaluated the vulnerability of these animals to CMS using behavioral tests of depression or anxiety and measuring serum corticosterone. Male Wistar rats were exposed to four weeks of CMS; the animals’ body weight and sucrose preference (indicator of anhedonia were assessed after three weeks, and, after the fourth week, some animals were evaluated in a behavioral battery (elevated plus maze, defensive burying behavior, and forced swimming tests; meanwhile, others were used to measure serum corticosterone. We found that CMS (1 did not affect sucrose preference, immobility behavior in the forced swimming test, or serum corticosterone; (2 decreased body weight gain; and (3 increased the rat’s entries into closed arms of the plus maze and the cumulative burying behavior. These data indicate that young male rats’ vulnerability to CMS is reflected as poor body weight gain and anxious-like instead of depressive-like behaviors.

Direct measurement of skeletal muscle fatigue in patients with chronic heart failure.

OpenAIRE

Buller, N P; Jones, D; Poole-Wilson, P A

1991-01-01

Skeletal muscle function was measured as force production and fatigue in both the quadriceps (a large locomotive muscle) and adductor pollicis (a small intrinsic hand muscle) in five healthy volunteers, five patients with mild chronic heart failure, and five patients with severe chronic heart failure. The quadriceps of patients with chronic heart failure had a reduced muscle cross sectional area, a reduced maximum isometric force production, and an increased tendency to fatigue. Isometric for...

Airway distensibility in Chronic Obstructive Airway Disease

DEFF Research Database (Denmark)

Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

2013-01-01

Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema......-20% (mild), 20%-30% (moderate) or >30% (severe). Spirometry was performed annually and participants were divided into severity groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Data were analysed in a mixed effects regression model with log(airway lumen diameter...... and emphysema, respectively. Conclusions – Airway distensibility decreases significantly with increasing severity of both GOLD status and emphysema, indicating that in COPD the dynamic change in airway calibre during respiration is compromised. Chronic bronchitis and emphysema appear to be interacting...

Distinctiveness revisited: unpredictable temporal isolation does not benefit short-term serial recall of heard or seen events.

Science.gov (United States)

Nimmo, Lisa M; Lewandowsky, Stephan

2006-09-01

The notion of a link between time and memory is intuitively appealing and forms the core assumption of temporal distinctiveness models. Distinctiveness models predict that items that are temporally isolated from their neighbors at presentation should be recalled better than items that are temporally crowded. By contrast, event-based theories consider time to be incidental to the processes that govern memory, and such theories would not imply a temporal isolation advantage unless participants engaged in a consolidation process (e.g., rehearsal or selective encoding) that exploited the temporal structure of the list. In this report, we examine two studies that assessed the effect of temporal distinctiveness on memory, using auditory (Experiment 1) and auditory and visual (Experiment 2) presentation with unpredictably varying interitem intervals. The results show that with unpredictable intervals temporal isolation does not benefit memory, regardless of presentation modality.

Mild asthma and chronic bronchitis seem to influence functional exercise capacity: a multi-case control study.

Science.gov (United States)

Marcon, Alessandro; Girardi, Paolo; Ferrari, Marcello; Olivieri, Mario; Accordini, Simone; Bombieri, Cristina; Bortolami, Oscar; Braggion, Marco; Cappa, Veronica; Cazzoletti, Lucia; Locatelli, Francesca; Nicolis, Morena; Perbellini, Luigi; Sembeni, Silvia; Verlato, Giuseppe; Zanolin, Maria Elisabetta; de Marco, Roberto

2013-01-01

In the Genes Environment Interaction in Respiratory Diseases population-based multi-case control study, we investigated whether asthma, chronic bronchitis (CB) and rhinitis were associated with a reduced 6-minute walk distance (6MWD), and whether the 6MWD determinants were similar for subjects with/without respiratory diseases. Cases of asthma (n = 360), CB (n = 120), rhinitis (n = 203) and controls (no respiratory diseases: n = 302) were recruited. The variation in the 6MWD across the groups was analyzed by ANCOVA, adjusting for gender, age, height, weight and comorbidity. The 6MWD determinants were studied by linear regression, and heterogeneity across the cases and controls was investigated. The 6MWD differed across cases and controls (p = 0.01). It was shorter for cases of asthma (-17.1, 95% CI -28.3 to -5.8 m) and CB (-20.7, 95% CI: -36.6 to -4.8 m) than for controls (604 ± 68 m on average), but not for cases of rhinitis. The negative association between age and the 6MWD was significant for cases of CB, but not for the other groups (p = 0.001). Even at the level of severity found in the general population, asthma and CB could influence the 6MWD, which seems to reflect the functional exercise level for daily physical activities. The negative association between ageing and the 6MWD was particularly strong in subjects with CB. Our report adds to the mounting evidence that CB is not a trivial condition, especially in the ageing adult population, and it supports the importance of monitoring functional capacity and of physical reconditioning in mild asthma. Copyright © 2013 S. Karger AG, Basel.

Effects of chronic mild stress on parameters of bone assessment in adult male and female rats

Directory of Open Access Journals (Sweden)

Fabrício L. Valente

Full Text Available Abstract: Osteoporosis is a multifactorial disease of high prevalence and has great impact on quality of life, because the effects on bone structure increase the risk of fractures, what may be very debilitating. Based on the observation that patients with depression have lower bone mineral density than healthy individuals, many studies have indicated that stress could be an aggravating factor for bone loss. This study evaluates the effect of a protocol of chronic mild stress (CMS on parameters of bone assessment in male and female rats. Five 5-monh-old rats of each sex underwent a schedule of stressor application for 28 days. Stressors included cold, heat, restraint, cage tilt, isolation, overnight illumination, and water and food deprivation. Five rats of each sex were kept under minimum intervention as control group. The animals were weighed at beginning and end of the period, and after euthanasia had their bones harvested. Femur, tibia and lumbar vertebrae were analyzed by bone densitometry. Biomechanical tests were performed in femoral head and diaphysis. Trabecular bone volume was obtained from histomorphometric analysis of femoral head and vertebral body, as well as of femoral midshaft cross-sectional measures. Not all parameters analyzed showed effect of CMS. However, tibial and L4 vertebral bone mineral density and cross-sectional cortical/medullar ratio of femoral shaft were lower in female rats submitted to the CMS protocol. Among male rats, the differences were significant for femoral trabecular bone volume and maximum load obtained by biomechanical test. Thus, it could be confirmed that CMS can affect the balance of bone homeostasis in rats, what may contribute to the establishment of osteopenia or osteoporosis.

Pervasive developmental disorder behavior in adolescents with intellectual disability and co-occurring somatic chronic diseases

NARCIS (Netherlands)

Oeseburg, B.; Groothoff, J. W.; Dijkstra, G. J.; Reijneveld, S. A.; Jansen, D. E. M. C.

2010-01-01

Evidence on the association between somatic chronic diseases in ID-adolescents and the full range of pervasive developmental disorder behavior (PDD behavior) is scarce. The aim of the present study is to assess the association between somatic chronic diseases in ID-adolescents and mild PDD behavior.

Decreased Prostaglandin D2 Levels in Major Depressive Disorder Are Associated with Depression-Like Behaviors.

Science.gov (United States)

Chu, Cuilin; Wei, Hui; Zhu, Wanwan; Shen, Yan; Xu, Qi

2017-09-01

Prostaglandin (PG) D2 is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD2 in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD2 synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD2 levels in major depressive disorder. Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD2 in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD2 levels in mice. Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD2 production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine. Decreased PGD2 levels in major depressive disorder are associated with depression-like behaviors. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Fat or lean: adjustment of endogenous energy stores to predictable and unpredictable changes in allostatic load

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Schultner, Jannik; Kitaysky, Alexander S.; Welcker, Jorg; Hatch, Scott

2013-01-01

1. The ability to store energy endogenously is an important ecological mechanism that allows animals to buffer predictable and unpredictable variation in allostatic load. The secretion of glucocorticoids, which reflects changes in allostatic load, is suggested to play a major role in the adjustment of endogenous stores to these varying conditions.

Neurodegeneration after mild and repetitive traumatic brain injury: Chronic traumatic encepalopathy

Directory of Open Access Journals (Sweden)

Stanescu Ioana

2015-09-01

Full Text Available Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE. Although research on the long-term effects of TBI is advancing quickly, the incidence and prevalence of post-traumatic neurodegeneration and CTE are unknown. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently under research. CTE can be diagnosed only by post mortem neuropathological examination of the brain. Great efforts are being made to better understand the clinical signs and symptoms of CTE, obtained in most cases retrospectively from families of affected persons.Patients with CTE are described as having behavioral, mood, cognitive and motor impairments, occurring after a long latency from the traumatic events. Recent pathogenetic studies have provided new insights to CTE mechanisms, offering important clues in understanding neurodegenerative process and relations between physical factors and pathologic protein deposition. Further research is needed to better identify the genetic and environmental risk factors for CTE, as well as rehabilitation and treatment strategies.

A systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury. Results of the International Collaboration on MTBI Prognosis (ICoMP)

DEFF Research Database (Denmark)

Godbolt, Allison; Cancelliere, Carol; Hincapié, Cesar A

2014-01-01

Objective: To synthesize the best available evidence regarding the risk of dementia and chronic cognitive impairment (CCI), following mild traumatic brain injury (MTBI). Data sources: MEDLINE and other databases were searched (2001–2012), using a previously published search strategy and pre...... was acceptable for 101 (33%), of which one considered dementia and seven CCI. The study examining the risk of dementia after MTBI did not find an association. One RCT found that being informed about possible cognitive dysfunction after MTBI was associated with worse cognitive performance on standard tests....... Children with MTBI and intracranial pathology (‘complicated’ MTBI) performed worse than children without intracranial pathology. Children showed higher rates of cognitive symptoms 1 year after MTBI than a control group. Conclusions: There is a lack of evidence of increased risk of dementia after MTBI...

Getting to grips with election night forecasting: Predicting the unpredictable world of politics

CSIR Research Space (South Africa)

Holloway, Jennifer P

2009-04-23

Full Text Available , it is an exhilarating experience being at the IEC's headquarters during the elections. "The whole building is abuzz, with political parties and media representatives all having their own booths and swarming around the floor. We have found that the smaller parties... with. Election night forecasting Predicting the unpredictable world of politics On 22 April 2009, after the voting population has used its right to cast its individual votes in the fourth democratic elections of South Africa, a team...

Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress.

Science.gov (United States)

Wang, Chunye; Guo, Jianyou; Guo, Rongjuan

2017-01-24

Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven't been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model. The rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested. The expression of cAMP, CREB, PKA and BDNF protein in hippocampus was examined with Elisa and Western Blot. The mRNA level of CREB and BDNF in hippocampus was measured with PCR. The results demonstrated that rats subjected to CUS exhibited decreases in sucrose preference, total ambulation, percentage of central ambulation, rearing in the open field test and spatial performance in the MWM. CUS reduced the expression of cAMP, PKA, CREB and BDNF in hippocampus of model rats. These effects could be reversed by XPJY. The results indicated that XPJY can improve depression and

Psychiatric aspec ts of chronic physical illness in adolescence

African Journals Online (AJOL)

2008-05-18

May 18, 2008 ... Survival rates for children who suffer chronic physical illnesses have increased dramatically in ... may have a profound impact on development, quality of life, treatment .... emotional, cognitive and social elements. ... trigger psychiatric disorder in a parent, which in .... attainment and employment suggest mild.

[Correlation of matrix metalloproteinase-9 polymorphisms with chronic periodontitis in Uygur adults].

Science.gov (United States)

Ma, T; Li, D D; Huang, P; Zhao, J

2017-06-09

Objective: To investigate the association between matrix metalloproteinase-9 (MMP-9) polymorphisms and chronic periodontitis in Uygur adults. Methods: A total of 196 patients with chronic periodontitis and 97 healthy controls were selected from 2 500 Uygur people. Buccal swab samples were taken, the genomic DNA was extracted and the genotype distribution and allele frequency of MMP-9 were determined by PCR-restriction fragment length polymorphism (PCR-RFLP). The distribution of genotypes, allele frequencies and risk factors were analyzed by chi-square test and multiple logistic regression. Results: Significant difference was found between healthy controls and the mild periodontitis and moderate to severe periodontitis in the MMP-9 1562C/T CC genotype expression (χ(2)=9.901, P= 0.002; χ(2)=13.397, Pperiodontitis and between the mild periodontitis and moderate to severe periodontitis (χ(2)=8.025, P= 0.005; χ(2)=11.159, Pperiodontitis and between mild periodontitis and moderate to severe periodontitis (χ(2)=6.270, P= 0.012; χ(2)=8.184, P= 0.004). Logistic analysis showed that age under 35 years old was the protective factor of chronic periodontitis ( OR= 0.061, 95% CI =0.035-0.108, Pchronic periodontitis ( OR= 2.392, 95% CI =1.496-3.819, Pchronic periodontitis in Uygur adults in Moyu county of Xinjiang is related to the age and gender and polymorphism of MMP-9. The age over 35 years old, male and CT genotype may be the risk factors of chronic periodontitis in Uygur adults.

Chronic traumatic encephalopathy: The unknown disease.

Science.gov (United States)

Martínez-Pérez, R; Paredes, I; Munarriz, P M; Paredes, B; Alén, J F

2017-04-01

Chronic traumatic encephalopathy is a neurodegenerative disease produced by accumulated minor traumatic brain injuries; no definitive premortem diagnosis and no treatments are available for chronic traumatic encephalopathy. Risk factors associated with chronic traumatic encephalopathy include playing contact sports, presence of the apolipoprotein E4, and old age. Although it shares certain histopathological findings with Alzheimer disease, chronic traumatic encephalopathy has a more specific presentation (hyperphosphorylated tau protein deposited as neurofibrillary tangles, associated with neuropil threads and sometimes with beta-amyloid plaques). Its clinical presentation is insidious; patients show mild cognitive and emotional symptoms before progressing to parkinsonian motor signs and finally dementia. Results from new experimental diagnostic tools are promising, but these tools are not yet available. The mainstay of managing this disease is prevention and early detection of its first symptoms. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Mild Cognitive Impairment (MCI)

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Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It ...

Effects of prenatal exposure to chronic mild stress and toluene in rats

DEFF Research Database (Denmark)

Hougaard, K. S.; Andersen, Maud Bering; Hansen, A. M.

2005-01-01

The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated in fe...

Neurocognitive, Social-Behavioral, and Adaptive Functioning in Preschool Children with Mild to Moderate Kidney Disease

Science.gov (United States)

Hooper, Stephen R.; Gerson, Arlene C.; Johnson, Rebecca J.; Mendley, Susan R.; Shinnar, Shlomo; Lande, Marc B.; Matheson, Matthew B.; Gipson, Debbie S.; Morgenstern, Bruce; Warady, Bradley A.; Furth, Susan L.

2016-01-01

Objective The negative impact of End Stage Kidney Disease on cognitive function in children is well established, but no studies have examined the neurocognitive, social-behavioral, and adaptive behavior skills of preschool children with mild to moderate chronic kidney disease (CKD). Methods Participants included 124 preschool children with mild to moderate CKD, ages 12-68 months (median=3.7 years), and an associated mean glomerular filtration rate (GFR) of 50.0 ml/min per 1.73m2. In addition to level of function and percent of participants scoring≥1SD below the test mean, regression models examined the associations between biomarkers of CKD (GFR, anemia, hypertension, seizures, abnormal birth history), and Developmental Level/IQ, attention regulation, and parent ratings of executive functions, social-behavior, and adaptive behaviors. Results Median scores for all measures were in the average range; however, 27% were deemed at-risk for a Developmental Level/IQpreschool children with mild to moderate CKD, but the need for ongoing developmental surveillance in this population remains warranted, particularly for those with abnormal birth histories, seizures, and heightened disease severity. PMID:26890559

Isolation stress and chronic mild stress induced immobility in the defensive burying behavior and a transient increased ethanol intake in Wistar rats.

Science.gov (United States)

Vázquez-León, Priscila; Martínez-Mota, Lucía; Quevedo-Corona, Lucía; Miranda-Páez, Abraham

2017-09-01

Stress can be experienced with or without adverse effects, of which anxiety and depression are two of the most important due to the frequent comorbidity with alcohol abuse in humans. Historically, stress has been considered a cause of drug use, particularly alcohol abuse due to its anxiolytic effects. In the present work we exposed male Wistar rats to two different stress conditions: single housing (social isolation, SI), and chronic mild stress (CMS). We compared both stressed groups to group-housed rats and rats without CMS (GH) to allow the determination of a clear behavioral response profile related to their respective endocrine stress response and alcohol intake pattern. We found that SI and CMS, to a greater extent, induced short-lasting increased sucrose consumption, a transient increase in serum corticosterone level, high latency/immobility, and low burying behavior in the defensive burying behavior (DBB) test, and a transient increase in alcohol intake. Thus, the main conclusion was that stress caused by both SI and CMS induced immobility in the DBB test and, subsequently, induced a transient increased voluntary ethanol intake in Wistar rats with a free-choice home-cage drinking paradigm. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.

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Steckert, Amanda V; Dominguini, Diogo; Michels, Monique; Abelaira, Helena M; Tomaz, Débora B; Sonai, Beatriz; de Moura, Airam B; Matos, Danyela; da Silva, Júlia B I; Réus, Gislaine Z; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe

2017-11-01

The present study was created to investigate the effects of chronic mild stress (CMS) on the depressive behavior and neurochemical parameters of rats that were subjected to sepsis. Wistar rats were subjected to a CMS protocol, and sepsis was induced by cecal ligation and perforation (CLP). The animals were then divided into 4 separate groups; Control + Sham (n = 20), Control + CLP (n = 30), CMS + Sham (n = 20) and CMS + CLP (n = 30). Body weight, food and water intake and mortality were measured on a daily basis for a period of 10 days after the induction of sepsis. Locomotor activity, splash and forced swimming tests were performed ten days after CLP. At the end of the test period, the animals were euthanized, and the prefrontal cortex and hippocampus were removed to determine the levels of cytokines and oxidative damage. Our results show that there was no significant interaction between CMS and CLP in relation to locomotor activity and the forced swimming test. However, we did observe a significant decrease in total grooming time in the Control + CLP and CMS + Sham groups, with the CMS + CLP group showing behavior similar to that of the control animals. This was found to be related to a decrease in the levels of brain cytokines, and not to oxidative damage parameters. Collectively, our results suggest that a previous stress caused by CMS can protect the brain against the systemic acute and severe stress elicited by sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Validation of the long-term assessment of hypothalamic-pituitary-adrenal activity in rats using hair corticosterone as a biomarker.

Science.gov (United States)

Scorrano, Fabrizio; Carrasco, Javier; Pastor-Ciurana, Jordi; Belda, Xavier; Rami-Bastante, Alicia; Bacci, Maria Laura; Armario, Antonio

2015-03-01

The evaluation of chronic activity of the hypothalamic-pituitary-adrenal (HPA) axis is critical for determining the impact of chronic stressful situations. However, current methods have important limitations. The potential use of hair glucocorticoids as a noninvasive retrospective biomarker of long-term HPA activity is gaining acceptance in humans and wild animals. However, there is no study examining hair corticosterone (HC) in laboratory animals. The present study validates a method for measuring HC in rats and demonstrates that it properly reflects chronic HPA activity. The HC concentration was similar in male and female rats, despite higher total plasma corticosterone levels in females, tentatively suggesting that it reflects free rather than total plasma corticosterone. Exposure of male rats to 2 different chronic stress protocols (chronic immobilization and chronic unpredictable stress) resulted in similarly higher HC levels compared to controls (1.8-fold). HC also increased after a mild chronic stressor (30 min daily restraint). Chronic administration of 2 different doses of a long-acting ACTH preparation dramatically increased HC (3.1- and 21.5-fold, respectively), demonstrating that a ceiling effect in HC accumulation is unlikely under other more natural conditions. Finally, adrenalectomy significantly reduced HC. In conclusion, HC measurement in rats appears appropriate to evaluate integrated chronic changes in circulating corticosterone. © FASEB.

Cerebral blood flow and CO2 reactivity in transient ischemic attacks: comparison between TIAs due to the ICA occlusion and ICA mild stenosis

International Nuclear Information System (INIS)

Tsuda, Y.; Kimura, K.; Yoneda, S.; Etani, H.; Asai, T.; Nakamura, M.; Abe, H.

1983-01-01

Hemispheric mean cerebral blood flow (CBF), together with its CO2 reactivity in response to hyperventilation, was investigated in 18 patients with transient ischemic attacks (TIAs) by intraarterial 133Xe injection method in a subacute-chronic stage of the clinical course. In 8 patients, the lesion responsible for symptoms was regarded as unilateral internal carotid artery (ICA) occlusion, and in 10 patients, it was regarded as unilateral ICA mild stenosis (less than 50% stenosis in diameter). Resting flow values were significantly decreased in the affected hemisphere of TIA due to the ICA occlusion as compared with the unaffected hemisphere of the same patient, regarded as the relative control. It was not decreased in the affected hemisphere of TIA due to the ICA mild stenosis as compared with the control. With respect to the responsiveness of CBF to changes in PaCO2, it was preserved in both TIAs, due to the ICA occlusion and ICA mild stenosis. Vasoparalysis was not observed in either types of TIAs in the subacute-chronic stage. However, in the relationship of blood pressure and CO2 reactivity, expressed as delta CBF(%)/delta PaCO2, pressure-dependent CO2 reactivity as a group was observed with significance in 8 cases of TIA due to the ICA occlusion, while no such relationship was noted in 10 cases of TIA due to the ICA mild stenosis. Moreover, clinical features were different between TIAs due to the ICA occlusion and ICA mild stenosis, i.e., more typical, repeatable TIA (6.3 +/- 3.7 times) with shorter duration (less than 30 minutes) was observed in TIAs due to the ICA mild stenosis, while more prolonged, less repeatable TIA (2.4 +/- 1.4 times) was observed in TIAs due to fixed obstruction of the ICA. From these observations, two different possible mechanisms as to the pathogenesis of TIA might be expected

Pervasive Developmental Disorder Behavior in Adolescents with Intellectual Disability and Co-Occurring Somatic Chronic Diseases

Science.gov (United States)

Oeseburg, B.; Groothoff, J. W.; Dijkstra, G. J.; Reijneveld, S. A.; Jansen, D. E. M. C.

2010-01-01

Evidence on the association between somatic chronic diseases in ID-adolescents and the full range of pervasive developmental disorder behavior (PDD behavior) is scarce. The aim of the present study is to assess the association between somatic chronic diseases in ID-adolescents and mild PDD behavior. We obtained data on 1044 ID-adolescents, aged…

Unpredictability of escape trajectory explains predator evasion ability and microhabitat preference of desert rodents.

Science.gov (United States)

Moore, Talia Y; Cooper, Kimberly L; Biewener, Andrew A; Vasudevan, Ramanarayan

2017-09-05

Mechanistically linking movement behaviors and ecology is key to understanding the adaptive evolution of locomotion. Predator evasion, a behavior that enhances fitness, may depend upon short bursts or complex patterns of locomotion. However, such movements are poorly characterized by existing biomechanical metrics. We present methods based on the entropy measure of randomness from Information Theory to quantitatively characterize the unpredictability of non-steady-state locomotion. We then apply the method by examining sympatric rodent species whose escape trajectories differ in dimensionality. Unlike the speed-regulated gait use of cursorial animals to enhance locomotor economy, bipedal jerboa (family Dipodidae) gait transitions likely enhance maneuverability. In field-based observations, jerboa trajectories are significantly less predictable than those of quadrupedal rodents, likely increasing predator evasion ability. Consistent with this hypothesis, jerboas exhibit lower anxiety in open fields than quadrupedal rodents, a behavior that varies inversely with predator evasion ability. Our unpredictability metric expands the scope of quantitative biomechanical studies to include non-steady-state locomotion in a variety of evolutionary and ecologically significant contexts.Biomechanical understanding of animal gait and maneuverability has primarily been limited to species with more predictable, steady-state movement patterns. Here, the authors develop a method to quantify movement predictability, and apply the method to study escape-related movement in several species of desert rodents.

Managing the continuum certainty, uncertainty, unpredictability in large engineering projects

CERN Document Server

Caron, Franco

2013-01-01

The brief will describe how to develop a risk analysis applied to a project , through a sequence of steps: risk management planning, risk identification, risk classification, risk assessment, risk quantification, risk response planning, risk monitoring and control, process close out and lessons learning. The project risk analysis and management process will be applied to large engineering projects, in particular related to the oil and gas industry. The brief will address the overall range of possible events affecting the project moving from certainty (project issues) through uncertainty (project risks) to unpredictability (unforeseeable events), considering both negative and positive events. Some quantitative techniques (simulation, event tree, Bayesian inference, etc.) will be used to develop risk quantification. The brief addresses a typical subject in the area of project management, with reference to large engineering projects concerning the realization of large plants and infrastructures. These projects a...

Combat Veterans with PTSD after Mild TBI Exhibit Greater ERPs from Posterior-medial Cortical Areas While Appraising Facial Features

Science.gov (United States)

2014-01-01

E.W., Karl , A., 2013. Meta-analytic review of P3 components in posttraumatic stress disorder and their clinical utility. Clin. EEG Neurosci.. Jorge...Weiner, J., Marx , C.E., Cernak, I., McCarthy, G., Group, M.W., 2012. Effects of chronic mild traumatic brain injury on white matter integrity in Iraq and

Self-esteem of young adults with chronic health conditions: appraising the effects of perceived impact.

Science.gov (United States)

Ireys, H T; Gross, S S; Werthamer-Larsson, L A; Kolodner, K B

1994-12-01

The relationships between selected condition characteristics and self-esteem were investigated in a randomly drawn, community-based sample of 286 young adults with chronic illnesses and disabilities. Whether appraisals of the impact of the condition mediated relationships between condition characteristics and self-esteem, as measured by the Rosenberg Self-Esteem Scale, was also measured. As a group, the youth in this sample reported positive self-esteem. When sociodemographic and condition-related variables were considered simultaneously, maternal education, unpredictability of symptoms, prognosis, sensory impairment, and the presence of a co-occurring learning disability were found to have direct effects on esteem. Perceived impact mediated the relationship between condition characteristics and self-esteem. The results are discussed in relation to the role of impact appraisal in determining the emotional well-being of young adults with chronic illnesses.

Synergist effects of n-acetylcysteine and deferoxamine treatment on behavioral and oxidative parameters induced by chronic mild stress in rats.

Science.gov (United States)

Arent, Camila O; Réus, Gislaine Z; Abelaira, Helena M; Ribeiro, Karine F; Steckert, Amanda V; Mina, Francielle; Dal-Pizzol, Felipe; Quevedo, João

2012-12-01

A growing body of evidence has pointed to a relationship between oxidative stress and depression. Thus, the present study was aimed at evaluating the effects of the antioxidants n-acetylcysteine (NAC), deferoxamine (DFX) or their combination on sweet food consumption and oxidative stress parameters in rats submitted to 40days of exposure to chronic mild stress (CMS). Our results showed that in stressed rats treated with saline, there was a decrease in sweet food intake and treatment with NAC or NAC in combination with DFX reversed this effect. Treatment with NAC and DFX decreased the oxidative damage, which include superoxide and TBARS production in submitochondrial particles, and also thiobarbituric acid reactive substances (TBARS) levels and carbonyl proteins in the prefrontal cortex, amygdala and hippocampus. Treatment with NAC and DFX also increased the activity of the antioxidant enzymes, superoxide dismutase and catalase in the same brain areas. Even so, a combined treatment with NAC and DFX produced a stronger increase of antioxidant activities in the prefrontal cortex, amygdala and hippocampus. The results described here indicate that co-administration may induce a more pronounced antidepressant activity than each treatment alone. In conclusion, these results suggests that treatment with NAC or DFX alone or in combination on oxidative stress parameters could have positive effects against neuronal damage caused by oxidative stress in major depressive disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

The prevalence of fibromyalgia in other chronic pain conditions.

Science.gov (United States)

Yunus, Muhammad B

2012-01-01

Central sensitivity syndromes (CSS) include fibromyalgia syndrome (FMS), irritable bowel syndrome, temporomandibular disorder, restless legs syndrome, chronic fatigue syndrome, and other similar chronic painful conditions that are based on central sensitization (CS). CSS are mutually associated. In this paper, prevalence of FMS among other members of CSS has been described. An important recent recognition is an increased prevalence of FMS in other chronic pain conditions with structural pathology, for example, rheumatoid arthritis, systemic lupus, ankylosing spondylitis, osteoarthritis, diabetes mellitus, and inflammatory bowel disease. Diagnosis and proper management of FMS among these diseases are of crucial importance so that unwarranted use of such medications as corticosteroids can be avoided, since FMS often occurs when RA or SLE is relatively mild.

Gallbladder emptying in chronic pancreatitis a scintigraphic evaluation

International Nuclear Information System (INIS)

Buchpiguel, C.A.; Pedroso, M.; Sapioenza, M.; Watanabe, T.; Costa, P.; Yamashiba, C.; Melo, I.; Garcez, A.

1997-01-01

Full text: Our purpose was to evaluate the gallbladder (GB) emptying in pts with chronic pancreatitis and to determine whether or not the use of pancreatic extract has an impact in improving that function. The GB emptying was evaluated in 11 patients (pts) with mild to moderate chronic pancreatitis, and in 10 normal volunteers. Pts and controls who presented any kind of condition that could interfere with the gastric or gallbladder emptying were excluded. The GB ejection fraction was calculated at 30, 45, and 60 minutes after a standardized fatty meal ingestion. In the pts group, this evaluation was obtained in two different periods of time, without and with the addition of pancreatic extract. The gastric emptying was previously determined in all patients and controls with Technetium-99m-sulfur colloid mixed in the same fatty meal used for the hepatobiliary scans. The results disclosed that the GB ejection fraction at 60 minutes was significantly lower in patients compared to controls ( 0,05). The gastric emptying was similar between the two groups (p>0,05). In conclusion, mild to moderate chronic pancreatitis is associated with GB function impairment. Our results suggest that the delay in GB emptying does not depend exclusively on the alteration in the intestinal phase of the GB stimulation, but may be a result of multiple other factors

Cut-Off Points for Mild, Moderate, and Severe Pain on the Numeric Rating Scale for Pain in Patients with Chronic Musculoskeletal Pain: Variability and Influence of Sex and Catastrophizing.

Science.gov (United States)

Boonstra, Anne M; Stewart, Roy E; Köke, Albère J A; Oosterwijk, René F A; Swaan, Jeannette L; Schreurs, Karlein M G; Schiphorst Preuper, Henrica R

2016-01-01

Objectives: The 0-10 Numeric Rating Scale (NRS) is often used in pain management. The aims of our study were to determine the cut-off points for mild, moderate, and severe pain in terms of pain-related interference with functioning in patients with chronic musculoskeletal pain, to measure the variability of the optimal cut-off points, and to determine the influence of patients' catastrophizing and their sex on these cut-off points. Methods: 2854 patients were included. Pain was assessed by the NRS, functioning by the Pain Disability Index (PDI) and catastrophizing by the Pain Catastrophizing Scale (PCS). Cut-off point schemes were tested using ANOVAs with and without using the PSC scores or sex as co-variates and with the interaction between CP scheme and PCS score and sex, respectively. The variability of the optimal cut-off point schemes was quantified using bootstrapping procedure. Results and conclusion: The study showed that NRS scores ≤ 5 correspond to mild, scores of 6-7 to moderate and scores ≥8 to severe pain in terms of pain-related interference with functioning. Bootstrapping analysis identified this optimal NRS cut-off point scheme in 90% of the bootstrapping samples. The interpretation of the NRS is independent of sex, but seems to depend on catastrophizing. In patients with high catastrophizing tendency, the optimal cut-off point scheme equals that for the total study sample, but in patients with a low catastrophizing tendency, NRS scores ≤ 3 correspond to mild, scores of 4-6 to moderate and scores ≥7 to severe pain in terms of interference with functioning. In these optimal cut-off schemes, NRS scores of 4 and 5 correspond to moderate interference with functioning for patients with low catastrophizing tendency and to mild interference for patients with high catastrophizing tendency. Theoretically one would therefore expect that among the patients with NRS scores 4 and 5 there would be a higher average PDI score for those with low

Extracorporeal shockwave therapy in a dog with chronic bicipital tenosynovitis.

Science.gov (United States)

Venzin, C; Ohlerth, S; Koch, D; Spreng, D

2004-03-01

A 15-month-old, spayed female, Bernese mountain dog was presented to the Institute of Small Animal Surgery at the University of Zurich because of chronic left forelimb lameness. The referring veterinarian diagnosed pain in the left shoulder region and had treated the dog with systemic non-steroidal anti-inflammatory drugs and restricted exercise for a two-week period. The follow-up examination revealed only minimal improvement and therefore, the dog was referred for further diagnostic evaluation. Chronic bicipital tenosynovitis and tendinitis of the infraspinatus muscle was diagnosed based on survey radiographs, arthrography, ultrasound, computed tomography (CT), and synovial fluid cytology. The dog underwent three sessions of extracorporeal shockwave therapy and substantial clinical improvement was observed. On follow-up examinations, only mild left forelimb lameness was evident following exercise, and changes in the intertubercular groove and at the supraglenoid tuberosity appeared less active on radiographs and CT. However, six months following treatment, mild degenerative joint disease was apparent.

Understanding mild persistent asthma in children

DEFF Research Database (Denmark)

Bisgaard, Hans; Szefler, Stanley J

2005-01-01

Limitations in asthma prevalence studies and difficulties in diagnosing pediatric asthma lead to uncertainty over the full extent of mild persistent asthma in children and adolescents. Although recent surveys have reported that the majority of pediatric patients with asthma in the United States...... and Europe have symptoms consistent with mild disease, these surveys have limitations in design. Thus, the true prevalence of mild asthma remains unknown. It is unclear whether children with mild persistent asthma progress to more severe asthma, but the risk of severe asthma exacerbations seems...... to be unrelated to the symptom severity. Clinical studies restricted to pediatric patients with mild asthma are limited, but available data do suggest substantial morbidity of mild persistent asthma in this population and support inhaled corticosteroid intervention. There is a need for further investigation...

Bilateral chronic sacral neuromodulation for treatment of lower urinary tract dysfunction.

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Hohenfellner, M; Schultz-Lampel, D; Dahms, S; Matzel, K; Thüroff, J W

1998-09-01

Chronic sacral neuromodulation aims at functional restoration of selected forms of nonneurogenic and neurogenic bladder dysfunction. The original technique, as described by Tanagho and Schmidt, provides unilateral sacral nerve stimulation via an implanted stimulator powering an electrode inserted into a sacral foramen. Its drawback was that the implant failed unpredictably in some patients despite previous successful percutaneous test stimulation. Therefore, we modified the stimulation technique to improve the efficacy of chronic sacral neuromodulation. Guarded bipolar electrodes powered by an implantable neurostimulator were attached bilaterally directly to the S3 nerves through a sacral laminectomy in 9 women and 2 men (mean age 43.4 years). Of the patients 5 had urinary incontinence due to detrusor hyperactivity and 6 had urinary retention from detrusor hypocontractility. Mean followup with repeated urodynamics was 13 months (range 9 to 28). Four significant complications were encountered in 4 patients. In 10 patients the urological sequelae of the neurological disorder were alleviated significantly (50% or more), including 5 who experienced complete relief of symptoms. The efficacy of chronic sacral neuromodulation can be improved by bilateral attachment of electrodes directly to the sacral nerves.

Parkinsonsim due to a Chronic Subdural Hematoma

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Bosuk Park

2009-05-01

Full Text Available Subdural hematoma is a rare cause of parkinsonism. We present the case of a 78-year-old man with right-side dominant parkinsonism about 3 months after a minor head injury. MRI reveals a chronic subdural hematoma on the left side with mildly displaced midline structures. The parkinsonian features were almost completely disappeared after neurosurgical evacuation of the hematoma without any anti-parkinson drug.

Parkinsonsim due to a Chronic Subdural Hematoma

Science.gov (United States)

Park, Bosuk; Song, Sook Keun; Hong, Jin Yong; Lee, Phil Hyu

2009-01-01

Subdural hematoma is a rare cause of parkinsonism. We present the case of a 78-year-old man with right-side dominant parkinsonism about 3 months after a minor head injury. MRI reveals a chronic subdural hematoma on the left side with mildly displaced midline structures. The parkinsonian features were almost completely disappeared after neurosurgical evacuation of the hematoma without any anti-parkinson drug. PMID:24868353

Depression and substance use comorbidity: What we have learned from animal studies.

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Ng, Enoch; Browne, Caleb J; Samsom, James N; Wong, Albert H C

2017-07-01

Depression and substance use disorders are often comorbid, but the reasons for this are unclear. In human studies, it is difficult to determine how one disorder may affect predisposition to the other and what the underlying mechanisms might be. Instead, animal studies allow experimental induction of behaviors relevant to depression and drug-taking, and permit direct interrogation of changes to neural circuits and molecular pathways. While this field is still new, here we review animal studies that investigate whether depression-like states increase vulnerability to drug-taking behaviors. Since chronic psychosocial stress can precipitate or predispose to depression in humans, we review studies that use psychosocial stressors to produce depression-like phenotypes in animals. Specifically, we describe how postweaning isolation stress, repeated social defeat stress, and chronic mild (or unpredictable) stress affect behaviors relevant to substance abuse, especially operant self-administration. Potential brain changes mediating these effects are also discussed where available, with an emphasis on mesocorticolimbic dopamine circuits. Postweaning isolation stress and repeated social defeat generally increase acquisition or maintenance of drug self-administration, and alter dopamine sensitivity in various brain regions. However, the effects of chronic mild stress on drug-taking have been much less studied. Future studies should consider standardizing stress-induction protocols, including female subjects, and using multi-hit models (e.g. genetic vulnerabilities and environmental stress).

Prevalence of pulmonary artery hypertension in patients of chronic obstructive pulmonary disease and its correlation with stages of chronic obstructive pulmonary disease, exercising capacity, and quality of life.

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Gupta, Kamlesh Kumar; Roy, Bidyut; Chaudhary, Shyam Chand; Mishra, Arvind; Patel, M L; Singh, Jitendra; Kumar, Vivek

2018-01-01

Pulmonary arterial hypertension (PAH) is a complication of chronic obstructive pulmonary disease (COPD) in advance stages, and its presence indicates poor prognosis. The present study was design to know the prevalence of PAH in patients with COPD and its correlation with stages of COPD, exercising capacity, and quality of life. It is a cross-sectional prevalence study over a period of 1 year from August 2015 to July 2016. The study included 109 COPD patients, diagnosed by spirometry, and severity was determined according Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification criteria. Screening two-dimensional echocardiography was done to determine pulmonary arterial hypertension and exercising capacity assessed by 6 min walk test (6MWT) while the quality of life was assessed by St George respiratory Questionnaire for COPD (SGRQ-C) Questionnaires. Out of 109 patients, PAH was present in 68 (62.4%) cases consisting of mild grade 41 (37.6%), moderate grade 11 (10.1%), and severe grade 16 (14.7%). In GOLD A stage, there were 20 cases of mild PAH and Stage B included 18 cases of mild and 3 cases of moderate PAH. Stage C had 3 cases of mild and 8 cases of moderate PAH while Stage D had 16 cases of severe PAH. In 6MWT, patients with severe grade PAH fail to perform the test while patients with mild to moderate PAH walked short distance. In SGRQ-C Questionnaires symptom, activity, impact, and total score were high with the severity of PAH. The prevalence of PAH in COPD was significant. Therefore, every COPD patient should be evaluated for PAH.

Chronic 'speech catatonia' with constant logorrhea, verbigeration and echolalia successfully treated with lorazepam: a case report.

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Lee, Joseph W Y

2004-12-01

Logorrhea, verbigeration and echolalia persisted unremittingly for 3 years, with occasional short periods of motoric excitement, in a patient with mild intellectual handicap suffering from chronic schizophrenia. The speech catatonic symptoms, previously refractory to various antipsychotics, responded promptly to lorazepam, a benzodiazepine with documented efficacy in the treatment of acute catatonia but not chronic catatonia. It is suggested that pathways in speech production were selectively involved in the genesis of the chronic speech catatonic syndrome, possibly a rare form of chronic catatonia not previously described.

The effect of chronic mild hyponatremia on bone mineral loss evaluated by retrospective national Danish patient data

DEFF Research Database (Denmark)

Kruse, Christian; Eiken, Pia; Verbalis, Joseph

2016-01-01

between 2004 and 2011, supplemented with national Danish patient diagnosis and prescription reimbursement databases, a retrospective cohort study was performed. All subjects with more than one DXA scan were included, then stratified into "normonatremia" ([Na(+)]=[137.00-147.00] mmol/L) and "mild...

Normal pancreatic exocrine function does not exclude MRI/MRCP chronic pancreatitis findings.

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Alkaade, Samer; Cem Balci, Numan; Momtahen, Amir Javad; Burton, Frank

2008-09-01

Abnormal pancreatic function tests have been reported to precede the imaging findings of chronic pancreatitis. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is increasingly accepted as the primary imaging modality for the detection of structural changes of early mild chronic pancreatitis. The aim of this study was to evaluate MRI/MRCP findings in patients with symptoms consistent with chronic pancreatitis who have normal Secretin Endoscopic Pancreatic Function test. A retrospective study of 32 patients referred for evaluation of chronic abdominal pain consistent with chronic pancreatitis and reported normal standard abdominal imaging (ultrasound, computed tomography, or MRI). All patients underwent Secretin Endoscopic Pancreatic Function testing and pancreatic MRI/MRCP at our institution. We reviewed the MRI/MRCP images in patients who had normal Secretin Endoscopic Pancreatic Function testing. MRI/MRCP images were assessed for pancreatic duct morphology, gland size, parenchymal signal and morphology, and arterial contrast enhancement. Of the 32 patients, 23 had normal Secretin Endoscopic Pancreatic Function testing, and 8 of them had mild to marked spectrum of abnormal MRI/MRCP findings that were predominantly focal. Frequencies of the findings were as follows: pancreatic duct stricture (n=3), pancreatic duct dilatation (n=3), side branch ectasia (n=4), atrophy (n=5), decreased arterial enhancement (n=5), decreased parenchymal signal (n=1), and cavity formation (n=1). The remaining15 patients had normal pancreatic structure on MRI/MRCP. Normal pancreatic function testing cannot exclude abnormal MRI/MRCP especially focal findings of chronic pancreatitis. Further studies needed to verify significance of these findings and establish MRI/MRCP imaging criteria for the diagnosis of chronic pancreatitis.

Effect of chronic mild stress on hippocampal transcriptome in mice selected for high and low stress-induced analgesia and displaying different emotional behaviors.

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Lisowski, Pawel; Juszczak, Grzegorz R; Goscik, Joanna; Wieczorek, Marek; Zwierzchowski, Lech; Swiergiel, Artur H

2011-01-01

There is increasing evidence that mood disorders may derive from the impact of environmental pressure on genetically susceptible individuals. Stress-induced hippocampal plasticity has been implicated in depression. We studied hippocampal transcriptomes in strains of mice that display high (HA) and low (LA) swim stress-induced analgesia and that differ in emotional behaviors and responses to different classes of antidepressants. Chronic mild stress (CMS) affected expression of a number of genes common for both strains. CMS also produced strain specific changes in expression suggesting that hippocampal responses to stress depend on genotype. Considerably larger number of genes, biological processes, molecular functions, biochemical pathways, and gene networks were affected by CMS in LA than in HA mice. The results suggest that potential drug targets against detrimental effects of stress include glutamate transporters, and cholinergic, cholecystokinin (CCK), glucocorticoids, and thyroid hormones receptors. Furthermore, some biological processes evoked by stress and different between the strains, such as apoptosis, neurogenesis and chromatin modifications, may be responsible for the long-term, irreversible effects of stress and suggest a role for epigenetic regulation of mood related stress responses. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

A meta-ethnography of patients' experiences of chronic pelvic pain: struggling to construct chronic pelvic pain as 'real'.

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Toye, Francine; Seers, Kate; Barker, Karen

2014-12-01

To review systematically and integrate the findings of qualitative research to increase our understanding of patients' experiences of chronic pelvic pain. Chronic pelvic pain is a prevalent pain condition with a high disease burden for men and women. Its multifactorial nature makes it challenging for clinicians and patients. Synthesis of qualitative research using meta-ethnography. Five electronic bibliographic databases from inception until March 2014 supplemented by citation tracking. Of 488 papers retrieved, 32 met the review aim. Central to meta-ethnography is identifying 'concepts' and developing a conceptual model through constant comparison. Concepts are the primary data of meta-ethnography. Two team members read each paper to identify and collaboratively describe the concepts. We next compared concepts across studies and organized them into categories with shared meaning. Finally, we developed a conceptual model, or line of argument, to explain the conceptual categories. Our findings incorporate the following categories into a conceptual model: relentless and overwhelming pain; threat to self; unpredictability, struggle to construct pain as normal or pathological; a culture of secrecy; validation by diagnosis; ambiguous experience of health care; elevation of experiential knowledge and embodiment of knowledge through a community. The innovation of our model is to demonstrate, for the first time, the central struggle to construct 'pathological' vs. 'normal' chronic pelvic pain, a struggle that is exacerbated by a culture of secrecy. More research is needed to explore men's experience and to compare this with women's experience. © 2014 John Wiley & Sons Ltd.

Biographical disruption, adjustment and reconstruction of everyday occupations and work participation after mild traumatic brain injury. A focus group study.

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Sveen, Unni; Søberg, Helene Lundgaard; Østensjø, Sigrid

2016-11-01

To explore traumatic brain injury (TBI) as a biographical disruption and to study the reconstruction of everyday occupations and work participation among individuals with mild TBI. Seven focus groups were conducted with 12 women and 8 men (22-60 years) who had sustained mild TBI and participated in a return-to-work program. Interviews were analyzed using qualitative content analysis. Four interrelated themes emerged: disruption of occupational capacity and balance; changes in self-perceptions; experience of time; and occupational adjustment and reconstruction. The meaning of the impairments lies in their impact on the individual's everyday occupations. The abandonment of meaningful daily occupations and the feeling of not recognizing oneself were experienced as threats to the sense of self. Successful integration of the past, present and future was paramount to continuing life activities. The unpredictability of the future seemed to permeate the entire process of adjustment and reconstruction of daily life. Our findings show that the concept of time is important in understanding and supporting the reconstruction of daily life after TBI. The fundamental work of rehabilitation is to ameliorate the disruptions caused by the injury, restoring a sense of personal narrative and supporting the ability to move forward with life. Implications for Rehabilitation Individuals with a protracted recovery after a mild traumatic brain injury must reconstruct a new way of being and acting in the world to achieve biographical continuity. The perceived anxiety regarding changes in self and occupational identity, as well as loss of control over the future, can be attenuated through informational sessions during the hospital stay and at follow-up visits. The significant personal costs of returning to full-time employment too early indicate the need for early and ongoing vocational support in achieving a successful return to work.

Interoceptive fear learning to mild breathlessness as a laboratory model for unexpected panic attacks

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Meike ePappens

2015-08-01

Full Text Available Fear learning is thought to play an important role in panic disorder. Benign interoceptive sensations can become predictors (conditioned stimuli - CSs of massive fear when experienced in the context of an initial panic attack (unconditioned stimulus – US. The mere encounter of these CSs on a later moment can induce anxiety and fear, and precipitate a new panic attack. It has been suggested that fear learning to interoceptive cues would result in unpredictable panic. The present study aimed to investigate whether fear learning to an interoceptive CS is possible without declarative knowledge of the CS-US contingency. The CS consisted of mild breathlessness (or: dyspnea, the US was a suffocation experience. During acquisition, the experimental group received 6 presentations of mild breathlessness immediately followed by suffocation; for the control group both experiences were always separated by an intertrial interval. In the subsequent extinction phase, participants received 6 unreinforced presentations of the CS. Expectancy of the US was rated continuously and startle eyeblink EMG, skin conductance and respiration were measured. Declarative knowledge of the CS-US relationship was also assessed with a post-experimental questionnaire. At the end of acquisition, both groups displayed the same levels of US expectancy and skin conductance in response to the CS, but the experimental group showed a fear potentiated startle eyeblink and a different respiratory response to the CS compared to the control group. Further analyses on a subgroup of CS-US unaware participants confirmed the presence of startle eyeblink conditioning in the experimental group but not in the control group. Our findings suggest that interoceptive fear learning is not dependent on declarative knowledge of the CS-US relationship. The present interoceptive fear conditioning paradigm may serve as an ecologically valid laboratory model for unexpected panic attacks.

Prenatal chronic mild stress induces depression-like behavior and sex-specific changes in regional glutamate receptor expression patterns in adult rats.

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Wang, Y; Ma, Y; Hu, J; Cheng, W; Jiang, H; Zhang, X; Li, M; Ren, J; Li, X

2015-08-20

Chronic stress during critical periods of human fetal brain development is associated with cognitive, behavioral, and mood disorders in later life. Altered glutamate receptor (GluR) expression has been implicated in the pathogenesis of stress-dependent disorders. To test whether prenatal chronic mild stress (PCMS) enhances offspring's vulnerability to stress-induced behavioral and neurobiological abnormalities and if this enhanced vulnerability is sex-dependent, we measured depression-like behavior in the forced swimming test (FST) and regional changes in GluR subunit expression in PCMS-exposed adult male and female rats. Both male and female PCMS-exposed rats exhibited stronger depression-like behavior than controls. Males and females exhibited unique regional changes in GluR expression in response to PCMS alone, FST alone (CON-FST), and PCMS with FST (PCMS-FST). In females, PCMS alone did not alter N-methyl-d-aspartate receptor (NMDAR) or metabotropic glutamate receptor (mGluR) expression, while in PCMS males, higher mGluR2/3, mGluR5, and NR1 expression levels were observed in the prefrontal cortex. In addition, PCMS altered the change in GluR expression induced by acute stress (the FST test), and this too was sex-specific. Male PCMS-FST rats expressed significantly lower mGluR5 levels in the hippocampus, lower mGluR5, NR1, postsynaptic density protein (PSD)95, and higher mGluR2/3 in the prefrontal cortex, and higher mGluR5 and PSD95 in the amygdala than male CON-FST rats. Female PCMS-FST rats expressed lower NR1 in the hippocampus, lower NR2B and PSD95 in the prefrontal cortex, lower mGluR2/3 in the amygdala, and higher PSD95 in the amygdala than female CON-FST rats. PCMS may increase the offspring's vulnerability to depression by altering sex-specific stress-induced changes in glutamatergic signaling. Copyright © 2015. Published by Elsevier Ltd.

Comparing Cognitive Profiles of Licensed Drivers with Mild Alzheimer’s Disease and Mild Dementia with Lewy Bodies

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Stephanie Yamin

2016-01-01

Full Text Available Purpose. Alzheimer’s disease (AD and dementia with Lewy Bodies (DLB constitute two of the most common forms of dementia in North America. Driving is a primary means of mobility among older adults and the risk of dementia increases with advanced age. The purpose of this paper is to describe the cognitive profile of licensed drivers with mild AD and mild DLB. Method. Licensed drivers with mild AD, mild DLB, and healthy controls completed neuropsychological tests measuring general cognition, attention, visuospatial/perception, language, and cognitive fluctuations. Results. The results showed differences between healthy controls and demented participants on almost all neuropsychological measures. Participants with early DLB were found to perform significantly worse on some measures of attention and visuospatial functioning in comparison with early AD. Discussion. Future research should examine the relationship between neuropsychological measures and driving outcomes among individuals with mild AD and mild DLB.

Dendritic Spines in Depression: What We Learned from Animal Models

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Hui Qiao

2016-01-01

Full Text Available Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS, chronic unpredictable mild stress (CUMS, and chronic social defeat stress (CSDS, have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression-like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms.

Absence of Wdr13 Gene Predisposes Mice to Mild Social Isolation – Chronic Stress, Leading to Depression-Like Phenotype Associated With Differential Expression of Synaptic Proteins

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Mitra, Shiladitya; Sameer Kumar, Ghantasala S.; Jyothi Lakshmi, B.; Thakur, Suman; Kumar, Satish

2018-01-01

We earlier reported that the male mice lacking the Wdr13 gene (Wdr13-/0) showed mild anxiety, better memory retention, and up-regulation of synaptic proteins in the hippocampus. With increasing evidences from parallel studies in our laboratory about the possible role of Wdr13 in stress response, we investigated its role in brain. We observed that Wdr13 transcript gets up-regulated in the hippocampus of the wild-type mice exposed to stress. To further dissect its function, we analyzed the behavioral and molecular phenotypes of Wdr13-/0 mice when subjected to mild chronic psychological stress, namely; mild (attenuated) social isolation. We employed iTRAQ based quantitative proteomics, real time PCR and western blotting to investigate molecular changes. Three weeks of social isolation predisposed Wdr13-/0 mice to anhedonia, heightened anxiety-measured by Open field test (OFT), increased behavior despair- measured by Forced swim test (FST) and reduced dendritic branching along with decreased spine density of hippocampal CA1 neurons as compared to wild-type counterparts. This depression-like-phenotype was however ameliorated when treated with anti-depressant imipramine. Molecular analysis revealed that out of 1002 quantified proteins [1% False discovery rate (FDR), at-least two unique peptides], strikingly, a significant proportion of synaptic proteins including, SYN1, CAMK2A, and RAB3A were down-regulated in the socially isolated Wdr13-/0 mice as compared to its wild-type counterparts. This was in contrast to the elevated levels of these proteins in non-stressed mutants as compared to the controls. We hypothesized that a de-regulated transcription factor upstream of the synaptic genes might be responsible for the observed phenotype. Indeed, in the socially isolated Wdr13-/0 mice, there was an up-regulation of GATA1 – a transcription factor that negatively regulates synaptic genes and has been associated with Major Depression (MD) in humans. The present study

Community health nursing practices in contexts of poverty, uncertainty and unpredictability: a systematization of personal experiences

OpenAIRE

Laperrière,Hélène

2007-01-01

Several years of professional nursing practices, while living in the poorest neighbourhoods in the outlying areas of Brazil's Amazon region, have led the author to develop a better understanding of marginalized populations. Providing care to people with leprosy and sex workers in riverside communities has taken place in conditions of uncertainty, insecurity, unpredictability and institutional violence. The question raised is how we can develop community health nursing practices in this contex...

Consumer preferences for mild cheddar cheese flavors.

Science.gov (United States)

Drake, S L; Gerard, P D; Drake, M A

2008-11-01

Flavor is an important factor in consumer selection of cheeses. Mild Cheddar cheese is the classification used to describe Cheddar cheese that is not aged extensively and has a "mild" flavor. However, there is no legal definition or age limit for Cheddar cheese to be labeled mild, medium, or sharp, nor are the flavor profiles or flavor expectations of these cheeses specifically defined. The objectives of this study were to document the distinct flavor profiles among commercially labeled mild Cheddar cheeses, and to characterize if consumer preferences existed for specific mild Cheddar cheese flavors or flavor profiles. Flavor descriptive sensory profiles of a representative array of commercial Cheddar cheeses labeled as mild (n= 22) were determined using a trained sensory panel and an established cheese flavor sensory language. Nine representative Cheddar cheeses were selected for consumer testing. Consumers (n= 215) assessed the cheeses for overall liking and other consumer liking attributes. Internal preference mapping, cluster analysis, and discriminant analysis were conducted. Mild Cheddar cheeses were diverse in flavor with many displaying flavors typically associated with more age. Four distinct consumer clusters were identified. The key drivers of liking for mild Cheddar cheese were: color, cooked/milky, whey and brothy flavors, and sour taste. Consumers have distinct flavor and color preferences for mild Cheddar cheese. These results can help manufacturers understand consumer preferences for mild Cheddar cheese.

Caecal impaction and chronic intestinal pseudo-obstruction in a dog.

Science.gov (United States)

Eastwood, J M; McInnes, E F; White, R N; Elwood, C M; Stock, G

2005-02-01

A 10-year-old female neutered cross-breed dog presented with a 4-month history of chronic intermittent diarrhoea and vomiting. Abdominal ultrasound showed dilated loops of small intestine and a suspected faecolith. Exploratory surgery revealed a caecal impaction and a typhlectomy was performed. Histopathological examination of caecal and full thickness small intestine sections demonstrated atrophy of smooth muscle fibres as well as an influx of plasma cells, lymphocytes and macrophages, and mild lymphoplasmacytic and eosinophilic enteritis. This combination of caecal impaction and chronic intestinal pseudo-obstruction has not been reported previously in the dog.

Compulsive masturbation and chronic penile lymphedema.

Science.gov (United States)

Calabrò, Rocco Salvatore; Galì, Alessandro; Marino, Silvia; Bramanti, Placido

2012-06-01

Chronic penile lymphedema arises from the abnormal retention of lymphatic fluid in the subcutaneous tissues and may be secondary to local and systemic medical conditions such as sexually transmitted diseases, filariasis, malignancy, local radiotherapy, and surgery. This case report aims to consider compulsive masturbation as a possible cause of chronic penile edema. A 40-year-old man was referred to our institute for behavioral disturbance, including compulsive masturbation. Neuropsychiatric evaluation showed moderate mental retardation, mild dysarthria and limb incoordination, anxiety, depressed mood, and impulse dyscontrol. Brain MRI pointed out diffuse white matter lesions. Urogenital examination revealed an uncircumcised penis with non-tender edema of the shaft and prepuce with areas of lichenification. Since the most common local and systemic causes of edema were excluded, chronic penile edema due to compulsive masturbation was diagnosed and the compulsive behavior treated with an antidepressant and low-dose neuroleptics. Compulsive masturbation should be taken into account when counselling patients with penile edema.

Chronic progressive multiple sclerosis

International Nuclear Information System (INIS)

Buffoli, A.; Micheletti, E.; Capra, R.; Mattioli, F.; Marciano', N.

1991-01-01

A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Istituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable

Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences.

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Marco, Eva M; Ballesta, Javier Antonio; Irala, Carlos; Hernández, María-Donina; Serrano, María Elisa; Mela, Virginia; López-Gallardo, Meritxell; Viveros, María-Paz

2017-01-01

Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited a higher preference for alcohol compared to male animals. In particular, alcohol consumption was significantly higher among CMS females compared to CMS male animals. Remarkably, similar changes in both male and female animals exposed to CMS were observed regarding the expression levels of NCAM-140KDa (decrease), GFAP and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels (increase). However, contrasting effects in males and females were reported in relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression (a decrease among male animals but an increase in females); while the opposite pattern was observed for NCAM-140KDa protein levels in the HF. A decrease in CB2R expression was only observed in the HF of CMS-females. The present study suggests that male and female animals might be differentially affected by CMS regarding later voluntary alcohol consumption. In this initial approach, cortical SYN, and NCAM-140KDa, CB1R and CB2R expression within the HF have arisen as potential candidates to explain such sex differences in behaviour. However, the depression

[Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

Science.gov (United States)

Yan, Ying; Xiang, Xue-Rong; Wang, Chun; Ye, Guo; Fan, Xiao-Ping

2016-08-01

To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (Pperiodontal treatment, CGRP content was significantly higher compared with that before treatment (Pperiodontitis (P>0.05). The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

Surgical management of acute necrotizing pancreatitis: a 13-year experience and a systematic review

NARCIS (Netherlands)

Nieuwenhuijs, V. B.; Besselink, M. G. H.; van Minnen, L. P.; Gooszen, H. G.

2003-01-01

BACKGROUND: The course of acute pancreatitis (AP) is unpredictable and can vary from mild to lethal. Mortality varies from low ( <2%) in mild cases to high (20%-70%) in the case of infected pancreatic necrosis. Surgical management has not been investigated in well-designed trials. Based on

Chronic Depressive Symptomatology in Mild Cognitive Impairment Is Associated with Frontal Atrophy Rate which Hastens Conversion to Alzheimer Dementia.

Science.gov (United States)

Sacuiu, Simona; Insel, Philip S; Mueller, Susanne; Tosun, Duygu; Mattsson, Niklas; Jack, Clifford R; DeCarli, Charles; Petersen, Ronald; Aisen, Paul S; Weiner, Michael W; Mackin, R Scott

2016-02-01

Investigate the association of chronic depressive symptomatology (chrDS) with cortical atrophy rates and conversion to Alzheimer dementia (AD) over 3 years in mild cognitive impairment (MCI). In a multicenter, clinic-based study, MCI elderly participants were selected from the Alzheimer's Disease Neuroimaging Initiative repository, based on availability of both serial structural magnetic resonance imaging and chrDS endorsed on three depression-related items from the Neuropsychiatric Inventory Questionnaire (chrDS N = 32 or no depressive symptoms N = 62) throughout follow-up. Clinical and laboratory investigations were performed every 6 months during the first 2 years and yearly thereafter (median follow-up: 3 years; interquartile range: 1.5-4.0 years). Cortical atrophy rates in 16 predefined frontotemporoparietal regions affected in major depression and AD and the rate of incident AD at follow-up. ChrDS in a single domain amnestic MCI sample were associated with accelerated cortical atrophy in the frontal lobe and anterior cingulate but not with atrophy rates in temporomedial or other AD-affected regions. During follow-up, 38 participants (42.7%) developed AD. Participants with chrDS had 60% shorter conversion time to AD than those without depressive symptoms. This association remained significant in survival models adjusted for temporomedial atrophy rates and showed the same trend in models adjusted for frontal cortical atrophy rate, which all increased the risk of AD. Our results suggest that chrDS associated with progressive atrophy of frontal regions may represent an additional risk factor for conversion to dementia in MCI as opposite to representing typical prodromal AD symptomatology. Published by Elsevier Inc.

Contribution of chronic diseases to the mild and severe disability burden in Belgium

NARCIS (Netherlands)

R.T.C. Yokota (Renata T. C.); J.H.A. van der Heyden; S. Demarest (Stefaan); J. Tafforeau (Jean); W.J. Nusselder (Wilma); P. Deboosere (Patrick); H. van Oyen (Herman)

2015-01-01

textabstractBackground: Population aging accompanied by an increased longevity with disability has raised international concern, especially due to its costs to the health care systems. Chronic diseases are the main causes of physical disability and their simultaneous occurrence in the population can

Chronic mild hypoxia promotes profound vascular remodeling in spinal cord blood vessels, preferentially in white matter, via an α5β1 integrin-mediated mechanism.

Science.gov (United States)

Halder, Sebok K; Kant, Ravi; Milner, Richard

2018-05-01

Spinal cord injury (SCI) leads to rapid destruction of neuronal tissue, resulting in devastating motor and sensory deficits. This is exacerbated by damage to spinal cord blood vessels and loss of vascular integrity. Thus, approaches that protect existing blood vessels or stimulate the growth of new blood vessels might present a novel approach to minimize loss or promote regeneration of spinal cord tissue following SCI. In light of the remarkable power of chronic mild hypoxia (CMH) to stimulate vascular remodeling in the brain, the goal of this study was to examine how CMH (8% O 2 for up to 7 days) affects blood vessel remodeling in the spinal cord. We found that CMH promoted the following: (1) endothelial proliferation and increased vascularity as a result of angiogenesis and arteriogenesis, (2) increased vascular expression of the angiogenic extracellular matrix protein fibronectin as well as concomitant increases in endothelial expression of the fibronectin receptor α5β1 integrin, (3) strongly upregulated endothelial expression of the tight junction proteins claudin-5, ZO-1 and occludin and (4) astrocyte activation. Of note, the vascular remodeling changes induced by CMH were more extensive in white matter. Interestingly, hypoxic-induced vascular remodeling in spinal cord blood vessels was markedly attenuated in mice lacking endothelial α5 integrin expression (α5-EC-KO mice). Taken together, these studies demonstrate the considerable remodeling potential of spinal cord blood vessels and highlight an important angiogenic role for the α5β1 integrin in promoting endothelial proliferation. They also imply that stimulation of the α5β1 integrin or controlled use of mild hypoxia might provide new approaches for promoting angiogenesis and improving vascular integrity in spinal cord blood vessels.

Necroscopic study of a Chagas' disease chronic case with normal electrocardiograms

International Nuclear Information System (INIS)

Lopes, E.R.; Rocha, A.; Adad, S.J.; Fernandes, E.L.; Chapadeiro, E.

1988-01-01

The morphological changes in the postmortem study of a man probably with the indeterminate form of Chagas' disease are described. The heart exhibited lesions of the epicardium, myocardium and endocardium, as well as of the conduction system, primarily small inflammatory foci. There was mild fibrosis of the myocardium, atrioventricular node, and left bundle branch (at its origin). These alterations, although mild, were similar, in quality, to those described in the other chronic forms of Chagas' disease, and suggest active lesions, with a potential for further development. In the esophagus, among other features, a striking reduction of the number of neurons was observed. (author)

Acute and chronic otitis media.

Science.gov (United States)

Morris, Peter S; Leach, Amanda J

2009-12-01

Otitis media (OM) is a common illness in young children. OM has historically been associated with frequent and severe complications. Nowadays it is usually a mild condition that often resolves without treatment. For most children, progression to tympanic membrane perforation and chronic suppurative OM is unusual (low-risk populations); this has led to reevaluation of many interventions that were used routinely in the past. Evidence from a large number of randomized controlled trials can help when discussing treatment options with families. Indigenous children in the United States, Canada, Northern Europe, Australia, and New Zealand experience more OM than other children. In some places, Indigenous children continue to suffer from the most severe forms of the disease. Communities with more than 4% of the children affected by chronic tympanic membrane perforation have a major public health problem (high-risk populations). Higher rates of invasive pneumococcal disease, pneumonia, and chronic suppurative lung disease (including bronchiectasis) are also seen. These children will often benefit from effective treatment of persistent (or recurrent) bacterial infection.

Lumbar Discectomy of a Patient of Mitral Stenosis with Chronic Atrial Fibrillation Under Epidural Anaesthesia

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Vinaya R Kulkarni

2008-01-01

Full Text Available A 60-year-old female patient posted for discectomy of lumbar region L 3 -L 4 was accidently diagnosed to have chronic atrial fibrillation of rheumatic aetiology.This is a case report of this patient of critical mitral stenosis with mild mitral regurgitation with chronic atrial fibrillation managed successfully under lower thoracic epidural anaesthesia,in prone position without any compli-cation.

Discrete Serotonin Systems Mediate Memory Enhancement and Escape Latencies after Unpredicted Aversive Experience in Drosophila Place Memory

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Divya Sitaraman

2017-12-01

Full Text Available Feedback mechanisms in operant learning are critical for animals to increase reward or reduce punishment. However, not all conditions have a behavior that can readily resolve an event. Animals must then try out different behaviors to better their situation through outcome learning. This form of learning allows for novel solutions and with positive experience can lead to unexpected behavioral routines. Learned helplessness, as a type of outcome learning, manifests in part as increases in escape latency in the face of repeated unpredicted shocks. Little is known about the mechanisms of outcome learning. When fruit fly Drosophilamelanogaster are exposed to unpredicted high temperatures in a place learning paradigm, flies both increase escape latencies and have a higher memory when given control of a place/temperature contingency. Here we describe discrete serotonin neuronal circuits that mediate aversive reinforcement, escape latencies, and memory levels after place learning in the presence and absence of unexpected aversive events. The results show that two features of learned helplessness depend on the same modulatory system as aversive reinforcement. Moreover, changes in aversive reinforcement and escape latency depend on local neural circuit modulation, while memory enhancement requires larger modulation of multiple behavioral control circuits.

Optimisation of quantitative lung SPECT applied to mild COPD: a software phantom simulation study.

Science.gov (United States)

Norberg, Pernilla; Olsson, Anna; Alm Carlsson, Gudrun; Sandborg, Michael; Gustafsson, Agnetha

2015-01-01

The amount of inhomogeneities in a (99m)Tc Technegas single-photon emission computed tomography (SPECT) lung image, caused by reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), is correlated to disease advancement. A quantitative analysis method, the CVT method, measuring these inhomogeneities was proposed in earlier work. To detect mild COPD, which is a difficult task, optimised parameter values are needed. In this work, the CVT method was optimised with respect to the parameter values of acquisition, reconstruction and analysis. The ordered subset expectation maximisation (OSEM) algorithm was used for reconstructing the lung SPECT images. As a first step towards clinical application of the CVT method in detecting mild COPD, this study was based on simulated SPECT images of an advanced anthropomorphic lung software phantom including respiratory and cardiac motion, where the mild COPD lung had an overall ventilation reduction of 5%. The best separation between healthy and mild COPD lung images as determined using the CVT measure of ventilation inhomogeneity and 125 MBq (99m)Tc was obtained using a low-energy high-resolution collimator (LEHR) and a power 6 Butterworth post-filter with a cutoff frequency of 0.6 to 0.7 cm(-1). Sixty-four reconstruction updates and a small kernel size should be used when the whole lung is analysed, and for the reduced lung a greater number of updates and a larger kernel size are needed. A LEHR collimator and 125 (99m)Tc MBq together with an optimal combination of cutoff frequency, number of updates and kernel size, gave the best result. Suboptimal selections of either cutoff frequency, number of updates and kernel size will reduce the imaging system's ability to detect mild COPD in the lung phantom.

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease.

Science.gov (United States)

Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

2015-01-01

We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

Bilateral chylothorax in a patient with chronic central vein thrombosis and chronic thromboembolic pulmonary hypertension

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Avdhesh Bansal

2015-01-01

Full Text Available The chylothorax is not a common presentation, and bilateral chylothorax in patients with chronically high central venous pressure secondary to venous thrombosis is a rare in incidence. We reported a case of bilateral chylothorax in a patient of chronic deep vein thrombosis (DVT in central veins with chronic thromboembolic pulmonary hypertension who presented with 2 weeks history of increased breathlessness, bilateral chest discomfort and weakness. Work-up with chest X-ray and ultrasonography-chest showed gross left sided and mild right sided pleural effusion, thoracocentesis was consistent with chylothorax. Contrast enhanced computed tomography-chest showed multiple collateral formation of left side subclavian vein, venous Doppler showed old DVT in right and left subclavian veins and two-dimensional echocardiogram showed finding of severe pulmonary hypertension. After 24 h of fasting and conservative management, pleural drain became clear and decreased in the amount. Patient′s video assisted thoracoscopic surgery was done, and thoracic duct was ligated and cut down at diaphragmatic level and bilateral talc pleurodesis done. Patient improved clinically and radiologically.

Protracted effects of chronic stress on serotonin dependent thermoregulation

Science.gov (United States)

Natarajan, Reka; Northrop, Nicole A.; Yamamoto, Bryan K.

2016-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. Body temperature is controlled in part, by the medial preoptic area of the hypothalamus (mPOA). To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress paradigm (CUS) produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 days of CUS. Four days after last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10°C were recorded. CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that CUS induced changes to the 5HTergic system alters mPOA function in thermoregulation. These findings help explain mechanisms underlying chronic stress induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed. PMID:26414686

Life stories of people on sick leave from work because of mild mental illness, pain and fatigue.

Science.gov (United States)

Brataas, Hildfrid V; Evensen, Aud E

2015-01-01

Many people experience some form of mild mental illness, chronic pain and fatigue feelings that lead to long-term absences from the workplace. The article examines narrations about developmental experiences and adult life of people in need of back to work rehabilitation. Narrative interviews were analyzed within a qualitative content analyses design. The sample was purposive, with 16 working-age adults at rehabilitation because of mild mental illnesses, chronic pain, and fatigue feelings. Ethical approval, was obtained from The Regional Committee for Medical Research Ethics, Health Region Central Norway. Reference no.: 2010/1323. There were stories about more or less stressful childhoods. In adult life, there were turns at various ages from meaningful work engagement, to struggle in private life from long lasting strain, stressful family situations or crises. Illness may develop when experiencing crises or strain over time in private situations, this in combination with expectations and requirements in working life. Not only working environments, but also the private situations, life history events, and self-esteem of individuals, should be taken into consideration in the rehabilitation program. There is a need of research on working life that support the employee's positive self-image, and on effective rehabilitation when needed.

Beneficial Effect of Chronic Treatment with Extracts from Rhodiola Rosea L. and Curcuma Longa L. on the Immunoreactivity of Animals Subjected to a Chronic Mild Stress Model

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Vasileva Liliya V.

2017-12-01

Full Text Available Background: Recent studies have suggested increased levels of pro-inflammatory cytokines in depression. Aim: The present study aimed to evaluate the effect of extracts from Rhodiola and Curcuma on immunoreactivity of animals subjected to a chronic mild stress (CMS model followed by lipopolysaccharide-induced inflammation. Materials and methods: Male Wistar rats (n=56 divided in 7 groups were treated orally with: distilled water 10 ml/kg (control and CMS model groups; Rhodiola 250 mg/kg; Rhodiola 500 mg/kg; Curcuma 250 mg/kg; Curcuma 500 mg/kg, Rhodiola 250 mg/kg and Curcuma 250 mg/kg. All groups except the control were stressed daily according to a CMS protocol. Changes in glucose preference, weight gain and locomotor activity were recorded. In the sixth week the animals were challenged with LPS and rats’ sera were obtained for ELISA evaluation of TNF-α and IL-6 levels. Results: The animals from the model group decreased their weight gain, glucose preference and locomotor activity compared to controls. The groups exposed to stress and treated with Rhodiola 500 mg/kg, Curcuma 500 mg/kg and their combination increased their locomotor activity compared to the model group. High expression of the pro-inflammatory cytokines TNF-α and IL-6 were found in all groups exposed to CMS and challenged by LPS. Conclusions: The groups exposed to the stress procedure showed a variety of depression-like behavioral changes. In addition, ELISA tests showed that CMS is affecting rats’ immunity by increasing the cytokines’ levels. These changes could be reversed by administration of Rhodiola and Curcuma in combination suggesting synergic interaction regarding their anti-inflammatory and anti-stress effects.

Mitigation of chronic unpredictable stress–induced cognitive deficits ...

African Journals Online (AJOL)

Morphological changes in pyramidal neurons in the hippocampus were studied by Nissl staining. ... mental disorders such as anxiety and depression. [8]. .... LBP increase the percentage of time spent in target quarter in Probe Trials. (d) LBP ...

Are NSAIDs useful to treat Alzheimer's disease or mild cognitive impairment?

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Bruno P Imbimbo

2010-05-01

Full Text Available Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs may protect subjects carrying one or more ε4 allele of the apolipoprotein E (APOE ε4 against the onset of Alzheimer’s disease (AD. The biological mechanism of this protection is not completely understood and may involve the anti-inflammatory properties of NSAIDs or their ability of interfering with the β-amyloid (Aβ cascade. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and cyclooxygenase-2 (COX-2 selective inhibitors in mild-to-moderate AD patients produced negative results. A secondary prevention study with rofecoxib, a COX-2 selective inhibitor, in patients with mild cognitive impairment was also negative. A primary prevention study (ADAPT trial of naproxen (a non-selective COX inhibitor and celecoxib (a COX-2 selective inhibitor in cognitively normal elderly subjects with a family history of AD was prematurely interrupted for safety reasons after a median period of treatment of 2 years. Although both drugs did not reduce the incidence of dementia after two years of treatment, a 4-year follow up assessment surprisingly revealed that subjects previously exposed to naproxen were protected from the onset of AD by 67% compared to placebo. Thus, it could be hypothesized that the chronic use of NSAIDs may be beneficial only in the very early stages of the AD process in coincidence of initial Aβ deposition, microglia activation and consequent release of pro-inflammatory mediators. When the Aβ deposition process is already started, NSAIDs are no longer effective and may even be detrimental because of their inhibitory activity on chronically activated microglia that on long-term may mediate Aβ clearance. The research community should conduct long-term trials with NSAIDs in cognitively normal APOE ε4 carriers.

Chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Karabulut, N.

2012-01-01

Full text: Chronic obstructive pulmonary diseases (COPD) denote progressive lung diseases characterized by airway obstruction. COPD exhibits specific morphologic changes in the lung parenchyma, central and peripheral airways and pulmonary vasculature. A person with COPD may have either emphysema or chronic bronchitis, but most have both. Some people with COPD may also have an asthma-like or reactive component. Imaging modalities play important role in the detection or exclusion of COPD, distribution and extent of disease processes. Combined inspiratory and expiratory high resolution CT allows phenotyping of COPD (emphysema predominant, airway predominant, or mixed) and quantification of severity. Magnetic resonance imaging enables functional evaluation and demonstrates ventilation defects correlating closely with pulmonary function tests. Imaging techniques are also helpful in guiding the treatment, such as bullectomy in patients with bullous emphysema, lung volume reduction surgery or endoscopic interventions in those with severe emphysema, and smoking cessation and medical treatment designed to stop lung destruction in patients with mild or moderate emphysema or bronchiectasis.

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

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Atsuko Hayashi

2015-09-01

Full Text Available Background/Aims: We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI and mild Alzheimer's disease (AD. To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji. Methods: A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results: For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions: The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

Fluoxetine coupled with zinc in a chronic mild stress model of depression: Providing a reservoir for optimum zinc signaling and neuronal remodeling.

Science.gov (United States)

Omar, Nesreen Nabil; Tash, Reham Fathy

2017-09-01

Recently, depression has been envisioned as more than an alteration in neurotransmitters centered around receptor signaling pathways. Consequently, the precise mechanisms of selective serotonin reuptake inhibitor (SSRI) antidepressant drugs such as fluoxetine are being revisited. Zinc is a trace element that has been long implicated in the psychopathology and therapy of depression. Zinc has been found to be sequestered and dispensed during stress and inflammation through a family of proteins called metallothioneins (MTs). In addition, MTs are well known for their antioxidant and therefore cytoprotective action. Changes in MTs, their upstream regulators and downstream effectors in response to fluoxetine have not been yet studied. The aim of the present study is to examine whether depression-induced changes in protein levels and mRNA levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), MTs, antioxidant defensive enzyme heme oxygenase (HO-1), zinc-specific receptor GPR39 and brain derived neurotrophic factor (BDNF) in the hippocampus can be reversed by fluoxetine treatment, zinc supplementation or a combination of the two. The present study investigated the effect of chronic (4weeks) combined treatment with zinc hydroaspartate (15mg/kg) and fluoxetine (10mg/kg) on a chronic mild stress model (CMS) in male Sprague-Dawley rats. Hippocampal mRNA and protein levels of Nrf2, HO-1, MTs, GPR39 (protein level only) and BDNF were significantly higher in response to a combined therapy of fluoxetine and zinc than to either monotherapy. Additionally, HO-1 and MTs gene expression was correlated with that of Nrf2 in the FLX-only group. Fluoxetine therapy activated the expression of MTs and HO-1 through an Nrf2-dependent pathway. When FLX was escorted by zinc, activated MTs had a positive impact on BDNF through the zinc signaling receptor GPR39, resulting in general improvement in neuronal plasticity as well as reduction of neuronal atrophy and neuronal cell loss. Copyright

Neuroplastic Correlates in the mPFC Underlying the Impairment of Stress-Coping Ability and Cognitive Flexibility in Adult Rats Exposed to Chronic Mild Stress during Adolescence

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Yu Zhang

2017-01-01

Full Text Available Using a valid chronic mild stress (CMS model of depression, we found that adolescent (postnatal days [PND] 28–41 CMS induced transient alterations in anhedonia that did not persist into adulthood after a 3-week recovery period. Previously stressed adult rats exhibited more immobility/despair behaviors in the forced swimming test and a greater number of trials to reach criterion in the set-shifting task, suggesting the impaired ability to cope with stressors and the cognitive flexibility that allows adaptation to dynamic environments during adulthood. In addition, adult rat exposure to adolescent CMS had a relatively inhibited activation in ERK signaling and downstream protein expression of phosphorylated cAMP-response element-binding protein (CREB and brain-derived neurotrophic factor (BDNF in the medial prefrontal cortex. Further correlation analysis demonstrated that immobility and set-shifting performance were positively correlated with the inhibition of ERK signaling. These results indicated adolescent CMS can be used as an effective stressor to model an increased predisposition to adult depression.

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model.

Science.gov (United States)

Thomsen, Gretchen M; Ko, Ara; Harada, Megan Y; Ma, Annie; Wyss, Livia; Haro, Patricia; Vit, Jean-Philippe; Avalos, Pablo; Dhillon, Navpreet K; Cho, Noell; Shelest, Oksana; Ley, Eric J

2017-06-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as "mild" or "severe" and further separated into "acute," "short," and "long" based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

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Bing Han

2017-03-01

Full Text Available Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57 mice caused by chronic unpredictable mild stress (CUMS, we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

[Comment on Earthquake precursors: Banished forever?] Comment: Unpredictability of earthquakes-Truth or fiction?

Science.gov (United States)

Lomnitz, Cinna

I was delighted to read Alexander Gusev's opinions on what he calls the “unpredictability paradigm” of earthquakes (Eos, February 10, 1998, p. 71). I always enjoy hearing from a good friend in the pages of Eos. I immediately looked up “paradigm” in my Oxford Dictionary and found this: paradigm n 1) set of all the different forms of a word: verb paradigms. 2) Type of something; pattern; model: a paradigm for others to copy.I wonder whether Sasha Gusev actually believes that branding earthquake prediction a “proven nonscience” [Geller, 1997] is a paradigm for others to copy. As for me, I choose to refrain from climbing on board this particular bandwagon for the following reasons.

Femoral rotation unpredictably affects radiographic anatomical lateral distal femoral angle measurements

DEFF Research Database (Denmark)

Miles, James Edward

2016-01-01

Objective: To describe the effects of internal and external femoral rotation on radiographic measurements of the anatomical lateral distal femoral angle (a-LDFA) using two methods for defining the anatomical proximal femoral axis (a-PFA). Methods: Digital radiographs were obtained of 14 right...... femora at five degree intervals from 10° external rotation to 10° internal rotation. Using freely available software, a-LDFA measurements were made using two different a-PFA by a single observer on one occasion. Results: Mean a-LDFA was significantly greater at 10° external rotation than at any other...... rotation. The response of individual femora to rotation was unpredictable, although fairly stable within ±5° of zero rotation. Mean a-LDFA for the two a-PFA methods differed by 1.5°, but were otherwise similarly affected by femoral rotation. Clinical significance: If zero femoral elevation can be achieved...

DOUBLE-BLIND PLACEBO-CONTROLLED STUDY OF IBOPAMINE AND DIGOXIN IN PATIENTS WITH MILD-TO-MODERATE HEART-FAILURE - RESULTS OF THE DUTCH IBOPAMINE MULTICENTER TRIAL (DIMT)

NARCIS (Netherlands)

VANVELDHUISEN, DJ; MANINTVELD, AJ; DUNSELMAN, PHJM; LOK, DJA; DOHMEN, HJM; POORTERMANS, JC; WITHAGEN, AJAM; PASTEUNING, WH; BROUWER, J; LIE, KI

1993-01-01

Objectives. This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo.

Trafficking of endoplasmic reticulum-retained recombinant proteins is unpredictable in Arabidopsis thaliana

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Thomas eDe Meyer

2014-09-01

Full Text Available A wide variety of recombinant proteins has been produced in the dicot model plant, Arabidopsis thaliana. Many of these proteins are targeted for secretion by means of an N terminal endoplasmic reticulum (ER signal peptide. In addition, they can also be designed for ER retention by adding a C terminal H/KDEL-tag. Despite extensive knowledge of the protein trafficking pathways, the final protein destination, especially of such H/KDEL-tagged recombinant proteins, is unpredictable. In this respect, glycoproteins are ideal study objects. Microscopy experiments reveal their deposition pattern and characterization of their N-glycans aids in elucidating the trafficking. Here, we combine microscopy and N glycosylation data generated in Arabidopsis leaves and seeds, and highlight the lack of a decent understanding of heterologous protein trafficking.

Effects of α2A Adrenoceptors on Norepinephrine Secretion from the Locus Coeruleus during Chronic Stress-Induced Depression

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Hong-ping Huang

2017-05-01

Full Text Available Chronic stressors can often lead to the development of psychological disorders, such as depression and anxiety. The locus coeruleus (LC is a stress sensitive brain region located in the pons, with noradrenergic neurons that project to the hypothalamus, especially the paraventricular nucleus (PVN of the hypothalamus. The purpose of this paper is to better understand how alpha 2A-adrenoceptors (α2A-ARs and LC-hypothalamus noradrenergic system participate in the pathophysiological mechanism of depression. In vivo norepinephrine (NE release in the PVN triggered by electrical stimulation in the LC was detected with carbon fiber electrodes in depression model of rats induced by chronic unpredictable mild stress (CUMS. Also, the extracellular level of NE in the PVN was measured by microdialysis in vivo without any stimulation in the LC. The alpha 2-adrenoceptor (α2-AR antagonist yohimbine and α2A-ARs antagonist BRL-44408 maleate were systemically administered to rats to determine the effects of α2A-ARs on NE release in the PVN. The peak value of elicited NE release signals in the PVN induced by electrical stimulation in the LC in the CUMS rats were lower than that in the control rats. The extracellular levels of NE in the PVN of the CUMS rats were significantly less than that of the control rats. Intraperitoneal injection of yohimbine or BRL-44408 maleate significantly potentiated NE release in the PVN of the CUMS rats. The CUMS significantly increased protein expression levels of α2A-AR in the hypothalamus, and BRL-44408 maleate significantly reversed the increase of α2A-AR protein expression levels in the CUMS rats. Our results suggest that the CUMS could significantly facilitate the effect of α2-adrenoceptor-mediated presynaptic inhibition and decrease the release of NE in the PVN from LC. Blockade of the inhibitory action of excessive α2A-adrenergic receptors in the CUMS rats could increase the level of NE in the PVN, which is effective in

Mild cognitive impairment in older adults with pre-dialysis patients with chronic kidney disease: Prevalence and association with physical function.

Science.gov (United States)

Otobe, Yuhei; Hiraki, Koji; Hotta, Chiharu; Nishizawa, Hajime; Izawa, Kazuhiro P; Taki, Yasuhiro; Imai, Naohiko; Sakurada, Tsutomu; Shibagaki, Yugo

2017-09-26

Chronic kidney disease (CKD) is a risk factor for declining cognitive and physical function. However, the prevalence of mild cognitive impairment (MCI) and its relationship with physical function is not clear. Therefore, our aim was to evaluate the prevalence of MCI and the relationship between MCI and physical function among older adults with pre-dialysis CKD. We conducted a cross-sectional study of 120 patients, aged ≥ 65 years (mean age, 77.3 years), with pre-dialysis CKD but without probable dementia (Mini Mental State Examination < 24). MCI was evaluated using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). For analysis, patients were classified into two cognitive function groups: normal (MoCA-J ≥26) and MCI (MoCA-J <26). Physical, clinical, and biochemical parameters were compared between the groups. Logistic and linear regression analyses were used to evaluate the specific association between cognitive and physical function. Seventy-five patients (62.5%) patients belonged to the MCI group. Significant differences between the two groups were identified for gait speed, balance, age, and haemoglobin concentration. After adjustment for covariates, only gait speed was significantly associated with MCI (odds ratio, 0.06; 95% confidence interval, 0.009-0,411). The prevalence of MCI among older adults with pre-dialysis CKD was as high as 62.5%. The association between MCI and reduced gait speed supports the possible interaction between physical and cognitive functions and the need for early screening. This article is protected by copyright. All rights reserved.

Vascular endothelial cell function and cardiovascular risk factors in patients with chronic renal failure

DEFF Research Database (Denmark)

Haaber, A B; Eidemak, I; Jensen, T

1995-01-01

Cardiovascular risk factors and markers of endothelial cell function were studied in nondiabetic patients with mild to moderate chronic renal failure. The transcapillary escape rate of albumin and the plasma concentrations of von Willebrand factor, fibrinogen, and plasma lipids were measured in 29...

Chaos and unpredictability in evolution of cooperation in continuous time

Science.gov (United States)

You, Taekho; Kwon, Minji; Jo, Hang-Hyun; Jung, Woo-Sung; Baek, Seung Ki

2017-12-01

Cooperators benefit others with paying costs. Evolution of cooperation crucially depends on the cost-benefit ratio of cooperation, denoted as c . In this work, we investigate the infinitely repeated prisoner's dilemma for various values of c with four of the representative memory-one strategies, i.e., unconditional cooperation, unconditional defection, tit-for-tat, and win-stay-lose-shift. We consider replicator dynamics which deterministically describes how the fraction of each strategy evolves over time in an infinite-sized well-mixed population in the presence of implementation error and mutation among the four strategies. Our finding is that this three-dimensional continuous-time dynamics exhibits chaos through a bifurcation sequence similar to that of a logistic map as c varies. If mutation occurs with rate μ ≪1 , the position of the bifurcation sequence on the c axis is numerically found to scale as μ0.1, and such sensitivity to μ suggests that mutation may have nonperturbative effects on evolutionary paths. It demonstrates how the microscopic randomness of the mutation process can be amplified to macroscopic unpredictability by evolutionary dynamics.

Indicators of complicated mild TBI predict MMPI-2 scores after 23 years.

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Hessen, Erik; Nestvold, Knut

2009-03-01

Research suggests that post-concussive syndrome may become persistent after mild traumatic brain injury (mTBI). The aim of this study was to investigate determinants of subjective complaints, characteristic for post-concussive syndrome, 23 years after mTBI. The study was a follow-up after a prospective head injury study at a general hospital in Norway. Ninety-seven patients were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) 23 years after sustaining primarily mTBI. A good overall outcome was found with scores close to the normative mean, average length of education and normal employment rate. However, the patients that sustained complicated mTBI showed somewhat more pathological scores, well-matched with mild post-concussive syndrome. The most important predictors of poor outcome were a combination of post-traumatic amnesia >30 minutes and EEG pathology within 24 hours after TBI. No influence of pre- and post-injury risk factors on current MMPI-2 profiles was found. The results are in line with previous research findings and support the notion of potentially differential impact of uncomplicated vs. complicated mTBI. The findings suggest that complicated mTBI may cause subtle chronic symptoms typical of post-concussive syndrome.

Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air

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Lopez Ivan A

2009-05-01

Full Text Available Abstract Background The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO exposure (25 parts per million subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5 to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO. At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS, neuronal (nNOS, and endothelial (eNOS nitric oxide synthases. Results Superoxide dismutase-1 (SOD1, SOD2, and hemeoxygenase-1 (HO-1 immunoreactivity increased in cells of the cerebellar cortex of CO-exposed pups. INOS and nitrotyrosine immunoreactivity also increased in blood vessels and Purkinje cells (PCs of pups from group-A, B and C. By contrast, nNOS immunoreactivity decreased in PCs from group-B. Endothelial NOS immunoreactivity showed no changes in any CO-exposed group. The mRNA levels for iNOS were significantly up-regulated in the cerebellum of rats from group B; however, mRNA levels for nNOS and eNOS remained relatively unchanged in groups A, B and C. Ferritin-H immunoreactivity increased in group-B. Immunocytochemistry for neurofilaments (structural protein, synapsin-1 (functional protein, and glutamic acid decarboxylase (the enzyme responsible for the synthesis of the inhibitory neurotransmitter GABA, were decreased in groups A and B. Immunoreactivity for two calcium binding proteins, parvalbumin and calbindin, remained

Troubling practices of control: re-visiting Hannah Arendt's ideas of human action as praxis of the unpredictable.

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Kohlen, Helen

2015-07-01

In this article, Hannah Arendt's concept of action will be used to problematize current transformations of the health care sector and examine some responses by ethicists in light of those transformations. The sphere of human interaction that should typify health care work is identified as an action of unpredictable praxis in contrast to controllable procedures and techniques which increasingly take place in the health care sector. © 2015 John Wiley & Sons Ltd.

Protracted effects of chronic stress on serotonin-dependent thermoregulation.

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Natarajan, Reka; Northrop, Nicole A; Yamamoto, Bryan K

2015-01-01

Chronic stress is known to affect serotonin (5HT) neurotransmission in the brain and to alter body temperature. The body temperature is controlled in part, by the medial preoptic area (mPOA) of the hypothalamus. To investigate the effect of chronic stress on 5HT and how it affects body temperature regulation, we examined whether exposure to a chronic unpredictable stress (CUS) paradigm produces long-term alterations in thermoregulatory function of the mPOA through decreased 5HT neurotransmission. Adult male Sprague-Dawley rats underwent 21 d of CUS. Four days after the last stress exposure, basal body temperature in the home cage and body temperature in a cold room maintained at 10 °C were recorded. The CUS rats had significantly higher subcutaneous basal body temperature at 13:00 h compared to unstressed (NoStress) rats. Whereas the NoStress rats were able to significantly elevate body temperature from basal levels at 30 and 60 min of exposure to the cold room, the CUS rats showed a hypothermic response to the cold. Treatment during CUS with metyrapone, a corticosterone synthesis inhibitor, blocked stress-induced decrease in body temperature in response to the cold challenge. CUS also decreased 5HT transporter protein immunoreactivity in the mPOA and 5HT2A/C agonist injection into the mPOA after CUS exposure caused stressed rats to exhibit a sensitized hyperthermic response to cold. These results indicate that the CUS induced changes to the 5HTergic system alter mPOA function in thermoregulation. These findings help us to explain the mechanisms underlying chronic stress-induced disorders such as chronic fatigue syndrome wherein long lasting thermoregulatory deficits are observed.

Enhanced fear recall and emotional arousal in rats recovering from chronic variable stress.

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McGuire, Jennifer; Herman, James P; Horn, Paul S; Sallee, Floyd R; Sah, Renu

2010-11-02

Emergence of posttraumatic-like behaviors following chronic trauma is of interest given the rising prevalence of combat-related posttraumatic stress disorder (PTSD). Stress associated with combat usually involves chronic traumatization, composed of multiple, single episode events occurring in an unpredictable fashion. In this study, we investigated whether rats recovering from repeated trauma in the form of chronic variable stress (CVS) express posttraumatic stress-like behaviors and dysregulated neuroendocrine responses. Cohorts of Long-Evans rats underwent a 7 day CVS paradigm followed by behavioral and neuroendocrine testing during early (16 h post CVS) and delayed (7 day) recovery time points. A fear conditioning-extinction-reminder shock paradigm revealed that CVS induces exaggerated fear recall to reminder shock, suggestive of potentiated fear memory. Rats with CVS experience also expressed a delayed expression of fearful arousal under aversive context, however, social anxiety was not affected during post-CVS recovery. Persistent sensitization of the hypothalamic-pituitary-adrenocorticotropic response to a novel acute stressor was observed in CVS exposed rats. Collectively, our data are consistent with the constellation of symptoms associated with posttraumatic stress syndrome, such as re-experiencing, and arousal to fearful contexts. The CVS-recovery paradigm may be useful to simulate trauma outcomes following chronic traumatization that is often associated with repeated combat stress. Copyright © 2010 Elsevier Inc. All rights reserved.

Allopurinol Against Progression of Chronic Kidney Disease.

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Golmohammadi, Sima; Almasi, Afshin; Manouchehri, M; Omrani, Hamid Reza; Zandkarimi, Mohammad Reza

2017-07-01

Hyperuricemia is common in approximately 50% of patients with kidney failure due to decreased uric acid excretion, and it has been recently known as an independent factor in the progression of renal insufficiency. Allopurinol inhibits the production of uric acid. The aim of this study was to evaluate the effect of allopurinol on chronic kidney disease progression. In a clinical trial, patients with stages 3 and 4 of chronic kidney disease were divided into two groups to receive allopurinol, 100 mg, daily and placebo for 12 months. Patients' kidney function and serum uric acid levels were assessed at baseline and 3, 6, and 12 months after initial administration. Subgroups of patients with severe and mild glomerular filtration rate (GFR) impairment (GFR, 15 mL/min/1.73 m2 to 30 mL/min/1.73 m2 and 30 mL/min/1.73 m2 to 60 mL/min/1.73 m2, respectively), were compared between the groups. Serum uric acid levels decreased significantly during after 12 months of allopurinol administration (P = .004). In patients with severe GFR impairment, serum creatinine levels did not decrease significantly and there was no significant increase in GFR, but in those with mild GFR impairment, serum creatinine levels decreased and GFR increase significantly (P kidney disease progression and could be administered with other effective medications for controlling the kidney disease.

Congenital anomalies, hereditary diseases of the pancreas, acute and chronic pancreatitis

International Nuclear Information System (INIS)

Brambs, Hans-Juergen; Juchems, Markus

2011-01-01

The most important congenital anomalies include pancreas divisum, annular pancreas and ectopic pancreas. Patients with pancreas divisum may be more susceptible to acute or chronic pancreatitis and patients with an annular pancreas may develop duodenal stenosis. In pancreas divisum the key finding is the visualization of the main duct draining into the duodenum via the small papilla, separated from the common bile duct. Annular pancreas may show as a well defined ring of pancreatic tissue that encircles the duodenum. Ectopic pancreas is usually asymptomatic but may give rise to abdominal complaints and may be confused with submucosal tumors. Acute pancreatitis is classified as mild or severe. In mild forms ultrasound is the imaging modality of choice whereas in severe forms with extensive pancreatic and peripancreatic necroses computed tomography is the favored method. It is crucial to identify signs and criteria that come along with an increased risk of infection of the necroses. MRI plays an inferior role in the assessment of acute pancreatitis. Chronic pancreatitis is a longstanding inflammatory and fibrosing process causing pain and loss of function. Cross-section imaging is particularly in demand for the detection of complications and the differentiation from pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by lymphoplasmacytic infiltration and fibrosis, and favourable response to corticosteroid treatment. (orig.)

Chronic periodontitis and oral health-related quality of life in Chinese adults: A population-based, cross-sectional study.

Science.gov (United States)

He, Songlin; Wei, Shicheng; Wang, Jinhua; Ji, Ping

2018-03-01

This population-based, cross-sectional study explored the association between chronic periodontitis and oral health-related quality of life (OHRQoL) in Chinese adults, independently of sociodemographic factors and other common oral conditions. The present study was carried out in a sample population of 480 adults aged 35 to 74 years from Chongqing municipality. A multi-stage stratified random sampling approach was adopted to select participants. The Chinese version of the short-form oral health impact profile (OHIP-14) was used to assess OHRQoL. Chronic periodontitis was trichotomized into mild, moderate, and severe periodontitis. Logistic regression models were adopted to explore the association between the severity of chronic periodontitis and OHIP-14 scores. After adjustment for sociodemographic factors and other common clinical conditions, participants with severe and moderate chronic periodontitis, respectively, had 1.63- (95% CI: 1.41 to 1.98) and 1.42-fold (95% CI: 1.29 to 1.63) higher odds for the OHIP-14 scores being above the median compared with participants without chronic periodontitis. However, participants with mild periodontitis did not have significantly higher odds for the OHIP-14 scores being above the median than participants without chronic periodontitis. Certain sociodemographic variables, including higher age, lower education level, number of missing teeth, and current smoker, had negative associations with OHRQoL. Chronic periodontitis was associated with poorer OHRQoL in Chinese adults. In addition, the impairment in OHRQoL showed a significant correlation with the severity of chronic periodontitis. © 2018 American Academy of Periodontology.

Salivary Levels of IL-6 and IL-17 Could Be an Indicator of Disease Severity in Patients with Calculus Associated Chronic Periodontitis

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Husniah Batool

2018-01-01

Full Text Available Background/Purpose. Chronic periodontitis is an inflammatory disease of gums that causes loss of supporting structures of teeth, that is, gingiva, periodontal ligament, cementum, and alveolar bone. Levels of various cytokines in the serum, gingival tissues, and gingival crevicular fluid in patients with chronic periodontitis have been studied, but limited data are available on the level of cytokines in saliva. Therefore, a study was designed to determine levels of salivary IL-6 and IL-17 in patients with calculus associated chronic periodontitis. Materials and Methods. It was a comparative, cross-sectional study that is comprised of 41 healthy controls and 41 calculus associated chronic periodontitis patients (CP patients. According to the degree of attachment loss, CP patients were subcategorized as mild (CAL 1-2 mm, moderate (CAL 3-4 mm, and severe (CAL > 5 mm forms of periodontitis. Salivary levels of IL-6 and IL-17 were determined using enzyme-linked immunosorbent assay (ELISA technique. Data was analyzed using SPSS 20.0. Results. Between healthy controls and CP patients (moderate and severe disease, a statistically significant difference was observed in the concentrations of IL-6 and IL-17. In CP patients, the highest mean ± SD of salivary IL-6 and IL-17 was observed in severe CP, followed by moderate and mild CP. Regarding level of IL-6, a statistically significant difference was observed between mild and severe disease and between moderate and severe subcategories of CP patients. Similarly, statistically significant difference was observed in the level of IL-17 between mild and moderate, mild and severe disease, and moderate and severe disease. Conclusion. The levels of salivary IL-6 and IL-17 were increased significantly in calculus associated CP patients as compared to healthy controls and these levels increased with the progression of CP. Clinical Significance. Salivary levels of IL-6 and IL-17 may help in the subcategorization

"I just cope from day to day": unpredictability and anxiety in the lives of women.

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Walters, V; Charles, N

1997-12-01

Data are presented from in-depth interviews with 35 women in an industrial town in South Wales, U.K., many of whom were from low income households. The research aimed to explore women's own concerns about their health and the ways in which health problems affected their lives. This paper focuses on one prominent theme in these interviews: unpredictability. In particular, women described how their lives had become less predictable and amenable to control as a result of health problems--epilepsy, asthma, ME, anxiety, nerves and panic attacks, for example. Women's accounts are used to show how they experienced these problems, how they influenced women's self-identity and the ways in which women struggled to cope with the dreadful uncertainty that characterized their days. They often hid these problems, and the privacy of this aspect of their lives is striking. The data are set within the context of class and gender relations which diminish women's control over their lives and erode their self-esteem and sense of autonomy. Class and gender combine with ill health to create the conditions for women's sense of unpredictability and powerlessness. They can aggravate and provoke the health problems women described: women spoke of the challenges they faced in their roles as wives and mothers, the problems associated with widowhood, the loss of their jobs, the impact of unemployment and their efforts to cope with severe financial problems. In part, these provided them with a framework for understanding the uncertainty, anxiety, nerves and panic they experienced.

THE UNPREDICTABILITY CLAUSE IN TRANSPORT CONTRACTS, ACCORDING TO THE NEW CIVIL CODE

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Adriana Elena BELU

2014-05-01

Full Text Available Until the enforcement of the highly controversial transport law, transport companies must already observe the provisions of the new Civil Code1 in their transport business. One of the novelties in the new Civil Code, that came into force on October 1, 2011, refers to the unpredictability clause: recurring to this clause, in certain situations to be precisely analysed by courts, parties may even be exempted from certain contractual obligations, when the court decides to rescind the contract based on objective criteria, not imputable to the party that no longer can properly fulfil the obligations that had been undertaken when the contract had been made. However, this solution only is provided after all means of negotiation and mediation between parties are exhausted. The clause meets current market requirements, under which many companies have to deal with bad paying partners.

Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress.

Science.gov (United States)

Herrera-Pérez, J J; Martínez-Mota, L; Jiménez-Rubio, G; Ortiz-López, L; Cabrera-Muñoz, E A; Galindo-Sevilla, N; Zambrano, E; Hernández-Luis, F; Ramírez-Rodríguez, G B; Flores-Ramos, M

2017-03-15

Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex-Specific Effects of Unpredictable Variable Prenatal Stress: Implications for Mammalian Developmental Programming During Spaceflight

Science.gov (United States)

Talyansky, Y.; Moyer, E. L.; Oijala, E.; Baer, L. A.; Ronca, A. E.

2016-01-01

During adaptation to the microgravity environment, adult mammals experience stress mediated by the Hypothalamic-Pituitary-Adrenal axis. In our previous studies of pregnant rats exposed to 2-g hypergravity via centrifugation, we reported decreased corticosterone and increased body mass and leptin in adult male, but not female, offspring. In this study, we utilized Unpredictable Variable Prenatal Stress to simulate the stressors of spaceflight by exposing dams to different stressors. Stress response modulation occurs via both positive and negative feedback in the hypothalamus, anterior pituitary gland, and adrenal cortex resulting in the differential release of corticosterone (CORT), a murine analog to human cortisol.

Chlorpyrifos chronic toxicity in broilers and effect of vitamin C

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A.M. Kammon

2011-02-01

Full Text Available An experiment was conducted to study chlorpyrifos chronic toxicity in broilers and the protective effect of vitamin C. Oral administration of 0.8 mg/kg body weight (bw (1/50 LD50 chlorpyrifos (Radar®, produced mild diarrhea and gross lesions comprised of paleness, flaccid consistency and slightly enlargement of liver. Histopathologically, chlorpyrifos produced degenerative changes in various organs. Oral administration of 100 mg/kg bw vitamin C partially ameliorated the degenerative changes in kidney and heart. There was insignificant alteration in biochemical and haematological profiles. It is concluded that supplementation of vitamin C reduced the severity of lesions induced by chronic chlorpyrifos toxicity in broilers.

Duloxetine in the treatment of chronic pain due to fibromyalgia and diabetic neuropathy

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Alan Wright

2010-12-01

Full Text Available Alan Wright, Kyle E Luedtke, Chad VanDenBergCenter for Clinical Research, Mercer University, Atlanta, Georgia, USAAbstract: Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved by the US Food and Drug Administration for the treatment of fibromyalgia and painful diabetic neuropathy at doses of 60 mg daily. Duloxetine has been shown to significantly improve the symptoms of chronic pain associated with these disorders, as measured by the Fibromyalgia Impact Questionnaire, Brief Pain Inventory scores, the Clinical Global Impressions Scale, and other various outcome measures in several placebo-controlled, randomized, double-blind, multicenter studies. Symptom improvement generally began within the first few weeks, and continued for the duration of the study. In addition, the efficacy of duloxetine was found to be due to direct effects on pain symptoms rather than secondary to improvements in depression or anxiety. Adverse events including nausea, constipation, dry mouth, and insomnia, were mild and transient and occurred at relatively low rates. In conclusion, duloxetine, a selective inhibitor for the serotonin and norepinephrine transporters, is efficacious in the treatment of chronic pain associated with fibromyalgia or diabetic neuropathy, and has a predictable tolerability profile, with adverse events generally being mild to moderate.Keywords: duloxetine, chronic pain, neuropathic pain, fibromyalgia, efficacy, safety

Can routine chest radiography be used to diagnose mild COPD? A nested case-control study.

Science.gov (United States)

den Harder, A M; Snoek, A M; Leiner, T; Suyker, W J; de Heer, L M; Budde, R P J; Lammers, J W J; de Jong, P A; Gondrie, M J A

2017-07-01

To determine whether mild stage chronic obstructive pulmonary disease (COPD) can be detected on chest radiography without substantial overdiagnosis. A retrospective nested case-control study (case:control, 1:1) was performed in 783 patients scheduled for cardiothoracic surgery who underwent both spirometry and a chest radiograph preoperative. Diagnostic accuracy of chest radiography for diagnosing mild COPD was investigated using objective measurements and overall appearance specific for COPD on chest radiography. Inter-observer variability was investigated and variables with a kappa >0.40 as well as baseline characteristics were used to make a diagnostic model which was aimed at achieving a high positive predictive value (PPV). Twenty percent (155/783) had COPD. The PPV of overall appearance specific for COPD alone was low (37-55%). Factors in the diagnostic model were age, type of surgery, gender, distance of the right diaphragm apex to the first rib, retrosternal space, sternodiaphragmatic angle, maximum height right diaphragm (lateral view) and subjective impression of COPD (using both views). The model resulted in a PPV of 100%, negative predictive value (NPV) of 82%, sensitivity of 10% and specificity of 100% with an area under the curve of 0.811. Detection of mild COPD without substantial overdiagnosis was not feasible on chest radiographs in our cohort. Copyright © 2017 Elsevier B.V. All rights reserved.

Mexiletine for treatment of chronic painful diabetic neuropathy

DEFF Research Database (Denmark)

Dejgard, A; Kastrup, J; Petersen, P

1988-01-01

Sixteen of nineteen patients completed a randomised double-blind crossover trial to assess the effect of oral mexiletine (10 mg/kg bodyweight daily) on the symptoms and signs of chronic painful diabetic neuropathy. The median age of the sixteen patients was 50 years (range 30-64). Assessment...... threshold levels, beat-to-beat variation in heart rate during deep breathing, and postural blood pressure response. Mild side-effects were seen in three of the sixteen patients during mexiletine treatment....

Chronic stress effects on hippocampal structure and synaptic function: relevance for depression and normalization by anti-glucocorticoid treatment

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Harmen J Krugers

2010-07-01

Full Text Available Exposure of an organism to environmental challenges activates two hormonal systems that help the organism to adapt. As part of this adaptational process, brain processes are changed such that appropriate behavioral strategies are selected that allow optimal performance at the short term, while relevant information is stored for the future. Over the past years it has become evident that chronic uncontrollable and unpredictable stress also exerts profound effects on structure and function of limbic neurons, but the impact of chronic stress is not a mere accumulation of repeated episodes of acute stress exposure. Dendritic trees are reduced in some regions but expanded in others, and cells are generally exposed to a higher calcium load upon depolarization. Synaptic strengthening is largely impaired. Neurotransmitter responses are also changed, e.g. responses to serotonin. We here discuss: a the main cellular effects after chronic stress with emphasis on the hippocampus, b how such effects could contribute to the development of psychopathology in genetically vulnerable individuals, and c their normalization by brief treatment with anti-glucocorticoids.

Mild induced hypothermia

DEFF Research Database (Denmark)

Johansen, Maria E; Jensen, Jens-Ulrik; Bestle, Morten H

2014-01-01

INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled...... trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). TRIAL REGISTRATION: NCT01455116. Thrombelastography (TEG) is performed three....... At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively. In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients...

Role of inflammatory markers in Elderly Type 2 Diabetic Patients with Mild Cognitive Impairment.

Science.gov (United States)

Hosny, Salwa S; Bahaaeldin, Ahmed M; Khater, Mohamed S; Bekhet, Meram M; Hebah, Hayam A; Hasanin, Ghada A

2018-04-22

Type 2 diabetes (T2DM) is a risk factor for Alzheimer's disease and mild cognitive impairment. The etiology of cognitive impairment in people with T2DM is uncertain but, chronic hyperglycemia, cerebral micro vascular disease, severe hypoglycemia, and increased prevalence of macro vascular disease are implicated. to determine the serum levels of soluble vascular adhesion molecule (sVCAM-1) and highly sensitive C-reactive protein (hs-CRP) in elderly type 2 diabetics with mild cognitive impairment (MCI). Our study was conducted on 90 elderly subjects (aged 60 years old or more). They were divided into Group І, 30 patients with T2DM and mild cognitive impairment, group ІІ, 30 patients with T2DM without cognitive impairment and group III, 30 healthy subjects as a control group. They were subjected to history taking, full clinical examination, anthropometric measurement, the Addenbrooke's Cognitive Examination III (ACE---III 2012), Fasting plasma glucose, 2 hours plasma glucose, HbA1c, lipid profile, protein/creatinine ratio, serum sVCAM-1 and hs-CRP. Serum levels of sVCAM-1 in diabetic elderly patients with MCI were significantly higher (946.7 ± 162.01 ng/ml) than diabetic elderly patients without cognitive impairment (479.06 ± 65.27 ng/ml) and control (263.7 ± 72.05 ng/ml) with (P=0.002). Serum levels of Hs-CRP in diabetic elderly patients with MCI were significantly higher than as diabetic elderly patients without cognitive impairment and control with (P=0.005). Elderly diabetic patients with mild cognitive impairment, have higher levels of soluble adhesion molecules and markers of low-grade systemic inflammation than other groups. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

In an Unpredictable and Changing Environment: Intrapreneurial Self-Capital As a Key Resource for Life Satisfaction and Flourishing

OpenAIRE

Annamaria Di Fabio; Letizia Palazzeschi; Ornella Bucci

2017-01-01

The twenty-first century is characterized by an unpredictable and challenging work environment, and the Intrapreneurial Self-Capital (ISC) career and life construct can be seen as a core of individual intrapreneurial resources that enables people to cope with ongoing challenges, changes, and transitions founding innovative solutions when confronted with the constraints imposed by such an environment. The ISC is a challenging construct since it can enhance behavior and attitudes through specif...

The Efficacy of Fibroblast Growth Factor for the Treatment of Chronic Vocal Fold Scarring: From Animal Model to Clinical Application.

Science.gov (United States)

Ban, Myung Jin; Park, Jae Hong; Kim, Jae Wook; Park, Ki Nam; Lee, Jae Yong; Kim, Hee Kyung; Lee, Seung Won

2017-12-01

This study assessed the regenerative efficacy of basic fibroblast growth factor (FGF) in a rabbit model of chronic vocal fold scarring and then confirmed its utility and safety in a prospective trial of patients with this condition. FGF was injected three times, at 1-week intervals, into a chronic vocal fold scar created in a rabbit model. After 1 month, mRNA level of procollagen I, hyaluronic acid synthetase 2 (HAS 2), and matrix metalloproteinase 2 (MMP 2) were analyzed by real-time polymerase chain reaction. The relative densities of hyaluronic acid (HA) and collagen were examined 3 months post-injection. From April 2012 to September 2014, a prospective clinical trial was conducted at a tertiary hospital in Korea. FGF was injected into the mild vocal fold scar of 17 consecutive patients with a small glottic gap. The patients underwent perceptual, stroboscopic, acoustic aerodynamic test, and Voice Handicap Index (VHI) survey prior to and 3, 6, and 12 months after FGF injection. FGF injection of the vocal fold scar decreased the density of collagen and increased mRNA level of HAS 2 and MMP 2 expression significantly compared to the control group injected with phosphate buffered solution in a rabbit model (Pvocal fold injections of FGF in patients with mild chronic vocal fold scarring can significantly improve voice quality for as long as 1 year and without side effects. Our results recommend the use of FGF vocal fold injection as an alternative treatment modality for mild chronic vocal fold scarring.

A2-3: Impact of Mild Chronic Kidney Disease Stage on Outcomes after Total Hip or Knee Arthroplasty

Science.gov (United States)

Graham, Jove; Deegan, Brian; Bowen, Thomas; Richard, Raveesh; Perkins, Robert; Foltzer, Michael

2014-01-01

Background/Aims Dialysis and kidney transplantation adversely impact outcomes of total hip or knee arthroplasty (THA, TKA), but complication rates have not been reported for patients with less advanced stages of chronic kidney disease (CKD). Surgeons lack the data necessary to have informed discussions regarding anticipated outcomes of joint replacement for these patients. Methods We retrospectively reviewed electronic health records of 779 adults with stages 1, 2, and 3 CKD not requiring dialysis or transplantation who underwent THA or TKA from 2004–2011, to assess infection, revision, 90-day readmission and mortality rates. Patients with less than 12 months follow-up, open fracture, prior joint surgery, pregnancy, or acute kidney injury were excluded. Chi-square analysis and Cox survival analysis compared these outcomes between the stage 1–2 and stage 3 groups, stratified by joint replaced (THA vs TKA). All models adjusted for age, sex and BMI at surgery. Results No statistically different rates of revision or infection between Stage 3 vs. Stages 1–2 were seen, although there was a trend toward increased infections in Stage 3. THA patients with Stage 3 showed a significantly increased mortality rate compared to Stage 1–2 THA patients (HR 3.40, 95% CI = 1.25–9.23, P = 0.02). Conclusions CKD affects nearly 15% of the U.S. population many of whom undergo joint replacement. End stage kidney disease (patients post-transplant or on hemodialysis) has been consistently associated with increased rates of infection and revision in excess of our observed outcomes, but the overall rate of infection/revision in our study population was only slightly higher than reported rates in the general population (2–7% vs. 1–2%, respectively). CKD should not preclude joint replacement, but these data can help clinicians engage in meaningful informed discussions with patients with mild kidney disease regarding risks for infection, revision and death following joint

[Minimal and mild endometriosis: Impact of the laparoscopic surgery on pelvic pain and fertility. CNGOF-HAS Endometriosis Guidelines].

Science.gov (United States)

Ploteau, S; Merlot, B; Roman, H; Canis, M; Collinet, P; Fritel, X

2018-03-01

Minimal and mild endometriosis (stage 1 and 2 AFSR) can lead to chronic pelvic pain and infertility but can also exist in asymptomatic patients. The prevalence of asymptomatic patients with minimal and mild endometriosis is not clear but typical endometriosis lesions are found in about 5 to 10% of asymptomatic women and more than 50% of painful and/or infertile women. Laparoscopic treatment of minimal and mild endometriotic lesions is justified in case of pelvic pain because their destruction decrease significatively the pain compared with diagnostic laparoscopy alone. In this context, ablation and excision give identical results in terms of pain reduction. Moreover, literature shows no interest in uterine nerve ablation in case of dysmenorrhea due to minimal and mild endometriosis. Then, it is recommended to treat these lesions during a laparoscopy realised as part of pelvic pain. On the other hand, it is not recommended to treat asymptomatic patients. With regard to treatment of minimal and mild endometriosis in infertile patients, only two studies can be selected and both show that laparoscopy with excision or ablation and ablation of adhesions is superior to diagnostic laparoscopy alone in terms of pregnancy rate. However, it is not recommended to treat these lesions when they are asymptomatic because there is no evidence that they can progress with symptomatic disease. There is no study assessing the interest to treat these lesions when they are found fortuitously. Adhesion barrier utilisation permits to reduce post-operative adhesions, however literature failed to demonstrate the clinical profit in terms of reduction of the risk of pain or infertility. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Long-term follow-up of chronic suppurative otitis media in a high-risk children cohort

DEFF Research Database (Denmark)

Jensen, Ramon Gordon; Homøe, Preben; Andersson, Mikael

2011-01-01

Chronic suppurative otitis media (CSOM) is the leading cause of mild to moderate hearing impairment in children worldwide and a major public health problem in many indigenous populations. There is a lack of basic epidemiological facts and knowledge on the development of CSOM, as the disease...

Regional analysis of the magnetization transfer ratio of the brain in mild Alzheimer disease and amnestic mild cognitive impairment.

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Mascalchi, M; Ginestroni, A; Bessi, V; Toschi, N; Padiglioni, S; Ciulli, S; Tessa, C; Giannelli, M; Bracco, L; Diciotti, S

2013-01-01

Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects. Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the

Disease in a more variable and unpredictable climate

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McMahon, T. A.; Raffel, T.; Rohr, J. R.; Halstead, N.; Venesky, M.; Romansic, J.

2014-12-01

Global climate change is shifting the dynamics of infectious diseases of humans and wildlife with potential adverse consequences for disease control. Despite this, the role of global climate change in the decline of biodiversity and the emergence of infectious diseases remains controversial. Climate change is expected to increase climate variability in addition to increasing mean temperatures, making climate less predictable. However, few empirical or theoretical studies have considered the effects of climate variability or predictability on disease, despite it being likely that hosts and parasites will have differential responses to climatic shifts. Here we present a theoretical framework for how temperature variation and its predictability influence disease risk by affecting host and parasite acclimation responses. Laboratory experiments and field data on disease-associated frog declines in Latin America support this framework and provide evidence that unpredictable temperature fluctuations, on both monthly and diurnal timescales, decrease frog resistance to the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Furthermore, the pattern of temperature-dependent growth of the fungus on frogs was inconsistent with the pattern of Bd growth in culture, emphasizing the importance of accounting for the host-parasite interaction when predicting climate-dependent disease dynamics. Consistent with our laboratory experiments, increased regional temperature variability associated with global El Niño climatic events was the best predictor of widespread amphibian losses in the genus Atelopus. Thus, incorporating the effects of small-scale temporal variability in climate can greatly improve our ability to predict the effects of climate change on disease.

THE MODIFICATION OF THE INDIVIDUAL EMPLOYMENT CONTRACT ASSUMING UNPREDICTABILITY

Directory of Open Access Journals (Sweden)

Ana Vidat

2012-11-01

Full Text Available Adapting a gainful occupation to technological or economical development may require the amendment of individual labor contract under which the activity is performed, taking into account the intrinsic dynamics of employment. If the parties, by agreement, determine the content of the individual labor contract, all in agreement, may agree at any time to amend it according to art. 41 para. 1 of the Labour Code. And trough the provisions of civil law – common law for the employment law – are established legal the review of the effects of the legal actdue because of the breakage contractual balance due to change in the circumstances envisaged by the parties in the moment of conclusion of the legal act (the so-called theory of unpredictability, rebus sic stantibus – exception to the principle "pacta sunt servanda". Recourse to the legal document review because its effects are other than the parties agreed to establish and be binding in the moment of conclusion of that agreement. In the present paper we will refer to administrative contracts, given the subject of this paper – namely that the common law for individual employment contract is the civil law rules applicable to civil contracts. So in this paper does not refer to former commercial contracts, since the new Civil Code was achieved unification of private law matter – giving up the commercial contracts.

[Chronic active hepatitis: clinical, biochemical, and histopathologic correlation].

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Subauste, M C

1989-01-01

A retrospective study over 26 female patients with chronic active hepatitis was made. The mean age was 39 years old, the mean length of illness of 8 months; 5 patients had positive markers for hepatitis B. Patients were selected with the grade of histological activity: 8 patients had a mild form from disease (2A) and 16 with a severe one (2B). The predominant group was 2B. Severe inflammatory infiltration was the hallmark and multiobulillar necrosis, bridging, eosinophils and hiperplasia of kuppfer cells were found only in this group. Clinical features range from hepatic manifestations to systemic ones. Chronic active hepatitis may present with cholestasis, but the latter is not always related with the grade of activity. Group 2B had elevated aminotransferases and a low concentration for protrobine.

Chronic meningoencephalomyelitis with spastic spinal paralysis. Case report

Energy Technology Data Exchange (ETDEWEB)

Mitsuyama, Y; Thompson, L R; Yuki, I; Tanemori, H

1973-01-01

A case of chronic meningoencephalomyelitis in a 48-year-old housewife is presented. The onset was characterized by spastic paralysis of the lower extremities. The course was progressive with repeated remissions and exacerbations, and the patient died approximately 7 years after the onset of disease. Laboratory tests showed slightly increased cell count in the spinal fluid, accelerated sedimentation rate, positive CRP and RA, and increased ASLO and gamma globulin levels. Neuropathologic examination revealed such changes as perivascular cellular infiltration, glial nodules, poorly demarcated demyelination, and recent necrosis in the spinal cord and basal ganglia. Only mild inflammatory findings were noted in the telencephalon and brain stem. The clinicopathologic findings in this case supported a diagnosis of chronic meningoencepalomyelitis which could not be classified as any known type of encephalomyelitis. (auth)

Neuropeptide Y stimulation as primary target for preventive measures of maladaptative cardiovascular reactions in occupational chronic stress exposure.

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Ciumaşu-Rîmbu, Mălina; Popa, Livia; Vulpoi, Carmen

2012-01-01

Chronic stress may produce a decrease in central NPY expression and subjects exposed to it may prove hypersensitivity to a novel stressor with dysfunctions in the NPY system and cardiovascular maladaptation to stress, even hypertension. Upregulation of NPY expression may contribute to successful behavioral adaptation to stress by reducing cardiovascular tone and suppressing anxious behaviors. Adaptogens, a new class of metabolic regulators stimulate NPY expression and release. The aim of this study is to increase tolerance and adaptation to stress of hypersensitive to novel stressor, occupational chronic stress exposed subjects with cardiovascular maladaptation to mild new stressor using adaptogens as part of prevention protocol. 40 military personnel with known cardiostressor reactional mode and occupational chronic stress exposure were exposed to mild novel stressor: occupational medicine routine evaluation and clinically assessed for maladaptative cardiovascular response prior and before application of 30 day prevention protocol. Employees were randomly split in two groups, one receiving standard prevention protocol (lifestyle counseling) plus adaptogens in multiple dose administration, twice daily and the other receiving only standard prevention protocol. We found significant statistic differences in all cardiovascular parameters in adaptogen group and only in diastolic blood pressure in control group. Adaptogens could be an important factor in successful prevention protocols of chronic occupational stress dysfunctions involving NPY systems.

Mild cognitive impairment impacts health outcomes of patients with atrial fibrillation undergoing a disease management intervention.

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Ball, Jocasta; Løchen, Maja-Lisa; Carrington, Melinda J; Wiley, Joshua F; Stewart, Simon

2018-01-01

Mild cognitive impairment (MCI) is prevalent in atrial fibrillation (AF) and has the potential to contribute to poor outcomes. We investigated the influence of MCI on survival and rehospitalisation in patients with chronic forms of AF undergoing a home-based, AF-specific disease management intervention (home-based intervention (HBI)) or standard management (SM). The Montreal Cognitive Assessment tool was administered at baseline (a score of event-free survival (OR 3.48 (95% CI 1.06 to 11.4)), all-cause rehospitalisation (OR 3.30 (95% CI 1.25 to 8.69)) and cardiovascular disease (CVD)-related rehospitalisation (OR 2.35 (95% CI 1.12 to 4.91)) in this group. The effectiveness of home-based, disease management for patients with chronic forms of AF is negatively affected by comorbid MCI. The benefit of adjunctive support for patients with MCI on CVD-related health outcomes requires further investigation.

Comparison of the quick mild cognitive impairment (Qmci) screen and the SMMSE in screening for mild cognitive impairment.

LENUS (Irish Health Repository)

O'Caoimh, Rónán

2012-09-01

differentiating mild cognitive impairment (MCI) from normal cognition (NC) is difficult. The AB Cognitive Screen (ABCS) 135, sensitive in differentiating MCI from dementia, was modified to improve sensitivity and specificity, producing the quick mild cognitive impairment (Qmci) screen.

inhibition performance of mild ste thiophene ac rmance of mild steel

African Journals Online (AJOL)

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d Industrial Chemistry, Faculty of Physical Science, Bayero University, Kan. P. M. B. 3011 ..... chemical studies on the inhibition potentials of some ... Efficiency of Thiophene Derivatives on. Mild Steel : A QSAR Model. International. Journal.

Mild Primary Hyperparathyroidism: A Literature Review

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Applewhite, Megan K.

2014-01-01

The biochemical profile of classic primary hyperparathyroidism (pHPT) consists of both elevated calcium and parathyroid hormone levels. The standard of care is parathyroidectomy unless prohibited by medical comorbidities. Because more patients are undergoing routine bone density evaluation and neck imaging studies for other purposes, there is a subset of people identified with a biochemically mild form of the pHPT that expresses itself as either elevated calcium or parathyroid hormone levels. These patients often do not fall into the criteria for operation based on the National Institutes of Health consensus guidelines, and they can present a challenge of diagnosis and management. The purpose of this paper is to review the available literature on mild pHPT in an effort to better characterize this patient population and to determine whether patients benefit from parathyroidectomy. Evidence suggests that there are patients with mild pHPT who have overt symptoms that are found to improve after parathyroidectomy. There is also a group of patients with biochemically mild pHPT who are found to progress to classic pHPT over time; however, it is not predictable which group of patients this will be. Early intervention for this group with mild pHPT may prevent progression of bone, psychiatric, and renal complications, and parathyroidectomy has proven safe in appropriately selected patients at high volume centers. PMID:25063228

Electroencephalography and quantitative electroencephalography in mild traumatic brain injury.

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Haneef, Zulfi; Levin, Harvey S; Frost, James D; Mizrahi, Eli M

2013-04-15

Mild traumatic brain injury (mTBI) causes brain injury resulting in electrophysiologic abnormalities visible in electroencephalography (EEG) recordings. Quantitative EEG (qEEG) makes use of quantitative techniques to analyze EEG characteristics such as frequency, amplitude, coherence, power, phase, and symmetry over time independently or in combination. QEEG has been evaluated for its use in making a diagnosis of mTBI and assessing prognosis, including the likelihood of progressing to the postconcussive syndrome (PCS) phase. We review the EEG and qEEG changes of mTBI described in the literature. An attempt is made to separate the findings seen during the acute, subacute, and chronic phases after mTBI. Brief mention is also made of the neurobiological correlates of qEEG using neuroimaging techniques or in histopathology. Although the literature indicates the promise of qEEG in making a diagnosis and indicating prognosis of mTBI, further study is needed to corroborate and refine these methods.

Discrepancy between functional exercise capacity and daily physical activity: a cross-sectional study in patients with mild to moderate COPD.

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Fastenau, Annemieke; van Schayck, Onno C P; Gosselink, Rik; Aretz, Karin C P M; Muris, Jean W M

2013-12-01

In patients with moderate to severe chronic obstructive pulmonary disease (COPD) the six-minute walk distance reflects the functional exercise level for daily physical activity. It is unknown if this also applies to patients with mild to moderate COPD in primary care. To assess the relationship between functional exercise capacity and physical activity in patients with mild to moderate COPD. A cross-sectional study was performed in 51 patients with mild to moderate COPD in primary care. Functional exercise capacity was assessed by the six-minute walk test and physical activity was measured with an accelerometer-based activity monitor. Functional exercise capacity was close to normal values. However, the daily physical activity of the patients could be classified as 'sedentary' and 'low active'. No significant correlations were observed between six-minute walk distance (% predicted) and any of the physical activity variables (steps per day, movement intensity during walking, total active time, total walking time, physical activity level, and time spent in moderate physical activity). A discrepancy was found between functional exercise capacity and daily physical activity in patients with mild to moderate COPD recruited and assessed in primary care. We conclude that these variables represent two different concepts. Our results reinforce the importance of measuring daily physical activity in order to fine-tune treatment (i.e. focusing on enhancement of exercise capacity or behavioural change, or both).

Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection.

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Xu, Zhengju; Shen, Jiankun; Pan, Xingnan; Wei, Meijuan; Liu, Liguan; Wei, Kaipeng; Liu, Lifei; Yang, Huanwen; Huang, Jinfa

2018-06-01

As a noninvasive marker, serum alanine aminotransferase (ALT) has limitations, because a large proportion of patients chronically infected with hepatitis B virus (HBV) suffer from severe hepatic necroinflammation, but have normal or mildly elevated ALT. In the present study, we aimed to investigate the potential value of serum Golgi protein 73 (GP73) in predicting significant hepatic necroinflamation among chronic HBV infected patients. A cohort of 497 chronic HBV infected patients was retrospectively recruited. Liver biopsy was performed in all patients and serum GP73 levels were measured by enzyme-linked immunosorbent assay. Serum GP73 increased in parallel with the increase in hepatic necroinflammatory activity grade (r = 0.682) and the stage of liver fibrosis (r = 0.539). The positive correlation of serum GP73 with the degree of hepatic necroinflammatory activity was statistically significant, while serum GP73 with the stage of liver fibrosis was weaker than that with hepatic necroinflammation. Furthermore, serum GP73 levels were significantly greater in patients with normal or mildly elevated ALT and significant hepatic necroinflammation (≥G2) than in patients with minimal to mild hepatic necroinflammation. The sensitivity and specificity of GP73 for the diagnosis of G2 hepatic necroinflammation was 42.35% and 95.0%, respectively, at a cut-off value of 88.38 ng/mL. When the cut-off value was set at 124.76 ng/mL, the sensitivity and specificity of GP73 for the diagnosis of G3 hepatic necroinflammation was 55.56% and 97.29%, respectively. These findings indicate that GP73 holds promise as an important candidate for diagnosing significant hepatic necroinflammation. © 2018 Wiley Periodicals, Inc.

Dual-task as a predictor of falls in older people with mild cognitive impairment and mild Alzheimer's disease: a prospective cohort study.

Science.gov (United States)

Gonçalves, Jessica; Ansai, Juliana Hotta; Masse, Fernando Arturo Arriagada; Vale, Francisco Assis Carvalho; Takahashi, Anielle Cristhine de Medeiros; Andrade, Larissa Pires de

2018-04-04

A dual-task tool with a challenging and daily secondary task, which involves executive functions, could facilitate the screening for risk of falls in older people with mild cognitive impairment or mild Alzheimer's disease. To verify if a motor-cognitive dual-task test could predict falls in older people with mild cognitive impairment or mild Alzheimer's disease, and to establish cutoff scores for the tool for both groups. A prospective study was conducted with community-dwelling older adults, including 40 with mild cognitive impairment and 38 with mild Alzheimer's disease. The dual-task test consisted of the Timed up and Go Test associated with a motor-cognitive task using a phone to call. Falls were recorded during six months by calendar and monthly telephone calls and the participants were categorized as fallers or non-fallers. In the Mild cognitive impairment Group, fallers presented higher values in time (35.2s), number of steps (33.7 steps) and motor task cost (116%) on dual-task compared to non-fallers. Time, number of steps and motor task cost were significantly associated with falls in people with mild cognitive impairment. Multivariate analysis identified higher number of steps spent on the test to be independently associated with falls. A time greater than 23.88s (sensitivity=80%; specificity=61%) and a number of steps over 29.50 (sensitivity=65%; specificity=83%) indicated prediction of risk of falls in the Mild cognitive impairment Group. Among people with Alzheimer's disease, no differences in dual-task between fallers and non-fallers were found and no variable of the tool was able to predict falls. The dual-task predicts falls only in older people with mild cognitive impairment. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

The behavioural and physiological strategies of bird and reptile embryos in response to unpredictable variation in nest temperature.

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Du, Wei-Guo; Shine, Richard

2015-02-01

Temperature profoundly affects the rate and trajectory of embryonic development, and thermal extremes can be fatal. In viviparous species, maternal behaviour and physiology can buffer the embryo from thermal fluctuations; but in oviparous animals (like most reptiles and all birds), an embryo is likely to encounter unpredictable periods when incubation temperatures are unfavourable. Thus, we might expect natural selection to have favoured traits that enable embryos to maintain development despite those fluctuations. Our review of recent research identifies three main routes that embryos use in this way. Extreme temperatures (i) can be avoided (e.g. by accelerating hatching, by moving within the egg, by cooling the egg by enhanced rates of evaporation, or by hysteresis in rates of heating versus cooling); (ii) can be tolerated (e.g. by entering diapause, by producing heat-shock proteins, or by changing oxygen use); or (iii) the embryo can adjust its physiology and/or developmental trajectory in ways that reduce the fitness penalties of unfavourable thermal conditions (e.g. by acclimating, by exploiting brief windows of favourable conditions, or by producing the hatchling phenotype best suited to those incubation conditions). Embryos are not simply passive victims of ambient conditions. Like free-living stages of the life cycle, embryos exhibit behavioural and physiological plasticity that enables them to deal with unpredictable abiotic challenges. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

Do we over treat mild hypertension?

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Zanchetti, Alberto

2015-06-01

The important question whether 'mild' hypertension should or should not be treated by drugs is difficult to answer, because the only randomized controlled trials (RCTs) investigating this question were conducted when the definition of 'mild' hypertension was based on diastolic blood pressure only, whereas the present definition of grade 1 hypertension includes both systolic and diastolic values (SBP/DBP), and the concept of 'mild' hypertension also includes that of low-moderate cardiovascular risk (hypertension only on the basis of expert opinion. However, recent meta-analyses have provided some support to drug treatment intervention in low-moderate risk grade 1 hypertensives and have shown that, when treatment is deferred until organ damage or cardiovascular disease occur, absolute residual risk (events occurring despite treatment) markedly increases. Although evidence favoring therapeutic intervention in mild hypertension is nowadays stronger than expert opinion, meta-analyses are not substitutes for specific RCTs, and the wide BP spans defining grade 1 hypertension as well as the span defining low-moderate risk leave a wide space for individualized or personalized decisions.

Serum C-reactive protein and thioredoxin levels in subjects with mildly reduced glomerular filtration rate

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Ishimura Eiji

2010-04-01

Full Text Available Abstract Background Chronic kidney disease (CKD is a newly recognized high-risk condition for cardiovascular disease (CVD, and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR. Methods The subjects were 182 participants of a health check-up program including those with normal (≥ 90 mL/min/1.73 m2, N = 79 and mildly reduced eGFR (60-89 mL/min/1.73 m2, N = 103 which was calculated based on serum creatinine, age and sex. We excluded those with reduced eGFR 2. No one had proteinuria. We measured serum levels of C-reactive protein (CRP and thioredoxin (TRX as the markers of inflammation and oxidative stress, respectively. Results As compared with subjects with normal eGFR, those with mildly reduced eGFR had increased levels of both CRP and TRX. Also, eGFR was inversely correlated with these biomarkers. The associations of eGFR with these biomarkers remained significant after adjustment for age and sex. When adjustment was done for eight possible confounders, CRP showed significant association with systolic blood pressure, high density lipoprotein cholesterol (HDL-C and non-HDL-C, whereas TRX was associated with sex significantly, and with eGFR and systolic blood pressure at borderline significance. Conclusions We showed the increased levels of CRP and TRX in subjects with mildly reduced eGFR. The eGFR-CRP link and the eGFR-TRX link appeared to be mediated, at least partly, by the alterations in blood pressure and plasma lipids in these subjects.

Response to CPAP Withdrawal in Patients with Mild Versus Severe Obstructive Sleep Apnea/Hypopnea Syndrome

Science.gov (United States)

Young, Laura R.; Taxin, Zachary H.; Norman, Robert G.; Walsleben, Joyce A.; Rapoport, David M.; Ayappa, Indu

2013-01-01

Background: Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), even those generally compliant with CPAP therapy, often intermittently discontinue CPAP. Study Objective: Examine the impact of CPAP withdrawal on sleep, sleep disordered breathing (SDB), and daytime function in subjects with varying severity of OSAHS. Patients and Interventions: Forty-two subjects (26M/16 F) with OSAHS (AHI4% = 45.2 ± 35.5/h pretreatment) on CPAP for 4 months were evaluated on the second night of CPAP withdrawal. Sleep architecture, SDB indices, and subjective/objective daytime function were assessed pretreatment, on CPAP therapy, and after CPAP withdrawal. Comparisons were made between pretreatment and CPAP withdrawal for the entire group, and for subgroups of mild/moderate (AHI4% 30/h, n = 20) SDB. Results: Overall, and for mild/moderate subjects, SDB indices returned to pretreatment values on CPAP withdrawal but with fewer apneas and more hypopneas/RERAs. For severe SDB, the event frequency (AI, AHI4%, and RDI) was lower and O2 desaturation was improved on CPAP withdrawal. Across SDB severity, sleep architecture showed lower %REM (15.6% vs 12.9%, P = 0.009) on the CPAP withdrawal compared to pretreatment. Stanford Sleepiness Score, MSLT, and PVT measures were not significantly different between pretreatment and CPAP withdrawal. Conclusions: Over a wide range of SDB severity CPAP withdrawal results in recurrence of SDB, albeit with less severe O2 desaturation. Subjective/objective daytime function returned to pretreatment levels. Sleep architecture changes on CPAP withdrawal (acute SDB) may reflect reduced sleep pressure compared to pretreatment chronic SDB. Our data suggest detrimental effects of even brief withdrawal of CPAP in subjects with both mild and severe OSAHS. Citation: Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea/hypopnea syndrome. SLEEP 2013

Chronic subordinate colony housing (CSC as a model of chronic psychosocial stress in male rats.

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Kewir D Nyuyki

Full Text Available Chronic subordinate colony housing (CSC is an adequate and reliable mouse model of chronic psychosocial stress, resulting in reduced body weight gain, reduced thymus and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Furthermore, CSC mice show increased corticotrophin (ACTH responsiveness to acute heterotypic stressors, suggesting a general mechanism which allows a chronically-stressed organism to adequately respond to a novel threat. Therefore, the aim of the present study was to extend the CSC model to another rodent species, namely male Wistar rats, and to characterize relevant physiological, immunological, and behavioural consequences; placing particular emphasis on changes in hypothalamo-pituitary-adrenal (HPA axis responsiveness to an acute heterotypic stressor. In line with previous mouse data, exposure of Wistar rats to 19 days of CSC resulted in a decrease in body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in stress-coping behaviour or social preference were seen; again in agreement with the mouse paradigm. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor (open arm, 5 min despite displaying similar basal levels and similar basal and stressor-induced plasma ACTH levels. In contrast to CSC mice, anxiety-related behaviour and absolute, as well as relative adrenal weights remained unchanged in CSC rats. In summary, the CSC paradigm could be established as an adequate model of chronic psychosocial stress in male rats. Our data further support the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed organism to adequately respond to novel challenges.

Neuronal apoptosis and synaptic density in the dentate gyrus of ischemic rats' response to chronic mild stress and the effects of Notch signaling.

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Shaohua Wang

Full Text Available Our previous research highlighted an inconsistency with Notch1 signaling-related compensatory neurogenesis after chronic mild stress (CMS in rodents suffering from cerebral ischemia, which continue to display post-stroke depressive symptoms. Here, we hypothesize that CMS aggrandized ischemia-related apoptosis injury and worsened synaptic integrity via gamma secretase-meditated Notch1 signaling. Adult rats were exposed to a CMS paradigm after left middle cerebral artery occlusion (MCAO. Open-field and sucrose consumption testing were employed to assess depression-like behavior. Gene expression of pro-apoptotic Bax, anti-apoptotic Bcl-2, and synaptic density-related synaptophysin were measured by western blotting and real-time PCR on Day 28 after MCAO surgery. CMS induced depressive behaviors in ischemic rats, which was accompanied by an elevation in Bax/bcl-2 ratio, TUNEL staining in neurons and reduced synaptophysin expression in the dentate gyrus. These collective effects were reversed by the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl]-S-phenyl-glycine t-butyl ester. We found that post-stroke stressors made neurons in the dentate gyrus vulnerable to apoptosis, which supports a putative role for Notch signaling in neural integrity, potentially in newborn cells' synaptic deficit with regard to preexisting cells. These findings suggest that post-stroke depression therapeutically benefits from blocking gamma secretase mediated Notch signaling, and whether this signaling pathway could be a therapeutic target needs to be further investigated.

Clinical characteristics and risk factors of pulmonary hypertension associated with chronic respiratory diseases: a retrospective study.

Science.gov (United States)

Chen, Yonghua; Liu, Chunli; Lu, Wenju; Li, Mengxi; Hadadi, Cyrus; Wang, Elizabeth Wenqian; Yang, Kai; Lai, Ning; Huang, Junyi; Li, Shiyue; Zhong, Nanshan; Zhang, Nuofu; Wang, Jian

2016-03-01

Chronic respiratory disease-associated pulmonary hypertension (PH) is an important subtype of PH, which lacks clinical epidemiological data in China. Six hundred and ninety three patients hospitalized from 2010 to 2013 were classified by echocardiography according to pulmonary arterial systolic pressure (PASP): mild (36≤ PASP increase of N-terminal pro brain natriuretic peptide (NT-proBNP) and right ventricular (RV) diameter (>20 mm) were associated with moderate-to-severe PH, while RV [odds ratio (OR) =3.53, 95% CI, 2.17-5.74], NT-proBNP (OR=2.44, 95% CI, 1.51-3.95), HCT (OR=1.03, 95% CI, 1.00-1.07) and PaCO2 (OR=1.01, 95% CI, 1.00-1.03) were independent risk factors. PH related to respiratory diseases is mostly mild to moderate, and the severity is associated with the category of respiratory disease. Increased HCT can be an independent risk factor for PH related to chronic respiratory diseases.

Effect of physical activity on memory function in older adults with mild Alzheimer's disease and mild cognitive impairment.

Science.gov (United States)

Tanigawa, Takanori; Takechi, Hajime; Arai, Hidenori; Yamada, Minoru; Nishiguchi, Shu; Aoyama, Tomoki

2014-10-01

It is very important to maintain cognitive function in patients with mild cognitive disorder. The aim of the present study was to determine whether the amount of physical activity is associated with memory function in older adults with mild cognitive disorder. A total of 47 older adults with mild cognitive disorder were studied; 30 were diagnosed with mild Alzheimer's disease and 17 with mild cognitive impairment. The global cognitive function, memory function, physical performance and amount of physical activity were measured in these patients. We divided these patients according to their walking speed (1 m/s). A total of 26 elderly patients were classified as the slow walking group, whereas 21 were classified as the normal walking group. The normal walking group was younger and had significantly better scores than the slow walking group in physical performance. Stepwise multiple linear regression analysis showed that only the daily step counts were associated with the Scenery Picture Memory Test in patients of the slow walking group (β=0.471, P=0.031), but not other variables. No variable was significantly associated with the Scenery Picture Memory Test in the normal walking group. Memory function was strongly associated with the amount of physical activity in patients with mild cognitive disorder who showed slow walking speed. The results show that lower physical activities could be a risk factor for cognitive decline, and that cognitive function in the elderly whose motor function and cognitive function are declining can be improved by increasing the amount of physical activity. © 2014 Japan Geriatrics Society.

Is Chronic Inflammation a Possible Cause of Obesity-Related Depression?

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Olszanecka-Glinianowicz, Magdalena; Zahorska-Markiewicz, Barbara; Kocełak, Piotr; Janowska, Joanna; Semik-Grabarczyk, Elżbieta; Wikarek, Tomasz; Gruszka, Wojciech; Dąbrowski, Piotr

2009-01-01

Adult obesity has been associated with depression, especially in women. Whether depression leads to obesity or obesity causes depression is unclear. Chronic inflammation is observed in obesity and depression. In 63 obese women without additional diseases depression level was assessed with the Beck's questionnaire. After evaluation of depression level study group was divided into groups according to the mood status (A—without depression, B—mild depression, and C—severe depression), and serum c...

Pain Catastrophizing Correlates with Early Mild Traumatic Brain Injury Outcome

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Geneviève Chaput

2016-01-01

Full Text Available Background. Identifying which patients are most likely to be at risk of chronic pain and other postconcussion symptoms following mild traumatic brain injury (MTBI is a difficult clinical challenge. Objectives. To examine the relationship between pain catastrophizing, defined as the exaggerated negative appraisal of a pain experience, and early MTBI outcome. Methods. This cross-sectional design included 58 patients diagnosed with a MTBI. In addition to medical chart review, postconcussion symptoms were assessed by self-report at 1 month (Time 1 and 8 weeks (Time 2 after MTBI. Pain severity, psychological distress, level of functionality, and pain catastrophizing were measured by self-report at Time 2. Results. The pain catastrophizing subscales of rumination, magnification, and helplessness were significantly correlated with pain severity (r=.31 to .44, number of postconcussion symptoms reported (r=.35 to .45, psychological distress (r=.57 to .67, and level of functionality (r=-.43 to -.29. Pain catastrophizing scores were significantly higher for patients deemed to be at high risk of postconcussion syndrome (6 or more symptoms reported at both Time 1 and Time 2. Conclusions. Higher levels of pain catastrophizing were related to adverse early MTBI outcomes. The early detection of pain catastrophizing may facilitate goal-oriented interventions to prevent or minimize the development of chronic pain and other postconcussion symptoms.

Wechsler Memory Scale-III Faces test performance in patients with mild cognitive impairment and mild Alzheimer's disease.

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Seelye, Adriana M; Howieson, Diane B; Wild, Katherine V; Moore, Mindy Milar; Kaye, Jeffrey A

2009-08-01

Little is known about the sensitivity of the Wechsler Memory Scale-Third Edition (WMS-III) Faces subtest to memory impairment associated with mild cognitive impairment (MCI). In this study, Faces performance was examined in 24 MCI patients, 46 mild Alzheimer's disease (AD) patients, and 98 elderly controls. We hypothesized that participants with diagnoses of MCI or AD would be impaired relative to controls on Faces. Analyses showed that AD participants performed significantly worse than MCI and intact participants, although there were no significant differences between MCI and intact participants. Data suggest that brain areas specialized for face recognition memory may be less affected by MCI and mild AD than regions specialized for verbal memory.

Histopathological analysis of Salmonella chronic carriage in the mouse hepatopancreatobiliary system.

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Geoffrey Gonzalez-Escobedo

Full Text Available Salmonella Typhi asymptomatic chronic carriage represents a challenge for the diagnosis and prevention of typhoid fever in endemic areas. Such carriers are thought to be reservoirs for further spread of the disease. Gallbladder carriage has been demonstrated to be mediated by biofilm formation on gallstones and by intracellular persistence in the gallbladder epithelium of mice. In addition, both gallstones and chronic carriage have been associated with chronic inflammation and the development of gallbladder carcinoma. However, the pathogenic relationship between typhoid carriage and the development of pre-malignant and/or malignant lesions in the hepatopancreatobiliary system as well as the host-pathogen interactions occurring during chronic carriage remains unclear. In this study, we monitored the histopathological features of chronic carriage up to 1 year post-infection. Chronic cholecystitis and hepatitis ranging from mild to severe were present in infected mice regardless of the presence of gallstones. Biliary epithelial hyperplasia was observed more commonly in the gallbladder of mice with gallstones (uninfected or infected. However, pre-malignant lesions, atypical hyperplasia and metaplasia of the gallbladder and exocrine pancreas, respectively, were only associated with chronic Salmonella carriage. This study has implications regarding the role of Salmonella chronic infection and inflammation in the development of pre-malignant lesions in the epithelium of the gallbladder and pancreas that could lead to oncogenesis.

Mild obstructive sleep apnoea: clinical relevance and approaches to management.

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McNicholas, Walter T; Bonsignore, Maria R; Lévy, Patrick; Ryan, Silke

2016-10-01

Obstructive sleep apnoea is highly prevalent in the general population worldwide, especially in its mild form. Clinical manifestations correlate poorly with disease severity measured by the apnoea-hypopnoea index (AHI), which complicates diagnosis. Full polysomnography might be more appropriate to assess suspected mild cases because limited ambulatory diagnostic systems are least accurate in mild disease. Treatment options in mild obstructive sleep apnoea include continuous positive airway pressure (CPAP) and oral appliance therapy, in addition to positional therapy and weight reduction when appropriate. The superior efficacy of CPAP in reducing AHI is offset by greater tolerance of oral appliances, especially in mild disease. Although severe obstructive sleep apnoea is associated with adverse health consequences, including cardiometabolic comorbidities, the association with mild disease is unclear, and reports differ regarding the clinical relevance of mild obstructive sleep apnoea. Improved diagnostic techniques and evidence-based approaches to management in mild obstructive sleep apnoea require further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Review of chronic ulcerative colitis cases at King Hussein Medical Centre, Jordan.

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Ghazzawi, I; Al-Mrayat, Z

2007-01-01

Chronic ulcerative colitis is being encountered with increasing frequency in developing countries. In Amman, Jordan, the records of 372 patients with chronic ulcerative colitis diagnosed between 1994 and 2001 were reviewed. Bloody diarrhoea and crampy abdominal pain were the most common presenting symptoms (84% of patients). The mean age at onset was 31.8 years. In two thirds of patients the diagnosis was made more than 1 year after the onset of symptoms. The pattern of the disease differed from that in industrialized countries in the mild course of the disease, the absence of skin manifestations, and the rarity of colorectal cancer in our patients. The mortality rate was 6%.

[Definition and clinical characteristics of mild hypertension].

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Saruta, Takao

2008-08-01

Mild hypertension is defined as blood pressure level of 140-159 mmHg systolic and/or 90-99 mmHg diastolic. The patients with blood pressure level of mild hypertension occupy about 60% of total hypertensive patients in Japan, and most of them are free of subjective symptoms except elevated blood pressure. However, some of the patients with mild hypertension develop cardiovascular events, since thay have occasionally cardiovascular damages on this level of blood pressure and several risk factors of cardiovascular diseases such as diabetes mellitus and hyperlipidemia.

Effects of common chronic medical conditions on psychometric tests used to diagnose minimal hepatic encephalopathy

DEFF Research Database (Denmark)

Lauridsen, M M; Poulsen, L; Rasmussen, C K

2016-01-01

Many chronic medical conditions are accompanied by cognitive disturbances but these have only to a very limited extent been psychometrically quantified. An exception is liver cirrhosis where hepatic encephalopathy is an inherent risk and mild forms are diagnosed by psychometric tests. The preferred...... diagnostic test battery in cirrhosis is often the Continuous Reaction Time (CRT) and the Portosystemic Encephalopathy (PSE) tests but the effect on these of other medical conditions is not known. We aimed to examine the effects of common chronic (non-cirrhosis) medical conditions on the CRT and PSE tests. We...

Efficacy of camostat mesilate against dyspepsia associated with non-alcoholic mild pancreatic disease

International Nuclear Information System (INIS)

Sai, J.K.; Suyama, Masafumi; Kubokawa, Yoshihiro; Matsumura, Yuji; Inami, Koichi; Watanabe, Sumio

2010-01-01

The aim of the present study was to examine the potential efficacy of camostat mesilate, a protease inhibitor, against dyspepsia associated with non-alcoholic mild pancreatic disease. Patients with upper abdominal pain suggesting pancreatic disease (persistent over hours, pain aggravated by ingestion of food, epigastric pain radiating to the back), without a history of alcohol consumption and who exhibited no abnormalities regarding serum amylase and lipase, ultrasonography, CT and upper gastrointestinal endoscopy, were prescribed 200 mg camostat mesilate three times daily for 2 weeks. The patients were subjected to endoscopic ultrasonography (EUS) while under treatment and were distributed into those who had 4 or more suggestive findings of chronic pancreatitis (suspected pancreatic disease group), 2 or 3 (equivalent group) and those with 1 or no findings (control group). Symptom severity was recorded before and after treatment using a 10-cm visual analog scale (VAS). Among 95 patients, 40 were in the suspected pancreatic disease group, 30 were in the equivalent group and 25 served as controls. A significant intra- and inter-group improvement of symptoms was observed not only in the suspected pancreatic disease group but also in the equivalent group. Camostat mesilate may serve as a therapeutic agent for patients with dyspepsia associated with mild pancreatic disease, who do not habitually drink alcohol. (author)

Impaired Latent Inhibition in GDNF-Deficient Mice Exposed to Chronic Stress

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Mona Buhusi

2017-10-01

Full Text Available Increased reactivity to stress is maladaptive and linked to abnormal behaviors and psychopathology. Chronic unpredictable stress (CUS alters catecholaminergic neurotransmission and remodels neuronal circuits involved in learning, attention and decision making. Glial-derived neurotrophic factor (GDNF is essential for the physiology and survival of dopaminergic neurons in substantia nigra and of noradrenergic neurons in the locus coeruleus. Up-regulation of GDNF expression during stress is linked to resilience; on the other hand, the inability to up-regulate GDNF in response to stress, as a result of either genetic or epigenetic modifications, induces behavioral alterations. For example, GDNF-deficient mice exposed to chronic stress exhibit alterations of executive function, such as increased temporal discounting. Here we investigated the effects of CUS on latent inhibition (LI, a measure of selective attention and learning, in GDNF-heterozygous (HET mice and their wild-type (WT littermate controls. No differences in LI were found between GDNF HET and WT mice under baseline experimental conditions. However, following CUS, GDNF-deficient mice failed to express LI. Moreover, stressed GDNF-HET mice, but not their WT controls, showed decreased neuronal activation (number of c-Fos positive neurons in the nucleus accumbens shell and increased activation in the nucleus accumbens core, both key regions in the expression of LI. Our results add LI to the list of behaviors affected by chronic stress and support a role for GDNF deficits in stress-induced pathological behaviors relevant to schizophrenia and other psychiatric disorders.

Treatment of chronic anterior shoulder dislocation by open reduction and simultaneous Bankart lesion repair

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Rouhani Alireza

2010-06-01

Full Text Available Abstract Background Untreated chronic shoulder dislocation eventually leads to functional disability and pain. Open reduction with different fixation methods have been introduced for most chronic shoulder dislocation. We hypothesized that open reduction and simultaneous Bankart lesion repair in chronic anterior shoulder dislocation obviates the need for joint fixation and leads to better results than previously reported methods. Methods Eight patients with chronic anterior dislocation of shoulder underwent open reduction and capsulolabral complex repair after an average delay of 10 weeks from injury. Early motion was allowed the day after surgery in the safe position and the clinical and radiographic results were analyzed at an average follow-up of one year. Results The average Rowe and Zarin's score was 86 points. Four out of eight shoulders were graded as excellent, three as good and one as fair (Rowe and Zarins system. All patients were able to perform their daily activities and they had either mild or no pain. Anterior active forward flexion loss averaged 18 degrees, external active rotation loss averaged 17.5 degrees and internal active rotation loss averaged 3 vertebral body levels. Mild degenerative joint changes were noted in one patient. Conclusion The results show that the overall prognosis for this method of operation is more favorable than the previously reported methods and we recommend concomitant open reduction and capsulolabral complex repair for the treatment of old anterior shoulder dislocation. Level of Evidence Therapeutic study, Level IV (case series [no, or historical, control group

Chronic Recurrent Multifocal Osteomyelitis in a 9-year-old Boy

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Abdolreza Malek

2017-05-01

Full Text Available Chronic recurrent multifocal osteomyelitis (CRMO is a rare aseptic, auto-inflammatory bone disorder. CRMO presents with bone pain with or without fever. The diagnosis of CRMO is a diagnosis of exclusion and should be included in the differential diagnosis of chronic inflammatory bone lesions in children. Cultures of the bone are typically sterile, antibiotic therapy does not result in clinical improvement whereas anti-inflammatory drugs improve the condition. Furthermore, biopsy should be considered in chronic and relapsing bone pain and swelling unresponsive to treatment. Herein, we present a nine-year-old boy complaining of recurrent pain in his upper and lower extremities. On examination he had mild fever and cervical lymphadenopathy. He also had experienced bone pain and weight loss in the recent month. Based on biopsy and bone scan he was finally diagnosed with CRMO. Naproxen and Pamidronate was prescribed and he was getting better and returned to normal life and activity without need to corticosteroids.

Mild Traumatic Brain Injury

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... mild Traumatic Brain Injury Resilience Families with Kids Depression Families & Friendships Tobacco Life Stress Spirituality Anger Physical Injury Stigma Health & Wellness Work Adjustment Community Peer-2-Peer Forum ...

Recent neuroimaging techniques in mild traumatic brain injury.

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Belanger, Heather G; Vanderploeg, Rodney D; Curtiss, Glenn; Warden, Deborah L

2007-01-01

Mild traumatic brain injury (TBI) is characterized by acute physiological changes that result in at least some acute cognitive difficulties and typically resolve by 3 months postinjury. Because the majority of mild TBI patients have normal structural magnetic resonance imaging (MRI)/computed tomography (CT) scans, there is increasing attention directed at finding objective physiological correlates of persistent cognitive and neuropsychiatric symptoms through experimental neuroimaging techniques. The authors review studies utilizing these techniques in patients with mild TBI; these techniques may provide more sensitive assessment of structural and functional abnormalities following mild TBI. Particular promise is evident with fMRI, PET, and SPECT scanning, as demonstrated by associations between brain activation and clinical outcomes.

Learning and memory alterations are associated with hippocampal N-acetylaspartate in a rat model of depression as measured by 1H-MRS.

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Guangjun Xi

Full Text Available It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS, to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI and magnetic resonance spectroscopy (MRS. Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume.

Chronic pulmonary disease - a multifacted disease complex in the horse

International Nuclear Information System (INIS)

Clarke, A.F.

1987-01-01

This paper reviews chronic pulmonary disease (CPD) as an insidiously developing disease capable of being manifest in many degrees. Horses may suffer mild, sub-clinical degrees of lower respiratory tract inflammation or small airway disease withouth showing symptoms at rest. This form of disease becomes manifest as poor performance when these horses take part in athletic competition. Factors relating to the aetiology, diagnosis, treatment and prevention of all degrees of small airway disease of horses are discussed. 30 refs

Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule

DEFF Research Database (Denmark)

Borcel, Erika; Pérez-Alvarez, Laura; Herrero, Ana Isabel

2008-01-01

In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed...... in the hippocampus. Interestingly, spatial-memory performance in the Morris water maze was positively correlated with the number of newborn cells that survived in the dentate gyrus: better spatial memory in the water maze was associated with more 5-bromo-2-deoxyuridine (BrdU)-labeled cells. Administration of FGL......, a peptide mimetic of neural cell adhesion molecule, during the 4 weeks of continuous stress not only prevented the deleterious effects of chronic stress on spatial memory, but also reduced the survival of the newly generated hippocampal cells in aging animals. FGL treatment did not, however, prevent...

Chronic pain and mortality: a systematic review.

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Diane Smith

Full Text Available Chronic pain is common, often widespread and has a substantial impact on health and quality of life. The relationship between chronic pain and mortality is unclear. This systematic review aimed to identify and evaluate evidence for a relationship between chronic pain and mortality.A search of ten electronic databases including EMBASE and MEDLINE was conducted in March 2012, and updated until March 2014. Observational studies investigating the association between chronic or widespread pain (including fibromyalgia and mortality were included. Risk of bias was assessed and a meta-analysis was undertaken to quantify heterogeneity and pool results. A narrative review was undertaken to explore similarities and differences between the included studies.Ten studies were included in the review. Three reported significant associations between chronic or widespread pain and mortality in unadjusted results. In adjusted analyses, four studies reported a significant association. The remaining studies reported no statistically significant association. A meta-analysis showed statistically significant heterogeneity of results from studies using comparable outcome measures (n = 7(I2 = 78.8% and a modest but non-significant pooled estimate (MRR1.14,95%CI 0.95-1.37 for the relationship between chronic pain and all-cause mortality. This association was stronger when analysis was restricted to studies of widespread pain (n = 5,I2 = 82.3% MRR1.22(95%CI 0.93-1.60. The same pattern was observed with deaths from cancer and cardiovascular diseases. Heterogeneity is likely to be due to differences in study populations, follow-up time, pain phenotype, methods of analysis and use of confounding factors.This review showed a mildly increased risk of death in people with chronic pain, particularly from cancer. However, the small number of studies and methodological differences prevented clear conclusions from being drawn. Consistently applied definitions of

Prazosin for Prophylaxis of Chronic Post Traumatic Headaches in OEF/OIF/OND Service Members and Veterans with Mild TBI

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2017-10-01

mild traumatic brain injury, improved posttraumatic stress disorder severity and sleep correlated with symptomatic improvement. J Rehabil Res Dev...frequency and severity of headaches, in addition to decreasing PTSD-related symptoms and improving the quality of sleep . The objectives of this study...improving quality of sleep . The objectives of this study will be accomplished by conducting a randomized placebo-controlled double blind trial of prazosin

Reduced Sympathetic Response to Head-Up Tilt in Subjects with Mild Cognitive Impairment or Mild Alzheimer's Dementia

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Marte Rognstad Mellingsæter

2015-03-01

Full Text Available Background: Hemodynamic control was compared in patients with mild cognitive impairment (MCI or mild Alzheimer's dementia (AD as well as in healthy elderly subjects. Methods: Noninvasive, continuous hemodynamic recordings were obtained from 14 patients and 48 controls during supine rest (tilt of 30 and 70°. Cardiac output, end-diastolic volume, total peripheral resistance, heart rate variability (HRV, systolic blood pressure variability (SBPV, and baroreceptor sensitivity were calculated. Results: At 70° tilt, the HRV indices differed significantly, with higher high-frequency (HF variability as well as lower low-frequency (LF variability and LF/HF ratios in the patients. The patients had significantly lower SBPV in the LF range at 30° tilt. Conclusions: The results indicate a poorer sympathetic response to orthostatic stress in MCI and mild AD.

Chiropractic chronic low back pain sufferers and self-report assessment methods. Part II. A reliability study of the Middlesex Hospital Questionnaire and the VAS Disability Scales Questionnaire.

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Leboeuf, C; Love, A; Crisp, T C

1989-04-01

The subjective complaints of 41 chronic low back pain sufferers attending a chiropractic clinic were assessed twice prior to therapy with a widely used psychological self-report assessment tool, the Middlesex Hospital Questionnaire (MHQ) and a newly developed VAS Disability Scales Questionnaire (DISQ), both of which investigate various aspects of certain basic positions and activities. Reliability was generally acceptable with these two questionnaires. Subjects participating in the study were commonly found to score within the normal range on the MHQ, indicating that psychological disturbance was not a major feature of their presentation. However, mild mood disturbance was commonly reported, and a more sensitive tool may need to be developed for this type of mildly affected chronic low back pain sufferers. The DISQ generally indicated subjects were mildly to moderately affected by their low back trouble and that sitting and leisure activities were the most pain provoking. Recommendations for further development of the disability scale are made.

MODERN VIEWS ON ETIOLOGY OF CHRONIC PANCREATITIS AND CORRECTION OF FUNCTIONAL INSUFFICIENCY OF THE PANCREAS

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E. А. Kornienko

2012-01-01

Full Text Available Chronic pancreatitis is a multietiological disorder characterized by progressive structural changes of the pancreas and development of its eccrine and endocrine insufficiency. The potential causes of chronic pancreatitis in children include obstruction of the pancreas ducts due to cholelithiasis, chronic cholecystitis with biliary sludge, excretory ducts anomalies; obesity and hyperlipidemia; abdominal traumas and infectious pancreatic diseases. Recently new possible variants of chronic pancreatitis — autoimmune and hereditary — have been diagnosed due to the widening of diagnostic potentials. Fifty children and adolescents with chronic pancreatitis were diagnosed. It was shown, that obstructive chronic pancreatitis was found in 50%, obesity-associated. According to the literature, more than 70% of children with idiopathic chronic pancreatitis have genetic mutations in genes SFTR, PRSS1 and SPINK1, both single and associated. These lead to imbalance of the trypsinogen activation and inactivation in the pancreas tissue. Severe mutations can be an independent cause of chronic pancreatitis, mild ones manifest after the impact of some external factors. Regardless of the cause of the disease, the mandatory component of the treatment is enzyme replacement therapy with the preference to microspherical forms.

A pilot study examining the effect of mindfulness-based stress reduction on symptoms of chronic mild traumatic brain injury/postconcussive syndrome.

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Azulay, Joanne; Smart, Colette M; Mott, Tasha; Cicerone, Keith D

2013-01-01

To evaluate the effectiveness of the mindfulness-based stress reduction (MBSR) program tailored to individuals with mild traumatic brain injury (mTBI). A convenience sample recruited from clinical referrals over a 2-year period completed outcome measures pre- and posttreatment intervention. Post-acute brain injury rehabilitation center within a suburban medical facility. Twenty-two individuals with mTBI and a time postinjury more than 7 months. Eleven participants were men and 11 were women, ranging in age from 18 to 62 years. A 10-week group (with weekly 2-hour sessions) modeled after the MBSR program of Kabat-Zinn, but with modifications designed to facilitate implementation in a population of individuals with brain injury. (The treatment involved enhancement of attentional skills, in addition to increased awareness of internal and external experiences associated with the perspective change of acceptance and nonjudgmental attitude regarding those experiences). Perceived Quality of Life Scale, Perceived Self-Efficacy Scale, and the Neurobehavioral Symptom Inventory. Secondary measures included neuropsychological tests, a self-report problem-solving inventory, and a self-report measure of mindfulness. Clinically meaningful improvements were noted on measures of quality of life (Cohen d = 0.43) and perceived self-efficacy (Cohen d = 0.50) with smaller but still significant effects on measures of central executive aspects of working memory and regulation of attention. The MBSR program can be adapted for participants with mTBI. Improved performance on measures associated with improved quality of life and self-efficacy may be related to treatment directed at improving awareness and acceptance, thereby minimizing the catastrophic assessment of symptoms associated with mTBI and chronic disability. Additional research on the comparative effectiveness of the MBSR program for people with mTBI is warranted.

An Unpredicted Side Effect of Bisphosphonates in a Patient with Chronic Renal Failure Due to Multiple Myeloma: Reversible Parkinsonism

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Barış İşak

2010-09-01

Full Text Available In this report, we present a unique case in which the chemotherapeutic agent, i.e., zoledronic acid, deepened the hypocalcemia on the basis of chronic renal failure secondary to multiple myeloma and caused parkinsonism episodes. An 80-year-old female patient, who had been diagnosed as multiple myeloma and had been administered bisphosphonate therapy monthly for six months, was ad¬mitted to our emergency room with two parkinsonism episodes. Low serum calcium levels accompanied parkinsonism symptoms, which subsided with calcium replacement therapy in both episodes. Imaging did not reveal any pathology in the basal ganglia. The fact that the patient was cured both times with calcium replacement suggests that hypocalcemia was the actual cause. This can be interpreted as a unique case, reflecting the reversible functional impairment due to metabolic side effects of a chemotherapeutic agent rather than destructive changes in the basal ganglia.

An Unpredicted Side Effect of Bisphosphonates in a Patient with Chronic Renal Failure Due to Multiple Myeloma: Reversible Parkinsonism

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Barış İşak

2010-09-01

Full Text Available In this report, we present a unique case in which the chemotherapeutic agent, i.e., zoledronic acid, deepened the hypocalcemia on the basis of chronic renal failure secondary to multiple myeloma and caused parkinsonism episodes. An 80-year-old female patient, who had been diagnosed as multiple myeloma and had been administered bisphosphonate therapy monthly for six months, was ad¬mitted to our emergency room with two parkinsonism episodes. Low serum calcium levels accompanied parkinsonism symptoms, which subsided with calcium replacement therapy in both episodes. Imaging did not reveal any pathology in the basal ganglia. The fact that the patient was cured both times with calcium replacement suggests that hypocalcemia was the actual cause. This can be interpreted as a unique case, reflecting the reversible functional impairment due to metabolic side effects of a chemotherapeutic agent rather than destructive changes in the basal ganglia

Visualizing Hyperactivation in Neurodegeneration Based on Prefrontal Oxygenation: A Comparative Study of Mild Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls

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Kah Hui Yap

2017-09-01

Full Text Available Background: Cognitive performance is relatively well preserved during early cognitive impairment owing to compensatory mechanisms.Methods: We explored functional near-infrared spectroscopy (fNIRS alongside a semantic verbal fluency task (SVFT to investigate any compensation exhibited by the prefrontal cortex (PFC in Mild Cognitive Impairment (MCI and mild Alzheimer's disease (AD. In addition, a group of healthy controls (HC was studied. A total of 61 volunteers (31 HC, 12 patients with MCI and 18 patients with mild AD took part in the present study.Results: Although not statistically significant, MCI exhibited a greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, the time taken for HC to achieve the activation level was shorter than MCI and mild AD (p = 0.0047 and 0.0498, respectively; in the right PFC, mild AD took a longer time to achieve the activation level than HC and MCI (p = 0.0469 and 0.0335, respectively; in the right PFC, HC, and MCI demonstrated a steeper slope compared to mild AD (p = 0.0432 and 0. 0107, respectively. The results were, however, not significant when corrected by the Bonferroni-Holm method. There was also found to be a moderately positive correlation (R = 0.5886 between the oxygenation levels in the left PFC and a clinical measure [Mini-Mental State Examination (MMSE score] in MCI subjects uniquely.Discussion: The hyperactivation in MCI coupled with a better SVFT performance may suggest neural compensation, although it is not known to what degree hyperactivation manifests as a potential indicator of compensatory mechanisms. However, hypoactivation plus a poorer SVFT performance in mild AD might indicate an inability to compensate due to the degree of structural impairment.Conclusion: Consistent with the scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms and

The reproducibility of the circadian BP rhythm in treated hypertensive patients with polycystic kidney disease and mild chronic renal impairment--a prospective ABPM study.

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Covic, Adrian; Mititiuc, Irina; Gusbeth-Tatomir, Paul; Goldsmith, David J

2002-01-01

Diurnal BP rhythm is known to be abnormal (reduced BP fall with sleep) in chronic renal failure, dialysis and renal transplantation patients. In subjects with primary hypertension and with reduced diurnal BP fall with sleep there is consistent evidence of increased target-organ damage. However, the few studies that have addressed the reproducibility of diurnal rhythm in normal or hypertensive subjects have concluded that the BP fall with sleep is poorly reproducible. It is not known whether the same is true for patients with renal disease. In 30 subjects with autosomal polycystic kidney disease (ADPKD), mild chronic renal failure and normal office BP levels on standardised anti-hypertensive treatment, ambulatory blood pressure monitoring (ABPM) was done three times over a twelve month period to assess the reproducibility of blood pressure fall with sleep. When comparing ABPM 2 with the ABPM 1 recording (3 months difference between measurements) only 43.3% of the patients maintained the initial dipping category (defined by quartiles of the ABPM 1 diurnal BP distribution). The same proportion of subjects had a similar dipping category, when ABPM 3 was compared to ABPM 1 (9 months difference between measurements), but a large (24%) subset of patients had dramatic shifts in their amplitude in nocturnal BP fall, significantly greater than those recorded after a shorter inter-measurement interval. Equally important, our study reveals the fact that, with time, there is no tendency to decrease circadian variation: a similar proportion (a quarter to one third) of patients increased or decreased their amplitude in nocturnal BP fall, at 3 and 9 months. When several ABPM measurements are repeated for the same patients, the repeatability is even worse, since only 36.6% of our study population maintained the initial dipping category across all three ABPM determinations (ABPM 1 and ABPM 2 and ABPM 3). There is a widespread abnormality in diurnal BP rhythm in ADPKD patients with

GLOBALISATION AND THE UNPREDICTABILITY OF CRISIS EPISODES: AN EMPIRICAL ANALYSIS OF COUNTRY RISK INDEXES

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San-Martín-Albizuri, Nerea

2012-05-01

Full Text Available The ongoing globalisation process has not put an end to international financial crises. On the contrary, it seems to have contributed to their appearance and to accentuating their degrees of unpredictability. In this context, the main objective of the present study is to establish whether the values of the best-known and most widely used country risk indexes, namely, the Euromoney index and the International Country Risk Group (ICRG, and the values of their representative variables could have forecasted well in advance the crises that took place between 1994 and 2002, a period which is herein termed the ‘globalisation era’. The results show that, although the selected indexes and their representative variables were able to identify certain vulnerabilities, they could not accurately identify the political, economic, and/or financial factors that developed prior to these crisis episodes.

Chronic urticaria in children: Etiologies, Clinical Manifestations, Diagnosis and Treatment

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Javad Ghaffari

2013-06-01

Full Text Available Chronic urticaria is defined as a skin disease with central induration (wheal and erythema formation around it (flare that appears at least twice a week and remains at least for 6 weeks continually. The incidence of urticaria in children is about 0.1-3%. Most cases of chronic urticaria occur in children between 6-11 years. Autoimmune and allergy immaturity is one of the reasons of lower incidence of chronic urticaria in younger children. Quality of life impairment in children with urticaria has been known to be similar to diseases with severe atopic dermatitis, epilepsy, diabetes mellitus and asthma. There are several causes for chronic urticaria in children in different reports. In most of cases the known etiologic agents are varies from 21 to 83%. Overall, infectious causes of chronic urticaria in children are more common and obvious than other in adults .In most cases, the cause of chronic urticaria are idiopathic or autoimmune. Urticaria severity divided to mild, moderate and severe was based on the number of wheals and severity of pruritus. Diagnosis of chronic urticaria is based on a good history and physical examination. The treatment of chronic urticaria is a patient education that is to remove the triggering and aggravating agents, resolving and treating of the known disease and the use of various medicines based on the history and clinical findings. The first medical therapeutics lines in children are anti-histamines, beta-blocker H1 and new generation of non-sedating agents.

Possibility of objective diagnosis in patients with mild Alzheimer-type dementia

International Nuclear Information System (INIS)

Kodama, Naoki; Shimada, Tetsuo; Kaeriyama, Tomoharu; Kaneko, Tomoyuki; Fukumoto, Ichiro; Okamoto, Koichiro

2003-01-01

In this study, patients with mild Alzheimer-type dementia were compared with healthy elderly volunteers by means of 12 features to evaluate the possibility of objective diagnosis of mild dementia. The subjects included 9 patients with questionable dementia, 14 patients with mild dementia, and 30 healthy elderly volunteers as controls. In addition, the 23 patients with questionable or mild dementia were included in the mild Alzheimer-type dementia group. A statistically significant difference was found between the mild Alzheimer-type dementia group and the healthy volunteers in 4 of the 10 textural features. Discriminant analysis using these 4 features demonstrated a sensitivity of 87.0% and a specificity of 66.7%. These results suggest the possibility of objective diagnosis in patients with mild Alzheimer-type dementia. (author)

Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD: results from a national database

Directory of Open Access Journals (Sweden)

Lee H

2016-04-01

prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD.Methods: Patients with mild-to-moderate COPD (≥40 years were extracted from Korean National Health and Nutrition Examination Survey data (2007–2012 and were linked to the national health insurance reimbursement database to obtain medical service utilization records.Results: Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6% had severe exacerbations over the 6 years (0.012/person-year. Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P<0.001. A multiple logistic regression presented that asthma was an independent risk factor of severe exacerbations in patients with mild-to-moderate COPD regardless of adjustment for all possible confounding factors (adjusted odds ratio, 1.67; 95% confidence interval, 1.002–2.77, P=0.049. In addition, age, female, poor lung function, use of inhalers, and low EuroQoL five dimensions questionnaire index values were independently associated with severe exacerbation in patients with mild-to-moderate COPD.Conclusion: In this population-based study, the prevalence of severe exacerbations in patients with mild-to-moderate COPD was relatively low, compared with previous clinical interventional studies. Coexisting asthma significantly impacted the frequency of severe exacerbations in patients with mild-to-moderate COPD, suggesting application of an exacerbation preventive strategy in these patients. Keywords: bronchial asthma, chronic obstructive pulmonary disease, acute exacerbation

Different perception of cognitive impairment, behavioral disturbances, and functional disabilities between persons with mild cognitive impairment and mild Alzheimer's disease and their caregivers.

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Onor, M L; Trevisiol, M; Negro, C; Aguglia, E

2006-01-01

Insight in dementia is a multifaceted concept and ability, which includes the persons' perception of their behavioral and cognitive symptoms and functional disability. This ability seems to deteriorate as dementia progresses. The aim of this study was to evaluate the level of insight in the cognitive, behavioral, and functional disorders in a group of persons with mild cognitive impairment (MCI) or mild AD (Alzheimer's disease) and to compare their perception of their illness with that of their caregivers. The study involved a group of 121 persons with MCI and mild AD and their caregivers. The persons with MCI and mild AD were administered the tests Mini-Mental State Examination, Instrumental Activities of Daily Living, Activities of Daily Living, Neuropsychiatric Inventory, Schedule for the Assessment of Insight, Clinical Insight Rating Scale, and a short interview. Major differences were identified between how the persons with MCI or mild AD and their caregivers perceived the persons' cognitive and behavioral disorders. The group with MCI or mild AD underestimated their deficits, which were considered serious and disabling by their caregivers.

[Treatment of chronic idiopathic urticaria unresponsive to type 1 antihistamines in monotherapy].

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Mateus, C

2003-05-01

The chronic idiopathic urticaria treatment is a difficult and often frustrating problem for physicians. Due to the lack of definitive medical therapeutic programs to relieve the symptoms and prevent from their recurrence, several pharmacologic approaches to the management of chronic idiopathic urticaria are proposed. The chronic urticaria pharmacologic therapy is therefore fit to abrogate effects of histamine and other mediators on cutaneous vasculature and inflammatory cells that participate in the pathogenesis of the urticaria. The most common approach is to avoid all aggravating factors and to block histamine. The mainstay therapy is the H1 antihistamines. A significant number of patients may remain unresponsive even after an increase in the dose or a change in the type of H1 antihistaminic drug. In these cases, several therapies can be associated: combinations of H1 antihistamines, nonsedating one tablet (morning) and one sedating (evening), this approach is very usual but no study has confirmed it rational; addition an H2 antagonist to the previous treatment for some patients may improve control of their symptoms; alternatively, the tricyclic antidepressant, Doxepin is usually prescribed. The results of other drugs reported in the literature is unpredictable, to include them in a strategy therapy. The results with Badrenergic agents, nifedipine, ketotifen, leukotriene antagonists and tranexamic acid are variable and don't appear better than those with H1 antagonists. The efficiency of danazol has to be confirmed by other controlled studies. Warfarin, sulfasalazine and ultraviolet radiation have been used apparently successfully, but no controlled study has been published. Only when the above treatments have failed then immunosuppresive therapies, intravenous immunoglobulin and plasmapheresis can be proposed for chronic idiopathic urticaria.

Chronic stress does not impair liver regeneration in rats

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Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove

2015-01-01

a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

Gait, dual task and history of falls in elderly with preserved cognition, mild cognitive impairment, and mild Alzheimer's disease.

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Ansai, Juliana H; Andrade, Larissa P; Rossi, Paulo G; Takahashi, Anielle C M; Vale, Francisco A C; Rebelatto, José R

Studies with functional and applicable methods and new cognitive demands involving executive function are needed to improve screening, prevention and rehabilitation of cognitive impairment and falls. to identify differences in gait, dual task performances, and history of falls between elderly people with preserved cognition, mild cognitive impairment and mild Alzheimer's disease. A cross-sectional study was conducted. The sample consisted of 40 community-dwelling older adults with preserved cognition, 40 older adults with mild cognitive impairment, and 38 older adults with mild Alzheimer's disease. The assessment consisted of anamneses, gait (measured by the 10-meter walk test), dual task (measured by the Timed Up and Go Test associated with the motor-cognitive task of calling a phone number), and history of falls in the past year. There were no differences among all groups for all variables. However, the Alzheimer's disease Group performed significantly worse in the dual task than the other groups. No item of dual task could distinguish people with preserved cognition from those with mild cognitive impairment. The groups with cognitive impairment included more fallers, and specific characteristics in history of falls between groups were identified. Dual task could distinguish Alzheimer's disease patients specifically from other cognitive profiles. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

The effect of chronic digitalization on pump function in systolic heart failure.

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Hassapoyannes, C A; Easterling, B M; Chavda, K; Chavda, K K; Movahed, M R; Welch, G W

2001-10-01

Short- and intermediate-term use of cardiac glycosides promotes inotropy and improves the ejection fraction in systolic heart failure. To determine whether chronic digitalization alters left ventricular function and performance. Eighty patients with mild-to-moderate systolic heart failure (baseline ejection fraction < or =45%) participated from our institution in a multi-center, chronic, randomized, double-blind study of digitalis vs. placebo. Of the 40 survivors, 38 (20 allocated to the digitalis arm and 18 to the placebo arm) were evaluated at the end of follow-up (mean, 48.4 months). Left ventricular systolic function was assessed by both nuclear ventriculography and echocardiography. The ejection fraction was measured scintigraphically, while the ventricular volumes were computed echocardiographically. The groups did not differ, at baseline or end-of-study, with respect to the ejection fraction and the loading conditions (arterial pressure, ventricular volumes and heart rate) by either intention-to-treat or actual-treatment-received analysis. Over the course of the trial, the digitalis arm exhibited no significant increase in the use of diuretics (18%, P=0.33), in distinction from the placebo group (78%, P=0.004), and a longer stay on study drug among those patients who withdrew from double-blind treatment (28.6 vs. 11.4 months, P=0.01). Following chronic use of digitalis for mild-to-moderate heart failure, cross-sectional comparison with a control group from the same inception cohort showed no appreciable difference in systolic function or performance. Thus, the suggested clinical benefit cannot be explained by an inotropic effect.

Mechanisms underlying chronic whiplash: contributions from an incomplete spinal cord injury?

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Elliott, James M; Dewald, Julius P A; Hornby, T George; Walton, David M; Parrish, Todd B

2014-11-01

To explore the association between findings on advanced, but available, magnetic resonance imaging (MRI) sequences of the cervical spinal cord and muscular system, in tandem with biomechanical measures of maximum volitional plantar flexion torques as a proxy for a mild incomplete spinal cord injury. Observational case series. University research laboratory. Three patients with chronic whiplash and one patient with history of whiplash injury but no current symptoms. We measured lower extremity muscle fat, morphological changes in descending spinal cord pathways with advanced MRI applications and maximal activation of the plantar flexors. Larger magnitudes of lower extremity muscle fat corresponded to altered spinal cord anatomy and reductions in the ability to maximally activate plantar flexor torques in the three subjects with chronic whiplash. Such findings were not present in the recovered participant. The potential value of MRI to quantify neuromuscular degeneration in chronic whiplash is recognized. Larger scaled prospective studies are warranted before stronger conclusions can be drawn. Wiley Periodicals, Inc.

CT of the kidney in chronic renal failure

International Nuclear Information System (INIS)

Kojima, Kanji

1988-01-01

The transverse size of the kidneys was measured by CT, and CT findings of the kidneys were studied in 94 patients with chronic renal failure under hemodialysis (HD), 58 patients with chronic renal failure not under hemodialysis (CRF) and 100 controls. The transverse size of the kidneys decreased according to the deterioration of renal function. The ratio of the maximal renal transverse size to the minimal vertebral size, which the author proposed as a new criterion for renal atrophy, was 1.8 in controls, 1.2 in CRF and 0.8 in HD. A kidney smaller than the vertebral body indicated chronic renal failure. Characteristic CT features in CRF were mild renal atrophy and cystic changes (41.4 %). In HD, renal atrophy was more advanced, the occurrence of cystic changes was more frequent (64.9 %), and there were frequent renal (68.1 %) and aortic calcifications. Furthermore acquired cystic disease of the kidney (ACD) was observed (27.7 %) only in HD. In this study no renal neoplasm was found in ACD. However, several complications in HD, one perirenal hematoma and six hydronephroses, were observed. (author)

Mechanical behaviour of Zn-Fe alloy coated mild steel

International Nuclear Information System (INIS)

Panagopoulos, C.N.; Georgiou, E.P.; Agathocleous, P.E.; Giannakopoulos, K.I.

2009-01-01

Zinc alloy coatings containing various amounts of Fe were deposited by electrodeposition technique on a mild steel substrate. The concentration of Fe in the produced alloy coatings ranged from 0 to 14 wt.%, whereas the thickness of the coatings was about 50 μm. Structural and metallurgical characterization of the produced coatings was performed with the aid of X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) techniques. This study aims in investigating the mechanical behaviour of Zn-Fe coated mild steel specimens, as no research investigation concerning the tensile behaviour of Zn alloy coated ferrous alloys has been reported in the past. The experimental results indicated that the ultimate tensile strength of the Zn-Fe coated mild steel was lower than the bare mild steel. In addition, the ductility of the Zn-Fe coated mild steel was found to decrease significantly with increasing Fe content in the coating.

Socioeconomic disparities in work performance following mild stroke.

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Brey, Joseph K; Wolf, Timothy J

2015-01-01

The purpose of this study was to investigate the relationships among the factors that influence return to work for young individuals with mild stroke from different socioeconomic backgrounds. Prospective cohort study of working adults with mild stroke (N = 21). Participants completed an assessment battery of cognitive, work environment and work performance measures at approximately 3 weeks and 7 months post mild stroke. Individuals were placed in "skilled" and "unskilled" worker categories based on the Hollingshead Index. Unskilled workers had significantly poorer scores on the majority of the cognitive assessments. Unskilled workers also perceived less social support (p = 0.017) and autonomy (p = 0.049) in work responsibilities than individuals in the skilled worker group and also reported significantly poorer work productivity due to stroke than those in the skilled group (p = 0.015). Individuals from low socioeconomic backgrounds have more difficulty returning to work following mild stroke than individuals from higher socioeconomic backgrounds. Future work is needed to identify factors that can increase long-term work success and quality of work performance following a mild stroke that specifically targets the needs of individuals who have a lower socioeconomic status.

Association between chronic periodontitis and oral health-related quality of life in Sri Lankan adults.

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Wellapuli, Nimali; Ekanayake, Lilani

2016-12-01

To determine the impact of chronic periodontitis on oral health-related quality of life in Sri Lankan adults. A cross-sectional study was conducted among 1,400 participants, 35-60 years of age, residing in the Colombo district of Sri Lanka. Data were collected using two interviewer-administered questionnaires and an oral examination. The prevalence, extent and severity of oral impacts increased with the increase in severity of chronic periodontitis. The most commonly experienced impacts were within the domain of physical pain. The adjusted Poisson regression model indicated that chronic periodontitis was significantly associated with the prevalence of oral impacts. The prevalence of oral impacts was 48% and 69% higher in those with moderate and severe periodontitis, respectively, compared with those with no/mild periodontitis. Oral health-related quality of life deteriorates with the increase in severity of chronic periodontitis. © 2016 FDI World Dental Federation.

Chronic Kidney Disease, Basal Insulin Glargine, and Health Outcomes in People with Dysglycemia: The ORIGIN Study.

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Papademetriou, Vasilios; Nylen, Eric S; Doumas, Michael; Probstfield, Jeff; Mann, Johannes F E; Gilbert, Richard E; Gerstein, Hertzel C

2017-12-01

Early stages of chronic kidney disease are associated with an increased cardiovascular risk in patients with established type 2 diabetes and macrovascular disease. The role of early stages of chronic kidney disease on macrovascular outcomes in prediabetes and early type 2 diabetes mellitus is not known. In the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, the introduction of insulin had no effect on cardiovascular outcomes compared with standard therapy. In this post hoc analysis of ORIGIN, we compared cardiovascular outcomes in subjects without to those with mild (Stages 1-2) or moderate chronic kidney disease (Stage 3). Τwo co-primary composite cardiovascular outcomes were assessed. The first was the composite end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes; and the second was a composite of any of these events plus a revascularization procedure, or hospitalization for heart failure. Several secondary outcomes were prespecified, including microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers. Complete renal function data were available in 12,174 of 12,537 ORIGIN participants. A total of 8114 (67%) had no chronic kidney disease, while 4060 (33%) had chronic kidney disease stage 1-3. When compared with nonchronic kidney disease participants, the risk of developing the composite primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) in those with mild to moderate chronic kidney disease was 87% higher; hazard ratio (HR) 1.87; 95% confidence interval (CI), 1.71-2.04 (P chronic kidney disease 1-3 was also associated with a greater than twofold higher risk for both all-cause mortality (HR 2.17; 95% CI, 1.98-2.38; P chronic kidney disease had significantly higher risk for nonfatal myocardial infarction (50%), nonfatal stroke (68%), any stroke (84%), the above composite primary end point plus revascularization or heart failure requiring

Chaos and the (un)predictability of evolution in a changing environment.

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Rego-Costa, Artur; Débarre, Florence; Chevin, Luis-Miguel

2018-02-01

Among the factors that may reduce the predictability of evolution, chaos, characterized by a strong dependence on initial conditions, has received much less attention than randomness due to genetic drift or environmental stochasticity. It was recently shown that chaos in phenotypic evolution arises commonly under frequency-dependent selection caused by competitive interactions mediated by many traits. This result has been used to argue that chaos should often make evolutionary dynamics unpredictable. However, populations also evolve largely in response to external changing environments, and such environmental forcing is likely to influence the outcome of evolution in systems prone to chaos. We investigate how a changing environment causing oscillations of an optimal phenotype interacts with the internal dynamics of an eco-evolutionary system that would be chaotic in a constant environment. We show that strong environmental forcing can improve the predictability of evolution by reducing the probability of chaos arising, and by dampening the magnitude of chaotic oscillations. In contrast, weak forcing can increase the probability of chaos, but it also causes evolutionary trajectories to track the environment more closely. Overall, our results indicate that, although chaos may occur in evolution, it does not necessarily undermine its predictability. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Comprehensive cardiac rehabilitation for secondary prevention after transient ischemic attack or mild stroke: I: feasibility and risk factors.

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Prior, Peter L; Hachinski, Vladimir; Unsworth, Karen; Chan, Richard; Mytka, Sharon; O'Callaghan, Christina; Suskin, Neville

2011-11-01

Comprehensive cardiac rehabilitation (CCR), which integrates structured lifestyle interventions and medications, reduces morbidity and mortality among cardiac patients. CCR has not typically been used with cerebrovascular populations, despite important commonalities with heart patients. We tested feasibility and effectiveness of 6-month outpatient CCR for secondary prevention after transient ischemic attack or mild, nondisabling stroke. This article presents risk factors. A future article will discuss psychological outcomes. Consecutive consenting subjects having sustained a transient ischemic attack or mild, nondisabling stroke within the previous 12 months (mean, 11.5 weeks; event-to-CCR entry) with ≥1 vascular risk factor, were recruited from a stroke prevention clinic providing usual care. We measured 6-month CCR outcomes following a prospective cohort design. Of 110 subjects recruited from January 2005 to April 2006, 100 subjects (mean age, 64.9 years; 46 women) entered and 80 subjects completed CCR. We obtained favorable, significant intake-to-exit changes in: aerobic capacity (+31.4%; Pstroke, offering a promising model for vascular protection across chronic disease entities. We know of no similar previous investigation, and are now conducting a randomized trial.

Behavioral Outcomes Differ Between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury

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Brian D. Stemper

2016-03-01

Full Text Available Mild traumatic brain injury (mTBI can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration of projectiles. Mechanism is likely to influence the type, severity, and chronicity of outcomes. The objective of this study was to determine differences in the severity and time-course of behavioral outcomes following blast and rotational mTBI. The Medical College of Wisconsin (MCW Rotational Injury model and a shock tube model of primary blast injury were used to induce mTBI in rats and behavioral assessments were conducted within the first week, as well as 30 and 60 days following injury. Acute recovery time demonstrated similar increases over protocol-matched shams, indicating acute injury severity equivalence between the two mechanisms. Post-injury behavior in the elevated plus maze demonstrated differing trends, with rotationally injured rats acutely demonstrating greater activity, whereas blast-injured rats had decreased activity that developed at chronic time points. Similarly, blast-injured rats demonstrated trends associated with cognitive deficits that were not apparent following rotational injuries. These findings demonstrate that rotational and blast injury result in behavioral changes with different qualitative and temporal manifestations. Whereas rotational injury was characterized by a rapidly emerging phenotype consistent with behavioral disinhibition, blast injury was associated with emotional and cognitive differences that were not evident acutely, but developed later, with an anxiety-like phenotype still present in injured animals at our most chronic measurements.

Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

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Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

2015-01-01

In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

Clinical Management of a Patient with Chronic Recurrent Vertigo Following a Mild Traumatic Brain Injury

Directory of Open Access Journals (Sweden)

Eric G. Johnson

2009-01-01

Full Text Available Vertigo, was provoked and right torsional up-beat nystagmus was observed in a 47-year-old patient when she was placed into the right Hallpike-Dix test position using infrared goggle technology. The clinical diagnosis was benign paroxysmal positional vertigo (BPPV, specifically right posterior canalithiasis, resulting from a mild traumatic brain injury (TBI suffered approximately six-months earlier. Previous medical consultations did not include vestibular system examination, and Meclizine was prescribed to suppress her chief complaint of vertigo. Ultimately, the patient was successfully managed by performing two canalith repositioning maneuvers during a single clinical session. The patient reported 100% resolution of symptoms upon reexamination the following day, and the Hallpike-Dix test was negative. Continued symptom resolution was subjectively reported 10 days postintervention via telephone consultation. This case report supports previous publications concerning the presence of BPPV following TBI and the need for inclusion of vestibular system examination during medical consultation.

Cognitive Profile of Elderly Patients with Mild Stroke

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Arne Gramstad

2011-11-01

Full Text Available Background: A pattern characterizing cognitive deficits in mild stroke could help in differential diagnosis and rehabilitation planning. Methods: Fifty patients with mild stroke (modified Rankin scale ≤2 at discharge aged >60 years were given the Mini Mental State Examination (MMSE, the Hopkins Verbal Learning Test-Revised (HVLT-R and the Stroop test. Results: On HVLT-R, significant impairments were found in learning and recall, but not in delayed recall. The Stroop test revealed significant impairments in reading speed, but not in color-word interference. Using the MMSE, significant deficits were only found in the youngest age group. Conclusion: Elderly patients with mild stroke show deficits in verbal learning/recall and in reading speed, but not in the MMSE, delayed recall or color-word interference. The deficits are consistent with a mild-to-moderate brain dysfunction, with relative sparing of medial brain structures.

Exogenous daytime melatonin modulates response of adolescent mice in a repeated unpredictable stress paradigm.

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Onaolapo, Adejoke Yetunde; Adebayo, Ajibola Nurudeen; Onaolapo, Olakunle James

2017-02-01

The immediate and short-term behavioural and physiological implications of exposure to stressful scenarios in the adolescent period are largely unknown; however, increases in occurrence of stress-related physiological and psychological disorders during puberty highlight the need to study substances that may modulate stress reactivity during a crucial stage of maturation. Seven groups of mice (12-15 g each) were administered distilled water (DW) (non-stressed and stressed controls), sertraline (10 mg/kg), diazepam (2 mg/kg) or one of three doses of melatonin (5, 10 and 15 mg/kg). Mice were exposed to 30 min of chronic mild stress (25 min of cage shaking, cage tilting, handling and 5 min of forced swimming in tepid warm water at 25 °C, in a random order) after administration of DW or drugs, daily for 21 days. Behavioural assessments were conducted on day 1 and day 21 (after which mice were sacrificed, blood taken for estimation of corticosterone levels and brain homogenates used for estimation of antioxidant activities). Administration of melatonin resulted in an increase in horizontal locomotion and self-grooming, while rearing showed a time-dependent increase, compared to non-stress and stress controls. Working memory improved with increasing doses of melatonin (compared to controls and diazepam); in comparison to setraline however, working memory decreased. A dose-related anxiolytic effect is seen when melatonin is compared to non-stressed and stressed controls. Melatonin administration reduced the systemic/oxidant response to repeated stress. Administration of melatonin in repeatedly stressed adolescent mice was associated with improved central excitation, enhancement of working memory, anxiolysis and reduced systemic response to stress.

Cognitive behavioural treatment for the chronic post-traumatic headache patient

DEFF Research Database (Denmark)

Kjeldgaard, Dorte; Forchhammer, Hysse B; Teasdale, Thomas William

2014-01-01

BACKGROUND: Chronic post-traumatic headache (CPTH) after mild head injury can be difficult to manage. Research is scarce and successful interventions are lacking.To evaluate the effect of a group-based Cognitive Behavioural Therapy (CBT) intervention in relation to headache, pain perception...... distress, and the overall experience of symptoms. The waiting-list group experienced no change in headache but, opposed to the treatment group, a significant decrease in somatic and cognitive symptoms indicating a spontaneous remission over time. CONCLUSIONS: Our primarily negative findings confirm...

Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

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Roncal-Jimenez, C; Lanaspa, M A; Jensen, T; Sanchez-Lozada, L G; Johnson, R J

2015-01-01

Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health. © 2015 S. Karger AG, Basel.

Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice

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Liu, Xiao-Long; Luo, Liu; Mu, Rong-Hao; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

2015-01-01

Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus. PMID:26522512

HYBRID SYSTEM BASED FUZZY-PID CONTROL SCHEMES FOR UNPREDICTABLE PROCESS

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M.K. Tan

2011-07-01

Full Text Available In general, the primary aim of polymerization industry is to enhance the process operation in order to obtain high quality and purity product. However, a sudden and large amount of heat will be released rapidly during the mixing process of two reactants, i.e. phenol and formalin due to its exothermic behavior. The unpredictable heat will cause deviation of process temperature and hence affect the quality of the product. Therefore, it is vital to control the process temperature during the polymerization. In the modern industry, fuzzy logic is commonly used to auto-tune PID controller to control the process temperature. However, this method needs an experienced operator to fine tune the fuzzy membership function and universe of discourse via trial and error approach. Hence, the setting of fuzzy inference system might not be accurate due to the human errors. Besides that, control of the process can be challenging due to the rapid changes in the plant parameters which will increase the process complexity. This paper proposes an optimization scheme using hybrid of Q-learning (QL and genetic algorithm (GA to optimize the fuzzy membership function in order to allow the conventional fuzzy-PID controller to control the process temperature more effectively. The performances of the proposed optimization scheme are compared with the existing fuzzy-PID scheme. The results show that the proposed optimization scheme is able to control the process temperature more effectively even if disturbance is introduced.

Toward a Comprehensive Hypothesis of Chronic Interstitial Nephritis in Agricultural Communities.

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Orantes-Navarro, Carlos Manuel; Herrera-Valdés, Raúl; Almaguer-López, Miguel; López-Marín, Laura; Vela-Parada, Xavier Fernando; Hernandez-Cuchillas, Marcelo; Barba, Lilly M

2017-03-01

Over the past 20 years, there has been an increase in chronic interstitial nephritis in agricultural communities (CINAC) not associated with traditional risk factors. This disease has become an important public health problem and is observed in several countries in Central America and Asia. CINAC predominantly affects young male farmers between the third and fifth decades of life with women, children, and adolescents less often affected. Clinically, CINAC behaves like a chronic tubulointerstitial nephropathy but with systemic manifestations not attributable to kidney disease. Kidney biopsy reveals chronic tubulointerstitial nephritis with variable glomerulosclerosis and mild chronic vascular damage, with the severity depending on sex, occupation, and CKD stage. The presence of toxicological, occupational, and environmental risk factors within these communities suggests a multifactorial etiology for CINAC. This may include exposure to agrochemicals, a contaminated environment, repeated episodes of dehydration with heat stress, and an underlying genetic predisposition. An understanding of these interacting factors using a multidisciplinary approach with international cooperation and the formulation of a comprehensive hypothesis are essential for the development of public health programs to prevent this devastating epidemic. Copyright © 2016 National Kidney Foundation, Inc. All rights reserved.

A simple LC-MS/MS method for quantitative analysis of underivatized neurotransmitters in rats urine: assay development, validation and application in the CUMS rat model.

Science.gov (United States)

Zhai, Xue-jia; Chen, Fen; Zhu, Chao-ran; Lu, Yong-ning

2015-11-01

Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25-12,800 ng mL(-1) with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group (n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of air preheat temperature on the MILD combustion of syngas

International Nuclear Information System (INIS)

Huang, Mingming; Zhang, Zhedian; Shao, Weiwei; Xiong, Yan; Liu, Yan; Lei, Fulin; Xiao, Yunhan

2014-01-01

Highlights: • MILD combustion is achieved with reaction zone covering the entire combustion chamber. • Critical equivalence ratio for the occurrence of MILD combustion is identified. • MILD regime can be established for syngas fuel under air preheating conditions. - Abstract: The effect of air preheat temperature on MILD (Moderate or Intense Low-oxygen Dilution) combustion of coal-derived syngas was examined in parallel jet forward flow combustor. The results were presented on flow field using numerical simulations and on global flame signatures, OH ∗ radicals distribution and exhaust emissions using experiments. The discrete and high speed air/fuel injections into the combustor is necessary for the establishment of MILD conditions, because they cause strong gas recirculation and form large mixing region between the air and fuel jets. The critical equivalence ratio above which MILD combustion occurred was identified. The MILD regime was established for syngas fuel under air preheating conditions with lean operational limit and suppressed NO x and CO emissions. In the MILD combustion regime, the air preheating resulted in higher NO x but lower CO emissions, while the increase of equivalence ratio led to the increase of NO x and the decrease of CO emissions

Cost-effectiveness of multidisciplinary care in mild to moderate chronic kidney disease in the United States: A modeling study.

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Eugene Lin

2018-03-01

Full Text Available Multidisciplinary care (MDC programs have been proposed as a way to alleviate the cost and morbidity associated with chronic kidney disease (CKD in the US.We assessed the cost-effectiveness of a theoretical Medicare-based MDC program for CKD compared to usual CKD care in Medicare beneficiaries with stage 3 and 4 CKD between 45 and 84 years old in the US. The program used nephrologists, advanced practitioners, educators, dieticians, and social workers. From Medicare claims and published literature, we developed a novel deterministic Markov model for CKD progression and calibrated it to long-term risks of mortality and progression to end-stage renal disease. We then used the model to project accrued discounted costs and quality-adjusted life years (QALYs over patients' remaining lifetime. We estimated the incremental cost-effectiveness ratio (ICER of MDC, or the cost of the intervention per QALY gained. MDC added 0.23 (95% CI: 0.08, 0.42 QALYs over usual care, costing $51,285 per QALY gained (net monetary benefit of $23,100 at a threshold of $150,000 per QALY gained; 95% CI: $6,252, $44,323. In all subpopulations analyzed, ICERs ranged from $42,663 to $72,432 per QALY gained. MDC was generally more cost-effective in patients with higher urine albumin excretion. Although ICERs were higher in younger patients, MDC could yield greater improvements in health in younger than older patients. MDC remained cost-effective when we decreased its effectiveness to 25% of the base case or increased the cost 5-fold. The program costed less than $70,000 per QALY in 95% of probabilistic sensitivity analyses and less than $87,500 per QALY in 99% of analyses. Limitations of our study include its theoretical nature and being less generalizable to populations at low risk for progression to ESRD. We did not study the potential impact of MDC on hospitalization (cardiovascular or other.Our model estimates that a Medicare-funded MDC program could reduce the need for

Cost-effectiveness of multidisciplinary care in mild to moderate chronic kidney disease in the United States: A modeling study

Science.gov (United States)

Malcolm, Elizabeth; Goldhaber-Fiebert, Jeremy D.

2018-01-01

Background Multidisciplinary care (MDC) programs have been proposed as a way to alleviate the cost and morbidity associated with chronic kidney disease (CKD) in the US. Methods and findings We assessed the cost-effectiveness of a theoretical Medicare-based MDC program for CKD compared to usual CKD care in Medicare beneficiaries with stage 3 and 4 CKD between 45 and 84 years old in the US. The program used nephrologists, advanced practitioners, educators, dieticians, and social workers. From Medicare claims and published literature, we developed a novel deterministic Markov model for CKD progression and calibrated it to long-term risks of mortality and progression to end-stage renal disease. We then used the model to project accrued discounted costs and quality-adjusted life years (QALYs) over patients’ remaining lifetime. We estimated the incremental cost-effectiveness ratio (ICER) of MDC, or the cost of the intervention per QALY gained. MDC added 0.23 (95% CI: 0.08, 0.42) QALYs over usual care, costing $51,285 per QALY gained (net monetary benefit of $23,100 at a threshold of $150,000 per QALY gained; 95% CI: $6,252, $44,323). In all subpopulations analyzed, ICERs ranged from $42,663 to $72,432 per QALY gained. MDC was generally more cost-effective in patients with higher urine albumin excretion. Although ICERs were higher in younger patients, MDC could yield greater improvements in health in younger than older patients. MDC remained cost-effective when we decreased its effectiveness to 25% of the base case or increased the cost 5-fold. The program costed less than $70,000 per QALY in 95% of probabilistic sensitivity analyses and less than $87,500 per QALY in 99% of analyses. Limitations of our study include its theoretical nature and being less generalizable to populations at low risk for progression to ESRD. We did not study the potential impact of MDC on hospitalization (cardiovascular or other). Conclusions Our model estimates that a Medicare-funded MDC

Predictive factors for and incidence of hospital readmissions of patients with acute and chronic pancreatitis.

Science.gov (United States)

Suchsland, Till; Aghdassi, Ali; Kühn, Kristina; Simon, Peter; Lerch, Markus M; Mayerle, Julia; Flessa, Steffen

2015-01-01

Acute and chronic pancreatitis are common gastroenterological disorders that have a fairly unpredictable long-term course often associated with unplanned hospital readmissions. Little is known about the factors that increase or decrease the risk for a hospital readmission. The aim of this study was to identify positive and negative predictive factors for hospital readmissions of patients with acute and chronic pancreatitis after in-hospital treatment. In a retrospective analysis data from the hospital information and reimbursement data system (HIS) were evaluated for 606 hospital stays for either acute or chronic pancreatitis between 2006 and 2011. Additional clinical data were obtained from a questionnaire covering quality of life and socio-economic status. A total of 973 patient variables were assessed by bivariate and multivariate analysis. Between 2006 and 2011, 373 patients were admitted for acute or chronic pancreatitis; 107 patients of them were readmitted and 266 had only one hospitalization. Predictors for readmission were concomitant liver disease, presence of a pseudocyst or a suspected tumor of the pancreas as well as alcohol, tobacco or substance abuse or coexisting mental disorders. Patients who had undergone a CT-scan were more susceptible to readmission. Lower readmissions rates were found in patients with diabetes mellitus or gallstone disease as co-morbidity. While factors like age and severity of the initial disease cannot be influenced to reduce the readmission rate for pancreatitis, variables like alcohol, tobacco and drug abuse can be addressed in outpatient programs to reduce disease recurrence and readmission rates for pancreatitis. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Clinical observation of the treatment for chronic dacryocystitis under lacrimal endoscope

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Hong-Ling Lü

2013-08-01

Full Text Available AIM:To evaluate the clinical efficacy of lacrimal dredge under lacrimal endoscope for treating chronic dacryocystitis. METHODS: Sixty patients(64 eyeswith chronic dacryocystitis were examined and treated by lacrimal endoscope combined with full lacrimal intubation. All patients were followed up for 3-6 months postoperatively. RESULTS: Forty-five eyes of 64 eyes were cured, no tears, irrigation of lacrimal passage unobstructed. Thirteen eyes get partly recover, but there were still mild overflow tears, and although lacrimal passages can be flushed, but there were still partly lacrimal duct obstruction. The rest 6 eyes were invalid and still tears, irrigation of lacrimal passage obstructed. The total effective rate was 90.6%. CONCLUSION: The diagnosis and treatment of nasolacrimal duct obstruction under lacrimal endoscope is a safe and effective way.

Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease

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Magdalena Jankowska

2017-03-01

Full Text Available Chronic kidney disease (CKD predisposes one to either deficiency or toxic excess of different micronutrients. The knowledge on micronutrients—specifically water-soluble vitamins and trace elements—in CKD is very limited. Consequently, current guidelines and recommendations are mostly based on expert opinions or poor-quality evidence. Abnormalities of micronutrient resources in CKD develop for several reasons. Dietary restrictions and anorexia lead to an insufficient micronutrient intake, while diuretics use and renal replacement therapy lead to their excessive losses. Absorption is unpredictable, and metabolism impaired. Better understanding of the micronutrient needs of CKD patients could have an impact on many complications linked to vitamin and trace element disorders, including high mortality, increased risk of atherosclerosis, inflammation, oxidative stress, anemia, polyneuropathy, encephalopathy, weakness and fragility, muscle cramps, bone disease, depression, or insomnia. Here, we summarize the up-to-date knowledge on micronutrient resources in different stages of CKD, and share our experience with the assessment of micronutrient status.

Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease.

Science.gov (United States)

Jankowska, Magdalena; Rutkowski, Bolesław; Dębska-Ślizień, Alicja

2017-03-15

Chronic kidney disease (CKD) predisposes one to either deficiency or toxic excess of different micronutrients. The knowledge on micronutrients-specifically water-soluble vitamins and trace elements-in CKD is very limited. Consequently, current guidelines and recommendations are mostly based on expert opinions or poor-quality evidence. Abnormalities of micronutrient resources in CKD develop for several reasons. Dietary restrictions and anorexia lead to an insufficient micronutrient intake, while diuretics use and renal replacement therapy lead to their excessive losses. Absorption is unpredictable, and metabolism impaired. Better understanding of the micronutrient needs of CKD patients could have an impact on many complications linked to vitamin and trace element disorders, including high mortality, increased risk of atherosclerosis, inflammation, oxidative stress, anemia, polyneuropathy, encephalopathy, weakness and fragility, muscle cramps, bone disease, depression, or insomnia. Here, we summarize the up-to-date knowledge on micronutrient resources in different stages of CKD, and share our experience with the assessment of micronutrient status.

Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease

Science.gov (United States)

Jankowska, Magdalena; Rutkowski, Bolesław; Dębska-Ślizień, Alicja

2017-01-01

Chronic kidney disease (CKD) predisposes one to either deficiency or toxic excess of different micronutrients. The knowledge on micronutrients—specifically water-soluble vitamins and trace elements—in CKD is very limited. Consequently, current guidelines and recommendations are mostly based on expert opinions or poor-quality evidence. Abnormalities of micronutrient resources in CKD develop for several reasons. Dietary restrictions and anorexia lead to an insufficient micronutrient intake, while diuretics use and renal replacement therapy lead to their excessive losses. Absorption is unpredictable, and metabolism impaired. Better understanding of the micronutrient needs of CKD patients could have an impact on many complications linked to vitamin and trace element disorders, including high mortality, increased risk of atherosclerosis, inflammation, oxidative stress, anemia, polyneuropathy, encephalopathy, weakness and fragility, muscle cramps, bone disease, depression, or insomnia. Here, we summarize the up-to-date knowledge on micronutrient resources in different stages of CKD, and share our experience with the assessment of micronutrient status. PMID:28294976

Memory complaints in subjective cognitive impairment, amnestic mild cognitive impairment and mild Alzheimer's disease.

Science.gov (United States)

Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun

2016-12-01

Memory complaints are a frequent phenomenon in elderly individuals and can lead to opportunistic help-seeking behavior. The aim of this study was to compare different aspects of memory complaints (i.e., prospective versus retrospective complaints) in individuals with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (aMCI), and mild Alzheimer's disease (AD). The study included a total of 115 participants (mean age: 68.82 ± 8.83 years) with SCI (n = 34), aMCI (n = 46), and mild AD (n = 35). Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which consists of 16 items that describe everyday memory failure of both prospective memory (PM) and retrospective memory (RM). For aMCI and AD subjects, informants also completed an informant-rating of the PRMQ. All participants completed detailed neuropsychological tests. Results show that PM complaints were equivalent among the three groups. However, RM complaints differed. Specifically, RM complaints in aMCI were higher than SCI, but similar to AD. Informant-reported memory complaints were higher for AD than aMCI. Our study suggests that RM complaints of memory complaints may be helpful in discriminating between SCI and aMCI, but both PM and RM complaints are of limited value in differentiating aMCI from AD.

Does the combination of the MMSE and clock drawing test (mini-clock) improve the detection of mild Alzheimer's disease and mild cognitive impairment?

Science.gov (United States)

Cacho, Jesús; Benito-León, Julián; García-García, Ricardo; Fernández-Calvo, Bernardino; Vicente-Villardón, José Luis; Mitchell, Alex J

2010-01-01

There is currently a need to develop tools to identify patients with mild AD and mild cognitive impairment (MCI). We determined the validity and reliability of a brief, easily administered cognitive screening battery consisting of fusion of two well-known brief tests (Mini-Mental Status Examination [MMSE] and Clock Drawing Test [CDT]) (Mini-clock) to differentiate between patients with mild AD, MCI, and healthy control subjects. 66 consecutive patients with mild AD, 21 with MCI, and 66 healthy controls seen in a memory clinic setting were compared. Receiver operating characteristic (ROC) curve analysis was used to calculate the cut-off value permitting discrimination between mild AD, MCI, and healthy control subjects. Interrater and test-retest reliability were also assessed. Mean cognitive scores for patients with AD, MCI, and control subjects on all two individual tests were significantly different (for each, p Mini-clock was higher than that obtained with MMSE or CDT in differentiating mild AD from controls (0.973 vs. 0.952 and 0.881, respectively) and MCI from controls (0.855 vs. 0.821 and 0.779, respectively). Test-retest reliability for the Mini-clock was 0.99, meanwhile interrater reliability was 0.87. The mean time to complete the test for all subjects was 8 min and 50 s. The Mini-clock is highly sensitive and specific in the detection of mild AD and reasonably accurate when attempting to separate MCI from health controls. It has a high interrater and test-retest reliability, can be quickly administered, and does not require major training.

Differences in Pain Processing Between Patients with Chronic Low Back Pain, Recurrent Low Back Pain, and Fibromyalgia.

Science.gov (United States)

Goubert, Dorien; Danneels, Lieven; Graven-Nielsen, Thomas; Descheemaeker, Filip; Meeus, Mira

2017-05-01

The impairment in musculoskeletal structures in patients with low back pain (LBP) is often disproportionate to their complaint. Therefore, the need arises for exploration of alternative mechanisms contributing to the origin and maintenance of non-specific LBP. The recent focus has been on central nervous system phenomena in LBP and the pathophysiological mechanisms underlying the various symptoms and characteristics of chronic pain. Knowledge concerning changes in pain processing in LBP remains ambiguous, partly due to the diversity in the LBP population. The purpose of this study is to compare quantitative sensory assessment in different groups of LBP patients with regard to chronicity. Recurrent low back pain (RLBP), mild chronic low back pain (CLBP), and severe CLBP are compared on the one hand with healthy controls (HC), and on the other hand with fibromyalgia (FM) patients, in which abnormal pain processing has previously been reported. Cross-sectional study. Department of Rehabilitation Sciences, Ghent University, Belgium. Twenty-three RLBP, 15 mild CLBP, 16 severe CLBP, 26 FM, and 21 HC participated in this study. Quantitative sensory testing was conducted by manual pressure algometry and computer-controlled cuff algometry. A manual algometer was used to evaluate hyperalgesia as well as temporal summation of pain and a cuff algometer was used to evaluate deep tissue hyperalgesia, the efficacy of the conditioned pain modulation and spatial summation of pain. Pressure pain thresholds by manual algometry were significantly lower in FM compared to HC, RLBP, and severe CLBP. Temporal summation of pain was significantly higher in FM compared to HC and RLBP. Pain tolerance thresholds assessed by cuff algometry were significantly lower in FM compared to HC and RLBP and also in severe CLBP compared to RLBP. No significant differences between groups were found for spatial summation or conditioned pain modulation. No psychosocial issues were taken into account for this

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats.

Science.gov (United States)

Smith, Brittany L; Morano, Rachel L; Ulrich-Lai, Yvonne M; Myers, Brent; Solomon, Matia B; Herman, James P

2017-11-22

The late adolescent period is characterized by marked neurodevelopmental and endocrine fluctuations in the transition to early adulthood. Adolescents are highly responsive to the external environment, which enhances their ability to adapt and recover from challenges when given nurturing influences, but also makes them vulnerable to aberrant development when exposed to prolonged adverse situations. Female rats are particularly sensitive to the effects of chronic stress in adolescence, which manifests as passive coping strategies and blunted hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood. We sought to intervene by exposing adolescent rats to environmental enrichment (EE) immediately prior to and during chronic stress, hypothesizing that EE would minimize or prevent the long-term effects of stress that emerge in adult females. To test this, we exposed male and female rats to EE on postnatal days (PND) 33-60 and implemented chronic variable stress (CVS) on PND 40-60. CVS consisted of twice-daily unpredictable stressors. Experimental groups included: CVS/unenriched, unstressed/EE, CVS/EE and unstressed/unenriched (n = 10 of each sex/group). In adulthood, we measured behavior in the open field test and forced swim test (FST) and collected blood samples following the FST. We found that environmental enrichment given during the adolescent period prevented the chronic stress-induced transition to passive coping in the FST and reversed decreases in peak adrenocortical responsiveness observed in adult females. Adolescent enrichment had little to no effect on males or unstressed females tested in adulthood, indicating that beneficial effects are specific to females that were exposed to chronic stress.

A REVIEW OF MILD COMBUSTION AND OPEN FURNACE DESIGN CONSIDERATION

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M.M. Noor

2012-12-01

Full Text Available Combustion is still very important to generate energy. Moderate or Intense Low-oxygen Dilution (MILD combustion is one of the best new technologies for clean and efficient combustion. MILD combustion has been proven to be a promising combustion technology in industrial applications with decreased energy consumption due to the uniformity of its temperature distribution. It is clean compared to traditional combustion due to producing low NOx and CO emissions. This article provides a review and discussion of recent research and developments in MILD. The issue and applications are summarized, with some suggestions presented on the upgrading and application of MILD in the future. Currently MILD combustion has been successfully applied in closed furnaces. The preheating of supply air is no longer required since the recirculation inside the enclosed furnace already self-preheats the supply air and self-dilutes the oxygen in the combustion chamber. The possibility of using open furnace MILD combustion will be reviewed. The design consideration for open furnace with exhaust gas re-circulation (EGR was discussed.

Mild Cognitive Impairment in Parkinson's Disease-What Is It?

Science.gov (United States)

Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

2018-03-10

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

Severe acute pancreatitis and selective decontamination (Results of a Illulticentel' contl'olled clinical trial)

NARCIS (Netherlands)

E.J.T. Luiten (Ernest)

1998-01-01

textabstractFrom a mild self-limiting disease, development of multiple organ failure and frequently septic complications towards a fulminant course resistant to any type of treatment, acute pancreatitis is a disorder that has numerous causes, an obscure pathogenesis and an often unpredictable

A clinico-pathological study of 163 untreated cases of chronic hepatitis C

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Joachim Graf

1996-02-01

Full Text Available We performed a clinico-pathological study of 163 untreated cases of chronic hepatitis C. Eighty five percent of the patients were clinically asymptomatic and their physical examinations sbowed unremarkable or minimal changes at the time of the liver biopsy Liver function tests tended to present slight abnormalities, involving mild elevations of the activity of the aminotransferases and gamma-glutamil transferase levels. In spite of these mild abnormalities advanced chronic liver disease ivas histologically detected in eighty nine percent of the patients, mainly showing chronic active hepatitis. The most characteristic histological finding ivas an interlobular bile duct damage which correlated with the presence of tymphoid aggregates in the portal tracts and with the development of fibrosis.Realizou-se estudo clinico-patológico de 163 casos não tratados de hepatite crônica C. A maioria dos pacientes era clinicamente assintomática e seus exames físicos demonstravam alterações inespecíficas ou mínimas por ocasião da biópsia hepática. As provas de função hepática tendiam a apresentar alterações discretas, envolvendo especialmente os níveis séricos das aminotransferases e gama-glutamil transpeptidase. Apesar destas alterações discretas, detectou-se doença hepática crônica histologicamente avançada, consistindo principalmente de hepatite crônica ativa. O achado histológico mais característico foi lesão de dueto biliar interlobular, que se correlacionou com a presença de agregados linfóides nos tratos portais e com o desenvolvimento de fibrose.

Detection of Mild Emphysema by Computed Tomography Density Measurements

International Nuclear Information System (INIS)

Vikgren, J.; Friman, O.; Borga, M.; Boijsen, M.; Gustavsson, S.; Bake, B.; Tylen, U.; Ekberg-Jansson, A.

2005-01-01

Purpose: To assess the ability of a conventional density mask method to detect mild emphysema by high-resolution computed tomography (HRCT); to analyze factors influencing quantification of mild emphysema; and to validate a new algorithm for detection of mild emphysema. Material and Methods: Fifty-five healthy male smokers and 34 never-smokers, 61-62 years of age, were examined. Emphysema was evaluated visually, by the conventional density mask method, and by a new algorithm compensating for the effects of gravity and artifacts due to motion and the reconstruction algorithm. Effects of the reconstruction algorithm, slice thickness, and various threshold levels on the outcome of the density mask area were evaluated. Results: Forty-nine percent of the smokers had mild emphysema. The density mask area was higher the thinner the slice irrespective of the reconstruction algorithm and threshold level. The sharp algorithm resulted in increased density mask area. The new reconstruction algorithm could discriminate between smokers with and those without mild emphysema, whereas the density mask method could not. The diagnostic ability of the new algorithm was dependent on lung level. At about 90% specificity, sensitivity was 65-100% in the apical levels, but low in the rest of the lung. Conclusion: The conventional density mask method is inadequate for detecting mild emphysema, while the new algorithm improves the diagnostic ability but is nevertheless still imperfect

Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood.

Directory of Open Access Journals (Sweden)

Sunil M Kurian

2009-07-01

Full Text Available Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression.We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total of kidney transplant patients with biopsy-documented histology.Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild and 63 (moderate/severe final candidates as CAN markers with predictive accuracy of 80% (mild and 92% (moderate/severe. Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN.This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

Digit Symbol Performance in Mild Dementia and Depression.

Science.gov (United States)

Hart, Robert P.; And Others

1987-01-01

Patients with mild dementia of the Alzheimer's type (DAT), patients with major depression, and normal control subjects completed the Wechsler Adult Intelligence Scale (WAIS) Digit Symbol test of incidental memory. Though mild DAT and depressed patients had equivalent deficits in psychomotor speed, DAT patients recalled fewer digit-symbol items.…

Hypercalcaemia associated with chronic lymphocytic leukaemia in a Giant Schnauzer.

Science.gov (United States)

Kleiter, M; Hirt, R; Kirtz, G; Day, M J

2001-05-01

A 7-year-old male Giant Schnauzer was referred with a history of severe vomiting, lethargy, weight loss, polydipsia and polyuria. Detailed investigations revealed leucocytosis with a marked lymphocytosis, mild non-regenerative anaemia, thrombocytopenia, hypercalcaemia and azotaemia. Circulating lymphocytes were small and well-differentiated, and the same lymphoid population was present in bone marrow. Chronic lymphocyctic leukaemia with associated paraneoplastic hypercalcaemia was diagnosed. Immunohistochemical staining of a bone marrow biopsy revealed a neoplastic B-cell line expressing CD79. The dog responded to therapy with prednisolone and chlorambucil for a period of 8 months.

Impact of Mild versus Moderate Intensity Aerobic Walking Exercise ...

African Journals Online (AJOL)

2014-03-01

Mar 1, 2014 ... Objective: To compare the effects of mild and moderate intensity treadmill walking exercises on markers of bone ... second group (B) received mild intensity aerobic exercise training. ..... Using functional loading to influence.

Molecular imaging of serotonin degeneration in mild cognitive impairment.

Science.gov (United States)

Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

2017-09-01

Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

Preliminary questions before studying mild traumatic brain injury outcome.

Science.gov (United States)

Fayol, P; Carrière, H; Habonimana, D; Dumond, J-J

2009-07-01

To point out from the literature the issues in mild traumatic brain injury outcome. METHODOLOGY-RESULTS: The literature review allows to point out several different factors involved in the difficulty to study mild traumatic brain injury: mild traumatic brain injury definition, postconcussional syndrome definition, diagnosis threshold, severity and functional symptoms outcome, neuropsychological tests, unspecific syndrome feature, individual factors, confounding factors and treatment interventions. The mild traumatic brain injury outcome study is complicated by the definitions issues and especially their practical use and by the multiplicity and the intricate interrelationships among involved factors. The individual outcome and social cost weight is widely emphasized for an event still considered as medically trivial. The well-ordered preventive interventions necessity and the targeted treatment programs need for the persisting postconcussive symptoms complete our critical review.

Responsiveness to Ipratropium Bromide in Male and Female Patients with Mild to Moderate Chronic Obstructive Pulmonary Disease

NARCIS (Netherlands)

Li, Xuan; Obeidat, Ma'en; Zhou, Guohai; Leung, Janice M; Tashkin, Donald P.; Wise, Robert; Connett, John; Joubert, Philippe; Bossé, Yohan; van den Berge, Maarten; Brandsma, Corry-Anke; Nickle, David C.; Hao, Ke; Paré, Peter D; Sin, Don

Introduction: Although the prevalence of chronic obstructive pulmonary disease (COPD) is similar between men and women, current evidence used to support bronchodilator therapy has been generated in therapeutic trials that have predominately enrolled male patients. Here, we determined whether there

Gait, dual task and history of falls in elderly with preserved cognition, mild cognitive impairment, and mild Alzheimer's disease

OpenAIRE

Ansai, Juliana H.; Andrade, Larissa P.; Rossi, Paulo G.; Takahashi, Anielle C.M.; Vale, Francisco A.C.; Rebelatto, Jos? R.

2017-01-01

Background Studies with functional and applicable methods and new cognitive demands involving executive function are needed to improve screening, prevention and rehabilitation of cognitive impairment and falls. Objective to identify differences in gait, dual task performances, and history of falls between elderly people with preserved cognition, mild cognitive impairment and mild Alzheimer's disease. Method A cross-sectional study was conducted. The sample consisted of 40 community-dwelling o...

Inhaled budesonide for adults with mild-to-moderate asthma: a randomized placebo-controlled, double-blind clinical trial

Directory of Open Access Journals (Sweden)

Ana Luisa Godoy Fernandes

2001-09-01

Full Text Available CONTEXT: Budesonide is an inhaled corticosteroid with high topical potency and low systemic activity recommended in the treatment of chronic asthma. OBJECTIVE: This study was conducted to determine the efficacy and safety of inhaled budesonide via a breath-activated, multi-dose, dry-powder inhaler. TYPE OF STUDY: Multicenter randomized parallel-group, placebo-controlled, double-blind, clinical trial. SETTING: Multicenter study in the university units. PARTICIPANTS: Adult patients with mild-to-moderate asthma that was not controlled using bronchodilator therapy alone. PROCEDURES: Comparison of budesonide 400 µg administered twice daily via a breath-activated, multi-dose, dry-powder inhaler with placebo, in 43 adult patients (aged 15 to 78 years with mild-to-moderate asthma (FEV1 71% of predicted normal that was not controlled using bronchodilator therapy alone. MAIN MEASUREMENTS: Efficacy was assessed by pulmonary function tests and asthma symptom control (as perceived by the patients and the use of rescue medication. RESULTS: Budesonide 400 µg (bid was significantly more effective than placebo in improving morning peak expiratory flow (mean difference: 67.9 l/min; P < 0.005 and FEV1 (mean difference: 0.60 l; P < 0.005 over the 8-week treatment period. Onset of action, assessed by morning peak expiratory flow, occurred within the first two weeks of treatment. CONCLUSIONS: Budesonide via a breath-activated, multi-dose, dry-powder inhaler results in a rapid onset of asthma control, which is maintained over time and is well tolerated in adults with mild-to-moderate asthma.

Reduction of cervical and respiratory muscle strength in patients with chronic nonspecific neck pain and having moderate to severe disability.

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López-de-Uralde-Villanueva, Ibai; Sollano-Vallez, Ernesto; Del Corral, Tamara

2017-06-11

To investigate whether patients with chronic nonspecific neck pain and having moderate to severe disability have a greater cervical motor function impairment and respiratory disturbances compared with patients with chronic nonspecific neck pain having mild disability and asymptomatic subjects; and the association between these outcomes in patients with chronic nonspecific neck pain and healthy controls. Cross-sectional study, 44 patients with chronic nonspecific neck pain and 31 healthy subjects participated. The neck disability index was used to divide the patients into 2 groups: 1) mild disability group (scores between 5 and 14 points); and 2) moderate to severe disability group (scores >14 points). Cervical motor function was measured by cervical range of motion, forward head posture, neck flexor, and extensor muscle strength. Respiratory function and maximum respiratory pressures were also measured. Statistically differences were found between the patients with chronic nonspecific neck pain having a moderate to severe disability and the asymptomatic subjects for cervical and respiratory muscle strength. Comparisons between chronic nonspecific neck pain and the asymptomatic groups showed differences for all the variables, except for forward head posture. The regression model determined that strength of cervical flexion explained 36.4 and 45.6% of the variance of maximum inspiratory pressures and maximum expiratory pressures, respectively. Only the chronic nonspecific neck pain group with moderate to severe disability showed differences compared with the healthy subjects. Neck muscle strength could be a good predictor of respiratory muscle function. Implications for rehabilitation Neck pain severity could be closely associated with decreased respiratory pressure in patients with chronic nonspecific neck pain. These findings suggest a new therapeutic approach for patients with moderate to severe disability, such as respiratory muscle training. The regression