Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains.

PubMed

Walker, Brendan M; Drimmer, David A; Walker, Jennifer L; Liu, Tianmin; Mathé, Aleksander A; Ehlers, Cindy L

2010-09-01

Depressive symptoms in alcohol-dependent individuals are well-recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol induced. To contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 h on/10 h off) or air exposure for 2 weeks and were then tested at three time points corresponding to acute withdrawal (8-12 h into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five-min FST consisted of latency to immobility, swim time, immobility time, and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors; for instance, decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60-day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared with the control animals, and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain. Copyright © 2010 Elsevier Inc. All rights reserved.

Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

PubMed

Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

2013-09-01

Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

Prevalence, withdrawal symptoms and associated factors of khat chewing among students at Jimma University in Ethiopia.

PubMed

Abdeta, Tilahun; Tolessa, Daniel; Adorjan, Kristina; Abera, Mubarek

2017-04-17

Recently, khat chewing has become a common practice among high school, college, and university students. Regular khat chewing is thought to be a predisposing factor for different physical and mental health problems. It can lead to absenteeism from work and classes. In Ethiopia, to our knowledge no published study has investigated khat withdrawal symptoms. Therefore, this study was conducted to determine the prevalence, withdrawal symptoms, and associated factors of khat chewing among regular undergraduate students on the main campus of Jimma University in Ethiopia. The institution-based, cross-sectional study was conducted in January 2016. Data were collected from 651 main campus regular undergraduate students with a structured, self-administered questionnaire, entered into Epidata 3.1 and exported to SPSS version 20 for Windows. Bivariate and multivariate logistic regressions were used to explore associations and identify variables independently associated with khat chewing. The study found that the lifetime and current prevalence of khat chewing among students were 26.3% (95% CI: 24.3, 28.3) and 23.9% (95% CI: 21.94, 25.86), respectively. About 25.7% of students started chewing after joining university, and 60.5% of these students started during their first year. The main reason given for starting khat chewing was for study purposes (54.6%), followed by socialization purposes (42.3%). Among current khat chewers, 72.9% reported that they had chewed khat for 1 year or more and 68.2% reported that they had experienced various withdrawal symptoms. The most frequently reported withdrawal symptoms were feeling depressed, craving, and feeling fatigued. Being male, attending a place of worship daily/2-3 times per week, cannabis use, smoking cigarettes, and having family members currently chewing khat were independently associated with khat chewing. This study found that large numbers of university students were currently chewing khat. In this study withdrawal symptoms and factors that significantly affect khat chewing were identified. Besides it gave new ideas regarding khat withdrawal symptoms in Ethiopia. It serves as a critical role of providing information to form rational foundation for public health policy, prevention and planning to bring change in contributing factors for Khat chewing. The finding will be serving as base line information for further study.

High-dose benzodiazepine dependence: a qualitative study of patients' perception on cessation and withdrawal.

PubMed

Liebrenz, Michael; Gehring, Marie-Therese; Buadze, Anna; Caflisch, Carlo

2015-05-13

Benzodiazepine withdrawal syndrome has been reported following attempts to withdraw even from low or therapeutic doses and has been compared to barbiturate and alcohol withdrawal. This experience is known to deter patients from future cessation attempts. Research on other psychotropic substances shows that the reasons and motivations for withdrawal attempts - as well as the experiences surrounding those attempts - at least partially predict future efforts at discontinuation as well as relapse. We therefore aimed to qualitatively explore what motivates patients to discontinue this medication as well as to examine their experiences surrounding previous and current withdrawal attempts and treatment interventions in order to positively influence future help-seeking behavior and compliance. To understand these patients better, we conducted a series of 41 unstructured, narrative, in-depth interviews among adult Swiss patients with a long-term dependent use of benzodiazepines in doses equivalent to more than 40 mg diazepam per day and/or otherwise problematic use (mixing benzodiazepines, escalating dosage, recreational use or illegal purchase). Mayring's qualitative content analysis was used to evaluate findings. These high-dose benzodiazepine-dependent patients decision to change consumption patterns were affected by health concerns, the feeling of being addicted and social factors. Discontinuation attempts were frequent and not very successful with fast relapse. Withdrawal was perceived to be a difficult, complicated, and highly unpredictable process. The first attempt at withdrawal occurred at home and typically felt better than at the clinic. Inpatient treatment was believed to be more effective with long term treatment (approaches) than short term. Patients preferred gradual reduction of usage to abrupt cessation (and had experienced both). While no clear preferences for withdrawal were found for benzodiazepines with specific pharmacokinetic properties, participants frequently based their decision to participate in treatment on the availability of their preferred brand name and furthermore discarding equivalent dosage rationales. Our findings provide greater understanding of the factors that motivate high-dose benzodiazepine-dependent individuals to stop taking these medications, and how they experience withdrawal and treatment strategies. They underscore how patients' perceptions of treatment approaches contribute to compliant or non-compliant behavior.

A Model of Student Workload

ERIC Educational Resources Information Center

Bowyer, Kyle

2012-01-01

Student workload is a contributing factor to students deciding to withdraw from their study before completion of the course, at significant cost to students, institutions and society. The aim of this paper is to create a basic workload model for a group of undergraduate students studying business law units at Curtin University in Western…

Factors related to physical activity adherence in women: review and suggestions for future research.

PubMed

White, Jennifer L; Ransdell, Lynda B; Vener, Jamie; Flohr, Judith A

2005-01-01

Approximately 50 percent of individuals who start an exercise program withdraw within 6 months. Thus, many individuals withdraw before health benefits have been realized. This is a disconcerting statistic considering the well known benefits of physical activity for decreasing risk of hypokinetic diseases and improving quality of life. The literature has suggested a plethora of factors to increase the number of individuals who initiate a physical activity program. However, little is known about the factors that keep women exercising-otherwise known as exercise adherence. The purpose of this paper is to: (a) systematically review the quantitative literature to discern the major factors contributing to adherence to physical activity in women and men and make recommendations for specific gender-based considerations that are important when designing PA interventions for women, and (b) suggest areas of future research related to increasing adherence to physical activity in women. Key factors reviewed in this paper may be useful in developing efficacious physical activity programs for women.

Protein Translation in the Nucleus Accumbens Is Dysregulated during Cocaine Withdrawal and Required for Expression of Incubation of Cocaine Craving.

PubMed

Werner, Craig T; Stefanik, Michael T; Milovanovic, Mike; Caccamise, Aaron; Wolf, Marina E

2018-03-14

Exposure to drug-associated cues can induce drug craving and relapse in abstinent addicts. Cue-induced craving that progressively intensifies ("incubates") during withdrawal from cocaine has been observed in both rats and humans. Building on recent evidence that aberrant protein translation underlies incubation-related adaptations in the NAc, we used male rats to test the hypothesis that translation is dysregulated during cocaine withdrawal and/or when rats express incubated cocaine craving. We found that intra-NAc infusion of anisomycin, a general protein translation inhibitor, or rapamycin, an inhibitor of mammalian target of rapamycin, reduced the expression of incubated cocaine craving, consistent with previous results showing that inhibition of translation in slices normalized the adaptations that maintain incubation. We then examined signaling pathways involved in protein translation using NAc synaptoneurosomes prepared after >47 d of withdrawal from cocaine or saline self-administration, or after withdrawal plus a cue-induced seeking test. The most robust changes were observed following seeking tests. Most notably, we found that eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 2α (eIF2α) are dephosphorylated when cocaine rats undergo a cue-induced seeking test; both effects are consistent with increased translation during the test. Blocking eIF2α dephosphorylation and thereby restoring its inhibitory influence on translation, via intra-NAc injection of Sal003 just before the test, substantially reduced cocaine seeking. These results are consistent with dysregulation of protein translation in the NAc during cocaine withdrawal, enabling cocaine cues to elicit an aberrant increase in translation that is required for the expression of incubated cocaine craving. SIGNIFICANCE STATEMENT Cue-induced cocaine craving progressively intensifies (incubates) during withdrawal in both humans and rats. This may contribute to persistent vulnerability to relapse. We previously demonstrated a role for protein translation in synaptic adaptations in the NAc closely linked to incubation. Here, we tested the hypothesis that translation is dysregulated during cocaine withdrawal, and this contributes to incubated craving. Analysis of signaling pathways regulating translation suggested that translation is enhanced when "incubated" rats undergo a cue-induced seeking test. Furthermore, intra-NAc infusions of drugs that inhibit protein translation through different mechanisms reduced expression of incubated cue-induced cocaine seeking. These results demonstrate that the expression of incubation depends on an acute increase in translation that may result from dysregulation of several pathways. Copyright © 2018 the authors 0270-6474/18/382683-15$15.00/0.

Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis.

PubMed

Greenberg, Gian D; Laman-Maharg, Abigail; Campi, Katharine L; Voigt, Heather; Orr, Veronica N; Schaal, Leslie; Trainor, Brian C

2013-01-01

Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.

Quantifying the Clinical Significance of Cannabis Withdrawal

PubMed Central

Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

2012-01-01

Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

Pro-apoptotic BIM is an essential initiator of physiological endothelial cell death independent of regulation by FOXO3.

PubMed

Koenig, M N; Naik, E; Rohrbeck, L; Herold, M J; Trounson, E; Bouillet, P; Thomas, T; Voss, A K; Strasser, A; Coultas, L

2014-11-01

The growth of new blood vessels by angiogenesis is essential for normal development, but can also cause or contribute to the pathology of numerous diseases. Recent studies have shown that BIM, a pro-apoptotic BCL2-family protein, is required for endothelial cell apoptosis in vivo, and can contribute to the anti-angiogenic effect of VEGF-A inhibitors in certain tumor models. Despite its importance, the extent to which BIM is autonomously required for physiological endothelial apoptosis remains unknown and its regulation under such conditions is poorly defined. While the transcription factor FOXO3 has been proposed to induce Bim in response to growth factor withdrawal, evidence for this function is circumstantial. We report that apoptosis was reduced in Bim(-/-) primary endothelial cells, demonstrating a cell-autonomous role for BIM in endothelial death following serum and growth factor withdrawal. In conflict with in vitro studies, BIM-dependent endothelial death in vivo did not require FOXO3. Moreover, endothelial apoptosis proceeded normally in mice lacking FOXO-binding sites in the Bim promoter. Bim mRNA was upregulated in endothelial cells starved of serum and growth factors and this was accompanied by the downregulation of miRNAs of the miR-17∼92 cluster. Bim mRNA levels were also elevated in miR-17∼92(+/-) endothelial cells cultured under steady-state conditions, suggesting that miR-17∼92 cluster miRNAs may contribute to regulating overall Bim mRNA levels in endothelial cells.

Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine.

PubMed

Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M

2017-07-01

In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine

PubMed Central

Adhikary, Sweta; Caprioli, Daniele; Venniro, Marco; Kallenberger, Paige; Shaham, Yavin; Bossert, Jennifer M.

2016-01-01

In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats’ response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6-h/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week, or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25, and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues. PMID:26989042

29 CFR 2520.104-49 - Alternative method of compliance for certain simplified employee pensions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... employer contributions will be made and those IRAs are subject to provisions that prohibit withdrawal of... or withdraw funds from the IRAs, including restrictions that allow rollovers or withdrawals but... purposes, (viii) The statutory provisions concerning withdrawal of funds from a SEP-IRA and the...

26 CFR 1.414(w)-1 - Permissible withdrawals from eligible automatic contribution arrangements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... contribution arrangements. 1.414(w)-1 Section 1.414(w)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT... Plans, Etc. § 1.414(w)-1 Permissible withdrawals from eligible automatic contribution arrangements. (a) Overview. Section 414(w) provides rules under which certain employees are permitted to elect to make a...

Tobacco withdrawal among opioid-dependent smokers.

PubMed

Streck, Joanna M; Heil, Sarah H; Higgins, Stephen T; Bunn, Janice Y; Sigmon, Stacey C

2018-04-01

Prevalence of cigarette smoking among opioid-dependent individuals is 6-fold that of the general U.S. adult population and their quit rates are notoriously poor. One possible reason for the modest cessation outcomes in opioid-dependent smokers may be that they experience more severe tobacco withdrawal upon quitting. In this secondary analysis, we evaluated tobacco withdrawal in opioid-dependent (OD) smokers versus smokers without co-occurring substance use disorders (SUDs). Participants were 47 methadone- or buprenorphine-maintained smokers and 25 non-SUD smokers who completed 1 of several 2-week studies involving daily visits for biochemical monitoring, delivery of financial incentives contingent on smoking abstinence, and assessment of withdrawal via the Minnesota Nicotine Withdrawal Scale (MNWS). Prior to quitting smoking, OD smokers presented with higher baseline withdrawal scores than non-SUD smokers (1.7 ± 0.2 vs. 0.7 ± 0.2, respectively; F [1, 63] = 7.31, p < .001). Withdrawal scores in both groups decreased over the subsequent 2-week period with no group differences, F (1, 910) = 0.50, p = .48. A similar pattern was observed on craving (i.e., Desire to Smoke item of MNWS), although the trajectory of decrease over time on this item was also moderated by gender. Overall, there was no difference in withdrawal during biochemically verified smoking abstinence between OD and non-SUD smokers, suggesting that elevated withdrawal severity following quitting may not be a major factor contributing to the poor cessation outcomes consistently observed among OD smokers. Further scientific efforts are needed to improve our understanding of the high smoking rates and modest cessation outcomes in this challenging population. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Factors Associated with Student Withdrawal from Community College

ERIC Educational Resources Information Center

Scoggin, Donna; Styron, Ronald

2006-01-01

Research was designed to identify commonalities of personal, enrollment, withdrawal, and evaluative factors as they relate to student withdrawal from community college. The study sought to identify interrelationships between identified reasons for student withdrawal and the variables of gender, race, classification status, degree sought, plans for…

Cardiovascular dysfunctions and sympathovagal imbalance in hypertension and prehypertension: physiological perspectives.

PubMed

Pal, Gopal Krushna; Pal, Pravati; Nanda, Nivedita; Amudharaj, Dharmalingam; Adithan, Chandrasekaran

2013-01-01

Hypertension (HTN) and prehypertension (pre-HTN) have been identified as independent risk factors for adverse cardiovascular events. Recently, increased psychosocial stress and work stress have contributed to the increased prevalence of HTN and pre-HTN, in addition to the contribution of obesity, diabetes, poor food habits and physical inactivity. Irrespective of the etiology, sympathetic overactivity has been recognized as the main pathophysiologic mechanism in the genesis of HTN and pre-HTN. Sympathovagal imbalance owing to sympathetic overactivity and vagal withdrawal is reported to be the basis of many clinical disorders. However, the role played by vagal withdrawal has been under-reported. In this review, we have analyzed the pathophysiologic involvement of sympathovagal imbalance in the development of HTN and pre-HTN, and the link of sympathovagal imbalance to cardiovascular dysfunctions. We have emphasized that adaptation to a healthier lifestyle will help improve sympathovagal homeostasis and prevent the occurrence of HTN and pre-HTN.

The effects of tobacco on aviation safety.

PubMed

Dille, J R; Linder, M K

1981-02-01

In 1976, the Federal Aviation Administration was petitioned to issue regulations that would prohibit all smoking in the cockpit during commercial flight operations and prohibit preflight smoking by flight crewmembers within 8 h before commercial flight operations. A review of the literature was conducted to determine the effects on pilot performance of carbon monoxide (CO), nicotine, and smoking withdrawal. The records of 2,660 fatal general aviation aircraft accidents in 1973-1976 have been examined. Smoking was not identified as a causal factor but may have contributed to the cause of some of these accidents. However, the compound factors that were often found and the dire consequences are far less likely to occur in air commerce operations. For some, withdrawal symptoms may occur and more than offset any benefits to aviation safety that are claimed for a ban on preflight and in-flight smoking.

Adaptations in AMPA receptor transmission in the nucleus accumbens contributing to incubation of cocaine craving

PubMed Central

Loweth, Jessica A.; Tseng, Kuei Y.; Wolf, Marina E.

2013-01-01

Cue-induced cocaine craving in rodents intensifies or “incubates” during the first months of withdrawal from long access cocaine self-administration. This incubation phenomenon is relevant to human users who achieve abstinence but exhibit persistent vulnerability to cue-induced relapse. It is well established that incubation of cocaine craving involves complex neuronal circuits. Here we will focus on neuroadaptations in the nucleus accumbens (NAc), a region of convergence for pathways that control cocaine seeking. A key adaptation is a delayed (~3–4 weeks) accumulation of Ca2+-permeable AMPAR receptors (CP-AMPARs) in synapses on medium spiny neurons (MSN) of the NAc. These CP-AMPARs mediate the expression of incubation after prolonged withdrawal, although different mechanisms must be responsible during the first weeks of withdrawal, prior to CP-AMPAR accumulation. The cascade of events leading to CP-AMPAR accumulation is still unclear. However, several candidate mechanisms have been identified. First, mGluR1 has been shown to negatively regulate CP-AMPAR levels in NAc synapses, and it is possible that a withdrawal-dependent decrease in this effect may help explain CP-AMPAR accumulation during incubation. Second, an increase in phosphorylation of GluA1 subunits (at the protein kinase A site) within extrasynaptic homomeric GluA1 receptors (CP-AMPARs) may promote their synaptic insertion and oppose their removal. Finally, elevation of brain-derived neurotrophic factor (BDNF) levels in the NAc may contribute to maintenance of incubation after months of withdrawal, although incubation-related increases in BDNF accumulation do not account for CP-AMPAR accumulation. Receptors and pathways that negatively regulate incubation, such as mGluR1, are promising targets for the development of therapeutic strategies to help recovering addicts maintain abstinence. PMID:23727437

PDL Progenitor-Mediated PDL Recovery Contributes to Orthodontic Relapse.

PubMed

Feng, L; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; He, D; Gan, Y; Kou, X; Zhou, Y

2016-08-01

Periodontal ligament (PDL) is subjected to mechanical force during physiologic activities. PDL stem /: progenitor cells are the main mesenchymal stem cells in PDL. However, how PDL progenitors participate in PDL homeostasis upon and after mechanical force is largely unknown. In this study, force-triggered orthodontic tooth movement and the following relapse were used as models to demonstrate the response of PDL progenitors and their role in PDL remodeling upon and after mechanical force. Upon orthodontic force, PDL collagen on the compression side significantly degraded, showing a broken and disorganized pattern. After force withdrawal, the degraded PDL collagen recovered during the early stage of relapse. Correspondingly, increased CD90(+) PDL progenitors with suppressed expression of type I collagen (Col-I) were observed upon orthodontic force, whereas these cells accumulated at the degradation regions and regained Col-I expression after force withdrawal during early relapse. Our results further showed that compressive force altered cell morphology and repressed collagen expression in cultured PDL progenitors, which both recovered after force withdrawal. Force withdrawal-induced recovery of collagen expression in cultured PDL progenitors could be regulated by transforming growth factor-β (TGF-β), a key molecule for tissue homeostasis and extracellular matrix remodeling. More interesting, inhibiting the regained Col-I expression in CD90(+) PDL progenitors by blocking TGF-β interrupted PDL collagen recovery and partially inhibited the early relapse. These data suggest that PDL progenitors can respond to mechanical force and may process intrinsic stability to recover to original status after force withdrawal. PDL progenitors with intrinsic stability are required for PDL recovery and consequently contribute to early orthodontic relapse, which can be regulated by TGF-β signaling. © International & American Associations for Dental Research 2016.

Perinatal risk factors and social withdrawal behaviour.

PubMed

Guedeney, Antoine; Marchand-Martin, Laetitia; Cote, Sylvana J; Larroque, Béatrice

2012-04-01

The objectives of the study were (1) to assess prevalence of social withdrawal behaviour in infants aged 12 months included in the French Perinatal Risk Factor Study Eden; (2) To study the correlation between relational withdrawal and several perinatal and parental factors assessed in the EDEN study. A longitudinal study using the ADBB scale was conducted within the Eden Cohort in the year 2008. 1,586 infants were included in the study. Fourteen percent of the children who had an ADBB assessment had a score at 5 and over on the ADBB, a scale designed to assess social withdrawal behaviour at age 0-24 months. Social withdrawal at 12 months was associated with low birth weight, low gestational age and with intra uterine growth retardation. Social withdrawal was independently associated with several maternal and paternal risk factors. The level of social withdrawal behaviour increased with a score of maternal difficulties. This study on a large longitudinally followed volunteer sample demonstrate a clear association of social withdrawal behaviour at age one with low birth weight and preterm birth, possibly mediated by parental vulnerabilities. Social withdrawal behaviour seems to be an important alarm signal to detect early on particularly in premature and small for date babies. © Springer-Verlag 2012

Medium density fiberboards from plantation grown Eucalyptus saligna

Treesearch

Andrzej Krzysik; John A. Youngquist; James H. Muehl; Fabio Spina Franca

1999-01-01

The production of industrial wood from natural forests is predicted to decline in the future. Factors that will contribute to this decline include changes in land use patterns, depletion of resources in some parts of the world, and the withdrawal of forest areas from industrial production in order to provide for environmental, recreational, and other social needs....

Pro-apoptotic BIM is an essential initiator of physiological endothelial cell death independent of regulation by FOXO3

PubMed Central

Koenig, M N; Naik, E; Rohrbeck, L; Herold, M J; Trounson, E; Bouillet, P; Thomas, T; Voss, A K; Strasser, A; Coultas, L

2014-01-01

The growth of new blood vessels by angiogenesis is essential for normal development, but can also cause or contribute to the pathology of numerous diseases. Recent studies have shown that BIM, a pro-apoptotic BCL2-family protein, is required for endothelial cell apoptosis in vivo, and can contribute to the anti-angiogenic effect of VEGF-A inhibitors in certain tumor models. Despite its importance, the extent to which BIM is autonomously required for physiological endothelial apoptosis remains unknown and its regulation under such conditions is poorly defined. While the transcription factor FOXO3 has been proposed to induce Bim in response to growth factor withdrawal, evidence for this function is circumstantial. We report that apoptosis was reduced in Bim−/− primary endothelial cells, demonstrating a cell-autonomous role for BIM in endothelial death following serum and growth factor withdrawal. In conflict with in vitro studies, BIM-dependent endothelial death in vivo did not require FOXO3. Moreover, endothelial apoptosis proceeded normally in mice lacking FOXO-binding sites in the Bim promoter. Bim mRNA was upregulated in endothelial cells starved of serum and growth factors and this was accompanied by the downregulation of miRNAs of the miR-17∼92 cluster. Bim mRNA levels were also elevated in miR-17∼92+/− endothelial cells cultured under steady-state conditions, suggesting that miR-17∼92 cluster miRNAs may contribute to regulating overall Bim mRNA levels in endothelial cells. PMID:24971484

Sector-wise midpoint characterization factors for impact assessment of regional consumptive and degradative water use.

PubMed

Lin, Chia-Chun; Lin, Jia-Yu; Lee, Mengshan; Chiueh, Pei-Te

2017-12-31

Water availability, resulting from either a lack of water or poor water quality is a key factor contributing to regional water stress. This study proposes a set of sector-wise characterization factors (CFs), namely consumptive and degradative water stresses, to assess the impact of water withdrawals with a life cycle assessment approach. These CFs consider water availability, water quality, and competition for water between domestic, agricultural and industrial sectors and ecosystem at the watershed level. CFs were applied to a case study of regional water management of industrial water withdrawals in Taiwan to show that both regional or seasonal decrease in water availability contributes to a high consumptive water stress, whereas water scarcity due to degraded water quality not meeting sector standards has little influence on increased degradative water stress. Degradative water stress was observed more in the agricultural sector than in the industrial sector, which implies that the agriculture sector may have water quality concerns. Reducing water intensity and alleviating regional scale water stresses of watersheds are suggested as approaches to decrease the impact of both consumptive and degradative water use. The results from this study may enable a more detailed sector-wise analysis of water stress and influence water resource management policies. Copyright © 2017 Elsevier B.V. All rights reserved.

Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling.

PubMed

Addicott, Merideth A; Froeliger, Brett; Kozink, Rachel V; Van Wert, Dana M; Westman, Eric C; Rose, Jed E; McClernon, Francis J

2014-11-01

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.

Nicotine and Non-Nicotine Smoking Factors Differentially Modulate Craving, Withdrawal and Cerebral Blood Flow as Measured with Arterial Spin Labeling

PubMed Central

Addicott, Merideth A; Froeliger, Brett; Kozink, Rachel V; Van Wert, Dana M; Westman, Eric C; Rose, Jed E; McClernon, Francis J

2014-01-01

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation. PMID:24820539

Comparison of cannabis and tobacco withdrawal: severity and contribution to relapse.

PubMed

Budney, Alan J; Vandrey, Ryan G; Hughes, John R; Thostenson, Jeff D; Bursac, Zoran

2008-12-01

This naturalistic telephone survey study compared perceptions of withdrawal severity in 67 daily cannabis users and 54 daily tobacco cigarette smokers who made quit attempts during the prior 30 days. A Withdrawal Symptom Checklist assessed the severity of abstinence symptoms and a Likert scale assessed perceived relations between abstinence symptoms and relapse. A composite Withdrawal Discomfort Score did not differ significantly between groups (M = 13.0 for cannabis, vs. M = 13.2 for tobacco). Individual symptom severity ratings were also of similar magnitude, except craving and sweating were slightly higher for tobacco. Both groups reported that withdrawal contributed substantially to relapse, and the strength of these ratings was similar across groups. The diverse convenience sample examined in this study adds external validity and generalizability to prior studies that included only users not planning to quit or excluded many common types of cannabis users. The comparable withdrawal experience from these heterogeneous cannabis and tobacco users supports previous findings from controlled laboratory studies and indicates that real-world, frequent cannabis users perceive that withdrawal symptoms negatively affect their desire and ability to quit.

Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast)

PubMed Central

Hutchinson, Mark R.; Lewis, Susannah S.; Coats, Benjamen D.; Skyba, David A.; Crysdale, Nicole Y.; Berkelhammer, Debra L.; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M.; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.; Johnson, Kirk W.

2009-01-01

Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused 3-to-5-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, whilst improving analgesia. PMID:18938237

Happiness as a Buffer of the Association Between Dependence and Acute Tobacco Abstinence Effects in African American Smokers.

PubMed

Liautaud, Madalyn M; Leventhal, Adam M; Pang, Raina D

2017-09-27

African-American (AA) smokers are at disproportionate risk of tobacco dependence, utilizing smoking to regulate stress, and poor cessation outcomes. Positive emotional traits may function as coping factors that buffer the extent to which dependence increases vulnerability to adverse responses to acute tobacco abstinence (i.e., tobacco withdrawal). This laboratory study examined subjective happiness (SH; dispositional orientation towards frequent and intense positive affect [PA] and life satisfaction) as a moderator of the relation between tobacco dependence and subjective and behavioral abstinence effects among AA smokers. AA smokers (N=420, 39.0% female) completed self-report measures of tobacco dependence and SH followed by two counterbalanced experimental sessions (non-abstinent vs. 16-hr abstinent) involving self-report measures of composite withdrawal, urge to smoke, and mood, and a behavioral smoking task in which participants could: (a) earn money to delay smoking reinstatement, and (b) subsequently purchase cigarettes to smoke. Tobacco dependence was positively associated with increased abstinence effects in composite withdrawal, urge to smoke, PA, and latency to smoking reinstatement (ps<.04). SH significantly moderated the relation between dependence and abstinence-induced increases in composite withdrawal (β =-.17, p<.001), such that the predictive power of dependence on withdrawal severity grew proportionately weaker as levels of SH increased. SH may insulate against adverse effects of dependence on withdrawal during acute smoking abstinence, particularly withdrawal symptom clusters that are craving- and mood-based. Consideration of positive emotional traits as stress-coping factors in the dependence-withdrawal link may be warranted in research and practice with AA smokers. The current study contributes to a growing body of literature examining the potentially advantageous role of positive emotional traits to smokers. We do so by identifying a relatively understudied psychological construct within tobacco research-subjective happiness-that may suppress the extent to which more severe tobacco dependence increases risk for subjective withdrawal-related distress during acute smoking abstinence in African American smokers. In doing so, the study provides a primer for future targeting of subjective happiness and other positive emotional traits as means to understand and treat acute tobacco abstinence effects among dependent African American smokers. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Psychometric evaluation of the Dutch version of the Subjective Opiate Withdrawal Scale (SOWS).

PubMed

Dijkstra, Boukje A G; Krabbe, Paul F M; Riezebos, Truus G M; van der Staak, Cees P F; De Jong, Cor A J

2007-01-01

To evaluate the psychometric properties of the Dutch version of the 16-item Subjective Opiate Withdrawal Scale (SOWS). The SOWS measures withdrawal symptoms at the time of assessment. The Dutch SOWS was repeatedly administered to a sample of 272 opioid-dependent inpatients of four addiction treatment centers during rapid detoxification with or without general anesthesia. Examination of the psychometric properties of the SOWS included exploratory factor analysis, internal consistency, test-retest reliability, and criterion validity. Exploratory factor analysis of the SOWS revealed a general pattern of four factors with three items not always clustered in the same factors at different points of measurement. After excluding these items from factor analysis four factors were identified during detoxification (temperature dysregulation, tractus locomotorius, tractus gastro-intestinalis and facial disinhibition). The 13-item SOWS shows high internal consistency and test-retest reliability and good validity at different stages of withdrawal. The 13-item SOWS is a reliable and valid instrument to assess opioid withdrawal during rapid detoxification. Three items were deleted because their content does not correspond directly with opioid withdrawal symptoms. Copyright (c) 2007 S. Karger AG, Basel.

26 CFR 1.411(a)-4 - Forfeitures, suspensions, etc.

Code of Federal Regulations, 2010 CFR

2010-04-01

... account benefits which are provided under the Social Security Act or under any other Federal or State law... retroactive effect in accordance with such section. (4) Other forfeiture rules—(i) Withdrawal of mandatory contributions. For rules allowing forfeitures on account of the withdrawal of mandatory contributions, see § 1...

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

PubMed Central

Kutlu, Munir Gunes

2016-01-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. PMID:27634143

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction.

PubMed

Kutlu, Munir Gunes; Gould, Thomas J

2016-10-01

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawal-induced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates. © 2016 Kutlu and Gould; Published by Cold Spring Harbor Laboratory Press.

Attrition in Smoking Cessation Intervention Studies: A Systematic Review.

PubMed

Belita, Emily; Sidani, Souraya

2015-12-01

Withdrawal of participants from intervention studies has dire methodological and clinical consequences. Attrition rates in smoking cessation studies have been found to be particularly high. Identifying factors that contribute to attrition may inform strategies to address the problem and prevent its consequences. This systematic review had 2 objectives: to report attrition rates, and to identify factors that influence attrition of adult smokers participating in smoking cessation intervention studies. Inclusion criteria were (1) published between 1980 and 2015; (2) experimental or quasi-experimental design; (3) pharmacological, educational, or behavioural intervention; (4) target population of adult smokers; (5) examination of attrition rate; and (6) exploration of factors associated with attrition and/or of reasons given by participants for withdrawing. These criteria were met by 10 studies. Attrition rates ranged from 10.8% to 77%. A small number of demographic, clinical, behavioural, health, health-related beliefs, and logistical factors were related to attrition. The report of high attrition rates underlines the importance of incorporating strategies to minimize attrition in smoking cessation studies. Strategies to reduce attrition are proposed. Copyright© by Ingram School of Nursing, McGill University.

Land subsidence caused by withdrawal of oil and gas in the Gulf coastal plain - The Houston, Texas, case history

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holzer, T.L.

1990-09-01

The extensive network of geodetic leveling lines in the Houston-Galveston, Texas, area, where at least 110 oil and gas fields have been developed, provides the most comprehensive opportunity in the Gulf Coast to search for the occurrence of land subsidence caused by withdrawal of oil and gas. Although the evaluation is complicated by regional subsidence caused by a decline of ground-water level in aquifers beneath the area, subsidence caused by oil and gas withdrawal can be examined by searching for local increases of subsidence at oil and gas fields crossed by leveling lines. Twenty-nine fields are crossed by lines withmore » repeated leveling surveys. Subsidence profiles across these fields indicate local increases of subsidence at six fields-Alco-Mag, Chocolate Bayou, Goose Creek, Hastings, Mykawa, and South Houston. Although ground-water withdrawal is undoubtedly the most important factor contributing to the total subsidence at each field, oil and gas withdrawal may be partly responsible for the local increases. Except for Chocolate Bayou, the volume of petroleum production at each field was sufficient to account for the increase. The volume of petroleum production, however, in general is not a reliable index for predicting the local increase because land within many fields with significant production did not show local increases of subsidence. With the exception of the 1 m subsidence caused by petroleum withdrawal at Goose Creek (1917-1925), local increases of subsidence were less than 0.3 m.« less

Evolution of Wernicke-Korsakoff syndrome in self-neglecting alcoholics: preliminary results of relation with Wernicke-delirium and diabetes mellitus.

PubMed

Wijnia, Jan W; van de Wetering, Ben J M; Zwart, Elles; Nieuwenhuis, K Gerrit A; Goossensen, M Anne

2012-01-01

We present a descriptive, retrospective study of initial symptoms, comorbidity, and alcohol withdrawal in 73 alcoholic patients with subsequent Korsakoff syndrome. In 25/73 (35%) of the patients the classic triad of Wernicke's encephalopathy with ocular symptoms, ataxia and confusion, was found. In at least 6/35 (17%) of the initial deliria (95% confidence interval: 10-25%) we observed no other underlying causes, thus excluding other somatic causes, medication, (recent) alcohol withdrawal, or intoxication. We suggest that these deliria may have been representing Wernicke's encephalopathy. A high frequency (15%) of diabetics may reflect a contributing factor of diabetes mellitus in the evolution of the Wernicke-Korsakoff syndrome. Copyright © American Academy of Addiction Psychiatry.

Understanding the addiction cycle: a complex biology with distinct contributions of genotype vs. sex at each stage.

PubMed

Wilhelm, C J; Hashimoto, J G; Roberts, M L; Sonmez, M K; Wiren, K M

2014-10-24

Ethanol abuse can lead to addiction, brain damage and premature death. The cycle of alcohol addiction has been described as a composite consisting of three stages: intoxication, withdrawal and craving/abstinence. There is evidence for contributions of both genotype and sex to alcoholism, but an understanding of the biological underpinnings is limited. Utilizing both sexes of genetic animal models with highly divergent alcohol withdrawal severity, Withdrawal Seizure-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) mice, the distinct contributions of genotype/phenotype and of sex during addiction stages on neuroadaptation were characterized. Transcriptional profiling was performed to identify expression changes as a consequence of chronic intoxication in the medial prefrontal cortex. Significant expression differences were identified on a single platform and tracked over a behaviorally relevant time course that covered each stage of alcohol addiction; i.e., after chronic intoxication, during peak withdrawal, and after a defined period of abstinence. Females were more sensitive to ethanol with higher fold expression differences. Bioinformatics showed a strong effect of sex on the data structure of expression profiles during chronic intoxication and at peak withdrawal irrespective of genetic background. However, during abstinence, differences were observed instead between the lines/phenotypes irrespective of sex. Confirmation of identified pathways showed distinct inflammatory signaling following intoxication at peak withdrawal, with a pro-inflammatory phenotype in females but overall suppression of immune signaling in males. Combined, these results suggest that each stage of the addiction cycle is influenced differentially by sex vs. genetic background and support the development of stage- and sex-specific therapies for alcohol withdrawal and the maintenance of sobriety. Published by Elsevier Ltd.

29 CFR 4204.21 - Requests to PBGC for variances and exemptions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... WITHDRAWAL LIABILITY FOR MULTIEMPLOYER PLANS VARIANCES FOR SALE OF ASSETS Procedures for Individual and Class... parties. When a contributing employer withdraws from a plan as a result of related sales of assets involving several purchasers, or withdraws from more than one plan as a result of a single sale, the...

29 CFR 4203.4 - Requests for PBGC approval of plan amendments.

Code of Federal Regulations, 2010 CFR

2010-07-01

... withdrawal rules in the plan amendment would operate in the event of a sale of assets by a contributing... 29 Labor 9 2010-07-01 2010-07-01 false Requests for PBGC approval of plan amendments. 4203.4... WITHDRAWAL LIABILITY FOR MULTIEMPLOYER PLANS EXTENSION OF SPECIAL WITHDRAWAL LIABILITY RULES § 4203.4...

Peer Relations and Behavioral Characteristics of Isolated Children in Elementary School: A Longitudinal Investigation

ERIC Educational Resources Information Center

Norwalk, Kate E.

2013-01-01

Research clearly shows that heterogeneity exists in the etiology, associated characteristics, and outcomes of social withdrawal/isolation. While individual level characteristics are thought to contribute to withdrawal and isolation, research suggests that peer relations may play an important role in the extent to which social withdrawal/isolation…

Neuropeptide systems and new treatments for nicotine addiction

PubMed Central

Bruijnzeel, Adriaan W.

2017-01-01

RATIONALE The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. OBJECTIVES The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking. RESULTS The reviewed studies indicate that several drugs that target neuropeptide systems diminish the rewarding effects of nicotine by preventing the activation of dopaminergic systems. Other peptide-based drugs diminish the hyperactivity of brain stress systems and diminish withdrawal-associated symptom severity. Blockade of hypocretin-1 and nociceptin receptors and stimulation of galanin and neurotensin receptors diminishes the rewarding effects of nicotine. Both corticotropin-releasing factor type 1 and kappa-opioid receptor antagonists diminish dysphoria and anxiety-like behavior associated with nicotine withdrawal and inhibit stress-induced reinstatement of nicotine seeking. Furthermore, blockade of vasopressin 1b receptors diminishes dysphoria during nicotine withdrawal and melanocortin 4 receptor blockade prevents stress-induced reinstatement of nicotine seeking. The role of neuropeptide systems in nicotine-primed and cue-induced reinstatement is largely unexplored, but there is evidence for a role of hypocretin-1 receptors in cue-induced reinstatement of nicotine seeking. CONCLUSION Drugs that target neuropeptide systems might decrease the euphoric effects of smoking and improve relapse rates by diminishing withdrawal symptoms and improving stress resilience. PMID:28028605

Consequences of brain-derived neurotrophic factor withdrawal in CNS neurons and implications in disease

PubMed Central

Mariga, Abigail; Mitre, Mariela; Chao, Moses V.

2017-01-01

Growth factor withdrawal has been studied across different species and has been shown to have dramatic consequences on cell survival. In the nervous system, withdrawal of nerve growth factor (NGF) from sympathetic and sensory neurons results in substantial neuronal cell death, signifying a requirement for NGF for the survival of neurons in the peripheral nervous system (PNS). In contrast to the PNS, withdrawal of central nervous system (CNS) enriched brain-derived neurotrophic factor (BDNF) has little effect on cell survival but is indispensible for synaptic plasticity. Given that most early events in neuropsychiatric disorders are marked by a loss of synapses, lack of BDNF may thus be an important part of a cascade of events that leads to neuronal degeneration. Here we review reports on the effects of BDNF withdrawal on CNS neurons and discuss the relevance of the loss in disease. PMID:27015693

Adaptations in AMPA receptor transmission in the nucleus accumbens contributing to incubation of cocaine craving.

PubMed

Loweth, Jessica A; Tseng, Kuei Y; Wolf, Marina E

2014-01-01

Cue-induced cocaine craving in rodents intensifies or "incubates" during the first months of withdrawal from long access cocaine self-administration. This incubation phenomenon is relevant to human users who achieve abstinence but exhibit persistent vulnerability to cue-induced relapse. It is well established that incubation of cocaine craving involves complex neuronal circuits. Here we will focus on neuroadaptations in the nucleus accumbens (NAc), a region of convergence for pathways that control cocaine seeking. A key adaptation is a delayed (~3-4 weeks) accumulation of Ca(2+)-permeable AMPAR receptors (CP-AMPARs) in synapses on medium spiny neurons (MSN) of the NAc. These CP-AMPARs mediate the expression of incubation after prolonged withdrawal, although different mechanisms must be responsible during the first weeks of withdrawal, prior to CP-AMPAR accumulation. The cascade of events leading to CP-AMPAR accumulation is still unclear. However, several candidate mechanisms have been identified. First, mGluR1 has been shown to negatively regulate CP-AMPAR levels in NAc synapses, and it is possible that a withdrawal-dependent decrease in this effect may help explain CP-AMPAR accumulation during incubation. Second, an increase in phosphorylation of GluA1 subunits (at the protein kinase A site) within extrasynaptic homomeric GluA1 receptors (CP-AMPARs) may promote their synaptic insertion and oppose their removal. Finally, elevation of brain-derived neurotrophic factor (BDNF) levels in the NAc may contribute to maintenance of incubation after months of withdrawal, although incubation-related increases in BDNF accumulation do not account for CP-AMPAR accumulation. Receptors and pathways that negatively regulate incubation, such as mGluR1, are promising targets for the development of therapeutic strategies to help recovering addicts maintain abstinence. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Youth Withdrawal Moderates the Relationhips between Neighborhood Factors and Internalizing Symptoms in Adolescence

PubMed Central

Rabinowitz, Jill A.; Drabick, Deborah A.G.; Reynolds, Maureen D.

2015-01-01

Adolescents higher in temperamental withdrawal are at risk for anxiety and depressive symptoms; however, not all youth higher in withdrawal exhibit internalizing symptoms, suggesting that contextual factors may influence these relationships. We examined whether youth withdrawal moderates the relationships between neighborhood processes (crime, social cohesion) and internalizing symptoms and whether findings were consistent with diathesis-stress or differential susceptibility hypotheses. Participants were 775 adolescents (M=15.50 ± 0.56 years, 72% male, 76% White). Adolescents higher in withdrawal manifested higher internalizing symptoms in the context of lower neighborhood crime and lower neighborhood social cohesion than youth lower in withdrawal, supporting diathesis-stress. These findings elucidate neighborhood processes associated with internalizing symptoms, which can inform models of risk and resilience for these symptoms among children who differ in temperamental withdrawal. PMID:26149949

Risk of seizure relapse after antiepileptic drug withdrawal in adult patients with focal epilepsy.

PubMed

He, Ru-Qian; Zeng, Qing-Yi; Zhu, Pan; Bao, Yi-Xin; Zheng, Rong-Yuan; Xu, Hui-Qin

2016-11-01

The objective of this study was to estimate the risk of a seizure relapse and the high-risk period of recurrence after antiepileptic drug (AED) withdrawal and to determine the predictive factors for a seizure relapse in adult patients with focal epilepsy who were seizure-free for more than 2years. Using the Wenzhou Epilepsy Follow-Up Registry Database, 200 adult patients with focal epilepsy were recruited, who were undergoing follow-up, met the inclusion criteria of this study, were seizure-free for more than 2years, began withdrawing between June 2003 and June 2014, and were followed up prospectively for at least 1year or until a seizure relapse. The risk of recurrence and the time to seizure relapse were analyzed by the Kaplan-Meier method, and the predictive factors were identified by the Cox proportional hazard regression model. A total of 99 patients had an unprovoked relapse during the follow-up period. The relapse rate was 49.5%, and each year, the recurrence probability of 12, 24, 36, 48, 60, 72, and 84months after AED withdrawal was 24.0%, 20.4%, 8.3%, 2.7%, 4.6%, 0.97%, and 0.98%, respectively. The two independent risk factors for recurrence after withdrawal in adult patients with focal epilepsy were a longer duration of active epilepsy and a shorter seizure-free period before withdrawal. The high-risk period of a seizure relapse in adult patients with focal epilepsy is the first 2years after withdrawal, and beyond 5years after withdrawal, seizures rarely relapse (relapse rate<1%). A seizure-free period for less than 4years before withdrawal is a predictive factor of risk for seizure recurrence after AED withdrawal in adult patients with focal epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

Factor Analysis and Psychometric Properties of the Minnesota Nicotine Withdrawal Scale and the Minnesota Nicotine Withdrawal Scale-Revised: Italian Version.

PubMed

Svicher, Andrea; Beghè, Agnese; Mangiaracina, Giacomo; Cosci, Fiammetta

2017-01-01

We run Exploratory and Confirmatory Factor Analyses of the Minnesota Nicotine Withdrawal Scale (MNWS) and of the MNWS-Revised (MNWS-R). Psychometric properties were also explored. Adult Italian smokers, 366 in all, were assessed via the MNWS-R together with rating scales measuring cigarette dependence, alcohol use, anxiety sensitivity and negative affect at baseline and after 3 months. The MNWS showed good psychometric properties (α = 0.85; rtt = 0.59) and a unidimensional factor structure. The 2-factor model of MNWS-R had the best fit and the factors were labelled psychological symptoms (α = 0.86; rtt = 0.59) and associated somatic features (α = 0.64; rtt = 0.45). MNWS showed 1 factor; MNWS-R showed 2 relatively dependent factors. The results need to be replicated in smokers in withdrawal. © 2017 S. Karger AG, Basel.

Medical collections in public libraries of the United States: a brief historical study.

PubMed Central

Wannarka, M

1968-01-01

During the late nineteenth and early twentieth centuries, it was not unusual for a public library in the United States to include a collection of medical books among its resources. The origin and development of these collections, the growth of the movement, and the factors which contributed to the eventual withdrawal of these collections from the public library are recounted here. PMID:4951139

The Phenomenon of Student Withdrawal at Universities in Australia: A Review of Literature Concerning Factors Associated with Academic Performance and Discontinuance.

ERIC Educational Resources Information Center

Eaton, Elena

Literature concerning factors associated with academic performance and withdrawal from college is reviewed separately for North American, United Kingdom, and Australian universities to help illuminate the problem of student withdrawal in Australia. V. Tinto's 1975 research review concerning North American college dropouts is summarized, and…

Differential Regulation of MAPK Phosphorylation in the Dorsal Hippocampus in Response to Prolonged Morphine Withdrawal-Induced Depressive-Like Symptoms in Mice

PubMed Central

Shi, Jianguo; Wu, Bin; Dang, Wei; Du, Ying; Zhou, Qiong; Wang, Jianhua; Zhang, Rui

2013-01-01

Depression is one of the most frequent neuropsychiatric comorbidities associated with opiate addiction. Mitogen activated protein kinase (MAPK) and MAPK phosphatase (MKP) are involved in drug addiction and depression. However, the potential role of MAPK and MKP in depression caused by morphine withdrawal remains unclear. We utilized a mouse model of repeated morphine administration to examine the molecular mechanisms that contribute to prolonged withdrawal induced depressive-like behaviors. Depressive-like behaviors were significant at 1 week after withdrawal and worsened over time. Phospho-ERK (extracellular signal-regulated protein kinase) was decreased and MKP-1 was elevated in the hippocampus, and JNK (c-Jun N-terminal protein kinase), p38 (p38 protein kinase) and MKP-3 were unaffected. A pharmacological blockade of MKP-1 by intra-hippocampal sanguinarine (SA) infusion prevented the development of depressive-like behaviors and resulted in relatively normal levels of MKP-1 and phospho-ERK after withdrawal. Our findings support the association between hippocampal MAPK phosphorylation and prolonged morphine withdrawal-induced depression, and emphasize the MKP-1 as an negative regulator of the ERK phosphorylation that contributes to depression. PMID:23823128

A Water-Withdrawal Input-Output Model of the Indian Economy.

PubMed

Bogra, Shelly; Bakshi, Bhavik R; Mathur, Ritu

2016-02-02

Managing freshwater allocation for a highly populated and growing economy like India can benefit from knowledge about the effect of economic activities. This study transforms the 2003-2004 economic input-output (IO) table of India into a water withdrawal input-output model to quantify direct and indirect flows. This unique model is based on a comprehensive database compiled from diverse public sources, and estimates direct and indirect water withdrawal of all economic sectors. It distinguishes between green (rainfall), blue (surface and ground), and scarce groundwater. Results indicate that the total direct water withdrawal is nearly 3052 billion cubic meter (BCM) and 96% of this is used in agriculture sectors with the contribution of direct green water being about 1145 BCM, excluding forestry. Apart from 727 BCM direct blue water withdrawal for agricultural, other significant users include "Electricity" with 64 BCM, "Water supply" with 44 BCM and other industrial sectors with nearly 14 BCM. "Construction", "miscellaneous food products"; "Hotels and restaurants"; "Paper, paper products, and newsprint" are other significant indirect withdrawers. The net virtual water import is found to be insignificant compared to direct water used in agriculture nationally, while scarce ground water associated with crops is largely contributed by northern states.

Cytokine involvement in stress may depend on corticotrophin releasing factor to sensitize ethanol withdrawal anxiety

PubMed Central

Knapp, Darin J.; Whitman, Buddy A.; Wills, Tiffany A.; Angel, Robert A.; Overstreet, David H.; Criswell, Hugh E.; Ming, Zhen; Breese, George R.

2011-01-01

Stress has been shown to facilitate ethanol withdrawal-induced anxiety. Defining neurobiological mechanisms through which stress has such actions is important given the associated risk of relapse. While CRF has long been implicated in the action of stress, current results show that stress elevates the cytokine TNFα in the rat brain and thereby implicates cytokines in stress effects. In support of this view, prior TNFα microinjection into the central amygdala (CeA) of rats facilitated ethanol withdrawal-induced anxiety—a response that could not be attributed to an increase in plasma corticosterone. To test for a possible interaction between cytokines and CRF, a CRF1-receptor antagonist (SSR125543) administered prior to the repeated administration of TNFα or MCP-1/CCL2 reduced the magnitude of the withdrawal-induced anxiety. This finding provided evidence for cytokine action being dependent upon CRF. Additionally, the sensitizing effect of stress on withdrawal-induced anxiety was reduced by treating the repeated stress exposure prior to ethanol with the MEK inhibitor SL327. Consistent with cytokines having a neuromediator function distinct from a neuroimmune action, TNFα increased firing rate and GABA release from CeA neurons. Thus, an interaction of glial and neuronal function is proposed to contribute to the interaction of stress and chronic ethanol. Interrupting this potential glial-neuronal interaction could provide a novel means by which to alter the development of emotional states induced by stress that predict relapse in the alcoholic. PMID:21377524

Imbalance in individual researcher's peer review activities quantified for four British Ecological Society journals, 2003-2010.

PubMed

Petchey, Owen L; Fox, Jeremy W; Haddon, Lindsay

2014-01-01

Researchers contribute to the scientific peer review system by providing reviews, and "withdraw" from it by submitting manuscripts that are subsequently reviewed. So far as we are aware, there has been no quantification of the balance of individual's contributions and withdrawals. We compared the number of reviews provided by individual researchers (i.e., their contribution) to the number required by their submissions (i.e. their withdrawals) in a large and anonymised database provided by the British Ecological Society. The database covered the Journal of Ecology, Journal of Animal Ecology, Journal of Applied Ecology, and Functional Ecology from 2003-2010. The majority of researchers (64%) did not have balanced contributions and withdrawals. Depending on assumptions, 12% to 44% contributed more than twice as much as required; 20% to 52% contributed less than half as much as required. Balance, or lack thereof, varied little in relation to the number of years a researcher had been active (reviewing or submitting). Researchers who contributed less than required did not lack the opportunity to review. Researchers who submitted more were more likely to accept invitations to review. These finding suggest overall that peer review of the four analysed journals is not in crisis, but only due to the favourable balance of over- and under-contributing researchers. These findings are limited to the four journals analysed, and therefore cannot include researcher's other peer review activities, which if included might change the proportions reported. Relatively low effort was required to assemble, check, and analyse the data. Broader analyses of individual researcher's peer review activities would contribute to greater quality, efficiency, and fairness in the peer review system.

Effects of CB1 and CRF1 receptor antagonists on binge-like eating in rats with limited access to a sweet fat diet: Lack of withdrawal-like responses

PubMed Central

Sabino, Valentina; Rice, Kenner C.; Zorrilla, Eric P.

2013-01-01

Positive reinforcement (e.g., appetitive, rewarding properties) has often been hypothesized to maintain excessive intake of palatable foods. Recently, rats receiving intermittent access to high sucrose diets showed binge-like intake with withdrawal-like signs upon cessation of access, suggesting negative reinforcement mechanisms contribute as well. Whether intermittent access to high fat diets also produces withdrawal-like syndromes is controversial. The present study therefore tested the hypothesis that binge-like eating and withdrawal-like anxiety would arise in a novel model of binge eating based on daily 10-min access to a sweet fat diet (35% fat kcal, 31% sucrose kcal). Within 2–3 weeks, female Wistar rats developed binge-like intake comparable to levels seen previously for high sucrose diets (~40% of daily caloric intake within 10 min) plus excess weight gain and adiposity, but absent increased anxiety-like behavior during elevated plus-maze or defensive withdrawal tests after diet withdrawal. Binge-like intake was unaffected by pretreatment with the corticotropin-releasing factor type 1 (CRF1) receptor antagonist R121919, and corticosterone responses to restraint stress did not differ between sweet-fat binge rats and chow-fed controls. In contrast, pretreatment with the cannabinoid type 1 (CB1) receptor antagonist SR147778 dose-dependently reduced binge-like intake, albeit less effectively than in ad lib chow or sweet fat controls. A priming dose of the sweet fat diet did not precipitate increased anxiety-like behavior, but rather increased plus-maze locomotor activity. The results suggest that CB1-dependent positive reinforcement rather than CRF1-dependent negative reinforcement mechanisms predominantly maintain excessive intake in this limited access model of sweet-fat diet binges. PMID:22776620

The Co-occurring Use and Misuse of Cannabis and Tobacco: A Review

PubMed Central

Agrawal, Arpana; Budney, Alan J.; Lynskey, Michael T.

2012-01-01

Aims Cannabis and tobacco use and misuse frequently co-occur. This review examines the epidemiological evidence supporting the lifetime co-occurrence of cannabis and tobacco use and outlines the mechanisms that link these drugs to each other. Mechanisms include (a) shared genetic factors; (b) shared environmental influences, including (c) route of administration (via smoking), (d) co-administration and (e) models of co-use. We also discuss respiratory harms associated with co-use of cannabis and tobacco, overlapping withdrawal syndromes and outline treatment implications for cooccurring use. Methods Selective review of published studies. Results Both cannabis and tobacco use and misuse are influenced by genetic factors and a proportion of these genetic factors influence both cannabis and tobacco use and misuse. Environmental factors such as availability play an important role, with economic models suggesting a complementary relationship where increases in price of one drug decrease the use of the other. Route of administration and smoking cues may contribute to their sustained use. Similar withdrawal syndromes, with many symptoms in common, may have important treatment implications. Emerging evidence suggests that dual abstinence may predict better cessation outcomes, yet empirically researched treatments tailored for co-occurring use are lacking. Conclusion There is accumulating evidence that some mechanisms linking cannabis and tobacco use are distinct from those contributing to co-occurring use of drugs in general. There is an urgent need for research to identify the underlying mechanisms and harness their potential etiological implications to tailor treatment options for this serious public health challenge. PMID:22300456

Confirming the Multidimensionality of Psychologically Controlling Parenting among Chinese-American Mothers: Love Withdrawal, Guilt Induction, and Shaming.

PubMed

Cheah, Charissa; Yu, Jing; Hart, Craig; Sun, Shuyan; Olsen, Joseph

2015-05-01

Despite the theoretical conceptualization of parental psychological control as a multidimensional construct, the majority of previous studies have examined psychological control as a unidimensional scale. Moreover, the conceptualization of shaming and its associations with love withdrawal and guilt induction are unclear. The current study aimed to fill these gaps by evaluating the latent factor structure underlying 18 items from Olsen et al. (2002) that were conceptually relevant to love withdrawal, guilt induction, and shaming practices in a sample of 169 mothers of Chinese-American preschoolers. A multidimensional three-factor model and bi-factor model were specified based on our formulated operational definitions for the three dimensions of psychological control. Both models were found to be superior to the unidimensional model. In addition, results from the bi-factor model and an additional second-order factor model indicated that psychological control is essentially empirically isomorphic with guilt induction. Although love withdrawal and shaming factors were also fairly strong indicators of psychological control, each exhibited important additional unique variability and mutual distinctiveness. Implications for the conceptualization of love withdrawal, guilt induction, and shaming as well as directions for future studies are discussed.

Confirming the Multidimensionality of Psychologically Controlling Parenting among Chinese-American Mothers: Love Withdrawal, Guilt Induction, and Shaming

PubMed Central

Cheah, Charissa; Yu, Jing; Hart, Craig; Sun, Shuyan; Olsen, Joseph

2014-01-01

Despite the theoretical conceptualization of parental psychological control as a multidimensional construct, the majority of previous studies have examined psychological control as a unidimensional scale. Moreover, the conceptualization of shaming and its associations with love withdrawal and guilt induction are unclear. The current study aimed to fill these gaps by evaluating the latent factor structure underlying 18 items from Olsen et al. (2002) that were conceptually relevant to love withdrawal, guilt induction, and shaming practices in a sample of 169 mothers of Chinese-American preschoolers. A multidimensional three-factor model and bi-factor model were specified based on our formulated operational definitions for the three dimensions of psychological control. Both models were found to be superior to the unidimensional model. In addition, results from the bi-factor model and an additional second-order factor model indicated that psychological control is essentially empirically isomorphic with guilt induction. Although love withdrawal and shaming factors were also fairly strong indicators of psychological control, each exhibited important additional unique variability and mutual distinctiveness. Implications for the conceptualization of love withdrawal, guilt induction, and shaming as well as directions for future studies are discussed. PMID:26052168

Assessing social isolation in motor neurone disease: a Rasch analysis of the MND Social Withdrawal Scale.

PubMed

Gibbons, Chris J; Thornton, Everard W; Ealing, John; Shaw, Pamela J; Talbot, Kevin; Tennant, Alan; Young, Carolyn A

2013-11-15

Social withdrawal is described as the condition in which an individual experiences a desire to make social contact, but is unable to satisfy that desire. It is an important issue for patients with motor neurone disease who are likely to experience severe physical impairment. This study aims to reassess the psychometric and scaling properties of the MND Social Withdrawal Scale (MND-SWS) domains and examine the feasibility of a summary scale, by applying scale data to the Rasch model. The MND Social Withdrawal Scale was administered to 298 patients with a diagnosis of MND, alongside the Hospital Anxiety and Depression Scale. The factor structure of the MND Social Withdrawal Scale was assessed using confirmatory factor analysis. Model fit, category threshold analysis, differential item functioning (DIF), dimensionality and local dependency were evaluated. Factor analysis confirmed the suitability of the four-factor solution suggested by the original authors. Mokken scale analysis suggested the removal of item five. Rasch analysis removed a further three items; from the Community (one item) and Emotional (two items) withdrawal subscales. Following item reduction, each scale exhibited excellent fit to the Rasch model. A 14-item Summary scale was shown to fit the Rasch model after subtesting the items into three subtests corresponding to the Community, Family and Emotional subscales, indicating that items from these three subscales could be summed together to create a total measure for social withdrawal. Removal of four items from the Social Withdrawal Scale led to a four factor solution with a 14-item hierarchical Summary scale that were all unidimensional, free for DIF and well fitted to the Rasch model. The scale is reliable and allows clinicians and researchers to measure social withdrawal in MND along a unidimensional construct. © 2013. Published by Elsevier B.V. All rights reserved.

Nicotine withdrawal-induced inattention is absent in alpha7 nAChR knockout mice

PubMed Central

Higa, K. K.; Grim, A.; Kamenski, M. E.; van Enkhuizen, J.; Zhou, X.; Li, K.; Naviaux, J. C.; Wang, L.; Naviaux, R. K.; Geyer, M. A.; Markou, A.; Young, J. W.

2017-01-01

Rationale Smoking is the leading cause of preventable death in the U.S., but quit attempts result in withdrawal-induced cognitive dysfunction and predicts relapse. Greater understanding of the neural mechanism(s) underlying these cognitive deficits is required to develop targeted treatments to aid quit attempts. Objectives We examined nicotine withdrawal-induced inattention in mice lacking the α7 nicotinic acetylcholine receptor (nAChR) using the 5-choice continuous performance test (5C-CPT). Methods Mice were trained in the 5C-CPT prior to osmotic minipump implantation containing saline or nicotine. Experiment 1 used 40 mg/kg/day nicotine treatment and tested C57BL/6 mice 4, 28, and 52 h after pump removal. Experiment 2 used 14 and 40 mg/kg/day nicotine treatment in α7 nAChR knockout (KO) and wildtype (WT) littermates tested 4 h after pump removal. Subsets of WT mice were sacrificed before and after pump removal to assess changes in receptor expression associated with nicotine administration and withdrawal. Results Nicotine withdrawal impaired attention in the 5C-CPT, driven by response inhibition and target detection deficits. The overall attentional deficit was absent in α7 nAChR KO mice despite response disinhibition in these mice. Synaptosomal glutamate mGluR5 and dopamine D4 receptor expression were reduced during chronic nicotine but increased during withdrawal, potentially contributing to cognitive deficits. Conclusions The α7 nAChR may underlie nicotine withdrawal-induced deficits in target detection but is not required for response disinhibition deficits. Alterations to the glutamatergic and dopaminergic pathways may also contribute to withdrawal-induced attentional deficits, providing novel targets to alleviate the cognitive symptoms of withdrawal during quit attempts. PMID:28243714

Simulation of ground-water flow and delineation of areas contributing recharge within the Mt. Simon-Hinckley Aquifer to well fields in the Prairie Island Indian Community, Minnesota

USGS Publications Warehouse

Ruhl, J.F.

2002-01-01

A steady state single layer, two-dimensional ground-water flow model constructed with the computer program MODFLOW,combined with the particle-tracking computer program MODPATH, was used to track water particles (upgradient) from the two well fields. A withdrawal rate of 625 m3/d was simulated for each well field. The ground-water flow paths delineated areas of contributing recharge that are 0.38 and 0.65 km2 based on 10- and 50-year travel times, respectively. The flow paths that define these areas extend for maximum distances of about 350 and 450 m, respectively, from the wells. At well field A the area of contributing recharge was delineated for each well as separate withdrawal points. At well field B the area of contributing recharge was delineated for the two wells as a single withdrawal point. Delineation of areas of contributing recharge to the well fields from land surface would require construction of a multi-layer ground-water flow model.

Indicators of streamflow alteration, habitat fragmentation, impervious cover, and water quality for Massachusetts stream basins

USGS Publications Warehouse

Weiskel, Peter K.; Brandt, Sara L.; DeSimone, Leslie A.; Ostiguy, Lance J.; Archfield, Stacey A.

2010-01-01

Massachusetts streams and stream basins have been subjected to a wide variety of human alterations since colonial times. These alterations include water withdrawals, treated wastewater discharges, construction of onsite septic systems and dams, forest clearing, and urbanization—all of which have the potential to affect streamflow regimes, water quality, and habitat integrity for fish and other aquatic biota. Indicators were developed to characterize these types of potential alteration for subbasins and groundwater contributing areas in Massachusetts. The potential alteration of streamflow by the combined effects of withdrawals and discharges was assessed under two water-use scenarios. Water-use scenario 1 incorporated publicly reported groundwater withdrawals and discharges, direct withdrawals from and discharges to streams, and estimated domestic-well withdrawals and septic-system discharges. Surface-water-reservoir withdrawals were excluded from this scenario. Water-use scenario 2 incorporated all the types of withdrawal and discharge included in scenario 1 as well as withdrawals from surface-water reservoirs—all on a long-term, mean annual basis. All withdrawal and discharge data were previously reported to the State for the 2000–2004 period, except domestic-well withdrawals and septic-system discharges, which were estimated for this study. The majority of the state’s subbasins and groundwater contributing areas were estimated to have relatively minor (less than 10 percent) alteration of streamflow under water-use scenario 1 (seasonally varying water use; no surface-water-reservoir withdrawals). However, about 12 percent of subbasins and groundwater contributing areas were estimated to have extensive alteration of streamflows (greater than 40 percent) in August; most of these basins were concentrated in the outer metropolitan Boston region. Potential surcharging of streamflow in August was most commonly indicated for main-stem river subbasins, although surcharging was also indicated for some smaller tributary subbasins. In the high-flow month of April, only 4.8 percent of subbasins and groundwater contributing areas had more than 10 percent potential flow alteration. A majority of the state’s subbasins and groundwater contributing areas were also indicated to have relatively minor alteration of streamflow under water-use scenario 2 (long-term average water use, including surface-water-reservoir withdrawals). Extensive alteration of mean annual flows was estimated for about 6 percent of the state’s subbasins and groundwater contributing areas. The majority of subbasins estimated to have extensive long-term flow alteration contained reservoirs that were specifically designed, constructed, and managed to supply drinking water to cities. Only a small number of subbasins and groundwater contributing areas (1 percent) were extensively surcharged on a long-term, mean annual basis. Because site-specific data concerning surface-water-reservoir storage dynamics and management practices are not available statewide, the seasonal effects of surface-water-reservoir withdrawals on downstream flows could not be assessed in this study. The impounded storage ratio (volume of impounded subbasin or groundwater-contributing-area storage divided by mean annual predevelopment outflow from the subbasin or contributing area, in units of days) indicates the potential for alteration of streamflow, sediment-transport, and temperature regimes by dams, independent of water use. Storage ratios were less than 1 day for 33 percent of the subbasins and groundwater contributing areas, greater than 1 month for about 40 percent of the cases, and greater than 1 year for 3.2 percent of the cases statewide. Dam density, an indicator of stream-habitat fragmentation by dams, averaged 1 dam for every 6.7 stream miles statewide. Many of these dams are not presently (2009) being managed. The highest dam densities were in portions of Worcester County and in the Plymouth-Carver region, respectively, reflecting the historical reliance of Massachusetts industry upon water power and agricultural water-management practices in southeastern Massachusetts. Impervious cover is a frequently used indicator of urban land use. About 33 percent of the state’s 1,429 subbasins and groundwater contributing areas are relatively undeveloped at the local scale, with a local impervious cover of less than 4 percent. About 18 percent of Massachusetts subbasins and contributing areas are highly developed, with a local impervious cover greater than 16 percent. The remaining 49 percent of subbasins and contributing areas have levels of urban development between these extremes (4 to 16 percent local impervious cover). Cumulative impervious cover, defined for the entire upstream area encompassed by each subbasin, shows a smaller range (0 to 55 percent) than local impervious cover. Both local and cumulative impervious cover were highest in metropolitan Boston and other urban centers. High elevated impervious-cover values were also found along major transportation corridors. The water-quality status of Massachusetts streams is assessed periodically by the Massachusetts Department of Environmental Protection pursuant to the requirements of the Federal Clean Water Act. Streams selected for assessment are commonly located in larger subbasins where some degree of impairment is expected. In the 72 percent of the state’s subbasins and groundwater contributing areas with assessed streams in 2002, more than 50 percent of the assessed stream miles were considered impaired. All of the assessed stream miles were considered impaired in 66 percent of the subbasins and groundwater contributing areas with assessed streams. Large streams, such as the main stems of rivers that make up most of the assessed stream miles, also are in many cases the receiving waters for treated wastewater discharges and for this reason may be more susceptible to water-quality impairments than smaller streams. Subbasins and contributing areas with large fractions of assessed stream miles that are listed as impaired are distributed across the state, but are more prevalent in eastern Massachusetts.

Similar precipitated withdrawal effects on intracranial self-stimulation during chronic infusion of an e-cigarette liquid or nicotine alone.

PubMed

Harris, A C; Muelken, P; Smethells, J R; Krueger, M; LeSage, M G

2017-10-01

The FDA recently extended their regulatory authority to electronic cigarettes (ECs). Because the abuse liability of ECs is a leading concern of the FDA, animal models are urgently needed to identify factors that influence the relative abuse liability of these products. The ability of tobacco products to induce nicotine dependence, defined by the emergence of anhedonia and other symptoms of nicotine withdrawal following cessation of their use, contributes to tobacco abuse liability. The present study compared the severity of precipitated withdrawal during chronic infusion of nicotine alone or nicotine-dose equivalent concentrations of three different EC refill liquids in rats, as indicated by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Because these EC liquids contain constituents that may enhance their abuse liability (e.g., minor alkaloids), we hypothesized that they would be associated with greater withdrawal effects than nicotine alone. Results indicated that the nicotinic acetylcholine receptor antagonist mecamylamine precipitated elevations in ICSS thresholds in rats receiving a chronic infusion of nicotine alone or EC liquids (3.2mg/kg/day, via osmotic pump). Magnitude of this effect did not differ between formulations. Our findings indicate that nicotine alone is the primary CNS determinant of the ability of ECs to engender dependence. Combined with our previous findings that nicotine alone and these EC liquids do not differ in other preclinical addiction models, these data suggest that product standards set by the FDA to reduce EC abuse liability should primarily target nicotine, other constituents with peripheral sensory effects (e.g. flavorants), and factors that influence product appeal (e.g., marketing). Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of marijuana relapse in the human laboratory: robust impact of tobacco cigarette smoking status.

PubMed

Haney, Margaret; Bedi, Gillinder; Cooper, Ziva D; Glass, Andrew; Vosburg, Suzanne K; Comer, Sandra D; Foltin, Richard W

2013-02-01

Few marijuana smokers in treatment achieve sustained abstinence, yet factors contributing to high relapse rates are unknown. Study 1: data from five inpatient laboratory studies assessing marijuana intoxication, withdrawal, and relapse were combined to assess factors predicting the likelihood and severity of relapse. Daily, nontreatment-seeking marijuana smokers (n = 51; 10 ± 5 marijuana cigarettes/day) were enrolled. Study 2: to isolate the effects of cigarette smoking, marijuana intoxication, withdrawal, and relapse were assessed in daily marijuana and cigarette smokers (n = 15) under two within-subject, counter-balanced conditions: while smoking tobacco cigarettes as usual (SAU), and after at least 5 days without cigarettes (Quit). Study 1: 49% of participants relapsed the first day active marijuana became available. Tobacco cigarette smokers (75%), who were not abstaining from cigarettes, were far more likely to relapse than non-cigarette smokers (odds ratio: 19, p < .01). Individuals experiencing more positive subjective effects (i.e., feeling "high") after marijuana administration and those with more negative affect and sleep disruption during marijuana withdrawal were more likely to have severe relapse episodes (p < .05). Study 2: most participants (>87%) relapsed to marijuana whether in the SAU or Quit phase. Tobacco cigarette smoking did not significantly influence relapse, nor did it affect marijuana intoxication or most symptoms of withdrawal relative to tobacco cessation. Daily marijuana smokers who also smoke cigarettes have high rates of marijuana relapse, and cigarette smoking versus recent abstinence does not directly influence this association. These data indicate that current cigarette smoking is a clinically important marker for increased risk of marijuana relapse. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Withdrawal: Expanding a Key Addiction Construct

PubMed Central

2015-01-01

Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. PMID:25744958

Age-dependent differences in nicotine reward and withdrawal in female mice.

PubMed

Kota, D; Martin, B R; Damaj, M I

2008-06-01

Adolescent smoking is an increasing epidemic in the US. Research has shown that the commencement of smoking at a young age increases addiction and decreases the probability of successful cessation; however, limited work has focused on nicotine dependence in the female. The goal of the present study was to identify the biological and behavioral factors that may contribute to nicotine's increased abuse liability in female adolescents using animal models of nicotine dependence. Early adolescent (PND 28) and adult (PND 70) female mice were compared in various aspects of nicotine dependence using reward and withdrawal models following sub-chronic nicotine exposure. Furthermore, in vivo acute sensitivity and tolerance to nicotine were examined. In the conditioned place preference model, adolescents demonstrated a significant preference at 0.5 mg/kg nicotine, an inactive dose in adults. Adults found higher doses (0.7 and 1.0 mg/kg) of nicotine to elicit rewarding effects. Furthermore, adolescents displayed increased physical, but not affective, withdrawal signs in three models. Upon acute exposure to nicotine, adolescent mice showed increased sensitivity in an analgesic measure as well as hypothermia. After chronic nicotine exposure, both adults and adolescents displayed tolerance to nicotine with adolescents having a lower degree of tolerance to changes in body temperature. These data indicate that differences in nicotine's rewarding and aversive effects may contribute to variations in certain components of nicotine dependence between adult and adolescent female mice. Furthermore, this implies that smoking cessation therapies may not be equally effective across all ages.

Parental views on withdrawing life-sustaining therapies in critically ill children.

PubMed

Michelson, Kelly Nicole; Koogler, Tracy; Sullivan, Christine; Ortega, María del Pilar; Hall, Emily; Frader, Joel

2009-11-01

To broaden existing knowledge of pediatric end-of-life decision making by exploring factors described by parents of patients in the pediatric intensive care unit (PICU) as important/influential if they were to consider withdrawing life-sustaining therapies. Quantitative and qualitative analysis of semi-structured one-on-one interviews. The PICUs at 2 tertiary care hospitals. English- or Spanish-speaking parents who were older than 17 years and whose child was admitted to the PICU for more than 24 hours to up to 1 week. Semi-structured one-on-one interviews. Forty of 70 parents (57%) interviewed said they could imagine a situation in which they would consider withdrawing life-sustaining therapies. When asked if specific factors might influence their decision making, 64% of parents said they would consider withdrawing life-sustaining therapies if their child were suffering; 51% would make such a decision based on quality-of-life considerations; 43% acknowledged the influence of physician-estimated prognosis in their decision; and 7% said financial burden would affect their consideration. Qualitative analysis of their subsequent comments identified 9 factors influential to parents when considering withdrawing life-sustaining therapies: quality of life, suffering, ineffective treatments, faith, time, financial considerations, general rejection of withdrawing life-sustaining therapies, mistrust/doubt toward physicians, and reliance on self/intuition. Parents describe a broad range of views regarding possible consideration of withdrawing life-sustaining therapies for their children and what factors might influence such a decision.

Parental Views on Withdrawing Life-Sustaining Therapies in Critically Ill Children

PubMed Central

Michelson, Kelly Nicole; Koogler, Tracy; Sullivan, Christine; del Pilar Ortega, María; Hall, Emily; Frader, Joel

2009-01-01

Objective To broaden existing knowledge of pediatric end-of-life decision making by exploring factors described by parents of patients in the pediatric intensive care unit (PICU) as important/influential if they were to consider withdrawing life-sustaining therapies. Design Quantitative and qualitative analysis of semi-structured one-on-one interviews. Setting The PICUs at 2 tertiary care hospitals. Participants English- or Spanish-speaking parents who were older than 17 years and whose child was admitted to the PICU for more than 24 hours to up to 1 week. Intervention Semi-structured one-on-one interviews. Results Forty of 70 parents (57%) interviewed said they could imagine a situation in which they would consider withdrawing life-sustaining therapies. When asked if specific factors might influence their decision making, 64% of parents said they would consider withdrawing life-sustaining therapies if their child were suffering; 51% would make such a decision based on quality-of-life considerations; 43% acknowledged the influence of physician-estimated prognosis in their decision; and 7% said financial burden would affect their consideration. Qualitative analysis of their subsequent comments identified 9 factors influential to parents when considering withdrawing life-sustaining therapies: quality of life, suffering, ineffective treatments, faith, time, financial considerations, general rejection of withdrawing life-sustaining therapies, mistrust/doubt toward physicians, and reliance on self/intuition. Conclusion Parents describe a broad range of views regarding possible consideration of withdrawing life-sustaining therapies for their children and what factors might influence such a decision. PMID:19884588

Youth social withdrawal behavior (hikikomori): A systematic review of qualitative and quantitative studies.

PubMed

Li, Tim M H; Wong, Paul W C

2015-07-01

Acute and/or severe social withdrawal behavior among youth was seen as a culture-bound psychiatric syndrome in Japan, but more youth social withdrawal cases in different countries have been discovered recently. However, due to the lack of a formal definition and diagnostic tool for youth social withdrawal, cross-cultural observational and intervention studies are limited. We aimed to consolidate existing knowledge in order to understand youth social withdrawal from diverse perspectives and suggest different interventions for different trajectories of youth social withdrawal. This review examined the current available scientific information on youth social withdrawal in the academic databases: ProQuest, ScienceDirect, Web of Science and PubMed. We included quantitative and qualitative studies of socially withdrawn youths published in English and academic peer-reviewed journals. We synthesized the information into the following categories: (1) definitions of youth social withdrawal, (2) developmental theories, (3) factors associated with youth social withdrawal and (4) interventions for socially withdrawn youths. Accordingly, there are diverse and controversial definitions for youth social withdrawal. Studies of youth social withdrawal are based on models that lead to quite different conclusions. Researchers with an attachment perspective view youth social withdrawal as a negative phenomenon, whereas those who adopt Erikson's developmental theory view it more positively as a process of seeking self-knowledge. Different interventions for socially withdrawn youths have been developed, mainly in Japan, but evidence-based practice is almost non-existent. We propose a theoretical framework that views youth social withdrawal as resulting from the interplay between psychological, social and behavioral factors. Future validation of the framework will help drive forward advances in theory and interventions for youth social withdrawal as an emerging issue in developed countries. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Acute Morphine, Chronic Morphine, and Morphine Withdrawal Differently Affect Pleiotrophin, Midkine, and Receptor Protein Tyrosine Phosphatase β/ζ Regulation in the Ventral Tegmental Area.

PubMed

García-Pérez, Daniel; Laorden, M Luisa; Milanés, M Victoria

2017-01-01

Pleiotrophin (PTN) and midkine (MK) are secreted growth factors and cytokines, proposed to be significant neuromodulators with multiple neuronal functions. PTN and MK are generally related with cell proliferation, growth, and differentiation by acting through different receptors. PTN or MK, signaling through receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), lead to the activation of extracellular signal-regulated kinases (ERKs) and thymoma viral proto-oncogene (Akt), which induce morphological changes and modulate addictive behaviors. Besides, there is increasing evidence that during the development of drug addiction, astrocytes contribute to the synaptic plasticity by synthesizing and releasing substances such as cytokines. In the present work, we studied the effect of acute morphine, chronic morphine, and morphine withdrawal on PTN, MK, and RPTPβ/ζ expression and on their signaling pathways in the ventral tegmental area (VTA). Present results indicated that PTN, MK, and RPTPβ/ζ levels increased after acute morphine injection, returned to basal levels during chronic opioid treatment, and were upregulated again during morphine withdrawal. We also observed an activation of astrocytes after acute morphine injection and during opiate dependence and withdrawal. In addition, immunofluorescence analysis revealed that PTN, but not MK, was overexpressed in astrocytes and that dopaminergic neurons expressed RPTPβ/ζ. Interestingly, p-ERK 1/2 levels during chronic morphine and morphine withdrawal correlated RPTPβ/ζ expression. All these observations suggest that the neuroprotective and behavioral adaptations that occur during opiate addiction could be, at least partly, mediated by these cytokines.

Association of testosterone and BDNF serum levels with craving during alcohol withdrawal.

PubMed

Heberlein, Annemarie; Lenz, Bernd; Opfermann, Birgitt; Gröschl, Michael; Janke, Eva; Stange, Katrin; Groh, Adrian; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas

2016-08-01

Preclinical and clinical studies show associations between testosterone and brain-derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone have been independently reported to influence alcohol consumption. Therefore, we aimed to investigate a possible interplay of testosterone and BDNF contributing to alcohol dependence. Regarding possible interplay of testosterone and BDNF and the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum levels in our research. We investigated testosterone and BDNF serum levels in a sample of 99 male alcohol-dependent patients during alcohol withdrawal (day 1, 7, and 14) and compared them to a healthy male control group (n = 17). The testosterone serum levels were significantly (p < 0.001) higher in the patients' group than in the control group and decreased significantly during alcohol withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol withdrawal (days 1-7) was significantly associated with the BDNF serum levels (day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels (putatively mirroring high HPA activity), we found a significant association of BDNF and testosterone as well as with alcohol craving measured by the Obsessive and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of BDNF and testosterone serum levels, which may be relevant for the symptomatology of alcohol dependence. Further studies are needed to clarify our results. Copyright © 2016 Elsevier Inc. All rights reserved.

Factors That Contribute to a Successful Nursing Student's Decision to Withdraw from a Bachelor of Science in Nursing Program before Graduation

ERIC Educational Resources Information Center

Randall, Shelly

2013-01-01

There is an extreme shortage of registered nurses (RNs) in the United States (U.S.). This shortage is projected to grow to 260,000 RNs by the year 2025 (American Association of Colleges Nursing [AACN], 2010a). In order to meet the current and future health care needs of the population of the U.S., nursing schools would have to graduate at least…

Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity

PubMed Central

Greenberg, Gian D.; Phillips, Tamara J.; Crabbe, John C.

2017-01-01

Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4 g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24 h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10 h of withdrawal in WSR-1 females and to the initial 24 h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity. PMID:27503811

Parental Expression of Disappointment: Should It Be a Factor in Hoffman's Model of Parental Discipline?

ERIC Educational Resources Information Center

Patrick, Renee B.; Gibbs, John C.

2007-01-01

The authors addressed whether parental expression of disappointment should be included as a distinct factor in M. L. Hoffman's (2000) well-established typology of parenting styles (induction, love withdrawal, power assertion). Hoffman's 3-factor model, along with a more inclusive 4-factor model (induction, love withdrawal, power assertion, and…

New mechanisms and perspectives in nicotine withdrawal

PubMed Central

Jackson, K.J.; Muldoon, P.P.; De Biasi, M.; Damaj, M.I.

2014-01-01

Diseases associated with tobacco use constitute a major health problem worldwide. Upon cessation of tobacco use, an unpleasant withdrawal syndrome occurs in dependent individuals. Avoidance of the negative state produced by nicotine withdrawal represents a motivational component that promotes continued tobacco use and relapse after smoking cessation. With the modest success rate of currently available smoking cessation therapies, understanding mechanisms involved in the nicotine withdrawal syndrome are crucial for developing successful treatments. Animal models provide a useful tool for examining neuroadaptative mechanisms and factors influencing nicotine withdrawal, including sex, age, and genetic factors. Such research has also identified an important role for nicotinic receptor subtypes in different aspects of the nicotine withdrawal syndrome (e.g., physical vs. affective signs). In addition to nicotinic receptors, the opioid and endocannabinoid systems, various signal transduction pathways, neurotransmitters, and neuropeptides have been implicated in the nicotine withdrawal syndrome. Animal studies have informed human studies of genetic variants and potential targets for smoking cessation therapies. Overall, the available literature indicates that the nicotine withdrawal syndrome is complex, and involves a range of neurobiological mechanisms. As research in nicotine withdrawal progresses, new pharmacological options for smokers attempting to quit can be identified, and treatments with fewer side effects that are better tailored to the unique characteristics of patients may become available. PMID:25433149

Adolescent personality factors in self-ratings and peer nominations and their prediction of peer acceptance and peer rejection.

PubMed

Scholte, R H; van Aken, M A; van Lieshout, C F

1997-12-01

In this study, the robustness of the Big Five personality factors in adolescents' self-ratings and peer nominations was investigated. Data were obtained on 2,001 adolescents attending secondary school (885 girls; 1,116 boys; M age = 14.5 years). Exploratory and confirmatory factor analyses on the self-ratings confirmed the Big Five personality factors. In contrast, exploratory analysis on the peer nominations revealed five different factors: Aggression-Inattentiveness, Achievement-Withdrawal, Self-Confidence, Sociability, and Emotionality-Nervousness. It is suggested that peers evaluate group members not in terms of their personality but in terms of their group reputation. Peer evaluations contributed substantially to the prediction of peer acceptance and rejection; the Big Five personality factors based on self-ratings did not.

Risk factors associated with iatrogenic opioid and benzodiazepine withdrawal in critically ill pediatric patients: a systematic review and conceptual model.

PubMed

Best, Kaitlin M; Boullata, Joseph I; Curley, Martha A Q

2015-02-01

Analgesia and sedation are common therapies in pediatric critical care, and rapid titration of these medications is associated with iatrogenic withdrawal syndrome. We performed a systematic review of the literature to identify all common and salient risk factors associated with iatrogenic withdrawal syndrome and build a conceptual model of iatrogenic withdrawal syndrome risk in critically ill pediatric patients. Multiple databases, including PubMed/Medline, EMBASE, CINAHL, and the Cochrane Central Registry of Clinical Trials, were searched using relevant terms from January 1, 1980, to August 1, 2014. Articles were included if they were published in English and discussed iatrogenic withdrawal syndrome following either opioid or benzodiazepine therapy in children in acute or intensive care settings. Articles were excluded if subjects were neonates born to opioid- or benzodiazepine-dependent mothers, children diagnosed as substance abusers, or subjects with cancer-related pain; if data about opioid or benzodiazepine treatment were not specified; or if primary data were not reported. In total, 1,395 articles were evaluated, 33 of which met the inclusion criteria. To facilitate analysis, all opioid and/or benzodiazepine doses were converted to morphine or midazolam equivalents, respectively. A table of evidence was developed for qualitative analysis of common themes, providing a framework for the construction of a conceptual model. The strongest risk factors associated with iatrogenic withdrawal syndrome include duration of therapy and cumulative dose. Additionally, evidence exists linking patient, process, and system factors in the development of iatrogenic withdrawal syndrome. Most articles were prospective observational or interventional studies. Given the state of existing evidence, well-designed prospective studies are required to better characterize iatrogenic withdrawal syndrome in critically ill pediatric patients. This review provides data to support the construction of a conceptual model of iatrogenic withdrawal syndrome risk that, if supported, could be useful in guiding future research.

Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity.

PubMed

Greenberg, Gian D; Phillips, Tamara J; Crabbe, John C

2016-10-15

Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10h of withdrawal in WSR-1 females and to the initial 24h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity. Published by Elsevier Inc.

7 CFR 3560.304 - Initial operating capital.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Financial Management § 3560.304 Initial operating... of 12 months prior to the withdrawal request; (4) The withdrawal will not affect the financial viability of the housing project; (5) Contributions to the reserve account are at authorized levels; (6) The...

Parental expression of disappointment: should it be a factor in Hoffman's model of parental discipline?

PubMed

Patrick, Renee B; Gibbs, John C

2007-06-01

The authors addressed whether parental expression of disappointment should be included as a distinct factor in M. L. Hoffman's well-established typology of parenting styles (induction, love withdrawal, power assertion). Hoffman's 3-factor model, along with a more inclusive 4-factor model (induction, love withdrawal, power assertion, and expressions of disappointment), were respectively evaluated in exploratory factor analyses. The analysis utilized extant data comprised of responses by children (N = 73) and their mothers (N = 67) to an adaptation of M. L. Hoffman and H. D. Saltzstein's parental discipline measure. The findings supported Hoffman's original model. Disappointment may be reducible to love withdrawal or induction, although disappointment may be a more appropriate induction for adolescents.

[An examination of the determinants of social withdrawal and affinity for social withdrawal].

PubMed

Watanabe, Asami; Matsui, Yutaka; Takatsuka, Yusuke

2010-12-01

This study examined the determinants of social withdrawal using data from a survey by the Tokyo Metropolitan Government Office for Youth Affairs and Public Safety (2008). In addition, this study identified young people who showed an affinity for social withdrawal although they were not in a state of withdrawal, and examined the determinants of an affinity for social withdrawal. The results of stepwise discriminant analysis showed that factors such as social phobia, depression, violence, and emotional bonds with family differentiated between the general youth group and the social withdrawal group and the "affinity group". Social phobia, violence, and refusal to be interfered in self-decision making differentiated between the social withdrawal group and the "affinity group". This study shows that an "affinity group" should be cared as well as an actual withdrawal group.

Withdrawal: Expanding a Key Addiction Construct.

PubMed

Piper, Megan E

2015-12-01

Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Trajectories of Social Withdrawal from Middle Childhood to Early Adolescence

ERIC Educational Resources Information Center

Oh, Wonjung; Rubin, Kenneth H.; Bowker, Julie C.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

2008-01-01

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in…

A Review of Operational Water Consumption and Withdrawal Factors for Electricity Generating Technologies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macknick, Jordan; Newmark, Robin; Heath, Garvin

2011-03-01

This report provides estimates of operational water withdrawal and water consumption factors for electricity generating technologies in the United States. Estimates of water factors were collected from published primary literature and were not modified except for unit conversions. The presented water factors may be useful in modeling and policy analyses where reliable power plant level data are not available.

Motor impairment: a new ethanol withdrawal phenotype in mice

PubMed Central

Philibin, Scott D.; Cameron, Andy J.; Metten, Pamela; Crabbe, John C.

2015-01-01

Alcoholism is a complex disorder with genetic and environmental risk factors. The presence of withdrawal symptoms is one criterion for alcohol dependence. Genetic animal models have followed a reductionist approach by quantifying various effects of ethanol withdrawal separately. Different ethanol withdrawal symptoms may have distinct genetic etiologies, and therefore differentiating distinct neurobiological mechanisms related to separate signs of withdrawal would increase our understanding of various aspects of the complex phenotype. This study establishes motor incoordination as a new phenotype of alcohol withdrawal in mice. Mice were made physically dependent on ethanol by exposure to ethanol vapor for 72 h. The effects of ethanol withdrawal in mice from different genetic backgrounds were measured on the accelerating rotarod, a simple motor task. Ethanol withdrawal disrupted accelerating rotarod behavior in mice. The disruptive effects of withdrawal suggest a performance rather than a learning deficit. Inbred strain comparisons suggest genetic differences in magnitude of this withdrawal phenotype. The withdrawal-induced deficits were not correlated with the selection response difference in handling convulsion severity in selectively bred Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant lines. The accelerating rotarod seems to be a simple behavioral measure of ethanol withdrawal that is suitable for comparing genotypes. PMID:18690115

Long-term trend analysis of reservoir water quality and quantity at the landscape scale in two major river basins of Texas, USA.

USGS Publications Warehouse

Patino, Reynaldo; Asquith, William H.; VanLandeghem, Matthew M.; Dawson, D.

2016-01-01

Trends in water quality and quantity were assessed for 11 major reservoirs of the Brazos and Colorado river basins in the southern Great Plains (maximum period of record, 1965–2010). Water quality, major contributing-stream inflow, storage, local precipitation, and basin-wide total water withdrawals were analyzed. Inflow and storage decreased and total phosphorus increased in most reservoirs. The overall, warmest-, or coldest-monthly temperatures increased in 7 reservoirs, decreased in 1 reservoir, and did not significantly change in 3 reservoirs. The most common monotonic trend in salinity-related variables (specific conductance, chloride, sulfate) was one of no change, and when significant change occurred, it was inconsistent among reservoirs. No significant change was detected in monthly sums of local precipitation. Annual water withdrawals increased in both basins, but the increase was significant (P < 0.05) only in the Colorado River and marginally significant (P < 0.1) in the Brazos River. Salinity-related variables dominated spatial variability in water quality data due to the presence of high- and low-salinity reservoirs in both basins. These observations present a landscape in the Brazos and Colorado river basins where, in the last ∼40 years, reservoir inflow and storage generally decreased, eutrophication generally increased, and water temperature generally increased in at least 1 of 3 temperature indicators evaluated. Because local precipitation remained generally stable, observed reductions in reservoir inflow and storage during the study period may be attributable to other proximate factors, including increased water withdrawals (at least in the Colorado River basin) or decreased runoff from contributing watersheds.

Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

García-Carmona, Juan-Antonio; Martínez-Laorden, Elena; Milanés, María-Victoria

There is large body evidence indicating that stress can lead to cardiovascular disease. However, the exact brain areas and the mechanisms involved remain to be revealed. Here, we performed a series of experiments to characterize the role of CRF1 receptor (CRF1R) in the stress response induced by naloxone-precipitated morphine withdrawal. The experiments were performed in the hypothalamic paraventricular nucleus (PVN) ventrolateral medulla (VLM), brain regions involved in the regulation of cardiovascular activity, and in the right ventricle by using genetically engineered mice lacking functional CRF1R levels (KO). Mice were treated with increasing doses of morphine and withdrawal was precipitated bymore » naloxone administration. Noradrenaline (NA) turnover, c-Fos, expression, PKA and TH phosphorylated at serine 40, was evaluated by high-performance liquid chromatography (HPLC), immunohistochemistry and immunoblotting. Morphine withdrawal induced an enhancement of NA turnover in PVN in parallel with an increase in TH neurons expressing c-Fos in VLM in wild-type mice. In addition we have demonstrated an increase in NA turnover, TH phosphorylated at serine 40 and PKA levels in heart. The main finding of the present study was that NA turnover, TH positive neurons that express c-Fos, TH phosphorylated at serine 40 and PKA expression observed during morphine withdrawal were significantly inhibited in CRF1R KO mice. Our results demonstrate that CRF/CRF1R activation may contribute to the adaptive changes induced by naloxone-precipitated withdrawal in the heart and in the brain areas which modulate the cardiac sympathetic function and suggest that CRF/CRF1R pathways could be contributing to cardiovascular disease associated to opioid addiction. - Highlights: • Naloxone-precipitated morphine withdrawal increases sympathetic activity in the PVN and heart. • Co-localization of TH phosphorylated at serine 40/c-Fos in the VLM after morphine withdrawal • Naloxone-precipitated morphine withdrawal increases PKA expression in the heart. • CRF1 receptor is implicated in the sympathetic activity induced by morphine withdrawal.« less

Sex Differences in the Contribution of Respiratory Sinus Arrhythmia and Trauma to Children's Psychopathology.

PubMed

Gray, Sarah A O; Theall, Katherine; Lipschutz, Rebecca; Drury, Stacy

2017-03-01

Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activity, has been shown to moderate the relation between adversity and child behavioral outcomes; however, this work has been conducted in primarily Caucasian samples and limited in focus to family-level adversity. The current analysis extends the previous literature to examine the co-contribution of exposure to potentially traumatic events (PTEs), baseline RSA, and RSA withdrawal to internalizing and externalizing behavior in a sample of primarily African American youth ( n = 92) recruited using neighborhood mapping techniques from communities high in epidemiological indicators of adversity. Exposure to PTEs was associated with lower baseline RSA. Complex interactions were observed between sex of the child, baseline RSA and RSA withdrawal, and PTE exposure predicting to internalizing behaviors. Among girls with high (4+) levels of PTEs, high baseline RSA and RSA withdrawal predicted higher internalizing; for RSA withdrawal only, the inverse was observed for girls with low PTE exposure, for whom high RSA withdrawal predicted lower internalizing. No associations were observed from RSA to externalizing, or among boys to internalizing. Findings are consistent with distinct patterns among primarily African American samples and suggest the need for sex-specific conceptualizations of the link between environmental adversity, physiological reactivity, and internalizing behaviors.

Sex Differences in the Contribution of Respiratory Sinus Arrhythmia and Trauma to Children’s Psychopathology

PubMed Central

Gray, Sarah A. O.; Theall, Katherine; Lipschutz, Rebecca; Drury, Stacy

2016-01-01

Respiratory sinus arrhythmia (RSA), a marker of parasympathetic activity, has been shown to moderate the relation between adversity and child behavioral outcomes; however, this work has been conducted in primarily Caucasian samples and limited in focus to family-level adversity. The current analysis extends the previous literature to examine the co-contribution of exposure to potentially traumatic events (PTEs), baseline RSA, and RSA withdrawal to internalizing and externalizing behavior in a sample of primarily African American youth (n = 92) recruited using neighborhood mapping techniques from communities high in epidemiological indicators of adversity. Exposure to PTEs was associated with lower baseline RSA. Complex interactions were observed between sex of the child, baseline RSA and RSA withdrawal, and PTE exposure predicting to internalizing behaviors. Among girls with high (4+) levels of PTEs, high baseline RSA and RSA withdrawal predicted higher internalizing; for RSA withdrawal only, the inverse was observed for girls with low PTE exposure, for whom high RSA withdrawal predicted lower internalizing. No associations were observed from RSA to externalizing, or among boys to internalizing. Findings are consistent with distinct patterns among primarily African American samples and suggest the need for sex-specific conceptualizations of the link between environmental adversity, physiological reactivity, and internalizing behaviors. PMID:28479668

Confirmatory Factor Analysis of the Minnesota Nicotine Withdrawal Scale

PubMed Central

Toll, Benjamin A.; O’Malley, Stephanie S.; McKee, Sherry A.; Salovey, Peter; Krishnan-Sarin, Suchitra

2008-01-01

The authors examined the factor structure of the Minnesota Nicotine Withdrawal Scale (MNWS) using confirmatory factor analysis in clinical research samples of smokers trying to quit (n = 723). Three confirmatory factor analytic models, based on previous research, were tested with each of the 3 study samples at multiple points in time. A unidimensional model including all 8 MNWS items was found to be the best explanation of the data. This model produced fair to good internal consistency estimates. Additionally, these data revealed that craving should be included in the total score of the MNWS. Factor scores derived from this single-factor, 8-item model showed that increases in withdrawal were associated with poor smoking outcome for 2 of the clinical studies. Confirmatory factor analyses of change scores showed that the MNWS symptoms cohere as a syndrome over time. Future investigators should report a total score using all of the items from the MNWS. PMID:17563141

Development of the caffeine withdrawal symptom questionnaire: caffeine withdrawal symptoms cluster into 7 factors.

PubMed

Juliano, Laura M; Huntley, Edward D; Harrell, Paul T; Westerman, Ashley T

2012-08-01

Habitual caffeine consumers who abstain from caffeine experience withdrawal symptoms such as headache, fatigue, difficulty concentrating, mood disturbances, and flu-like symptoms (Juliano and Griffiths, 2004). The caffeine withdrawal syndrome has been documented across many experimental studies; however, little is known about how withdrawal symptoms co-vary during a discrete episode. Furthermore, a validated measure of caffeine withdrawal is lacking. To develop, evaluate, and reduce a 23-item measure of caffeine withdrawal symptoms; the Caffeine Withdrawal Symptom Questionnaire (CWSQ), to a set of composite variables. Caffeine consumers (N=213) completed the CWSQ after 16h of caffeine abstinence. A subset of participants also completed the CWSQ during a preceding baseline period and/or after double-blind consumption of caffeinated coffee. Principal components analysis resulted in a solution comprised of 7-factors: (1) Fatigue/drowsiness; (2) Low alertness/difficulty concentrating; (3) Mood disturbances; (4) Low sociability/motivation to work; (5) Nausea/upset stomach; (6) Flu-like feelings; and (7) Headache. With the exception of nausea/upset stomach, the CWSQ total score and individual composite scores were significantly greater during caffeine abstinence relative to both baseline and double-blind consumption of caffeinated coffee, thereby demonstrating sensitivity of the measure. Compared to non-daily coffee consumers, daily consumers had greater increases in total withdrawal, fatigue/drowsiness, low alertness/difficulty concentrating, mood disturbances, and headache. Future directions include replication, assessment on a clinical population, and further examination of psychometric properties of the CWSQ. The CWSQ should facilitate the assessment and diagnosis of caffeine withdrawal and increase our knowledge of the caffeine withdrawal syndrome. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A Postpartum Model in Rat: Behavioral and Gene Expression Changes Induced by Ovarian Steroid Deprivation

PubMed Central

Suda, Shiro; Segi-Nishida, Eri; Newton, Samuel S.; Duman, Ronald S.

2013-01-01

Background Postpartum depression (PPD) affects approximately 10% to 20% of women during the first 4 weeks of the postpartum period and is characterized by labile mood with prominent anxiety and irritability, insomnia,and depressive mood. During the postpartum period, elevated ovarian hormones abruptly decrease to the early follicular phase levels that are postulated to play a major role in triggering PPD. However, the underlying neurobiological mechanisms that contribute to PPD have not been determined. Methods In the present study, we examined the effect of ovarian steroids, administered at levels that occur during human pregnancy followed by rapid withdrawal to simulate postpartum conditions, on behavior and gene expression in the rat. Results The results of behavioral testing reveal that the hormone-simulated postpartum treatment results in the development of a phenotype relevant to PPD, including vulnerability for helplessness, increased anxiety, and aggression. Real-time quantitative polymerase chain reaction (PCR) demonstrated transient regulation of several genes, including Ca2+/calmodulin-dependent protein kinase II (CAMKII), serotonin transporter (SERT), myocyte enhancer factor 2A (MEF2A), brain-derived neurotrophic factor (BDNF), gamma-aminobutyric acid type A receptor α4 (GABAARA4), mothers against decapentaplegic homolog 4 (SMAD4), and aquaporin 4 (AQP4) that could underlie these behavioral effects. Conclusions These studies provide an improved understanding of the effects of withdrawal from high doses of ovarian hormones on behavior and gene expression changes in the brain that could contribute to the pathophysiology of PPD. PMID:18471802

Withdrawal Phenomena: A Concept Analysis for the Development of a Nursing Diagnosis.

PubMed

Dändliker, This; Kolbe, Nina

This study explored the concept of withdrawal phenomena from the perspective of nurses, with the aim of developing a nursing diagnosis. Concept analysis was used as the framework of the study, a systematized review was conducted to identify relevant studies, and interpretation was based on qualitative content analysis. Specifying aspects, defining characteristics, related factors, and risk factors were extracted and classified into categories. Thirteen studies were identified as a basis for the construction of two nursing diagnoses: "withdrawal phenomena" and "risk of withdrawal complications." The proposed nursing diagnoses require further discussion. The NANDA International Diagnosis Development Committee was asked to examine the proposed diagnoses. However, it was too early to determine implications for nursing practice based on the results of this study.

Factors Impacting the Likelihood of Student Withdrawals in Core Business Classes

ERIC Educational Resources Information Center

Boldt, David J.; Kassis, Mary M.; Smith, William J.

2017-01-01

The course withdrawal decision includes both monetary and time costs for the student. Institutional costs include the misallocation of scarce seats to noncompleting students. Understanding the course withdrawal decision process can aid advisors and administrators as they seek ways to improve retention and progression. This study uses 21,318 course…

Childhood Social Withdrawal, Interpersonal Impairment, and Young Adult Depression: A Mediational Model

ERIC Educational Resources Information Center

Katz, Shaina J.; Conway, Christopher C.; Hammen, Constance L.; Brennan, Patricia A.; Najmanm, Jake M.

2011-01-01

Building on interpersonal theories of depression, the current study sought to explore whether early childhood social withdrawal serves as a risk factor for depressive symptoms and diagnoses in young adulthood. The researchers hypothesized that social impairment at age 15 would mediate the association between social withdrawal at age 5 and…

Reconstruction of global gridded monthly sectoral water withdrawals for 1971-2010 and analysis of their spatiotemporal patterns

NASA Astrophysics Data System (ADS)

Huang, Zhongwei; Hejazi, Mohamad; Li, Xinya; Tang, Qiuhong; Vernon, Chris; Leng, Guoyong; Liu, Yaling; Döll, Petra; Eisner, Stephanie; Gerten, Dieter; Hanasaki, Naota; Wada, Yoshihide

2018-04-01

Human water withdrawal has increasingly altered the global water cycle in past decades, yet our understanding of its driving forces and patterns is limited. Reported historical estimates of sectoral water withdrawals are often sparse and incomplete, mainly restricted to water withdrawal estimates available at annual and country scales, due to a lack of observations at seasonal and local scales. In this study, through collecting and consolidating various sources of reported data and developing spatial and temporal statistical downscaling algorithms, we reconstruct a global monthly gridded (0.5°) sectoral water withdrawal dataset for the period 1971-2010, which distinguishes six water use sectors, i.e., irrigation, domestic, electricity generation (cooling of thermal power plants), livestock, mining, and manufacturing. Based on the reconstructed dataset, the spatial and temporal patterns of historical water withdrawal are analyzed. Results show that total global water withdrawal has increased significantly during 1971-2010, mainly driven by the increase in irrigation water withdrawal. Regions with high water withdrawal are those densely populated or with large irrigated cropland production, e.g., the United States (US), eastern China, India, and Europe. Seasonally, irrigation water withdrawal in summer for the major crops contributes a large percentage of total annual irrigation water withdrawal in mid- and high-latitude regions, and the dominant season of irrigation water withdrawal is also different across regions. Domestic water withdrawal is mostly characterized by a summer peak, while water withdrawal for electricity generation has a winter peak in high-latitude regions and a summer peak in low-latitude regions. Despite the overall increasing trend, irrigation in the western US and domestic water withdrawal in western Europe exhibit a decreasing trend. Our results highlight the distinct spatial pattern of human water use by sectors at the seasonal and annual timescales. The reconstructed gridded water withdrawal dataset is open access, and can be used for examining issues related to water withdrawals at fine spatial, temporal, and sectoral scales.

Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal

PubMed Central

Kaufling, Jennifer

2015-01-01

Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA–VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA–VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. SIGNIFICANCE STATEMENT Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal. PMID:26180204

Sleep disruption in critically ill patients--pharmacological considerations.

PubMed

Bourne, R S; Mills, G H

2004-04-01

Sleep disturbances are common in critically ill patients and contribute to morbidity. Environmental factors, patient care activities and acute illness are all potential causes of disrupted sleep. Additionally, it is important to consider drug therapy as a contributing factor to this adverse experience, which patients perceive as particularly stressful. Sedative and analgesic combinations used to facilitate mechanical ventilation are among the most sleep disruptive drugs. Cardiovascular, gastric protection, anti-asthma, anti-infective, antidepressant and anticonvulsant drugs have also been reported to cause a variety of sleep disorders. Withdrawal reactions to prescribed and occasionally recreational drugs should also be considered as possible triggers for sleep disruption. Tricyclic antidepressants and benzodiazepines are commonly prescribed in the treatment of sleep disorders, but have problems with decreasing slow wave and rapid eye movement sleep phases. Newer non-benzodiazepine hypnotics offer little practical advantage. Melatonin and atypical antipsychotics require further investigation before their routine use can be recommended.

Extinction of conditioned opiate withdrawal in rats in a two-chambered place conditioning apparatus

PubMed Central

Myers, Karyn M.; Bechtholt-Gompf, Anita J.; Coleman, Brian R.; Carlezon, William A.

2016-01-01

Conditioned opiate withdrawal contributes to relapse in addicts and can be studied in rats using the opiate withdrawal-induced conditioned place aversion (OW-CPA) paradigm. Attenuation of conditioned withdrawal through extinction may be beneficial in the treatment of addiction. Here we describe a protocol for studying OW-CPA extinction using a two-chambered place conditioning apparatus. Rats are made dependent on morphine through subcutaneous implantation of morphine pellets and then trained to acquire OW-CPA through pairings of one chamber with naloxone-precipitated withdrawal and the other chamber with saline. Extinction training consists of re-exposures to both chambers in the absence of precipitated withdrawal. Rats tested following the completion of training show a decline in avoidance of the formerly naloxone-paired chamber with increasing numbers of extinction training sessions. The protocol takes a minimum of seven days; the exact duration varies with the amount of extinction training, which is determined by the goals of the experiment. PMID:22362157

Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal

PubMed Central

Cunningham, Christopher L.; Fidler, Tara L.; Murphy, Kevin V.; Mulgrew, Jennifer A.; Smitasin, Phoebe J.

2012-01-01

Background Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Methods Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; non-dependent controls received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. Results The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7-9 h and returning to baseline within 24 h; withdrawal severity was greater in D2 than in B6 mice (Exp. 1). Post-withdrawal delays in initial ethanol access (1, 3 or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (Exp. 2). The post-withdrawal enhancement of ethanol intake persisted over a 5-d abstinence period in D2 mice (Exp. 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than non-dependent mice (Exp. 4). Conclusions Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. PMID:22999529

Factors associated with poor satisfaction with treatment and trial discontinuation in chronic schizophrenia.

PubMed

Schoemaker, Joep H; Vingerhoets, Ad J J M; Emsley, Robin A

2018-06-05

IntroductionDespite consistently high discontinuation rates due to withdrawal of consent (WOC) and insufficient therapeutic effect (ITE) in schizophrenia trials, insight into the underlying factors contributing to poor satisfaction with treatment and dropout is limited. A better understanding of these factors could help to improve trial design and completion rates. Using data from 1,136 trial participants with schizophrenia or schizoaffective disorder, we explored associations between predictor variables with (1) dropout due to WOC and ITE and (2) satisfaction with treatment among patients and investigators by means of hierarchic multiple regression analyses. ITE was associated with poor clinical improvement, poor investigator satisfaction with treatment, and poor patient insight into their own disease, whereas WOC only showed a meaningful association with poor patient satisfaction with treatment. Investigator satisfaction with treatment appeared most strongly associated with Positive and Negative Syndrome Scale (PANSS) positive factor endpoint scores, whereas patient satisfaction with treatment was best predicted by the endpoint score on the PANSS emotional distress factor. The occurrence of severe side effects showed no meaningful association to satisfaction with treatment among investigators and patients, and neither did a patient's experienced psychopathology, nor their self-rating of functional impairment. Whereas trial discontinuation due to ITE is associated with poor treatment effectiveness, a patient's decision to withdraw from an antipsychotic trial remains unpredictable and may occur even when the investigator observes a global clinical improvement and is satisfied with the treatment.

A mechanistic hypothesis of the factors that enhance vulnerability to nicotine use in females

PubMed Central

O'Dell, Laura E.; Torres, Oscar V.

2013-01-01

Women are particularly more vulnerable to tobacco use than men. This review proposes a unifying hypothesis that females experience greater rewarding effects of nicotine and more intense stress produced by withdrawal than males. We also provide a neural framework whereby estrogen promotes greater rewarding effects of nicotine in females via enhanced dopamine release in the nucleus accumbens (NAcc). During withdrawal, we suggest that corticotropin-releasing factor (CRF) stress systems are sensitized and promote a greater suppression of dopamine release in the NAcc of females versus males. Taken together, females display enhanced nicotine reward via estrogen and amplified effects of withdrawal via stress systems. Although this framework focuses on sex differences in adult rats, it is also applied to adolescent females who display enhanced rewarding effects of nicotine, but reduced effects of withdrawal from this drug. Since females experience strong rewarding effects of nicotine, a clinical implication of our hypothesis is that specific strategies to prevent smoking initiation among females are critical. Also, anxiolytic medications may be more effective in females that experience intense stress during withdrawal. Furthermore, medications that target withdrawal should not be applied in a unilateral manner across age and sex, given that nicotine withdrawal is lower during adolescence. This review highlights key factors that promote nicotine use in females, and future studies on sex-dependent interactions of stress and reward systems are needed to test our mechanistic hypotheses. Future studies in this area will have important translational value toward reducing health disparities produced by nicotine use in females. PMID:23684991

Personal Factors That Influence the Voluntary Withdrawal of Undergraduates with Disabilities

ERIC Educational Resources Information Center

Thompson-Ebanks, Valerie

2014-01-01

This qualitative study explored personal factors students with invisible disabilities (SWIDs) associate with their voluntary withdrawal from a mid-western state land grant university (LGU) after completing 60 or more college credits. In-depth, semi-structured interviews were used to gather data from the five participants, all former students with…

Examining the Distinctiveness and the Socio-Emotional Correlates of Anxious-Withdrawal and Unsociability during Early Adolescence in Finland

ERIC Educational Resources Information Center

Ojanen, Tiina; Findley-Van Nostrand, Danielle; Bowker, Julie C.; Markovic, Andrea

2017-01-01

This study examined the distinctiveness of and the correlates associated with anxious-withdrawal and unsociability during early adolescence in Finland (N = 384; 12-14 years; 53% girls). As expected, confirmatory factor analyses revealed that anxious-withdrawal and unsociability were distinct and moderately positively correlated constructs. Only…

Withdrawal of antiepileptic drugs in glioma patients after long-term seizure freedom: design of a prospective observational study.

PubMed

Koekkoek, Johan A F; Kerkhof, Melissa; Dirven, Linda; Heimans, Jan J; Postma, Tjeerd J; Vos, Maaike J; Bromberg, Jacoline E C; van den Bent, Martin J; Reijneveld, Jaap C; Taphoorn, Martin J B

2014-08-15

Epilepsy is common in patients with a glioma. Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment, but may cause side effects and may negatively impact neurocognitive functioning and quality of life. Besides antiepileptic drugs, anti-tumour treatment, which currently consists of surgery, radiotherapy and/or chemotherapy, may contribute to seizure control as well. In glioma patients with seizure freedom after anti-tumour therapy the question emerges whether AEDs should be continued, particularly in the case where anti-tumour treatment has been successful. We propose to explore the possibility of AED withdrawal in glioma patients with long-term seizure freedom after anti-tumour therapy and without signs of tumour progression. We initiate a prospective, observational study exploring the decision-making process on the withdrawal or continuation of AEDs in low-grade and anaplastic glioma patients with stable disease and prolonged seizure freedom after anti-tumour treatment, and the effects of AED withdrawal or continuation on seizure freedom. We recruit participants through the outpatient clinics of three tertiary referral centers for brain tumour patients in The Netherlands. The patient and the treating physician make a shared decision to either withdraw or continue AED treatment. Over a one-year period, we aim to include 100 glioma patients. We expect approximately half of the participants to be willing to withdraw AEDs. The primary outcome measures are: 1) the outcome of the shared-decision making on AED withdrawal or continuation, and decision related arguments, and 2) seizure freedom at 12 months and 24 months of follow-up. We will also evaluate seizure type and frequency in case of seizure recurrence, as well as neurological symptoms, adverse effects related to AED treatment or withdrawal, other anti-tumour treatments and tumour progression. This study addresses two issues that are currently unexplored. First, it will explore the willingness to withdraw AEDs in glioma patients, and second, it will assess the risk of seizure recurrence in case AEDs are withdrawn in this specific patient population. This study aims to contribute to a more tailored AED treatment, and prevent unnecessary and potentially harmful use of AEDs in glioma patients.

The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal.

PubMed

Contarino, Angelo; Papaleo, Francesco

2005-12-20

The negative affective symptoms of opiate withdrawal powerfully motivate drug-seeking behavior and may trigger relapse to heroin abuse. To date, no medications exist that effectively relieve the negative affective symptoms of opiate withdrawal. The corticotropin-releasing factor (CRF) system has been hypothesized to mediate the motivational effects of drug dependence. The CRF signal is transmitted by two distinct receptors named CRF receptor-1 (CRF1) and CRF2. Here we report that genetic disruption of CRF1 receptor pathways in mice eliminates the negative affective states of opiate withdrawal. In particular, neither CRF1 receptor heterozygous (CRF1+/-) nor homozygous (CRF1-/-) null mutant mice avoided environmental cues repeatedly paired with the early phase of opiate withdrawal. These results were not due to altered associative learning processes because CRF1+/- and CRF1-/- mice displayed reliable, conditioned place aversions to environmental cues paired with the kappa-opioid receptor agonist U-50,488H. We also examined the impact of CRF1 receptor-deficiency upon opiate withdrawal-induced dynorphin activity in the nucleus accumbens, a brain molecular mechanism thought to underlie the negative affective states of drug withdrawal. Consistent with the behavioral indices, we found that, during the early phase of opiate withdrawal, neither CRF1+/- nor CRF1-/- showed increased dynorphin mRNA levels in the nucleus accumbens. This study reveals a cardinal role for CRF/CRF1 receptor pathways in the negative affective states of opiate withdrawal and suggests therapeutic strategies for the treatment of opiate addiction.

An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence

PubMed Central

Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida

2016-01-01

Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides. PMID:27818644

Anxiety level and correlates in methamphetamine-dependent patients during acute withdrawal.

PubMed

Su, Hang; Zhang, Jie; Ren, Wenwei; Xie, Ying; Tao, Jingyan; Zhang, Xiangyang; He, Jincai

2017-04-01

Anxiety is often a core element of withdrawal symptoms; however, risk factors associated with anxiety symptoms during the early stage of withdrawal in methamphetamine (METH) users are not well understood. Two hundred ten METH-dependent subjects who had been abstinent for 1 to 7 days were recruited. We used a set of self-administrative questionnaires eliciting information on sociodemographics, detailed drug use history and anxiety. Beck Anxiety Inventory (BAI) was used to measure anxiety symptoms. METH users had a mean BAI score of 6.9; 72 (34.3%) of the study sample had anxiety symptoms during acute METH withdrawal, including 42 (20.0%) with mild anxiety, 25 (11.9%) with moderate anxiety, and 5 (2.4%) with severe anxiety. In addition, gender (female), higher frequency of drug use, and history of polysubstance use were significantly correlated with anxiety symptoms during acute METH withdrawal. Anxiety symptoms appear to be common during the first week of METH abstinence, and several risk factors are identified.

Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice

PubMed Central

Riegle, Melissa A.; Masicampo, Melissa M.; Caulder, Erin H.; Godwin, Dwayne W.

2015-01-01

Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound hyperexcitability can result in withdrawal seizure. Withdrawal symptoms, including seizures, may drive individuals to relapse, thus representing a significant barrier to recovery. Our lab previously identified an upregulation of the thalamic T-type calcium (T channel) isoform CaV3.2 as a potential contributor to the generation and propagation of seizures in a model of withdrawal. In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity. DBA/2J mice were exposed to an intermittent ethanol exposure paradigm. Mice were treated with saline or ETX in each withdrawal period, and cortical EEG activity was recorded to determine seizure severity. We observed a progression in seizure activity with each successive withdrawal period. Treatment with ETX reduced ethanol withdrawal-induced spike and wave discharges (SWDs), in terms of absolute number, duration of events, and contribution to EEG power reduction in the 6–10 Hz frequency range. We also evaluated the effects of ETX on handling-induced convulsions. Overall, we observed a decrease in handling-induced convulsion severity in mice treated with ETX. Our findings suggest that ETX may be a useful pharmacological agent for studies of alcohol withdrawal and treatment of resulting seizures. PMID:24933286

Neurobiological Substrates for the Dark Side of Compulsivity in Addiction

PubMed Central

Koob, George F.

2009-01-01

Drug addiction can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreases in dopamine and opioid peptide function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, increases in anxiety-like responses, and increases in extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of addiction. Other components of brain stress systems in the extended amygdala that interact with CRF and may contribute to the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least in part, the compulsivity of addiction. PMID:18725236

Withdrawal From Chronic Nicotine Reduces Thyroid Hormone Levels and Levothyroxine Treatment Ameliorates Nicotine Withdrawal-Induced Deficits in Hippocampus-Dependent Learning in C57BL/6J Mice

PubMed Central

Leach, Prescott T.; Holliday, Erica; Kutlu, Munir G.

2015-01-01

Introduction: Cigarette smoking alters a variety of endocrine systems including thyroid hormones. Altered thyroid hormone signaling may lead to a subclinical or overt hypothyroid condition that could contribute to nicotine withdrawal-related symptoms, such as cognitive deficits. Thus, normalizing thyroid hormone levels may represent a novel therapeutic target for ameliorating nicotine withdrawal-associated cognitive deficits. Methods: The current studies conducted an analysis of serum thyroid hormone levels after chronic and withdrawal from chronic nicotine treatment in C57BL/6J mice using an enzyme-linked immunosorbent assay. The present studies also evaluated the effect of synthetic thyroid hormone (levothyroxine) on contextual and cued memory. Results: The current studies found that nicotine withdrawal reduces secreted thyroid hormone levels by 9% in C57BL/6J mice. Further, supplemental thyroid hormone not only enhanced memory in naïve animals, but also ameliorated deficits in hippocampus-dependent learning associated with nicotine withdrawal. Conclusions: These results suggest that smokers attempting to quit should be monitored closely for changes in thyroid function. If successfully treated, normalization of thyroid hormone levels may ameliorate some deficits associated with nicotine withdrawal and this may lead to higher rates of successful abstinence. PMID:25358661

"Is That A Method of Birth Control?" A Qualitative Exploration of Young Women's Use of Withdrawal.

PubMed

Arteaga, Stephanie; Gomez, Anu Manchikanti

2016-01-01

Despite its ubiquity, withdrawal is understudied as a family planning method. We investigated the context of and decision making around withdrawal use, drawing on in-depth, qualitative interviews with 38 Black and Latina women (ages 18 to 24). We examined contraceptive use histories to understand when and why participants used withdrawal. The majority of participants (n = 29; 76%) had used withdrawal in their lifetimes, though two-thirds of users mentioned withdrawal in their contraceptive histories only after interviewer prompts. Withdrawal was primarily used during transitions between contraceptive methods and when other methods were not desired. Relationship context was also an important factor, as many used withdrawal to increase intimacy with their partners; because they felt condoms were no longer necessary due to monogamy; or to fulfill their partners' preferences to increase sexual pleasure. Our findings indicate that decision making around withdrawal is embedded in situational and relational contexts. Future research should explore how health care providers and sex educators can engage young women in discussions of withdrawal's benefits and constraints. A harm reduction framework, which recognizes that optimal use of withdrawal is preferable to not using a pregnancy prevention method at all, may inform the ways that withdrawal can be addressed in clinical and educational settings.

Revised scoring and improved reliability for the Communication Patterns Questionnaire.

PubMed

Crenshaw, Alexander O; Christensen, Andrew; Baucom, Donald H; Epstein, Norman B; Baucom, Brian R W

2017-07-01

The Communication Patterns Questionnaire (CPQ; Christensen, 1987) is a widely used self-report measure of couple communication behavior and is well validated for assessing the demand/withdraw interaction pattern, which is a robust predictor of poor relationship and individual outcomes (Schrodt, Witt, & Shimkowski, 2014). However, no studies have examined the CPQ's factor structure using analytic techniques sufficient by modern standards, nor have any studies replicated the factor structure using additional samples. Further, the current scoring system uses fewer than half of the total items for its 4 subscales, despite the existence of unused items that have content conceptually consistent with those subscales. These characteristics of the CPQ have likely contributed to findings that subscale scores are often troubled by suboptimal psychometric properties such as low internal reliability (e.g., Christensen, Eldridge, Catta-Preta, Lim, & Santagata, 2006). The present study uses exploratory and confirmatory factor analyses on 4 samples to reexamine the factor structure of the CPQ to improve scale score reliability and to determine if including more items in the subscales is warranted. Results indicate that a 3-factor solution (constructive communication and 2 demand/withdraw scales) provides the best fit for the data. That factor structure was confirmed in the replication samples. Compared with the original scales, the revised scales include additional items that expand the conceptual range of the constructs, substantially improve reliability of scale scores, and demonstrate stronger associations with relationship satisfaction and sensitivity to change in therapy. Implications for research and treatment are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Fearfulness moderates the link between childhood social withdrawal and adolescent reward response

PubMed Central

Shaw, Daniel S.; Forbes, Erika E.

2015-01-01

Withdrawal from peers during childhood may reflect disruptions in reward functioning that heighten vulnerability to affective disorders during adolescence. The association between socially withdrawn behavior and reward functioning may depend on traits that influence this withdrawal, such as fearfulness or unsociability. In a study of 129 boys, we evaluated how boys’ fearfulness and sociability at age 5 and social withdrawal at school at ages 6 to 10 and during a summer camp at age 9/10 were associated with their neural response to reward at age 20. Greater social withdrawal during childhood was associated with heightened striatal and mPFC activation when anticipating rewards at age 20. Fearfulness moderated this effect to indicate that social withdrawal was associated with heightened reward-related response in the striatum for boys high on fearfulness. Altered striatal response associated with social withdrawal and fearfulness predicted greater likelihood to have a lifetime history of depression and social phobia at age 20. These findings add greater specificity to previous findings that children high in traits related to fear of novelty show altered reward responses, by identifying fearfulness (but not low levels of sociability) as a potential underlying mechanism that contributes to reward alterations in withdrawn children. PMID:25193948

30 CFR 880.14 - Administration of contributions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... work. Withdrawals and expenditures from the trust fund will be made only for costs connected with the project. Any part of the money contributed by a State, Indian tribe, local authority, or another Federal...

Reconstruction of global gridded monthly sectoral water withdrawals for 1971–2010 and analysis of their spatiotemporal patterns

DOE PAGES

Huang, Zhongwei; Hejazi, Mohamad; Li, Xinya; ...

2018-04-06

Human water withdrawal has increasingly altered the global water cycle in past decades, yet our understanding of its driving forces and patterns is limited. Reported historical estimates of sectoral water withdrawals are often sparse and incomplete, mainly restricted to water withdrawal estimates available at annual and country scales, due to a lack of observations at seasonal and local scales. In this study, through collecting and consolidating various sources of reported data and developing spatial and temporal statistical downscaling algorithms, we reconstruct a global monthly gridded (0.5°) sectoral water withdrawal dataset for the period 1971–2010, which distinguishes six water use sectors, i.e., irrigation,more » domestic, electricity generation (cooling of thermal power plants), livestock, mining, and manufacturing. Based on the reconstructed dataset, the spatial and temporal patterns of historical water withdrawal are analyzed. Results show that total global water withdrawal has increased significantly during 1971–2010, mainly driven by the increase in irrigation water withdrawal. Regions with high water withdrawal are those densely populated or with large irrigated cropland production, e.g., the United States (US), eastern China, India, and Europe. Seasonally, irrigation water withdrawal in summer for the major crops contributes a large percentage of total annual irrigation water withdrawal in mid- and high-latitude regions, and the dominant season of irrigation water withdrawal is also different across regions. Domestic water withdrawal is mostly characterized by a summer peak, while water withdrawal for electricity generation has a winter peak in high-latitude regions and a summer peak in low-latitude regions. Despite the overall increasing trend, irrigation in the western US and domestic water withdrawal in western Europe exhibit a decreasing trend. Our results highlight the distinct spatial pattern of human water use by sectors at the seasonal and annual timescales. Here, the reconstructed gridded water withdrawal dataset is open access, and can be used for examining issues related to water withdrawals at fine spatial, temporal, and sectoral scales.« less

Reconstruction of global gridded monthly sectoral water withdrawals for 1971–2010 and analysis of their spatiotemporal patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Zhongwei; Hejazi, Mohamad; Li, Xinya

Human water withdrawal has increasingly altered the global water cycle in past decades, yet our understanding of its driving forces and patterns is limited. Reported historical estimates of sectoral water withdrawals are often sparse and incomplete, mainly restricted to water withdrawal estimates available at annual and country scales, due to a lack of observations at seasonal and local scales. In this study, through collecting and consolidating various sources of reported data and developing spatial and temporal statistical downscaling algorithms, we reconstruct a global monthly gridded (0.5°) sectoral water withdrawal dataset for the period 1971–2010, which distinguishes six water use sectors, i.e., irrigation,more » domestic, electricity generation (cooling of thermal power plants), livestock, mining, and manufacturing. Based on the reconstructed dataset, the spatial and temporal patterns of historical water withdrawal are analyzed. Results show that total global water withdrawal has increased significantly during 1971–2010, mainly driven by the increase in irrigation water withdrawal. Regions with high water withdrawal are those densely populated or with large irrigated cropland production, e.g., the United States (US), eastern China, India, and Europe. Seasonally, irrigation water withdrawal in summer for the major crops contributes a large percentage of total annual irrigation water withdrawal in mid- and high-latitude regions, and the dominant season of irrigation water withdrawal is also different across regions. Domestic water withdrawal is mostly characterized by a summer peak, while water withdrawal for electricity generation has a winter peak in high-latitude regions and a summer peak in low-latitude regions. Despite the overall increasing trend, irrigation in the western US and domestic water withdrawal in western Europe exhibit a decreasing trend. Our results highlight the distinct spatial pattern of human water use by sectors at the seasonal and annual timescales. Here, the reconstructed gridded water withdrawal dataset is open access, and can be used for examining issues related to water withdrawals at fine spatial, temporal, and sectoral scales.« less

Reconstruction of global gridded monthly sectoral water withdrawals for 1971–2010 and analysis of their spatiotemporal patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Zhongwei; Hejazi, Mohamad; Li, Xinya

Human water withdrawal has increasingly altered the global water cycle in past decades, yet our understanding of its driving forces and patterns is limited. Reported historical estimates of sectoral water withdrawals are often sparse and incomplete, mainly restricted to water withdrawal estimates available at annual and country scales, due to a lack of observations at seasonal and local scales. In this study, through collecting and consolidating various sources of reported data and developing spatial and temporal statistical downscaling algorithms, we reconstruct a global monthly gridded (0.5°) sectoral water withdrawal dataset for the period 1971–2010, which distinguishes six water use sectors, i.e., irrigation,more » domestic, electricity generation (cooling of thermal power plants), livestock, mining, and manufacturing. Based on the reconstructed dataset, the spatial and temporal patterns of historical water withdrawal are analyzed. Results show that total global water withdrawal has increased significantly during 1971–2010, mainly driven by the increase in irrigation water withdrawal. Regions with high water withdrawal are those densely populated or with large irrigated cropland production, e.g., the United States (US), eastern China, India, and Europe. Seasonally, irrigation water withdrawal in summer for the major crops contributes a large percentage of total annual irrigation water withdrawal in mid- and high-latitude regions, and the dominant season of irrigation water withdrawal is also different across regions. Domestic water withdrawal is mostly characterized by a summer peak, while water withdrawal for electricity generation has a winter peak in high-latitude regions and a summer peak in low-latitude regions. Despite the overall increasing trend, irrigation in the western US and domestic water withdrawal in western Europe exhibit a decreasing trend. Our results highlight the distinct spatial pattern of human water use by sectors at the seasonal and annual timescales. The reconstructed gridded water withdrawal dataset is open access, and can be used for examining issues related to water withdrawals at fine spatial, temporal, and sectoral scales.« less

Imbalance in Individual Researcher's Peer Review Activities Quantified for Four British Ecological Society Journals, 2003-2010

PubMed Central

Petchey, Owen L.; Fox, Jeremy W.; Haddon, Lindsay

2014-01-01

Researchers contribute to the scientific peer review system by providing reviews, and “withdraw” from it by submitting manuscripts that are subsequently reviewed. So far as we are aware, there has been no quantification of the balance of individual's contributions and withdrawals. We compared the number of reviews provided by individual researchers (i.e., their contribution) to the number required by their submissions (i.e. their withdrawals) in a large and anonymised database provided by the British Ecological Society. The database covered the Journal of Ecology, Journal of Animal Ecology, Journal of Applied Ecology, and Functional Ecology from 2003–2010. The majority of researchers (64%) did not have balanced contributions and withdrawals. Depending on assumptions, 12% to 44% contributed more than twice as much as required; 20% to 52% contributed less than half as much as required. Balance, or lack thereof, varied little in relation to the number of years a researcher had been active (reviewing or submitting). Researchers who contributed less than required did not lack the opportunity to review. Researchers who submitted more were more likely to accept invitations to review. These finding suggest overall that peer review of the four analysed journals is not in crisis, but only due to the favourable balance of over- and under-contributing researchers. These findings are limited to the four journals analysed, and therefore cannot include researcher's other peer review activities, which if included might change the proportions reported. Relatively low effort was required to assemble, check, and analyse the data. Broader analyses of individual researcher's peer review activities would contribute to greater quality, efficiency, and fairness in the peer review system. PMID:24658631

Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management

PubMed Central

Sharma, Hari S; Ali, Syed F; Patnaik, Ranjana; Zimmermann-Meinzingen, Sibilla; Sharma, Aruna; Muresanu, Dafin F

2011-01-01

The possibility that pain perception and processing in the CNS results in cellular stress and may influence heat shock protein (HSP) expression was examined in a rat model of morphine dependence and withdrawal. Since activation of pain pathways result in exhaustion of growth factors, we examined the influence of cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,) on morphine induced HSP expression. Rats were administered morphine (10 mg/kg, s.c. /day) for 12 days and the spontaneous withdrawal symptoms were developed by cessation of the drug administration on day 13th that were prominent on day 14th and continued up to day 15th (24 to 72 h periods). In a separate group of rats, cerebrolysin was infused intravenously (5 ml/kg) once daily from day one until day 15th. In these animals, morphine dependence and withdrawal along with HSP immunoreactivity was examined using standard protocol. In untreated group mild HSP immunoreaction was observed during morphine tolerance, whereas massive upregulation of HSP was seen in CNS during withdrawal phase that correlated well with the withdrawal symptoms and neuronal damage. Pretreatment with cerebrolysin did not affect morphine tolerance but reduced the HSP expression during this phase. Furthermore, cerebrolysin reduced the withdrawal symptoms on day 14th to 15th. Taken together these observations suggest that cellular stress plays an important role in morphine induced pain pathology and exogenous supplement of growth factors, i.e. cerebrolysin attenuates HSP expression in the CNS and induce neuroprotection. This indicates a new therapeutic role of cerebrolysin in the pathophysiology of drugs of abuse, not reported earlier. PMID:21886595

A comparison of the psychometric properties of three cigarette withdrawal scales.

PubMed

Etter, Jean-François; Hughes, John R

2006-03-01

To compare the psychometric properties of three cigarette withdrawal scales. An internet cohort study. Each of 4,644 current (44%), former (49%) and never smokers (7%) completed the three scales via the internet. A subsample completed the scales again after 14 days (n=1309), and indicated their smoking status after 42 days (n=1431). The Cigarette Withdrawal Scale (CWS), the Wisconsin Withdrawal Scale (WWS) and the Minnesota Withdrawal Form (MWF). All three scales covered the main elements in the Diagnostic and Statistical Manual version IV (DSM-IV) and the International Classification of Diseases version 10 (ICD-10) definitions of tobacco withdrawal, but WWS did not cover weight gain. Factor analyses indicated that only six factors were present in WWS, instead of the expected seven factors. Cronbach's alpha coefficients (0.76-0.93) were high for all scales. Test-retest coefficients were in the range of 0.66-0.86 for CWS and WWS, but were somewhat lower for some MWF items (range 0.52-0.80). In 324 ex-smokers who had quit smoking 31 days or less before baseline, craving predicted relapse at 14-day follow-up (CWS: odds ratio=1.53 per point, P=0.003; WWS: odds ratio=1.40, P=0.04; MWF: odds ratio=1.49, P=0.002). In 34 baseline smokers who had quit smoking by 14-day retest, an increase in craving (WWS and MWF), depressed mood (MWF) and difficulty concentrating (WWS) between baseline and retest predicted relapse at 42-day follow-up. In terms of construct validity, scales performed similarly, but performance on some key tests (e.g. withdrawal will increase post-cessation) were inadequate, due perhaps to methodological limitations. No scale showed a decisive advantage over the others. MWF has the advantage of brevity.

Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal

PubMed Central

Cosgrove, Kelly P.; McKay, Reese; Esterlis, Irina; Kloczynski, Tracy; Perkins, Evgenia; Bois, Frederic; Pittman, Brian; Lancaster, Jack; Glahn, David C.; O’Malley, Stephanie; Carson, Richard E.; Krystal, John H.

2014-01-01

Understanding the effects of tobacco smoking on neuroadaptations in GABAA receptor levels over alcohol withdrawal will provide critical insights for the treatment of comorbid alcohol and nicotine dependence. We conducted parallel studies in human subjects and nonhuman primates to investigate the differential effects of tobacco smoking and nicotine on changes in GABAA receptor availability during acute and prolonged alcohol withdrawal. We report that alcohol withdrawal with or without concurrent tobacco smoking/nicotine consumption resulted in significant and robust elevations in GABAA receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABAA receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABAA receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABAA receptor levels normalized by 1 mo of abstinence in both groups—that is, those that consumed alcohol alone or the combination of alcohol and nicotine. These data suggest that constituents in tobacco smoke other than nicotine block the recovery of GABAA receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking. PMID:25453062

Timing of nicotine lozenge administration to minimize trigger induced craving and withdrawal symptoms.

PubMed

Kotlyar, Michael; Lindgren, Bruce R; Vuchetich, John P; Le, Chap; Mills, Anne M; Amiot, Elizabeth; Hatsukami, Dorothy K

2017-08-01

Smokers are often advised to use nicotine lozenge when craving or withdrawal symptoms occur. This may be too late to prevent lapses. This study assessed if nicotine lozenge use prior to a common smoking trigger can minimize trigger induced increases in craving and withdrawal symptoms. Eighty-four smokers completed two laboratory sessions in random order. At one session, nicotine lozenge was given immediately after a stressor (to approximate current recommended use - i.e., after craving and withdrawal symptoms occur); at the other session subjects were randomized to receive nicotine lozenge at time points ranging from immediately to 30min prior to the stressor. Withdrawal symptoms and urge to smoke were measured using the Minnesota Nicotine Withdrawal Scale and the Questionnaire of Smoking Urges (QSU). Relative to receiving lozenge after the stressor, a smaller increase in pre-stressor to post-stressor withdrawal symptom scores occurred when lozenge was used immediately (p=0.03) and 10min prior (p=0.044) to the stressor. Results were similar for factors 1 and 2 of the QSU when lozenge was used immediately prior to the stressor (p<0.03) and for factor 1 of the QSU when lozenge was used 10min prior to the stressor (p=0.028). Absolute levels of post-stressor withdrawal symptom and urge to smoke severity were lower when lozenge was given prior to versus after a stressor. Administering the nicotine lozenge prior to a smoking trigger can decrease trigger induced craving and withdrawal symptoms. Future studies are needed to determine if such use would increase cessation rates. Clinicaltrials.gov # NCT01522963. Copyright © 2017 Elsevier Ltd. All rights reserved.

Withdrawal times and associated factors in colonoscopy: a quality assurance multicenter assessment.

PubMed

Overholt, Bergein F; Brooks-Belli, Linda; Grace, Michael; Rankin, Kristin; Harrell, Royce; Turyk, Mary; Rosenberg, Fred B; Barish, Robert W; Gilinsky, Norman H

2010-04-01

To evaluate the use and impact of the recommended withdrawal time of at least 6 minutes from the cecum in colonoscopy in multiple gastroenterology endoscopy ambulatory surgery centers serving a wide geographical area. An observational prospective multicenter quality assurance review was conducted in 49 ambulatory surgery centers in 17 states with 315 gastroenterologists. There was no intervention with this quality assessment program as care of patients and the routine of gastroenterologists continued as standard practice. Multivariable analysis was applied to the database to examine factors affecting withdrawal time and polyp detection. There were 15,955 consecutive qualified patients receiving colonoscopies in a designated 4-week period. Gastroenterologists with average withdrawal times of 6 minutes or more in patients with no polyps were 1.8 times more likely to detect 1 or more polyps and had a significantly higher rate (P<0.0001) of polyp detection in patients with findings of polyps compared to gastroenterologists with average withdrawal times of less than 6 minutes in patients with no polyps. For patients with no pathology, the mean time of withdrawal was 6.98 (SD=4.34) minutes and for patients with pathology mean time of withdrawal was 11.27 (SD=6.71) minutes. Strongest predictors of withdrawal time of 6 minutes or more were presence of carcinoma (3.7 times more likely than those with no pathology), adenoma (2.0 times more likely than those with no pathology), and number of polyps visualized (1.7 times more likely for each polyp). This quality assurance assessment from standard colonoscopy practices of 315 gastroenterologists in 49 endoscopic ambulatory surgery centers serving a wide geographical area provides support for the merits of a colonoscopy withdrawal time from the cecum of 6 minutes or more to improve the detection of polyps.

Clinical pharmacokinetics of non-opiate abused drugs.

PubMed

Busto, U; Bendayan, R; Sellers, E M

1989-01-01

The present review discusses the available data on the kinetic properties of non-opiate abused drugs including psychomotor stimulants, hallucinogens and CNS-depressants. Some of the drugs of abuse reviewed here are illicit drugs (e.g. cannabis, cocaine), while others are effective pharmacological agents but have the potential to be abused (e.g. benzodiazepines). Although some of the drugs mentioned in this review have been in use for centuries (e.g. caffeine, nicotine, cocaine, cannabis), knowledge of their kinetics and metabolism is very recent and in some cases still incomplete. This is partially due to the difficulties inherent in studying drugs of abuse in humans, and to the complex metabolism of some of these drugs (e.g. cannabis, caffeine) which has made it difficult to develop sensitive assays to determine biological pathways. Although drugs of abuse may have entirely different intrinsic pharmacological effects, the kinetic properties of such drugs are factors contributing to abuse and dependence. The pharmacokinetic properties that presumably contribute to self-administration and drug abuse include rapid delivery of the drug into the central nervous system and high free drug clearance. Kinetic characteristics also play an important role in the development of physical dependence and on the appearance of a withdrawal syndrome: the longer the half-life, the greater the likelihood of the development of physical dependence; the shorter the half-life, the earlier and more severe the withdrawal. The balance between these 2 factors, which has not yet been carefully studied, will also influence abuse patterns. The clinical significance of kinetic characteristics with respect to abuse is discussed where possible.

Addiction as a Stress Surfeit Disorder

PubMed Central

Koob, George F.; Buck, Cara L.; Cohen, Ami; Edwards, Scott; Park, Paula E.; Schlosburg, Joel E.; Schmeichel, Brooke; Vendruscolo, Leandro F.; Wade, Carrie L.; Whitfield, Timothy W.; George, Olivier

2013-01-01

Drug addiction has been conceptualized as a chronically relapsing disorder of compulsive drug seeking and taking that progresses through three stages: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from positive reinforcement (binge/intoxication stage) to negative reinforcement (withdrawal/negative affect stage). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. Our hypothesis is that the negative emotional state that drives such negative reinforcement is derived from dysregulation of key neurochemical elements involved in the brain stress systems within the frontal cortex, ventral striatum, and extended amygdala. Specific neurochemical elements in these structures include not only recruitment of the classic stress axis mediated by corticotropin-releasing factor (CRF) in the extended amygdala as previously hypothesized but also recruitment of dynorphin-κ opioid aversive systems in the ventral striatum and extended amygdala. Additionally, we hypothesized that these brain stress systems may be engaged in the frontal cortex early in the addiction process. Excessive drug taking engages activation of CRF not only in the extended amygdala, accompanied by anxiety-like states, but also in the medial prefrontal cortex, accompanied by deficits in executive function that may facilitate the transition to compulsive-like responding. Excessive activation of the nucleus accumbens via the release of mesocorticolimbic dopamine or activation of opioid receptors has long been hypothesized to subsequently activate the dynorphin-κ opioid system, which in turn can decrease dopaminergic activity in the mesocorticolimbic dopamine system. Blockade of the κ opioid system can also block anxiety-like and reward deficits associated with withdrawal from drugs of abuse and block the development of compulsive-like responding during extended access to drugs of abuse, suggesting another powerful brain stress/anti-reward system that contributes to compulsive drug seeking. Thus, brain stress response systems are hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the development and persistence of addiction. The recruitment of anti-reward systems provides a powerful neurochemical basis for the negative emotional states that are responsible for the dark side of addiction. PMID:23747571

Effects of Chronic Alcohol Exposure on the Modulation of Ischemia-Induced Glutamate Release via Cannabinoid Receptors in the Dorsal Hippocampus.

PubMed

Zheng, Lei; Wu, Xiaoda; Dong, Xiao; Ding, Xinli; Song, Cunfeng

2015-10-01

Chronic alcohol consumption is a critical contributing factor to ischemic stroke, as it enhances ischemia-induced glutamate release, leading to more severe excitotoxicity and brain damage. But the neural mechanisms underlying this phenomenon are poorly understood. We evaluated the effects of chronic alcohol exposure on the modulation of ischemia-induced glutamate release via CB1 and CB2 cannabinoid receptors during middle cerebral artery occlusion, using in vivo microdialysis coupled with high-performance liquid chromatography, in alcohol-naïve rats or rats after 1 or 30 days of withdrawal from chronic ethanol intake (6% v/v for 14 days). Intra-dorsal hippocampus (DH) infusions of ACEA or JWH133, selective CB1 or CB2 receptor agonists, respectively, decreased glutamate release in the DH in alcohol-naïve rats in a dose-dependent manner. Such an effect was reversed by co-infusions of SR141716A or AM630, selective CB1 or CB2 receptor antagonists, respectively. After 30 days, but not 1 day of withdrawal, ischemia induced an enhancement in glutamate release in the DH, as compared with non-alcohol-treated control group. Intra-DH infusions of JWH133, but not ACEA, inhibited ischemia-induced glutamate release in the DH after 30 days of withdrawal. Finally, 1 day of withdrawal did not alter the protein level of CB1 or CB2 receptors in the DH, as compared to non-alcohol-treated control rats. Whereas 30 days of withdrawal robustly decreased the protein level of CB1 receptors, but failed to alter the protein level of CB2 receptors, in the DH, as compared to non-alcohol-treated control rats. Together, these findings suggest that loss of expression/function of CB1 receptors, but not CB2 receptors in the DH, is correlated with the enhancement of ischemia-induced glutamate release after prolonged alcohol withdrawal. Copyright © 2015 by the Research Society on Alcoholism.

Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic- pituitary-adrenal axis activation

PubMed Central

Reynolds, Anna R.; Saunders, Meredith A.; Brewton, Honoree’ W.; Winchester, Sydney R.; Elgumati, Ibrahim S.; Prendergast, Mark A.

2015-01-01

Background The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Methods Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 1100 hrs on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60 mg/kg/i.g.) or a placebo and withdrawal was monitored. Results Peak BELs of 225.52 mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g. aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. Conclusions The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. PMID:26143299

Sex Differences in Acute Ethanol Withdrawal Severity After Adrenalectomy and Gonadectomy in WSP and WSR Mice

PubMed Central

Strong, Moriah N.; Kaufman, Katherine R.; Crabbe, John C.; Finn, Deborah A.

2009-01-01

Recent findings suggest that the ability of ethanol (EtOH) to increase the levels of neurosteroids with potent γ-aminobutyric acid (GABA)ergic properties can influence measures of EtOH sensitivity. Earlier studies determined that removal of the adrenals and gonads diminished the steroidogenic effect of EtOH and significantly increased acute EtOH withdrawal severity in two inbred mouse strains that differed in withdrawal severity, suggesting the contribution of anticonvulsant GABAergic steroids to acute withdrawal in intact animals. Thus, the goal of the present studies was to investigate the consequence of steroid removal on acute EtOH withdrawal through excision of the adrenals and gonads, in another genetic animal model of EtOH withdrawal differences, the Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) selected lines. Male and female WSP and WSR mice underwent surgical removal of the adrenals and gonads or no organ removal (SHAM). One to two weeks later, baseline handling-induced convulsions (HICs) were assessed, mice were given a 4 g/kg dose of ethanol, and HICs were measured hourly for 12 hours and then at 24 hours. The combination surgery significantly increased EtOH withdrawal in WSP and WSR female mice, as measured by area under the curve (AUC) and peak HIC scores. AUC was significantly positively correlated with plasma corticosterone levels and significantly negatively correlated with progesterone levels. In contrast, surgical status did not alter withdrawal severity in male WSP and WSR mice. Overall, the increase in acute ethanol withdrawal severity in female WSP and WSR mice following adrenalectomy and gonadectomy corroborate our recent evidence that withdrawal from a high dose of EtOH can be modulated by anticonvulsant steroids produced in the periphery. PMID:19671463

Opiate withdrawal induces dynamic expressions of AMPA receptors and its regulatory molecule CaMKIIalpha in hippocampal synapses.

PubMed

Zhong, Weixia; Dong, Zhifang; Tian, Meng; Cao, Jun; Xu, Tianle; Xu, Lin; Luo, Jianhong

2006-07-24

Adaptive changes in brain areas following drug withdrawal are believed to contribute to drug seeking and relapse. Cocaine withdrawal alters the expression of GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in nucleus accumbens or amygdala, but the influence of drug withdrawal on hippocampus is little known. Here, we have examined the expression of GluR1 and GluR2/3 in hippocampal membrane and synaptic fractions following repeated morphine exposure and subsequent withdrawal. Repeated morphine exposure for 12 d increased GluR1 and GluR2/3 in synaptosome but not in membrane fraction. Interestingly, CaMKIIalpha, known to be able to regulate the function of AMPA receptors, was decreased in synaptosome but not in membrane fraction; pCaMKIIalpha, the phosphorylated form of CaMKIIalpha, was increased in both fractions. However, during opiate withdrawal, GluR1 was generally reduced while GluR2/3 was prominently increased in both fractions; pCaMKIIalpha was strongly decreased immediately after withdrawal, but detectably increased in late phase of morphine withdrawal in both fractions. Importantly, the opiate withdrawal-induced increase in GluR2/3 was dependent on the activation of glucocorticoid receptors and NMDA receptors, as it was prevented by the glucocorticoid receptor antagonist RU38486, or intrahippocampal injection of the NMDA receptor antagonist AP-5 or the antagonist to NR2B-containing NMDA receptors, Ro25-6981. These findings indicate that opiate withdrawal induces dynamic expression of GluR1 and GluR2/3 subunits of AMPA receptors in hippocampal synapses, possibly revealing an adaptive process of the hippocampal functions following opiate withdrawal.

Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation.

PubMed

Reynolds, Anna R; Saunders, Meredith A; Brewton, Honoree' W; Winchester, Sydney R; Elgumati, Ibrahim S; Prendergast, Mark A

2015-09-01

The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored. Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Evaluation of selected socioeconomic factors in patients with acute ethanol intoxication and alcohol withdrawal syndrome].

PubMed

Lukasik-Głębocka, Magdalena; Sommerfeld, Karina

2014-01-01

Ethanol is commonly overused psychoactive substance in Poland and all around the world. It causes addiction, which occurs as a result of its chronic administration. One of the main symptoms of addiction is hunger due to psychoactive substance that prevents interruption of its adoption and contributes to relapse drinking. Acute poisoning with ethyl alcohol and alcohol withdrawal syndrome are diseases causing a potential danger to life. The prevalence of use and abuse of alcoholic beverages is a potential risk, causing health problems, including permanent damage of the central and peripheral nervous system and socio-economic problems. The aim of this study is to analyze certain aspects of the socio-economic situation of the patients hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome in 2010. 299 patients history was evaluated, among which 161 were treated for acute intoxication with ethanol and 138 due to alcohol withdrawal syndrome. Objects of interest were elements of subjective tests including: marital status of patients, their education and professional activity and the problem of homelessness. The study group consisted of 299 patients in age from 16 to 77 years, hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome. It was found that the largest group consisted of patients remaining married (42.81%) and unmarried (30.43%). Alcohol abuse affects people of all levels of education. In the present study, most patients had a vocational education (37.79%) and medium (23.08%). Patients were analyzed in terms of economic activity, among which about 40% were unemployed. In the whole group more than 10% of those were homeless. Ethyl alcohol intoxication and alcohol withdrawal represents a significant hazard. As a result of reliance, patients lose control of alcohol consumption and they cannot reduce the amount and the time of its adoption. Reducing the dose of alcohol can lead to unpleasant withdrawal symptoms that the patient eliminate by adopting another dose. Typical is to continue the alcohol consumption despite knowledge of its harmful health and difficulties such as professional (problems at work or loss), financial (lack of livelihood, poverty) and interpersonal (loss of friends, marriage breakdown, loss of relationships with relatives).

Map visualization of groundwater withdrawals at the sub-basin scale

NASA Astrophysics Data System (ADS)

Goode, Daniel J.

2016-06-01

A simple method is proposed to visualize the magnitude of groundwater withdrawals from wells relative to user-defined water-resource metrics. The map is solely an illustration of the withdrawal magnitudes, spatially centered on wells—it is not capture zones or source areas contributing recharge to wells. Common practice is to scale the size (area) of withdrawal well symbols proportional to pumping rate. Symbols are drawn large enough to be visible, but not so large that they overlap excessively. In contrast to such graphics-based symbol sizes, the proposed method uses a depth-rate index (length per time) to visualize the well withdrawal rates by volumetrically consistent areas, called "footprints". The area of each individual well's footprint is the withdrawal rate divided by the depth-rate index. For example, the groundwater recharge rate could be used as a depth-rate index to show how large withdrawals are relative to that recharge. To account for the interference of nearby wells, composite footprints are computed by iterative nearest-neighbor distribution of excess withdrawals on a computational and display grid having uniform square cells. The map shows circular footprints at individual isolated wells and merged footprint areas where wells' individual footprints overlap. Examples are presented for depth-rate indexes corresponding to recharge, to spatially variable stream baseflow (normalized by basin area), and to the average rate of water-table decline (scaled by specific yield). These depth-rate indexes are water-resource metrics, and the footprints visualize the magnitude of withdrawals relative to these metrics.

Map visualization of groundwater withdrawals at the sub-basin scale

USGS Publications Warehouse

Goode, Daniel J.

2016-01-01

A simple method is proposed to visualize the magnitude of groundwater withdrawals from wells relative to user-defined water-resource metrics. The map is solely an illustration of the withdrawal magnitudes, spatially centered on wells—it is not capture zones or source areas contributing recharge to wells. Common practice is to scale the size (area) of withdrawal well symbols proportional to pumping rate. Symbols are drawn large enough to be visible, but not so large that they overlap excessively. In contrast to such graphics-based symbol sizes, the proposed method uses a depth-rate index (length per time) to visualize the well withdrawal rates by volumetrically consistent areas, called “footprints”. The area of each individual well’s footprint is the withdrawal rate divided by the depth-rate index. For example, the groundwater recharge rate could be used as a depth-rate index to show how large withdrawals are relative to that recharge. To account for the interference of nearby wells, composite footprints are computed by iterative nearest-neighbor distribution of excess withdrawals on a computational and display grid having uniform square cells. The map shows circular footprints at individual isolated wells and merged footprint areas where wells’ individual footprints overlap. Examples are presented for depth-rate indexes corresponding to recharge, to spatially variable stream baseflow (normalized by basin area), and to the average rate of water-table decline (scaled by specific yield). These depth-rate indexes are water-resource metrics, and the footprints visualize the magnitude of withdrawals relative to these metrics.

Attitudes and Approaches for Withdrawing Drugs for Children with Clinically Inactive Nonsystemic JIA: A Survey of the Childhood Arthritis and Rheumatology Research Alliance.

PubMed

Horton, Daniel B; Onel, Karen B; Beukelman, Timothy; Ringold, Sarah

2017-03-01

To assess the attitudes and strategies of pediatric rheumatology clinicians toward withdrawing medications for children with clinically inactive juvenile idiopathic arthritis (JIA). Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an anonymous electronic survey on decision making and approaches for withdrawing medications for inactive nonsystemic JIA. Data were analyzed using descriptive statistics. Of 388 clinicians in CARRA, 124 completed surveys (32%), predominantly attending pediatric rheumatologists. The most highly ranked factors in decision making for withdrawing medications were the duration of clinical inactivity, drug toxicity, duration of prior activity, patient/family preferences, joint damage, and JIA category. Diagnoses of rheumatoid factor-positive polyarthritis and persistent oligoarthritis made respondents less likely and more likely, respectively, to withdraw JIA medications. Three-quarters of respondents waited for 6-12 months of inactive disease before stopping methotrexate (MTX) or biologics, but preferences varied. There was also considerable variability in the strategies used to reduce, taper, or stop medications for clinically inactive JIA; most commonly, clinicians reported slow medication tapers lasting at least 2 months. For children receiving combination MTX-biologic therapy, 63% of respondents preferred stopping MTX first. Most clinicians reported using imaging only seldom or sometimes to guide decision making, but most were also reluctant to withdraw medications in the presence of asymptomatic imaging abnormalities suggestive of subclinical inflammation. Considerable variability exists among pediatric rheumatology clinicians regarding when and how to withdraw medications for children with clinically inactive JIA. More research is needed to identify the most effective approaches to withdraw medications and predictors of outcomes.

Donation After Circulatory Death for Liver Transplantation: A Meta-Analysis on the Location of Life Support Withdrawal Affecting Outcomes.

PubMed

Cao, Yiming; Shahrestani, Sara; Chew, Hong Chee; Crawford, Michael; Macdonald, Peter Simon; Laurence, Jerome; Hawthorne, Wayne John; Dhital, Kumud; Pleass, Henry

2016-07-01

Liver transplantation using donation after circulatory death (DCD) donors is associated with inferior outcomes compared to donation after brain death (DBD). Prolonged donor warm ischemic time has been identified as the key factor responsible for this difference. Various aspects of the donor life support withdrawal procedure, including location of withdrawal and administration of antemortem heparin, are thought to play important roles in mitigating the effects of warm ischemia. However, a systematic exploration of these factors is important for more confident integration of these practices into a standard DCD protocol. Medline, EMBASE, and Cochrane libraries were systematically searched and 23 relevant studies identified for analysis. Donation after circulatory death recipients were stratified according to location of life support withdrawal (intensive care unit or operating theater) and use of antemortem heparin. Donation after circulatory death recipients had comparable 1-year patient survival to DBD recipients if the location of withdrawal of life support was the operating theater, but not if the location was the intensive care unit. Likewise, the inferior 1-year graft survival and higher incidence of ischemic cholangiopathy of DCD compared with DBD recipients were improved by withdrawal in operating theater, although higher rates of ischemic cholangiopathy and worse graft survival were still observed in DCD recipients. Furthermore, administering heparin before withdrawal of life support reduced the incidence of primary nonfunction of the allograft. Our evidence suggests that withdrawal in the operating theater and premortem heparin administration improve DCD liver transplant outcomes, thus allowing for the most effective usage of these valuable organs.

Contribution of Nutrient Pollution to Water Scarcity in the Water-Rich Northeastern United States

NASA Astrophysics Data System (ADS)

Hale, R. L.; Lopez, C.; Vorosmarty, C. J.

2015-12-01

Most studies of water stress focus on water-scarce regions such as drylands. Yet, even water-rich regions can be water stressed due to local water withdrawals that exceed supply or due to water pollution that makes water unusable. The northeastern United States (NE) is a water-rich region relative to the rest of the country, as it concentrates about 50% of total renewable water of the country. Yes the NE features relatively high water withdrawals, ~50 km3/yr, for thermo-power generation, agriculture, and industry, as well as to support a human population of about 70 million. At the same time, rivers and streams in the NE suffer from nutrient pollution, largely from agricultural and urban land uses. We asked: to what extent is the NE water stressed, and how do water withdrawals and water quality each contribute to water scarcity across the NE? We used information on county-level water withdrawals and runoff to calculate a water scarcity index (WSI) for 200 hydrologic units across the NE from 1987 to 2002. We used data on surface water concentrations of nitrogen to calculate the additional water necessary to dilute surface water pollution to weak, moderate, and strong water quality standards derived from the literature. Only considering withdrawals, we found that approximately 10% of the NE was water stressed. Incorporating a moderate water quality standard, 25% of the NE was water stressed. We calculated a dilution burden by sectors of water users and found that public utilities faced 41% of the total dilution burden for the region, followed by irrigation users at 21%. Our results illustrate that even water rich regions can experience water stress and even scarcity, where withdrawals exceed surface water supplies. Water quality contributes to water stress and can change the spatial patterns of water stress across a region. The common approach to address scarcity has required the use of inter-basin water transfers, or in the case of water quality-caused scarcity, water treatment and nutrient management. Our analysis by sector highlights that the economic cost of water scarcity due to pollution in this region is largely borne by the public.

Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lai, H.; Prather, P.L.

1990-02-26

Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats weremore » trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms of withdrawal which returned to baseline within 3 days. During the protracted withdrawal period, the authors then redetermined the blockade of the PTZ-IDS. Significant tolerance was observed to the effectiveness of diazepam and pentobarbital, but not to phenobarbital. Since diazepam and pentobarbital produce significantly more enhancement of GABAergic activity than does phenobarbital, these data further suggest alteration of brain GABAergic systems during protracted withdrawal from ethanol.« less

Persistent Adaptations in Afferents to Ventral Tegmental Dopamine Neurons after Opiate Withdrawal.

PubMed

Kaufling, Jennifer; Aston-Jones, Gary

2015-07-15

Protracted opiate withdrawal is accompanied by altered responsiveness of midbrain dopaminergic (DA) neurons, including a loss of DA cell response to morphine, and by behavioral alterations, including affective disorders. GABAergic neurons in the tail of the ventral tegmental area (tVTA), also called the rostromedial tegmental nucleus, are important for behavioral responses to opiates. We investigated the tVTA-VTA circuit in rats after chronic morphine exposure to determine whether tVTA neurons participate in the loss of opiate-induced disinhibition of VTA DA neurons observed during protracted withdrawal. In vivo recording revealed that VTA DA neurons, but not tVTA GABAergic neurons, are tolerant to morphine after 2 weeks of withdrawal. Optogenetic stimulation of tVTA neurons inhibited VTA DA neurons similarly in opiate-naive and long-term withdrawn rats. However, tVTA inactivation increased VTA DA activity in opiate-naive rats, but not in withdrawn rats, resembling the opiate tolerance effect in DA cells. Thus, although inhibitory control of DA neurons by tVTA is maintained during protracted withdrawal, the capacity for disinhibitory control is impaired. In addition, morphine withdrawal reduced both tVTA neural activity and tonic glutamatergic input to VTA DA neurons. We propose that these changes in glutamate and GABA inputs underlie the apparent tolerance of VTA DA neurons to opiates after chronic exposure. These alterations in the tVTA-VTA DA circuit could be an important factor in opiate tolerance and addiction. Moreover, the capacity of the tVTA to inhibit, but not disinhibit, DA cells after chronic opiate exposure may contribute to long-term negative affective states during withdrawal. Dopaminergic (DA) cells of the ventral tegmental area (VTA) are the origin of a brain reward system and are critically involved in drug abuse. Morphine has long been known to affect VTA DA cells via GABAergic interneurons. Recently, GABAergic neurons caudal to the VTA were discovered and named the tail of VTA (tVTA). Here, we show that tVTA GABA neurons lose their capacity to disinhibit, but not to inhibit, VTA DA cells after chronic opiate exposure. The failure of disinhibition was associated with a loss of glutamatergic input to DA neurons after chronic morphine. These findings reveal mechanisms by which the tVTA may play a key role in long-term negative affective states during opiate withdrawal. Copyright © 2015 the authors 0270-6474/15/3510290-14$15.00/0.

Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.

PubMed

Bagley, Elena E; Hacker, Jennifer; Chefer, Vladimir I; Mallet, Christophe; McNally, Gavan P; Chieng, Billy C H; Perroud, Julie; Shippenberg, Toni S; Christie, MacDonald J

2011-10-30

Neurotransmitter transporters can affect neuronal excitability indirectly via modulation of neurotransmitter concentrations or directly via transporter currents. A physiological or pathophysiological role for transporter currents has not been described. We found that GABA transporter 1 (GAT-1) cation currents directly increased GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG) during opioid withdrawal in rodents. In contrast, GAT-1 did not indirectly alter GABA receptor responses via modulation of extracellular GABA concentrations. Notably, we found that GAT-1-induced increases in GABAergic activity contributed to many PAG-mediated signs of opioid withdrawal. Together, these data support the hypothesis that GAT-1 activity directly produces opioid withdrawal signs through direct hyperexcitation of GABAergic PAG neurons and nerve terminals, which presumably enhances GABAergic inhibition of PAG output neurons. These data provide, to the best of our knowledge, the first evidence that dysregulation of a neurotransmitter transporter current is important for the maladaptive plasticity that underlies opiate withdrawal.

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal.

PubMed

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin; Liang, Wenmei

2017-08-02

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal.

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal

PubMed Central

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Wang, Yanlin

2017-01-01

Neurotrophins, brain-derived neurotrophic factors (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), have been implicated in the modulation of heroin dependency. This study was designed to explore the expression alterations of BDNF, NT-3, and NT-4 in the context of heroin dependence and withdrawal in the rat nucleus accumbens (NAc). Heroin dependence was induced by a progressive intraperitoneal treatment of heroin. The results showed that the expression levels of BDNF and NT-4 were significantly decreased in the NAc of rats with heroin addiction in comparison with the control group, whereas there was a significant increase in BDNF and NT-4 expressions in the groups of rats with both naloxone-induced and spontaneous withdrawal. Moreover, NT-3 expression was markedly increased in the NAc of rats with heroin addiction and spontaneous withdrawal in comparison with the control group, but decreased in the NAc of rats with naloxone-induced withdrawal. These results indicated that chronic administration of heroin results in the alterations of BDNF, NT-3, and NT-4 expressions in the rat NAc. BDNF, NT-3, and NT-4 may play a critical role in the development of heroin dependency and withdrawal. PMID:28538519

Fearfulness moderates the link between childhood social withdrawal and adolescent reward response.

PubMed

Morgan, Judith K; Shaw, Daniel S; Forbes, Erika E

2015-06-01

Withdrawal from peers during childhood may reflect disruptions in reward functioning that heighten vulnerability to affective disorders during adolescence. The association between socially withdrawn behavior and reward functioning may depend on traits that influence this withdrawal, such as fearfulness or unsociability. In a study of 129 boys, we evaluated how boys' fearfulness and sociability at age 5 and social withdrawal at school at ages 6 to 10 and during a summer camp at age 9/10 were associated with their neural response to reward at age 20. Greater social withdrawal during childhood was associated with heightened striatal and mPFC activation when anticipating rewards at age 20. Fearfulness moderated this effect to indicate that social withdrawal was associated with heightened reward-related response in the striatum for boys high on fearfulness. Altered striatal response associated with social withdrawal and fearfulness predicted greater likelihood to have a lifetime history of depression and social phobia at age 20. These findings add greater specificity to previous findings that children high in traits related to fear of novelty show altered reward responses, by identifying fearfulness (but not low levels of sociability) as a potential underlying mechanism that contributes to reward alterations in withdrawn children. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Medical withdrawals from college for mental health reasons and their relation to academic performance.

PubMed

Meilman, P W; Manley, C; Gaylor, M S; Turco, J H

1992-03-01

A collaborative study among the university health service, the dean's office, and the registrar's office examined the academic performance of 77 students who took medical withdrawals for mental health reasons from Dartmouth College during a 3-year period. In 71.4% of the cases, students withdrew from a term in progress; the remainder arranged to withdraw after they had completed a term but before starting a new term. Depression was a major factor in approximately half of the withdrawals. Grade point average improved significantly after return from the withdrawal, with a large jump in individual term averages occurring between the terms immediately preceding and immediately following return. We found no significant difference between the number of students who experienced disciplinary trouble before withdrawal and those who were disciplined afterward. Students who were depressed at the time of withdrawal did not fare as well academically upon return as those students who had not been depressed. The data suggest that procedures for handling mental health withdrawals and readmission are important ways in which the campus counseling center can support the university's academic mission.

Mixed-grade rejection and its association with overt aggression, relational aggression, anxious-withdrawal, and psychological maladjustment.

PubMed

Bowker, Julie C; Etkin, Rebecca G

2014-01-01

The authors examined the associations between mixed-grade rejection (rejection by peers in a different school grade), anxious-withdrawal, aggression, and psychological adjustment in a middle school setting. Participants were 181 seventh-grade and 180 eighth-grade students (M age = 13.20 years, SD = 0.68 years) who completed peer nomination and self-report measures in their classes. Analyses indicated that in general, same- and mixed-grade rejection were related to overt and relational aggression, but neither type was related to anxious-withdrawal. Mixed-grade rejection was associated uniquely and negatively with self-esteem for seventh-grade boys, while increasing the loneliness associated with anxious-withdrawal. The results suggest that school-wide models of peer relations may be promising for understanding the ways in which different peer contexts contribute to adjustment in middle school settings.

A science plan for a comprehensive assessment of water supply in the region underlain by fractured rock in Maryland

USGS Publications Warehouse

Fleming, Brandon J.; Hammond, Patrick A.; Stranko, Scott A.; Duigon, Mark T.; Kasraei, Saeid

2012-01-01

The fractured rock region of Maryland, which includes land areas north and west of the Interstate 95 corridor, is the source of water supply for approximately 4.4 million Marylanders, or approximately 76 percent of the State's population. Whereas hundreds of thousands of residents rely on wells (both domestic and community), millions rely on surface-water sources. In this region, land use, geology, topography, water withdrawals, impoundments, and other factors affect water-flow characteristics. The unconfined groundwater systems are closely interconnected with rivers and streams, and are affected by seasonal and climatic variations. During droughts, groundwater levels drop, thereby decreasing well yields, and in some cases, wells have gone dry. Low ground-water levels contribute to reduced streamflows, which in turn, can lead to reduced habitat for aquatic life. Increased demand, over-allocation, population growth, and climate change can affect the future sustainability of water supplies in the region of Maryland underlain by fractured rock. In response to recommendations of the 2008 Advisory Committee on the Management and Protection of the State's Water Resources report, the Maryland Department of the Environment's Water Supply Program, the Maryland Geological Survey, the Maryland Department of Natural Resources, Monitoring and Non-Tidal Assessment (MANTA) Division, and the U.S. Geological Survey have developed a science plan for a comprehensive assessment that will provide new scientific information, new data analysis, and new tools for the State to better manage water resources in the fractured rock region of Maryland. The science plan lays out five goals for the comprehensive assessment: (1) develop tools for the improved management and investigation of groundwater and surface-water resources; (2) characterize factors affecting reliable yields of individual groundwater and surface-water supplies; (3) investigate impacts on nearby water withdrawal users caused by groundwater and surface-water withdrawals; (4) assess the role of streamflow and water withdrawals on the ecological integrity of streams; and (5) improve understanding of the distribution of water-quality conditions in fractured rock aquifers. To accomplish these goals, accurate data collection, review, and analysis are needed, including the study of "Research Watersheds" that can provide detailed information about the potential effects that climate change and water withdrawals may have on groundwater, streamflow, and aquatic life. The assessment planning started in 2009 and is being conducted with close interagency coordination. A Fractured Rock Aquifer Information System is currently (2012) undergoing initial development. Other major tasks that will be performed include the development of work plans for each science goal, the estimation of daily streamflow at ungaged streams, and the design and implementation of Research Watersheds. Finally, scenarios will be modeled to evaluate current water allocation permitting methodologies, investigate effects on nearby water withdrawal users caused by groundwater and surface-water withdrawals, and assess the potential impacts of climate change on water resources. Desktop and Web-based tools will be developed in order to meet the diverse research needs of the assessment. These tools, including the Fractured Rock Aquifer Information System will be continuously improved during the assessment to store relevant groundwater and surface-water data in spatially referenced databases, estimate streamflows, locate higher-yielding wells, estimate the impacts of withdrawals on nearby users, and assess the cumulative impacts of withdrawals on the aquatic resource. Tools will be developed to serve the needs of many audiences, including water resource managers, water suppliers, planners, policymakers, and other scientific investigators.

Trajectories of Social Withdrawal from Middle Childhood to Early Adolescence

PubMed Central

Oh, Wonjung; Bowker, Julie C.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

2013-01-01

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N=392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend’s withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class. PMID:18193479

Increased CRF signaling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal

PubMed Central

Zhao-Shea, Rubing; DeGroot, Steven R.; Liu, Liwang; Vallaster, Markus; Pang, Xueyan; Su, Qin; Gao, Guangping; Rando, Oliver J.; Martin, Gilles E.; George, Olivier; Gardner, Paul D.; Tapper, Andrew R.

2015-01-01

Increased anxiety is a predominant withdrawal symptom in abstinent smokers, yet the neuroanatomical and molecular bases underlying it are unclear. Here, we show that withdrawal-induced anxiety increases activity of neurons in the interpeduncular intermediate (IPI), a subregion of the interpeduncular nucleus (IPN). IPI activation during nicotine withdrawal was mediated by increased corticotropin releasing factor (CRF) receptor-1 expression and signaling, which modulated glutamatergic input from the medial habenula (MHb). Pharmacological blockade of IPN CRF1 receptors or optogenetic silencing of MHb input reduced IPI activation and alleviated withdrawal-induced anxiety; whereas IPN CRF infusion in mice increased anxiety. We identified a meso-interpeduncular circuit, consisting of ventral tegmental area (VTA) dopaminergic neurons projecting to the IPN, as a potential source of CRF. Knock-down of CRF synthesis in the VTA prevented IPI activation and anxiety during nicotine withdrawal. These data indicate that increased CRF receptor signaling within a VTA-IPN-MHb circuit triggers anxiety during nicotine withdrawal. PMID:25898242

Trajectories of social withdrawal from middle childhood to early adolescence.

PubMed

Oh, Wonjung; Rubin, Kenneth H; Bowker, Julie C; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett

2008-05-01

Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend's withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class.

Modulation of ethanol withdrawal-induced anxiety-like behavior during later withdrawals by treatment of early withdrawals with benzodiazepine/gamma-aminobutyric acid ligands.

PubMed

Knapp, Darin J; Overstreet, David H; Breese, George R

2005-04-01

Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal-associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of gamma-aminobutyric acid-modulating drugs on social interaction behavior-an established model of anxiety-in rats exposed to repeated cycles of ethanol treatment and withdrawal. Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl-6, 7-dymerhoxy-4-ethyl-beta-carboline-3-carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Single-dose administration of drugs that enhance or diminish activity at benzodiazepine-gamma-aminobutyric acid- receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals.

Addiction is a Reward Deficit and Stress Surfeit Disorder

PubMed Central

Koob, George F.

2013-01-01

Drug addiction can be defined by a three-stage cycle – binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation – that involves allostatic changes in the brain reward and stress systems. Two primary sources of reinforcement, positive and negative reinforcement, have been hypothesized to play a role in this allostatic process. The negative emotional state that drives negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in the brain reward and stress systems. Specific neurochemical elements in these structures include not only decreases in reward system function (within-system opponent processes) but also recruitment of the brain stress systems mediated by corticotropin-releasing factor (CRF) and dynorphin-κ opioid systems in the ventral striatum, extended amygdala, and frontal cortex (both between-system opponent processes). CRF antagonists block anxiety-like responses associated with withdrawal, block increases in reward thresholds produced by withdrawal from drugs of abuse, and block compulsive-like drug taking during extended access. Excessive drug taking also engages the activation of CRF in the medial prefrontal cortex, paralleled by deficits in executive function that may facilitate the transition to compulsive-like responding. Neuropeptide Y, a powerful anti-stress neurotransmitter, has a profile of action on compulsive-like responding for ethanol similar to a CRF1 antagonist. Blockade of the κ opioid system can also block dysphoric-like effects associated with withdrawal from drugs of abuse and block the development of compulsive-like responding during extended access to drugs of abuse, suggesting another powerful brain stress system that contributes to compulsive drug seeking. The loss of reward function and recruitment of brain systems provide a powerful neurochemical basis that drives the compulsivity of addiction. PMID:23914176

Sleep in schizophrenia: A systematic review and meta-analysis of polysomnographic findings in case-control studies.

PubMed

Chan, Man-Sum; Chung, Ka-Fai; Yung, Kam-Ping; Yeung, Wing-Fai

2017-04-01

Polysomnographic studies have been performed to examine the sleep abnormalities in schizophrenia, but the results are inconsistent. An updated systematic review, meta-analysis, and moderator analysis was conducted. Major databases were searched without language restriction from 1968 to January 2014. Data were analyzed using the random-effects model and summarized using the Hedges's g. Thirty-one studies with 574 patients and 515 healthy controls were evaluated. Limited by the number of studies and a lack of patient-level data, moderator analysis was restricted to medication status, duration of medication withdrawal, and illness duration. We showed that patients with schizophrenia have significantly shorter total sleep time, longer sleep onset latency, more wake time after sleep onset, lower sleep efficiency, and decreased stage 4 sleep, slow wave sleep, and duration and latency of rapid eye movement sleep compared to healthy controls. The findings on delta waves and sleep spindles were inconsistent. Moderator analysis could not find any abnormalities in sleep architecture in medication-naïve patients. Patients with antipsychotic withdrawal for longer than eight weeks were shown to have less sleep architectural abnormalities, compared to shorter duration of withdrawal, but the abnormalities in sleep continuity were similar. Slow wave sleep deficit was found in patients with schizophrenia for more than three years, while sleep onset latency was increased in medication-naïve, medication-withdrawn, and medicated patients. Our study showed that polysomnographic abnormalities are present in schizophrenia. Illness duration, medication status, and duration of medication withdrawal are several of the clinical factors that contribute to the heterogeneity between studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Methods to determine pumped irrigation-water withdrawals from the Snake River between Upper Salmon Falls and Swan Falls Dams, Idaho, using electrical power data, 1990-95

USGS Publications Warehouse

Maupin, Molly A.

1999-01-01

Pumped withdrawals compose most of the irrigation-water diversions from the Snake River between Upper Salmon Falls and Swan Falls Dams in southwestern Idaho. Pumps at 32 sites along the reach lift water as high as 745 feet to irrigate croplands on plateaus north and south of the river. The number of pump sites at which withdrawals are being continuously measured has been steadily decreasing, from 32 in 1990 to 7 in 1998. A cost-effective and accurate means of estimating annual irrigation-water withdrawals at pump sites that are no longer continuously measured was needed. Therefore, the U.S. Geological Survey began a study in 1998, as part of its Water-Use Program, to determine power-consumption coeffi- cients (PCCs) for each pump site so that withdrawals could be estimated by using electrical powerconsumption and total head data. PCC values for each pump site were determined by using withdrawal data that were measured by the U.S. Geological Survey during 1990–92 and 1994–95, energy data reported by Idaho Power Company during the same period, and total head data collected at each site during a field inventory in 1998. Individual average annual withdrawals for the 32 pump sites ranged from 1,120 to 44,480 acre-feet; average PCC values ranged from 103 to 1,248 kilowatthours per acre-foot. During the 1998 field season, power demand, total head, and withdrawal at 18 sites were measured to determine 1998 PCC values. Most of the 1998 PCC values were within 10 percent of the 5-year average, which demonstrates that withdrawals for a site that is no longer continuously measured can be calculated with reasonable accuracy by using the PCC value determined from this study and annual power-consumption data. K-factors, coefficients that describe the amount of energy necessary to lift water, were determined for each pump site by using values of PCC and total head and ranged from 1.11 to 1.89 kilowatthours per acre-foot per foot. Statistical methods were used to define the relations among PCC values and selected pumpsite characteristics. Multiple correlation analysis between average PCC values and total head, total horsepower, and total number of pumps revealed the strongest correlation was between average PCC and total head. Linear regression of these two variables resulted in a strong coefficient of determination R2=0 .9 86) and a representative K-factor of 1.463. Pump sites were subdivided into two groups on the basis of total head—0 to 300 feet and greater than 300 feet. Regression of average PCC values for eight pump sites with total head less than 300 feet produced a good correlation of determination (R2=0.870) and a representative K-factor of 1.682. The second group consisted of 10 pump sites with total head greater than 300 feet; regression produced a correlation of R2=0.939 and a representative K-factor of 1.405. Data on pump-site characteristics were successfully used to determine individual PCC and K-factor values. Statistical relations between pumpsite characteristics and PCC values were defined and used to determine regression equations that resulted in good coefficients of determination and representative K-factors. The individual PCC values will be used in the future to calculate irrigation- water withdrawals at sites that are no longer continuously measured. The representative K-factors and regression equations will be used to calculate irrigation-water withdrawals at sites that have not been previously measured and where total head and power consumption are known.

Withdrawal of ventilation at the patient's request in MND: a retrospective exploration of the ethical and legal issues that have arisen for doctors in the UK.

PubMed

Phelps, Kay; Regen, Emma; Oliver, David; McDermott, Chris; Faull, Christina

2017-06-01

Ventilatory support has benefits including prolonging survival for respiratory failure in motor neurone disease (MND). At some point some patients may wish to stop the intervention. The National Institute of Health and Care Excellence (NICE) guidance recommends research is needed on ventilation withdrawal. There is little literature focusing on the issues doctors encounter when withdrawing ventilation at the request of a patient. To identify and explore with doctors the ethical and legal issues that they had encountered in the withdrawal of ventilation at the request of a patient with MND. A retrospective thematic analysis of interviews of 24 doctors (including palliative care, respiratory, neurology and general practice) regarding their experiences with withdrawal of ventilation support from patients with MND. Respondents found withdrawal of ventilation at the request of patients with MND to pose legal, ethical and moral challenges in five themes: ethical and legal rights to withdrawal from treatment; discussions with family; discussions with colleagues; experiences of legal advice; issues contributing to ethical complexity. Though clear about the legality of withdrawal of treatment in theory, the practice led to ethical and moral uncertainty and mixed feelings. Many respondents had experienced negative reactions from other healthcare professionals when these colleagues were unclear of the distinction between palliation of symptoms, withdrawal of treatment and assisted death. Legal, ethical and practical guidance is needed for professionals who support a patient with MND who wishes to withdraw from ventilation. Open discussion of the ethical challenges is needed as well as education and support for professionals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Withdrawal of ventilation at the patient's request in MND: a retrospective exploration of the ethical and legal issues that have arisen for doctors in the UK

PubMed Central

Phelps, Kay; Regen, Emma; Oliver, David; McDermott, Chris; Faull, Christina

2017-01-01

Background Ventilatory support has benefits including prolonging survival for respiratory failure in motor neurone disease (MND). At some point some patients may wish to stop the intervention. The National Institute of Health and Care Excellence (NICE) guidance recommends research is needed on ventilation withdrawal. There is little literature focusing on the issues doctors encounter when withdrawing ventilation at the request of a patient. Aim To identify and explore with doctors the ethical and legal issues that they had encountered in the withdrawal of ventilation at the request of a patient with MND. Method A retrospective thematic analysis of interviews of 24 doctors (including palliative care, respiratory, neurology and general practice) regarding their experiences with withdrawal of ventilation support from patients with MND. Results Respondents found withdrawal of ventilation at the request of patients with MND to pose legal, ethical and moral challenges in five themes: ethical and legal rights to withdrawal from treatment; discussions with family; discussions with colleagues; experiences of legal advice; issues contributing to ethical complexity. Though clear about the legality of withdrawal of treatment in theory, the practice led to ethical and moral uncertainty and mixed feelings. Many respondents had experienced negative reactions from other healthcare professionals when these colleagues were unclear of the distinction between palliation of symptoms, withdrawal of treatment and assisted death. Conclusions Legal, ethical and practical guidance is needed for professionals who support a patient with MND who wishes to withdraw from ventilation. Open discussion of the ethical challenges is needed as well as education and support for professionals. PMID:26362794

Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal.

PubMed

Cunningham, Christopher L; Fidler, Tara L; Murphy, Kevin V; Mulgrew, Jennifer A; Smitasin, Phoebe J

2013-02-01

Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; nondependent control animals received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7 to 9 hours and returning to baseline within 24 hours; withdrawal severity was greater in D2 than in B6 mice (experiment 1). Postwithdrawal delays in initial ethanol access (1, 3, or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (experiment 2). The postwithdrawal enhancement of ethanol intake persisted over a 5-day abstinence period in D2 mice (experiment 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than nondependent mice (experiment 4). Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

To which extent social withdrawal at the age of 1 year is associated with IQ at 5-6 years old? Results of the EDEN mother-child cohort.

PubMed

Guedeney, Antoine; Doukhan, Sarah; Forhan, Anne; Heude, Barbara; Peyre, Hugo

2017-11-01

The present study aims to determine to which extent social withdrawal at 1 year is associated with the child's IQ at the end of the preschool period. Children (N = 1045) from the EDEN mother-child cohort were assessed for social withdrawal behaviours at 1 year by trained midwives using the Alarm Distress BaBy (ADBB) scale. Midwives also examined infants' language and motor development at 1 year. At the age 5-6 years, IQ scores were based on the WPPSI-III. Linear regression models were used to determine the association between IQ and ADBB, adjusted for a broad range of pre- and postnatal environmental factors and for language and motor skills scores at 1 year. After adjusting for environmental factors, children with social withdrawal at 1 years (ADBB ≥5; N = 195) had significantly lower IQ scores at 5-6 years (-2.81 IQ points; p value 0.007) compared to children without social withdrawal (ADBB <5; N = 847). When motor and language skills at 1 year were included in the previous model, no association between social withdrawal and IQ at 5-6 years was found. Being socially withdrawn at 1 year is associated with lower IQ scores at 5-6 years. The potential influence of these developmental aspects on each other (withdrawal behaviour and language/motor skills) may occur early in development. Our results improve our understanding of the outcomes of early social withdrawal behaviour and call for early detection of delay in acquisition of language/motor skills among socially withdrawn young children.

Systematic meta-analysis of childhood social withdrawal in schizophrenia, and comparison with data from at-risk children aged 9-14 years.

PubMed

Matheson, Sandra L; Vijayan, Hena; Dickson, Hannah; Shepherd, Alana M; Carr, Vaughan J; Laurens, Kristin R

2013-08-01

Social withdrawal is a robust childhood risk factor for later schizophrenia. The aims of this paper were to assess the evidence for childhood social withdrawal among adults with schizophrenia and, comparatively, in children aged 9-14 years who are putatively at-risk of developing schizophrenia. We conducted a meta-analysis, including cohort and case-control studies reporting social withdrawal measured by the Child Behavior Checklist (CBCL) in adults with schizophrenia vs. controls. Further, an experimental study compared CBCL withdrawal scores from typically-developing children with scores from two groups of putatively at-risk children: (i) children displaying a triad of replicated antecedents for schizophrenia, and (ii) children with at least one first- or second-degree relative with schizophrenia or schizoaffective disorder. Six studies met inclusion criteria for the meta-analysis (N = 3828), which demonstrated a large effect of increased childhood social withdrawal in adults with schizophrenia (standardized mean difference [SMD] score = 1.035, 95% CI = 0.304-1.766, p = 0.006), with no indication of publication bias, but considerable heterogeneity (I(2) = 91%). Results from the experimental study also indicated a large effect of increased social withdrawal in children displaying the antecedent triad (SMD = 0.743, p = 0.001), and a weaker effect in children with a family history of schizophrenia (SMD = 0.442, p = 0.051). Childhood social withdrawal may constitute a vulnerability marker for schizophrenia in the presence of other antecedents and/or genetic risk factors for schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effects of e-cigarette visual appearance on craving and withdrawal symptoms in abstinent smokers.

PubMed

Dawkins, Lynne; Munafò, Marcus; Christoforou, Gina; Olumegbon, Naomi; Soar, Kirstie

2016-02-01

Electronic cigarette (e-cigarette) use is becoming increasing popular among smokers, and there is a plethora of devices available. Nicotine delivery is clearly important for reducing tobacco craving and withdrawal symptoms, but other sensorimotor aspects of e-cigarettes (such as visual appearance) may contribute to this effect. This study explored whether it is important for an e-cigarette to visually resemble a tobacco cigarette in order to reduce craving and withdrawal symptoms. Sixty-three cigarette smokers (40% female, aged 18-65 years) who were not current e-cigarette users were randomly allocated to take ten 3-s puffs from either a white or a red first-generation e-cigarette following overnight abstinence. Current craving (urge to smoke) and nicotine withdrawal symptoms (using the Mood and Physical Symptoms Scale [MPSS]) were measured before and 10 min after use. Linear regression revealed higher craving and withdrawal symptoms in the red condition versus the white condition, but only among those who were e-cigarette naive (craving: B = .76, p = .009; withdrawal symptoms: B = 2.18, p = .009), not among those with e-cigarette experience (craving: B = -.08, p = .89; withdrawal symptoms: B = .24, p = .81), and these effects differed between groups (p = .04 and 0.01 for craving and withdrawal symptoms, respectively). In conclusion, cigarette-like appearance was associated with lower craving and withdrawal symptoms, but only for those with no prior e-cigarette experience. This effect, putatively mediated via classical conditioning or expectancies, may aid understanding of smokers' initial preferences for "cigalike" e-cigarette devices. (c) 2016 APA, all rights reserved).

Evaluation of the appropriate use of a CIWA-Ar alcohol withdrawal protocol in the general hospital setting.

PubMed

Eloma, Amanda S; Tucciarone, Jason M; Hayes, Edmund M; Bronson, Brian D

2018-01-01

The Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) is an assessment tool used to quantify alcohol withdrawal syndrome (AWS) severity and inform benzodiazepine treatment for alcohol withdrawal. To evaluate the prescribing patterns and appropriate use of the CIWA-Ar protocol in a general hospital setting, as determined by the presence or absence of documented AWS risk factors, patients' ability to communicate, and provider awareness of the CIWA-Ar order. This retrospective chart review included 118 encounters of hospitalized patients placed on a CIWA-Ar protocol during one year. The following data were collected for each encounter: patient demographics, admitting diagnosis, ability to communicate, and admission blood alcohol level; and medical specialty of the clinician ordering CIWA-Ar, documentation of the presence or absence of established AWS risk factors, specific parameters of the protocol ordered, service admitted to, provider documentation of awareness of the active protocol within 48 h of initial order, total benzodiazepine dose equivalents administered and associated adverse events. 57% of patients who started on a CIWA-Ar protocol had either zero or one documented risk factor for AWS (19% and 38% respectively). 20% had no documentation of recent alcohol use. 14% were unable to communicate. 19% of medical records lacked documentation of provider awareness of the ordered protocol. Benzodiazepine associated adverse events were documented in 15% of encounters. The judicious use of CIWA-Ar protocols in general hospitals requires mechanisms to ensure assessment of validated alcohol withdrawal risk factors, exclusion of patients who cannot communicate, and continuity of care during transitions.

THE PREVALENCE OF CANNABIS WITHDRAWAL AND ITS INFLUENCE ON ADOLESCENTS’ TREATMENT RESPONSE AND OUTCOMES: A 12-MONTH PROSPECTIVE INVESTIGATION

PubMed Central

Greene, M. Claire; Kelly, John F.

2014-01-01

Background Withdrawal, a diagnostic indicator of cannabis use disorder, is often minimized or ignored as a consequence of cannabis use, particularly among adolescents. This study aims to characterize cannabis withdrawal among adolescents in outpatient treatment for substance use disorder and evaluate the clinical significance of withdrawal as a predictor of substance-related outcomes. Methods Adolescent outpatients (N=127) reporting cannabis as their drug of choice (n=90) were stratified by presence of withdrawal and compared on demographic and clinical variables at treatment intake. Hierarchical linear models compared the effect of withdrawal on percent days abstinent (PDA) and related outcomes over a 1-year follow-up period. Results Adolescents reporting withdrawal (40%) were more likely to meet criteria for cannabis dependence, have higher levels of substance use severity, report more substance-related consequences, and have a mood disorder. Withdrawal was not associated with PDA over the follow-up period; however, this relationship was moderated by problem recognition such that adolescents reporting withdrawal and a drug problem improved at a greater rate with respect to PDA than those that didn’t recognize a problem with drugs and didn’t report withdrawal. Discussion Withdrawal is common among adolescent outpatients and is associated with a more clinically severe profile. In this sample, all adolescents reporting withdrawal met criteria for cannabis dependence, suggesting that withdrawal is a highly specific indicator of cannabis use disorder. While withdrawal doesn’t appear to be independently associated with substance use outcomes post-treatment, moderating factors such as drug problem recognition should be taken into account when formulating treatment and continuing care plans. PMID:25100311

The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice.

PubMed

Valero, E; Gómez-Milanés, I; Almela, P; Ribeiro Do Couto, B; Laorden, M L; Milanés, M V; Núñez, C

2018-06-08

Drug withdrawal-associated aversive memories trigger relapse to drug-seeking behavior. Corticotrophin-releasing factor (CRF) is an important mediator of the reinforcing properties of drugs of abuse. However, the involvement of CRF1 receptor (CRF1R) in aversive memory induced by opiate withdrawal has yet to be elucidated. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of CRF1R on opiate withdrawal memory acquisition, along with plasticity-related processes that occur after CPA within the basolateral amygdala (BLA) and dentate gyrus (DG). Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The CPA scores as well as the number of TH-positive neurons (in the NTS-A2 noradrenergic cell group), and the expression of the transcription factors Arc and pCREB (in the BLA and DG) were measured with and without CRF1R blockade. Mice subjected to conditioned naloxone-induced morphine withdrawal robustly expressed CPA. Pre-treatment with the selective CRF1R antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition. CP-154,526 also antagonized the enhanced number of TH-positive neurons in the NTS-A2 that was seen after CPA. Increased Arc expression and Arc-pCREB co-localization were seen in the BLA after CPA, which was not modified by CP-154,526. In the DG, CPA was accompanied by a decrease of Arc expression and no changes in Arc-pCREB co-localization, whereas pre-treatment with CP-154,526 induced an increase in both parameters. These results indicate that CRF-CRF1R pathway could be a critical factor governing opiate withdrawal memory storage and retrieval and might suggest a role for TH-NA pathway in the effects of withdrawal on memory. Our results might indicate that the blockade of CRF1R could represent a promising pharmacological treatment strategy approach for the attenuation of the relapse to drug-seeking/taking behavior triggered by opiate withdrawal-associated aversive memories. Copyright © 2018 Elsevier Inc. All rights reserved.

A Single Brain-Derived Neurotrophic Factor Infusion into the Dorsomedial Prefrontal Cortex Attenuates Cocaine Self-Administration-Induced Phosphorylation of Synapsin in the Nucleus Accumbens during Early Withdrawal

PubMed Central

Sun, Wei-Lun; Eisenstein, Sarah A.; Zelek-Molik, Agnieszka

2015-01-01

Background: Dysregulation in the prefrontal cortex-nucleus accumbens pathway has been implicated in cocaine addiction. We have previously demonstrated that one intra-dorsomedial prefrontal cortex brain-derived neurotrophic factor (BDNF) infusion immediately following the last cocaine self-administration session caused a long-lasting inhibition of cocaine-seeking and normalized the cocaine-induced disturbance of glutamate transmission in the nucleus accumbens after extinction and a cocaine prime. However, the molecular mechanism mediating the brain-derived neurotrophic factor effect on cocaine-induced alterations in extracellular glutamate levels is unknown. Methods: In the present study, we determined the effects of brain-derived neurotrophic factor on cocaine-induced changes in the phosphorylation of synapsin (p-synapsin), a family of presynaptic proteins that mediate synaptic vesicle mobilization, in the nucleus accumbens during early withdrawal. Results: Two hours after cocaine self-administration, p-synapsin Ser9 and p-synapsin Ser62/67, but not p-synapsin Ser603, were increased in the nucleus accumbens. At 22 hours, only p-synapsin Ser9 was still elevated. Elevations at both time points were attenuated by an intra-dorsomedial prefrontal cortex brain-derived neurotrophic factor infusion immediately after the end of cocaine self-administration. Brain-derived neurotrophic factor also reduced cocaine self-administration withdrawal-induced phosphorylation of the protein phosphatase 2A C-subunit, suggesting that brain-derived neurotrophic factor disinhibits protein phosphatase 2A C-subunit, consistent with p-synapsin Ser9 dephosphorylation. Further, co-immunoprecipitation demonstrated that protein phosphatase 2A C-subunit and synapsin are associated in a protein-protein complex that was reduced after 2 hours of withdrawal from cocaine self-administration and reversed by brain-derived neurotrophic factor. Conclusions: Taken together, these findings demonstrate that brain-derived neurotrophic factor normalizes the cocaine self-administration–induced elevation of p-synapsin in nucleus accumbens that may underlie a disturbance in the probability of neurotransmitter release or represent a compensatory neuroadaptation in response to the hypofunction within the prefrontal cortex-nucleus accumbens pathway during cocaine withdrawal. PMID:25522393

Data Collection and Simulation of Ecological Habitat and Recreational Habitat in the Shenandoah River, Virginia

USGS Publications Warehouse

Krstolic, Jennifer L.

2015-01-01

Time-series analyses were used to investigate changes in habitat availability with increased water withdrawals of 10, 20, and almost 50 percent (48.6 percent) up to the 2040 amounts projected by local water supply plans. Adult and sub-adult smallmouth bass frequently had habitat availability outside the normal range for habitat conditions during drought years, yet 10- or 20-percent increases in withdrawals did not contribute to a large reduction in habitat. When withdrawals were increased by 50 percent, there was an additional decrease in habitat. During 2002 drought scenarios, reduced habitat availability for sub-adult redbreast sunfish or river chub was only slightly evident with 50-percent increased withdrawal scenarios. Recreational habitat represented by canoeing decreased lower than normal during the 2002 drought. For a recent normal year, like 2012, increased water-withdrawal scenarios did not affect habitat availability for fish such as adult and sub-adult smallmouth bass, sub-adult redbreast sunfish, or river chub. Canoeing habitat availability was within the normal range most of 2012, and increased water-withdrawal scenarios showed almost no affect. For both ecological fish habitat and recreational canoeing habitat, the antecedent conditions (habitat within normal range of habitat or below normal) appear to govern whether additional water withdrawals will affect habitat availability. As human populations and water demands increase, many of the ecological or recreational stresses may be lessened by managing the timing of water withdrawals from the system.

Modulation of Ethanol Withdrawal–Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/γ-Aminobutyric Acid Ligands

PubMed Central

Knapp, Darin J.; Overstreet, David H.; Breese, George R.

2010-01-01

Background Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal–associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of γ-aminobutyric acid–modulating drugs on social interaction behavior—an established model of anxiety—in rats exposed to repeated cycles of ethanol treatment and withdrawal. Methods Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl–6, 7–dymerhoxy–4–ethyl–beta–carboline–3–carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Results Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Conclusions Single-dose administration of drugs that enhance or diminish activity at benzodiazepine–γ-aminobutyric acid- receptors during earlier withdrawals reduced or potentiated, respectively, anxiety-like behavior during later, drug-free withdrawals. These results support the potential of the novel strategy of using prophylactic therapy administered during early withdrawals to ameliorate symptoms of later withdrawals. PMID:15834220

Non-voluntary passive euthanasia: the social consequences of euphemisms.

PubMed

Sayers, Gwen M

2007-11-01

Non-voluntary passive euthanasia, the commonest form of euthanasia, is seldom mentioned in the UK. This article illustrates how the legal reasoning in Airedale NHS Trust v Bland contributed towards this conceptual deletion. By upholding the impermissibility of euthanasia, whilst at the same time permitting 'euthanasia' under the guise of 'withdrawing futile treatment', it is argued that the court (logically) allowed (withdrawing futile treatment and euthanasia). The Bland reasoning was incorporated into professional guidance, which extended the court's ruling to encompass patients who, unlike Anthony Bland, were sentient. But since the lawfulness of (withdrawing futile treatment and euthanasia) hinges on the futility of treatment, and since the guidance provides advice about withdrawing treatment from patients who differ from those considered in court, the lawfulness of such 'treatment decisions' is unclear. Legislation is proposed in order to redress the ambiguity that arose when moral decisions about 'euthanasia' were translated into medical decisions about 'treatment'.

Land subsidence near oil and gas fields, Houston, Texas.

USGS Publications Warehouse

Holzer, T.L.; Bluntzer, R.L.

1984-01-01

Subsidence profiles across 29 oil and gas fields in the 12 200 km2 Houston, Texas, regional subsidence area, which is caused by the decline of ground-water level, suggest that the contribution of petroleum withdrawal to local land subsidence is small. In addition to land subsidence, faults with an aggregate length of more than 240 km have offset the land surface in historical time. Natural geologic deformation, ground-water pumping, and petroleum withdrawal have all been considered as potential causes of the historical offset across these faults. The minor amount of localized land subsidence associated with oil and gas fields, suggests that petroleum withdrawal is not a major cause of the historical faulting. -from Authors

Nicotine Withdrawal Induces Neural Deficits in Reward Processing.

PubMed

Oliver, Jason A; Evans, David E; Addicott, Merideth A; Potts, Geoffrey F; Brandon, Thomas H; Drobes, David J

2017-06-01

Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task. Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors. Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p < .001). Exploratory analyses indicated withdrawal increased time to initiate the next trial following unexpected punishment trials (p < .001) and response time on reward trials during withdrawal was positively related to nicotine dependence (p < .001). Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes. Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and unpleasant stimuli may be particularly effective for alleviating nicotine withdrawal. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory.

PubMed

Wise, Laura E; Varvel, Stephen A; Selley, Dana E; Wiebelhaus, Jason M; Long, Kelly A; Middleton, Lisa S; Sim-Selley, Laura J; Lichtman, Aron H

2011-10-01

Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. In cannabinoid-dependent rodents, the CB(1) antagonist rimonabant precipitates somatic withdrawal and enhances forskolin-stimulated adenylyl cyclase activity in cerebellum, an effect opposite that of acutely administered ∆(9)-tetrahydrocannabinol (THC), the primary constituent in cannabis. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice. Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state. Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.

A systematic nurse-led approach to withdrawal risk screening, prevention and treatment among inpatients with an alcohol use disorder in an ear, nose, throat and jaw surgery department-A formative evaluation.

PubMed

Leuenberger, Deborah Linda; Fierz, Katharina; Hinck, Andreas; Bodmer, Daniel; Hasemann, Wolfgang

2017-02-01

Among patients with head and neck cancer comorbid alcohol use disorder is frequent which contributes to higher risk of developing perioperative alcohol withdrawal syndrome/delirium or delirium due to medical conditions. Although guidelines emphasize prevention and treatment of alcohol withdrawal in hospitalized patients, a validated systematic approach for management of these patients is still lacking. Our aim was to formatively evaluate our newly developed systematic approach in view of nurses' adherence to screening patients for regular alcohol consumption and managing their withdrawal symptoms using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised. We conducted a formative evaluation to improve the project's design and performance and used a retrospective chart review in a consecutive sample of all adult inpatients with head and neck cancer being assigned for surgery in a university hospital. Our bundle of interventions consisted of nurses' screenings for regular alcohol consumption, withdrawal risk assessment, offering patients a substitution therapy, nurses' assessments of withdrawal symptoms and symptom oriented withdrawal management. Proximate endpoints were analyzed descriptively at each component of the bundle in terms of frequencies and severity of withdrawal symptoms, frequencies of nurses' and doctors' screenings and nurses' assessments performed as required. Between 2013 and 2014, 87 inpatients met inclusion criteria and screenings by doctors/ nurses revealed 49 alcohol consumers, where six screenings were omitted by nurses and six by doctors. Twenty-one consumers were at risk and six of them developed an alcohol withdrawal syndrome. None of the 87 showed an alcohol withdrawal delirium, but five developed a delirium due to medical conditions. Nurses correctly conducted all preventive elements of the intervention bundle in 14 (58%) patients at risk but overall, only performed 50% of the required assessments. Although nurses safely managed patients' symptoms, nurses' adherence to the interventions was suboptimal and requires stronger leadership. Copyright © 2016 Elsevier Inc. All rights reserved.

Withdrawal of antiepileptic drugs.

PubMed

Shinnar, S; Berg, A T

1995-04-01

Recent literature on withdrawing antiepileptic drug therapy in patients who are seizure free on antiepileptic drugs is reviewed. The average recurrence risk across studies is 29% at 2 years. Factors such as age of onset, etiology of seizures, the electroencephalogram and the epileptic syndrome influence outcome. Factors that need to be considered by the clinician include not just the statistical risk of recurrence but also the consequences of a recurrence, which will be a function of age and sex.

Amphetamine withdrawal differentially affects hippocampal and peripheral corticosterone levels in response to stress.

PubMed

Bray, Brenna; Scholl, Jamie L; Tu, Wenyu; Watt, Michael J; Renner, Kenneth J; Forster, Gina L

2016-08-01

Amphetamine withdrawal is associated with heightened anxiety-like behavior, which is directly driven by blunted stress-induced glucocorticoid receptor-dependent serotonin release in the ventral hippocampus. This suggests that glucocorticoid availability in the ventral hippocampus during stress may be reduced during amphetamine withdrawal. Therefore, we tested whether amphetamine withdrawal alters either peripheral or hippocampal corticosterone stress responses. Adult male rats received amphetamine (2.5mg/kg, ip) or saline for 14 days followed by 2 weeks of withdrawal. Contrary to our prediction, microdialysis samples from freely-moving rats revealed that restraint stress-induced corticosterone levels in the ventral hippocampus are enhanced by amphetamine withdrawal relative to controls. In separate groups of rats, plasma corticosterone levels increased immediately after 20min of restraint and decreased to below stress-naïve levels after 1h, indicating negative feedback regulation of corticosterone following stress. However, plasma corticosterone responses were similar in amphetamine-withdrawn and control rats. Neither amphetamine nor stress exposure significantly altered protein expression or enzyme activity of the steroidogenic enzymes 11β-hydroxysteroid dehydrogenase (11β-HSD1) or hexose-6-phosphate dehydrogenase (H6PD) in the ventral hippocampus. Our findings demonstrate for the first time that amphetamine withdrawal potentiates stress-induced corticosterone in the ventral hippocampus, which may contribute to increased behavioral stress sensitivity previously observed during amphetamine withdrawal. However, this is not mediated by either changes in plasma corticosterone or hippocampal steroidogenic enzymes. Establishing enhanced ventral hippocampal corticosterone as a direct cause of greater stress sensitivity may identify the glucocorticoid system as a novel target for treating behavioral symptoms of amphetamine withdrawal. Copyright © 2016 Elsevier B.V. All rights reserved.

Mitochondrial respiratory control is lost during growth factor deprivation.

PubMed

Gottlieb, Eyal; Armour, Sean M; Thompson, Craig B

2002-10-01

The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-x(L), restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control.

Autophagy: not good OR bad, but good AND bad.

PubMed

Altman, Brian J; Rathmell, Jeffrey C

2009-05-01

Autophagy is a well-established mechanism to degrade intracellular components and provide a nutrient source to promote survival of cells in metabolic distress. Such stress can be caused by a lack of available nutrients or by insufficient rates of nutrient uptake. Indeed, growth factor deprivation leads to internalization and degradation of nutrient transporters, leaving cells with limited means to access extracellular nutrients even when plentiful.This loss of growth factor signaling and extracellular nutrients ultimately leads to apoptosis, but also activates autophagy, which may degrade intracellular components and provide fuel for mitochondrial bioenergetics. The precise metabolic role of autophagy and how it intersects with the apoptotic pathways in growth factor withdrawal, however, has been uncertain. Our recent findings ingrowth factor-deprived hematopoietic cells show that autophagy can simultaneously contribute to cell metabolism and initiate a pathway to sensitize cells to apoptotic death. This pathway may promote tissue homeostasis by ensuring that only cells with high resistance to apoptosis may utilize autophagy as a survival mechanism when growth factors are limiting and nutrient uptake decreases.

Conducting a Withdrawal Survey.

ERIC Educational Resources Information Center

Aldridge, Sue; Rowley, Jennifer

2001-01-01

A survey at Edge Hill College of Higher Education in Canada, designed to be part of the mechanism for monitoring and evaluating the quality of the student experience, revealed that key factors influencing withdrawal were: course not as expected, traveling difficulties, institution not as expected, domestic difficulties, and financial difficulties.…

Predictors of smoking lapse in a human laboratory paradigm.

PubMed

Roche, Daniel J O; Bujarski, Spencer; Moallem, Nathasha R; Guzman, Iris; Shapiro, Jenessa R; Ray, Lara A

2014-07-01

During a smoking quit attempt, a single smoking lapse is highly predictive of future relapse. While several risk factors for a smoking lapse have been identified during clinical trials, a laboratory model of lapse was until recently unavailable and, therefore, it is unclear whether these characteristics also convey risk for lapse in a laboratory environment. The primary study goal was to examine whether real-world risk factors of lapse are also predictive of smoking behavior in a laboratory model of smoking lapse. After overnight abstinence, 77 smokers completed the McKee smoking lapse task, in which they were presented with the choice of smoking or delaying in exchange for monetary reinforcement. Primary outcome measures were the latency to initiate smoking behavior and the number of cigarettes smoked during the lapse. Several baseline measures of smoking behavior, mood, and individual traits were examined as predictive factors. Craving to relieve the discomfort of withdrawal, withdrawal severity, and tension level were negatively predictive of latency to smoke. In contrast, average number of cigarettes smoked per day, withdrawal severity, level of nicotine dependence, craving for the positive effects of smoking, and craving to relieve the discomfort of withdrawal were positively predictive of number of cigarettes smoked. The results suggest that real-world risk factors for smoking lapse are also predictive of smoking behavior in a laboratory model of lapse. Future studies using the McKee lapse task should account for between subject differences in the unique factors that independently predict each outcome measure.

Catatonia Secondary to Sudden Clozapine Withdrawal: A Case with Three Repeated Episodes and a Literature Review

PubMed Central

Bilbily, John; McCollum, Betsy

2017-01-01

A literature search identified 9 previously published cases that were considered as possible cases of catatonia secondary to sudden clozapine withdrawal. Two of these 9 cases did not provide enough information to make a diagnosis of catatonia according to the Diagnostic and Statistical Manual, 5th Edition (DSM-5). The Liverpool Adverse Drug Reaction (ADR) Causality Scale was modified to assess ADRs secondary to drug withdrawal. From the 7 published cases which met DSM-5 catatonia criteria, using the modified scale, we established that 3 were definitive and 4 were probable cases of catatonia secondary to clozapine withdrawal. A new definitive case is described with three catatonic episodes which (1) occurred after sudden discontinuation of clozapine in the context of decades of follow-up, (2) had ≥3 of 12 DSM-5 catatonic symptoms and serum creatinine kinase elevation, and (3) required medical hospitalization and intravenous fluids. Clozapine may be a gamma-aminobutyric acid (GABA) receptor agonist; sudden clozapine withdrawal may explain a sudden decrease in GABA activity that may contribute to the development of catatonic symptoms in vulnerable patients. Based on the limited information from these cases, the pharmacological treatment for catatonia secondary to sudden clozapine withdrawal can include benzodiazepines and/or restarting clozapine. PMID:28396815

Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit Disorder

PubMed Central

2012-01-01

Alcoholism can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of specific neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreased dopamine and γ-aminobutyric acid function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from chronic alcohol, sufficient to produce dependence, increases reward thresholds, increases anxiety-like responses, decreases dopamine system function, and increases extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of alcoholism. Other components of brain stress systems in the extended amygdala that interact with CRF and that may contribute to the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least partially, the compulsivity of alcoholism. PMID:21744309

Effect of 6 days of support withdrawal on characteristics of balance function

NASA Astrophysics Data System (ADS)

Sayenko, D.; Artamonov, A. A.; Ivanov, O. G.; Kozlovskaya, I. B.

2005-08-01

The role of different sensorimotor and sensory factors on postural disorders at different stages of the exposure to microgravity still remains unknown. The results obtained after the Dry Immersion (DI) exposure, showed that after 6 days of DI the subjects' ability to resist to posture perturbations was highly reduced, the EMG response of corrective muscles was increased, and the structure of corrective responses was modified, so that the equilibrium was maintained by the elimination of excessive degrees of freedom. Thus, the results of the study have revealed profound changes in postural synergies suggesting a significant contribution of the support afferentation to posture control.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Navarro-Zaragoza, J.; Martínez-Laorden, E.; Mora, L.

Opioid addiction is associated with cardiovascular disease. However, mechanisms linking opioid addiction and cardiovascular disease remain unclear. This study investigated the role of corticotropin-releasing factor (CRF) 1 receptor in mediating somatic signs and the behavioural states produced during withdrawal from morphine dependence. Furthermore, it studied the efficacy of CRF1 receptor antagonist, CP-154,526 to prevent the cardiac sympathetic activity induced by morphine withdrawal. In addition, tyrosine hydroxylase (TH) phosphorylation pathways were evaluated. Like stress, morphine withdrawal induced an increase in the hypothalamic–pituitary–adrenal (HPA) axis activity and an enhancement of noradrenaline (NA) turnover. Pre-treatment with CRF1 receptor antagonist significantly reduced morphine withdrawal-inducedmore » increases in plasma adrenocorticotropic hormone (ACTH) levels, NA turnover and TH phosphorylation at Ser31 in the right ventricle. In addition, CP-154,526 reduced the phosphorylation of extracellular signal-regulated kinase (ERK) after naloxone-precipitated morphine withdrawal. In addition, CP-154,526 attenuated the increases in body weight loss during morphine treatment and suppressed some of morphine withdrawal signs. Altogether, these results support the idea that cardiac sympathetic pathways are activated in response to naloxone-precipitated morphine withdrawal suggesting that treatment with a CRF1 receptor antagonist before morphine withdrawal would prevent the development of stress-induced behavioural and autonomic dysfunction in opioid addicts. - Highlights: • Morphine withdrawal caused an increase in myocardial sympathetic activity. • ERK regulates TH phosphorylation after naloxone-induced morphine withdrawal. • CRF1R is involved in cardiac adaptive changes during morphine dependence.« less

Doctorate Motivation: An (Auto)ethnography

ERIC Educational Resources Information Center

Templeton, Robert

2016-01-01

Intrinsic motivation is considered the dominant factor in the motivation of adult students in continuing postgraduate education. However, the strength of an intrinsic motivation to learn does not explain the phenomenon of dropout where the student withdraws and does not return or where the student withdraws and then recommences their postgraduate…

Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

PubMed Central

Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

2012-01-01

The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

Seizure recurrence and risk factors after antiepilepsy drug withdrawal in children with brain tumors.

PubMed

Khan, Raja B; Onar, Arzu

2006-02-01

To study seizure outcome after antiepilepsy drug (AED) withdrawal in brain tumor patients and to analyze risk factors for seizure recurrence. Brain tumor patients with seizures and at least one attempt at AED discontinuation were identified from the hospital database and neurology clinic records. After defining study variables, patient charts were abstracted for clinical and demographic data. Statistical analyses used log-rank tests and multivariable Cox proportional hazards models. Sixty-two patients discontinued AEDs at a median time of 5.6 years from the first seizure (range, 1.2-19.6 years). Median time since AED withdrawal was 2.3 years (range, 0.4-15.1 years). Seizures recurred in 17 (27%) patients within a median time of 0.8 years (range, 0.06-7.7 years). Median seizure-free period before AED withdrawal was 1.3 years (range, 0.1-11 years). More than one tumor resection and whole-brain radiation treatment (WBRT) were associated with seizure recurrence, whereas posterior fossa tumor location was correlated with reduced seizure recurrence risk. At seizure recurrence, control was easily reestablished in 10 patients with AED reinstitution and after dose adjustment in five; two patients with poor drug compliance continue to have seizures. In 48 patients who had an EEG before AED withdrawal, spikes or slow waves did not correlate with seizure recurrence. AED withdrawal can be successfully achieved in majority of carefully selected patients. WBRT and multiple tumor resections seem to be associated with an increased hazard for seizure recurrence.

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects.

PubMed

Faulkner, Paul; Ghahremani, Dara G; Tyndale, Rachel F; Cox, Chelsea M; Kazanjian, Ari S; Paterson, Neil; Lotfipour, Shahrdad; Hellemann, Gerhard S; Petersen, Nicole; Vigil, Celia; London, Edythe D

2017-07-01

The use of cigarettes delivering different nicotine doses allows evaluation of the contribution of nicotine to the smoking experience. We compared responses of 46 young adult smokers to research cigarettes, delivering 0.027, 0.110, 0.231, or 0.763 mg nicotine, and conventional cigarettes. On five separate days, craving, withdrawal, affect, and sustained attention were measured after overnight abstinence and again after smoking. Participants also rated each cigarette, and the nicotine metabolite ratio (NMR) was used to identify participants as normal or slow metabolizers. All cigarettes equally alleviated craving, withdrawal, and negative affect in the whole sample, but normal metabolizers reported greater reductions of craving and withdrawal than slow metabolizers, with dose-dependent effects. Only conventional cigarettes and, to a lesser degree, 0.763-mg nicotine research cigarettes increased sustained attention. Finally, there were no differences between ratings of lower-dose cigarettes, but the 0.763-mg cigarettes and (even more so) conventional cigarettes were rated more favorably than lower-dose cigarettes. The findings indicate that smoking-induced relief of craving and withdrawal reflects primarily non-nicotine effects in slow metabolizers, but depends on nicotine dose in normal metabolizers. By contrast, relief of withdrawal-related attentional deficits and cigarette ratings depend on nicotine dose regardless of metabolizer status. These findings have bearing on the use of reduced-nicotine cigarettes to facilitate smoking cessation and on policy regarding regulation of nicotine content in cigarettes. They suggest that normal and slow nicotine metabolizers would respond differently to nicotine reduction in cigarettes, but that irrespective of metabolizer status, reductions to <0.763 mg/cigarette may contribute to temporary attentional deficits.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation.

PubMed

Muelken, Peter; Schmidt, Clare E; Shelley, David; Tally, Laura; Harris, Andrew C

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome.

A Two-Day Continuous Nicotine Infusion Is Sufficient to Demonstrate Nicotine Withdrawal in Rats as Measured Using Intracranial Self-Stimulation

PubMed Central

Muelken, Peter; Schmidt, Clare E.; Shelley, David; Tally, Laura; Harris, Andrew C.

2015-01-01

Avoidance of the negative affective (emotional) symptoms of nicotine withdrawal (e.g., anhedonia, anxiety) contributes to tobacco addiction. Establishing the minimal nicotine exposure conditions required to demonstrate negative affective withdrawal signs in animals, as well as understanding moderators of these conditions, could inform tobacco addiction-related research, treatment, and policy. The goal of this study was to determine the minimal duration of continuous nicotine infusion required to demonstrate nicotine withdrawal in rats as measured by elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior). Administration of the nicotinic acetylcholine receptor antagonist mecamylamine (3.0 mg/kg, s.c.) on alternate test days throughout the course of a 2-week continuous nicotine infusion (3.2 mg/kg/day via osmotic minipump) elicited elevations in ICSS thresholds beginning on the second day of infusion. Magnitude of antagonist-precipitated withdrawal did not change with further nicotine exposure and mecamylamine injections, and was similar to that observed in a positive control group receiving mecamylamine following a 14-day nicotine infusion. Expression of a significant withdrawal effect was delayed in nicotine-infused rats receiving mecamylamine on all test days rather than on alternate test days. In a separate study, rats exhibited a transient increase in ICSS thresholds following cessation of a 2-day continuous nicotine infusion (3.2 mg/kg/day). Magnitude of this spontaneous withdrawal effect was similar to that observed in rats receiving a 9-day nicotine infusion. Our findings demonstrate that rats exhibit antagonist-precipitated and spontaneous nicotine withdrawal following a 2-day continuous nicotine infusion, at least under the experimental conditions studied here. Magnitude of these effects were similar to those observed in traditional models involving more prolonged nicotine exposure. Further development of these models, including evaluation of more clinically relevant nicotine dosing regimens and other measures of nicotine withdrawal (e.g., anxiety-like behavior, somatic signs), may be useful for understanding the development of the nicotine withdrawal syndrome. PMID:26658557

Mitragynine Attenuates Withdrawal Syndrome in Morphine-Withdrawn Zebrafish

PubMed Central

Khor, Beng-Siang; Amar Jamil, Mohd Fadzly; Adenan, Mohamad Ilham; Chong Shu-Chien, Alexander

2011-01-01

A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway. PMID:22205946

Alteration of synaptic plasticity in rat dorsal striatum induced by chronic ethanol intake and withdrawal via ERK pathway.

PubMed

Cui, Sheng-zhong; Wang, Shen-jun; Li, Jing; Xie, Gui-qin; Zhou, Rong; Chen, Ling; Yuan, Xiao-ru

2011-02-01

The dorsal striatum has been proposed to contribute to the formation of drug-seeking behaviors, leading to excessive and compulsive drug usage, such as addiction. The current study aimed to investigate the involvement of extracellular signal-regulated kinase (ERK) pathway in the modification of striatal synaptic plasticity. Ethanol was administered to rats in drinking water at concentration of 6% (v/v) for 30 days. Rats were sacrificed on day 10, 20, or 30 during ethanol intake or on withdrawal day 1, 3, or 7 following 30-d ethanol intake. The striata were removed either for electrophysiological recording or for protein immuno-blot analysis. Extracellular recording technique was used to record population spikes (PS) induced by high-frequency stimulation (HFS) in the dorsolateral striatum (DLS). Corticostriatal long-term depression (LTD) was determined to be dependent upon ERK signaling. Chronic ethanol intake (CEI) attenuated ERK phosphorylation and LTD induction, whereas withdrawal for one day (W1D) potentiated ERK phosphorylation and LTD induction. These results showed that the impact of chronic ethanol intake and withdrawal on corticostriatal synaptic plasticity was associated with ethanol's effect on ERK phosphorylation. In particular, pharmacological inhibition of ERK hyper-phosphorylation by U0126 prevented LTD induction in the DLS and attenuated ethanol withdrawal syndrome as well. In rat DLS, chronic ethanol intake and withdrawal altered LTD induction via ERK signaling pathway. Ethanol withdrawal syndrome is mediated, at least partly, by ERK hyper-phosphorylation in the DLS.

Users of withdrawal method in the Islamic Republic of Iran: are they intending to use oral contraceptives? Applying the theory of planned behaviour.

PubMed

Rahnama, P; Hidarnia, A; Shokravi, F A; Kazemnejad, A; Montazeri, A; Najorkolaei, F R; Saburi, A

2013-09-01

Many couples in the Islamic Republic of Iran rely on coital withdrawal for contraception. The purpose of this cross-sectional study was to use the theory of planned behaviour to explore factors that influence withdrawal users' intent to switch to oral contraception (OC). Participants were 336 sexually active, married women, who were current users of withdrawal and were recruited from 5 public family planning clinics in Tehran. A questionnair included measures of the theory of planned behaviour: attitude (behavioural beliefs, outcome evaluations), subjective norms (normative beliefs, motivation to comply), perceived behaviour control, past behaviour and behavioural intention. Linear regression analyses showed that past behaviour, perceived behaviour control, attitude and subjective norms accounted for the highest percentage of total variance observed for intention to use OC (36%). Beliefs-based family planning education and counsellingshould to be designed for users of the withdrawal method.

The Role of Interleukin-6/GP130 Signaling in Prostate Cancer Progression and its Contribution to Bone Metastasis Morbidity

DTIC Science & Technology

2008-11-01

cancer cell survival, post-androgen withdrawal Task 1. To obtain BM18 tumor tissue that has regressed post-androgen withdrawal +/- IL-6...for analysis of IL-6 pathway molecules. Remaining tumor tissue was processed for routine histology and stained with Masson’s Trichome (Fig 2): - 7...recombinant human IL-6 or TSU xenografts yielded sera with detectable human IL-6 levels by ELISA (3pg/mL and 30pg/mL, respectively) (Twillie et al

Placebo caffeine reduces withdrawal in abstinent coffee drinkers.

PubMed

Mills, Llewellyn; Boakes, Robert A; Colagiuri, Ben

2016-04-01

Expectancies have been shown to play a role in the withdrawal syndrome of many drugs of addiction; however, no studies have examined the effects of expectancies across a broad range of caffeine withdrawal symptoms, including craving. The purpose of the current study was to use caffeine as a model to test the effect of expectancy on withdrawal symptoms, specifically whether the belief that one has ingested caffeine is sufficient to reduce caffeine withdrawal symptoms and cravings in abstinent coffee drinkers. We had 24-h abstinent regular coffee drinkers complete the Caffeine Withdrawal Symptom Questionnaire (CWSQ) before and after receiving decaffeinated coffee. One-half of the participants were led to believe the coffee was regular caffeinated coffee (the 'Told Caffeine' condition) and one-half were told that it was decaffeinated (the 'Told Decaf' condition). Participants in the Told Caffeine condition reported a significantly greater reduction in the factors of cravings, fatigue, lack of alertness and flu-like feelings of the CWSQ, than those in the Told Decaf condition. Our results indicated that the belief that one has consumed caffeine can affect caffeine withdrawal symptoms, especially cravings, even when no caffeine was consumed. © The Author(s) 2016.

Marital, parental, and whole-family predictors of toddlers' emotion regulation: The role of parental emotional withdrawal.

PubMed

Gallegos, Martin I; Murphy, Sarah E; Benner, Aprile D; Jacobvitz, Deborah B; Hazen, Nancy L

2017-04-01

The present study aims to address how dyadic and triadic family interactions across the transition to parenthood contribute to the later development of toddlers' adaptive emotion regulation using structural equation modeling methods. Specifically, we examined the interrelations of observed marital negative affect before childbirth, parents' emotional withdrawal during parent-infant interactions at 8 months, and coparenting conflict at 24 months as predictors of toddlers' adaptive emotion regulation at 24 months. Data for the present study were drawn from a longitudinal dataset in which 125 families were observed across the transition to parenthood. Results suggested that prenatal marital negativity predicted mothers' and fathers' emotional withdrawal toward their infants at 8 months postbirth as well as coparenting conflict at 24 months postbirth. Coparenting conflict and father-infant emotional withdrawal were negatively associated with toddlers' adaptive emotion regulation; however, mother-infant emotional withdrawal was not related. The implications of our study extend family systems research to demonstrate how multiple levels of detrimental family functioning over the first 2 years of parenthood influence toddlers' emotion regulation and highlight the importance of fathers' emotional involvement with their infants. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

End of life decisions: nurses perceptions, feelings and experiences.

PubMed

McMillen, Rachel E

2008-08-01

Decisions to withdraw treatment are made on a regular basis in intensive care units. While nurses play a central role in patient care, previous studies have found that they are not always involved in withdrawal decisions. To explore the experiences of ICU nurses caring for patients who have had their treatment withdrawn and to answer two research questions: what role do nurses play and how does this affect them? Constructivist grounded theory was used to explore the experiences and feelings of ICU nurses. A purposive sample of eight ICU nurses participated and semi-structured interviews were used to collect data. Framework analysis was used to facilitate systematic analysis. The analysis revealed two major themes (1) the nurse's role: experience counts, not really a nurse's decision, planting the seed, supporting the family and being a patient advocate and (2) perceptions of the withdrawal of treatment: getting the timing right and emotional labour. Nurses make an important contribution to end of life decisions and care. Guidelines recommend they have input into withdrawal decisions, therefore it is imperative that nurses are supported in this role and their responsibilities to continue to provide care during withdrawal.

Neural correlates of social approach and withdrawal in patients with major depression.

PubMed

Derntl, Birgit; Seidel, Eva-Maria; Eickhoff, Simon B; Kellermann, Thilo; Gur, Ruben C; Schneider, Frank; Habel, Ute

2011-01-01

Successful human interaction is based on correct recognition, interpretation, and appropriate reaction to facial affect. In depression, social skill deficits are among the most restraining symptoms leading to social withdrawal, thereby aggravating social isolation and depressive affect. Dysfunctional approach and withdrawal tendencies to emotional stimuli have been documented, but the investigation of their neural underpinnings has received limited attention. We performed an fMRI study including 15 depressive patients and 15 matched, healthy controls. All subjects performed two tasks, an implicit joystick task as well as an explicit rating task, both using happy, neutral, and angry facial expressions. Behavioral data analysis indicated a significant group effect, with depressed patients showing more withdrawal than controls. Analysis of the functional data revealed significant group effects for both tasks. Among other regions, we observed significant group differences in amygdala activation, with patients showing less response particularly during approach to happy faces. Additionally, significant correlations of amygdala activation with psychopathology emerged, suggesting that more pronounced symptoms are accompanied by stronger decreases of amygdala activation. Hence, our results demonstrate that depressed patients show dysfunctional social approach and withdrawal behavior, which in turn may aggravate the disorder by negative social interactions contributing to isolation and reinforcing cognitive biases.

Jogging Therapy for Hikikomori Social Withdrawal and Increased Cerebral Hemodynamics: A Case Report.

PubMed

Nishida, Masaki; Kikuchi, Senichiro; Fukuda, Kazuhito; Kato, Satoshi

2016-01-01

Severe social withdrawal, called hikikomori, has drawn increased public attention. However, an optimal clinical approach and strategy of treatment has not been well established. Here, we report a case of hikikomori for which an exercise intervention using jogging therapy was effective, showing cerebral hemodynamic improvement. The patient was a 20 year old Japanese male who was hospitalized in order to evaluate and treat severe social withdrawal. Although depressive and anxiety symptoms partially subsided with sertraline alone, social withdrawal persisted due to a lack of self confidence. With his consent, we implemented exercise therapy with 30 minutes of jogging three times a week for three months. We did not change the pharmacotherapy, and his social withdrawal remarkably improved with continuous jogging exercise. Using near infrared spectroscopy to evaluate hemodynamic alteration, bilateral temporal hemodynamics considerably increased after the three-month jogging therapy. Regarding exercise therapy for mental illness, numerous studies have reported the effectiveness of exercise therapy for major depression. This case implied, however, that the applicability of exercise therapy is not limited to major depressive disorder. Jogging therapy may contribute to reinforcing self confidence associated with "resilience" in conjunction with neurophysiological modulation of neural networks.

Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

PubMed Central

Richey, Laura; Doremus-Fitzwater, Tamara L.; Buck, Hollin M.; Deak, Terrence

2012-01-01

Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as “sickness behaviors,” with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100 μg/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5 g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed. PMID:22921768

INTRINSIC NEURONAL PLASTICITY IN THE JUXTACAPSULAR NUCLEUS OF THE BED NUCLEI OF THE STRIA TERMINALIS (jcBNST)

PubMed Central

Francesconi, Walter; Berton, Fulvia; Koob, George F.; Sanna, Pietro Paolo

2010-01-01

The juxtacapsular nucleus of the anterior division of the BNST (jcBNST) receives robust glutamatergic projections from the basolateral nucleus of the amygdala (BLA), the postpiriform transition area, and the insular cortex as well as dopamine (DA) inputs from the midbrain. In turn the jcBNST sends GABAergic projections to the medial division of the central nucleus of the amygdala (CEAm) as well as other brain regions. We recently described a form of long-term potentiation of the intrinsic excitability (LTP-IE) of neurons of the juxtacapsular nucleus of BNST (jcBNST) in response to high-frequency stimulation (HFS) of the stria terminalis that was impaired during protracted withdrawal from alcohol, cocaine, and heroin and in rats chronically treated with corticotropin releasing factor (CRF) intracerebroventricularly. Here we show that DAergic neurotransmission is required for the induction of LTP-IE of jcBNTS neurons through dopamine (DA) D1 receptors. Thus, activation of the central CRF stress system and altered DAergic neurotransmission during protracted withdrawal from alcohol and drugs of abuse may contribute to the disruption of LTP-IE in the jcBNST. Impairment of this form of intrinsic neuronal plasticity in the jcBNST could result in inadequate neuronal integration and reduced inhibition of the CEA, contributing to the negative affective state that characterizes protracted abstinence in post-dependent individuals. These results provide a novel neurobiological target for vulnerability to alcohol and drug dependence. PMID:19683025

[The nursing profession regarding limitation of life support treatment in the intensive care units. Technical and practical features].

PubMed

Falcó-Pegueroles, A

2009-01-01

The scientific and technical developments in medicine in the recent decades have greatly helped to increase life expectancy and quality of life of many patients. In hospitals, this technological scenario has clearly influenced patient care, for example, in the Intensive Medicine Departments, leading to new clinical perspectives and has made the growing complexity of giving treatment and making decisions more evident. In some cases, it is difficult to predict how beneficial intensive medical care can be when there is no reasonable prospect of improving the patient's health, prolonging their life in situations with poor prognosis or dramatically reducing their quality of life. The clinical diagnosis of irreversibility, through indicators of severity and principles of beneficence, autonomy and justice in the professional conduct are the elements that give rise to the consideration of withholding and withdrawing treatment in the critical patient. However, there are other factors that need to be taken into consideration and that are analyzed by professional ethics and bioethics. It is from this approach that any decision involving withholding and withdrawing treatment should be taken so that these decisions can be considered estimable form an ethical point of view. The nursing professional in intensive care units is expected to actively participate in decision making by contributing with their humanizing vision and care ethics. They should be aware of their contribution in the medical team behaving, representing and encouraging the requirements of bioethics.

Redox-based epigenetic status in drug addiction: a potential contributor to gene priming and a mechanistic rationale for metabolic intervention

PubMed Central

Trivedi, Malav S.; Deth, Richard

2015-01-01

Alcohol and other drugs of abuse, including psychostimulants and opioids, can induce epigenetic changes: a contributing factor for drug addiction, tolerance, and associated withdrawal symptoms. DNA methylation is a major epigenetic mechanism and it is one of more than 200 methylation reactions supported by methyl donor S-adenosylmethionine (SAM). Levels of SAM are controlled by cellular redox status via the folate and vitamin B12-dependent enzyme methionine synthase (MS). For example, under oxidative conditions MS is inhibited, diverting its substrate homocysteine (HCY) to the trans sulfuration pathway. Alcohol, dopamine, and morphine, can alter intracellular levels of glutathione (GSH)-based cellular redox status, subsequently affecting SAM levels and DNA methylation status. Here, existing evidence is presented in a coherent manner to propose a novel hypothesis implicating the involvement of redox-based epigenetic changes in drug addiction. Further, we discuss how a “gene priming” phenomenon can contribute to the maintenance of redox and methylation status homeostasis under various stimuli including drugs of abuse. Additionally, a new mechanistic rationale for the use of metabolic interventions/redox-replenishers as symptomatic treatment of alcohol and other drug addiction and associated withdrawal symptoms is also provided. Hence, the current review article strengthens the hypothesis that neuronal metabolism has a critical bidirectional coupling with epigenetic changes in drug addiction exemplified by the link between redox-based metabolic changes and resultant epigenetic consequences under the effect of drugs of abuse. PMID:25657617

Redox-based epigenetic status in drug addiction: a potential contributor to gene priming and a mechanistic rationale for metabolic intervention.

PubMed

Trivedi, Malav S; Deth, Richard

2014-01-01

Alcohol and other drugs of abuse, including psychostimulants and opioids, can induce epigenetic changes: a contributing factor for drug addiction, tolerance, and associated withdrawal symptoms. DNA methylation is a major epigenetic mechanism and it is one of more than 200 methylation reactions supported by methyl donor S-adenosylmethionine (SAM). Levels of SAM are controlled by cellular redox status via the folate and vitamin B12-dependent enzyme methionine synthase (MS). For example, under oxidative conditions MS is inhibited, diverting its substrate homocysteine (HCY) to the trans sulfuration pathway. Alcohol, dopamine, and morphine, can alter intracellular levels of glutathione (GSH)-based cellular redox status, subsequently affecting SAM levels and DNA methylation status. Here, existing evidence is presented in a coherent manner to propose a novel hypothesis implicating the involvement of redox-based epigenetic changes in drug addiction. Further, we discuss how a "gene priming" phenomenon can contribute to the maintenance of redox and methylation status homeostasis under various stimuli including drugs of abuse. Additionally, a new mechanistic rationale for the use of metabolic interventions/redox-replenishers as symptomatic treatment of alcohol and other drug addiction and associated withdrawal symptoms is also provided. Hence, the current review article strengthens the hypothesis that neuronal metabolism has a critical bidirectional coupling with epigenetic changes in drug addiction exemplified by the link between redox-based metabolic changes and resultant epigenetic consequences under the effect of drugs of abuse.

Symptomatic hyponatremia in association with a low-iodine diet and levothyroxine withdrawal prior to I131 in patients with metastatic thyroid carcinoma.

PubMed

Shakir, Mohamed K M; Krook, Linda S; Schraml, Frank V; Hays, James H; Clyde, Patrick W

2008-07-01

Strategies to improve I131 uptake in thyroid carcinoma include levothyroxine (LT4) withdrawal or thyrotropin (TSH) administration along with a low-iodine diet. We report five patients with papillary or follicular thyroid carcinoma who developed symptomatic hyponatremia during LT4 withdrawal and low-iodine diet. Four patients had pulmonary and/or brain metastases. All had restricted iodine intakes during LT4 withdrawal. Presenting complaints included weakness, dizziness, fainting spells, lethargy, and/or nausea. Baseline serum sodium levels while on LT4 suppression were normal. During presentation all were hypothyroid and serum sodium ranged from 110 to 121 mmol/L (normal 135-148). Despite hyponatremia, the plasma renin activity and serum aldosterone levels were suppressed, indicating volume expansion. The hyponatremia responded to fluid restriction and normalized after LT4 replacement. Low sodium intake, inappropriate antidiuretic hormone secretion syndrome (SIADH)-like disorder secondary to hypothyroidism and/or lung or cerebral metastases may have contributed to hyponatremia. The development of hyponatremia during LT4 withdrawal and low-iodine diet in otherwise healthy patients with thyroid carcinoma is extremely rare. However, elderly patients with metastatic thyroid carcinoma need observation during LT4 withdrawal combined with a low-iodine diet and should receive instruction to take iodine-free sodium chloride. Free water restriction may be necessary in some patients.

Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

PubMed

Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

2018-05-01

Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Impacts of crop insurance on water withdrawals for irrigation

NASA Astrophysics Data System (ADS)

Deryugina, Tatyana; Konar, Megan

2017-12-01

Agricultural production remains particularly vulnerable to weather fluctuations and extreme events, such as droughts, floods, and heat waves. Crop insurance is a risk management tool developed to mitigate some of this weather risk and protect farmer income in times of poor production. However, crop insurance may have unintended consequences for water resources sustainability, as the vast majority of freshwater withdrawals go to agriculture. The causal impact of crop insurance on water use in agriculture remains poorly understood. Here, we determine the empirical relationship between crop insurance and irrigation water withdrawals in the United States. Importantly, we use an instrumental variables approach to establish causality. Our methodology exploits a major policy change in the crop insurance system - the 1994 Federal Crop Insurance Reform Act - which imposed crop insurance requirements on farmers. We find that a 1% increase in insured crop acreage leads to a 0.223% increase in irrigation withdrawals, with most coming from groundwater aquifers. We identify farmers growing more groundwater-fed cotton as an important mechanism contributing to increased withdrawals. A 1% increase in insured crop acreage leads to a 0.624% increase in cotton acreage, or 95,602 acres. These results demonstrate that crop insurance causally leads to more irrigation withdrawals. More broadly, this work underscores the importance of determining causality in the water-food nexus as we endeavor to achieve global food security and water resources sustainability.

Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats.

PubMed

Schunck, Rebeca Vargas Antunes; Macedo, Isabel Cristina; Laste, Gabriela; de Souza, Andressa; Valle, Marina Tuerlinckx Costa; Salomón, Janaína L O; Nunes, Ellen Almeida; Campos, Andreia Cristina Wildner; Gnoatto, Simone Cristina Baggio; Bergold, Ana Maria; Konrath, Eduardo L; Dallegrave, Eliane; Arbo, Marcelo Dutra; Torres, Iraci L S; Leal, Mirna Bainy

2017-08-01

Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Tolerance and Withdrawal From Prolonged Opioid Use in Critically Ill Children

PubMed Central

Anand, Kanwaljeet J. S.; Willson, Douglas F.; Berger, John; Harrison, Rick; Meert, Kathleen L.; Zimmerman, Jerry; Carcillo, Joseph; Newth, Christopher J. L.; Prodhan, Parthak; Dean, J. Michael; Nicholson, Carol

2012-01-01

OBJECTIVE After prolonged opioid exposure, children develop opioid-induced hyperalgesia, tolerance, and withdrawal. Strategies for prevention and management should be based on the mechanisms of opioid tolerance and withdrawal. PATIENTS AND METHODS Relevant manuscripts published in the English language were searched in Medline by using search terms “opioid,” “opiate,” “sedation,” “analgesia,” “child,” “infant-newborn,” “tolerance,” “dependency,” “withdrawal,” “analgesic,” “receptor,” and “individual opioid drugs.” Clinical and preclinical studies were reviewed for data synthesis. RESULTS Mechanisms of opioid-induced hyperalgesia and tolerance suggest important drug- and patient-related risk factors that lead to tolerance and withdrawal. Opioid tolerance occurs earlier in the younger age groups, develops commonly during critical illness, and results more frequently from prolonged intravenous infusions of short-acting opioids. Treatment options include slowly tapering opioid doses, switching to longer-acting opioids, or specifically treating the symptoms of opioid withdrawal. Novel therapies may also include blocking the mechanisms of opioid tolerance, which would enhance the safety and effectiveness of opioid analgesia. CONCLUSIONS Opioid tolerance and withdrawal occur frequently in critically ill children. Novel insights into opioid receptor physiology and cellular biochemical changes will inform scientific approaches for the use of opioid analgesia and the prevention of opioid tolerance and withdrawal. PMID:20403936

Betaxolol, a selective β1-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats

PubMed Central

Rudoy, C.A.; Van Bockstaele, E.J.

2007-01-01

Background Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on β-adrenergic receptor (β1 and β2) expression in the amygdala. Methods Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that β1–adrenergic receptor, but not β2–adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective β1–adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 hours following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 hours following the last betaxolol injection. Following behavioral testing, betaxolol effects on β1-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Results Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline. Furthermore, treatment with betaxolol during early cocaine withdrawal significantly decreased β1-adrenergic receptor protein expression in the amygdala to levels comparable to those of control animals. Conclusions The present findings suggest that the anxiolytic-like effect of betaxolol on cocaine-induced anxiety may be related to its effect on amygdalar β1-adrenergic receptors that are up-regulated during early phases of drug withdrawal. These data support the efficacy of betaxolol as a potential effective pharmacotherapy in treating cocaine withdrawal-induced anxiety during early phases of abstinence. PMID:17513029

Betaxolol, a selective beta(1)-adrenergic receptor antagonist, diminishes anxiety-like behavior during early withdrawal from chronic cocaine administration in rats.

PubMed

Rudoy, C A; Van Bockstaele, E J

2007-06-30

Anxiety has been indicated as one of the main symptoms of the cocaine withdrawal syndrome in human addicts and severe anxiety during withdrawal may potentially contribute to relapse. As alterations in noradrenergic transmission in limbic areas underlie withdrawal symptomatology for many drugs of abuse, the present study sought to determine the effect of cocaine withdrawal on beta-adrenergic receptor (beta(1) and beta(2)) expression in the amygdala. Male Sprague Dawley rats were administered intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once daily for 14 days. Two days following the last cocaine injection, amygdala brain regions were micro-dissected and processed for Western blot analysis. Results showed that beta(1)-adrenergic receptor, but not beta(2)-adrenergic receptor expression was significantly increased in amygdala extracts of cocaine-withdrawn animals as compared to controls. This finding motivated further studies aimed at determining whether treatment with betaxolol, a highly selective beta(1)-adrenergic receptor antagonist, could ameliorate cocaine withdrawal-induced anxiety. In these studies, betaxolol (5 mg/kg via i.p. injection) was administered at 24 and then 44 h following the final chronic cocaine administration. Anxiety-like behavior was evaluated using the elevated plus maze test approximately 2 h following the last betaxolol injection. Following behavioral testing, betaxolol effects on beta(1)-adrenergic receptor protein expression were examined by Western blotting in amygdala extracts from rats undergoing cocaine withdrawal. Animals treated with betaxolol during cocaine withdrawal exhibited a significant attenuation of anxiety-like behavior characterized by increased time spent in the open arms and increased entries into the open arms compared to animals treated with only saline during cocaine withdrawal. In contrast, betaxolol did not produce anxiolytic-like effects in control animals treated chronically with saline. Furthermore, treatment with betaxolol during early cocaine withdrawal significantly decreased beta(1)-adrenergic receptor protein expression in the amygdala to levels comparable to those of control animals. The present findings suggest that the anxiolytic-like effect of betaxolol on cocaine-induced anxiety may be related to its effect on amygdalar beta(1)-adrenergic receptors that are up-regulated during early phases of drug withdrawal. These data support the efficacy of betaxolol as a potential effective pharmacotherapy in treating cocaine withdrawal-induced anxiety during early phases of abstinence.

Differential involvement of 3', 5'-cyclic adenosine monophosphate-dependent protein kinase in regulation of Fos and tyrosine hydroxylase expression in the heart after naloxone induced morphine withdrawal.

PubMed

Almela, Pilar; Cerezo, Manuela; González-Cuello, A; Milanés, M Victoria; Laorden, M Luisa

2007-01-01

We previously demonstrated that morphine withdrawal induced hyperactivity of the heart by the activation of noradrenergic pathways innervating the left and right ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. We investigated whether cAMP-dependent protein kinase (PKA) plays a role in this process by estimating changes in PKA immunoreactivity and the influence of inhibitor of PKA on Fos protein expression, tyrosine hydroxylase (TH) immunoreactivity levels and NA turnover in the left and right ventricle. Dependence on morphine was induced by a 7-day s.c. implantation of morphine pellets. Morphine withdrawal was precipitated on day 8 by an injection of naloxone (5 mg/kg). When opioid withdrawal was precipitated, an increase in PKA immunoreactivity and phospho-CREB (cyclic AMP response element protein) levels were observed in the heart. Moreover, morphine withdrawal induces Fos expression, an enhancement of NA turnover and an increase in the total TH levels. When the selective PKA inhibitor HA-1004 was infused, concomitantly with morphine pellets, it diminished the increase in NA turnover and the total TH levels observed in morphine-withdrawn rats. However, this inhibitor neither modifies the morphine withdrawal induced Fos expression nor the increase of nonphosphorylated TH levels. The present findings indicate that an up-regulated PKA-dependent transduction pathway might contribute to the activation of the cardiac catecholaminergic neurons in response to morphine withdrawal and suggest that Fos is not a target of PKA at heart levels.

Voluntary Withdrawal: Why Don't They Return?

ERIC Educational Resources Information Center

Ironside, Ellen M.

Factors that influence voluntary withdrawal from the University of North Carolina at Chapel Hill are investigated. A survey based on a cohort of students admitted for the first time in fall 1977 was conducted with a response rate of approximately 50 percent. Major and minor reasons for not returning to the university are tabulated for males and…

Treatment for amphetamine withdrawal.

PubMed

Shoptaw, Steven J; Kao, Uyen; Heinzerling, Keith; Ling, Walter

2009-04-15

Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different. To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes. MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles. All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms. Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes. Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear. One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms. No medication is effective for treatment of amphetamine withdrawal. Amineptine showed reduction in discontinuation rates and improvement in clinical presentation compared to placebo, but had no effect on reducing withdrawal symptoms or craving. In spite of these limited benefits, amineptine is not available for use due to concerns over abuse liability when using the drug. The benefits of mirtazapine as a withdrawal agent are less clear based on findings from two randomised controlled trials: one report showed improvements in amphetamine withdrawal symptoms over placebo; a second report showed no differences in withdrawal symptoms compared to placebo. Further potential treatment studies should examine medications that increase central nervous system activity involving dopamine, norepinephrine and/or serotonin neurotransmitters, including mirtazapine.

Understanding Older Adult's Technology Adoption and Withdrawal for Elderly Care and Education: Mixed Method Analysis from National Survey.

PubMed

Chiu, Ching-Ju; Liu, Chia-Wen

2017-11-03

Elderly adults have comprised the fastest growing population adopting the Internet and computer technology over the past decade. However, how their experiences can shed light on elderly learning theory has not been examined much in the literature. This study investigated the factors and reasons associated with Internet adoption and withdrawal among older adults in Taiwan, and if any gender differences exist in this context. Data on participants aged 50 years and older from the nationally representative "Digital Opportunity Survey on Individuals and Households in Taiwan," who did not use the Internet in 2005 but adopted it in 2007 (n=1548), and those who reported using Internet in 2011 but then withdrew (n=1575), were analyzed. Factors and reasons associated with Internet adoption and withdrawal were examined using both quantitative and qualitative data. Education level independently predicted Internet adoption behavior. With regard to the reasons for adoption, 66% (62/94) of participants indicated they started using the Internet to meet certain "needs"; for example, "keeping up with the world" (40.4%, 38/94) was listed as the most critical reason, followed by "job needs" (25.5%, 24/94). Older adults with a positive attitude toward the Internet with regard to increasing employment opportunities (OR 2.0, 95% CI 1.0-3.9, P=.04) and the amount of information obtained (OR 0.5, 95% CI 0.3-0.9, P=.01), as well as enriching recreation and entertainment (OR 0.6, 95% CI 0.4-0.9, P=.02), were less likely to withdraw from the Internet. The most common reason for Internet withdrawal was "psychological barriers" (eg, no available time, no meaningful use, or nothing worth reading/watching; 66.3%, 193/291), followed by "health barriers" (eg, eyes or body deteriorate with Internet use; 21.0%, 61/291). Although psychological barriers were the most important factor for Internet withdrawal for both men (72.5%, 100/138) and women (62%, 93/150), women were more likely than men to be affected by health barriers (26.0%, 39/150 vs 15.9%, 22/138; P=.004) and anthropic factors or accidental barriers (7.3%, 11/150 vs 2.9%, 4/138; P=.02). Our findings that the need to keep up with the world associated with Internet adoption, and gender differences in reasons behind Internet withdrawal, such that women reported more health and anthropic factors or accidental barriers than man, may provide a new perspective that help health educators understand strategies that encourage older adults to keep learning, an important component of active aging. ©Ching-Ju Chiu, Chia-Wen Liu. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 03.11.2017.

Understanding Older Adult's Technology Adoption and Withdrawal for Elderly Care and Education: Mixed Method Analysis from National Survey

PubMed Central

Liu, Chia-Wen

2017-01-01

Background Elderly adults have comprised the fastest growing population adopting the Internet and computer technology over the past decade. However, how their experiences can shed light on elderly learning theory has not been examined much in the literature. Objective This study investigated the factors and reasons associated with Internet adoption and withdrawal among older adults in Taiwan, and if any gender differences exist in this context. Methods Data on participants aged 50 years and older from the nationally representative “Digital Opportunity Survey on Individuals and Households in Taiwan,” who did not use the Internet in 2005 but adopted it in 2007 (n=1548), and those who reported using Internet in 2011 but then withdrew (n=1575), were analyzed. Factors and reasons associated with Internet adoption and withdrawal were examined using both quantitative and qualitative data. Results Education level independently predicted Internet adoption behavior. With regard to the reasons for adoption, 66% (62/94) of participants indicated they started using the Internet to meet certain “needs”; for example, “keeping up with the world” (40.4%, 38/94) was listed as the most critical reason, followed by “job needs” (25.5%, 24/94). Older adults with a positive attitude toward the Internet with regard to increasing employment opportunities (OR 2.0, 95% CI 1.0-3.9, P=.04) and the amount of information obtained (OR 0.5, 95% CI 0.3-0.9, P=.01), as well as enriching recreation and entertainment (OR 0.6, 95% CI 0.4-0.9, P=.02), were less likely to withdraw from the Internet. The most common reason for Internet withdrawal was “psychological barriers” (eg, no available time, no meaningful use, or nothing worth reading/watching; 66.3%, 193/291), followed by “health barriers” (eg, eyes or body deteriorate with Internet use; 21.0%, 61/291). Although psychological barriers were the most important factor for Internet withdrawal for both men (72.5%, 100/138) and women (62%, 93/150), women were more likely than men to be affected by health barriers (26.0%, 39/150 vs 15.9%, 22/138; P=.004) and anthropic factors or accidental barriers (7.3%, 11/150 vs 2.9%, 4/138; P=.02). Conclusions Our findings that the need to keep up with the world associated with Internet adoption, and gender differences in reasons behind Internet withdrawal, such that women reported more health and anthropic factors or accidental barriers than man, may provide a new perspective that help health educators understand strategies that encourage older adults to keep learning, an important component of active aging. PMID:29101093

Neuronal BDNF Signaling Is Necessary for the Effects of Treadmill Exercise on Synaptic Stripping of Axotomized Motoneurons

PubMed Central

Krakowiak, Joey; Liu, Caiyue; Papudesu, Chandana; Ward, P. Jillian; Wilhelm, Jennifer C.; English, Arthur W.

2015-01-01

The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells. PMID:25918648

Disruption of the CRF(2) receptor pathway decreases the somatic expression of opiate withdrawal.

PubMed

Papaleo, Francesco; Ghozland, Sandy; Ingallinesi, Manuela; Roberts, Amanda J; Koob, George F; Contarino, Angelo

2008-11-01

Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF(1) and CRF(2). To investigate the role for the CRF(2) receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF(2) receptor (CRF(2)-/-). We employed a novel, clinically relevant mouse model of 'spontaneous' opiate withdrawal as well as a classical opioid receptor antagonist (naloxone)-precipitated opiate withdrawal paradigm. To induce opiate dependence, mice were treated with intermittent escalating morphine doses (20-100 mg/kg, i.p.). We found that 8-128 h after the last opiate injection, CRF(2)-/- mice showed decreased levels of major somatic signs of spontaneous opiate withdrawal, such as paw tremor and wet dog shake, as compared to wild-type mice. Similarly, challenge with naloxone 2 h after the last morphine injection induced lower levels of paw tremor and wet dog shake in CRF(2)-/- mice as compared to wild-type mice. Despite the differences in somatic signs, wild-type and CRF(2)-/- mice displayed similar plasma corticosterone responses to opiate dosing and withdrawal, indicating a marginal role for the hypothalamus-pituitary-adrenal axis in the CRF(2) receptor mediation of opiate withdrawal. Our results unravel a novel role for the CRF(2) receptor pathway in opiate withdrawal. The CRF(2) receptor pathway might be a critical target of therapies aimed at alleviating opiate withdrawal symptoms and reducing relapse to drug intake.

Disruption of the CRF2 Receptor Pathway Decreases the Somatic Expression of Opiate Withdrawal

PubMed Central

Papaleo, Francesco; Ghozland, Sandy; Ingallinesi, Manuela; Roberts, Amanda J; Koob, George F; Contarino, Angelo

2009-01-01

Escape from the extremely aversive opiate withdrawal symptoms powerfully motivates compulsive drug-seeking and drug-taking behaviors. The corticotropin-releasing factor (CRF) system is hypothesized to mediate the motivational properties of drug dependence. CRF signaling is transmitted by two receptor pathways, termed CRF1 and CRF2. To investigate the role for the CRF2 receptor pathway in somatic opiate withdrawal, in the present study we used genetically engineered mice deficient in the CRF2 receptor (CRF2−/−). We employed a novel, clinically relevant mouse model of ‘spontaneous’ opiate withdrawal as well as a classical opioid receptor antagonist (naloxone)-precipitated opiate withdrawal paradigm. To induce opiate dependence, mice were treated with intermittent escalating morphine doses (20–100 mg/kg, i.p.). We found that 8–128 h after the last opiate injection, CRF2−/− mice showed decreased levels of major somatic signs of spontaneous opiate withdrawal, such as paw tremor and wet dog shake, as compared to wild-type mice. Similarly, challenge with naloxone 2 h after the last morphine injection induced lower levels of paw tremor and wet dog shake in CRF2−/− mice as compared to wild-type mice. Despite the differences in somatic signs, wild-type and CRF2−/− mice displayed similar plasma corticosterone responses to opiate dosing and withdrawal, indicating a marginal role for the hypothalamus–pituitary–adrenal axis in the CRF2 receptor mediation of opiate withdrawal. Our results unravel a novel role for the CRF2 receptor pathway in opiate withdrawal. The CRF2 receptor pathway might be a critical target of therapies aimed at alleviating opiate withdrawal symptoms and reducing relapse to drug intake. PMID:18288089

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice

PubMed Central

Lee, Bridgin G.; Anastasia, Agustin; Hempstead, Barbara L.; Lee, Francis S.

2015-01-01

Introduction: Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. Methods: This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNFMet/Met) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Results: Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNFMet/Met mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNFMet/Met mice; and (3) an increase in BDNF prodomain in BDNFMet/Met mice following nicotine withdrawal. Conclusions: Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNFMet/Met mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. PMID:25744957

Simulation of the Effects of Water Withdrawals, Wastewater Return Flows, and Land-Use Change on Streamflow in the Blackstone River Basin, Massachusetts and Rhode Island

USGS Publications Warehouse

Barbaro, Jeffrey R.

2007-01-01

Streamflow in many parts of the Blackstone River Basin in south-central Massachusetts and northern Rhode Island is altered by water-supply withdrawals, wastewater-return flows, and land-use change associated with a growing population. Simulations from a previously developed and calibrated Hydrological Simulation Program?FORTRAN (HSPF) precipitation-runoff model for the basin were used to evaluate the effects of water withdrawals, wastewater-return flows, and land-use change on streamflow. Most of the simulations were done for recent (1996?2001) conditions and potential buildout conditions in the future when all available land is developed to provide a long-range assessment of the effects of possible future human activities on water resources in the basin. The effects of land-use change were evaluated by comparing the results of long-term (1960?2004) simulations with (1) undeveloped land use, (2) 1995?1999 land use, and (3) potential buildout land use at selected sites across the basin. Flow-duration curves for these land-use scenarios were similar, indicating that land-use change, as represented in the HSPF model, had little effect on flow in the major tributary streams and rivers in the basin. However, land-use change?particularly increased effective impervious area?could potentially have greater effects on the hydrology, water quality, and aquatic habitat of the smaller streams in the basin. The effects of water withdrawals and wastewater-return flows were evaluated by comparing the results of long-term simulations with (1) no withdrawals and return flows, (2) actual (measured) 1996?2001 withdrawals and wastewater-return flows, and (3) potential withdrawals and wastewater-return flows at buildout. Overall, the results indicated that water use had a much larger effect on streamflow than did land use, and that the location and magnitude of wastewater-return flows were important for lessening the effects of withdrawals on streamflow in the Blackstone River Basin. Ratios of long-term (1960?2004) simulated flows with 1996?2001 water use (representing the net effect of withdrawals and wastewater-return flows) to long-term simulated flows with no water use indicated that, for many reaches, 1996?2001 water use did not deplete flows at the 90-percent flow duration substantially compared to flows unaffected by water use. Flows generally were more severely depleted in the reaches that include surface-water supplies for the larger cities in the basin (Kettle and Tatnuck Brooks, Worcester, Mass. water supply; Quinsigamond River, Shrewsbury, Mass. water supply; Crookfall Brook, Woonsocket, R.I. water supply; and Abbott Run, Pawtucket, R.I. water supply). These reaches did not have substantial wastewater-return flows that could offset the effects of the withdrawals. In contrast, wastewater-return flows from the Upper Blackstone Wastewater Treatment Facility in Millbury, Mass. increased flows at the 90-percent flow duration in the main stem of the Blackstone River compared to no-water-use conditions. Under the assumptions used to develop the buildout scenario, nearly all of the new water withdrawals were returned to the Blackstone River Basin at municipal wastewater-treatment plants or on-site septic systems. Consequently, buildout generally had small effects on simulated low flows in the Blackstone River and most of the major tributary streams compared to flows with 1996?2001 water use. To evaluate the effects of water use on flows in the rivers and major tributary streams in the Rhode Island part of the basin in greater detail, the magnitudes of water withdrawals and wastewater-return flows in relation to simulated streamflow were calculated as unique ratios for individual HSPF subbasins, total contributing areas to HSPF subbasins, and total contributing areas to the major tributary streams. For recent conditions (1996?2001 withdrawals and 1995?1999 land use), ratios of average summer (June through September) withdrawals to the l

Effects of ground-water withdrawals on flow in the Sauk River Valley Aquifer and on streamflow in the Cold Spring area, Minnesota

USGS Publications Warehouse

Lindgren, R.J.

2001-01-01

The simulated contributing areas for selected watersupply wells in the Cold Spring area generally extend to and possibly beyond the model boundaries to the north and to the southeast. The contributing areas for the Gold'n Plump Poultry Processing Plant supply wells extend: (1) to the Sauk River, (2) to the north to and possibly beyond to the northern model boundary, and (3) to the southeast to and possibly beyond the southeastern model boundary. The primary effects of projected increased ground-water withdrawals of 0.23 cubic feet per second (7.5 percent increase) were to: (1) decrease outflow from the Sauk River Valley aquifer through constant-head boundaries and (2) decrease leakage from the valley unit of the Sauk River Valley aquifer to the streams. No appreciable differences were discernible between the simulated steady-state contributing areas to wells with 1998 pumpage and those with the projected pumpage.

Distinct Mu, Delta, and Kappa Opioid Receptor Mechanisms Underlie Low Sociability and Depressive-Like Behaviors During Heroin Abstinence

PubMed Central

Lutz, Pierre-Eric; Ayranci, Gulebru; Chu-Sin-Chung, Paul; Matifas, Audrey; Koebel, Pascale; Filliol, Dominique; Befort, Katia; Ouagazzal, Abdel-Mouttalib; Kieffer, Brigitte L

2014-01-01

Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse. PMID:24874714

Opioid dependence

PubMed Central

2011-01-01

Introduction Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three stages to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final stage is relapse prevention. This treatment process contributes to recovery of the individual, which also includes improved overall health and wellbeing, as well as engagement in society. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimens. PMID:21929827

Climate, water use, and land surface transformation in an irrigation intensive watershed - streamflow responses from 1950 through 2010

USGS Publications Warehouse

Dale, Joseph; Zou, Chris B.; Andrews, William J.; Long, James M.; Liang, Ye; Qiao, Lei

2015-01-01

Climatic variability and land surface change have a wide range of effects on streamflow and are often difficult to separate. We analyzed long-term records of climate, land use and land cover, and re-constructed the water budget based on precipitation, groundwater levels, and water use from 1950 through 2010 in the Cimarron–Skeleton watershed and a portion of the Cimarron–Eagle Chief watershed in Oklahoma, an irrigation-intensive agricultural watershed in the Southern Great Plains, USA. Our results show that intensive irrigation through alluvial aquifer withdrawal modifies climatic feedback and alters streamflow response to precipitation. Increase in consumptive water use was associated with decreases in annual streamflow, while returning croplands to non-irrigated grasslands was associated with increases in streamflow. Along with groundwater withdrawal, anthropogenic-induced factors and activities contributed nearly half to the observed variability of annual streamflow. Streamflow was more responsive to precipitation during the period of intensive irrigation between 1965 and 1984 than the period of relatively lower water use between 1985 and 2010. The Cimarron River is transitioning from a historically flashy river to one that is more stable with a lower frequency of both high and low flow pulses, a higher baseflow, and an increased median flow due in part to the return of cropland to grassland. These results demonstrated the interrelationship among climate, land use, groundwater withdrawal and streamflow regime and the potential to design agricultural production systems and adjust irrigation to mitigate impact of increasing climate variability on streamflow in irrigation intensive agricultural watershed.

Opioid dependence.

PubMed

Praveen, K Thyarappa; Law, Fergus; O'Shea, Jacinta; Melichar, Jan

2011-09-20

Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three stages to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final stage is relapse prevention. This treatment process contributes to recovery of the individual, which also includes improved overall health and wellbeing, as well as engagement in society. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimens.

Pinellia ternata Attenuates Mucus Secretion and Airway Inflammation after Inhaled Corticosteroid Withdrawal in COPD Rats.

PubMed

Du, Wei; Su, Jinyu; Ye, Dan; Wang, Yuegang; Huang, Qiaobing; Gong, Xiaowei

2016-01-01

Inhaled corticosteroids (ICS) are widely used to manage chronic obstructive pulmonary disease (COPD). However, withdrawal of ICS generally causes various adverse effects, warranting careful management of the ICS withdrawal. Pinellia ternata, a traditional Chinese herbal medicine, has been used to treat respiratory diseases in China for centuries. Here, we investigated its role in antagonizing ICS withdrawal-induced side effects, and explored the underlying mechanisms. The rat COPD model was established using a combination of passive cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS). COPD rats were treated with saline or budesonide inhalation, or with budesonide inhalation followed by saline inhalation or Pinellia ternata gavage. The number of goblet cells and the level of mucin 5AC (MUC5AC) were enhanced by budesonide withdrawal. Pinellia ternata treatment significantly blocked these effects. Further, Pinellia ternata treatment reversed budesonide withdrawal-induced increase of interleukin 1[Formula: see text] (IL-1[Formula: see text] and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) levels in bronchoalveolar lavage fluid (BALF). Extracellular signal-regulated kinase (ERK), but neither p38 nor c-Jun N-terminal kinase (JNK), was activated by budesonide withdrawal, and the activation was blocked by Pinellia ternata treatment. The MUC5AC expression was positively correlated with goblet cell number, IL-1[Formula: see text] and TNF-[Formula: see text] levels, and ERK activity. Pinellia ternata treatment protected the airway from ICS withdrawal-induced mucus hypersecretion and airway inflammation by inhibiting ERK activation. Pinellia ternata treatment may represent a novel therapeutic strategy to prevent ICS withdrawal-induced side effects in COPD patients.

Generalised pustular psoriasis induced by cyclosporin a withdrawal responding to the tumour necrosis factor alpha inhibitor etanercept.

PubMed

Kamarashev, J; Lor, P; Forster, A; Heinzerling, L; Burg, G; Nestle, F O

2002-01-01

We report a 50-year-old male patient with a 15-year history of psoriasis including mutilating psoriatic arthritis, in whom the withdrawal of cyclosporin A induced a generalised pustular exacerbation and a aggravation of the joint condition. Two weekly injections of 25 mg of the tumour necrosis factor alpha inhibitor etanercept led to a rapid improvement of his psoriatic arthritis, as well as regression of the pustular eruption, while residual erythema was still present. The clinical response was reflected by an increase in circulating interleukin (IL) 10 and a decrease in IL-6 and IL-8 serum levels during treatment. We conclude that etanercept may be a safe and effective therapy not only in severe psoriatic arthritis, but also in cases of pustular rebound after withdrawal of immunosuppressive agents. Copyright 2002 S. Karger AG, Basel

Mitochondrial respiratory control is lost during growth factor deprivation

PubMed Central

Gottlieb, Eyal; Armour, Sean M.; Thompson, Craig B.

2002-01-01

The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-xL, restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control. PMID:12228733

Very early withdrawal from treatment in patients starting peritoneal dialysis

PubMed Central

Luo, Qimei; Xia, Xi; Lin, Zhenchuan; Lin, Jianxiong; Yang, Xiao; Huang, Fengxian; Yu, Xueqing

2018-01-01

Abstract Introduction: Very early withdrawal from treatment in patients undergoing peritoneal dialysis (PD) is an increasingly important, but poorly understood, issue. Here, we identified the reasons and risk factors for very early withdrawal from PD. Methods: Incident PD patients from The First Affiliated Hospital of Sun Yat-sen University above 18 years who started treatment between January 1 2006 and December 31 2011 were included. Cessation of PD therapy within the first 90 days after beginning dialysis was classified as very early withdrawal. Results: Totally 1444 patients were enrolled. Of these, 71 (4.9%) withdrew from PD therapy during the first 90 days. Primary reasons for very early withdrawal included death (34 patients, 47.9%), transplantation (21 patients, 29.6%) and transfer to hemodialysis (14 patients, 19.7%). The leading reasons for death were cardiovascular and infectious disease, accounting for 41.2% (14 patients) and 23.5% (8 patients) of total deaths, respectively. Dialysate leakage (six patients, 42.9%) and catheter dysfunction (five patients, 35.7%) were the main reasons for transfer to hemodialysis. In multivariate analysis, predictors for very early PD withdrawal were older age (per decade increasing; hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.03–1.45; p = .019), higher systolic blood pressure (per 10 mmHg increasing; HR, 1.35; 95% CI, 1.20–1.50; p < .001), lower hemoglobin (per 10 g/l increasing; HR, 0.67; 95% CI, 0.57–0.78; p < .001), lower high-density lipoprotein cholesterol (HR, 0.24; 95% CI, 0.10–0.54; p = .001) and lower residual urine volume (per 100 ml/d increasing; HR, 0.90; 95% CI, 0.84–0.95; p = .001). Conclusions: Death was the primary reason for very early withdrawal from PD. Risk factors for very early withdrawal from PD were older in age, had higher systolic blood pressure, lower hemoglobin, lower high-density lipoprotein cholesterol and lower residual urine volume. PMID:29297246

[Preventive withdrawal from work, psychosocial work demands and major depressive symptoms].

PubMed

Fall, A; Goulet, L; Vézina, M

2015-12-01

Our study objectives were as follows: assess exposure to psychosocial work demands among working pregnant women and women on preventive withdrawal from work; and measure the association between psychosocial work demands and major depressive symptoms, according to time of withdrawal from work. Karasek's abbreviated scale was used to measure psychosocial work demands (Job strain and "Iso-strain") and CES-D scale (Center for Epidemiological Studies Depression Scale) was used to measure major depressive symptoms (CES-D score≥23), at 24-26 weeks of pregnancy, among 3043 pregnant women in Montreal (Quebec) who worked at paid jobs at least 15 h/week and at least four consecutive weeks since the beginning of their pregnancy. Multivariate logistic regression models were built. At 24-26 weeks of pregnancy, 31.4% (956/3043) of pregnant women were on preventive withdrawal from work. They were more in "high-strain" (31.1% vs. 21.1%) and "Iso-strain" groups (21.0% vs. 14.2%) than those who continued to work (P<0.0001). The prevalence of major depressive symptoms was higher in women on preventive withdrawal from work (10.8%; CI 95%: 8.9 to 12.9) compared to working women (7.1%; CI 95%: 6.1-8.3). After adjustment for personal and professional risk factors, "Iso-strain" remained significantly associated with major depressive symptoms in working women (adjusted OR=1.75; CI 95%: [1.05 to 2.92]) and women on preventive withdrawal from work, regardless of duration of activity before withdrawal: 4 to 12 weeks (adjusted OR=2.72; CI 95%: [1.19-6.12]), 13 to 20 weeks (adjusted OR=3.51; CI 95%: [1.54-7.97]), and ≥21 weeks (adjusted OR=2.39; CI 95%: [1.10-5.20]). Psychosocial work demands are an important risk factor for the mental health of pregnant workers and require that preventive actions be put forward. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

PubMed

Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

2016-05-01

Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus. Copyright © 2016 Elsevier Inc. All rights reserved.

Patient and Health Care Professional Decision-Making to Commence and Withdraw from Renal Dialysis: A Systematic Review of Qualitative Research

PubMed Central

Flemming, Kate; Murtagh, Fliss E.M.; Johnson, Miriam J.

2015-01-01

Background and objective To ensure that decisions to start and stop dialysis in ESRD are shared, the factors that affect patients and health care professionals in making such decisions must be understood. This systematic review sought to explore how and why different factors mediate the choices about dialysis treatment. Design, setting, participants, & measurements MEDLINE, Embase, CINAHL, and PsychINFO were searched for qualitative studies of factors that affect patients’ or health care professionals’ decisions to commence or withdraw from dialysis. A thematic synthesis was conducted. Results Of 494 articles screened, 12 studies (conducted from 1985 to 2014) were included. These involved 206 patients (most receiving hemodialysis) and 64 health care professionals (age ranges: patients, 26–93 years; professionals, 26–61 years). For commencing dialysis, patients based their choice on "gut instinct," as well as deliberating over the effect of treatment on quality of life and survival. How individuals coped with decision-making was influential: Some tried to take control of the problem of progressive renal failure, whereas others focused on controlling their emotions. Health care professionals weighed biomedical factors and were led by an instinct to prolong life. Both patients and health care professionals described feeling powerless. With regard to dialysis withdrawal, only after prolonged periods on dialysis were the realities of life on dialysis fully appreciated and past choices questioned. By this stage, however, patients were physically dependent on treatment. As was seen with commencing dialysis, individuals coped with treatment withdrawal in a problem- or emotion-controlling way. Families struggled to differentiate between choosing versus allowing death. Health care teams avoided and queried discussions regarding dialysis withdrawal. Patients, however, missed the dialogue they experienced during predialysis education. Conclusions Decision-making in ESRD is complex and dynamic and evolves over time and toward death. The factors at work are multifaceted and operate differently for patients and health professionals. More training and research on open communication and shared decision-making are needed. PMID:25943310

Final Straws: Factors in Decisions of Young Males Withdrawing from a Vocational Business Course

ERIC Educational Resources Information Center

Zorbas, Mark; O'Neill, Marnie; Chapman, Anne

2004-01-01

This purpose of this study was to identify influences on young males' decisions to withdraw from their studies in certificate courses at a Western Australia College of Technical and Further Education (TAFE). The research focused on males aged between 17 and 21 years, and their reasons for either dropping out of or persisting in entry-level…

Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

PubMed

Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

2017-06-01

Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Noradrenaline Triggers GABAA Inhibition of Bed Nucleus of the Stria Terminalis Neurons Projecting to the Ventral Tegmental Area

PubMed Central

Dumont, Éric C.; Williams, John T.

2014-01-01

The lateral part of the ventral bed nucleus of the stria terminalis (vlBNST) is a critical site for the antiaversive effects of noradrenergic drugs during opioid withdrawal. The objective of the present study is to identify the cellular action(s) of noradrenaline in the vlBNST after withdrawal from a 5 d treatment with morphine. The vlBNST is a heterogeneous cell group with multiple efferent projections. Therefore, neurons projecting to the midbrain were identified by retrograde transport of fluorescent microspheres injected in the ventral tegmental area (VTA). Whole-cell voltage clamp recordings of these neurons and of those sharing physiological properties were done in brain slices. Noradrenaline activated α1-adrenergic receptors to increase GABAA-IPSC frequency. Noradrenaline produced a similar increase in GABAA-IPSCs during acute opioid withdrawal, but this increase resulted from activation of β-adrenergic receptors, adenylyl cyclase, and protein kinase A, as well as α1-adrenergic receptors. Given that neurons in the vlBNST send an excitatory projection to the VTA, noradrenaline may reduce excitatory drive to mesolimbic dopamine cells. This mechanism might contribute to the withdrawal-induced inhibition of dopamine neurons and explain how noradrenergic drugs microinjected into the vlBNST reduce aversive aspects of opioid withdrawal. PMID:15385602

Examining the effect of the CaMKII inhibitor administration in the locus coeruleus on the naloxone-precipitated morphine withdrawal signs in rats.

PubMed

Navidhamidi, M; Semnanian, S; Javan, M; Goudarzvand, M; Rohampour, K; Azizi, H

2012-01-15

Drug addiction is an occurrence with physiological, psychological, and social outcomes. Repeated drug exposure causes neuronal adaptations and dependency. It has been shown that CaMKIIα enzyme contributes to morphine dependency. The locus coeruleus nucleus has been implied in the morphine withdrawal syndrome. This research focuses on the behavioral and molecular adaptations that occur in the locus coeruleus neurons in response to the chronic morphine exposure. Adult male Wistar rats were injected by morphine sulfate (10 mg/kg/s.c.) at an interval of 12 h for a period of nine subsequent days. On the tenth day, naloxone (1 mg/kg/i.p.) was injected 2 h after the morphine administration. Somatic withdrawal signs were investigated for 30 min. We concluded that the inhibition of CaMKIIα by administration of KN-93, the specific inhibitor of this enzyme, significantly attenuated some of the withdrawal signs. In molecular method, the expression of CaMKIIα protein has been enhanced in locus coeruleus of the morphine dependent rats. These findings indicate that CaMKIIα may be involved in the modulation of the naloxone-induced withdrawal syndrome, and treatment with KN-93 may have some effects on this system. Copyright © 2011 Elsevier B.V. All rights reserved.

Corticotropin-releasing factor-1 receptor activation mediates nicotine withdrawal-induced deficit in brain reward function and stress-induced relapse.

PubMed

Bruijnzeel, Adrie W; Prado, Melissa; Isaac, Shani

2009-07-15

Tobacco addiction is a chronic brain disorder that is characterized by a negative affective state upon smoking cessation and relapse after periods of abstinence. Previous research has shown that blockade of corticotropin-releasing factor (CRF) receptors with a nonspecific CRF1/CRF2 receptor antagonist prevents the deficit in brain reward function associated with nicotine withdrawal and stress-induced reinstatement of extinguished nicotine-seeking in rats. The aim of these studies was to investigate the role of CRF1 and CRF2 receptors in the deficit in brain reward function associated with precipitated nicotine withdrawal and stress-induced reinstatement of nicotine-seeking. The intracranial self-stimulation (ICSS) procedure was used to assess the negative affective state of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. Stress-induced reinstatement of nicotine-seeking was investigated in animals in which responding for intravenously infused nicotine was extinguished by substituting saline for nicotine. In the ICSS experiments, the nicotinic receptor antagonist mecamylamine elevated the brain reward thresholds of the nicotine-dependent rats but not those of the control rats. The CRF1 receptor antagonist R278995/CRA0450 but not the CRF2 receptor antagonist astressin-2B prevented the elevations in brain reward thresholds associated with precipitated nicotine withdrawal. Furthermore, R278995/CRA0450 but not astressin-2B prevented stress-induced reinstatement of extinguished nicotine-seeking. Neither R278995/CRA0450 nor astressin-2B affected operant responding for chocolate-flavored food pellets. These studies indicate that CRF(1) receptors but not CRF(2) receptors play an important role in the anhedonic-state associated with acute nicotine withdrawal and stress-induced reinstatement of nicotine-seeking.

Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

PubMed Central

MOMOZONO, HIROYUKI; MIYAKE, HIDEAKI; TEI, HIROMOTO; HARADA, KEN-ICHI; FUJISAWA, MASATO

2016-01-01

The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC. PMID:27123292

Marijuana Dependence: Not Just Smoke and Mirrors

PubMed Central

Ramesh, Divya; Schlosburg, Joel E.; Wiebelhaus, Jason M.; Lichtman, Aron H.

2012-01-01

Marijuana (Cannabis sativa) is the most commonly used illicit drug worldwide as well as in the Unites States. Prolonged use of marijuana or repeated administration of its primary psychoactive constituent, Δ9-tetrahydrocannabinol (THC), can lead to physical dependence in humans and laboratory animals. The changes that occur with repeated cannabis use include alterations in behavioral, physiological, and biochemical responses. A variety of withdrawal responses occur in cannabis-dependent individuals: anger, aggression, irritability, anxiety and nervousness, decreased appetite or weight loss, restlessness, and sleep difficulties with strange dreams. But the long half-life and other pharmacokinetic properties of THC result in delayed expression of withdrawal symptoms, and because of the lack of contiguity between drug cessation and withdrawal responses the latter are not readily recognized as a clinically relevant syndrome. Over the past 30 years, a substantial body of clinical and laboratory animal research has emerged supporting the assertion that chronic exposure to cannabinoids produces physical dependence and may contribute to drug maintenance in cannabis-dependent individuals. However, no medications are approved to treat cannabis dependence and withdrawal. In this review, we describe preclinical and clinical research that supports the existence of a cannabinoid withdrawal syndrome. In addition, we review research evaluating potential pharmacotherapies (e.g., THC, a variety of antidepressant drugs, and lithium) to reduce cannabis withdrawal responses and examine how expanded knowledge about the regulatory mechanisms in the endocannabinoid system may lead to promising new therapeutic targets. PMID:23382144

Interactions of Stress and CRF in Ethanol-Withdrawal Induced Anxiety in Adolescent and Adult Rats

PubMed Central

Wills, Tiffany A.; Knapp, Darin J.; Overstreet, David H.; Breese, George R.

2010-01-01

Background Repeated stress or administration of corticotropin-releasing factor (CRF) prior to ethanol exposure sensitizes anxiety-like behavior in adult rats. Current experiments determined whether adolescent rats were more sensitive to these challenges in sensitizing ethanol withdrawal-induced anxiety and altering CRF levels in brain during withdrawal. Methods Male adult and adolescent Sprague–Dawley rats were restraint stressed (1 hour) twice 1 week apart prior to a single 5-day cycle of ethanol diet (ED; stress/withdrawal paradigm). Other rats received control diet (CD) and three 1-hour restraint stress sessions. Rats were then tested 5, 24, or 48 hours after the final withdrawal for anxiety-like behavior in the social interaction (SI) test. In other experiments, adolescent rats were given two microinjections of CRF icv 1 week apart followed by 5-days of either CD or ED and tested in social interaction 5 hours into withdrawal. Finally, CRF immunoreactivity was measured in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) after rats experienced control diet, repeated ethanol withdrawals, or stress/withdrawal. Results Rats of both ages had reduced SI following the stress/withdrawal paradigm, and this effect recovered within 24 hours. Higher CRF doses were required to reduce SI in adolescents than previously reported in adults. CRF immunohistochemical levels were higher in the PVN and CeA of CD-exposed adolescents. In adolescent rats, repeated ethanol withdrawals decreased CRF in the CeA but was not associated with decreased CRF cell number. There was no change in CRF from adult treatments. Conclusions In the production of anxiety-like behavior, adolescent rats have equal sensitivity with stress and lower sensitivity with CRF compared to adults. Further, adolescents had higher basal levels of CRF within the PVN and CeA and reduced CRF levels following repeated ethanol withdrawals. This reduced CRF within the CeA could indicate increased release of CRF, and future work will determine how this change relates to behavior. PMID:20586753

Relations between precipitation, groundwater withdrawals, and changes in hydrologic conditions at selected monitoring sites in Volusia County, Florida, 1995--2010

USGS Publications Warehouse

Murray, Louis C.

2012-01-01

A study to examine the influences of climatic and anthropogenic stressors on groundwater levels, lake stages, and surface-water discharge at selected sites in northern Volusia County, Florida, was conducted in 2009 by the U.S. Geological Survey. Water-level data collected at 20 monitoring sites (17 groundwater and 3 lake sites) in the vicinity of a wetland area were analyzed with multiple linear regression to examine the relative influences of precipitation and groundwater withdrawals on changes in groundwater levels and lake stage. Analyses were conducted across varying periods of record between 1995 and 2010 and included the effects of groundwater withdrawals aggregated from municipal water-supply wells located within 12 miles of the project sites. Surface-water discharge data at the U.S. Geological Survey Tiger Bay canal site were analyzed for changes in flow between 1978 and 2001. As expected, water-level changes in monitoring wells located closer to areas of concentrated groundwater withdrawals were more highly correlated with withdrawals than were water-level changes measured in wells further removed from municipal well fields. Similarly, water-level changes in wells tapping the Upper Floridan aquifer, the source of municipal supply, were more highly correlated with groundwater withdrawals than were water-level changes in wells tapping the shallower surficial aquifer system. Water-level changes predicted by the regression models over precipitation-averaged periods of record were underestimated for observations having large positive monthly changes (generally greater than 1.0 foot). Such observations are associated with high precipitation and were identified as points in the regression analyses that produced large standardized residuals and/or observations of high influence. Thus, regression models produced by multiple linear regression analyses may have better predictive capability in wetland environments when applied to periods of average or below average precipitation conditions than during wetter than average conditions. For precipitation-averaged hydrologic conditions, water-level changes in the surficial aquifer system were statistically correlated solely with precipitation or were more highly correlated with precipitation than with groundwater withdrawals. Changes in Upper Floridan aquifer water levels and in water-surface stage (stage) at Indian and Scoggin Lakes tended to be highly correlated with both precipitation and withdrawals. The greater influence of withdrawals on stage changes, relative to changes in nearby surficial aquifer system water levels, indicates that these karstic lakes may be better connected hydraulically with the underlying Upper Floridan aquifer than is the surficial aquifer system at the other monitoring sites. At most sites, and for both aquifers, the 2-month moving average of precipitation or groundwater withdrawals included as an explanatory variable in the regression models indicates that water-level changes are not only influenced by stressor conditions across the current month, but also by those of the previous month. The relations between changes in water levels, precipitation, and groundwater withdrawals varied seasonally and in response to a period of drought. Water-level changes tended to be most highly correlated with withdrawals during the spring, when relatively large increases contributed to water-level declines, and during the fall when reduced withdrawal rates contributed to water-level recovery. Water-level changes tended to be most highly (or solely) correlated with precipitation in the winter, when withdrawals are minimal, and in the summer when precipitation is greatest. Water-level changes measured during the drought of October 2005 to June 2008 tended to be more highly correlated with groundwater withdrawals at Upper Floridan aquifer sites than at surficial aquifer system sites, results that were similar to those for precipitation-averaged conditions. Also, changes in stage at Indian and Scoggin Lakes were highly correlated with precipitation and groundwater withdrawals during the drought. Groundwater-withdrawal rates during the drought were, on average, greater than those for precipitation-averaged conditions. Accounting only for withdrawals aggregated from pumping wells located within varying radial distances of less than 12 miles of each site produced essentially the same relation between water-level changes and groundwater withdrawals as that determined for withdrawals aggregated within 12 miles of the site. Similarly, increases in withdrawals aggregated over distances of 1 to 12 miles of the sites had little effect on adjusted R-squared values. Analyses of streamflow measurements collected between 1978 and 2001 at the U.S. Geological Survey Tiger Bay canal site indicate that significant changes occurred during base-flow conditions during that period. Hypothesis and trend testing, together with analyses of flow duration, the number of zero-flow days, and double-mass curves indicate that, after 1988, when a municipal well field began production, base flow was statistically lower than the period before 1988. This decrease in base flow could not be explained by variations in precipitation between these two periods.

A framework for analysis of sentinel events in medical student education.

PubMed

Cohen, Daniel M; Clinchot, Daniel M; Werman, Howard A

2013-11-01

Although previous studies have addressed student factors contributing to dismissal or withdrawal from medical school for academic reasons, little information is available regarding institutional factors that may hinder student progress. The authors describe the development and application of a framework for sentinel event (SE) root cause analysis to evaluate cases in which students are dismissed or withdraw because of failure to progress in the medical school curriculum. The SE in medical student education (MSE) framework was piloted at the Ohio State University College of Medicine (OSUCOM) during 2010-2012. Faculty presented cases using the framework during academic oversight committee discussions. Nine SEs in MSE were presented using the framework. Major institution-level findings included the need for improved communication, documentation of cognitive and noncognitive (e.g., mental health) issues, clarification of requirements for remediation and fitness for duty, and additional psychological services. Challenges related to alternative and combined programs were identified as well. The OSUCOM undertook system changes based on the action plans developed through the discussions of these SEs. An SE analysis process appears to be a useful method for making system changes in response to institutional issues identified in evaluation of cases in which students fail to progress in the medical school curriculum. The authors plan to continue to refine the SE in MSE framework and analysis process. Next steps include assessing whether analysis using this framework yields improved student outcomes with universal applications for other institutions.

Trade Openness and Domestic Water Use

NASA Astrophysics Data System (ADS)

Dang, Qian; Konar, Megan

2018-01-01

We contribute to the debate over globalization and the environment by asking, what is the impact of trade on national water use? To address this question, we employ econometric methods to quantify the causal relationship between trade openness and water use. Specifically, we use the instrumental variables methodology to evaluate the impact of trade openness on domestic water withdrawals in agriculture and industry. We find that trade openness does not have a significant impact on total or industrial water withdrawals. However, we show that one percentage point increase in trade openness leads to a 5.21% decrease in agricultural water withdrawals. We find that trade openness reduces water use in agriculture primarily through the intensive margin effect, by leading farmers to produce more with less water, such as through the adoption of technology. We do not find evidence for extensive margin or crop mix impacts on agricultural water withdrawals. Significantly, these results demonstrate that trade openness leads to less water use in agriculture. This finding has broad scientific and policy relevance as we endeavor to untangle causal relationships in the complex global food system and develop policies to achieve water and food security.

Psychometric properties of the Spanish version of the Cocaine Selective Severity Assessment to evaluate cocaine withdrawal in treatment-seeking individuals.

PubMed

Pérez de los Cobos, José; Trujols, Joan; Siñol, Núria; Vasconcelos e Rego, Lisiane; Iraurgi, Ioseba; Batlle, Francesca

2014-09-01

Reliable and valid assessment of cocaine withdrawal is relevant for treating cocaine-dependent patients. This study examined the psychometric properties of the Spanish version of the Cocaine Selective Severity Assessment (CSSA), an instrument that measures cocaine withdrawal. Participants were 170 cocaine-dependent inpatients receiving detoxification treatment. Principal component analysis revealed a 4-factor structure for CSSA that included the following components: 'Cocaine Craving and Psychological Distress', 'Lethargy', 'Carbohydrate Craving and Irritability', and 'Somatic Depressive Symptoms'. These 4 components accounted for 56.0% of total variance. Internal reliability for these components ranged from unacceptable to good (Chronbach's alpha: 0.87, 0.65, 0.55, and 0.22, respectively). All components except Somatic Depressive Symptoms presented concurrent validity with cocaine use. In summary, while some properties of the Spanish version of the CSSA are satisfactory, such as interpretability of factor structure and test-retest reliability, other properties, such as internal reliability and concurrent validity of some factors, are inadequate. Copyright © 2014 Elsevier Inc. All rights reserved.

Corticotropin-Releasing Factor (CRF) Neurocircuitry and Neuropharmacology in Alcohol Drinking.

PubMed

Schreiber, Allyson L; Gilpin, Nicholas W

2018-01-28

Alcohol use is pervasive in the United States. In the transition from nonhazardous drinking to hazardous drinking and alcohol use disorder, neuroadaptations occur within brain reward and brain stress systems. One brain signaling system that has received much attention in animal models of excessive alcohol drinking and alcohol dependence is corticotropin-releasing factor (CRF). The CRF system is composed of CRF, the urocortins, CRF-binding protein, and two receptors - CRF type 1 and CRF type 2. This review summarizes how acute, binge, and chronic alcohol dysregulates CRF signaling in hypothalamic and extra-hypothalamic brain regions and how this dysregulation may contribute to changes in alcohol reinforcement, excessive alcohol consumption, symptoms of negative affect during withdrawal, and alcohol relapse. In addition, it summarizes clinical work examining CRF type 1 receptor antagonists in humans and discusses why the brain CRF system is still relevant in alcohol research.

Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react?

PubMed

Nielsen, Margrethe; Hansen, Ebba Holme; Gøtzsche, Peter C

2013-01-01

Our objective was to explore communications from drug agencies about benzodiazepine dependence and selective serotonin reuptake inhibitors (SSRIs) withdrawal reactions over time. Documentary study. We searched the web-sites of the European Medicines Agency and the drug agencies in USA, UK, and Denmark for documents mentioning benzodiazepines or SSRIs. We supplemented with other relevant literature that could contribute to our study. The searches were performed in 2009 in PubMed, Google, BMJ and JAMA. It took many years before the drug regulators acknowledged benzodiazepine dependence and SSRI withdrawal reactions and before the prescribers and the public were informed. Drug regulators relied mainly on the definitions of dependence and withdrawal reactions from the diagnostic psychiatric manuals, which contributed to the idea that SSRIs do not cause dependence, although it is difficult for many patients to stop treatment. In the perspective of a precautionary principle, drug agencies have failed to acknowledge that SSRIs can cause dependence and have minimised the problem with regard to its frequency and severity. In the perspective of a risk management principle, the drug agencies have reacted in concordance with the slowly growing knowledge of adverse drug reactions and have sharpened the information to the prescribers and the public over time. However, solely relying on spontaneous reporting of adverse effects leads to underestimation and delayed information about the problems. Given the experience with the benzodiazepines, we believe the regulatory bodies should have required studies from the manufacturers that could have elucidated the dependence potential of the SSRIs before marketing authorization was granted.

BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine.

PubMed

Manning, Elizabeth E; Halberstadt, Adam L; van den Buuse, Maarten

2016-04-01

One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychosis and neuronal responses to methamphetamine. We therefore examined persistent psychosis-like behavioral effects of methamphetamine in brain-derived neurotrophic factor heterozygous mice. Mice were chronically treated with methamphetamine from 6 to 9 weeks of age, and locomotor hyperactivity to an acute D-amphetamine challenge was tested in photocell cages after a 2-week withdrawal period. Methamphetamine-treated wild-type mice, but not brain-derived neurotrophic factor heterozygous mice, showed locomotor sensitization to acute 3mg/kg D-amphetamine. Qualitative analysis of exploration revealed tolerance to D-amphetamine effects on entropy in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice, but not wild-type mice. Chronic methamphetamine exposure induces contrasting profiles of behavioral changes in wild-type and brain-derived neurotrophic factor heterozygous mice, with attenuation of behaviors relevant to psychosis in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice. This suggests that brain-derived neurotrophic factor signalling changes may contribute to development of psychosis in methamphetamine users. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Persistence and withdrawal by students in a preservice science and mathematics teacher education course

NASA Astrophysics Data System (ADS)

Tulip, David F.; Lucas, Keith B.

1991-12-01

At a time when recruitment into preservice teacher education courses in mathematics and science is difficult, one strategy to increase the number of graduates is to minimise the number of students who fail to complete their university courses. This study sought to determine factors which distinguish withdrawers from persisters in the first semester of a B.Ed course. Discriminant analysis was employed; a discriminant function employing seven factors resulted in correct classification in 81% of cases. Further analysis distinguishing between dropouts and transferees resulted in two discriminant functions with some common variables.

Assessment of nicotine withdrawal-induced changes in sucrose preference in mice.

PubMed

Alkhlaif, Yasmin; Bagdas, Deniz; Jackson, Asti; Park, Abigail J; Damaj, Imad M

2017-10-01

Anhedonia, induced by nicotine withdrawal, may serve as an important affective sign that reinforces tobacco use and smoking relapse rates in humans. Animal models provide a way to investigate the underlying neurobiological factors involved in the decrease in responding for positive affective stimuli during nicotine withdrawal and may aid in drug development for nicotine dependence. Thus, we explored the use of the sucrose preference test to measure nicotine withdrawal-induced reduction in response for positive affective stimuli in mice. C57BL/6J and knockout (KO) mice were chronically exposed to different doses of nicotine through surgically implanted subcutaneous osmotic minipumps for 14days and underwent spontaneous nicotine withdrawal on day 15. A sucrose preference time course was performed and the results were compared to another well-established affective sign of nicotine withdrawal, the reduction in time spent in light side, using the Light Dark Box test. Subsequently, our results demonstrated a time-dependent and dose-related reduction in sucrose preference in nicotine withdrawn male C57BL/6J mice, indicative of a decrease in responding for positive affective stimuli. Furthermore, the sucrose preference reduction during nicotine withdrawal was consistent with decrease in time spent in the light side of the Light Dark Box test. We also found the reduction for positive affective stimuli and time spent in the light side was not present in nicotine withdrawn β2 and α6 KO mice, suggesting that these nicotinic subunits are involved in the affective signs of nicotine withdrawal. Thus, this report highlights the potential utility of the sucrose preference test as a useful measure of the decrease in responding for positive affective stimuli during spontaneous nicotine withdrawal. Copyright © 2017 Elsevier Inc. All rights reserved.

Variations in the neonatal environment modulate adult behavioral and brain responses to palatable food withdrawal in adult female rats.

PubMed

Colman, Juliana Barcellos; Laureano, Daniela Pereira; Reis, Tatiane Madeira; Krolow, Rachel; Dalmaz, Carla; Benetti, Carla da Silva; Silveira, Patrícia Pelufo

2015-02-01

Early handling alters adult behavioral responses to palatable food and to its withdrawal following a period of chronic exposure. However, the central mechanisms involved in this phenomenon are not known. Since neonatal handling has persistent effects on stress and anxiety responses, we hypothesized that its involvement in the aforementioned association may be associated with differential neuroadaptations in the amygdala during withdrawal periods. Litters were randomized into two groups: handled (H, removed from their dam for 10min per day from the first to the tenth postnatal day and placed in an incubator at 32°C) and non-handled (NH). Experiment 1: on PNDs 80-100, females were assigned to receive palatable food+rat chow for 15 or 30 days, and these two groups were compared in terms of palatable food preference, body weight and abdominal fat deposition. In Experiment 2, H and NH rats were exposed to a chronic diet of palatable food+rat chow for 15 days, followed by (a) no withdrawal, (b) 24h withdrawal from palatable food (receiving only rat chow) or (c) 7-day withdrawal from palatable food (receiving only rat chow). Body weight, 10-min rebound palatable food intake, abdominal fat deposition, serum corticosterone as well as TH and pCREB levels in the amygdala were then compared between groups. Experiment 1-chronic exposure to palatable food induces comparable metabolic effects after 15 and 30 days. Experiment 2-neonatal handling is associated with a peculiar response to palatable food withdrawal following chronic exposure for 15 days. Rats exposed to early handling ingested less of this food after a 24h withdrawal period, and displayed increased amygdala TH and pCREB levels. Variations in the neonatal environment affect both behavioral responses and amygdala neuroadaptation to acute withdrawal from a palatable diet. These findings contribute to the comprehension of the mechanisms that link early life events and altered feeding behavior and related morbidities such as obesity in adulthood. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Evaluation and comparison of methods to estimate irrigation withdrawal for the National Water Census Focus Area Study of the Apalachicola-Chattahoochee-Flint River Basin in southwestern Georgia

USGS Publications Warehouse

Painter, Jaime A.; Torak, Lynn J.; Jones, John W.

2015-09-30

Methods to estimate irrigation withdrawal using nationally available datasets and techniques that are transferable to other agricultural regions were evaluated by the U.S. Geological Survey as part of the Apalachicola-Chattahoochee-Flint (ACF) River Basin focus area study of the National Water Census (ACF–FAS). These methods investigated the spatial, temporal, and quantitative distributions of water withdrawal for irrigation in the southwestern Georgia region of the ACF–FAS, filling a vital need to inform science-based decisions regarding resource management and conservation. The crop– demand method assumed that only enough water is pumped onto a crop to satisfy the deficit between evapotranspiration and precipitation. A second method applied a geostatistical regimen of variography and conditional simulation to monthly metered irrigation withdrawal to estimate irrigation withdrawal where data do not exist. A third method analyzed Landsat satellite imagery using an automated approach to generate monthly estimates of irrigated lands. These methods were evaluated independently and compared collectively with measured water withdrawal information available in the Georgia part of the ACF–FAS, principally in the Chattahoochee-Flint River Basin. An assessment of each method’s contribution to the National Water Census program was also made to identify transfer value of the methods to the national program and other water census studies. None of the three methods evaluated represent a turnkey process to estimate irrigation withdrawal on any spatial (local or regional) or temporal (monthly or annual) extent. Each method requires additional information on agricultural practices during the growing season to complete the withdrawal estimation process. Spatial and temporal limitations inherent in identifying irrigated acres during the growing season, and in designing spatially and temporally representative monitor (meter) networks, can belie the ability of the methods to produce accurate irrigation-withdrawal estimates that can be used to produce dependable and consistent assessments of water availability and use for the National Water Census. Emerging satellite-data products and techniques for data analysis can generate high spatial-resolution estimates of irrigated-acres distributions with near-term temporal frequencies compatible with the needs of the ACF–FAS and the National Water Census.

Nephrologists' perceptions regarding dialysis withdrawal and palliative care in Europe: lessons from a European Renal Best Practice survey

PubMed Central

van Biesen, Wim; van de Luijtgaarden, Moniek W.M.; Brown, Edwina A.; Michel, Jean-Pierre; van Munster, Barbara C.; Jager, Kitty J.; van der Veer, Sabine N.

2015-01-01

Background There is a variation in dialysis withdrawal rates, but reasons for this variation across European countries are largely unknown. We therefore surveyed nephrologists' perceptions of factors concerning dialysis withdrawal and palliative care and explored relationships between these perceptions and reports of whether withdrawal actually occurred in practice. Methods We developed a 33-item electronic survey, disseminated via an email blast to all European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) members. In our data analyses, we distinguished those respondents who reported occurrence from those reporting no dialysis withdrawal in their unit. With multilevel logistic regression, we investigated the association between respondents' characteristics and perceptions and whether they reported occurrence of dialysis withdrawal or not. Results Five hundred and twenty-eight nephrologists from 45 countries completed the questionnaire; 42% reported occurrence of withdrawal in their unit in the past year, and 56% perceived that stopping life-prolonging treatment in terminally ill patients was allowed. Few respondents reported presence in their unit of protocols on withdrawal decision making (7%) or palliative care (10%) or the common involvement of a geriatrician in withdrawal decisions (10%). The majority stated that palliative care had not been part of their core curriculum (74%) and that they had not recently attended continuous medical education sessions on this topic (73%). Respondents from Eastern and Southern Europe had a 42 and 40% lower probability, respectively, of reporting withdrawal compared with those from North European countries. Working in a public centre [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.36–4.25] and respondents' perception that stopping life-prolonging treatment in terminally ill patients was allowed (OR, 1.96; 95% CI, 1.23–3.12), that withdrawal decisions were commonly shared between doctor and patient (OR, 1.97; 95% CI, 1.26–3.08) and that palliative care was reimbursed (OR, 1.81; 95% CI, 1.16–2.83) increased the odds of reporting occurrence of withdrawal. Conclusion Reports of dialysis withdrawal occurrence varied between European countries. Occurrence reports were more likely if respondents worked in a public centre, if stopping life-prolonging treatments was perceived as allowed, if withdrawal decisions were considered shared between doctors and patients and if reimbursement of palliative care was believed to be in place. There is room for improvement regarding protocols on withdrawal and palliative care processes and regarding nephrologists' training and education on end-of-life care. PMID:26268713

Strain-dependent Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

PubMed Central

Portugal, George S.; Wilkinson, Derek S.; Kenney, Justin W.; Sullivan, Colleen

2013-01-01

The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute nicotine and nicotine withdrawal on contextual fear conditioning, somatic signs, and the elevated plus maze were observed, but no association between the effects of acute nicotine and nicotine withdrawal on contextual fear conditioning were observed, suggesting that different genetic substrates may mediate these effects. The identification of genetic factors that may alter the effects of nicotine on cognition may lead to more efficacious treatments for nicotine addiction. PMID:21822688

Childhood social withdrawal, interpersonal impairment, and young adult depression: a mediational model.

PubMed

Katz, Shaina J; Conway, Christopher C; Hammen, Constance L; Brennan, Patricia A; Najman, Jake M

2011-11-01

Building on interpersonal theories of depression, the current study sought to explore whether early childhood social withdrawal serves as a risk factor for depressive symptoms and diagnoses in young adulthood. The researchers hypothesized that social impairment at age 15 would mediate the association between social withdrawal at age 5 and depression by age 20. This mediational model was tested in a community sample of 702 Australian youth followed from mother's pregnancy to youth age 20. Structural equation modeling analyses found support for a model in which childhood social withdrawal predicted adolescent social impairment, which, in turn, predicted depression in young adulthood. Additionally, gender was found to moderate the relationship between adolescent social impairment and depression in early adulthood, with females exhibiting a stronger association between social functioning and depression at the symptom and diagnostic level. This study illuminates one potential pathway from early developing social difficulties to later depressive symptoms and disorders.

Childhood Social Withdrawal, Interpersonal Impairment, and Young Adult Depression: A Mediational Model

PubMed Central

Katz, Shaina J.; Conway, Christopher C.; Hammen, Constance L.; Brennan, Patricia A.; Najman, Jake M.

2012-01-01

Building on interpersonal theories of depression, the current study sought to explore whether early childhood social withdrawal serves as a risk factor for depressive symptoms and diagnoses in young adulthood. The researchers hypothesized that social impairment at age 15 would mediate the association between social withdrawal at age 5 and depression by age 20. This mediational model was tested in a community sample of 702 Australian youth followed from mother’s pregnancy to youth age 20. Structural equation modeling analyses found support for a model in which childhood social withdrawal predicted adolescent social impairment, which, in turn, predicted depression in young adulthood. Additionally, gender was found to moderate the relationship between adolescent social impairment and depression in early adulthood, with females exhibiting a stronger association between social functioning and depression at the symptom and diagnostic level. This study illuminates one potential pathway from early developing social difficulties to later depressive symptoms and disorders. PMID:21744059

Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice.

PubMed

Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L; Lee, Francis S; Blendy, Julie A

2015-12-01

Nicotine withdrawal is characterized by both affective and cognitive symptoms. Identifying genetic polymorphisms that could affect the symptoms associated with nicotine withdrawal are important in predicting withdrawal sensitivity and identifying personalized cessation therapies. In the current study we used a mouse model of a non-synonymous single nucleotide polymorphism in the translated region of the brain-derived neurotrophic factor (BDNF) gene that substitutes a valine (Val) for a methionine (Met) amino acid (Val66Met) to examine the relationship between the Val66Met single nucleotide polymorphism and nicotine dependence. This study measured proBDNF and the BDNF prodomain levels following nicotine and nicotine withdrawal and examined a mouse model of a common polymorphism in this protein (BDNF(Met/Met)) in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test. Using the BDNF knock-in mouse containing the BDNF Val66Met polymorphism we found: (1) blunted anxiety-like behavior in BDNF(Met/Met) mice following withdrawal in three behavioral paradigms: novelty-induced hypophagia, marble burying, and the open-field test; (2) the anxiolytic effects of chronic nicotine are absent in BDNF(Met/Met) mice; and (3) an increase in BDNF prodomain in BDNF(Met/Met) mice following nicotine withdrawal. Our study is the first to examine the effect of the BDNF Val66Met polymorphism on the affective symptoms of withdrawal from nicotine in mice. In these mice, a single-nucleotide polymorphism in the translated region of the BDNF gene can result in a blunted withdrawal, as measured by decreased anxiety-like behavior. The significant increase in the BDNF prodomain in BDNF(Met/Met) mice following nicotine cessation suggests a possible role of this ligand in the circuitry remodeling after withdrawal. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Stochastic analyses to identify wellfield withdrawal effects on surface-water and groundwater in Miami-Dade County, Florida.

PubMed

Swain, Eric

2012-12-30

Several stochastic analyses were conducted in Miami-Dade County, Florida, to evaluate the effects of wellfield withdrawal on aquifer water levels, canal stage, and canal flow. Multiyear data for withdrawals at four water-supply wellfields, water levels at the S-121 canal control structure and groundwater head at a nearby monitoring well were used to determine the interrelation between wellfield withdrawals and water levels in the canal and aquifer. A spectral analysis was performed first on the wellfield withdrawals, showing similar patterns of fluctuations, but no well-defined seasonality. In order to compare water-level response with withdrawals at each wellfield, the intercorrelation effects between wellfields was removed through a 'causal chain' approach where the inter-wellfield correlation is used to isolate the wellfield/water-level correlation. Most computed correlations have magnitudes less than 5 percent, but with statistical significance above 90 percent. Results indicate that withdrawals from the wellfields most distant from the canal had no significant correlation to the canal levels. However the highest correlation was not at the wellfield closest to the canal, but at the two wellfields at the intermediate distance that have higher withdrawal rates. The hydraulic interconnectivity of the canal with the rest of the canal network, covering the study area, allows the canal equalizes with all connected canals. This explains why proximity to a particular canal location does not appear to be as important a factor as the withdrawal rate. Groundwater levels are more highly correlated to a wellfield on the same side of the canal, and to pumping wells in the same wellfield on the same side of the canal. This indicates that canals are an effective barrier and source/sink for the groundwater. Further nonlinear correlation analysis indicates that high withdrawal rates disproportionally affect water levels and are the predominant effect on the canal. Published by Elsevier Ltd.

Delivery room management of extremely preterm infants: the EPIPAGE-2 study.

PubMed

Perlbarg, J; Ancel, P Y; Khoshnood, B; Durox, M; Boileau, P; Garel, M; Kaminski, M; Goffinet, F; Foix-L'Hélias, L

2016-09-01

To analyse the delivery room management of babies born between 22 and 26 weeks of completed gestational age and to identify the factors associated with the withholding or withdrawal of intensive care. Population-based cohort study. Our study population comprised 2145 births between 22 and 26 completed weeks enrolled in the EPIPAGE-2 study, a French cohort of very preterm infants born in 2011. The primary outcome measure was withholding or withdrawal of intensive care in the delivery room. Among infants born alive at 22-23 weeks, intensive care was withheld or withdrawn for >90%. At 24 weeks, resuscitative measures were withheld or withdrawn for 38%, at 25 weeks for 8% and at 26 weeks for 3%. Other factors besides gestational age at birth associated with this withholding or withdrawal for infants born at 24-26 weeks were birth weight <600 g, emergency delivery (within 24 h of the mother's admission) and singleton pregnancy. Although rates of withholding or withdrawal of intensive care varied substantially between maternity units (from 0% to 100%), the variability was primarily explained by differences in distributions of gestational age at birth. Although gestational age is only one factor predicting survival of preterm infants, practices in France appear to be based primarily on this factor, which thus has direct effects on the survival of extremely preterm infants. The ethical implications of basing life and death decisions only on gestational age before 25 weeks require further examination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Treatment for amphetamine withdrawal.

PubMed

Srisurapanont, M; Jarusuraisin, N; Kittirattanapaiboon, P

2001-01-01

Amphetamine withdrawal has been less studied although it is a common problem with a prevalent rate of 87% among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse of amphetamine use. In clinical practice, treatment for cocaine withdrawal has been recommended for the management of amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two substances are not the same. To search and determine risks, benefits, and costs of a variety of treatments for the management of amphetamine withdrawal. Electronic searches of MEDLINE (1966 - December 2000), EMBASE (1980 - February 2001), CINAHL (1982 - January 2001) and Cochrane Controlled Trials Register (Cochrane Library 2000 issue 4) were undertaken. References to the articles obtained by any means were searched. All relevant randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were included. Participants were people with amphetamine withdrawal, diagnosed by any set of criteria. Any kinds of biological and psychological treatments both alone and combined were examined. A variety of outcomes, for example, number of treatment responders, score changes, were considered. Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis in which the dropouts were assigned as participants with the worst outcomes. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess the dichotomous data. The Weighted Mean Difference (WMD) with 95% CI was used to assessed the continuous data. The results of two studies have shown some benefits of amineptine in the treatment of amphetamine withdrawal. Those benefits can be seen in the respects of discontinuation rate and global state, as measured by Clinical Global Impression Scale. However, no direct benefit of amineptine on amphetamine withdrawal symptoms or craving was shown. The evidence about the treatment for amphetamine withdrawal is very limited. Amineptine has limited benefits on some amphetamine withdrawal symptoms. Due to a number of reports of amineptine abuse, it has been withdrawn from the market for a few years. At present, no available treatment has been demonstrated to be effective in the treatment of amphetamine withdrawal. The medications that should be considered for further treatment studies may be those with the propensities to increase dopamine, norepinephrine and/or serotonin activities of the brain. Naturalistic studies of amphetamine withdrawal symptoms and course are also crucial for the development of study designs appropriate for further treatment studies of amphetamine withdrawal.

Contribution of the ethics committee of the French Intensive Care Society to describing a scenario for implementing organ donation after Maastricht type III cardiocirculatory death in France

PubMed Central

2012-01-01

French law allows organ donation after death due to cardiocirculatory arrest. In the Maastricht classification, type III non-heart-beating donors are those who experience cardiocirculatory arrest after the withdrawal of life-sustaining treatments. French authorities in charge of regulating organ donation (Agence de la Biomédecine, ABM) are considering organ collection from Maastricht type III donors. We describe a scenario for Maastricht type III organ donation that fully complies with the ethical norms governing care to dying patients. That organ donation may occur after death should have no impact on the care given to the patient and family. The dead-donor rule must be followed scrupulously: the organ retrieval procedure must neither cause nor hasten death. The decision to withdraw life-sustaining treatments, withdrawal modalities, and care provided to the patient and family must adhere strictly to the requirements set forth in patient-rights legislation (the 2005 Léonetti law in France) and should not be influenced in any way by the possibility of organ donation. A major ethical issue regarding the family is how best to transition from discussing treatment-withdrawal decisions to discussing possible organ retrieval for donation should the patient die rapidly after treatment withdrawal. Close cooperation between the healthcare team and the organ retrieval team is crucial to minimize the distress of family members during this transition. Modalities for implementing Maastricht type III organ donation are discussed here, including the best location for withdrawing life-sustaining treatments (operating room or intensive care unit). PMID:22747673

Inhibition of monoamine oxidase isoforms modulates nicotine withdrawal syndrome in the rat.

PubMed

Malin, D H; Moon, W D; Goyarzu, P; Barclay, E; Magallanes, N; Vela, A J; Negrete, A P; Mathews, H; Stephens, B; Mills, W R

2013-10-06

There have been many reports of monoamine oxidase (MAO) inhibition by non-nicotine ingredients in tobacco smoke, persisting for days after smoking cessation. This study determined the effect of inhibiting MAO and its isoforms on nicotine withdrawal syndrome. Rats were rendered nicotine-dependent by seven days of subcutaneous (s.c.) 9 mg/kg/day infusion of nicotine bitartrate. Twenty-two hours after termination of infusion, they were observed over 20 min for somatically expressed nicotine withdrawal signs. Three hours before observation, rats were injected intraperitoneally (i.p.) with 4 mg/kg each of the MAO A antagonist clorgyline and the MAO B antagonist deprenyl, or with saline alone. A similar experiment was performed with non-dependent, saline-infused rats. Another experiment compared nicotine-dependent rats that received injections of either saline or 4 mg/kg clorgyline alone. A further experiment compared rats receiving either saline or 4 mg/kg deprenyl alone. Combined treatment with both MAO inhibitors markedly and significantly exacerbated somatically expressed nicotine withdrawal signs in nicotine infused rats, while having no significant effects in saline-infused rats. Rats injected s.c. with 4 mg/kg clorgyline alone had significantly more withdrawal signs than saline-injected rats, while deprenyl-injected rats had significantly fewer signs than saline controls. Assays confirmed that clorgyline thoroughly reduced MAO A enzymatic activity and deprenyl thoroughly reduced MAO B activity. The results suggest that inhibition of MAO A may contribute to the intensity of withdrawal syndrome in smoking cessation. © 2013 Elsevier Inc. All rights reserved.

Navigating communication with families during withdrawal of life-sustaining treatment in intensive care: a qualitative descriptive study in Australia and New Zealand.

PubMed

Bloomer, Melissa J; Endacott, Ruth; Ranse, Kristen; Coombs, Maureen A

2017-03-01

To explore how nurses navigate communication with families during withdrawal of life-sustaining treatment in intensive care. Death in the intensive care unit is seldom unexpected and often happens following the withdrawal of life-sustaining treatment. A family-centred approach to care relies on the development of a therapeutic relationship and understanding of what is happening to the patient. Whilst previous research has focused on the transition from cure to palliation and the nurse's role in supporting families, less is known about how nurses navigate communication with families during treatment withdrawal. A qualitative descriptive approach was used. Semi-structured focus groups were conducted with adult critical care nurses from four intensive care units, two in Australia and two in New Zealand. Twenty-one nurses participated in the study. Inductive content analysis revealed five key themes relating to how nurses navigate family communication: (1) establishing the WHO; (2) working out HOW; (3) judging WHEN; (4) assessing the WHAT; and (5) WHERE these skills were learnt. Navigating an approach to family communication during treatment withdrawal is a complex and multifaceted nursing activity that is known to contribute to family satisfaction with care. There is need for support and ongoing education opportunities that develop the art of communication in this frequently encountered aspect of end-of-life care. How nurses navigate communication with families during treatment withdrawal is just as important as what is communicated. Nurses need access to supports and education opportunities in order to be able to perform this vital role. © 2016 John Wiley & Sons Ltd.

A Remarkable Military Feat: The Hungnam Redeployment, December 1950

DTIC Science & Technology

2012-04-01

Dunkirk , France Britain, France 338,000 troops April 1941 Attica and Peloponnesus, Greece Britain 43,000 troops Oct. 1941 Odessa USSR 86,000 troops...amphibious withdrawal demands our attention. Dunkirk and Hungnam represent the antipodes of the twentieth-century amphibious withdrawal. Dunkirk in...1950. Hungnam was no Dunkirk , nor from the Navy and the Marine Corps perspective had it at any time been likely to become one. Many factors

Evidence for the Discriminant Validity of the Revised Social Anhedonia Scale From Social Anxiety.

PubMed

Cicero, David C; Krieg, Alexander; Becker, Theresa M; Kerns, John G

2016-10-01

Social anhedonia and social anxiety are two constructs with similar behaviors including avoidance of and withdrawal from social situations. In three studies, the current research aimed to test whether social anhedonia could be discriminated from social anxiety using the most common measure of social anhedonia, the Revised Social Anhedonia Scale (RSAS). In Study 1, an item-level factor analysis of the RSAS found two factors: Social Apathy/Aversion and Social Withdrawal. In Study 2, this two-factor structure was confirmed in a separate sample. In Study 3, a model with social anhedonia and anxiety scale scores loading on separate factors fit better than a model with social anhedonia and anxiety loading on a single factor. Social anhedonia and anxiety displayed differential associations with negative schizotypy and emotion processing. Findings suggest that the RSAS is successful in measuring social anhedonia distinct from social anxiety. © The Author(s) 2015.

Probabilistic analysis on the failure of reactivity control for the PWR

NASA Astrophysics Data System (ADS)

Sony Tjahyani, D. T.; Deswandri; Sunaryo, G. R.

2018-02-01

The fundamental safety function of the power reactor is to control reactivity, to remove heat from the reactor, and to confine radioactive material. The safety analysis is used to ensure that each parameter is fulfilled during the design and is done by deterministic and probabilistic method. The analysis of reactivity control is important to be done because it will affect the other of fundamental safety functions. The purpose of this research is to determine the failure probability of the reactivity control and its failure contribution on a PWR design. The analysis is carried out by determining intermediate events, which cause the failure of reactivity control. Furthermore, the basic event is determined by deductive method using the fault tree analysis. The AP1000 is used as the object of research. The probability data of component failure or human error, which is used in the analysis, is collected from IAEA, Westinghouse, NRC and other published documents. The results show that there are six intermediate events, which can cause the failure of the reactivity control. These intermediate events are uncontrolled rod bank withdrawal at low power or full power, malfunction of boron dilution, misalignment of control rod withdrawal, malfunction of improper position of fuel assembly and ejection of control rod. The failure probability of reactivity control is 1.49E-03 per year. The causes of failures which are affected by human factor are boron dilution, misalignment of control rod withdrawal and malfunction of improper position for fuel assembly. Based on the assessment, it is concluded that the failure probability of reactivity control on the PWR is still within the IAEA criteria.

Prognostic analysis of patients with epilepsy according to time of relapse after withdrawal of antiepileptic drugs following four seizure-free years.

PubMed

Park, Soochul; Lee, Dong Hyun; Kim, Seung Woo; Roh, Yun Ho

2017-01-01

We performed a retrospective, prognostic analysis of a cohort of patients with epilepsy according to time of relapse after four seizure-free years. Planned withdrawal of antiepileptic drugs (AEDs) and at least 3 years of follow-up after AED discontinuation were performed. The following two groups were assessed: (1) an early relapse (ER) group of patients who experienced recurrence during AED withdrawal and (2) a late relapse (LR) group of patients who experienced recurrence after completion of the AED discontinuation process. After dichotomization, the relapse rate, prognostic factors, and their impacts for each group were compared with those of a group of patients who continued to be seizure-free after AED withdrawal (SF group) using multiple logistic regression analysis. The AED intake mode was also analyzed. Two hundred seventeen (64.6%) of the 336 total patients experienced relapse. One hundred thirty-nine patients (41.4%) and 78 patients (23.2%) were included in the LR and ER groups, respectively. Symptom duration >120 months showed the strongest negative prognostic impact as demonstrated by the 4.7-fold higher risk of recurrence in the ER group compared with the SF group. Additional factors with a negative prognostic impact included an age at epilepsy onset of ≤20 years and the presence of localization-related epilepsy. No reliable predictor between the SF and LR groups was revealed. After exclusion of the SF group, post hoc analysis according to age at epilepsy onset and symptom duration showed that the above-mentioned negative prognostic factors significantly affected the relapse patterns of the LR and ER groups. The results suggest that longer symptom duration, which could be associated with intrinsic reactivation of epilepsy, is the strongest negative prognostic factor for relapse. Relapse after AED withdrawal in prolonged follow-up of seizure-free patients is one aspect of the natural history of epilepsy. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Parents, Peers, and Social Withdrawal in Childhood: A Relationship Perspective

PubMed Central

Rubin, Kenneth H.; Root, Amy Kennedy; Bowker, Julie

2013-01-01

In this chapter, the authors review the history of the Waterloo Longitudinal Project (WLP), the first longitudinal study (1980–1992) dedicated to the study of social withdrawal, its correlates, and consequences. Theories underlying the WLP are described, as are its empirical findings. Recent research from other labs that has extended the findings of the original WLP is briefly described. The authors’ research that draws on the findings of WLP are noted as well. An underlying theme in this work is that relationships (and interactions) with parents and friends can serve as protective or exacerbating factors in the developmental course of social withdrawal and its concomitants (including social anxiety). PMID:20205181

Prediction of emergence agitation using withdrawal reaction following rocuronium injection in preschool-aged patients undergoing inguinal herniorrhaphy: a preliminary exploratory observational trial.

PubMed

Kim, Dae Hee; Roh, Go Un; Lee, Young Bok; Choi, Chang Ik; Lee, Jae Moon; Chae, Yun Jeong

2018-01-01

The development of emergence agitation (EA) is associated with several factors including age, preoperative anxiety, postoperative pain, anesthesia method, and surgery type. No studies have investigated whether the withdrawal reaction following rocuronium injection can predict the occurrence of EA. Therefore, we investigated this relationship in preschool-aged children undergoing inguinal herniorrhaphy, and which grade of withdrawal reaction is appropriate for identifying patients at risk of experiencing EA. A total of 40 patients were enrolled in this study. During anesthesia induction, the withdrawal reaction after loss of consciousness following rocuronium injection was assessed using a 4-point scale. After surgery, EA was assessed using the Watcha scale. There was a correlation between withdrawal reaction and EA on admission to the postanesthesia care unit (PACU). Patients with a severe withdrawal reaction (grade 3) showed a significantly higher incidence of severe EA requiring medication on admission to the PACU. The findings of this preliminary exploratory observational study suggest that it is possible for withdrawal movement following rocuronium injection during anesthesia induction to reflect pain sensitivity of pediatric patients, which in turn may be useful in identifying those at risk of severe EA on admission to the PACU among preschool children undergoing inguinal herniorrhaphy. Further studies with a larger sample size are required to validate these findings. The exact correlation between pain reaction following rocuronium injection and postoperative pain or pain-related phenomenon should be elucidated.

Tobacco Withdrawal Components and Their Relations with Cessation Success

PubMed Central

Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Sheffer, Megan A.; Smith, Stevens S.; Loh, Wei-Yin; Bolt, Daniel M.; Kim, Su-Young; Kaye, Jesse T.; Hefner, Kathryn R.; Baker, Timothy B.

2011-01-01

Rationale Tobacco withdrawal is a key factor in smoking relapse, but important questions about the withdrawal phenomenon remain. Objectives This research was intended to provide information about two core components of withdrawal (negative affect and craving): 1) how various withdrawal symptom profile dimensions (e.g., mean level, volatility, extreme values) differ between negative affect and craving; and 2) how these dimensions relate to cessation outcome. Methods Adult smokers (N=1504) in a double-blind randomized placebo-controlled smoking cessation trial provided real-time withdrawal symptom data four times per day for 4 weeks (2 weeks pre-quit and 2 weeks post-quit) via palmtop computers. Cessation outcome was biochemically confirmed 8-week point-prevalence abstinence. Results Examination of craving and negative affect dimensions following a cessation attempt revealed that craving symptoms differed from negative affect symptoms, with higher means, greater variability, and a greater incidence of extreme peaks. Regression analyses revealed that abstinence was associated with lower mean levels of both craving and negative affect and fewer incidences of extreme craving peaks. In a multivariate model, the increase in mean craving and negative affect scores each uniquely predicted relapse. Conclusions Real-time reports revealed different patterns of abstinence-related negative affect and craving and that dimensions of both predict cessation outcome, suggesting that negative affect and craving dimensions each has motivational significance. This underscores the complexity of withdrawal as a determinant of relapse and the need to measure its distinct components and dimensions. PMID:21416234

Effect of forced exercise and exercise withdrawal on memory, serum and hippocampal corticosterone levels in rats.

PubMed

Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

2015-10-01

Evidence suggests that there are positive effects of exercise on learning and memory. Moreover, some studies have demonstrated that forced exercise plays the role of a stressor. This study was aimed at investigating the effects of different timing of exercise and exercise withdrawal on memory, and serum and hippocampal corticosterone (CORT) levels. Wistar rats were randomly divided into five groups: control, sham, exercise-rest (exercise withdrawal), rest-exercise (exercised group), and exercise-exercise (continuous exercise). Rats were forced to run on a treadmill for 1 h/day at a speed 20-21-m/min. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. Findings showed that after the exercise withdrawal, short-term and mid-term memories, had significant enhancement compared to the control group, while the long-term memory did not present this result. In addition, the serum and hippocampal CORT levels were at the basal levels after the rest period in the exercise-rest group. In the rest-exercise group, exercise improved mid- and long-term memories, whereas continuous exercise improved all types short-, mid- and long-term memories, particularly the mid-term memory. Twenty-one and forty-two days of exercise significantly decreased the serum and hippocampal CORT levels. It seems that exercise for at least 21 days with no rest could affect biochemical factors in the brain. Also, regular continuous exercise plays an important role in memory function. Hence, the duration and withdraw of exercise are important factors for the neurobiological aspects of the memory responses.

Workplace relational factors and physicians' intention to withdraw from practice.

PubMed

Masselink, Leah E; Lee, Shoou-Yih D; Konrad, Thomas R

2008-01-01

Physician turnover threatens continuity of care for patients and is a huge expense for health care organizations. Health care organizations have been advised to help physicians build positive relations with colleagues, staff, and patients as a strategy to socially integrate physicians in the workplace and to increase physician retention. Although these recommendations are touted as "evidence-based" practices, the importance of workplace relationships for physician retention has not been established empirically. The purpose of this study is to examine two questions: Are physicians who report better relationships with colleagues, staff, and patients less likely to intend to withdraw from practice? Do the effects of these relational factors differ for large-group and solo/small-group practice physicians? Using data from the Physician Worklife Survey, we analyzed the associations between physicians' reported relationships with colleagues, staff, and patients and intention to withdraw from practice within 2 years using logistic regression. : Relationships with colleagues had a significant and negative association with intended withdrawal from practice for large-group practice physicians. The joint effect of relationships with colleagues, staff, and patients was significant for large-group practice physicians, but it only approached significance for solo/small-group practice physicians. This study suggests that workplace relationships may influence physicians' intention to withdraw from practice, but the mechanisms by which they do so are unclear. Possible interventions to improve physician retention include promotion of informal mentoring and efforts to support community involvement of physicians and their families. Further research examining the role of these and other programs in promoting physician retention can help employers to foster positive workplace relationships and improve retention.

Review. Neurobiological mechanisms for opponent motivational processes in addiction.

PubMed

Koob, George F; Le Moal, Michel

2008-10-12

The conceptualization of drug addiction as a compulsive disorder with excessive drug intake and loss of control over intake requires motivational mechanisms. Opponent process as a motivational theory for the negative reinforcement of drug dependence has long required a neurobiological explanation. Key neurochemical elements involved in reward and stress within basal forebrain structures involving the ventral striatum and extended amygdala are hypothesized to be dysregulated in addiction to convey the opponent motivational processes that drive dependence. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission such as dopamine and opioid peptides in the ventral striatum, but also recruitment of brain stress systems such as corticotropin-releasing factor (CRF), noradrenaline and dynorphin in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, anxiety-like responses and extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence and to contribute to stress-induced relapse. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for the long hypothesized opponent motivational processes responsible for the negative reinforcement driving addiction.

Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics.

PubMed

Migale, Roberta; MacIntyre, David A; Cacciatore, Stefano; Lee, Yun S; Hagberg, Henrik; Herbert, Bronwen R; Johnson, Mark R; Peebles, Donald; Waddington, Simon N; Bennett, Phillip R

2016-06-13

Preterm birth is now recognized as the primary cause of infant mortality worldwide. Interplay between hormonal and inflammatory signaling in the uterus modulates the onset of contractions; however, the relative contribution of each remains unclear. In this study we aimed to characterize temporal transcriptome changes in the uterus preceding term labor and preterm labor (PTL) induced by progesterone withdrawal or inflammation in the mouse and compare these findings with human data. Myometrium was collected at multiple time points during gestation and labor from three murine models of parturition: (1) term gestation; (2) PTL induced by RU486; and (3) PTL induced by lipopolysaccharide (LPS). RNA was extracted and cDNA libraries were prepared and sequenced using the Illumina HiSeq 2000 system. Resulting RNA-Seq data were analyzed using multivariate modeling approaches as well as pathway and causal network analyses and compared against human myometrial transcriptome data. We identified a core set of temporal myometrial gene changes associated with term labor and PTL in the mouse induced by either inflammation or progesterone withdrawal. Progesterone withdrawal initiated labor without inflammatory gene activation, yet LPS activation of uterine inflammation was sufficient to override the repressive effects of progesterone and induce a laboring phenotype. Comparison of human and mouse uterine transcriptomic datasets revealed that human labor more closely resembles inflammation-induced PTL in the mouse. Labor in the mouse can be achieved through inflammatory gene activation yet these changes are not a requisite for labor itself. Human labor more closely resembles LPS-induced PTL in the mouse, supporting an essential role for inflammatory mediators in human "functional progesterone withdrawal." This improved understanding of inflammatory and progesterone influence on the uterine transcriptome has important implications for the development of PTL prevention strategies.

Growth factor withdrawal in combination with sodium butyrate addition extends culture longevity and enhances antibody production in CHO cells.

PubMed

Hong, Jong Kwang; Lee, Gyun Min; Yoon, Sung Kwan

2011-09-10

The effect of growth factor (GF) and sodium butyrate (NaBu) on Chinese hamster ovary (CHO) cell growth, cell viability and antibody production was investigated using shaking flasks in GF-containing and GF-deficient medium containing 0, 1 and 3mM NaBu. The withdrawal of GF and the addition of NaBu suppressed cell growth, but they significantly increased specific antibody productivity, q(Ab). Interestingly, the withdrawal of GF in combination with the addition of NaBu markedly retarded cell death, leading to extended culture longevity. For instance, at 3mM NaBu, cell viability fell below 80% after day 4 in GF-containing medium, but it remained over 80% until day 18 in GF-deficient medium. Due to the enhanced q(Ab) and the extended culture longevity, approximately 2-fold increase in total antibody production was achieved in pseudo-perfusion culture with 1mM NaBu in GF-deficient medium, compared to the culture in GF-containing medium. The effect of GF and NaBu on the change in the expression and activity of cellular proteins, c-Myc, Bcl-2 and pyruvate dehydrogenase (PDH), was also investigated. Both the withdrawal of GF and the addition of NaBu decreased the expression of c-Myc. The expression of Bcl-2 was enhanced by the addition of NaBu in a dose-dependent manner while it was not affected by the withdrawal of GF. In addition, both the withdrawal of GF and the addition of NaBu reduced metabolic rates, q(Glc), q(Lac) and Y(Lac/Glc), and increased PDH activity while not affecting PDH expression, suggesting that they may reduce the glycolytic rates, but enhance the conversion rates of pyruvate to TCA intermediates. Taken together, the withdrawal of GF in combination with the addition of NaBu can be considered as a relevant strategy for alleviating NaBu-induced cell apoptosis and enhancing antibody production since it can be easily implemented as well as enhance q(Ab) and extend culture longevity. Copyright © 2011 Elsevier B.V. All rights reserved.

Conditional Switching of Vascular Endothelial Growth Factor (VEGF) Expression in Tumors: Induction of Endothelial Cell Shedding and Regression of Hemangioblastoma-Like Vessels by VEGF Withdrawal

NASA Astrophysics Data System (ADS)

Benjamin, Laura E.; Keshet, Eli

1997-08-01

We have recently shown that VEGF functions as a survival factor for newly formed vessels during developmental neovascularization, but is not required for maintenance of mature vessels. Reasoning that expanding tumors contain a significant fraction of newly formed and remodeling vessels, we examined whether abrupt withdrawal of VEGF will result in regression of preformed tumor vessels. Using a tetracycline-regulated VEGF expression system in xenografted C6 glioma cells, we showed that shutting off VEGF production leads to detachment of endothelial cells from the walls of preformed vessels and their subsequent death by apoptosis. Vascular collapse then leads to hemorrhages and extensive tumor necrosis. These results suggest that enforced withdrawal of vascular survival factors can be applied to target preformed tumor vasculature in established tumors. The system was also used to examine phenotypes resulting from over-expression of VEGF. When expression of the transfected VEGF cDNA was continuously ``on,'' tumors became hyper-vascularized with abnormally large vessels, presumably arising from excessive fusions. Tumors were significantly less necrotic, suggesting that necrosis in these tumors is the result of insufficient angiogenesis.

Negative Effects of SRD5A1 on Nuclear Activity of Progesterone Receptor Isoform B in JEG3 Cells.

PubMed

Miao, Zhuo; Sun, Min; Jiang, Feng; Yao, Yuanqing; Li, Yi

2016-02-01

Progesterone withdrawal signals labor in mammals. Elevated intracellular metabolism contributes to progesterone functional withdrawal through unknown mechanism, which is thought to act via progesterone receptor (PR). This study aims to investigate molecular mechanisms underlying progesterone withdrawal during pregnancy and labor. We investigated the role of 5α-reductase type I (SRD5A1) in enzymatic catalysis of progesterone and loss of PR function in a human trophoblast choriocarcinoma cell line JEG3. The PR isoform B (PR-B) was robustly expressed in JEG3 cells. The SRD5A1 small-interfering RNA knockdown led to significant increase in PR-B nuclear import, ectopic, whereas SRD5A1 overexpression resulted in remarkable inhibition of nuclear PR-B in P4-treated cells. Repression of SRD5A1 activated PR-B responsive gene, whereas overexpression of SRD5A1 possessed an inhibitory effect. JEG3 cell line is a valuable tool to study mechanisms responsible for loss of PR function and screening of drugs for preterm birth treatment. Our study aims to investigate the molecular mechanisms underlying progesterone withdrawal during pregnancy and labor. © The Author(s) 2015.

Cellular, Molecular, and Genetic Substrates Underlying the Impact of Nicotine on Learning

PubMed Central

Gould, Thomas J.; Leach, Prescott T.

2013-01-01

Addiction is a chronic disorder marked by long-lasting maladaptive changes in behavior and in reward system function. However, the factors that contribute to the behavioral and biological changes that occur with addiction are complex and go beyond reward. Addiction involves changes in cognitive control and the development of disruptive drug-stimuli associations that can drive behavior. A reason for the strong influence drugs of abuse can exert on cognition may be the striking overlap between the neurobiological substrates of addiction and of learning and memory, especially areas involved in declarative memory. Declarative memories are critically involved in the formation of autobiographical memories, and the ability of drugs of abuse to alter these memories could be particularly detrimental. A key structure in this memory system is the hippocampus, which is critically involved in binding multimodal stimuli together to form complex long-term memories. While all drugs of abuse can alter hippocampal function, this review focuses on nicotine. Addiction to tobacco products is insidious, with the majority of smokers wanting to quit; yet the majority of those that attempt to quit fail. Nicotine addiction is associated with the presence of drug-context and drug-cue associations that trigger drug seeking behavior and altered cognition during periods of abstinence, which contributes to relapse. This suggests that understanding the effects of nicotine on learning and memory will advance understanding and potentially facilitate treating nicotine addiction. The following sections examine: 1) how the effects of nicotine on hippocampus-dependent learning change as nicotine administration transitions from acute to chronic and then to withdrawal from chronic treatment and the potential impact of these changes on addiction, 2) how nicotine usurps the cellular mechanisms of synaptic plasticity, 3) the physiological changes in the hippocampus that may contribute to nicotine withdrawal deficits in learning, and 4) the role of genetics and developmental stage (i.e., adolescence) in these effects. PMID:23973448

Attitudes and approaches for withdrawing drugs for children with clinically inactive non-systemic JIA: a survey of the Childhood Arthritis and Rheumatology Research Alliance

PubMed Central

Horton, Daniel B.; Onel, Karen B.; Beukelman, Timothy; Ringold, Sarah

2016-01-01

Objective To assess the attitudes and strategies of pediatric rheumatology clinicians towards withdrawing medications for children with clinically inactive juvenile idiopathic arthritis (JIA). Methods Members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) completed an anonymous electronic survey on decision-making and approaches for withdrawing medications for inactive non-systemic JIA. Data were analyzed using descriptive statistics. Results Of 388 clinicians in CARRA, 124 completed surveys (32%), predominantly attending pediatric rheumatologists. The most highly ranked factors in decision-making for withdrawing medications were duration of clinical inactivity, drug toxicity, duration of prior activity, patient/family preferences, joint damage, and JIA category. Diagnoses of RF-positive polyarthritis and persistent oligoarthritis made respondents less likely and more likely, respectively, to withdraw JIA medications. Three-quarters of respondents waited for 6–12 months of inactive disease before stopping methotrexate or biologics, but preferences varied. There was also considerable variability in the strategies used to reduce, taper, or stop medications for clinically inactive JIA; most commonly, clinicians reported slow medication tapers lasting at least 2 months. For children on combination methotrexate-biologic therapy, 63% of respondents preferred stopping methotrexate first. Most clinicians reported using imaging only seldom or sometimes to guide decision-making, but most were also reluctant to withdraw medications in the presence of asymptomatic imaging abnormalities suggestive of subclinical inflammation. Conclusion Considerable variability exists among pediatric rheumatology clinicians regarding when and how to withdraw medications for children with clinically inactive JIA. More research is needed to identify the most effective approaches to withdraw medications and predictors of outcomes. PMID:28148696

Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy.

PubMed

Hui, C-K; Cheung, W W W; Au, W-Y; Lie, A K W; Zhang, H-Y; Yueng, Y-H; Wong, B C Y; Leung, N; Kwong, Y-L; Liang, R; Lau, G K K

2005-11-01

The hepatic outcome of hepatitis B surface antigen (HBsAg) positive patients undergoing chemotherapy after withdrawal of pre-emptive lamivudine is unknown. To examine the occurrence of hepatitis B virus (HBV) reactivation after withdrawal of pre-emptive lamivudine. Pre-emptive lamivudine was started one week before initiation of chemotherapy in 46 consecutive HBsAg positive patients and continued for the entire duration of chemotherapy. Pre-emptive lamivudine was stopped at a median 3.1 (range 3.0-3.4) months after completion of chemotherapy. Patients were longitudinally followed up after withdrawal of pre-emptive lamivudine. Median time of follow up after withdrawal of lamivudine was 25.7 (range 5.7-75.7) months. Eleven of the 46 patients (23.9%) developed HBV reactivation after withdrawal of pre-emptive lamivudine. Eight of the 16 patients with high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) compared with three of the 30 patients with low pre-chemotherapy HBV DNA (<10(4) copies/ml) developed HBV reactivation (50.0% v 10.0%, respectively; p<0.001). Hepatitis B e antigen positive patients were also more likely to develop HBV reactivation (5/11 (45.5%) v 6/35 (17.1%), respectively; p = 0.041). A high pre-chemotherapy HBV DNA (> or =10(4) copies/ml) was the most important risk factor for HBV reactivation after withdrawal of pre-emptive lamivudine on Cox proportional hazards analysis (relative risk 16.13, (95% confidence interval 2.99-87.01; p = 0.001). HBV reactivation is more likely to occur in patients with high pre-chemotherapy HBV DNA after withdrawal of pre-emptive lamivudine. A more prolonged course of antiviral therapy may be necessary in these patients after completion of chemotherapy in order to reduce post-chemotherapy HBV reactivation.

Factors influencing riverine fish assemblages in Massachusetts

USGS Publications Warehouse

Armstrong, David S.; Richards, Todd A.; Levin, Sara B.

2011-01-01

The U.S. Geological Survey, in cooperation with the Massachusetts Department of Conservation and Recreation, Massachusetts Department of Environmental Protection, and the Massachusetts Department of Fish and Game, conducted an investigation of fish assemblages in small- to medium-sized Massachusetts streams. The objective of this study was to determine relations between fish-assemblage characteristics and anthropogenic factors, including impervious cover and estimated flow alteration, relative to the effects of environmental factors, including physical-basin characteristics and land use. The results of this investigation supersede those of a preliminary analysis published in 2010. Fish data were obtained for 669 fish-sampling sites from the Massachusetts Division of Fisheries and Wildlife fish-community database. A review of the literature was used to select fish metrics - species richness, abundance of individual species, and abundances of species grouped on life history traits - responsive to flow alteration. The contributing areas to the fish-sampling sites were delineated and used with a geographic information system to determine a set of environmental and anthropogenic factors that were tested for use as explanatory variables in regression models. Reported and estimated withdrawals and return flows were used together with simulated unaltered streamflows to estimate altered streamflows and indicators of flow alteration for each fish-sampling site. Altered streamflows and indicators of flow alteration were calculated on the basis of methods developed in a previous U.S. Geological Survey study in which unaltered daily streamflows were simulated for a 44-year period (water years 1961-2004), and streamflow alterations were estimated by use of water-withdrawal and wastewater-return data previously reported to the State for the 2000-04 period and estimated domestic-well withdrawals and septic-system discharges. A variable selection process, conducted using principal components analysis and Spearman rank correlation, was used to select a set of 15 non-redundant environmental and anthropogenic factors to test for use as explanatory variables in the regression analyses. Twenty-one fish species were used in a multivariate analysis of fish-assemblage patterns. Results of nonmetric multidimensional scaling and hierarchical cluster analysis were used to group fish species into fluvial and macrohabitat generalist habitat-use classes. Two analytical techniques, quantile regression and generalized linear modeling, were applied to characterize the association between fish-response variables and environmental and anthropogenic explanatory variables. Quantile regression demonstrated that as percent impervious cover and an indicator of percent alteration of August median flow from groundwater withdrawals increase, the relative abundance and species richness of fluvial fish decrease. The quantile regression plots indicate that (1) as many as seven fluvial fish species are expected in streams with little flow alteration or impervious cover, (2) no more than four fluvial fish species are expected in streams where flow alterations from groundwater withdrawals exceed 50 percent of the August median flow or the percent area of impervious cover exceeds 15 percent, and (3) few fluvial fish remain at high rates of withdrawal (approaching 100 percent) or high rates of impervious cover (between 25 and 30 percent). Three generalized linear models (GLMs) were developed to quantify the response of fluvial fish to multiple environmental and anthropogenic variables. All variables in the GLM equations were demonstrated to be significant (p less than 0.05, with most less than 0.01). Variables in the fluvial-fish relative-abundance model were channel slope, estimated percent alteration of August median flow from groundwater withdrawals, percent wetland in a 240-meter buffer strip, and percent impervious cover. Variables in the fluvial-fish species-richness model were drainage area, channel slope, total undammed reach length, percent wetland in a 240-meter buffer strip, and percent impervious cover. Variables in the brook trout relativeabundance model were drainage area, percent open water, and percent impervious cover. The variability explained by the GLM models, as measured by the pseudo R2, ranged from 18.2 to 34.6, and correlations between observed and predicted values ranged from 0.50 to 0.60. Results of GLM models indicated that, keeping all other variables the same, a one-unit (1 percent) increase in the percent depletion of August median flow would result in a 0.9-percent decrease in the relative abundance (in counts per hour) of fluvial fish. The results of GLM models also indicated that a unit increase in impervious cover (1 percent) resulted in a 3.7-percent decrease in the relative abundance of fluvial fish, a 5.4-percent decrease in fluvial-fish species richness, and an 8.7-percent decrease in brook trout relative abundance.

Considering groundwater use to improve the assessment of groundwater pumping for irrigation in North Africa

NASA Astrophysics Data System (ADS)

Massuel, Sylvain; Amichi, Farida; Ameur, Fatah; Calvez, Roger; Jenhaoui, Zakia; Bouarfa, Sami; Kuper, Marcel; Habaieb, Hamadi; Hartani, Tarik; Hammani, Ali

2017-09-01

Groundwater resources in semi-arid areas and especially in the Mediterranean face a growing demand for irrigated agriculture and, to a lesser extent, for domestic uses. Consequently, groundwater reserves are affected and water-table drops are widely observed. This leads to strong constraints on groundwater access for farmers, while managers worry about the future evolution of the water resources. A common problem for building proper groundwater management plans is the difficulty in assessing individual groundwater withdrawals at regional scale. Predicting future trends of these groundwater withdrawals is even more challenging. The basic question is how to assess the water budget variables and their evolution when they are deeply linked to human activities, themselves driven by countless factors (access to natural resources, public policies, market, etc.). This study provides some possible answers by focusing on the assessment of groundwater withdrawals for irrigated agriculture at three sites in North Africa (Morocco, Tunisia and Algeria). Efforts were made to understand the different features that influence irrigation practices, and an adaptive user-oriented methodology was used to monitor groundwater withdrawals. For each site, different key factors affecting the regional groundwater abstraction and its past evolution were identified by involving farmers' knowledge. Factors such as farmer access to land and groundwater or development of public infrastructures (electrical distribution network) are crucial to decode the results of well inventories and assess the regional groundwater abstraction and its future trend. This leads one to look with caution at the number of wells cited in the literature, which could be oversimplified.

Time-Dependent Serum Brain-Derived Neurotrophic Factor Decline During Methamphetamine Withdrawal.

PubMed

Ren, Wenwei; Tao, Jingyan; Wei, Youdan; Su, Hang; Zhang, Jie; Xie, Ying; Guo, Jun; Zhang, Xiangyang; Zhang, Hailing; He, Jincai

2016-02-01

Methamphetamine (METH) is a widely abused illegal psychostimulant, which is confirmed to be neurotoxic and of great damage to human. Studies on the role of brain-derived neurotrophic factor (BDNF) in human METH addicts are limited and inconsistent. The purposes of this study are to compare the serum BDNF levels between METH addicts and healthy controls during early withdrawal, and explore the changes of serum BDNF levels during the first month after METH withdrawal.179 METH addicts and 90 age- and gender-matched healthy controls were recruited in this study. We measured serum BDNF levels at baseline (both METH addicts and healthy controls) and at 1 month after abstinence of METH (METH addicts only).Serum BDNF levels of METH addicts at baseline were significantly higher than controls (1460.28  ±  490.69 vs 1241.27  ±  335.52  pg/mL; F = 14.51, P < 0.001). The serum BDNF levels of 40 METH addicts were re-examined after 1 month of METH abstinence, which were significantly lower than that at baseline (1363.70  ±  580.59 vs 1621.41  ±  591.07  pg/mL; t = 2.26, P = .03), but showed no differences to the controls (1363.70  ±  580.59 vs 1241.27  ±  335.52  pg/mL; F = 2.29, P = 0.13).Our study demonstrated that serum BDNF levels were higher in METH addicts than controls during early withdrawal, and were time dependent decreased during the first month of abstinence. These findings may provide further evidence that increased serum BDNF levels may be associated with the pathophysiology of METH addiction and withdrawal and may be a protective response against the subsequent METH-induced neurotoxicity. Besides, these findings may also promote the development of medicine in the treatment of METH addiction and withdrawal.

Similarities between obesity in pets and children: the addiction model.

PubMed

Pretlow, Robert A; Corbee, Ronald J

2016-09-01

Obesity in pets is a frustrating, major health problem. Obesity in human children is similar. Prevailing theories accounting for the rising obesity rates - for example, poor nutrition and sedentary activity - are being challenged. Obesity interventions in both pets and children have produced modest short-term but poor long-term results. New strategies are needed. A novel theory posits that obesity in pets and children is due to 'treats' and excessive meal amounts given by the 'pet-parent' and child-parent to obtain affection from the pet/child, which enables 'eating addiction' in the pet/child and results in parental 'co-dependence'. Pet-parents and child-parents may even become hostage to the treats/food to avoid the ire of the pet/child. Eating addiction in the pet/child also may be brought about by emotional factors such as stress, independent of parental co-dependence. An applicable treatment for child obesity has been trialled using classic addiction withdrawal/abstinence techniques, as well as behavioural addiction methods, with significant results. Both the child and the parent progress through withdrawal from specific 'problem foods', next from snacking (non-specific foods) and finally from excessive portions at meals (gradual reductions). This approach should adapt well for pets and pet-parents. Pet obesity is more 'pure' than child obesity, in that contributing factors and treatment points are essentially under the control of the pet-parent. Pet obesity might thus serve as an ideal test bed for the treatment and prevention of child obesity, with focus primarily on parental behaviours. Sharing information between the fields of pet and child obesity would be mutually beneficial.

Groundwater/surface-water interactions in the Tunk, Bonaparte, Antoine, and Tonasket Creek Subbasins, Okanogan River Basin, North-Central Washington, 2008

USGS Publications Warehouse

Sumioka, S.S.; Dinicola, R.S.

2009-01-01

An investigation into groundwater/surface-water interactions in four tributary subbasins of the Okanogan River determined that streamflows and shallow groundwater levels beneath the streams varied seasonally and by location. Streamflows measured in June 2008 indicated net losses of streamflow along 10 of 17 reaches, and hydraulic gradients measured between streams and shallow groundwater indicated potential recharge of surface water to groundwater at 11 of 21 measurement sites. In September 2008, net losses of streamflow were indicated along 9 of 17 reaches, and potential recharge of surface water to groundwater was indicated at 18 of 21 measurement sites. The greatest losses of streamflow occurred near the confluences with the Okanogan River, likely due to the presence of thick layers of unconsolidated deposits in the flood plain of the Okanogan River. Based on available geologic information compiled from drillers' logs, a surficial geologic map, and streamflow records, the extensive and thick deposits of unconsolidated material in the Tunk and Bonaparte Creek subbasins are factors in sustaining the almost perennial streamflow in those creeks. The less extensive and generally thinner unconsolidated deposits in the Tonasket and Antoine subbasins are contributing factors to the occasional extended periods of zero flow (a dry stream channel) in those creeks. Even though groundwater withdrawals would affect streamflows, relatively low precipitation in the area, along with limited groundwater storage capacity and the presence of permeable, unconsolidated deposits underlying the stream channels, would likely lead to loss of surface water to the groundwater system without any withdrawals.

Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure.

PubMed

Dominguez, G; Dagnas, M; Decorte, L; Vandesquille, M; Belzung, C; Béracochéa, D; Mons, N

2016-03-01

Both human and animal studies indicate that alcohol withdrawal following chronic alcohol consumption (CAC) impairs many of the cognitive functions which rely on the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive element binding (CREB) cascade, although the role of PKA/CREB cascade in behavioral and molecular changes during sustained withdrawal period remains largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1 region (dCA1) of the hippocampus compared with CAC and water conditions. In contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared with water controls. Next, we showed that enhancing CREB activity through rolipram administration prior to testing improved WM performance in withdrawn mice but impaired WM function in water mice. In addition, WM improvement correlates positively with increased pCREB level selectively in the PFC of withdrawn mice. Results further indicate that direct infusion of the PKA activator (Sp-cAMPS) into the PFC significantly improves or impairs, respectively, WM performance in withdrawn and water animals. In contrast, Sp-cAMPS had no effect on WM when infused into the dCA1. Collectively, these results provide strong support that dysregulation of PKA/CREB-dependent processes in prefrontal neurons is a critical molecular signature underlying cognitive decline during alcohol withdrawal.

Contribution of the ethics committee of the French society of intensive care medicine to a scenario for the implementation of organ donation after Maastricht III-type cardiac death in France.

PubMed

Graftieaux, J-P; Bollaert, P-E; Haddad, L; Kentish-Barnes, N; Nitenberg, G; Robert, R; Villers, D; Dreyfuss, D

2014-02-01

French law allows organ donation after death due to cardiocirculatory arrest. In the Maastricht classification, type III non-heart-beating donors are those who experience cardiocirculatory arrest after the withdrawal of life-sustaining treatments. French authorities in charge of regulating organ donation (Agence de la Biomédecine, ABM) are considering organ collection from Maastricht type III donors. We describe a scenario for Maastricht type III organ donation that fully complies with the ethical norms governing care to dying patients. That organ donation may occur after death should have no impact on the care given to the patient and family. The dead-donor rule must be followed scrupulously: the organ retrieval procedure must neither cause nor hasten death. The decision to withdraw life-sustaining treatments, withdrawal modalities, and care provided to the patient and family must adhere strictly to the requirements set forth in patient-rights legislation (the 2005 Léonetti law in France) and should not be influenced in any way by the possibility of organ donation. A major ethical issue regarding the family is how best to transition from discussing treatment-withdrawal decisions to discussing possible organ retrieval for donation should the patient die rapidly after treatment withdrawal. Close cooperation between the healthcare team and the organ retrieval team is crucial to minimize the distress of family members during this transition. Modalities for implementing Maastricht type III organ donation are discussed here, including the best location for withdrawing life-sustaining treatments (operating room or intensive care unit). Copyright © 2014. Published by Elsevier SAS.

Role of orbitofrontal cortex neuronal ensembles in the expression of incubation of heroin craving

PubMed Central

Fanous, Sanya; Goldart, Evan M.; Theberge, Florence R.M.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.

2012-01-01

In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin-seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6-h/d for 10 d) and assessed cue-induced heroin-seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin-seeking increased from 1 day to 14 days and was accompanied by increased Fos expression in ~12% of OFC neurons. Non-selective inactivation of OFC neurons with the GABA agonists baclofen+muscimol decreased cue-induced heroin-seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin-seeking after 14 withdrawal days. We trained cfos-lacZ transgenic rats to self-administer heroin and 11 days later re-exposed them to heroin-associated cues or novel cues for 15 min (induction day) followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 days later. Daun02 selectively decreased cue-induced heroin-seeking in rats previously re-exposed to the heroin-associated cues on induction day, but not in rats previously exposed to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving. PMID:22915104

Benzodiazepine-induced hippocampal CA1 neuron alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor plasticity linked to severity of withdrawal anxiety: differential role of voltage-gated calcium channels and N-methyl-D-aspartic acid receptors.

PubMed

Xiang, Kun; Tietz, Elizabeth I

2007-09-01

Withdrawal from 1-week oral administration of the benzodiazepine, flurazepam (FZP) is associated with increased alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor (AMPAR) miniature excitatory postsynaptic currents (mEPSCs) but reduction of N-methyl-D-aspartic acid (NMDA) receptor (NMDAR)-evoked (e)EPSCs in hippocampal CA1 neurons. A positive correlation was observed between increased AMPAR-mediated mEPSC amplitude and anxiety-like behavior in 1-day FZP-withdrawn rats. These effects were disrupted by systemic AMPAR antagonist administration (GYKI-52466, 0.5 mg/kg, intraperitoneal) at withdrawal onset, strengthening the hypothesis that CA1 neuron AMPAR-mediated hyperexcitability is a central component of a functional anatomic circuit associated with the expression of withdrawal anxiety. Abolition of AMPAR current upregulation in 2-day FZP withdrawn rats by GYKI-52466 injection also reversed the reduction in NMDAR-mediated eEPSC amplitude in CA1 neurons from the same rats, suggesting that downregulation of NMDAR function may serve a protective, negative-feedback role to prevent AMPAR-mediated neuronal overexcitation. NMDAR antagonist administration (MK-801, 0.25 mg/kg intraperitoneally) had no effect on modifying increased glutamatergic strength or on withdrawal anxiety, whereas injection of an L-type voltage-gated calcium channel antagonist, nimodipine (10 mg/kg, intraperitoneally) averted AMPAR current enhancement and anxiety-like behavior, suggesting that these manifestations may be initiated by a voltage-gated calcium channel-dependent signal transduction pathway. An evidence-based model of likely cellular mechanisms in the hippocampus contributing to benzodiazepine withdrawal anxiety was proposed implicating regulation of multiple CA1 neuron ion channels.

Sex differences in effects of dopamine D1 receptors on social withdrawal.

PubMed

Campi, Katharine L; Greenberg, Gian D; Kapoor, Amita; Ziegler, Toni E; Trainor, Brian C

2014-02-01

Dopamine signaling in the nucleus accumbens (NAc) plays a critical role in the regulation of motivational states. Recent studies in male rodents show that social defeat stress increases the activity of ventral tegmental dopamine neurons projecting to the NAc, and that this increased activity is necessary for stress-induced social withdrawal. Domestic female mice are not similarly aggressive, which has hindered complementary studies in females. Using the monogamous California mouse (Peromyscus californicus), we found that social defeat increased total dopamine, DOPAC, and HVA content in the NAc in both males and females. These results are generally consistent with previous studies in Mus, and suggest defeat stress also increases NAc dopamine signaling in females. However, these results do not explain our previous observations that defeat stress induces social withdrawal in female but not male California mice. Pharmacological manipulations provided more insights. When 500 ng of the D1 agonist SKF38393 was infused in the NAc shell of females that were naïve to defeat, social interaction behavior was reduced. This same dose of SKF38393 had no effect in males, suggesting that D1 receptor activation is sufficient to induce social withdrawal in females but not males. Intra-accumbens infusion of the D1 antagonist SCH23390 increased social approach behavior in females exposed to defeat but not in females naïve to defeat. This result suggests that D1 receptors are necessary for defeat-induced social withdrawal. Overall, our results suggest that sex differences in molecular pathways that are regulated by D1 receptors contribute to sex differences in social withdrawal behavior. Copyright © 2013 Elsevier Ltd. All rights reserved.

DIFFERENTIAL EFFECTS OF SINGLE VERSUS REPEATED ALCOHOL WITHDRAWAL ON THE EXPRESSION OF ENDOCANNABINOID SYSTEM-RELATED GENES IN THE RAT AMYGDALA

PubMed Central

Serrano, Antonia; Rivera, Patricia; Pavon, Francisco J.; Decara, Juan; Suárez, Juan; de Fonseca, Fernando Rodriguez; Parsons, Loren H.

2011-01-01

Background Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity and affective control. Methods The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol-exposed rats were generated by maintenance on an ethanol liquid diet (10%): one group received continuous access to ethanol for 15 days, while the second group was given intermittent access to the ethanol diet (5 days/week for 3 weeks). Control subjects were maintained on an isocaloric ethanol-free liquid diet. To provide an initial profile of acute withdrawal amygdala tissue was harvested following either 6 or 24 hours of ethanol withdrawal. Results Acute ethanol withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (FAAH and MAGL, respectively) were evident, as were reductions in mRNA expression for CB1, CB2 and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent ethanol exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g. CB1, CB2, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in 2-AG biosynthesis (e.g. DAGL-α/β) were found in any condition. Conclusions These findings suggest that ethanol dependence and withdrawal are associated with dysregulated endocannabinoid signaling in the amygdala. These alterations may contribute to withdrawal-related dysregulation of amygdalar neurotransmission. PMID:22141465

Sex Differences in the Effect of Finasteride on Acute Ethanol Withdrawal Severity in C57BL/6J and DBA/2J Mice

PubMed Central

Gorin-Meyer, Rebecca E.; Wiren, Kristine M.; Tanchuck, Michelle A.; Long, Season L.; Yoneyama, Naomi; Finn, Deborah A.

2007-01-01

The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of γ-aminobutyric acidA (GABAA) receptors that can modulate ethanol (EtOH) withdrawal. The 5α-reductase inhibitor finasteride can block the formation of ALLO and other GABAergic neurosteroids and also reduce certain effects of EtOH. Treatment with finasteride during chronic EtOH exposure decreased EtOH withdrawal severity and blood EtOH concentrations (BECs), suggesting an additional effect of finasteride on EtOH pharmacokinetics. Thus, the purpose of the present study was to determine the effect of finasteride on acute EtOH withdrawal severity, to minimize the effect of finasteride on EtOH metabolism. Male and female C57BL/6J and DBA/2J mice received a pretreatment of finasteride (50 mg/kg i.p.) or vehicle 24 hours prior to an injection of EtOH (4 g/kg i.p.) or saline. Handling-induced convulsions (HICs) were scored at baseline, and then over a 24 hr period after EtOH or saline injection. In another experiment, plasma estradiol and corticosterone levels were assessed at selected time points (0, 2, 8, and 24 hrs). In a final study, retro-orbital blood samples were collected at 30, 60, 120, and 240 minutes post-EtOH administration to access finasteride’s effects on EtOH clearance parameters. Pretreatment with finasteride increased acute EtOH withdrawal severity in female C57BL/6J and DBA/2J mice but decreased withdrawal severity in male mice of both strains. Finasteride did not alter BECs, EtOH clearance, estradiol, or corticosterone concentrations in a manner that appeared to contribute to the sex difference in finasteride’s effect on acute EtOH withdrawal severity. These findings suggest that male and female C57BL/6J and DBA/2J mice differ in their sensitivity to changes in ALLO or other GABAergic neurosteroid levels during acute EtOH withdrawal. Sex differences in the modulation of GABAergic 5α-reduced steroids may be an important consideration in understanding and developing therapeutic interventions in alcoholics. PMID:17428611

Social withdrawal of persons with vascular dementia associated with disturbance of basic daily activities, apathy, and impaired social judgment.

PubMed

Honda, Yukiko; Meguro, Kenichi; Meguro, Mitsue; Akanuma, Kyoko

2013-01-01

Patients with vascular dementia (VaD) are often isolated, withdrawn from society because of negative symptoms and functional disabilities. The aim of this study was to detect factors associated with social withdrawal in patients with VaD. The participants were 36 institutionalized patients with VaD. Social withdrawal was assessed with the social withdrawal of the Multidimensional Observation Scale for Elderly Subjects (MOSES). Possible explanatory variables were the MOSES items depression and self-care, Cognitive Abilities Screening Instrument (CASI), apathy evaluation scale (AES), and Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity Scale (BEHAVE-AD-FW). Multiple regression analyses were conducted for two groups: Analysis 1 was performed in all patients (N = 36) and Analysis 2 was performed in the patients with the ability to move by themselves (i.e., independent walking or independent movement with a cane or a wheelchair; n = 28). In Analysis 1, MOSES item social withdrawal was correlated with AES and MOSES item self-care. In Analysis 2, MOSES item social withdrawal was correlated with AES and CASI domain abstraction and judgment. Decreased social activities of VaD were not related to general cognitive function or depression. Disturbed activities of daily living (ADLs) for self-care may involve decreased frontal lobe function, indicating that comprehensive rehabilitation for both ADL and dementia are needed to improve the social activities of patients with VaD.

Estimating the relative contributions of human withdrawals and climate variability to changes in groundwater

NASA Astrophysics Data System (ADS)

Swenson, S. C.; Lawrence, D. M.

2014-12-01

Estimating the relative contributions of human withdrawals and climate variability to changes in groundwater is a challenging task at present. One method that has been used recently is a model-data synthesis combining GRACE total water storage estimates with simulated water storage estimates from land surface models. In this method, water storage changes due to natural climate variations simulated by a model are removed from total water storage changes observed by GRACE; the residual is then interpreted as anthropogenic groundwater change. If the modeled water storage estimate contains systematic errors, these errors will also be present in the residual groundwater estimate. For example, simulations performed with the Community Land Model (CLM; the land component of the Community Earth System Model) generally show a weak (as much as 50% smaller) seasonal cycle of water storage in semi-arid regions when compared to GRACE satellite water storage estimates. This bias propagates into GRACE-CLM anthropogenic groundwater change estimates, which then exhibit unphysical seasonal variability. The CLM bias can be traced to the parameterization of soil evaporative resistance. Incorporating a new soil resistance parameterization in CLM greatly reduces the seasonal bias with respect to GRACE. In this study, we compare the improved CLM water storage estimates to GRACE and discuss the implications for estimates of anthropogenic groundwater withdrawal, showing examples for the Middle East and Southwestern United States.

The Effect of Co-occurring Substance Use on Gamma-hydroxybutyric Acid Withdrawal Syndrome.

PubMed

Kamal, Rama M; Dijkstra, Boukje A G; Loonen, Anton J; De Jong, Cornelis A J

2016-01-01

Gamma-hydroxybutyric acid (GHB) withdrawal is a complex syndrome which can be potentially life-threatening. Additionally, GHB-dependent patients frequently report co-occurring substance use of other psychoactive drugs. We assessed the add-on effect of co-use on GHB withdrawal symptoms. We conducted an open-label, pretest-posttest design study with 95 patients selected from 229 inpatients admitted for detoxification, who were divided into GHB only (GO, n = 40), GHB plus sedatives (GSE, n = 38), and GHB plus stimulants (GST, n = 17) groups. GHB withdrawal was evaluated by means of the Subjective Withdrawal Scale. Co-use add-on effects on the severity of withdrawal symptoms were evaluated 2.5 hours after the last illicit GHB self-administration (T1) when withdrawal was expected and 2.5 hours later, after administration of a very low dose of pharmaceutical GHB (T2). The GO group reported high scores of psychomotor retardation symptoms at both T1 and T2, and also high cravings, agitation, and restlessness at T1, and anxiety at T2. The GSE group reported the highest score in psycho-autonomic distress symptoms at both T1 and T2, whereas the GST group reported the highest score in psycho-motor stress factor at T2. There was no significant difference in withdrawal intensity in all symptom clusters between T1 and T2 for both GSE and GO groups. However, after 5 hours, the GST group reported significant decreases in intensity for all symptoms except for psycho-motor stress. At T1, GST and GSE groups reported more muscle twitches than the GO group as a significant add-on effect to the GHB withdrawal. At T2, the GST group experienced more agitation (P = 0.009), restlessness (P = 0.001), and rapid pulse (P = 0.034) than the GO group. Co-use, especially of stimulants, caused an add-on effect on the GHB withdrawal symptoms within the first 5 hours.

Asymmetric Partner Pronoun Use and Demand-Withdraw Interaction in Couples Coping with Health Problems

PubMed Central

Rentscher, Kelly E.; Rohrbaugh, Michael J.; Shoham, Varda; Mehl, Matthias R.

2014-01-01

Recent research links first-person plural pronoun use (we-talk) by individual romantic partners to adaptive relationship functioning and individual health outcomes. To examine a possible boundary condition of adaptive we-talk in couples coping with health problems, we correlated asymmetric couple-level we/I-ratios (more we-talk relative to I-talk by the spouse than the patient) with a concurrent pattern of directional demand-withdraw (D-W) interaction in which the spouse demands change while the patient withdraws. Couples in which a partner who abused alcohol (n = 65), smoked cigarettes despite having heart or lung disease (n = 24), or had congestive heart failure (n = 58) discussed a health-related disagreement during a video-recorded interaction task. Transcripts of these conversations provided measures of pronoun use for each partner, and trained observers coded D-W patterns from the recordings. As expected, partner asymmetry in we/I-ratio scores predicted directional demand-withdraw, such that spouses who used more we-talk (relative to I-talk) than patients tended to assume the demand role in concurrent D-W interaction. Asymmetric I-talk rather than we-talk accounted for this association, and asymmetric you-talk contributed independently as well. In contrast to previous studies of we-talk by individual partners, the present results identify dyad-level pronoun patterns that clearly do not mark beneficent processes: asymmetric partner we/I-ratios and you-talk reflect problematic demand-withdraw interaction. PMID:24098961

Spanish adaptation of social withdrawal motivation and frequency scales.

PubMed

Indias García, Sílvia; De Paúl Ochotorena, Joaquín

2016-11-01

To adapt into Spanish three scales measuring frequency (SWFS) and motivation for social withdrawal (CSPS and SWMS) and to develop a scale capable of assessing the five motivations for social withdrawal. Participants were 1,112 Spanish adolescents, aged 12-17 years. The sample was randomly split into two groups in which exploratory and confirmatory (CFA) factor analyses were performed separately. A sample of adolescents in residential care (n = 128) was also used to perform discriminant validity analyses. SWFS was reduced to eight items that account for 40% of explained variance (PVE), and its reliability is high. SWMS worked adequately in the original version, according to CFA. Some items from the CSPS were removed from the final Spanish version. The newly developed scale (SWMS-5D) is composed of 20 items including five subscales: Peer Isolation, Unsociability, Shyness, Low Mood and Avoidance. Analyses reveal adequate convergent and discriminant validities. The resulting SWFS-8 and SWMS-5D could be considered useful instruments to assess frequency and motivation for social withdrawal in Spanish samples.

Leukemia inhibitory factor influences the timing of programmed synapses withdrawal from neonatal muscles.

PubMed

Kwon, Y W; Abbondanzo, S J; Stewart, C L; Gurney, M E

1995-09-01

We show that leukemia inhibitory factor (LIF) plays a physiological role in the programmed withdrawal of synapses from neonatal muscles. First, LIF mRNA is present in embryonic skeletal muscle and is developmentally regulated. We detect high levels of LIF mRNA at embryonic day 17 (E17) in mouse hind leg muscles. The content of LIF mRNA falls 10-fold between E17 and birth and then remains low in the neonate and adult. The decrease in LIF mRNA in skeletal muscle coincides with the end of secondary myogenesis and the completion of the adult number of myofibers. Second, treatment of the mouse tensor fascia latae (TFL), a superficial muscle of the hind leg, with LIF from birth (100 ng/day), transiently delays the withdrawal of excess inputs from polyneuronally innervated myofibers by approximately 3 days. The midpoint of the process is shifted from 7.5 +/- 10.2 +/- 0.6 days of age. LIF treatment delays synapse withdrawal by altering its timing without an appreciable effect on its rate. Third, in mice homozygous for a disruption of the LIF gene, the midpoint in the reduction of multiply innervated TFL myofibers occurs 1 day earlier, at 6.5 +/- 0.5 days of age. Muscle fiber number is unchanged in LIF null mice. Treatment with LIF does not alter the rate of neonatal growth, the number of muscle fibers in the TFL, or the reappearance of inputs that have been eliminated. Instead, LIF appears to delay maturation of the motor unit by transiently delaying the onset of synapse withdrawal. We hypothesize that this is a necessary component of a selective process that will operate simultaneously and equally on multiple, competing motor units.

Regional Responses to Constrained Water Availability

NASA Astrophysics Data System (ADS)

Cui, Y.; Calvin, K. V.; Hejazi, M. I.; Clarke, L.; Kim, S. H.; Patel, P.

2017-12-01

There have been many concerns about water as a constraint to agricultural production, electricity generation, and many other human activities in the coming decades. Nevertheless, how different countries/economies would respond to such constraints has not been explored. Here, we examine the responding mechanism of binding water availability constraints at the water basin level and across a wide range of socioeconomic, climate and energy technology scenarios. Specifically, we look at the change in water withdrawals between energy, land-use and other sectors within an integrated framework, by using the Global Change Assessment Model (GCAM) that also endogenizes water use and allocation decisions based on costs. We find that, when water is taken into account as part of the production decision-making, countries/basins in general fall into three different categories, depending on the change of water withdrawals and water re-allocation between sectors. First, water is not a constraining factor for most of the basins. Second, advancements in water-saving technologies of the electricity generation cooling systems are sufficient of reducing water withdrawals to meet binding water availability constraints, such as in China and the EU-15. Third, water-saving in the electricity sector alone is not sufficient and thus cannot make up the lowered water availability from the binding case; for example, many basins in Pakistan, Middle East and India have to largely reduce irrigated water withdrawals by either switching to rain-fed agriculture or reducing production. The dominant responding strategy for individual countries/basins is quite robust across the range of alternate scenarios that we test. The relative size of water withdrawals between energy and agriculture sectors is one of the most important factors that affect the dominant mechanism.

Predictors of Flare Following Etanercept Withdrawal in Patients with Rheumatoid Factor-negative Juvenile Idiopathic Arthritis Who Reached Remission while Taking Medication.

PubMed

Aquilani, Angela; Pires Marafon, Denise; Marasco, Emiliano; Nicolai, Rebecca; Messia, Virginia; Perfetti, Francesca; Magni-Manzoni, Silvia; De Benedetti, Fabrizio

2018-05-01

To evaluate the rate of flare after etanercept (ETN) withdrawal in patients with juvenile idiopathic arthritis (JIA) who attained clinical remission while taking medication, and to identify predictors of flare. Patients were included with oligo- (oJIA) and rheumatoid factor-negative polyarticular JIA (pJIA) who received a first course of ETN for at least 18 months, maintained clinically inactive disease (CID) for at least 6 months during treatment, and were followed for 12 months after ETN withdrawal. Demographic and clinical features were collected at onset, at baseline (initiation of ETN), and at time of disease flare. After ETN withdrawal, 66 of the 110 patients enrolled (60%) flared with arthritis (of whom 7 flared with concurrent anterior uveitis; none with uveitis alone). The median time to flare was 4.3 months (interquartile range 2.5-6.4) with no evident differences between oJIA and pJIA. The number and type of joints involved at baseline and characteristics of ETN treatment/discontinuation were not associated with flare. Patients who flared were more frequently males (p = 0.034), positive for antinuclear antibody (ANA; p = 0.047), and had higher values of C-reactive protein (CRP; p = 0.012) at baseline. These variables remained significantly associated with flare in a multivariate logistic analysis, a model accounting for only 14% of the variability of the occurrence of the flare. Our results show that a significant proportion of patients with JIA who maintain CID for at least 6 months experience a relapse after ETN withdrawal. Male sex, presence of ANA, and elevated CRP at baseline were associated with higher risk of flare.

Dopamine agonist withdrawal syndrome: implications for patient care.

PubMed

Nirenberg, Melissa J

2013-08-01

Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer.

PubMed Central

Sehgal, I; Powers, S; Huntley, B; Powis, G; Pittelkow, M; Maihle, N J

1994-01-01

After therapeutic hormone deprivation, prostate cancer cells often develop androgen-insensitive growth through mechanisms thus far undefined. Neuropeptides have been previously implicated as growth factors in some prostate cancers. Here, we demonstrate that androgen-sensitive LNCaP human prostate cancer cells produce and secrete neurotensin following androgen withdrawal. We show that while LNCaP cells express the neurotensin receptor, only androgen-deprived cells exhibit a growth response to exogenous neurotensin. We further demonstrate that androgen-stimulated cells may be refractory to exogenous neurotensin due to androgen induction of a metalloprotease active toward neurotensin. Thus, prostate cancer cells deprived of androgen develop an alternative autocrine growth mechanism involving neurotensin. Images PMID:8197117

Effects of Changes in Irrigation Practices and Aquifer Development on Groundwater Discharge to the Jobos Bay National Estuarine Research Reserve near Salinas, Puerto Rico

USGS Publications Warehouse

Kuniansky, Eve L.; Rodriguez, Jose M.

2010-01-01

Since 1990, about 75 acres of black mangroves have died in the Jobos Bay National Estuarine Research Reserve near Salinas, Puerto Rico. Although many factors can contribute to the mortality of mangroves, changes in irrigation practices, rainfall, and water use resulted in as much as 25 feet of drawdown in the potentiometric surface of the aquifer in the vicinity of the reserve between 1986 and 2002. To clarify the issue, the U.S. Geological Survey, in cooperation with the Puerto Rico Department of Natural and Environmental Resources, conducted a study to ascertain how aquifer development and changes in irrigation practices have affected groundwater levels and groundwater flow to the Mar Negro area of the reserve. Changes in groundwater flow to the mangrove swamp and bay from 1986 to 2004 were estimated in this study by developing and calibrating a numerical groundwater flow model. The transient simulations indicate that prior to 1994, high irrigation return flows more than offset the effect of reduced groundwater withdrawals. In this case, the simulated discharge to the coast in the modeled area was 19 million gallons per day. From 1994 through 2004, furrow irrigation was completely replaced by micro-drip irrigation, thus eliminating return flows and the simulated average coastal discharge was 7 million gallons per day, a reduction of 63 percent. The simulated average groundwater discharge to the coastal mangrove swamps in the reserve from 1986 to 1993 was 2 million gallons per day, compared to an average simulated discharge of 0.2 million gallons per day from 1994 to 2004. The average annual rainfall for each of these periods was 38 inches. The groundwater discharge to the coastal mangrove swamps in the Jobos Bay National Estuarine Research Reserve was estimated at about 0.5 million gallons per day for 2003-2004 because of higher than average annual rainfall during these 2 years. The groundwater flow model was used to test five alternatives for increasing groundwater discharge to the coastal mangrove swamps to approximately 1.4 million gallons per day: (1) artificially recharging the aquifer with injection wells or (2) by increasing irrigation return flow by going back to furrow irrigation; (3) termination of groundwater withdrawals near the mangroves; (4) reduction of groundwater withdrawals at irrigation wells by 50 percent; and (5) a combination of alternatives 2 and 4 increasing irrigation return flows and decreasing irrigation withdrawals. Each alternative assumed average climatic conditions and groundwater withdrawals at 2004 rates. Alternative 1 required 1.5 million gallons per day of injected water. Alternative 2 required flooding 958 acres with a rate of 1.84 million gallons per day if no crops are grown. Alternative 3 required the termination of 2.44 million gallons per day of withdrawals to achieve 1.34 million gallons per day of discharge to the mangroves. Alternative 4 did not achieve the objective with only 0.80 million gallons per day simulated discharge to the mangroves, while requiring a 1.26 million gallon per day reduction in groundwater withdrawals. Alternative 5 required flooding fields with additional 1.13 million gallons of day and the same reduction in groundwater withdrawals, but did achieve the objective of about 1.4 million gallons per day discharge to the mangroves. Alternative 1, incorporating injection wells near the reserve required the least amount of water to raise groundwater levels and maintain discharge of 1.4 million gallons per day through the mangroves.

Caffeine deprivation affects vigilance performance and mood.

PubMed

Lane, J D; Phillips-Bute, B G

1998-08-01

The effects of brief caffeine deprivation on vigilance performance, mood, and symptoms of caffeine withdrawal were studied in habitual coffee drinkers. Thirty male and female coffee drinkers were tested twice at midday (1130 to 1330 hours) after mornings in which they either consumed caffeinated beverages ad lib or abstained. Vigilance performance was tested with a 30-min computerized visual monitoring task. Mood and withdrawal symptom reports were collected by questionnaires. Caffeine deprivation was associated with impaired vigilance performance characterized by a reduction in the percentage of targets detected and an increase in response time, and by subjective reports of decreased vigor and increased fatigue and symptoms characterized by sleepiness, headache, and reduced ability to work. Even short periods of caffeine deprivation, equivalent in length to skipping regular morning coffee, can produce deficits in sustained attention and noticeable unpleasant caffeine-withdrawal symptoms in habitual coffee drinkers. Such symptoms may be a common side-effect of habitual caffeine consumption that contributes to the maintenance of this behavior.

Carisoprodol: update on abuse potential and legal status.

PubMed

Reeves, Roy R; Burke, Randy S; Kose, Samet

2012-11-01

Carisoprodol is a centrally acting skeletal muscle relaxant of which meprobamate, a controlled substance, is the primary active metabolite. The abuse of carisoprodol has increased dramatically in the last several years. A withdrawal syndrome occurs in some patients who abruptly cease carisoprodol intake. The symptoms of this syndrome are similar to those seen with meprobamate withdrawal, suggesting that they may result from withdrawal from meprobamate accumulated with intake of excessive carisoprodol; however, carisoprodol is capable of modulating GABAA function, which may contribute to its abuse potential.There has been considerable debate about whether carisoprodol should be considered a controlled substance. Carisoprodol was removed from the market in Norway on May 1, 2008, but may still be used by specially approved patients. Carisoprodol was classified as a controlled substance in several US states, and effective January 11, 2012, became a schedule IV controlled substance at the US federal level. This article updates the literature on abuse potential and examines recent developments regarding the legal status of carisoprodol.

Skin β-endorphin mediates addiction to UV light.

PubMed

Fell, Gillian L; Robinson, Kathleen C; Mao, Jianren; Woolf, Clifford J; Fisher, David E

2014-06-19

UV light is an established carcinogen, yet evidence suggests that UV-seeking behavior has addictive features. Following UV exposure, epidermal keratinocytes synthesize proopiomelanocortin (POMC) that is processed to melanocyte-stimulating hormone, inducing tanning. We show that, in rodents, another POMC-derived peptide, β-endorphin, is coordinately synthesized in skin, elevating plasma levels after low-dose UV. Increases in pain-related thresholds are observed and reversed by pharmacologic opioid antagonism. Opioid blockade also elicits withdrawal signs after chronic UV exposure. This effect was sufficient to guide operant behavioral choices to avoidance of opioid withdrawal (conditioned place aversion). These UV-induced nociceptive and behavioral effects were absent in β-endorphin knockout mice and in mice lacking p53-mediated POMC induction in epidermal keratinocytes. Although primordial UV addiction, mediated by the hedonic action of β-endorphin and anhedonic effects of withdrawal, may theoretically have enhanced evolutionary vitamin D biosynthesis, it now may contribute to the relentless rise in skin cancer incidence in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Skin β-endorphin mediates addiction to ultraviolet light

PubMed Central

Fell, Gillian L.; Robinson, Kathleen C.; Mao, Jianren; Woolf, Clifford J.; Fisher, David E.

2014-01-01

SUMMARY Ultraviolet light is an established carcinogen yet evidence suggests that UV-seeking behavior has addictive features. Following UV exposure, epidermal keratinocytes synthesize Proopiomelanocortin that is processed to Melanocyte Stimulating Hormone, inducing tanning. We show that in rodents another POMC-derived peptide, β-endorphin, is coordinately synthesized in skin, elevating plasma levels after low-dose UV. Increases in pain-related thresholds are observed, and reversed by pharmacologic opioid antagonism. Opioid blockade also elicits withdrawal signs after chronic UV exposure. This effect was sufficient to guide operant behavioral choices to avoidance of opioid withdrawal (conditioned place aversion). These UV-induced nociceptive and behavioral effects were absent in β-endorphin knockout mice and in mice lacking p53-mediated POMC induction in epidermal keratinocytes. While primordial UV addiction, mediated by the hedonic action of β-endorphin and anhedonic effects of withdrawal, may theoretically have enhanced evolutionary vitamin D biosynthesis, it now may contribute to the relentless rise in skin cancer incidence in man. PMID:24949966

Behavioral Dimensions in One-Year-Olds and Dimensional Stability in Infancy.

ERIC Educational Resources Information Center

Hagekull, Berit; And Others

1980-01-01

The dimensional structure of infants' behavioral repertoire was shown to be highly stable over 3 to 15 months of age. Factor analysis of parent questionnaire data produced seven factors named Intensity/Activity, Regularity, Approach-Withdrawal, Sensory Sensitivity, Attentiveness, Manageability and Sensitivity to New Food. An eighth factor,…

Events and decision-making in the long-term care of Dutch nursing home patients in a vegetative state.

PubMed

Lavrijsen, Jan; van den Bosch, Hans; Koopmans, Raymond; van Weel, Chris; Froeling, Paul

2005-01-01

To clarify characteristics of long-term care and treatment of patients in a vegetative state. Qualitative, descriptive study in a Dutch nursing home. Review of clinical records of patients in a vegetative state after acute brain damage between 1978-2002. Five patients received intensive care of a multi-disciplinary team and showed considerable co-morbidity. There was no standard scenario for end-of-life decisions. Physicians play a more proactive role by evaluating the total medical treatment instead of withholding therapy in case of incidental complications. The families' attitude is a crucial factor in their ultimate decision. There is no standard solution to alleviate the fate of patients in a vegetative state and their families. Withdrawing all medical treatment, including artificial nutrition and hydration, can be an acceptable scenario for letting the patient die. More research is needed to identify the factors that contribute to acceptance of the physician's decision by the family.

Allostasis and Addiction: Role of the Dopamine and Corticotropin-Releasing Factor Systems

PubMed Central

George, Olivier; Le Moal, Michel; Koob, George F.

2011-01-01

Allostasis, originally conceptualized to explain persistent morbidity of arousal and autonomic function, is defined as the process of achieving stability through physiological or behavioral change. Two types of biological processes have been proposed to describe the mechanisms underlying allostasis in drug addiction, a within-system adaptation and a between-system adaptation. In the within-system process, the drug elicits an opposing, neutralizing reaction within the same system in which the drug elicits its primary and unconditioned reinforcing actions, while in the between-system process, different neurobiological systems that the one initially activated by the drug are recruited. In this review, we will focus our interest on alterations in the dopaminergic and corticotropin releasing factor systems as within-system and between-system neuroadaptations respectively, that underlie the opponent process to drugs of abuse. We hypothesize that repeated compromised activity in the dopaminergic system and sustained activation of the CRF-CRF1R system with withdrawal episodes may lead to an allostatic load contributing significantly to the transition to drug addiction. PMID:22108506

Scenarios for future biodiversity loss due to multiple drivers reveal conflict between mitigating climate change and preserving biodiversity

NASA Astrophysics Data System (ADS)

Powell, Thomas W. R.; Lenton, Timothy M.

2013-06-01

We assess the potential for future biodiversity loss due to three interacting factors: energy withdrawal from ecosystems due to biomass harvest, habitat loss due to land-use change, and climate change. We develop four scenarios to 2050 with different combinations of high or low agricultural efficiency and high or low meat diets, and use species-energy and species-area relationships to estimate their effects on biodiversity. In our scenarios, natural ecosystems are protected except when additional land is necessary to fulfil the increasing dietary demands of the global population. Biomass energy with carbon capture and storage (BECCS) is used as a means of carbon dioxide removal (CDR) from the atmosphere (and offsetting fossil fuel emissions). BECCS is based on waste biomass, with the addition of bio-energy crops only when already managed land is no longer needed for food production. Forecast biodiversity loss from natural biomes increases by more than a factor of five in going from high to low agricultural efficiency scenarios, due to destruction of productive habitats by the expansion of pasture. Biodiversity loss from energy withdrawal on managed land varies by a factor of two across the scenarios. Biodiversity loss due to climate change varies only modestly across the scenarios. Climate change is lowest in the ‘low meat high efficiency’ scenario, in which by 2050 around 660 million hectares of pasture are converted to biomass plantation that is used for BECCS. However, the resulting withdrawal of energy from managed ecosystems has a large negative impact on biodiversity. Although the effects of energy withdrawal and climate change on biodiversity cannot be directly compared, this suggests that using bio-energy to tackle climate change in order to limit biodiversity loss could instead have the opposite effect.

Climatic and environmental aspects of the Mongol withdrawal from Hungary in 1242 CE

PubMed Central

Büntgen, Ulf; Di Cosmo, Nicola

2016-01-01

The Mongol invasion of Eastern Europe, and especially its sudden withdrawal from Hungary in 1242 CE, has generated much speculation and an array of controversial theories. None of them, however, considered multifaceted environmental drivers and the coupled analysis of historical reports and natural archives. Here we investigate annually resolved, absolutely dated and spatially explicit paleoclimatic evidence between 1230 and 1250 CE. Documentary sources and tree-ring chronologies reveal warm and dry summers from 1238–1241, followed by cold and wet conditions in early-1242. Marshy terrain across the Hungarian plain most likely reduced pastureland and decreased mobility, as well as the military effectiveness of the Mongol cavalry, while despoliation and depopulation ostensibly contributed to widespread famine. These circumstances arguably contributed to the determination of the Mongols to abandon Hungary and return to Russia. While overcoming deterministic and reductionist arguments, our ‘environmental hypothesis’ demonstrates the importance of minor climatic fluctuations on major historical events. PMID:27228400

Factors influencing variation in physician adenoma detection rates: a theory-based approach for performance improvement.

PubMed

Atkins, Louise; Hunkeler, Enid M; Jensen, Christopher D; Michie, Susan; Lee, Jeffrey K; Doubeni, Chyke A; Zauber, Ann G; Levin, Theodore R; Quinn, Virginia P; Corley, Douglas A

2016-03-01

Interventions to improve physician adenoma detection rates for colonoscopy have generally not been successful, and there are little data on the factors contributing to variation that may be appropriate targets for intervention. We sought to identify factors that may influence variation in detection rates by using theory-based tools for understanding behavior. We separately studied gastroenterologists and endoscopy nurses at 3 Kaiser Permanente Northern California medical centers to identify potentially modifiable factors relevant to physician adenoma detection rate variability by using structured group interviews (focus groups) and theory-based tools for understanding behavior and eliciting behavior change: the Capability, Opportunity, and Motivation behavior model; the Theoretical Domains Framework; and the Behavior Change Wheel. Nine factors potentially associated with adenoma detection rate variability were identified, including 6 related to capability (uncertainty about which types of polyps to remove, style of endoscopy team leadership, compromised ability to focus during an examination due to distractions, examination technique during withdrawal, difficulty detecting certain types of adenomas, and examiner fatigue and pain), 2 related to opportunity (perceived pressure due to the number of examinations expected per shift and social pressure to finish examinations before scheduled breaks or the end of a shift), and 1 related to motivation (valuing a meticulous examination as the top priority). Examples of potential intervention strategies are provided. By using theory-based tools, this study identified several novel and potentially modifiable factors relating to capability, opportunity, and motivation that may contribute to adenoma detection rate variability and be appropriate targets for future intervention trials. Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

The effect of environmental factors on morphine withdrawal in C57BL/6J mice: running wheel access and group housing.

PubMed

Balter, Rebecca E; Dykstra, Linda A

2012-11-01

There is evidence to suggest that the rewarding effects of drugs of abuse can be altered by environmental manipulations such as housing conditions and access to running wheels. There is less information about how these environmental manipulations alter withdrawal behaviors following the termination of chronic drug administration. The objective of this study is to examine the effects of access to running wheels and group housing on spontaneous morphine withdrawal. C57BL/6J mice were assigned to one of the three housing conditions: wheel access (singly housed), no wheels (singly housed), or group-housed (no wheels). Mice received 30 or 56 mg/kg morphine or saline (s.c.) twice daily for 5.5 days. At baseline and at 8, 24, 32, and 48 h following the final injection, latency to respond on a hot plate was determined across a range of temperatures (50, 52, 54, and 56 °C). Latency to respond decreased as a function of temperature. Response latencies during the withdrawal period were decreased in mice without wheel access treated with both 30 and 56 mg/kg of morphine. This increase in thermal sensitivity was significantly attenuated in singly housed mice with wheel access and in group-housed mice; however, the effects were less pronounced in the group-housed mice and depended upon the time during withdrawal. Both wheel access and group housing attenuate the increase in thermal sensitivity seen in morphine-treated mice during morphine withdrawal.

Withdrawing to a virtual world: Associations between subtypes of withdrawal, media use, and maladjustment in emerging adults.

PubMed

Nelson, Larry J; Coyne, Sarah M; Howard, Emily; Clifford, Brandon N

2016-06-01

An approach-avoidance model of social withdrawal (Asendorpf, 1990) identifies 3 types of social withdrawal including shyness, unsociability, and avoidance. Each appears to be uniquely associated with varying indicators of maladjustment in emerging adulthood (Nelson, 2013) but little, if any, work has been done to see how they might be linked to media use in the third decade of life. Therefore, the purpose of this study was to examine longitudinally the links between subtypes of social withdrawal, connective media (e.g., e-mail, social networking) and problematic (forms of media such as violent video games that, when used in high amounts, have been found to be linked to indices of maladjustment) media use, and internalizing and externalizing behaviors. The participants in the study (Mage = 20.70, SD = 1.98, range = 18-29 at Time 2) consisted of 204 undergraduate students (58% female) recruited from 2 large public universities in the United States who completed questionnaires at 2 points of time separated by 1 year. Results revealed that avoidant individuals use problematic forms of media more than average, unsociable, and shy individuals. Furthermore, problematic media use predicted more withdrawn behavior at Time 2 and mediated the relation between avoidance and externalizing behaviors over time. Few problems were found for unsociable behavior. The need to differentiate between multiple forms of withdrawal in emerging adulthood and their links with problematic forms of media and subsequent risk factors is discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal

PubMed Central

Wang, Li; Shen, Minjie; Jiang, Changyou

2016-01-01

Background: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the CeA and its effects in the negative reinforcement of drug dependents are poorly understood. Method: We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+ interneurons in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal–induced negative affective states, such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like (assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via optogenetic inhibition or activation of PV+ interneurons in the CeA. Result: Chronic morphine withdrawal increased the firing rate of CeA PV+ interneurons. Optogenetic inhibition of the activity of CeA PV+ interneurons attenuated the morphine withdrawal–induced negative affective states, such as the aversive, anxiety, and anhedonic-like behaviors, while direct activation of CeA PV+ interneurons could trigger those negative affective-like behaviors. Optogenetic inhibition of the CeA PV+ interneurons during the morphine withdrawal significantly attenuated the elevated CRH mRNA level in the CeA. Conclusion: The activity of PV+ interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation of PV+ interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation of CRH mRNA levels in the CeA. PMID:27385383

Dispositional Mindful Attention in Relation to Negative Affect, Tobacco Withdrawal, and Expired Carbon Monoxide On and After Quit Day.

PubMed

Paulus, Daniel J; Langdon, Kirsten J; Wetter, David W; Zvolensky, Michael J

Mindfulness (or "Mindful Attention") has been described as the presence or absence of attention to, and awareness of, what is occurring in the present moment. Among smokers, greater mindfulness is associated with greater effect stability and reduced cue-induced craving. While studies have shown that mindfulness is associated with other smoking-related factors such as reduced withdrawal symptoms using cross-sectional data, relatively little is known about the associations between baseline mindful attention and future abstinence-related effect/withdrawal. The current study sought to examine whether levels of mindful attention before cessation predicts negative affect, withdrawal, and level of expired carbon monoxide (CO) on quit day, and also 3 and 7 days after quitting, during a self-quit attempt. Data from 58 adults (mean age = 34.9; 65.5% male) participating in a self-quit study were available for analysis. Self-report measures of mindful attention, negative affect, and withdrawal symptoms were collected. Biochemical measurement of expired CO was also collected. Dependent variables were assessed on quit day, and also 3 and 7 days after quitting. Covariates included age, race, sex, self-reported level of cigarette dependence, and smoking status through 7 days. Multivariate regression was used to evaluate the association of baseline mindful attention in relation to the studied outcomes. Greater mindful attention predicted lower negative affect and reduced withdrawal at all 3 time-points. Mindful attention did not predict levels of expired CO. The findings suggest that mindful attention before or during smoking-cessation treatment may help to reduce negative affect and withdrawal, which serve as barriers to cessation for many smokers.

Social Withdrawal Among Individuals Receiving Psychiatric Care: Derivation of a Scale Using Routine Clinical Assessment Data to Support Screening and Outcome Measurement.

PubMed

Rios, Sebastian; Perlman, Christopher M

2017-04-24

Social withdrawal is a symptom experienced by individuals with an array of mental health conditions, particularly those with schizophrenia and mood disorders. Assessments of social withdrawal are often lengthy and may not be routinely integrated within the comprehensive clinical assessment of the individual. This study utilized item response and classical test theory methods to derive a Social Withdrawal Scale (SWS) using items embedded within a routine clinical assessment, the RAI-Mental Health (RAI-MH). Using data from 60,571 inpatients in Ontario, Canada, a common factor analysis identified seven items from the RAI-MH that measure social withdrawal. A graded response model found that six items had acceptable discrimination parameters: lack of motivation, reduced interaction, decreased energy, flat affect, anhedonia, and loss of interest. Summing these items, the SWS was found to have strong internal consistency (Cronbach's alpha = 0.82) and showed a medium to large effect size (d = 0.77) from admission to discharge. Fewer individuals with high SWS scores participated in social activity or reported having a confidant compared to those with lower scores. Since the RAI-MH is available across clinical subgroups in several jurisdictions, the SWS is a useful tool for screening, clinical decision support, and evaluation.

Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats.

PubMed

Stinus, Luis; Cador, Martine; Zorrilla, Eric P; Koob, George F

2005-01-01

Conditioned place aversion in rats has face validity as a measure of the aversive stimulus effects of opiate withdrawal that reflects an important motivational component of opiate dependence. The purpose of the present study was to validate conditioned place aversion as sensitive to medications that will alleviate the aversive stimulus effects of opiate withdrawal in humans, and to extend this model to the exploration of the neuropharmacological basis of the motivational effects of opiate withdrawal. Male Sprague-Dawley rats were implanted with two subcutaneous morphine pellets and 5 days later began place conditioning training following subcutaneous administration of a low dose of naloxone. Animals were subjected to three pairings of a low dose of naloxone (15 microg/kg, s.c.) to one arm of a three-chambered place conditioning apparatus. Buprenorphine administered prior to each pairing dose-dependently blocked the place aversion produced by precipitated opiate withdrawal. A corticotropin-releasing factor-1 (CRF1) receptor antagonist (antalarmin) also reversed the place aversion produced by precipitated opiate withdrawal. Antalarmin did not produce a place preference or place aversion by itself in morphine-dependent rats. No effect was observed with pretreatment of the dopamine partial agonist terguride or the selective serotonin reuptake inhibitor fluoxetine. Also, chronic pretreatment with acamprosate (a glutamate receptor modulator used to prevent relapse in alcohol dependence) did not alter naloxone-induced place aversion. Buprenorphine by itself in dependent rats produced a mild place preference at low doses and a mild place aversion at higher doses. These results suggest that buprenorphine blocks the aversive stimulus effects of precipitated opiate withdrawal in rats and provides some validity for the use of place conditioning as a measure that is sensitive to potential opiate-dependence medications. In addition, these results suggest that CRF1 antagonists can block the aversive stimulus effects of opiate withdrawal and may be potential therapeutic targets for opiate dependence.

Hepatitis B reactivation after withdrawal of pre-emptive lamivudine in patients with haematological malignancy on completion of cytotoxic chemotherapy

PubMed Central

Hui, C-K; Cheung, W W W; Au, W-Y; Lie, A K W; Zhang, H-Y; Yueng, Y-H; Wong, B C Y; Leung, N; Kwong, Y-L; Liang, R; Lau, G K K

2005-01-01

Background: The hepatic outcome of hepatitis B surface antigen (HBsAg) positive patients undergoing chemotherapy after withdrawal of pre-emptive lamivudine is unknown. Aims: To examine the occurrence of hepatitis B virus (HBV) reactivation after withdrawal of pre-emptive lamivudine. Methods: Pre-emptive lamivudine was started one week before initiation of chemotherapy in 46 consecutive HBsAg positive patients and continued for the entire duration of chemotherapy. Pre-emptive lamivudine was stopped at a median 3.1 (range 3.0–3.4) months after completion of chemotherapy. Patients were longitudinally followed up after withdrawal of pre-emptive lamivudine. Results: Median time of follow up after withdrawal of lamivudine was 25.7 (range 5.7–75.7) months. Eleven of the 46 patients (23.9%) developed HBV reactivation after withdrawal of pre-emptive lamivudine. Eight of the 16 patients with high pre-chemotherapy HBV DNA (⩾104 copies/ml) compared with three of the 30 patients with low pre-chemotherapy HBV DNA (<104 copies/ml) developed HBV reactivation (50.0% v 10.0%, respectively; p<0.001). Hepatitis B e antigen positive patients were also more likely to develop HBV reactivation (5/11 (45.5%) v 6/35 (17.1%), respectively; p = 0.041). A high pre-chemotherapy HBV DNA (⩾104 copies/ml) was the most important risk factor for HBV reactivation after withdrawal of pre-emptive lamivudine on Cox proportional hazards analysis (relative risk 16.13, (95% confidence interval 2.99-87.01; p = 0.001). Conclusions: HBV reactivation is more likely to occur in patients with high pre-chemotherapy HBV DNA after withdrawal of pre-emptive lamivudine. A more prolonged course of antiviral therapy may be necessary in these patients after completion of chemotherapy in order to reduce post-chemotherapy HBV reactivation. PMID:16000641

Private Domestic-Well Characteristics and the Distribution of Domestic Withdrawals among Aquifers in the Virginia Coastal Plain

USGS Publications Warehouse

Pope, Jason P.; McFarland, Randolph E.; Banks, R. Brent

2008-01-01

A comprehensive analysis of private domestic wells and self-supplied domestic ground-water withdrawals in the Coastal Plain Physiographic Province of Virginia indicates that the magnitudes of these withdrawals and their effects on local and regional ground-water flow are larger and more important than previous reports have stated. Self-supplied ground-water withdrawals for domestic use in the Virginia Coastal Plain are estimated to be approximately 40 million gallons per day, or about 28 percent of all ground-water withdrawals in the area. Contrary to widely held assumptions, only 22 percent of domestic wells in the Virginia Coastal Plain are completed in the shallow, unconfined surficial aquifer to which the water is returned directly by home septic systems. Fifty-three percent of the wells are completed in six deeper confined aquifers, and the remaining 25 percent are completed in the Potomac aquifer and confining zone, the deepest units in the confined system. Assuming an equal rate of withdrawal per well, 78 percent of domestic ground-water withdrawal, or about 30 million gallons per day, is removed from the regional confined ground-water system. Domestic ground-water withdrawal from an estimated 200,000 private wells supplies more than 15 percent of the population of the area and provides almost the entire source of water in some rural counties. The geographic distribution of these withdrawals is dependent on the self-supplied population and is highly variable. Domestic-well characteristics vary spatially as well, primarily because of geographic differences in depths to particular aquifers, but also because of well-drilling practices that are influenced by geographic, regulatory, and socioeconomic factors. Domestic ground-water withdrawals in the Virginia Coastal Plain were characterized as part of a larger study to analyze the regional ground-water flow system. Characterizing the withdrawals required differentiation of the withdrawals among the aquifers in the area in addition to determination of the geographic distribution of the withdrawals. Because of a lack of comprehensive data on private-well construction and distribution, a sample of private domestic-well records was used to estimate well characteristics and approximate the proportion of wells and withdrawals associated with each aquifer. Construction data on 2,846 private domestic wells were collected from 29 counties and independent cities (localities) having appreciable self-supplied populations and representing private domestic withdrawals of about 31 million gallons per day. Within each locality, geographically stratified random sampling of well records by tax plat characterized details of well construction for the population of domestic wells. Because neither specific location data nor aquifer elevations were available for individual wells, the primary aquifer in which each well is completed was estimated by cross-referencing the screen elevation estimated from the well record with a generalized configuration of hydrogeologic units underlying the locality in which the well is located. For each locality, summarizing the results of this process allowed the determination of the proportion of wells and withdrawals associated with each aquifer. Additional evaluation of spatial data was used to apply the domestic withdrawal rates developed for each aquifer in each locality to a detailed ground-water study of the portion of the Virginia Coastal Plain east of the Chesapeake Bay, which is known as the Eastern Shore Peninsula. Because domestic withdrawal estimates are based on the self-supplied population, the geographic distribution of withdrawals within each of the Eastern Shore counties was estimated by using population data from the 2000 U.S. Census at the resolution of census block groups and further refining the distribution based on road density. The allocation of withdrawals among aquifers was then determined by cross-referencing the spatial distribut

Caffeinated Energy Drinks -- A Growing Problem

PubMed Central

Reissig, Chad J.; Strain, Eric C.; Griffiths, Roland R.

2009-01-01

Since the introduction of Red Bull in Austria in 1987 and in the United States in 1997, the energy drink market has grown exponentially. Hundreds of different brands are now marketed, with caffeine content ranging from a modest 50 mg to an alarming 505 mg per can or bottle. Regulation of energy drinks, including content labeling and health warnings differs across countries, with some of the most lax regulatory requirements in the U.S. The absence of regulatory oversight has resulted in aggressive marketing of energy drinks, targeted primarily toward young males, for psychoactive, performance-enhancing and stimulant drug effects. There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase. In children and adolescents who are not habitual caffeine users, vulnerability to caffeine intoxication may be markedly increased due to an absence of pharmacological tolerance. Genetic factors may also contribute to an individual’s vulnerability to caffeine related disorders including caffeine intoxication, dependence, and withdrawal. The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury. Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence. Regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed. PMID:18809264

End-of-life choices for African-American and white infants in a neonatal intensive-care unit: a pilot study.

PubMed Central

Moseley, Kathryn L.; Church, Annamaria; Hempel, Bridget; Yuan, Harry; Goold, Susan Door; Freed, Gary L.

2004-01-01

BACKGROUND: African-American adults are more likely than white adults to desire the continuation of life-sustaining medical treatment (LSMT) at the end of life. No studies have examined racial differences in parental end-of-life decisions for neonates. OBJECTIVE: To collect preliminary data to determine whether differences exist in the choices made by parents of African-American and white infants when a physician has recommended withholding or withdrawing LSMT from their infant to develop hypotheses for future work. DESIGN/METHODS: A retrospective chart review of African-American and white infants who died in an urban neonatal intensive care unit (NICU) over a two-year period. Charts were abstracted for demographics, cause of death, and documentation of meetings where the physician recommended withholding or withdrawing LSMT. RESULTS: Thirty-eight infant charts met study criteria (58% African-American, 42% white). Documentation of physician recommendations to limit LSMT was present in 61% of charts. Approached families of white infants agreed to limit LSMT 80% of the time compared to 62% of the families of African-American infants. CONCLUSIONS: In this pilot study, parents of African-American and white infants appeared to make different end-of-life choices for their children. A larger study is needed to confirm these findings and further explore contributing factors such as mistrust, religiosity, and perceived discrimination. PMID:15253324

Caffeinated energy drinks--a growing problem.

PubMed

Reissig, Chad J; Strain, Eric C; Griffiths, Roland R

2009-01-01

Since the introduction of Red Bull in Austria in 1987 and in the United States in 1997, the energy drink market has grown exponentially. Hundreds of different brands are now marketed, with caffeine content ranging from a modest 50 mg to an alarming 505 mg per can or bottle. Regulation of energy drinks, including content labeling and health warnings differs across countries, with some of the most lax regulatory requirements in the U.S. The absence of regulatory oversight has resulted in aggressive marketing of energy drinks, targeted primarily toward young males, for psychoactive, performance-enhancing and stimulant drug effects. There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase. In children and adolescents who are not habitual caffeine users, vulnerability to caffeine intoxication may be markedly increased due to an absence of pharmacological tolerance. Genetic factors may also contribute to an individual's vulnerability to caffeine-related disorders including caffeine intoxication, dependence, and withdrawal. The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury. Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence. Regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed.

The impact of nicotine lozenges and stimulus expectancies on cigarette craving.

PubMed

Schlagintweit, Hera E; Good, Kimberley P; Barrett, Sean P

2014-08-01

Reduced craving associated with nicotine replacement therapy use is frequently attributed to the effects of nicotine pharmacology, however non-pharmacological factors may also play a role. This study examined the impact of nicotine pharmacology and non-pharmacological components of an acute nicotine lozenge (4 mg) on cigarette craving, mood and heart rate in 70 daily smokers (36 male). Smoking-related stimuli were used to assess cue-induced craving. Participants were randomly assigned to one of four conditions in a balanced placebo design where half the participants were provided deceptive information regarding the nicotine content of a lozenge. Subjective ratings of craving and mood were collected and heart rate was assessed before and after neutral and smoking cues. Nicotine expectancy reduced withdrawal-related craving (p = 0.006) regardless of actual nicotine administration while combined nicotine expectancy and administration reduced intentions to smoke (p = 0.046) relative to each of the other conditions. Exposure to smoking-related stimuli increased cigarette craving (p ≤ 0.001) and negative affect (p ≤ 0.001) regardless of expectancy or pharmacology. Following the smoking cue, women reported a greater increase in withdrawal-related craving than men (p = 0.027). Findings suggest that both pharmacological and non-pharmacological components of nicotine lozenge administration contribute to its acute effects on craving, yet neither appears effective in preventing craving triggered by exposure to environmental smoking stimuli. © The Author(s) 2014.

Refeeding syndrome is uncommon in alcoholics admitted to a hospital detoxification unit.

PubMed

Manning, S; Gilmour, M; Weatherall, M; Robinson, G M

2014-05-01

The refeeding syndrome is increasingly recognised. It is a serious change in electrolytes when nutrition is reintroduced to malnourished patients. Alcohol dependence is a risk factor for the refeeding syndrome. We report a prospective cohort study of 36 alcoholics hospitalised for withdrawal management. We found no evidence of refeeding syndrome in any patient after 3 days of hospitalisation, despite hypomagnesaemia, a risk factor for the refeeding syndrome being prevalent (44% of subjects). Low thiamine levels were infrequent affecting 3/29 (10%). We recommend that in alcoholics admitted for managed withdrawal, risk of refeeding syndrome appears to be low, and routine testing of repeat electrolytes appears unnecessary. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Feed withdrawal and transportation effects on Salmonella enterica levels in market-weight pigs.

PubMed

Eicher, S D; Rostagno, M H; Lay, D C

2017-07-01

Feed withdrawal and transport commonly occur together in pigs. Objectives of this study were to determine if these preslaughter stressors, feed withdrawal and transportation, affect the levels of , stress hormone concentrations, and immune functions in infected market pigs. A 2 × 2 factorial analysis of a randomized complete block design with feed withdrawal and transport as fixed effects was used. Sixty market-weight pigs were individually inoculated with serovar Typhimurium. The experiment was replicated 3 times (blocking factor) with 20 pigs per replicate. Three days after inoculation, the pigs were randomly assigned to 1 of 4 treatments (5 pigs per treatment in each/replicate), including 1) control (Control; or no stress), 2) feed withdrawal for 12 h (FW), 3) transportation for 2 h (T), and 4) feed withdrawal for 12 h followed by transportation for 2 h (FWT). Feed withdrawal by itself or followed by transportation caused an increase of levels in ileal contents ( < 0.05), whereas only FWT caused an increase of levels in cecal contents ( < 0.05). Rectal contents (feces) consistently contained very low levels of , with no difference among treatments ( > 0.10). Cortisol increased in pigs from all 3 stress treatments ( < 0.001), with T and FWT pigs having greater concentrations than Control pigs ( < 0.05), although total white blood cell counts were lower for FWT pigs compared with Controls ( > 0.03). Each granulocyte percentage (neutrophil, eosinophils, and basophils) increased ( < 0.05) following transport but was attenuated ( > 0.05) by feed withdrawal with transport. Lymphocytes were suppressed ( < 0.05) by all stressors, and the greatest suppression occurred when pigs were transported (T and FWT). However, monocytes were suppressed ( < 0.05) compared with Controls only by FWT. Expression of IL-1 (produced by monocytes/macrophages) from the spleen cells increased ( < 0.05) with FW compared with Controls, whereas its receptor antagonist was suppressed by FWT ( < 0.05). It is concluded that some typical preslaughter practices, such as feed withdrawal and transportation, lead to greater intestinal levels and gut-associated lymphoid tissue markers of inflammation in market pigs and, consequently, to an increased food safety risk.

PKMζ Maintains Drug Reward and Aversion Memory in the Basolateral Amygdala and Extinction Memory in the Infralimbic Cortex

PubMed Central

He, Ying-Ying; Xue, Yan-Xue; Wang, Ji-shi; Fang, Qin; Liu, Jian-Feng; Xue, Li-Fen; Lu, Lin

2011-01-01

The intense associative memories that develop between drug-paired contextual cues and rewarding stimuli or the drug withdrawal-associated aversive feeling have been suggested to contribute to the high rate of relapse. Various studies have elucidated the mechanisms underlying the formation and expression of drug-related cue memories, but how this mechanism is maintained is unknown. Protein kinase M ζ (PKMζ) was recently shown to be necessary and sufficient for long-term potentiation maintenance and memory storage. In the present study, we used conditioned place preference (CPP) and aversion (CPA) to examine whether PKMζ maintains both morphine-associated reward memory and morphine withdrawal-associated aversive memory in the basolateral amygdala (BLA). We also investigate the role of PKMζ in the infralimbic cortex in the extinction memory of morphine reward-related cues and morphine withdrawal-related aversive cues. We found that intra-BLA but not central nucleus of the amygdala injection of the selective PKMζ inhibitor ZIP 1 day after CPP and CPA training impaired the expression of CPP and CPA 1 day later, and the effect of ZIP on memory lasted at least 2 weeks. Inhibiting PKMζ activity in the infralimbic cortex, but not prelimbic cortex, disrupted the expression of the extinction memory of CPP and CPA. These results indicate that PKMζ in the BLA is required for the maintenance of associative morphine reward memory and morphine withdrawal-associated aversion memory, and PKMζ in the infralimbic cortex is required for the maintenance of extinction memory of morphine reward-related cues and morphine withdrawal-related aversive cues. PMID:21633338

Changes in serum biochemical factors associated with opium addiction after addiction desertion.

PubMed

Afarinesh, Mohammad Reza; Haghpanah, Tahereh; Divsalar, Kouros; Dehyadegary, Elham; Shaikh-Aleslami, Azar; Mahmoodi, Majid

2014-01-01

The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients.

Activation of inactivation process initiates rapid eye movement sleep.

PubMed

Mallick, Birendra Nath; Singh, Abhishek; Khanday, Mudasir Ahmad

2012-06-01

Interactions among REM-ON and REM-OFF neurons form the basic scaffold for rapid eye movement sleep (REMS) regulation; however, precise mechanism of their activation and cessation, respectively, was unclear. Locus coeruleus (LC) noradrenalin (NA)-ergic neurons are REM-OFF type and receive GABA-ergic inputs among others. GABA acts postsynaptically on the NA-ergic REM-OFF neurons in the LC and presynaptically on the latter's projection terminals and modulates NA-release on the REM-ON neurons. Normally during wakefulness and non-REMS continuous release of NA from the REM-OFF neurons, which however, is reduced during the latter phase, inhibits the REM-ON neurons and prevents REMS. At this stage GABA from substantia nigra pars reticulate acting presynaptically on NA-ergic terminals on REM-ON neurons withdraws NA-release causing the REM-ON neurons to escape inhibition and being active, may be even momentarily. A working-model showing neurochemical-map explaining activation of inactivation process, showing contribution of GABA-ergic presynaptic inhibition in withdrawing NA-release and dis-inhibition induced activation of REM-ON neurons, which in turn activates other GABA-ergic neurons and shutting-off REM-OFF neurons for the initiation of REMS-generation has been explained. Our model satisfactorily explains yet unexplained puzzles (i) why normally REMS does not appear during waking, rather, appears following non-REMS; (ii) why cessation of LC-NA-ergic-REM-OFF neurons is essential for REMS-generation; (iii) factor(s) which does not allow cessation of REM-OFF neurons causes REMS-loss; (iv) the association of changes in levels of GABA and NA in the brain during REMS and its deprivation and associated symptoms; v) why often dreams are associated with REMS. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Smoking Abstinence Questionnaire: Measurement of smokers’ abstinence-related expectancies

PubMed Central

Hendricks, Peter S.; Wood, Sabrina B.; Baker, Majel R.; Delucchi, Kevin L.; Hall, Sharon M.

2011-01-01

AIM To develop and validate a measure of smokers’ expectancies for the abstinence process upon quitting smoking: the Smoking Abstinence Questionnaire (SAQ). DESIGN Principal component analysis and other psychometric analyses of self-report data. SETTING San Francisco, California. PARTICIPANTS 507 adult smokers of at least 10 cigarettes per day diverse in gender, sexual orientation, and ethnoracial status. MEASUREMENTS The primary measure was a draft version of the SAQ. Additional measures assessed a variety of other smoking-related constructs. FINDINGS Principal component analyses revealed 10 factors of the SAQ: Withdrawal, Social Improvement/Nonsmoker Identity, Adverse Outcomes, Treatment Effectiveness, Common Reasons, Barriers to Treatment, Social Support, Optimistic Outcomes, Coffee Use, and Weight Gain. The SAQ factors demonstrated internal consistencies ranging from .62 to .85 and were associated with tobacco dependence, motivation to quit, abstinence self-efficacy, withdrawal symptoms, dietary restraint, shape and weight concern, and tobacco use expectancies. The SAQ predicted smoking-related constructs above and beyond tobacco use expectancies, suggesting that abstinence-related expectancies and tobacco use expectancies are distinct from one another. CONCLUSIONS A newly developed questionnaire, the SAQ, appears to reliably capture smokers’ expectancies for abstinence (Withdrawal, Social Improvement/Nonsmoker Identity, Adverse Outcomes, Common Reasons, Optimistic Outcomes, Coffee Use, and Weight Gain) and expectancies related to the success of a quit attempt (Treatment Effectiveness, Barriers to Treatment, and Social Support). It remains to be seen how far any of these expectancies predict attempts to quit, withdrawal, treatment utilization and response, and quitting success above and beyond existing measures. PMID:21205053

Emotional Reactivity, Behavior Problems, and Social Adjustment at School Entry in a High-risk Sample

PubMed Central

Kalvin, Carla B.; Bierman, Karen L.; Gatzke-Kopp, Lisa M.

2016-01-01

Prior research suggests that heightened emotional reactivity to emotionally distressing stimuli may be associated with elevated internalizing and externalizing behaviors, and contribute to impaired social functioning. These links were explored in a sample of 169 economically-disadvantaged kindergarteners (66 % male; 68 % African American, 22 % Hispanic, 10 % Caucasian) oversampled for elevated aggression. Physiological measures of emotional reactivity (respiratory sinus arrhythmia [RSA], heart rate [HR], and cardiac pre-ejection period [PEP]) were collected, and teachers and peers provided ratings of externalizing and internalizing behavior, prosocial competence, and peer rejection. RSA withdrawal, HR reactivity, and PEP shortening (indicating increased arousal) were correlated with reduced prosocial competence, and RSA withdrawal and HR reactivity were correlated with elevated internalizing problems. HR reactivity was also correlated with elevated externalizing problems and peer rejection. Linear regressions controlling for age, sex, race, verbal proficiency, and resting physiology showed that HR reactivity explained unique variance in both teacher-rated prosocial competence and peer rejection, and contributed indirectly to these outcomes through pathways mediated by internalizing and externalizing problems. A trend also emerged for the unique contribution of PEP reactivity to peer-rated prosocial competence. These findings support the contribution of emotional reactivity to behavior problems and social adjustment among children living in disadvantaged urban contexts, and further suggest that elevated reactivity may confer risk for social difficulties in ways that overlap only partially with internalizing and externalizing behavior problems. PMID:26943804

Fuzi attenuates diabetic neuropathy in rats and protects schwann cells from apoptosis induced by high glucose.

PubMed

Han, Jing; Tan, Peng; Li, Zhiyong; Wu, Yan; Li, Chun; Wang, Yong; Wang, Beibei; Zhao, Shuang; Liu, Yonggang

2014-01-01

Radix aconite lateralis preparata (Fuzi), a folk medicine, has long been used for the treatment of diabetes and paralysis in China. We examined the effect of Fuzi alone on diabetic rats and Schwann cells in high glucose and the components responsible for its activity. The major constituents of FZE were identified by HPLC-MS/MS data. Male Sprague Dawley rats (n = 36) were randomly divided into control, diabetic, FZE 1.75 g/kg, FZE 3.50 g/kg, FZE 7.00 g/kg, and methylcobalamin groups. After two weeks treatment, nerve conduction velocity and paw withdrawal latency were measured. In vitro, the Schwann cells were grouped according to exposure: normal glucose (NG), normal glucose plus mannitol (NG+M), high glucose (HG), and HG plus different concentrations of FZE (0.1 µg/ml, 1.0 µg/ml, and 10.0 µg/ml). Oxygen free radicals and apoptosis were evaluated through DCFH2DA, DHE and annexin-PE/7-AAD assay, respectively. Apoptosis factors (Bax, Bcl-2, CytoC, caspase-3, and caspase-9) were analyzed using immunofluorescence. Nine alkaloids were identified. The results from animal model showed that FZE was effective in accelerating nerve conduction velocity and shortening paw withdrawal latency in diabetic rats. And in vitro, FZE was also found to protect Schwann cells against high glucose injury. FZE could significantly decrease the apoptotic ratio, superoxide anion and peroxide level. Furthermore, the apoptosis factors, including Bax, Bcl-2, CytoC, caspase-3, and caspase-9 were ameliorated in FZE treated groups. The HPLC-MS(n) method is simple and suitable for the identification of alkaloids in Fuzi. FZE has a protective effect in diabetic neuropathic rats, which is probably achieved by the antiapoptotic effect of FZE on Schwann cells. Apoptosis factor data imply that FZE protected Schwann cells through the mitochondria pathway. Alkaloids are major components contributing to the protective effect.

Dynamics of neuronal circuits in addiction: reward, antireward, and emotional memory.

PubMed

Koob, G F

2009-05-01

Drug addiction is conceptualized as chronic, relapsing compulsive use of drugs with significant dysregulation of brain hedonic systems. Compulsive drug use is accompanied by decreased function of brain substrates for drug positive reinforcement and recruitment of brain substrates mediating the negative reinforcement of motivational withdrawal. The neural substrates for motivational withdrawal ("dark side" of addiction) involve recruitment of elements of the extended amygdala and the brain stress systems, including corticotropin-releasing factor and norepinephrine. These changes, combined with decreased reward function, are hypothesized to persist in the form of an allostatic state that forms a powerful motivational background for relapse. Relapse also involves a key role for the basolateral amygdala in mediating the motivational effects of stimuli previously paired with drug seeking and drug motivational withdrawal. The basolateral amygdala has a key role in mediating emotional memories in general. The hypothesis argued here is that brain stress systems activated by the motivational consequences of drug withdrawal can not only form the basis for negative reinforcement that drives drug seeking, but also potentiate associative mechanisms that perpetuate the emotional state and help drive the allostatic state of addiction.

Development of personal narratives as a mediator of the impact of deficits in social cognition and social withdrawal on negative symptoms in schizophrenia.

PubMed

Lysaker, Paul H; Erikson, Molly; Macapagal, Kathryn R; Tunze, Chloe; Gilmore, Emily; Ringer, Jamie M

2012-04-01

Although negative symptoms are a barrier to recovery from schizophrenia, little is understood about the psychological processes that reinforce and sustain them. To explore this issue, this study used structural equation modeling to test whether the impact of social withdrawal and emotion recognition deficits upon negative symptoms is mediated by the richness or poverty of personal narratives. The participants were 99 adults with schizophrenia spectrum disorders. Social cognition was assessed using the Bell-Lysaker Emotional Recognition Task; social withdrawal, using the Quality of Life Scale; narrative coherence, using the Scale To Assess Narrative Development; and negative symptoms, using the Positive and Negative Syndrome Scale. The findings reveal that although social cognition deficits and social withdrawal are significantly associated with negative symptom severity, these relationships become nonsignificant when personal narrative integrity is examined as a mediating factor. These results indicate that the development of personal narratives may be directly linked to the severity of negative symptoms; this construct may be a useful target for future interventions.

Bullying: Proactive Physical Educators' Contribution to School-Wide Prevention

ERIC Educational Resources Information Center

Gibbone, Anne; Manson, Mara

2010-01-01

Although not a new concept, bullying continues to be a problem in schools across the nation. Bullying involves the intention to hurt the feelings of the victim. Research demonstrates that victims of bullying often experience low self-esteem, depression, anxiety, insecurity, oversensitivity, introversion, and withdrawal from social activities. This…

Fight, Flight, or Better Choices: Teaching Nonviolent Responses to Young Children.

ERIC Educational Resources Information Center

Guetzloe, Eleanor; Rockwell, Sylvia

1998-01-01

Discusses factors associated with violent behavior in young children and strategies for addressing those factors, including using the "Turtle Technique" for practicing withdrawal and problem-solving, using social-learning curricula, using success-oriented instructional strategies for teaching academics, listing and practicing alternative…

Contribution of capsaicin-sensitive primary afferents to mechanical hyperalgesia induced by ventral root transection in rats: the possible role of BDNF.

PubMed

Li, Wei; Wang, Jian-Xiu; Zhou, Zhong-He; Lu, Yao; Li, Xiao-Qiu; Liu, Bao-Jun; Chen, Hui-Sheng

2016-01-01

A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed. The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT. The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin. Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model.

Prediction of flunixin tissue residue concentrations in livers from diseased cattle.

PubMed

Wu, H; Baynes, R E; Tell, L A; Riviere, J E

2013-12-01

Flunixin, a widely used non-steroidal anti-inflammatory drug, was a leading cause of violative residues in cattle. The objective of this analysis was to explore how the changes in pharmacokinetic (PK) parameters that may be associated with diseased animals affect the predicted liver residue of flunixin in cattle. Monte Carlo simulations for liver residues of flunixin were performed using the PK model structure and relevant PK parameter estimates from a previously published population PK model for flunixin in cattle. The magnitude of a change in the PK parameter value that resulted in a violative residue issue in more than one percent of a cattle population was compared. In this regard, elimination clearance and volume of distribution affected withdrawal times. Pathophysiological factors that can change these parameters may contribute to the occurrence of violative residues of flunixin.

Withdrawal from high-carbohydrate, high-saturated-fat diet changes saturated fat distribution and improves hepatic low-density-lipoprotein receptor expression to ameliorate metabolic syndrome in rats.

PubMed

Hazarika, Ankita; Kalita, Himadri; Kalita, Mohan Chandra; Devi, Rajlakshmi

2017-06-01

The "lipid hypothesis" determined that saturated fatty acid (SFA) raises low-density lipoprotein cholesterol, thereby increasing the risk for metabolic syndrome (MetS). The aim of this study was to investigate the effect of subchronic withdrawal from a high-carbohydrate, high-saturated fat (HCHF) diet during MetS with reference to changes in deleterious SFA (C12:0, lauric acid; C14:0, myristic acid; C16:0, palmitic acid; C18:0, stearic acid) distribution in liver, white adipose tissue (WAT), and feces. MetS induced by prolonged feeding of an HCHF diet in Wistar albino rat is used as a model of human MetS. The MetS-induced rats were withdrawn from the HCHF diet and changed to a basal diet for final 4 wk of the total experimental duration of 16 wk. SFA distribution in target tissues and hepatic low-density lipoprotein receptor (LDLr) expression were analyzed. Analyses of changes in SFA concentration of target tissues indicate that C16:0 and C18:0 reduced in WAT and liver after withdrawal of the HCHF diet. There was a significant (P < 0.001) decrease in fecal C12:0 with HCHF feeding, which significantly (P < 0.01) increased after withdrawal of this diet. Also, an improvement in expression of hepatic LDLr was observed after withdrawal of HCHF diet. The prolonged consumption of an HCHF diet leads to increased SFA accumulation in liver and WAT, decreased SFA excretion, and reduced hepatic LDLr expression during MetS, which is prominently reversed after subchronic withdrawal of the HCHF diet. This can contribute to better understanding of the metabolic fate of dietary SFA during MetS and may apply to the potential reversal of complications by the simple approach of nutritional modification. Copyright © 2017 Elsevier Inc. All rights reserved.

Status of ground-water resources at U.S. Navy Support Facility, Diego Garcia; summary of hydrologic and climatic data, January 1994 through September 1996

USGS Publications Warehouse

Torikai, J.D.

1996-01-01

This report describes the status of ground-water resources at U.S. Navy Support Facility, Diego Garcia. Data presented are from January 1994 through September 1996, with a focus on data from July through September 1996 (third quarter of 1996). A complete database of ground-water withdrawals and chloride-concentration records since 1985 is maintained by the U.S. Geological Survey. Total rainfall for the period July through September 1996 was 8.94 inches, which is 60 percent less than the mean rainfall of 22.23 inches for the period July through September. July and August are part of the annual dry season, while September is the start of the annual wet season. Ground-water withdrawal during July through September 1996 averaged 1,038,300 gallons per day. Withdrawal for the same 3 months in 1995 averaged 888,500 gallons per day. Ground-water withdrawals have steadily increased since about April 1995. At the end of September 1996, the chloride concentration of water from the elevated tanks at Cantonment and Air Operations were 68 and 150 milligrams per liter, respectively. The chloride concentration from all five production areas increased throughout the third quarter of 1996, and started the upward trend in about April 1995. Chloride concentration of ground water in monitoring wells at Cantonment and Air Operations also increased throughout the third quarter of 1996, with the largest increases from water in the deepest monitoring wells. Chloride concentrations have not been at this level since the dry season of 1994. A fuel-pipeline leak at Air Operations in May 1991 decreased total islandwide withdrawals by 15 percent. This lost pumping capacity is being offset by increased pumpage at Cantonment. Six wells do not contribute to the water supply because they are being used to hydraulically divert fuel migration away from water-supply wells by a program of ground-water withdrawal and injection.

Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment

PubMed Central

Bagley, Elena E.

2014-01-01

Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1) currents in periaqueductal gray (PAG) neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than Ek. Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1 effector. PMID:25009497

Opioid and GABAB receptors differentially couple to an adenylyl cyclase/protein kinase A downstream effector after chronic morphine treatment.

PubMed

Bagley, Elena E

2014-01-01

Opioids are intensely addictive, and cessation of their chronic use is associated with a highly aversive withdrawal syndrome. A cellular hallmark of withdrawal is an opioid sensitive protein kinase A-dependent increase in GABA transporter-1 (GAT-1) currents in periaqueductal gray (PAG) neurons. Elevated GAT-1 activity directly increases GABAergic neuronal excitability and synaptic GABA release, which will enhance GABAergic inhibition of PAG output neurons. This reduced activity of PAG output neurons to several brain regions, including the hypothalamus and medulla, contributes to many of the PAG-mediated signs of opioid withdrawal. The GABAB receptor agonist baclofen reduces some of the PAG mediated signs of opioid withdrawal. Like the opioid receptors the GABAB receptor is a Gi/Go coupled G-protein coupled receptor. This suggests it could be modulating GAT-1 activity in PAG neurons through its inhibition of the adenylyl cyclase/protein kinase A pathway. Opioid modulation of the GAT-1 activity can be detected by changes in the reversal potential of opioid membrane currents. We found that when opioids are reducing the GAT-1 cation conductance and increasing the GIRK conductance the opioid agonist reversal potential is much more negative than E k . Using this approach for GABAB receptors we show that the GABAB receptor agonist, baclofen, does not couple to inhibition of GAT-1 currents during opioid withdrawal. It is possible this differential signaling of the two Gi/Go coupled G-protein coupled receptors is due to the strong compartmentalization of the GABAB receptor that does not favor signaling to the adenylyl cyclase/protein kinase A/GAT-1 pathway. This highlights the importance of studying the effects of G-protein coupled receptors in native tissue with endogenous G-protein coupled receptors and the full complement of relevant proteins and signaling molecules. This study suggests that baclofen reduces opioid withdrawal symptoms through a non-GAT-1 effector.

Evaluating Iowa Community College Student Demographics, Characteristics, Enrollment Factors, and Educational Goals Influence on Retention Rates

ERIC Educational Resources Information Center

Mitchley-McAvoy, Joan A.

2012-01-01

This study examined the influence that previously researched and affirmed persistence and early withdrawal factors such as student demographics, enrollment status factors, student characteristics, and student educational goals had on Iowa community college retention rates for the 2005, 2007, and 2009 academic years. It is the researcher's…

Plasma cortisol and oxytocin levels predict help-seeking intentions for depressive symptoms.

PubMed

Thomas, Susan; Larkin, Theresa

2018-01-01

Depressed individuals often refuse or withdraw from help, a phenomenon termed help-negation, which is a risk factor for poor outcomes. Most previous research has investigated psychosocial factors including stigma as causes of low help-seeking intentions for depression, however these do not adequately explain the problem. We hypothesised that because help-negation worsens with symptom severity, it might be linked to important biological changes associated with depression itself. We investigated the relative contributions of cortisol, a stress hormone linked to depression, and oxytocin, a hormone which mediates social behaviours, alongside psychosocial factors, to help-seeking intentions among depressed and non-depressed individuals. Morning plasma cortisol and oxytocin levels, psychopathology, suicidal ideation, help-seeking intentions from informal sources including family and friends, and formal sources including health professionals, and perceived social support were quantified in 63 adults meeting DSM-5 criteria for major depressive disorder (MDD) who were not receiving any treatment, and 60 healthy controls. Between-group analyses of variance, correlations, and hierarchical multiple regressions were employed. Help-seeking intentions were lower in depressed than healthy participants, negatively correlated to cortisol and positively correlated to oxytocin. Cortisol negatively, and oxytocin positively, predicted help-seeking intentions from informal but not formal sources, after controlling for psychopathology and psychosocial factors. Neuroendocrine changes associated with depression may contribute to low help-seeking from friends and family, which may have implications for interpersonal support and outcomes. Research and clinical approaches which incorporate biological as well as psychosocial factors may allow for more targeted and effective early interventions to address lack of help-seeking and depression progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

PubMed

Morais-Silva, G; Fernandes-Santos, J; Moreira-Silva, D; Marin, M T

2016-01-01

Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

Estimating pumping time and ground-water withdrawals using energy- consumption data

USGS Publications Warehouse

Hurr, R.T.; Litke, D.W.

1989-01-01

Evaluation of the hydrology of an aquifer requires knowledge about the volume of groundwater in storage and also about the volume of groundwater withdrawals. Totalizer flow meters may be installed at pumping plants to measure withdrawals; however, it generally is impractical to equip all pumping plants in an area with meters. A viable alternative is the use of rate-time methods. Rate-time methods may be used at individual pumping plants to decrease the data collection necessary for determining withdrawals. At sites where pumping-time measurement devices are not installed, pumping time may be determined on the basis of energy consumption and power demand. At pumping plants where energy consumption is metered, data acquired by reading of meters is used to estimate pumping time. Care needs to be taken to read these meters correctly. At pumping plants powered by electricity, the calculations need to be modified if transformers are present. At pumping plants powered by natural gas, the effects of the pressure-correction factor need to be included in the calculations. At pumping plants powered by gasoline, diesel oil, or liquid petroleum gas, the geometry of storage tanks needs to be analyzed as part of the calculations. The relation between power demand and pumping rate at a pumping plant can be described through the use of the power-consumption coefficient. Where equipment and hydrologic conditions are stable, this coefficient can be applied to total energy consumption at a site to estimate total groundwater withdrawals. Random sampling of power consumption coefficients can be used to estimate area-wide groundwater withdrawal. (USGS)

Estimated water use and availability in the Pawcatuck Basin, southern Rhode Island and southeastern Connecticut, 1995-99

USGS Publications Warehouse

Wild, Emily C.; Nimiroski, Mark T.

2004-01-01

In 1988, the Pawcatuck Basin (302.4 square miles) in southern Rhode Island (245.3 square miles) and southeastern Connecticut (57.12 square miles) was defined as a sole-source aquifer for 14 towns in southern Rhode Island and 4 towns in southeastern Connecticut. To determine water use and availability, the six subbasins in the Pawcatuck Basin were delineated on the basis of the surface- and ground-water system drainage areas. From 1995 through 1999, five major water suppliers in the basin withdrew an average of 6.768 million gallons per day from the aquifers. The estimated water withdrawals from minor water suppliers during the study period were 0.099 million gallons per day. Self-supplied domestic, industrial, commercial, and agricultural withdrawals from the basin averaged 4.386 million gallons per day. Water use in the basin averaged 7.401 million gallons per day. The average return flow in the basin was 7.855 million gallons per day, which included effluent from permitted facilities and self-disposed water users. The PART program, a computerized hydrographseparation application, was used for five selected index streamgaging stations to determine water availability on the basis of the 75th, 50th, and 25th percentiles of the total base flow, the base flow minus the 7-day, 10-year flow criteria, and the base flow minus the Aquatic Base Flow criteria at the index stations. The differences in the surface- and ground-water system drainage areas in the summer were applied to the water availability calculated at the index stations and subbasins. The base-flow contributions from sand and gravel deposits at the index stations were computed for June, July, August, and September, and applied to the percentage of surficial deposits at each index station. The base-flow contributions were converted to a per unit area at the station for the till, and for the sand and gravel deposits, and applied to the subbasins. The statistics used to estimate the gross yield of base flow, as well as subtracting out the two low-flow criteria, resulted in various wateravailability values at each index station, which were present in the subbasin after applying the per unit area rates from the index station. The results from the Chipuxet and Arcadia streamgaging stations were lowest in September at the 75th and 25th percentiles, and August flows were lowest for the summer at the 50th percentile. For the other three index stations, September flows were the lowest for the summer. Because water withdrawals and use are greater during the summer than other times of the year, water availability in June, July, August, and September was assessed and compared to water withdrawals in the basin and subbasins. The ratios were calculated by using the water-availability flow scenarios at the 75th, 50th, and 25th percentiles for the subbasins, which are based on total water available from base-flow contributions from till deposits and sand and gravel deposits in the subbasins. For the study period, the withdrawals in August were higher than the other summer months. The ratios were close to one in August for the estimated gross yield and 7-day, 10-year flow criterion, and were close to one in September for the estimated Aquatic Base Flow criterion water-availability scenarios in the Pawcatuck Basin. The closer the ratio is to one, the closer the withdrawals are to the estimated water available, and the net water available decreases. To determine the effects of streamflow depletion from continuous water withdrawals, the program STRMDEPL was used to simulate public wells and well fields at a constant pumping rate based on the 1999 summer average for each withdrawal, over a period of 180 days. The streamflow depletion was 86, 95, 93, 96, and 98 percent at 30 days for Kingston wells 1 and 2, Westerly well fields 1 and 2, and well 3, respectively. A long-term hydrologic budget was calculated for the Pawcatuck Basin to identify and assess the basin and subbasin inflow and outflows. The water withdrawals and return flows used in the budget were from 1995 through 1999. For the hydrologic budget, it was assumed that inflow equals outflow, which resulted in 723.1 million gallons per day in the basin. The estimated inflows from precipitation and water return flow were 99 and 1 percent in the basin, respectively. The estimated outflows from evapotranspiration, streamflow, and water withdrawals were 43, 56, and 1 percent, respectively.

Short-Term Plasticity in a Computational Model of the Tail-Withdrawal Circuit in Aplysia

PubMed Central

Baxter, Douglas A.; Byrne, John H.

2007-01-01

The tail-withdrawal circuit of Aplysia provides a useful model system for investigating synaptic dynamics. Sensory neurons within the circuit manifest several forms of synaptic plasticity. Here, we developed a model of the circuit and investigated the ways in which depression (DEP) and potentiation (POT) contributed to information processing. DEP limited the amount of motor neuron activity that could be elicited by the monosynaptic pathway alone. POT within the monosynaptic pathway did not compensate for DEP. There was, however, a synergistic interaction between POT and the polysynaptic pathway. This synergism extended the dynamic range of the network, and the interplay between DEP and POT made the circuit responded preferentially to long-duration, low-frequency inputs. PMID:17957237

Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumrejkanchanakij, Piyamas; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330; Eto, Kazuhiro

2006-02-03

The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, amore » process that was inhibited by p16{sup INK4a}, a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis.« less

Cytoplasmic sequestration of cyclin D1 associated with cell cycle withdrawal of neuroblastoma cells.

PubMed

Sumrejkanchanakij, Piyamas; Eto, Kazuhiro; Ikeda, Masa-Aki

2006-02-03

The regulation of D-type cyclin-dependent kinase activity is critical for neuronal differentiation and apoptosis. We recently showed that cyclin D1 is sequestered in the cytoplasm and that its nuclear localization induces apoptosis in postmitotic primary neurons. Here, we further investigated the role of the subcellular localization of cyclin D1 in cell cycle withdrawal during the differentiation of N1E-115 neuroblastoma cells. We show that cyclin D1 became predominantly cytoplasmic after differentiation. Targeting cyclin D1 expression to the nucleus induced phosphorylation of Rb and cdk2 kinase activity. Furthermore, cyclin D1 nuclear localization promoted differentiated N1E-115 cells to reenter the cell cycle, a process that was inhibited by p16(INK4a), a specific inhibitor of D-type cyclin activity. These results indicate that cytoplasmic sequestration of cyclin D1 plays a role in neuronal cell cycle withdrawal, and suggests that the abrogation of machinery involved in monitoring aberrant nuclear cyclin D1 activity contributes to neuronal tumorigenesis.

The relation between Bulimic symptoms and the social withdrawal syndrome during early adolescence.

PubMed

Rotenberg, Ken J; Sangha, Rajvir

2015-12-01

The short-term longitudinal study tested the hypothesis that there was a prospective relation between the social withdrawal syndrome and Bulimic symptoms during early adolescence. Ninety-six adolescents (47 males, mean age=13 years - 10 months) completed standardized scales assessing Bulimic symptoms, trust beliefs in others and loneliness at Time 1/T1 and again 5 months later at Time 2/T2. Analyses showed that: (1) Bulimic symptoms were negatively correlated with trust beliefs, (2) Bulimic symptoms were positively correlated with loneliness, and (3) trust beliefs were negatively correlated with loneliness. The SEM and mediation analyses showed that trust beliefs at T1 were negatively and concurrently associated with Bulimic symptoms at T1 and longitudinally (and negatively) predicted changes in Bulimic symptoms. It was found that loneliness at T1 statistically mediated those concurrent and longitudinal relations. The findings yielded support for the conclusion that the social withdrawal syndrome, as assessed by low trust beliefs and resulting experiences of loneliness, contributes to Bulimia nervosa during early adolescence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Market withdrawal of new molecular entities approved in the United States from 1980 to 2009.

PubMed

Qureshi, Zaina P; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Stevenson, Kurt B; Szeinbach, Sheryl L

2011-07-01

Economic factors, market dynamics, and safety issues are largely responsible for decisions to withdraw pharmaceutical products from the market. In this study, new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) were examined in the USA from 1980 to 2009. Data were obtained from the FDA, Micromedex, Medline, and Lexis-Nexis. Descriptive analyses were used to classify product discontinuations by therapeutic category, time frame for discontinuation, and reason for withdrawal. There were 740 NMEs approved by the FDA during the study period. As of 1 December 2010, the number of drugs discontinued was 118 (15.9%). Discontinuations were the highest for antiparasitic products, insecticides, and repellents (6, 33.3% of approvals), systemic hormonal preparations excluding sex hormones and insulins (5, 33.3%), musculo-skeletal system (11, 32.4%), diagnostic agents (16, 28.1%), and anti-infectives for systemic use (27, 25.2%). Safety was the primary reason for withdrawing 26 drugs (3.5% of approvals). Approximately one in seven approved NMEs were discontinued from the market in the period of 1980-2009. Less than one-quarter (22%) of the total withdrawals were attributed to safety reasons. An ongoing evaluation of new drugs throughout their product life cycle is important to determine their efficacy, safety, and value to society. Copyright © 2011 John Wiley & Sons, Ltd.

Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.

PubMed

Franchitto, Nicolas; Jullian, Benedicte; Salles, Juliette; Pelissier, Fanny; Rolland, Benjamin

2017-06-01

Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.

Past and future water use in Pacific Coast states.

Treesearch

Laurie L. Houston; Michio Watanabe; Jeffrey D. Kline; Ralph J. Alig

2003-01-01

We examine socioeconomic factors affecting water demand and expected trends in these factors. Based on these trends, we identify past, current, and projected withdrawal of surface water for various uses in Pacific Coast States (California, Idaho, Oregon, and Washington), including public, domestic, commercial, industrial, thermoelectric, livestock, and irrigation....

Involvement of the central melanocortin system in the effects of caffeine on anxiety-like behavior in mice.

PubMed

Bhorkar, Amita A; Dandekar, Manoj P; Nakhate, Kartik T; Subhedar, Nishikant K; Kokare, Dadasaheb M

2014-01-30

To investigate the role of the melanocortin (MC) system in the framework of the central nucleus of the amygdala (CeA) in the differential effects of the adenosine receptor blocker caffeine on anxiety-like behavior, using the social interaction (SI) test. Caffeine was injected intraperitoneally, alone or in combination with alpha-melanocyte stimulating hormone (α-MSH), the MC4 receptor agonist RO27-3225 or the antagonist HS014 via the intra-CeA route. The effects of chronic (21 days) caffeine, given alone or concurrently with α-MSH, or RO27-3225, were investigated. The effects of withdrawal of these treatments on SI time were also evaluated. Furthermore, the acute effects of HS014 were investigated in different sets of caffeine-withdrawn mice. Acute injection of caffeine, RO27-3225, or α-MSH produced anxiety-like behavior. Prior treatment with α-MSH, or RO27-3225 potentiated the caffeine-induced anxiety-like behavior. Subchronic treatment with HS014 increased the SI time, which was attenuated by caffeine. Chronic administration of caffeine resulted in tolerance to caffeine's anxiogenic effect, while abrupt discontinuation of the treatment produced peak anxiety-like behavior at 72 h post-withdrawal. Concurrent administration of α-MSH, or RO27-3225 with chronic caffeine delayed the development of tolerance and prevented withdrawal-induced anxiety-like behavior. Moreover, acute treatment with HS014 at 72 h post-withdrawal attenuated the anxiety-like behavior. α-MSH, possibly via MC4 receptor in the neuroanatomical framework of the CeA, may contribute to the acute, chronic and withdrawal actions of caffeine associated with anxiety-like behavior in the neuroanatomical framework of the CeA. Copyright © 2013 Elsevier Inc. All rights reserved.

An investigation into drug products withdrawn from the EU market between 2002 and 2011 for safety reasons and the evidence used to support the decision-making.

PubMed

McNaughton, Rhian; Huet, Gwenaël; Shakir, Saad

2014-01-15

The objective of this study was to determine the nature of evidence used to support the withdrawal of marketing authorisations of drug products for safety reasons throughout the European Union (EU) between 2002 and 2011. Products withdrawn, either by a medicines agency or a marketing authorisation holder, during the period 2002-2011 were identified by conducting detailed searches of the WHO, the European Medicines Agency (EMA) and national medicines agency websites throughout the EU plus Norway, Iceland and Liechtenstein. The scientific evidence used to support the decision was identified from a search within PubMed, the EMA and national medicines agencies websites. Information about spontaneous case reports entered into EudraVigilance and unavailable on the EMA website was received by email from the EMA. 19 drugs were withdrawn from the market, throughout the EU, for safety reasons from 2002 to 2011. Case reports were cited in 95% of withdrawals (18/19) and case-control studies (4/19), cohort studies (4/19), randomised controlled trials (RCTs) (12/19) or meta-analysis (5/19) were cited in 63% of withdrawals (12/19). Cardiovascular events or disorders were the main reason for withdrawal (9/19), followed by hepatic disorders (4/19) and neurological or psychiatric disorders (4/19). This study has shown that the level of evidence used to support drug withdrawal has improved during the past 10 years, with an increased use of case-control studies, cohort studies, RCTs and meta-analyses. This research has demonstrated that such studies have contributed to decision-making in almost two-thirds of cases.

Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

PubMed

Santoro, Giovanni C; Carrion, Joseph; Patel, Krishna; Vilchez, Crystal; Veith, Jennifer; Brodie, Jonathan D; Dewey, Stephen L

2017-08-01

Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using 18 FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal gray, were noted. However, compared with males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared with sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, whereas buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, whereas these posttreatment sex differences contribute to clinical treatment failure more commonly experienced by the former.

Extinction of conditioned opiate withdrawal in rats is blocked by intracerebroventricular infusion of an NMDA receptor antagonist.

PubMed

Coleman, Brian R; Carlezon, William A; Myers, Karyn M

2013-04-29

Maladaptive conditioned responses (CRs) contribute to psychiatric disorders including anxiety disorders and addiction. Methods of reducing these CRs have been considered as possible therapeutic approaches. One such method is extinction, which involves exposure to CR-eliciting cues in the absence of the event they once predicted. In animal models, extinction reduces both fear and addiction-related CRs, and in humans, extinction-based cue exposure therapy (CET) reduces fear CRs. However, CET is less effective in drug addicts, for reasons that are not clear. Increased understanding of the neurobiology of extinction of drug-related CRs as compared to fear CRs may help illuminate this issue. Here, we examine the N-methyl-d-aspartate (NMDA) receptor-dependence of extinction of conditioned opiate withdrawal in rats. Using a place conditioning paradigm, we trained morphine-dependent rats to associate an environment with naloxone-precipitated withdrawal. We then extinguished that association by returning the rats repeatedly to the environment in the absence of acute withdrawal. In some rats we administered the NMDA receptor antagonist d,l-2-amino-5-phosphovaleric acid (AP5) intracerebroventricularly immediately prior to extinction training. In a subsequent test session, these rats avoided the formerly naloxone-paired environment, similar to rats that had not undergone extinction training. By contrast, rats that received vehicle prior to extinction training did not avoid the formerly naloxone-paired environment. This finding indicates that extinction of a drug-related CR (conditioned opiate withdrawal) is dependent on NMDA receptors, similar to extinction of conditioned fear. The locus of the critical NMDA receptors is unclear but may include basolateral amygdala and/or medial prefrontal cortex. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Sex differences in acute relief of abstinence-induced withdrawal and negative affect due to nicotine content in cigarettes.

PubMed

Perkins, Kenneth A; Karelitz, Joshua L

2015-04-01

Acute cigarette smoking may relieve withdrawal and negative affect due to tobacco abstinence to a greater extent in women versus men. Yet, the relative contribution of the cigarette's nicotine content to this sex difference is not clear. Non-quitting dependent adult smokers (N = 44; 21 males, 23 females) participated in 2 virtually identical sessions, each after abstaining overnight (CO < 10 ppm) and differing only in the nicotine content of the designated cigarette. While blind to brand markings, they consumed a total of 24 puffs in controlled fashion for 2 hr in each session, either from a nicotine (Quest 1, 0.6 mg) or denicotinized (Quest 3, 0.05 mg) cigarette. Withdrawal symptoms were obtained before and after smoking, and negative affect was assessed after each period of cigarette exposure consisting of 6 puffs every 25 min. Men and women did not differ in baseline withdrawal and negative affect due to overnight abstinence, but reductions in each symptom were significantly influenced by the interaction of sex × nicotine/denicotinized cigarette (both p < .05). In men, but not in women, each symptom was generally decreased more by the nicotine versus denicotinized cigarette, and the nicotine cigarette reduced each to a greater degree in men versus women. Sex differences in relief of abstinence-induced withdrawal and negative affect due to the nicotine content in cigarettes are consistent with prior research indicating that nicotine per se, compared to non-nicotine smoke stimuli, is less rewarding in women versus men. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Extinction of conditioned opiate withdrawal in rats is blocked by intracerebroventricular infusion of an NMDA receptor antagonist

PubMed Central

Coleman, Brian R.; Carlezon, William A.; Myers, Karyn M.

2015-01-01

Maladaptive conditioned responses (CRs) contribute to psychiatric disorders including anxiety disorders and addiction. Methods of reducing these CRs have been considered as possible therapeutic approaches. One such method is extinction, which involves exposure to CR-eliciting cues in the absence of the event they once predicted. In animal models, extinction reduces both fear and addiction-related CRs, and in humans, extinction-based cue exposure therapy (CET) reduces fear CRs. However, CET is less effective in drug addicts, for reasons that are not clear. Increased understanding of the neurobiology of extinction of drug-related CRs as compared to fear CRs may help illuminate this issue. Here, we examine the N-methyl-D-aspartate (NMDA) receptor-dependence of extinction of conditioned opiate withdrawal in rats. Using a place conditioning paradigm, we trained morphine-dependent rats to associate an environment with naloxone-precipitated withdrawal. We then extinguished that association by returning the rats repeatedly to the environment in the absence of acute withdrawal. In some rats we administered the NMDA receptor antagonist D,L-2-amino-5-phosphovaleric acid (AP5) intracerebroventricularly immediately prior to extinction training. In a subsequent test session, these rats avoided the formerly naloxone-paired environment, similar to rats that had not undergone extinction training. By contrast, rats that received vehicle prior to extinction training did not avoid the formerly naloxone-paired environment. This finding indicates that extinction of a drug-related CR (conditioned opiate withdrawal) is dependent on NMDA receptors, similar to extinction of conditioned fear. The locus of the critical NMDA receptors is unclear but may include basolateral amygdala and/or medial prefrontal cortex. PMID:23416323

Model Refinement and Simulation of Groundwater Flow in Clinton, Eaton, and Ingham Counties, Michigan

USGS Publications Warehouse

Luukkonen, Carol L.

2010-01-01

A groundwater-flow model that was constructed in 1996 of the Saginaw aquifer was refined to better represent the regional hydrologic system in the Tri-County region, which consists of Clinton, Eaton, and Ingham Counties, Michigan. With increasing demand for groundwater, the need to manage withdrawals from the Saginaw aquifer has become more important, and the 1996 model could not adequately address issues of water quality and quantity. An updated model was needed to better address potential effects of drought, locally high water demands, reduction of recharge by impervious surfaces, and issues affecting water quality, such as contaminant sources, on water resources and the selection of pumping rates and locations. The refinement of the groundwater-flow model allows simulations to address these issues of water quantity and quality and provides communities with a tool that will enable them to better plan for expansion and protection of their groundwater-supply systems. Model refinement included representation of the system under steady-state and transient conditions, adjustments to the estimated regional groundwater-recharge rates to account for both temporal and spatial differences, adjustments to the representation and hydraulic characteristics of the glacial deposits and Saginaw Formation, and updates to groundwater-withdrawal rates to reflect changes from the early 1900s to 2005. Simulations included steady-state conditions (in which stresses remained constant and changes in storage were not included) and transient conditions (in which stresses changed in annual and monthly time scales and changes in storage within the system were included). These simulations included investigation of the potential effects of reduced recharge due to impervious areas or to low-rainfall/drought conditions, delineation of contributing areas with recent pumping rates, and optimization of pumping subject to various quantity and quality constraints. Simulation results indicate potential declines in water levels in both the upper glacial aquifer and the upper sandstone bedrock aquifer under steady-state and transient conditions when recharge was reduced by 20 and 50 percent in urban areas. Transient simulations were done to investigate reduced recharge due to low rainfall and increased pumping to meet anticipated future demand with 24 months (2 years) of modified recharge or modified recharge and pumping rates. During these two simulation years, monthly recharge rates were reduced by about 30 percent, and monthly withdrawal rates for Lansing area production wells were increased by 15 percent. The reduction in the amount of water available to recharge the groundwater system affects the upper model layers representing the glacial aquifers more than the deeper bedrock layers. However, with a reduction in recharge and an increase in withdrawals from the bedrock aquifer, water levels in the bedrock layers are affected more than those in the glacial layers. Differences in water levels between simulations with reduced recharge and reduced recharge with increased pumping are greatest in the Lansing area and least away from pumping centers, as expected. Additionally, the increases in pumping rates had minimal effect on most simulated streamflows. Additional simulations included updating the estimated 10-year wellhead-contributing areas for selected Lansing-area wells under 2006-7 pumping conditions. Optimization of groundwater withdrawals with a water-resource management model was done to determine withdrawal rates while minimizing operational costs and to determine withdrawal locations to achieve additional capacity while meeting specified head constraints. In these optimization scenarios, the desired groundwater withdrawals are achieved by simulating managed wells (where pumping rates can be optimized) and unmanaged wells (where pumping rates are not optimized) and by using various combinations of existing and proposed well locations.

29 CFR 4211.4 - Contributions for purposes of the numerator and denominator of the allocation fractions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of the allocation fractions. 4211.4 Section 4211.4 Labor Regulations Relating to Labor (Continued... denominator of the allocation fractions. Each of the allocation fractions used in the presumptive, modified... five-year period. (a) The numerator of the allocation fraction, with respect to a withdrawing employer...

Peer Acceptance and Self-Perceptions of Verbal and Behavioural Aggression and Social Withdrawal

ERIC Educational Resources Information Center

Chang, Lei; Li, Kin Kit; Lei, Li; Liu, Hongyun; Guo, Boliang; Wang, Yan; Fung, Kitty Y.

2005-01-01

This study presents a model of maladaptive social interactions that includes both behavioural and communication correlates of peer acceptance and self-perceived social competence. Tested in a sample of 377 Hong Kong secondary school students, verbal and nonverbal aggression contributed concurrently and longitudinally to peer acceptance.…

Contribution of parents' adult attachment and separation attitudes to parent-adolescent conflict resolution.

PubMed

García-Ruiz, Marta; Rodrigo, María José; Hernández-Cabrera, Juan A; Máiquez, María Luisa

2013-12-01

This study examined the contribution to parent-adolescent conflict resolution of parental adult attachment styles and attitudes toward adolescent separation. Questionnaires were completed by 295 couples with early to late adolescent children. Structural equation models were used to test self and partner influences on conflict resolution for three attachment orientations: confidence (model A), anxiety (model B) and avoidance (model C). Model A showed self influences between parents' confidence orientation and negotiation and also via positive attitudes towards separation. Also, the fathers' use of negotiation was facilitated by the mothers' confidence orientation and vice versa, indicating partner influences as well. Model B showed self influences between parents' anxiety orientation and the use of dominance and withdrawal and also via negative attitudes towards separation. Model C showed self influences between parents' avoidance orientation and dominance and withdrawal, and a partner influence between fathers' avoidance and mothers' use of dominance. The results indicated that the parents' adult attachment system and the parenting system were related in the area of conflict resolution, and that self influences were stronger than partner influences. © 2013 The Scandinavian Psychological Associations.

Changes in Serum Biochemical Factors Associated with Opium Addiction after Addiction Desertion

PubMed Central

Afarinesh, Mohammad Reza; Haghpanah, Tahereh; Divsalar, Kouros; Dehyadegary, Elham; Shaikh-Aleslami, Azar; Mahmoodi, Majid

2014-01-01

Background The long time use of opium has some effects on serums biochemical factors, the determination of this variation is a new approach in understanding off addiction and relive of drug abuser health. Hence in this study, these indicators in person who were withdrawing of opium have been studied. Methods In this cross-sectional study bloods biochemical factors such as fasting blood sugar (FBS), sodium (Na), calcium (Ca), uric acid (UA), blood urea nitrogen (BUN), creatinine, cholesterol, total protein, and fibrinogen in three groups serum were studied: (1) Who had been permanent opium users more than 2 years (case). (2) Dependent person who has taken one month addiction withdrawal course (control). (3) A healthy group that had been demographically similar to the other groups. Findings According to these study findings, FBS serum level in the case group is lower than control group. Serum level of Na, creatinine, and blood triglyceride (TG) in case study are higher than group control. Concentration of potassium, Ca, UA, BUN, cholesterol, total serum protein, fibrinogen, and thrombin time in case study and group control showed no significant difference. Also, in withdrawing case serum level of Na, Ca, UA, BUN, creatinine, and TG significantly increase and thrombin time decrease. Conclusion According to this study not only the longtime use of opium but also opium with drawerin opium dependent people can change their serum biochemical factors. So recognition, treatment, and prevention of this change could be a new step in improving of health and condition of patients. PMID:25984281

Common Psychiatric Disorders and Caffeine Use, Tolerance, and Withdrawal: An Examination of Shared Genetic and Environmental Effects

PubMed Central

Bergin, Jocilyn E.; Kendler, Kenneth S.

2012-01-01

Background Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Method Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. Results GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation = 0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. Conclusions There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes. PMID:22854069

Common psychiatric disorders and caffeine use, tolerance, and withdrawal: an examination of shared genetic and environmental effects.

PubMed

Bergin, Jocilyn E; Kendler, Kenneth S

2012-08-01

Previous studies examined caffeine use and caffeine dependence and risk for the symptoms, or diagnosis, of psychiatric disorders. The current study aimed to determine if generalized anxiety disorder (GAD), panic disorder, phobias, major depressive disorder (MDD), anorexia nervosa (AN), or bulimia nervosa (BN) shared common genetic or environmental factors with caffeine use, caffeine tolerance, or caffeine withdrawal. Using 2,270 women from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, bivariate Cholesky decomposition models were used to determine if any of the psychiatric disorders shared genetic or environmental factors with caffeine use phenotypes. GAD, phobias, and MDD shared genetic factors with caffeine use, with genetic correlations estimated to be 0.48, 0.25, and 0.38, respectively. Removal of the shared genetic and environmental parameter for phobias and caffeine use resulted in a significantly worse fitting model. MDD shared unique environmental factors (environmental correlation=0.23) with caffeine tolerance; the genetic correlation between AN and caffeine tolerance and BN and caffeine tolerance were 0.64 and 0.49, respectively. Removal of the genetic and environmental correlation parameters resulted in significantly worse fitting models for GAD, phobias, MDD, AN, and BN, which suggested that there was significant shared liability between each of these phenotypes and caffeine tolerance. GAD had modest genetic correlations with caffeine tolerance, 0.24, and caffeine withdrawal, 0.35. There was suggestive evidence of shared genetic and environmental liability between psychiatric disorders and caffeine phenotypes. This might inform us about the etiology of the comorbidity between these phenotypes.

Volcanic aquifers of Hawai‘i—Hydrogeology, water budgets, and conceptual models

USGS Publications Warehouse

Izuka, Scot K.; Engott, John A.; Rotzoll, Kolja; Bassiouni, Maoya; Johnson, Adam G.; Miller, Lisa D.; Mair, Alan

2016-06-13

Hawai‘i’s aquifers have limited capacity to store fresh groundwater because each island is small and surrounded by saltwater. Saltwater also underlies much of the fresh groundwater. Fresh groundwater resources are, therefore, particularly vulnerable to human activity, short-term climate cycles, and long-term climate change. Availability of fresh groundwater for human use is constrained by the degree to which the impacts of withdrawal—such as lowering of the water table, saltwater intrusion, and reduction in the natural discharge to springs, streams, wetlands, and submarine seeps—are deemed acceptable. This report describes the hydrogeologic framework, groundwater budgets (inflows and outflows), conceptual models of groundwater occurrence and movement, and the factors limiting groundwater availability for the largest and most populated of the Hawaiian Islands—Kaua‘i, O‘ahu, Maui, and Hawai‘i Island.The bulk of each of Hawai‘i’s islands is built of many thin lava flows erupted from shield volcanoes; the great piles of lava flows form highly permeable aquifers. In some areas, low-permeability dikes cutting across the lava flows, or low-permeability ash and soil horizons interlayered with the lava flows, can substantially alter groundwater flow. On some islands, sedimentary rocks form thick semiconfining coastal-plain deposits, locally known as caprock, that impede natural groundwater discharge to the ocean. In some regions, thick lava flows that ponded in preexisting depressions form aquifers that are much less permeable than aquifers formed by thin lava flows.Fresh groundwater inflow to Hawai‘i’s aquifers comes from recharge. For predevelopment conditions (1870), estimates of groundwater recharge from this study are 871, 675, 1,279, and 5,291 million gallons per day (Mgal/d) for Kaua‘i, O‘ahu, Maui, and Hawai‘i Island, respectively. Estimates of recharge for recent conditions (2010 land cover and 1978–2007 rainfall for Kaua‘i, O‘ahu, and Maui; 2008 land cover and 1916–1983 rainfall for Hawai‘i Island) are 875, 660, 1,308, and 6,595 Mgal/d for Kaua‘i, O‘ahu, Maui, and Hawai‘i Island, respectively. Recent recharge values differ from predevelopment recharge values by only a few percent for all islands except Hawai‘i Island, where changes in forest cover affected recharge. Spatial distribution of recharge mimics the orographic rainfall pattern—recharge is high on windward slopes and mountain peaks below the top of the trade-wind inversion. Human activity such as irrigation also contributes to recharge in some areas.Outflows from Hawai‘i’s aquifers include withdrawals from wells and natural groundwater discharge to springs, streams, wetlands, and submarine seeps. Under predevelopment conditions, groundwater withdrawal is assumed to be negligible and natural groundwater discharge probably was equal, or close, to recharge. Under recent conditions (2000–2010), groundwater withdrawal averaged 19, 209, 104, and 103 Mgal/d on Kaua‘i, O‘ahu, Maui, and Hawai‘i Island, respectively. If recent withdrawal and recharge rates are maintained until steady state is achieved, natural groundwater discharge will be reduced by an amount equal to the withdrawal rate. Total recent withdrawal for the four islands is only about 5 percent of total recharge, but about half of the withdrawal comes from O‘ahu, whereas O‘ahu receives only 7 percent of the total recharge. Effects of high withdrawals on O‘ahu cannot be mitigated by the lower withdrawals on other islands because no freshwater flows between islands. Even within an island, high withdrawals from one area cannot be completely mitigated by recharge in another area. Water-level, saltwater/freshwater-transition-zone, spring, and stream base-flow data indicate an overall reduction in storage for most areas where groundwater has been developed.Groundwater occurrence and movement in Hawai‘i’s volcanic aquifers can be described in terms of four conceptual models: (1) fresh groundwater lenses in high-permeability lava-flow aquifers, (2) aquifers with groundwater impounded by dikes, (3) thickly saturated low-permeability aquifers, and (4) perched aquifers. In Hawai‘i, most fresh groundwater withdrawn for human use comes from freshwater lenses in the dike-free high-permeability lava-flow aquifers where the principal limiting factor to groundwater availability is saltwater intrusion, but impacts of reduced natural groundwater discharge may also limit availability. Dike-impounded groundwater is common near the center of Hawaiian shield volcanoes, where water moves and is stored in permeable lava flows between the dikes; groundwater availability in these aquifers is primarily limited by storage depletion and reduction of flow to adjacent aquifers and natural groundwater discharge. Thickly saturated low-permeability aquifers have been identified on Kaua‘i and Maui; groundwater availability is primarily limited by streamflow depletion and water-table decline. Perched groundwater is postulated to exist in some areas of Hawai‘i, but store much less water than other modes ofgroundwater occurrence. Limits on groundwater availability in perched aquifers include the potential of reducing inflow to other groundwater settings and reducing natural discharge and stream seepage. Some groundwater bodies in Hawai‘i are enigmatic; consequences of groundwater development in these bodies and their relation to groundwater availability are not completely understood.

Modeling the Diagnostic Criteria for Alcohol Dependence with Genetic Animal Models

PubMed Central

Kendler, Kenneth S.; Hitzemann, Robert J.

2012-01-01

A diagnosis of alcohol dependence (AD) using the DSM-IV-R is categorical, based on an individual’s manifestation of three or more symptoms from a list of seven. AD risk can be traced to both genetic and environmental sources. Most genetic studies of AD risk implicitly assume that an AD diagnosis represents a single underlying genetic factor. We recently found that the criteria for an AD diagnosis represent three somewhat distinct genetic paths to individual risk. Specifically, heavy use and tolerance versus withdrawal and continued use despite problems reflected separate genetic factors. However, some data suggest that genetic risk for AD is adequately described with a single underlying genetic risk factor. Rodent animal models for alcohol-related phenotypes typically target discrete aspects of the complex human AD diagnosis. Here, we review the literature derived from genetic animal models in an attempt to determine whether they support a single-factor or multiple-factor genetic structure. We conclude that there is modest support in the animal literature that alcohol tolerance and withdrawal reflect distinct genetic risk factors, in agreement with our human data. We suggest areas where more research could clarify this attempt to align the rodent and human data. PMID:21910077

29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass...

29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass...

Effects of Irrigation, Drought, and Ground-Water Withdrawals on Ground-Water Levels in the Southern Lihue Basin, Kauai, Hawaii

USGS Publications Warehouse

Izuka, Scot K.

2006-01-01

A numerical ground-water-flow model was used to investigate the effects of irrigation on ground-water levels in the southern Lihue Basin, Kauai, Hawaii, and the relation between declining ground-water levels observed in the basin in the 1990s and early 2000s and concurrent drought, irrigation reduction, and changes in ground-water withdrawal. Results of steady-state model simulations indicate that changing from pre-development to 1981 irrigation and ground-water-withdrawal conditions could, given enough time for steady state to be achieved, raise ground-water levels in some areas of the southern Lihue Basin by as much as 200 feet, and that changing from 1981 to 1998 irrigation and ground-water-withdrawal conditions could lower ground-water levels in some areas by as much as 100 feet. Transient simulations combining drought, irrigation reduction, and changes in ground-water withdrawal show trends that correspond with those observed in measured water levels. Results of this study indicate that irrigation reduction was the primary cause of the observed decline in ground-water-levels. In contrast, ground-water withdrawal had a long-duration but small-magnitude effect, and drought had a widespread, high-magnitude but short-duration effect. Inasmuch as irrigation in the future is unlikely to return to the same levels as during the period of peak sugarcane agriculture, the decline in ground-water levels resulting from the reduction and ultimate end of sugarcane irrigation can be considered permanent. Assuming that irrigation does not return to the southern Lihue Basin and that, on average, normal rainfall persists and ground-water withdrawal remains at 1998 rates, model projections indicate that average ground-water levels in the Kilohana-Puhi area will continue to recover from the drought of 1998-2002 and eventually rise to within about 4 feet of the pre-drought conditions. Long-term climate trends, increases in ground-water withdrawal, or other factors not simulated in the model could also affect ground-water levels in the southern Lihue Basin in the future.

Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat.

PubMed

Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

2011-04-01

Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat). Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. Copyright © 2011 by the Research Society on Alcoholism.

Successful withdrawal from high-dose benzodiazepine in a young patient through electronic monitoring of polypharmacy: a case report in an ambulatory setting.

PubMed

Loscertales, Hèctor R; Wentzky, Valerie; Dürsteler, Kenneth; Strasser, Johannes; Hersberger, Kurt E; Arnet, Isabelle

2017-05-01

Dependence on high-dose benzodiazepines (BZDs) is well known and discontinuation attempts are generally unsuccessful. A well established protocol for high-dose BZD withdrawal management is lacking. We present the case of withdrawal from high-dose lorazepam (>20 mg daily) in an unemployed 35-year-old male outpatient through agonist substitution with long-acting clonazepam and electronic monitoring over 28 weeks. All medicines were repacked into weekly 7 × 4 cavity multidose punch cards with an electronic monitoring system. The prescribed daily dosages of BZDs were translated into an optimal number of daily tablets, divided into up to four units of use. Withdrawal was achieved by individual leftover of a small quantity of BZDs that was placed in a separate compartment. Feedback with visualization of intake over the past week was given during weekly psychosocial sessions. Stepwise reduction was obtained by reducing the mg content of the cavities proportionally to the leftovers, keeping the number of cavities in order to maintain regular intake behavior, and to determine the dosage decrease. At week 28, the primary objectives were achieved, that is, lorazepam reduction to 5 mg daily and cannabis abstinence. Therapy was continued using multidrug punch cards without electronic monitoring to maintain the management system. At week 48, a smaller size weekly pill organizer with detachable daily containers was dispensed. At week 68, the patient's therapy was constant with 1.5 mg clonazepam + 5 mg lorazepam daily for anxiety symptoms and the last steps of withdrawal were started. Several key factors led to successful withdrawal from high-dose BZD in this outpatient, such as the use of weekly punch cards coupled with electronic monitoring, the patient's empowerment over the withdrawal process, and the collaboration of several healthcare professionals. The major implication for clinical care is reduction by following the leftovers, and not a diktat from the healthcare professionals.

System-Level Barriers and Facilitators for Foregoing or Withdrawing Dialysis: A Qualitative Study of Nephrologists in the United States and England.

PubMed

Grubbs, Vanessa; Tuot, Delphine S; Powe, Neil R; O'Donoghue, Donal; Chesla, Catherine A

2017-11-01

Despite a growing body of literature suggesting that dialysis does not confer morbidity or mortality benefits for all patients with chronic kidney failure, the initiation and continuation of dialysis therapy in patients with poor prognosis is commonplace. Our goal was to elicit nephrologists' perspectives on factors that affect decision making regarding end-stage renal disease. Semistructured, individual, qualitative interviews. Participants were purposively sampled based on age, race, sex, geographic location, and practice type. Each was asked about his or her perspectives and experiences related to foregoing and withdrawing dialysis therapy. Interviews were audiotaped, transcribed, and analyzed using narrative and thematic analysis. We conducted 59 semistructured interviews with nephrologists from the United States (n=41) and England (n=18). Most participants were 45 years or younger, men, and white. Average time since completing nephrology training was 14.2±11.6 (SD) years. Identified system-level facilitators and barriers for foregoing and withdrawing dialysis therapy stemmed from national and institutional policies and structural factors, how providers practice medicine (the culture of medicine), and beliefs and behaviors of the public (societal culture). In both countries, the predominant barriers described included lack of training in end-of-life conversations and expectations for aggressive care among non-nephrologists and the general public. Primary differences included financial incentives to dialyze in the United States and widespread outpatient conservative management programs in England. Participants' views may not fully capture those of all American or English nephrologists. Nephrologists in the United States and England identified several system-level factors that both facilitated and interfered with decision making around foregoing and withdrawing dialysis therapy. Efforts to expand facilitators while reducing barriers could lead to care practices more in keeping with patient prognosis. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Early EEG for outcome prediction of postanoxic coma: prospective cohort study with cost-minimization analysis.

PubMed

Sondag, Lotte; Ruijter, Barry J; Tjepkema-Cloostermans, Marleen C; Beishuizen, Albertus; Bosch, Frank H; van Til, Janine A; van Putten, Michel J A M; Hofmeijer, Jeannette

2017-05-15

We recently showed that electroencephalography (EEG) patterns within the first 24 hours robustly contribute to multimodal prediction of poor or good neurological outcome of comatose patients after cardiac arrest. Here, we confirm these results and present a cost-minimization analysis. Early prognosis contributes to communication between doctors and family, and may prevent inappropriate treatment. A prospective cohort study including 430 subsequent comatose patients after cardiac arrest was conducted at intensive care units of two teaching hospitals. Continuous EEG was started within 12 hours after cardiac arrest and continued up to 3 days. EEG patterns were visually classified as unfavorable (isoelectric, low-voltage, or burst suppression with identical bursts) or favorable (continuous patterns) at 12 and 24 hours after cardiac arrest. Outcome at 6 months was classified as good (cerebral performance category (CPC) 1 or 2) or poor (CPC 3, 4, or 5). Predictive values of EEG measures and cost-consequences from a hospital perspective were investigated, assuming EEG-based decision- making about withdrawal of life-sustaining treatment in the case of a poor predicted outcome. Poor outcome occurred in 197 patients (51% of those included in the analyses). Unfavorable EEG patterns at 24 hours predicted a poor outcome with specificity of 100% (95% CI 98-100%) and sensitivity of 29% (95% CI 22-36%). Favorable patterns at 12 hours predicted good outcome with specificity of 88% (95% CI 81-93%) and sensitivity of 51% (95% CI 42-60%). Treatment withdrawal based on an unfavorable EEG pattern at 24 hours resulted in a reduced mean ICU length of stay without increased mortality in the long term. This gave small cost reductions, depending on the timing of withdrawal. Early EEG contributes to reliable prediction of good or poor outcome of postanoxic coma and may lead to reduced length of ICU stay. In turn, this may bring small cost reductions.

Factors influencing social distance toward people with mental illness.

PubMed

Lauber, Christoph; Nordt, Carlos; Falcato, Luis; Rössler, Wulf

2004-06-01

When identifying ways to reduce stigmatization because of mental illness it is crucial to understand contributing factors. Social distance-the willingness to engage in relationships of varying intimacy with a person--is an indicator of public attitudes toward persons with mental illness. Multiple linear regression analysis of the results of a vignette-based opinion survey conducted on a representative population sample in Switzerland (n = 594). The level of social distance increases if situations imply 'social closeness.' The vignette describing a person with schizophrenia, attitudes to general aspects of mental health (lay helping, community psychiatry), emotions toward those affected, and the attitude toward consequences of mental illness (medical treatment, medication side effects, negative sanctions, e.g. withdrawal of the driver license) were found to predict social distance. Demographic factors such as age, gender, and the cultural background influence social distance. The explained variance (R2) is 44.8%. Social distance is a multifaceted concept influenced by, e.g., socio-economic and cultural factors, but also by the respondent's general attitude toward (mental) health issues. These results suggest that more knowledge about mental illnesses, especially schizophrenia, may increase social distance. The findings presented here may help to focus anti-stigma campaigns not only on transmission of knowledge, but on integrating different approaches.

Case study for delineating a contributing area to a well in a fractured siliciclastic-bedrock aquifer near Lansdale, Pennsylvania

USGS Publications Warehouse

Barton, Gary J.; Risser, Dennis W.; Galeone, Daniel G.; Goode, Daniel J.

2003-01-01

A supply well used by the North Penn Water Authority near Lansdale, Pa., was selected as a case study for delineating a contributing area in a fractured siliciclastic-bedrock aquifer. The study emphasized the importance of refining the understanding of factors that control ground-water movement to the well by conducting (1) geophysical logging and flow measurements, (2) ground-water level monitoring, (3) aquifer testing, and (4) geochemical sampling. This approach could be applicable for other wells in siliciclastic-bedrock terranes, especially those of Triassic age in southeastern Pennsylvania.The principal methods for refining the understanding of hydrology at supply well MG-1125 were aquifer testing, water-level measurements, and geophysical logging. Results of two constant-discharge aquifer tests helped estimate the transmissivity of water-producing units and evaluate the anisotropy caused by dipping beds. Results from slug tests provided estimates of transmissivity that were used to evaluate the results from the constant-discharge aquifer tests. Slug tests also showed the wide distribution of transmissivity, indicating that ground-water velocities must vary considerably in the well field. Water-level monitoring in observation wells allowed maps of the potentiometric surface near the well field to be drawn. The measurements also showed that the hydraulic gradient can change abruptly in response to pumping from nearby supply wells. Water levels measured at a broader regional scale in an earlier study also provided a useful view of the potentiometric surface for purposes of delineating the contributing area. Geophysical logging and measurements of flow within wells showed that about 60 percent of water from supply well MG-1125 probably is contributed from relatively shallow water-producing fractures from 60 to 125 feet below land surface, but measurable amounts of water are contributed by fractures to a depth of 311 feet below land surface. Chemical samples supported the evidence that shallow fractures probably contribute significant amounts of water to well MG-1125. The large contribution of water from shallow fractures indicates that the area providing part of the recharge to the well is not far removed from the wellhead.Preliminary delineations of the contributing area and the 100-day time-of travel area were computed from a water budget and time-of-travel equation. These delineations provided insight into the size (but not the shape) of the contributing areas. Three other approaches were used and results compared: (1) uniform-flow equation, (2) hydrogeologic mapping, and (3) numerical modeling. The uniform-flow equation predicted a contributing area that seemed unrealistic—extending far across the ground-water divide into an adjacent watershed. Hydrogeologic mapping, if used with the potentiometric surface and constrained by the water budget, produced contributing area that was similar to that from numerical modeling. Numerical modeling allowed the incorporation of anisotropy caused by dipping water-producing units, differing transmissivity values of geologic units, and ground-water withdrawals from nearby supply wells. The numerical modeling showed that groundwater withdrawals from nearby supply wells affected the contributing area to supply well MG-1125 but had less effect on the 100-day time-of-travel area.

Emotional Reactivity, Behavior Problems, and Social Adjustment at School Entry in a High-risk Sample.

PubMed

Kalvin, Carla B; Bierman, Karen L; Gatzke-Kopp, Lisa M

2016-11-01

Prior research suggests that heightened emotional reactivity to emotionally distressing stimuli may be associated with elevated internalizing and externalizing behaviors, and contribute to impaired social functioning. These links were explored in a sample of 169 economically-disadvantaged kindergarteners (66 % male; 68 % African American, 22 % Hispanic, 10 % Caucasian) oversampled for elevated aggression. Physiological measures of emotional reactivity (respiratory sinus arrhythmia [RSA], heart rate [HR], and cardiac pre-ejection period [PEP]) were collected, and teachers and peers provided ratings of externalizing and internalizing behavior, prosocial competence, and peer rejection. RSA withdrawal, HR reactivity, and PEP shortening (indicating increased arousal) were correlated with reduced prosocial competence, and RSA withdrawal and HR reactivity were correlated with elevated internalizing problems. HR reactivity was also correlated with elevated externalizing problems and peer rejection. Linear regressions controlling for age, sex, race, verbal proficiency, and resting physiology showed that HR reactivity explained unique variance in both teacher-rated prosocial competence and peer rejection, and contributed indirectly to these outcomes through pathways mediated by internalizing and externalizing problems. A trend also emerged for the unique contribution of PEP reactivity to peer-rated prosocial competence. These findings support the contribution of emotional reactivity to behavior problems and social adjustment among children living in disadvantaged urban contexts, and further suggest that elevated reactivity may confer risk for social difficulties in ways that overlap only partially with internalizing and externalizing behavior problems.

Molecular regulation of sex change induced by methyltestosterone -feeding and methyltestosterone -feeding withdrawal in the protogynous orange-spotted grouper.

PubMed

Wang, Qing; Liu, Yun; Peng, Cheng; Wang, Xiang; Xiao, Ling; Wang, Dengdong; Chen, Jiaxing; Zhang, Haifa; Zhao, Huihong; Li, Shuisheng; Zhang, Yong; Lin, Haoran

2017-08-01

The sex identity of fish can be easily manipulated by exogenous hormones. Treatment with 17-methyltestosterone (MT) has been widely used to induce a male fate, but the molecular and cellular processes underlying sex changes induced by MT treatments and the withdrawal of MT are not well studied. In this study, we systematically investigated gonadal histology, gene expression profiles, sex steroid hormone levels, and cellular changes during sex changes induced by MT-feeding and MT-feeding withdrawal in the protogynous orange-spotted grouper, Epinephelus coioides. Based on gonadal histology, we demonstrated that MT-feeding-induced sex reversal can be divided into early and late phases: in the early phase, male and female germ cells coexist, and MT-feeding withdrawal leads to a female fate; in the late phase, only male germ cells are observed, and MT-feeding withdrawal does not reverse the process, leading to a male fate. In both the early and late phases, cytochrome P450 family19 subfamily A member 1 (cyp19a1a) gene expression increased in response to MT-feeding withdrawal. Finally, by tracing doublesex- and Mab-3-related transcription factor 1 (dmrt1)-expressing cells, we found that gonia-like cells in the germinal epithelium might be the major germ cell sources for developing testes during sex reversal. Collectively, our findings provide insights into the molecular and cellular mechanisms underlying sex changes induced by exogenous hormones. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

CRF2 Receptor Deficiency Eliminates the Long-Lasting Vulnerability of Motivational States Induced by Opiate Withdrawal

PubMed Central

Morisot, Nadège; Rouibi, Khalil; Contarino, Angelo

2015-01-01

Vulnerability to stressful life events is a hallmark of drug dependence that may persist long after cessation of drug intake and dramatically fuel key clinical features, such as deregulated up-shifted motivational states and craving. However, to date, no effective therapy is available for reducing vulnerability to stressful events in former drug users and drug-dependent patients, mostly because of poor knowledge of the mechanisms underlying it. In this study, we report that genetic inactivation of the stress-responsive corticotropin-releasing factor receptor-2 (CRF2−/−) completely eliminates the reemergence of increased nonrewarded nose-pokes, reflecting up-shifted motivational states, triggered by ethological environmental stressors long after cessation of morphine administration in mice. Accordingly, CRF2 receptor deficiency completely abolishes the increase in biomarkers of synthesis of major brain motivational substrates, such as ventral tegmental area (VTA) dopamine (DA) and amygdala γ-aminobutyric acid (GABA) systems, associated with the stress-induced reemergence of up-shifted motivational states long after opiate withdrawal. Nevertheless, neither CRF2 receptor deficiency nor long-term opiate withdrawal affects amygdala CRF or hypothalamus CRF expression, indicating preserved brain stress-coping systems. Moreover, CRF2 receptor deficiency does not influence the locomotor or the anxiety-like effect of long-term opiate withdrawal. Thus, the present results reveal an essential and specific role for the CRF2 receptor in the stress-induced reemergence of up-shifted motivational states and related alterations in brain motivational systems long after opiate withdrawal. These findings suggest new strategies for the treatment of the severe and long-lasting vulnerability that inexorably follows drug withdrawal and hinder drug abstinence. PMID:25672976

BDNF–TrkB signaling in the nucleus accumbens shell of mice has key role in methamphetamine withdrawal symptoms

PubMed Central

Ren, Q; Ma, M; Yang, C; Zhang, J-C; Yao, W; Hashimoto, K

2015-01-01

Depression is a core symptom of methamphetamine (METH) withdrawal during the first several weeks of abstinence. However, the precise mechanisms underlying METH withdrawal symptoms remain unknown. Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), have a role the in pathophysiology of depression. In this study, we examined the role of BDNF–TrkB signaling in different brain regions of male mice with METH withdrawal symptoms. Repeated METH (3 mg kg−1 per day for 5 days) administration to mice caused a long-lasting depression-like behavior including anhedonia. Western blot analysis showed that BDNF levels in the nucleus accumbens (NAc) of METH-treated mice were significantly higher than those of control mice whereas BDNF levels in other regions, including the prefrontal cortex and hippocampus, were not altered. METH-induced depression-like behavior, behavioral sensitization and dendritic changes in the NAc shell were improved by subsequent subchronic administration of TrkB antagonist ANA-12 (0.5 mg kg−1 per day for 14 days), but not TrkB agonist 7,8-dihydroxyflavone (10 mg kg−1 per day for 14 days). In vivo microdialysis showed that METH (1 mg kg−1)-induced dopamine release in NAc shell of METH-treated mice was attenuated after subsequent subchronic ANA-12 administration. Interestingly, a single bilateral infusion of ANA-12 into the NAc shell, but not NAc core, showed a rapid and long-lasting therapeutic effect. However, ketamine and paroxetine had no effect. These findings suggest that increased BDNF–TrkB signaling in the NAc shell has an important role in the behavioral abnormalities after withdrawal from repeated METH administration, and that TrkB antagonists are potential therapeutic drugs for withdrawal symptoms in METH abusers. PMID:26506052

Pressure deflected: Japan and the 1973 Arab oil embargo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burridge, J.M.

1988-01-01

Japanese policy toward the Arab states for the five years before the embargo are compared with the five years that followed. Significant events from October 1973 through the February 1974 Washington Conference are described on a virtually daily basis. The study concludes that the late 1973 oil-supply reduction did not result in significantly greater Japanese political support or economic assistance in the 1974-1978 period. Japan did not even carry the only specific commitment in the November 22 statement - that it would reconsider relations with Israel if that country didn't withdraw from the occupied Arab territories. Many factors contributed tomore » this failure - American counter-pressure, Arab disunity, and a worldwide drop in oil demand. In terms of political demands, neither OAPEC nor any individual Arab state ever articulated any specific actions Japan was to take. Finally, the supply of oil was rapidly depoliticized after 1974.« less

Ordinal Logistic Regression to Detect Differential Item Functioning for Gender in the Institutional Integration Scale

ERIC Educational Resources Information Center

Breidenbach, Daniel H.; French, Brian F.

2011-01-01

Many factors can influence a student's decision to withdraw from college. Intervention programs aimed at retention can benefit from understanding the factors related to such decisions, especially in underrepresented groups. The Institutional Integration Scale (IIS) has been suggested as a predictor of student persistence. Accurate prediction of…

Groundwater quality and simulation of sources of water to wells in the Marsh Creek valley at the U.S. Geological Survey Northern Appalachian Research Laboratory, Tioga County, Pennsylvania

USGS Publications Warehouse

Risser, Dennis W.; Breen, Kevin J.

2012-01-01

This report provides a November 2010 snapshot of groundwater quality and an analysis of the sources of water to wells at the U.S. Geological Survey (USGS) Northern Appalachian Research Laboratory (NARL) near Wellsboro, Pennsylvania. The laboratory, which conducts fisheries research, currently (2011) withdraws 1,000 gallons per minute of high-quality groundwater from three wells completed in the glacial sand and gravel aquifer beneath the Marsh Creek valley; a fourth well that taps the same aquifer provides the potable supply for the facility. The study was conducted to document the source areas and quality of the water supply for this Department of Interior facility, which is surrounded by the ongoing development of natural gas from the Marcellus Shale. Groundwater samples were collected from the four wells used by the NARL and from two nearby domestic-supply wells. The domestic-supply wells withdraw groundwater from bedrock of the Catskill Formation. Samples were analyzed for major ions, nutrients, trace metals, radiochemicals, dissolved gases, and stable isotopes of oxygen and hydrogen in water and carbon in dissolved carbonate to document groundwater quality. Organic constituents (other than hydrocarbon gases) associated with hydraulic fracturing and other human activities were not analyzed as part of this assessment. Results show low concentrations of all constituents. Only radon, which ranged from 980 to 1,310 picocuries per liter, was somewhat elevated. These findings are consistent with the pristine nature of the aquifer in the Marsh Creek valley, which is the reason the laboratory was sited at this location. The sources of water and areas contributing recharge to wells were identified by the use of a previously documented MODFLOW groundwater-flow model for the following conditions: (1) withdrawals of 1,000 to 3,000 gallons per minute from the NARL wells, (2) average or dry hydrologic conditions, and (3) withdrawals of 1,000 gallons per minute from a new well 3,500 feet to the southwest that was drilled to provide water for Marcellus gas-well operations. Results of simulations indicate that during average hydrologic conditions, infiltration from Straight Run, a tributary to Marsh Creek, provides nearly all the water to the NARL wells. During dry conditions, the areas contributing recharge expand such that Asaph Run contributes about half of the water to the NARL wells when withdrawals are 1,000 or 2,000 gallons per minute. The addition of a simulated withdrawal of 1,000 gallons per minute from the nearby new well does not substantially affect the sources of water captured by the NARL wells. These results are subject to some limitations. The water-quality samples represent a snapshot of groundwater chemistry for only one hydrologic condition; the concentrations of some constituents may change temporally. In addition, samples were collected and analyzed for hydrocarbon gases, but not organic constituents associated with hydraulic fracturing; additional sampling for these constituents would provide a more complete water-quality baseline. The sources contributing water to the NARL wells and the new well were simulated by use of a simplified one-layer model of the glacial sand and gravel aquifer for steady-state conditions that in reality are never achieved. Steady-state simulations of dry hydrologic conditions show that it is possible for the NARL wells to capture water from Asaph Run; however, maps of simulated groundwater time-of-travel indicate that a dry period of unusually long duration would be required. A better analysis could be done by recalibrating the groundwater-flow model with a finite-difference grid having multiple layers, cells smaller than the 200-foot by 200-foot cells used in this study, and transient stress periods.

$100 Bills on the Sidewalk: Suboptimal Investment in 401(k) Plans*

PubMed Central

Choi, James J.; Laibson, David; Madrian, Brigitte C.

2010-01-01

We identify employees at seven companies whose 401(k) investment choices are dominated because they are contributing less than the employer matching contribution threshold despite being vested in their match and being able to make penalty-free 401(k) withdrawals for any reason because they are older than 59½. At the average firm, 36% of match-eligible employees over 59½ forego arbitrage profits that average 1.6% of their annual pay, or $507. A survey educating employees about the free lunch they are foregoing raised contribution rates by a statistically insignificant 0.67 percent of income among those completing the survey. PMID:21860536

An integrated assessment of energy-water nexus at the state level in the United States: Projections and analyses under different scenarios through 2095

NASA Astrophysics Data System (ADS)

Liu, L.; Patel, P. L.; Hejazi, M. I.; Kyle, P.; Davies, E. G.; Zhou, Y.; Clarke, L.; Edmonds, J.

2013-12-01

Water withdrawals for thermoelectric power plants account for approximately half of the total water use in the United States. With growing electricity demands in the future and limited water supplies in many water-scarce states in the U.S., grasping the trade-off between energy and water requires an integrated modeling approach that can capture the interactions among energy, water availability, climate, technology, and economic factors at various scales. In this study, the Global Change Assessment Model (GCAM), a technologically-detailed integrated model of the economy, energy, agriculture and land use, water, and climate systems, with 14 geopolitical regions that are further dissaggregated into up to 18 agro-ecological zones, was extended to model the electricity and water systems at the state level in the U.S. More specifically, GCAM was employed to estimate future state-level electricity generation and demands, and the associated water withdrawals and consumptions under a set of six scenarios with extensive levels of details on generation fuel portfolio, cooling technology mix, and water use intensities. The state-level estimates were compared against available inventories where good agreement was achieved on national and regional levels. We then explored the electric-sector water use up to 2095, focusing on implications from: 1) socioeconomics and growing demands, 2) the adoption of climate mitigation policy (e.g., RCP4.5 W/m2 vs. a reference scenario), 3) the transition of cooling systems, 4) constraints on electricity trading across states (full trading vs. limited trading), and 5) the adoption of water saving technologies. Overall, the fast retirement of once-through cooling, together with the gradual transition from fossil fuels dominant to a mixture of different fuels, accelerate the decline of water withdrawals and correspondingly compensate consumptive water use. Results reveal that U.S. electricity generation expands significantly as population grows, while U.S. electric-sector water withdrawals are projected to decline by 8.6% - 89% by 2095 and water consumptions are projected to increase by 14% - 101%. Some regional patterns could be observed when analyzing the state-level results spatially. Under the climate mitigation policy (RCP4.5) scenario, nuclear power plants contribute heavily to total electric-sector water withdrawal and consumption in Eastern U.S., while under the reference scenario, coal power plants are the primary water users in Eastern U.S. In the reference scenario, Eastern U.S. is projected to experience substantial drops in water withdrawals, while the Western U.S. will likely endure a moderate increase over the century. The highly-resolved nature of this study both geographically and technologically provides a useful platform to address scientific and policy relevant and emerging issues at the heart of the water-energy nexus in the U.S. Although this study is focused on the U.S., it is performed in the context of the global framework of GCAM where local changes can propagate to influence decisions in other regions outside of the U.S. and vice versa.

Contributions of climate change and human activities to runoff change in seven typical catchments across China.

PubMed

Zhai, Ran; Tao, Fulu

2017-12-15

Climate change and human activities are two major factors affecting water resource change. It is important to understand the roles of the major factors in affecting runoff change in different basins for watershed management. Here, we investigated the trends in climate and runoff in seven typical catchments in seven basins across China from 1961 to 2014. Then we attributed the runoff change to climate change and human activities in each catchment and in three time periods (1980s, 1990s and 2000s), using the VIC model and long-term runoff observation data. During 1961-2014, temperature increased significantly, while the trends in precipitation were insignificant in most of the catchments and inconsistent among the catchments. The runoff in most of the catchments showed a decreasing trend except the Yingluoxia catchment in the northwestern China. The contributions of climate change and human activities to runoff change varied in different catchments and time periods. In the 1980s, climate change contributed more to runoff change than human activities, which was 84%, 59%, -66%, -50%, 59%, 94%, and -59% in the Nianzishan, Yingluoxia, Xiahui, Yangjiaping, Sanjiangkou, Xixian, and Changle catchment, respectively. After that, human activities had played a more essential role in runoff change. In the 1990s and 2000s, human activities contributed more to runoff change than in the 1980s. The contribution by human activities accounted for 84%, -68%, and 67% in the Yingluoxia, Xiahui, and Sanjiangkou catchment, respectively, in the 1990s; and -96%, -67%, -94%, and -142% in the Nianzishan, Yangjiaping, Xixian, and Changle catchment, respectively, in the 2000s. It is also noted that after 2000 human activities caused decrease in runoff in all catchments except the Yingluoxia. Our findings highlight that the effects of human activities, such as increase in water withdrawal, land use/cover change, operation of dams and reservoirs, should be well managed. Copyright © 2017 Elsevier B.V. All rights reserved.

Contributions of Racial and Sociobehavioral Homophily to Friendship Stability and Quality among Same-Race and Cross-Race Friends

ERIC Educational Resources Information Center

McDonald, Kristina L.; Dashiell-Aje, Ebony; Menzer, Melissa M.; Rubin, Kenneth H.; Oh, Wonjung; Bowker, Julie C.

2013-01-01

The current study examined how racial and sociobehavioral similarities were associated with friendship stability and friendship quality. Cross-race friends were not significantly similar to each other in peer-nominated shyness/withdrawal, victimization, exclusion, and popularity/sociability. Relative to same-race friends, cross-race friends were…

Social Problem Solving in High-Risk Mother-Child Dyads: An Intergenerational Study

ERIC Educational Resources Information Center

Martin, Julie P.; Stack, Dale M.; Serbin, Lisa A.; Schwartzman, Alex E.; Ledingham, Jane

2012-01-01

This study examined the contribution of maternal childhood histories of aggression and social withdrawal to the prediction of mother-child social problem solving in the next generation. Fifty-seven women (M = 37.32 years), previously rated (on a version of the pupil evaluation inventory) by their peers during childhood on measures of aggression…

Nicotine administration in adolescence reprograms the subsequent response to nicotine treatment and withdrawal in adulthood: sex-selective effects on cerebrocortical serotonergic function.

PubMed

Slotkin, Theodore A; Card, Jennifer; Seidler, Frederic J

2014-03-01

Nicotine exposure in adolescence produces lasting changes in subsequent behavioral responses to addictive agents. We gave nicotine to adolescent rats (postnatal days PN30-47), simulating plasma levels in smokers, and then examined the subsequent effects of nicotine given again in adulthood (PN90-107), focusing on cerebrocortical serotonin levels and utilization (turnover) as an index of presynaptic activity of circuits involved in emotional state. Our evaluations encompassed responses during the period of adult nicotine treatment (PN105) and withdrawal (PN110, PN120, PN130), as well as long-term changes (PN180). In males, prior exposure to nicotine in adolescence greatly augmented the increase in serotonin turnover evoked by nicotine given in adulthood, an interaction that was further exacerbated during withdrawal. The effect was sufficiently large that it led to significant depletion of serotonin stores, an effect that was not seen with nicotine given alone in either adolescence or adulthood. In females, adolescent nicotine exposure blunted or delayed the spike in serotonin turnover evoked by withdrawal from adult nicotine treatment, a totally different effect from the interaction seen in males. Combined with earlier work showing persistent dysregulation of serotonin receptor expression and receptor coupling, the present results indicate that adolescent nicotine exposure reprograms future responses of 5HT systems to nicotine, changes that may contribute to life-long vulnerability to relapse and re-addiction. Copyright © 2014 Elsevier Inc. All rights reserved.

Improvement of ketamine-induced social withdrawal in rats: the role of 5-HT7 receptors.

PubMed

Hołuj, Małgorzata; Popik, Piotr; Nikiforuk, Agnieszka

2015-12-01

Social withdrawal, one of the core negative symptoms of schizophrenia, can be modelled in the social interaction (SI) test in rats using N-methyl-D-aspartate receptor glutamate receptor antagonists. We have recently shown that amisulpride, an antipsychotic with a high affinity for serotonin 5-HT7 receptors, reversed ketamine-induced SI deficits in rats. The aim of the present study was to further elucidate the potential involvement of 5-HT7 receptors in the prosocial action of amisulpride. Acute administration of amisulpride (3 mg/kg) and SB-269970 (1 mg/kg), a 5-HT7 receptor antagonist, reversed ketamine-induced social withdrawal, whereas sulpiride (20 or 30 mg/kg) and haloperidol (0.2 mg/kg) were ineffective. The 5-HT7 receptor agonist AS19 (10 mg/kg) abolished the prosocial efficacy of amisulpride (3 mg/kg). The coadministration of an inactive dose of SB-269970 (0.2 mg/kg) showed the prosocial effects of inactive doses of amisulpride (1 mg/kg) and sulpiride (20 mg/kg). The anxiolytic chlordiazepoxide (2.5 mg/kg) and the antidepressant fluoxetine (2.5 mg/kg) were ineffective in reversing ketamine-induced SI deficits. The present study suggests that the antagonism of 5-HT7 receptors may contribute towards the mechanisms underlying the prosocial action of amisulpride. These results may have therapeutic implications for the treatment of negative symptoms in schizophrenia and other disorders characterized by social withdrawal.

Assessment and Implications of Social Withdrawal Subtypes in Young Chinese Children: The Chinese Version of the Child Social Preference Scale.

PubMed

Li, Yan; Zhu, Jing-Jing; Coplan, Robert J; Gao, Zhu-Qing; Xu, Pin; Li, Linhui; Zhang, Huimin

2016-01-01

The authors' goals were to evaluate the psychometric properties of the Chinese version of the Child Social Preference Scale (CSPS; R. J. Coplan, K. Prakash, K. O'Neil, & M. Armer, 2004) and examine the links between both shyness and unsociability and indices of socioemotional functioning in young Chinese children. Participants included of two samples recruited from kindergarten classes in two public schools in Shanghai, China. Both samples included children 3-5 years old (Sample 1: n = 350, Mage = 4.72 years, SD = 0.58 years; Sample 2: n = 129, Mage = 4.40 years, SD = 0.58 years). In both samples, mothers rated children's social withdrawal using the newly created Chinese version of the CSPS, and in Sample 2, teachers also provided ratings of socioemotional functioning. Consistent with previous findings from other cultures, results from factor analyses suggested a 2-factor model for the CSPS (shyness and unsociability) among young children in China. In contrast to findings from North America, child shyness and unsociability were associated with socioemotional difficulties in kindergarten. Some gender differences were also noted. Results are discussed in terms of the assessment and implications of social withdrawal in early childhood in China.

A Two-Factor Model Better Explains Heterogeneity in Negative Symptoms: Evidence from the Positive and Negative Syndrome Scale.

PubMed

Jang, Seon-Kyeong; Choi, Hye-Im; Park, Soohyun; Jaekal, Eunju; Lee, Ga-Young; Cho, Young Il; Choi, Kee-Hong

2016-01-01

Acknowledging separable factors underlying negative symptoms may lead to better understanding and treatment of negative symptoms in individuals with schizophrenia. The current study aimed to test whether the negative symptoms factor (NSF) of the Positive and Negative Syndrome Scale (PANSS) would be better represented by expressive and experiential deficit factors, rather than by a single factor model, using confirmatory factor analysis (CFA). Two hundred and twenty individuals with schizophrenia spectrum disorders completed the PANSS; subsamples additionally completed the Brief Negative Symptom Scale (BNSS) and the Motivation and Pleasure Scale-Self-Report (MAP-SR). CFA results indicated that the two-factor model fit the data better than the one-factor model; however, latent variables were closely correlated. The two-factor model's fit was significantly improved by accounting for correlated residuals between N2 (emotional withdrawal) and N6 (lack of spontaneity and flow of conversation), and between N4 (passive social withdrawal) and G16 (active social avoidance), possibly reflecting common method variance. The two NSF factors exhibited differential patterns of correlation with subdomains of the BNSS and MAP-SR. These results suggest that the PANSS NSF would be better represented by a two-factor model than by a single-factor one, and support the two-factor model's adequate criterion-related validity. Common method variance among several items may be a potential source of measurement error under a two-factor model of the PANSS NSF.

Estimated use of water in the United States in 2015

USGS Publications Warehouse

Dieter, Cheryl A.; Maupin, Molly A.; Caldwell, Rodney R.; Harris, Melissa A.; Ivahnenko, Tamara I.; Lovelace, John K.; Barber, Nancy L.; Linsey, Kristin S.

2018-06-19

Water use in the United States in 2015 was estimated to be about 322 billion gallons per day (Bgal/d), which was 9 percent less than in 2010. The 2015 estimates put total withdrawals at the lowest level since before 1970, following the same overall trend of decreasing total withdrawals observed from 2005 to 2010. Freshwater withdrawals were 281 Bgal/d, or 87 percent of total withdrawals, and saline-water withdrawals were 41.0 Bgal/d, or 13 percent of total withdrawals. Fresh surface-water withdrawals (198 Bgal/d) were 14 percent less than in 2010, and fresh groundwater withdrawals (82.3 Bgal/day) were about 8 percent greater than in 2010. Saline surface-water withdrawals were 38.6 Bgal/d, or 14 percent less than in 2010. Total saline groundwater withdrawals in 2015 were 2.34 Bgal/d, mostly for mining use.Thermoelectric power and irrigation remained the two largest uses of water in 2015, and total withdrawals decreased for thermoelectric power but increased for irrigation. With­drawals in 2015 for thermoelectric power were 18 percent less and withdrawals for irrigation were 2 percent greater than in 2010. Similarly, other uses showed reductions compared to 2010, specifically public supply (–7 percent), self-supplied domestic (–8 percent), self-supplied industrial (–9 percent), and aquaculture (–16 percent). In addition to irrigation (2 percent), mining (1 percent) reported larger withdrawals in 2015 than in 2010. Livestock withdrawals remained essentially the same in 2015 compared to 2010 (0 percent change). Thermoelectric power, irrigation, and public-supply withdrawals accounted for 90 percent of total withdrawals in 2015.Withdrawals for thermoelectric power were 133 Bgal/d in 2015 and represented the lowest levels since before 1970. Surface-water withdrawals accounted for more than 99 percent of total thermoelectric-power withdrawals, and 72 percent of those surface-water withdrawals were from freshwater sources. Saline surface-water withdrawals for thermoelectric power accounted for 97 percent of total saline surface-water withdrawals for all uses. Thermoelectric-power withdrawals accounted for 41 percent of total withdrawals for all uses, and freshwater withdrawals for thermoelectric power accounted for 34 percent of the total freshwater withdrawals for all uses. Total consumptive use for thermoelectric power was 4.31 Bgal/d in 2015 or 3 percent of the total thermoelectric-power withdrawals.Irrigation withdrawals were 118 Bgal/d in 2015, an increase of 2 percent from 2010 (116 Bgal/d), but were approximately equal to withdrawals estimated in the 1960s. Irrigation withdrawals, all freshwater, accounted for 42 percent of total freshwater withdrawals for all uses and 64 percent of total freshwater withdrawals for all uses excluding thermoelectric power. Surface-water withdrawals (60.9 Bgal/d) accounted for 52 percent of the total irrigation withdrawals, or about 8 percent less than in 2010. Ground­water withdrawals for irrigation were 57.2 Bgal/d in 2015, about 16 percent more than in 2010. About 63,500 thousand acres (or 63.5 million acres) were irrigated in 2015, an increase from 2010 of about 1,130 thousand acres (2 percent). The number of acres irrigated using sprinkler and microirrigation systems accounted for 63 percent of the total irrigated lands in 2015. Total consumptive use for irrigation was 73.2 Bgal/d in 2015 or 62 percent of the total use (withdrawals and reclaimed wastewater).Public-supply withdrawals in 2015 were 39.0 Bgal/d, or 7 percent less than in 2010, continuing the declines observed from 2005 to 2010. Total population in the United States increased from 312.6 million people in 2010 to 325.0 million people in 2015, an increase of 4 percent. Public-supply withdrawals accounted for 14 percent of the total freshwater withdrawals for all uses and 21 percent of freshwater with­drawals for all uses, excluding thermoelectric power. The number of people that received potable water from public-supply facilities in 2015 was 283 million, or about 87 percent of the total United States population. This percentage is 1 percent greater than in 2010. Self-supplied domestic withdrawals were 3.26 Bgal/d, or 8 percent less than in 2010. More than 98 percent of the self-supplied domestic withdrawals were from groundwater sources.Self-supplied industrial withdrawals were 14.8 Bgal/d in 2015, a 9 percent decline from 2010, continuing the downward trend since the peak of 47 Bgal/d in 1970. Total self-supplied industrial withdrawals were 5 percent of total withdrawals for all uses and 8 percent of total withdrawals for all uses, excluding thermoelectric power. Most of the total self-supplied industrial withdrawals were from surface-water sources (82 percent), and nearly all (94 percent) of those surface-water withdrawals were from freshwater sources. Nearly all of the groundwater withdrawals for self-supplied industrial use (98 percent) were from freshwater sources.Total aquaculture withdrawals were 7.55 Bgal/d in 2015, or 16 percent less than in 2010, and surface water was the primary source (79 percent). Most of the surface-water withdrawals occurred at facilities that operated flow-through raceways, which returned the water to the source directly after use. Aquaculture withdrawals accounted for 2 percent of the total withdrawals for all uses and 4 percent of the total withdrawals for all uses, excluding thermoelectric.Total mining withdrawals in 2015 were 4.00 Bgal/d, or about 1 percent of total withdrawals from all uses and 2 percent of total withdrawals from all uses, excluding thermoelectric. Mining withdrawals increased 1 percent from 2010 to 2015. Groundwater withdrawals accounted for 72 percent of the total mining withdrawals, and most of the groundwater was saline (65 percent). Most (77 percent) of the surface-water withdrawals for mining was freshwater.Livestock withdrawals in 2015 were 2.00 Bgal/d, the same as in 2010. All livestock withdrawals were from freshwater sources, mostly from groundwater (62 percent). Livestock withdrawals accounted for about 1 percent of total freshwater withdrawals for all uses, excluding thermoelectric power.In 2015, more than 50 percent of the total withdrawals in the United States were accounted for by 12 States (California, Texas, Idaho, Florida, Arkansas, New York, Illinois, Colorado, North Carolina, Michigan, Montana, and Nebraska). California accounted for almost 9 percent of the total withdrawals and 9 percent of freshwater withdrawals in the United States, predominantly for irrigation. Texas accounted for almost 7 percent of total withdrawals, predominantly for thermoelectric power, irrigation, and public supply. Florida accounted for 23 percent of the total saline-water withdrawals in the United States, mostly from surface-water sources for thermoelectric power. Texas and California accounted for 59 percent of the total saline groundwater withdrawals in the United States, mostly for mining.

Modulating weak interactions for molecular recognition: a dynamic combinatorial analysis for assessing the contribution of electrostatics to the stability of CH-π bonds in water.

PubMed

Jiménez-Moreno, Ester; Gómez, Ana M; Bastida, Agatha; Corzana, Francisco; Jiménez-Oses, Gonzalo; Jiménez-Barbero, Jesús; Asensio, Juan Luis

2015-03-27

Electrostatic and charge-transfer contributions to CH-π complexes can be modulated by attaching electron-withdrawing substituents to the carbon atom. While clearly stabilizing in the gas phase, the outcome of this chemical modification in water is more difficult to predict. Herein we provide a definitive and quantitative answer to this question employing a simple strategy based on dynamic combinatorial chemistry. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sex-Related Factors and Attrition Among College Women

ERIC Educational Resources Information Center

Cope, Robert G.

1970-01-01

Data reveals that females who appear to be less cultured (music, art, poetry), less attractive, and less skilled verbally in a cultured and socially competitive environment are inclined to be less successful and withdraw. (Author)

Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

PubMed

Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

2015-09-14

Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine

PubMed Central

Fitzgerald, Paul J.

2013-01-01

A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general. PMID:24151426

Status of ground-water resources at U.S. Navy Support Facility, Diego Garcia; summary of hydrologic and climatic data, January 1994 through June 1996

USGS Publications Warehouse

Torikai, J.D.

1996-01-01

This report describes the status of ground-water resources at U.S. Navy Support Facility, Diego Garcia. Data presented are from January 1994 through June 1996, with a focus on data from April through June 1996 (second quarter of 1996). A complete database of ground-water withdrawals and chloride-concentration records since 1985 is maintained by the U.S. Geological Survey. Cumulative rainfall for April through June 1996 was 22.64 inches, which is 12 percent more than the mean cumulative rainfall of 20.21 inches for April through June. The period April through June is part of the annual dry season. Ground-water withdrawal during April through June 1996 averaged 1,048,000 gallons per day. Withdrawal for the same 3 months in 1995 averaged 833,700 gallons per day. Withdrawal patterns during the second quarter of 1996 did not change significantly since 1991, with the Cantonment and Air Operations areas supplying about 99 percent of total islandwide pumpage. At the end of June 1996, the chloride concentration of water from the elevated tanks at Cantonment and Air Operations were 52 and 80 milligrams per liter, respectively. The chloride data from all five production areas showed no significant upward or downward trends throughout the second quarter of 1996. Potable levels of chloride concentrations have been maintained by adjusting individual pumping rates, and also because of the absence of long-term droughts. Chloride concentration of ground water in monitoring wells at Cantonment and Air Operations also showed no significant trends throughout the second quarter of 1996. Chloride concentrations have been about the same since the last quarter of 1995. A fuel-pipeline leak at Air Operations in May 1991 decreased total islandwide withdrawals by 15 percent. This lost pumping capacity is being offset by increased pumpage at Cantonment. Six wells do not contribute to the water supply because they are being used to hydraulically divert fuel migration away from water-supply wells by a program of ground-water withdrawal and injection.

Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial.

PubMed

Rich, Josiah D; McKenzie, Michelle; Larney, Sarah; Wong, John B; Tran, Liem; Clarke, Jennifer; Noska, Amanda; Reddy, Manasa; Zaller, Nickolas

2015-07-25

Methadone is an effective treatment for opioid dependence. When people who are receiving methadone maintenance treatment for opioid dependence are incarcerated in prison or jail, most US correctional facilities discontinue their methadone treatment, either gradually, or more often, abruptly. This discontinuation can cause uncomfortable symptoms of withdrawal and renders prisoners susceptible to relapse and overdose on release. We aimed to study the effect of forced withdrawal from methadone upon incarceration on individuals' risk behaviours and engagement with post-release treatment programmes. In this randomised, open-label trial, we randomly assigned (1:1) inmates of the Rhode Island Department of Corrections (RI, USA) who were enrolled in a methadone maintenance-treatment programme in the community at the time of arrest and wanted to remain on methadone treatment during incarceration and on release, to either continuation of their methadone treatment or to usual care--forced tapered withdrawal from methadone. Participants could be included in the study only if their incarceration would be more than 1 week but less than 6 months. We did the random assignments with a computer-generated random permutation, and urn randomisation procedures to stratify participants by sex and race. Participants in the continued-methadone group were maintained on their methadone dose at the time of their incarceration (with dose adjustments as clinically indicated). Patients in the forced-withdrawal group followed the institution's standard withdrawal protocol of receiving methadone for 1 week at the dose at the time of their incarceration, then a tapered withdrawal regimen (for those on a starting dose >100 mg, the dose was reduced by 5 mg per day to 100 mg, then reduced by 3 mg per day to 0 mg; for those on a starting dose >100 mg, the dose was reduced by 3 mg per day to 0 mg). The main outcomes were engagement with a methadone maintenance-treatment clinic after release from incarceration and time to engagement with methadone maintenance treatment, by intention-to-treat and as-treated analyses, which we established in a follow-up interview with the participants at 1 month after their release from incarceration. Our study paid for 10 weeks of methadone treatment after release if participants needed financial help. This trial is registered with ClinicalTrials.gov, number NCT01874964. Between June 14, 2011, and April 3, 2013, we randomly assigned 283 prisoners to our study, 142 to continued methadone treatment, and 141 to forced withdrawal from methadone. Of these, 60 were excluded because they did not fit the eligibility criteria, leaving 114 in the continued-methadone group and 109 in the forced-withdrawal group (usual care). Participants assigned to continued methadone were more than twice as likely than forced-withdrawal participants to return to a community methadone clinic within 1 month of release (106 [96%] of 110 in the continued-methadone group compared with 68 [78%] of 87 in the forced-withdrawal group; adjusted hazard ratio [HR] 2·04, 95% CI 1·48-2·80). We noted no differences in serious adverse events between groups. For the continued-methadone and forced-withdrawal groups, the number of deaths were one and zero, non-fatal overdoses were one and two, admissions to hospital were one and four; and emergency-room visits were 11 and 16, respectively. Although our study had several limitations--eg, it only included participants incarcerated for fewer than 6 months, we showed that forced withdrawal from methadone on incarceration reduced the likelihood of prisoners re-engaging in methadone maintenance after their release. Continuation of methadone maintenance during incarceration could contribute to greater treatment engagement after release, which could in turn reduce the risk of death from overdose and risk behaviours. National Institute on Drug Abuse and the Lifespan/Tufts/Brown Center for AIDS Research from the National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial

PubMed Central

Rich, Josiah D; McKenzie, Michelle; Larney, Sarah; Wong, John B; Tran, Liem; Clarke, Jennifer; Noska, Amanda; Reddy, Manasa; Zaller, Nickolas

2015-01-01

Summary Background Methadone is an effective treatment for opioid dependence. When people who are receiving methadone maintenance treatment for opioid dependence are incarcerated in prison or jail, most US correctional facilities discontinue their methadone treatment, either gradually, or more often, abruptly. This discontinuation can cause uncomfortable symptoms of withdrawal and renders prisoners susceptible to relapse and overdose on release. We aimed to study the effect of forced withdrawal from methadone upon incarceration on individuals’ risk behaviours and engagement with post-release treatment programmes. Methods In this randomised, open-label trial, we randomly assigned (1:1) inmates of the Rhode Island Department of Corrections (RI, USA) who were enrolled in a methadone maintenance-treatment programme in the community at the time of arrest and wanted to remain on methadone treatment during incarceration and on release, to either continuation of their methadone treatment or to usual care—forced tapered withdrawal from methadone. Participants could be included in the study only if their incarceration would be more than 1 week but less than 6 months. We did the random assignments with a computer-generated random permutation, and urn randomisation procedures to stratify participants by sex and race. Participants in the continued-methadone group were maintained on their methadone dose at the time of their incarceration (with dose adjustments as clinically indicated). Patients in the forced-withdrawal group followed the institution’s standard withdrawal protocol of receiving methadone for 1 week at the dose at the time of their incarceration, then a tapered withdrawal regimen (for those on a starting dose >100 mg, the dose was reduced by 5 mg per day to 100 mg, then reduced by 3 mg per day to 0 mg; for those on a starting dose ≤100 mg, the dose was reduced by 3 mg per day to 0 mg). The main outcomes were engagement with a methadone maintenance-treatment clinic after release from incarceration and time to engagement with methadone maintenance treatment, by intention-to-treat and as-treated analyses, which we established in a follow-up interview with the participants at 1 month after their release from incarceration. Our study paid for 10 weeks of methadone treatment after release if participants needed financial help. This trial is registered with ClinicalTrials.gov, number NCT01874964. Findings Between June 14, 2011, and April 3, 2013, we randomly assigned 283 prisoners to our study, 142 to continued methadone treatment, and 141 to forced withdrawal from methadone. Of these, 60 were excluded because they did not fit the eligibility criteria, leaving 114 in the continued-methadone group and 109 in the forced-withdrawal group (usual care). Participants assigned to continued methadone were more than twice as likely than forced-withdrawal participants to return to a community methadone clinic within 1 month of release (106 [96%] of 110 in the continued-methadone group compared with 68 [78%] of 87 in the forced-withdrawal group; adjusted hazard ratio [HR] 2·04, 95% CI 1·48–2·80). We noted no differences in serious adverse events between groups. For the continued-methadone and forced-withdrawal groups, the number of deaths were one and zero, non-fatal overdoses were one and two, admissions to hospital were one and four; and emergency-room visits were 11 and 16, respectively. Interpretation Although our study had several limitations—eg, it only included participants incarcerated for fewer than 6 months, we showed that forced withdrawal from methadone on incarceration reduced the likelihood of prisoners re-engaging in methadone maintenance after their release. Continuation of methadone maintenance during incarceration could contribute to greater treatment engagement after release, which could in turn reduce the risk of death from overdose and risk behaviours. PMID:26028120

78 FR 20160 - Self-Regulatory Organizations; Chicago Mercantile Exchange Inc.; Notice of Withdrawal of Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

... change to make adjustments to the liquidity risk factor component of its credit default swap (``CDS'') margin model. The proposed rule change would permit CME to use an index portfolio's market risk rather... Liquidity Factor of CME's CDS Margin Methodology March 28, 2013. On December 10, 2012, Chicago Mercantile...

Fight Dispersion through Education: The Results of The First Cycle of the NoOut Project

ERIC Educational Resources Information Center

Batini, Federico; Bartolucci, Marco; De Carlo, Ermelinda

2017-01-01

Dropping out of school can involve several internal and external factors. Regarding internal factors, learning difficulties and the experience of failure could trigger the withdrawal of commitment, rejection of and resistance to school, as well as a general perception of inadequacy. Here, we show the results of a series of interventions…

Water use and quality of fresh surface-water resources in the Barataria-Terrebonne Basins, Louisiana

USGS Publications Warehouse

Johnson-Thibaut, Penny M.; Demcheck, Dennis K.; Swarzenski, Christopher M.; Ensminger, Paul A.

1998-01-01

Approximately 170 Mgal/d (million gallons per day) of ground- and surface-water was withdrawn from the Barataria-Terrebonne Basins in 1995. Of this amount, surface water accounted for 64 percent ( 110 MgaVd) of the total withdrawal rates in the basins. The largest surface-water withdrawal rates were from Bayou Lafourche ( 40 Mgal/d), Bayou Boeuf ( 14 MgaVd), and the Gulf Intracoastal Waterway (4.2 Mgal/d). The largest ground-water withdrawal rates were from the Mississippi River alluvial aquifer (29 Mgal/d), the Gonzales-New Orleans aquifer (9.5 Mgal/d), and the Norco aquifer (3.6 MgaVd). The amounts of water withdrawn in the basins in 1995 differed by category of use. Public water suppliers within the basins withdrew 41 Mgal/d of water. The five largest public water suppliers in the basins withdrew 30 Mgal/d of surface water: Terrebonne Waterworks District 1 withdrew the largest amount, almost 15 MgaVd. Industrial facilities withdrew 88 Mgal/d, fossil-fuel plants withdrew 4.7 MgaVd, and commercial facilities withdrew 0.67 MgaVd. Aggregate water-withdrawal rates, compiled by parish for aquaculture (37 Mgal/d), livestock (0.56 Mgal/d), rural domestic (0.44 MgaVd), and irrigation uses (0.54 MgaVd), totaled about 38 MgaVd in the basins. Ninety-five percent of aquaculture withdrawal rates, primarily for crawfish and alligator farming, were from surface-water sources. >br> Total water-withdrawal rates increased 221 percent from 1960–95. Surface-water withdrawal rates have increased by 310 percent, and ground-water withdrawal rates have increased by 133 percent. The projection for the total water-withdrawal rates in 2020 is 220 MgaVd, an increase of 30 percent from 1995. Surface-water withdrawal rates would account for 59 percent of the total, or 130 Mgal/d. Surface-water withdrawal rates are projected to increase by 20 percent from 1995 to 2020. Analysis of water-quality data from the Mississippi River indicates that the main threats to surface water resources are from the herbicide atrazine and excessive nutrients. Atrazine concentrations in the Mississippi River at Baton Rouge briefly exceed the U.S. Environmental Protection Agency maximum contaminant level of 3.0 micrograms per liter during periods in the late spring and early summer. Trace metals in bottom material collected from Bayou Lafourche indicate that the reach of Bayou Lafourche from Donaldsonville to Golden Meadow is adversely affected by low-level contamination. Dissolved nitrate had a mean concentration of 1.4 milligrams per liter in the Mississippi River near Bayou Lafourche and can contribute to excessive plant growth. Long-term salinity records near Bayou Lafourche indicate no pronounced trends, with the exception of the Gulf Intracoastal Waterway at Houma. At this site, salinities remained low until 1961, when the Gulf Intracoastal Waterway was connected to the Gulf of Mexico by the Houma Navigation Canal. The sources of saltwater are variable. Some saltwater has entered Bayou Lafourche south of the Gulf Intracoastal Waterway; at other times saltwater has moved up the Houma Navigation Canal and has flowed east in the Gulf Intracoastal Waterway, north into Company Canal, and southeast in Bayou Lafourche towards Larose, Louisiana.

Alcohol and Alzheimer's Disease-Does Alcohol Dependence Contribute to Beta-Amyloid Deposition, Neuroinflammation and Neurodegeneration in Alzheimer's Disease?

PubMed

Venkataraman, Ashwin; Kalk, Nicola; Sewell, Gavin; Ritchie, Craig W; Lingford-Hughes, Anne

2017-03-09

To investigate the underlying neurobiology between alcohol use, misuse and dependence and cognitive impairment, particularly Alzheimer's disease (AD). Review of the literature using searches of Medline, Pubmed, EMBASE, PsycInfo, and meeting abstracts and presentations. The role of alcohol as a risk factor and contributor for cognitive decline associated with AD has received little attention. This is despite the high prevalence of alcohol use, the potential reversibility of a degree of cognitive impairment and the global burden of AD. Until now the focus has largely been on the toxic effects of alcohol, neuronal loss and the role of thiamine. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. We describe the common underlying neurobiology in alcohol and AD, and examine ways alcohol likely contributes to neuroinflammation directly via stimulation of Toll-like receptors and indirectly from small bowel changes, hepatic changes, withdrawal and traumatic brain injury to the pathogenesis of AD. Alcohol use, misuse and dependence cause cognitive impairment. We propose alcohol adds to the cognitive burden seen in dementia through additional mechanisms to neurodegenerative processes or may contribute at various mechanistic points in the genesis and sustenance of AD pathology via neuroinflammation. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Evaluation of the effect of intensity of care on mortality after traumatic brain injury

PubMed Central

Thompson, Hilaire J.; Rivara, Frederick P.; Jurkovich, Gregory J.; Wang, Jin; Nathens, Avery B.; MacKenzie, Ellen J.

2008-01-01

Objectives To evaluate the effect of age on intensity of care provided to traumatically brain-injured adults and to determine the influence of intensity of care on mortality at discharge and 12 months postinjury, controlling for injury severity. Design Cohort study using the National Study on the Costs and Outcomes of Trauma (NSCOT) database. Risk ratio and Poisson regression analyses were performed using data weighted according to the population of eligible patients. Setting and Patients A total of 18 level 1 and 51 level 2 non-trauma centers located in 14 states in the United States and 1,776 adults aged 25−84 yrs with a diagnosis of traumatic brain injury. Measurements Injury severity was determined by the motor component of the Glasgow Coma Scale score, the Injury Severity Score, pupillary reactivity, and presence of midline shift. Factors evaluated as contributing to intensity of care included: admission to the intensive care unit, mechanical ventilation, placement of an intracranial pressure monitor, placement of a jugular bulb catheter, placement of a pulmonary artery catheter, critical care consultation, the number of specialty care consultations, mannitol use, treatment with barbiturate coma, decompressive craniectomy, number of nonneurosurgical procedures performed, the presence of a do-not-resuscitate order, and withdrawal of therapy. Main Results Controlling for injury-related factors, sex, and comorbidity, as age increased, the overall likelihood of receiving various interventions decreased. After controlling for injury severity, sex, and comorbidity, factors associated with higher risk of in-hospital death were: being aged 75−84 yrs (relative risk [RR] 1.32, 95% confidence interval [CI] 1.13, 1.55), pulmonary artery catheter use (RR 1.56, 95% CI 1.30, 1.86), intubation (RR 4.17, 95% CI 2.28, 7.61), the presence of a do-not-resuscitate order (RR 3.21, 95% CI 2.21, 4.65), and withdrawal of therapy (RR 2.33, 95% CI 1.69, 3.23). In contrast, a higher number of specialty care consultations (surgical consults: RR 0.63, 95% CI 0.54, 0.74; medical consults: RR 0.87, 95% CI 0.79, 0.95; and other consults: RR 0.43, 95% CI 0.26, 0.69) were associated with decreased risk of death. The results were similar for factors associated with death at 12 months, with the exception that the number of medical consultations was not significant, whereas the number of nonneurosurgical procedures performed was associated with lower risk of death (RR 0.96, 95% CI 0.92, 0.99), as was obtaining critical care consultation services (RR 0.84, 95% CI 0.71, 1.0). Conclusions There is a lower intensity of care provided to older adults with traumatic brain injury. Although the specific contributions of specialists to patient management are unknown, their consultation was associated with decreased risk of in-hospital death and death within 12 months. It is important that careproviders have an increased awareness of the potential contribution of multidisciplinary clinical decision making to patient outcomes in older traumatically brain-injured patients. PMID:18007264

The Perceptions of Fair Interpersonal Treatment Scale: development and validation of a measure of interpersonal treatment in the workplace.

PubMed

Donovan, M A; Drasgow, F; Munson, L J

1998-10-01

The Perceptions of Fair Interpersonal Treatment (PFIT) scale was designed to assess employees' perceptions of the interpersonal treatment in their work environment. Analyses of the factor structure and reliability of this new instrument indicate that the PFIT scale is a reliable instrument composed of 2 factors: supervisor treatment and coworker treatment. It was hypothesized that the PFIT scale would be positively correlated with job satisfaction variables and negatively correlated with work withdrawal, job withdrawal, experiences of sexual harassment, and an organization's tolerance of sexual harassment. Results based on 509 employees in a private-sector organization and 217 female faculty and staff members at a large midwestern university supported these hypotheses. Arguments that common method variance and employees' dispositions are responsible for the significant correlations between the PFIT scale and other job-related variables were eliminated. The implications of these results are discussed.

Organic brain syndrome in rheumatoid arthritis following corticosteroid withdrawal.

PubMed

Gupta, V P; Ehrlich, G E

1976-01-01

Six patients with seropositive nodule-forming rheumatoid arthritis developed severe central nervous system manifestations consistent with a diagnosis of organic brain syndrome. Organic brain syndrome occurred while 5 of these patients were undergoing corticosteroid withdrawal after prolonged administration. Neuropsychiatric symptoms rapidly cleared, responding to reinstitution of oral or parenteral corticosteroids in large doses in 4 patients, to increase in dosage in 1 patient, and to no drug therapy in the remaining 1. Marked reduction in rheumatoid factor in sera and demonstration of IgM deposits in the choroid plexus in 1 of the patients raised the possibility of immune complex-mediated central nervous system vasculitis.

A comprehensive surface-groundwater flow model

NASA Astrophysics Data System (ADS)

Arnold, Jeffrey G.; Allen, Peter M.; Bernhardt, Gilbert

1993-02-01

In this study, a simple groundwater flow and height model was added to an existing basin-scale surface water model. The linked model is: (1) watershed scale, allowing the basin to be subdivided; (2) designed to accept readily available inputs to allow general use over large regions; (3) continuous in time to allow simulation of land management, including such factors as climate and vegetation changes, pond and reservoir management, groundwater withdrawals, and stream and reservoir withdrawals. The model is described, and is validated on a 471 km 2 watershed near Waco, Texas. This linked model should provide a comprehensive tool for water resource managers in development and planning.

The Developmental Origins of Cognitive Vulnerability to Depression: Temperament, Parenting, and Negative Life Events in Childhood as Contributors to Negative Cognitive Style

ERIC Educational Resources Information Center

Mezulis, Amy H.; Hyde, Janet Shibley; Abramson, Lyn Y.

2006-01-01

Cognitive models of depression have been well supported with adults, but the developmental origins of cognitive vulnerability are not well understood. The authors hypothesized that temperament, parenting, and negative life events in childhood would contribute to the development of cognitive style, with withdrawal negativity and negative parental…

Borderline Symptoms and Suicidality/Self-injury in Late Adolescence: Prospectively Observed Relationship Correlates in Infancy and Childhood

PubMed Central

Lyons-Ruth, Karlen; Bureau, Jean-Francois; Holmes, Bjarne; Easterbrooks, Ann; Brooks, Nancy Hall

2012-01-01

The primary objective was to assess whether prospectively observed quality of parent-child interaction in infancy and middle childhood contributed to the prediction of borderline symptoms and recurrent suicidality/self-injury in late adolescence. Adolescents (mean 19.9 years) from 56 families participating in a longitudinal study since infancy (retention rate 74%) were assessed on the SCID-II for symptoms of borderline personality disorder, including suicidality/self-injury. Early clinical risk was indexed by clinical referral to parent-infant services. Attachment security and parent-child interaction were assessed from videotape at 18 months and 8 years. Severity of childhood abuse was rated from interview and self-report measures. Maternal withdrawal in infancy was a significant predictor of both borderline symptoms and suicidality/self-injury in late adolescence. Disorganizedcontrolling child behavior at age 8 contributed independently to the prediction of borderline symptoms. The effect of maternal withdrawal was independent of, and additive to, variability explained by severity of childhood abuse. Borderline symptoms and suicidality/self-injury may be preceded developmentally by disturbed interactions as early as 18 months of age. A parent-child transactional model is proposed to account for the findings. PMID:23123044

Antinociception induced by chronic exposure of rats to cigarette smoke.

PubMed

Anderson, Kenton L; Pinkerton, Kent E; Uyeminami, Dale; Simons, Christopher T; Carstens, Mirela Iodi; Carstens, E

2004-08-05

To investigate if chronic exposure to cigarette smoke induces analgesia, rats were exposed to concentrated cigarette smoke in an environmental chamber over four successive 5-day blocks (6 h/day), with 2 smoke-free days between blocks. A control group was exposed to room air. Tail flick latencies increased significantly (analgesia) during each smoke exposure block, with a relative decline in analgesia across blocks (tolerance) and a return to control levels during the first three smoke-free interludes while remaining higher after the conclusion of the 4-week exposure period. Mechanical (von Frey) withdrawal thresholds declined over time in smoke-exposed and control groups, with the smoke-exposed group showing significantly lower thresholds. Plasma nicotine reached 95.4 +/- 32 (S.D.) ng/ml at the end of weekly smoke exposure and declined to 44.9 +/- 10.6 ng/ml 24 h after withdrawal. Rats lost weight during smoke exposure and quickly regained weight during smoke-free interludes and at the cessation of smoke exposure. Analgesia may contribute to the initiation of smoking, and rapid reversal of the analgesic effect following acute exposure may contribute to the difficulty in quitting smoking.

Legislation affecting governmental assistance for children of parents with substance use: a policy analysis of social justice.

PubMed

Raynor, Phyllis; Williams, Pamela Holtzclaw

2012-11-01

There is legislation that withdraws governmental assistance where parents are using drugs. Social justice is an important consideration in any policy that modifies governmental assistance that benefits vulnerable children. The purpose of this policy analysis is to analyze identified legislation that effect governmental assistance for children in response to parents' substance misuse. A selective review of data-driven studies examined findings describing actual or potential effects on children of legislation targeting parental substance misuse. Challenges in design, processes, and implementation contribute to poor child outcomes. Identifiable constructs of social justice were missing in the reviewed legislation. Social injustice is a potential outcome for children when legislative intent focuses solely on addressing parental drug behaviors. Legislative alternatives to withdrawing support can address substance abuse while maintaining health promotion for these vulnerable children.

Narcotic addiction, pregnancy, and the newborn.

PubMed

Fricker, H S; Segal, S

1978-04-01

Between 1954 and 1973, 101 heroin-addicted mothers gave birth to 149 babies at Vancouver General Hospital. Thirty-seven percent of the infants had low birth weights and two thirds were born preterm. Average birth weight was 2,710 gm as compared with an overall average of 3,420 gm for this hospital. Tobacco and alcohol abuse, and poor maternal nutrition probably contributed to the growth retardation. Withdrawal symptoms were observed in 68% of the babies, and this may have been aggravated by multiple drug use, which was prevalent, including alcohol, barbiturates, and "soft drugs." Neonatal mortality rate of 6.7% and a stillbirth rate of 4% resulted in a perinatal mortality rate of 10.7%. Prematurity, respiratory distress syndrome, and other perinatal complications related to an unfavorable social background accounted for most neonatal deaths, but none was attributable directly to narcotic withdrawal.

Habitual reappraisal in context: peer victimisation moderates its association with physiological reactivity to social stress.

PubMed

Christensen, Kara A; Aldao, Amelia; Sheridan, Margaret A; McLaughlin, Katie A

2017-02-01

Although the emotion regulation strategy of reappraisal has been associated with adaptive outcomes, there is a growing evidence that it may not be adaptive in all contexts. In the present study, adolescents reported their use of habitual reappraisal and their experiences with peer victimisation, a chronic stressor that is associated with reduced well-being in this population. We examined how these variables predicted physiological reactivity (vagal withdrawal and changes in pre-ejection period) during a social stressor (i.e., Trier Social Stress Task). In line with previous research, at high levels of victimisation, habitual reappraisal predicted adaptive physiological reactivity (i.e., greater vagal withdrawal). Conversely, at low levels of victimisation, habitual reappraisal predicted maladaptive physiological reactivity (i.e., blunted vagal withdrawal). These findings were specific to parasympathetic reactivity. They suggest that habitual reappraisal may exert different effects on parasympathetic reactivity depending on the presence of stressors, and highlight the importance of examining the role of contextual factors in determining the adaptiveness of emotion regulation strategies.

Habitual reappraisal in context: peer victimisation moderates its association with physiological reactivity to social stress

PubMed Central

Christensen, Kara A.; Aldao, Amelia; Sheridan, Margaret A.; McLaughlin, Katie A.

2016-01-01

Although the emotion regulation strategy of reappraisal has been associated with adaptive outcomes, there is a growing evidence that it may not be adaptive in all contexts. In the present study, adolescents reported their use of habitual reappraisal and their experiences with peer victimisation, a chronic stressor that is associated with reduced well-being in this population. We examined how these variables predicted physiological reactivity (vagal withdrawal and changes in pre-ejection period) during a social stressor (i.e., Trier Social Stress Task). In line with previous research, at high levels of victimisation, habitual reappraisal predicted adaptive physiological reactivity (i.e., greater vagal withdrawal). Conversely, at low levels of victimisation, habitual reappraisal predicted maladaptive physiological reactivity (i.e., blunted vagal withdrawal). These findings were specific to parasympathetic reactivity. They suggest that habitual reappraisal may exert different effects on parasympathetic reactivity depending on the presence of stressors, and highlight the importance of examining the role of contextual factors in determining the adaptiveness of emotion regulation strategies. PMID:26654477

High water-stressed population estimated by world water resources assessment including human activities under SRES scenarios

NASA Astrophysics Data System (ADS)

Kiguchi, M.; Shen, Y.; Kanae, S.; Oki, T.

2009-04-01

In an argument of the reduction and the adaptation for the climate change, the evaluation of the influence by the climate change is important. When we argue in adaptation plan from a damage scale and balance with the cost, it is particularly important. Parry et al (2001) evaluated the risks in shortage of water, malaria, food, the risk of the coast flood by temperature function and clarified the level of critical climate change. According to their evaluation, the population to be affected by the shortage of water suddenly increases in the range where temperature increases from 1.5 to 2.0 degree in 2080s. They showed how much we need to reduce emissions in order to draw-down significantly the number at risk. This evaluation of critical climate change threats and targets of water shortage did not include the water withdrawal divided by water availability. Shen et al (2008a) estimated the water withdrawal of projection of future world water resources according to socio-economic driving factors predicted for scenarios A1b, A2, B1, and B2 of the Special Report on Emission Scenarios (SRES). However, these results were in function of not temperature but time. The assessment of the highly water-stressed population considered the socioeconomic development is necessary for a function of the temperature. Because of it is easy to understand to need to reduce emission. We present a multi-GCM analysis of the global and regional populations lived in highly water-stressed basin for a function of the temperature using the socioeconomic data and the outputs of GCMs. In scenario A2, the population increases gradually with warming. On the other hand, the future projection population in scenario A1b and B1 increase gradually until the temperature anomaly exceeds around from +1 to +1.5 degree. After that the population is almost constant. From Shen et al (2008b), we evaluated the HWSP and its ratio in the world with temperature function for scenarios A1B, A2, and B1 by the index of W/Q. In global, the HWSP in scenario A2 increased rapidly when the anomaly of temperature is exceeding to about +1.5 degree. In the case of the scenario A1b, the gradient of increase of HWSP was less than that in the case of the scenario A2. When the value of temperature anomaly was exceeding to about + 1.5 degree, the gradient of increase of HWSP became loose. On the other hand, the HWSP in the scenario B1 decreased when the temperature anomaly was exceeding to about +1.2 degree. According to the estimation of the HWSP when the effect of climate change was ignored (that is, runoff was not changed), the HWSP was almost same (not shown). This result implied that it is strongly contributed by not the climate change but the socio-economical factors (ex; an irrigated area, increase of industrial water use, increase of population itself). In Parry et al (2001), the renewed high stressed population by coastal flooding, hunger, malaria, and water shortage were estimated. The risks of hunger and coastal flooding increase gradually with the warming. Risk of malaria widely increases. Meanwhile, the risk of water shortage rapidly increases after the temperature anomaly exceeds around +2.0 degree. From this result, they insist that the "dangerous level" for sustainable development is +2.0 degree and the target emission level is 550 ppmv. However, they did not consider the quantity of water intake. We estimated the HWSP considering the quantity of water withdrawal and its projection in future. From our result, the "dangerous level" is disagreed. We can insist that the climate change is not so effective within the water withdrawal. If anything, the socio-economic elements, for instance the variation of irrigation areas, industrial water withdrawal, and population itself, contribute to the HWSP. The HWSP and its ratio in each country should be necessary for not only scientific issue but also political issue.

The moderating role of peer norms in the associations of social withdrawal and aggression with peer victimization.

PubMed

Guimond, Fanny-Alexandra; Brendgen, Mara; Correia, Stephanie; Turgeon, Lyse; Vitaro, Frank

2018-06-21

This study examined the moderating role of classroom injunctive norms salience regarding social withdrawal and regarding aggression in the longitudinal association between these behaviors and peer victimization. A total of 1,769 fourth through sixth graders (895 girls, M = 10.25 years, SD = 1.03) from 23 schools (67 classrooms) completed a peer nomination inventory in the fall (T1) and spring (T2) of the same academic year. Participants circled the name of each student who fit the description provided for social withdrawal, aggression, and peer victimization at T1 and T2. The salience of injunctive norms was sex-specific and operationalized by the extent to which children displaying the behavior were socially rewarded or sanctioned by their classmates. Generalized estimation equations (GEE) showed that the association between social withdrawal at T1 and peer victimization at T2 was moderated by injunctive norms. Social withdrawal at T1 was positively associated with peer victimization at T2 in classrooms where injunctive norms for this behavior were salient and unfavorable, as well as in classrooms where injunctive norms for aggression were salient and favorable, albeit for girls only. The association between aggression at T1 and peer victimization at T2 was also moderated by the injunctive norms regarding this behavior. Aggressive children were less likely to be victimized in classrooms where this behavior was rewarded. These results support bullying interventions that target factors related to the larger peer context, including social norms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Attenuated effects of experimenter-administered heroin in adolescent vs. adult male rats: physical withdrawal and locomotor sensitization

PubMed Central

Doherty, James M.; Frantz, Kyle J.

2012-01-01

Objectives Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely correlates of sensitivity to behavioral reinforcement in rats: physical withdrawal and locomotor sensitization. Methods Adolescent (35 days old at start) and adult (79 days old) male Sprague-Dawley rats were administered escalating doses of heroin, increasing from 1.0 to 8.0 mg/kg (i.p.) every 12 hr, across 13 days. Somatic signs of spontaneous withdrawal were scored 12 and 24 hr after the last injection, then every 24 hr for 5 days; locomotion was recorded concurrently. Challenge injections of heroin (1 mg/kg i.p.) were given at 4 points: as the first of the escalating doses (day 1), at days 7 and 13 during the escalating regimen, and after 12 days of forced abstinence. Body mass and food intake were measured throughout experimentation. Results A heroin withdrawal syndrome was not observed among adolescents as it was among adults, including somatic signs as well as reduced locomotion, body mass, and food intake. On the other hand, heroin-induced locomotor sensitization did not differ across ages. Conclusion Reduced withdrawal is consistent with the attenuated reinforcing effects of heroin among adolescent male rats that we reported previously. Thus, it is possible that adolescent rats could reveal important neuroprotective factors for use in treatment of heroin dependence. PMID:22941050

Diagnostic Criteria for Cannabis Withdrawal Syndrome

PubMed Central

Gorelick, David A.; Levin, Kenneth H.; Copersino, Marc L.; Heishman, Stephen J.; Liu, Fang; Boggs, Douglas L.; Kelly, Deanna L.

2011-01-01

Objective Cannabis withdrawal occurs in frequent users who quit, but there are no accepted diagnostic criteria for a cannabis withdrawal syndrome (CWS). This study evaluated diagnostic criteria for CWS proposed in DSM-V and two earlier proposals. Method A convenience sample of 384 adult, non-treatment-seeking lifetime cannabis smokers provided retrospective self-report data on their “most difficult” quit attempt without formal treatment, which was used in this secondary analysis. Prevalence, time of onset, and peak intensity (5-point Likert scale) for 39 withdrawal symptoms (drawn from the literature) were assessed via computer-administered questionnaire. Subject groups were compared using chi-square or ANOVA. Symptom clustering was evaluated with principal components analysis. Results 40.9% of subjects met the DSM-V criterion of ≥ 3 symptoms from a list of 7. There were no associations with sex, race, or type of cannabis preparation used. There were significant positive associations between duration or frequency of cannabis use prior to the quit attempt and experiencing CWS. Subjects with CWS had a significantly shorter duration of abstinence. Alternative syndromal criteria (dropping physical symptoms from DSM-V list; requiring ≥ 2or ≥ 4 symptoms from a list of 11) yielded a similar prevalence of CWS and similar associations with prior cannabis use and relapse. The PCA yielded 12 factors, including some symptom clusters not included in DSM-V. Conclusions Findings support the concurrent and predictive validity of the proposed DSM-V CWS, but suggest that the list of withdrawal symptoms and number required for diagnosis warrant further evaluation. PMID:22153944

5 CFR 841.404 - Demographic factors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... available data will be used. (1) Distributions of new entrants by age, sex, and service; (2) Withdrawal... disability annuitants; (12) Child survivor termination and death rates; (13) Family characteristics for..., except those rates for child survivors and merit salary increases. ...

5 CFR 841.404 - Demographic factors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... available data will be used. (1) Distributions of new entrants by age, sex, and service; (2) Withdrawal... disability annuitants; (12) Child survivor termination and death rates; (13) Family characteristics for..., except those rates for child survivors and merit salary increases. ...

5 CFR 841.404 - Demographic factors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... available data will be used. (1) Distributions of new entrants by age, sex, and service; (2) Withdrawal... disability annuitants; (12) Child survivor termination and death rates; (13) Family characteristics for..., except those rates for child survivors and merit salary increases. ...

5 CFR 841.404 - Demographic factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... available data will be used. (1) Distributions of new entrants by age, sex, and service; (2) Withdrawal... disability annuitants; (12) Child survivor termination and death rates; (13) Family characteristics for..., except those rates for child survivors and merit salary increases. ...

5 CFR 841.404 - Demographic factors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... available data will be used. (1) Distributions of new entrants by age, sex, and service; (2) Withdrawal... disability annuitants; (12) Child survivor termination and death rates; (13) Family characteristics for..., except those rates for child survivors and merit salary increases. ...

Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

PubMed

Pizon, Anthony F; Lynch, Michael J; Benedict, Neal J; Yanta, Joseph H; Frisch, Adam; Menke, Nathan B; Swartzentruber, Greg S; King, Andrew M; Abesamis, Michael G; Kane-Gill, Sandra L

2018-05-08

Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. Retrospective observational cohort study. Academic tertiary care hospital. Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13). Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was associated with reduced gamma-aminobutyric acid agonist requirements, shorter ICU length of stay, lower likelihood of intubation, and a trend toward a shorter hospitalization.

Regulation of glutamate transporter 1 (GLT-1) gene expression by cocaine self-administration and withdrawal.

PubMed

Kim, Ronald; Sepulveda-Orengo, Marian T; Healey, Kati L; Williams, Emily A; Reissner, Kathryn J

2018-01-01

Downregulation of the astroglial glutamate transporter GLT-1 is observed in the nucleus accumbens (NAc) following administration of multiple drugs of abuse. The decrease in GLT-1 protein expression following cocaine self-administration is dependent on both the amount of cocaine self-administered and the length of withdrawal, with longer access to cocaine and longer withdrawal periods leading to greater decreases in GLT-1 protein. However, the mechanism(s) by which cocaine downregulates GLT-1 protein remains unknown. We used qRT-PCR to examine gene expression of GLT-1 splice isoforms (GLT-1A, GLT-1B) in the NAc, prelimbic cortex (PL) and basolateral amygdala (BLA) of rats, following two widely used models of cocaine self-administration: short-access (ShA) self-administration, and the long-access (LgA) self-administration/incubation model. While downregulation of GLT-1 protein is observed following ShA cocaine self-administration and extinction, this model did not lead to a change in GLT-1A or GLT-1B gene expression in any brain region examined. Forced abstinence following ShA cocaine self-administration also was without effect. In contrast, LgA cocaine self-administration and prolonged abstinence significantly decreased GLT-1A gene expression in the NAc and BLA, and significantly decreased GLT-1B gene expression in the PL. No change was observed in NAc GLT-1A gene expression one day after LgA cocaine self-administration, indicating withdrawal-induced decreases in GLT-1A mRNA. In addition, LgA cocaine self-administration and withdrawal induced hypermethylation of the GLT-1 gene in the NAc. These results indicate that a decrease in NAc GLT-1 mRNA is only observed after extended access to cocaine combined with protracted abstinence, and that epigenetic mechanisms likely contribute to this effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors affecting the persistence of drug-induced reprogramming of the cancer methylome

PubMed Central

Bell, Joshua S. K.; Kagey, Jacob D.; Barwick, Benjamin G.; Dwivedi, Bhakti; McCabe, Michael T.; Kowalski, Jeanne; Vertino, Paula M.

2016-01-01

ABSTRACT Aberrant DNA methylation is a critical feature of cancer. Epigenetic therapy seeks to reverse these changes to restore normal gene expression. DNA demethylating agents, including 5-aza-2′-deoxycytidine (DAC), are currently used to treat certain leukemias, and can sensitize solid tumors to chemotherapy and immunotherapy. However, it has been difficult to pin the clinical efficacy of these agents to specific demethylation events, and the factors that contribute to the durability of response remain largely unknown. Here we examined the genome-wide kinetics of DAC-induced DNA demethylation and subsequent remethylation after drug withdrawal in breast cancer cells. We find that CpGs differ in both their susceptibility to demethylation and propensity for remethylation after drug removal. DAC-induced demethylation was most apparent at CpGs with higher initial methylation levels and further from CpG islands. Once demethylated, such sites exhibited varied remethylation potentials. The most rapidly remethylating CpGs regained >75% of their starting methylation within a month of drug withdrawal. These sites had higher pretreatment methylation levels, were enriched in gene bodies, marked by H3K36me3, and tended to be methylated in normal breast cells. In contrast, a more resistant class of CpG sites failed to regain even 20% of their initial methylation after 3 months. These sites had lower pretreatment methylation levels, were within or near CpG islands, marked by H3K79me2 or H3K4me2/3, and were overrepresented in sites that become aberrantly hypermethylated in breast cancers. Thus, whereas DAC-induced demethylation affects both endogenous and aberrantly methylated sites, tumor-specific hypermethylation is more slowly regained, even as normal methylation promptly recovers. Taken together, these data suggest that the durability of DAC response is linked to its selective ability to stably reset at least a portion of the cancer methylome. PMID:27082926

Ethanol-mediated facilitation of AMPA receptor function in the dorsomedial striatum: implications for alcohol drinking behavior.

PubMed

Wang, Jun; Ben Hamida, Sami; Darcq, Emmanuel; Zhu, Wenheng; Gibb, Stuart L; Lanfranco, Maria Fe; Carnicella, Sebastien; Ron, Dorit

2012-10-24

We found previously that acute ex vivo as well as repeated cycles of in vivo ethanol exposure and withdrawal, including excessive voluntary consumption of ethanol, produces a long-lasting increase in the activity of NR2B-containing NMDA receptors (NR2B-NMDARs) in the dorsomedial striatum (DMS) of rats (Wang et al., 2010a). Activation of NMDARs is required for the induction of long-term potentiation (LTP) of AMPA receptor (AMPAR)-mediated synaptic response. We therefore examined whether the ethanol-mediated upregulation of NMDAR activity alters the induction of LTP in the DMS. We found that ex vivo acute exposure of striatal slices to, and withdrawal from, ethanol facilitates the induction of LTP in DMS neurons, which is abolished by the inhibition of NR2B-NMDARs. We also report that repeated systemic administration of ethanol causes an NR2B-NMDAR-dependent facilitation of LTP in the DMS. LTP is mediated by the insertion of AMPAR subunits into the synaptic membrane, and we found that repeated systemic administration of ethanol, as well as cycles of excessive ethanol consumption and withdrawal, produced a long-lasting increase in synaptic localization of the GluR1 and GluR2 subunits of AMPARs in the DMS. Importantly, we report that inhibition of AMPARs in the DMS attenuates operant self-administration of ethanol, but not of sucrose. Together, our data suggest that aberrant synaptic plasticity in the DMS induced by repeated cycles of ethanol exposure and withdrawal contributes to the molecular mechanisms underlying the development and/or maintenance of excessive ethanol consumption.

Opiate physical dependence and N-methyl-D-aspartate receptors.

PubMed

Noda, Yukihiro; Nabeshima, Toshitaka

2004-10-01

The present review focused the involvement of N-methyl-D-aspartate (NMDA) receptors in morphine physical dependence. The increased levels of extracellular glutamate, NMDA receptor zeta subunit (NR1) mRNA, NMDA receptor epsilon 1 subunit (NR2A) protein, phosphorylated Ca(2+)/calmodulin kinase II (p-CaMKII) protein, c-fos mRNA, c-Fos protein, are observed in the specific brain areas of mice and/or rats showing signs of naloxone-precipitated withdrawal. In preclinical and clinical studies, a variety of NMDA receptor antagonists and pretreatment with an antisense oligonucleotide of the NR1 have been reported to inhibit the development, expression and/or maintenance of opiate physical dependence. In contrast to data obtained in adult animals, NMDA receptor antagonists are neither effective in blocking the development of opiate dependence nor the expression of opiate withdrawal in neonatal rats. In the NMDA receptor-deficient mice, the NR2A knockout mice show the marked loss of typical withdrawal abstinence behaviors precipitated by naloxone. The rescue of NR2A protein by electroporation into the nucleus accumbens of NR2A knockout mice reverses the loss of abstinence behaviors. The activation of CaMKII and increased expression of c-Fos protein in the brain of animals with naloxone-precipitated withdrawal syndrome are prevented by NMDA receptor antagonists, whereas the increased levels of extracellular glutamate are not prevented by them. These findings indicate that glutamatergic neurotransmission at the NMDA receptor site contributes to the development, expression and maintenance of opiate dependence, and suggest that NMDA receptor antagonists may be a useful adjunct in the treatment of opiate dependence.

Keeping Our Students: Identifying Factors that Influence Student Withdrawal and Strategies to Enhance the Experience and Retention of First-Year Students

ERIC Educational Resources Information Center

Parmar, Deeba; Trotter, Eileen

2004-01-01

This article derives from local research at two UK universities as part of their institutional strategies to address retention and progression and enhance their students' experiences of higher education. In both Middlesex University and the University of Salford, research has been undertaken to identify factors which influence the retention and…

Retaining Army Engineer Officers

DTIC Science & Technology

2010-04-01

withdrawal behavior: organization-wide factors (e.g. pay and promotion), immediate work environment factors (e.g. supervisory style), job -content... embeddedness construct. It is a departure from the traditional model focus on employee attitudes and alternatives. Job embeddedness is a web of influence...more embedded than one who perceives less links. Job embeddedness is highly individualized and classified as links, fit, and sacrifice. Links are formal

Antireward, compulsivity, and addiction: seminal contributions of Dr. Athina Markou to motivational dysregulation in addiction.

PubMed

Koob, George F

2017-05-01

Addiction is defined as a chronically relapsing disorder characterized by compulsive drug seeking that is hypothesized to derive from multiple sources of motivational dysregulation. Dr. Athina Markou made seminal contributions to our understanding of the neurobiology of addiction with her studies on the dysregulation of reward function using animal models with construct validity. Repeated overstimulation of the reward systems with drugs of abuse decreases reward function, characterized by brain stimulation reward and presumbably reflecting dysphoria-like states. The construct of negative reinforcement, defined as drug taking that alleviates a negative emotional state that is created by drug abstinence, is particularly relevant as a driving force in both the withdrawal/negative affect and preoccupation/anticipation stages of the addiction cycle. The negative emotional state that drives such negative reinforcement is hypothesized to derive from the dysregulation of key neurochemical circuits that drive incentive-salience/reward systems (dopamine, opioid peptides) in the ventral striatum and from the recruitment of brain stress systems (corticotropin-releasing factor, dynorphin) within the extended amygdala. As drug taking becomes compulsive-like, the factors that motivate behavior are hypothesized to shift to drug-seeking behavior that is driven not only by positive reinforcement but also by negative reinforcement. This shift in motivation is hypothesized to reflect the allostatic misregulation of hedonic tone such that drug taking makes the hedonic negative emotional state worse during the process of seeking temporary relief with compulsive drug taking.

Teacher factors contributing to dosage of the KiVa anti-bullying program.

PubMed

Swift, Lauren E; Hubbard, Julie A; Bookhout, Megan K; Grassetti, Stevie N; Smith, Marissa A; Morrow, Michael T

2017-12-01

The KiVa Anti-Bullying Program (KiVa) seeks to meet the growing need for anti-bullying programming through a school-based, teacher-led intervention for elementary school children. The goals of this study were to examine how intervention dosage impacts outcomes of KiVa and how teacher factors influence dosage. Participants included 74 teachers and 1409 4th- and 5th-grade students in nine elementary schools. Teachers and students completed data collection at the beginning and end of the school year, including measures of bullying and victimization, correlates of victimization (depression, anxiety, peer rejection, withdrawal, and school avoidance), intervention cognitions/emotions (anti-bullying attitudes, and empathy toward victims), bystander behaviors, and teacher factors thought to relate to dosage (self-efficacy for teaching, professional burnout, perceived principal support, expected effectiveness of KiVa, perceived feasibility of KiVa). The dosage of KiVa delivered to classrooms was measured throughout the school year. Results highlight dosage as an important predictor of change in bullying, victimization, correlates of victimization, bystander behavior, and intervention cognitions/emotions. Of the teacher factors, professional burnout uniquely predicted intervention dosage. A comprehensive structural equation model linking professional burnout to dosage and then to child-level outcomes demonstrated good fit. Implications for intervention design and implementation are discussed. Copyright © 2017 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

19 CFR 144.27 - Withdrawal from warehouse by transferee.

Code of Federal Regulations, 2012 CFR

2012-04-01

...; DEPARTMENT OF THE TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Transfer of Right To Withdraw Merchandise from Warehouse § 144.27 Withdrawal from warehouse by transferee. At any time within... withdraw all or part of the merchandise covered by the transfer by filing any authorized kind of withdrawal...

19 CFR 144.27 - Withdrawal from warehouse by transferee.

Code of Federal Regulations, 2010 CFR

2010-04-01

...; DEPARTMENT OF THE TREASURY (CONTINUED) WAREHOUSE AND REWAREHOUSE ENTRIES AND WITHDRAWALS Transfer of Right To Withdraw Merchandise from Warehouse § 144.27 Withdrawal from warehouse by transferee. At any time within... withdraw all or part of the merchandise covered by the transfer by filing any authorized kind of withdrawal...

Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing cholangitis.

PubMed

Wunsch, Ewa; Trottier, Jocelyn; Milkiewicz, Malgorzata; Raszeja-Wyszomirska, Joanna; Hirschfield, Gideon M; Barbier, Olivier; Milkiewicz, Piotr

2014-09-01

Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P<0.0001; gamma-glutamyl transpeptidase of 117.9%, P<0.0001; bilirubin of 50.0%, P<0.001; alanine aminotransferase of 63.9%, P<0.005; and aspartate aminotransferase of 45.0%, P<0.005) and increase of Mayo Risk Score for PSC (change from baseline of +0.5 point; P<0.003). Bile acid analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal, but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic acid correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed; however, 42% of patients reported a deterioration in their pruritus. At 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short-term markers of quality of life are unaffected. © 2014 by the American Association for the Study of Liver Diseases.

Weight bearing of the limb as a confounding factor in assessment of mechanical allodynia in the rat.

PubMed

Kauppila, T; Kontinen, V K; Pertovaara, A

1998-01-01

Effect of weight bearing of the hindlimbs on the assessment of mechanically-induced hindlimb withdrawal threshold was determined in intact rats and in rats with various pathophysiological conditions causing allodynia or hyperalgesia. Hindlimb withdrawal was elicited by applying a series of calibrated monofilaments to the plantar or the dorsal surface of the paw. During testing the rat was either in a restraint tube with hindlimbs hanging semi-extended without weight bearing or it was standing on a metal grid (bearing its own weight). In intact rats, the withdrawal thresholds were significantly lower when the stimulus site was the dorsal hairy skin rather than the plantar glabrous skin. Also, thresholds were significantly lower when the hindlimbs were not bearing weight. Following carrageenan-induced unilateral inflammation of the plantar paw or a tibial nerve cut there was a marked threshold decrease to test stimuli applied to plantar or dorsal paw, respectively, ipsilateral to the pathological condition in standing rats. However, when the hindlimbs were not weight bearing the unilateral threshold decrease was markedly attenuated (carrageenan-treated rats) or completely abolished (tibial cut). In contrast, in rats with a unilateral spinal nerve ligation the threshold decrease ipsilateral to the nerve lesion was highly significant independent of the weight bearing of the hindlimbs. The results indicate that weight bearing of hindlimbs is an important confounding factor in the assessment of tactile allodynia in rats.

Cannabis use during a voluntary quit attempt: an analysis from ecological momentary assessment.

PubMed

Buckner, Julia D; Zvolensky, Michael J; Ecker, Anthony H

2013-10-01

There is little research that has sought to identify factors related to quit success and failure among cannabis users. The current study examined affective, cognitive, and situational factors related to cannabis use among current cannabis users undergoing a voluntary, self-guided quit attempt. The sample consisted of 30 (33% female) current cannabis users, 84% of whom evinced a current cannabis use disorder. Ecological momentary assessment was used to collect multiple daily ratings of cannabis withdrawal, negative affect, peer cannabis use, reasons for use, and successful coping strategies over two weeks. Findings from generalized linear models indicated that cannabis withdrawal and positive and negative affect were significantly higher during cannabis use than non-use episodes. Additionally, when negative and positive affect were entered simultaneously, negative affect, but not positive affect, remained significantly related to use. Participants were significantly more likely to use in social situations than when alone. When participants were in social situations, they were significantly more likely to use if others were using. Participants tended to use more behavioral than cognitive strategies to abstain from cannabis. The most common reason for use was to cope with negative affect. Overall, these novel findings indicate that cannabis withdrawal, affect (especially negative affect), and peer use play important roles in cannabis use among self-quitters. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The association between perceived distress tolerance and cannabis use problems, cannabis withdrawal symptoms, and self-efficacy for quitting cannabis: The explanatory role of pain-related affective distress.

PubMed

Manning, Kara; Rogers, Andrew H; Bakhshaie, Jafar; Hogan, Julianna B D; Buckner, Julia D; Ditre, Joseph W; Zvolensky, Michael J

2018-10-01

Rates of cannabis use and related problems continue to rise, ranking as the third most common substance use disorder in the United States, behind tobacco and alcohol use. Past work suggests that perceived distress tolerance is related to several clinically significant features of cannabis use (e.g., coping-oriented use). However, there has been little exploration of the mechanisms that may underlie relations between perceived distress tolerance and cannabis use problems, withdrawal severity, and self-efficacy for quitting. The current study sought to examine the experience of pain, which frequently co-occurs with cannabis use (Ashrafioun, Bohnert, Jannausch, & Ilgen, 2015), as an underlying factor in the relation between perceived distress tolerance and cannabis related problems among 203 current cannabis-using adults (29.2% female, M = 37.7 years, SD = 10.2, 63% African American). Results indicated that perceived distress tolerance via pain related affective distress significantly predicted the severity of cannabis use problems (Pm = 0.60), degree of cannabis withdrawal (Pm = 0.39), and lower self-efficacy for quitting cannabis (Pm = 0.36). Future work may usefully explore the role of pain-related affective distress as a mechanistic factor in the context of perceived distress tolerance-cannabis relations. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Longitudinal Study on the Effects of Negative Rearing Experiences on Adolescents' Social Withdrawal and Aggression.

PubMed

Lee, Kyung-Suk; Choi, Ok-Joo; Kim, Joon-Ho

2017-09-01

Children who have experienced negative rearing behaviors show a lack of self-confidence due to emotional instability and are reserved in interpersonal relationships. This can lead to failure in social adaptation and a high risk of depression, suicide, criminal acts, and anti-social behaviors. Therefore, this study aims to analyze the effects of experiencing negative parental rearing behaviors, such as neglect and abuse, on adolescents' social withdrawal and aggression, by utilizing multivariate latent growth models. Data from the Korean Children and Youth Panel Study (KCYPS), a survey conducted by the National Youth Policy Institute targeting a cohort of three different age groups (grade 1, grade 4, and grade 7), from 2010 to 2016 was used. Multi-stage stratified sampling methods were used in the KCYPS, which surveyed the students and parents of the selected grade levels. This study analyzed the data for grade 7, from second year (grade 8) to fourth year (grade 10). Negative rearing experiences had a significant effect on social withdrawal and aggression, and this influence was shown to persist over the long term. This study examined the long-term developmental trajectory in the relationship between risk factors for adolescent development. Furthermore, the relationship between risk factors was shown to have not only short term but long-term effects as well, which reinforces the limitations of previous studies.

A Longitudinal Study on the Effects of Negative Rearing Experiences on Adolescents' Social Withdrawal and Aggression

PubMed Central

Lee, Kyung-Suk; Choi, Ok-Joo

2017-01-01

Background Children who have experienced negative rearing behaviors show a lack of self-confidence due to emotional instability and are reserved in interpersonal relationships. This can lead to failure in social adaptation and a high risk of depression, suicide, criminal acts, and anti-social behaviors. Therefore, this study aims to analyze the effects of experiencing negative parental rearing behaviors, such as neglect and abuse, on adolescents' social withdrawal and aggression, by utilizing multivariate latent growth models. Methods Data from the Korean Children and Youth Panel Study (KCYPS), a survey conducted by the National Youth Policy Institute targeting a cohort of three different age groups (grade 1, grade 4, and grade 7), from 2010 to 2016 was used. Multi-stage stratified sampling methods were used in the KCYPS, which surveyed the students and parents of the selected grade levels. This study analyzed the data for grade 7, from second year (grade 8) to fourth year (grade 10). Results Negative rearing experiences had a significant effect on social withdrawal and aggression, and this influence was shown to persist over the long term. Conclusion This study examined the long-term developmental trajectory in the relationship between risk factors for adolescent development. Furthermore, the relationship between risk factors was shown to have not only short term but long-term effects as well, which reinforces the limitations of previous studies. PMID:29026488

Relapse following antithyroid drug therapy for Graves' hyperthyroidism.

PubMed

Laurberg, Peter; Krejbjerg, Anne; Andersen, Stine Linding

2014-10-01

In most patients with hyperthyroidism caused by Graves' disease, antithyroid drug (ATD) therapy is followed by a gradual amelioration of the autoimmune abnormality, but about half of the patients will experience relapse of hyperthyroidism when the ATDs are withdrawn after a standard 1 to 2 years of therapy. This is a major drawback of ATD therapy, and a major concern to patients. We review current knowledge on how to predict and possibly reduce the risk of such relapse. Several patient and disease characteristics, as well as environmental factors and duration of ATD therapy, may influence the risk of relapse after ATD withdrawal. Depending on the presence of such factors, the risk of relapse after ATD withdrawal may vary from around 10 to 90%. Risk factors for relapse should be taken into account when choosing between therapeutic modalities in a patient with newly diagnosed disease, and also when discussing duration of ATD therapy. Prolonged low-dose ATD therapy may be feasible in patients with high risk of relapse, such as children and patients with active Graves' orbitopathy, and in patients with previous relapse who prefer such therapy rather than surgery or radioiodine.

Gender differences in self-reported withdrawal symptoms and reducing or quitting smoking three years later: A prospective, longitudinal examination of U.S. adults

PubMed Central

Weinberger, Andrea H.; Platt, Jonathan; Shuter, Jonathan; Goodwin, Renee D.

2016-01-01

Background Little is known about gender differences in withdrawal symptoms among smokers in the community. This study used longitudinal epidemiologic data to examine gender differences in current smokers’ report of withdrawal symptoms during past quit attempts and the relationship between withdrawal symptoms and the odds of reducing or quitting smoking three years later. Methods Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 1, 2001–2001, n=43,093; Wave 2, 2004–2005, n=34,653). Analyses were conducted on respondents who reported current daily cigarette smoking at Wave 1 (n=6,911). Withdrawal symptoms during past quit attempts were assessed at Wave 1. Current smoking status was assessed at Wave 2. Results Wave 1 current smoking women, compared to men, were more likely to endorse any withdrawal symptoms, withdrawal-related discomfort, and withdrawal-related relapse (ps<0.0001). Women endorsed a greater number of withdrawal symptoms than men (M=2.37, SE=0.05 versus M=1.78, SE=0.04; p<0.0001). The odds of reducing and quitting smoking were significantly lower for respondents who reported any Wave 1 withdrawal symptoms, withdrawal-related discomfort, and withdrawal-related relapse. These relationships did not differ for women versus men. Among men, the odds of reducing smoking at Wave 2 decreased significantly with each cumulative withdrawal symptom compared to women (β interaction= 0.87; p=0.01). Conclusions Women were more likely to report withdrawal while the relationship between withdrawal symptoms and decreased likelihood of reducing smoking was stronger in men. Identifying gender differences in withdrawal can help develop strategies to help reduce withdrawal for both men and women. PMID:27350655

Differential associations between components of anxiety sensitivity and smoking-related characteristics.

PubMed

Guillot, Casey R; Zvolensky, Michael J; Leventhal, Adam M

2015-01-01

Anxiety sensitivity (AS)-the tendency to fear anxiety-related experiences-is a risk factor for anxiety disorders and may contribute to smoking motivation and maintenance. Few studies have examined the relations between conceptually distinct components of AS and smoking behavior. The purpose of the current study was to examine the associations between AS components-physical concerns, mental concerns, and social concerns-and an array of smoking-related characteristics. In a cross-sectional design, we administered the Anxiety Sensitivity Index (ASI) and self-report measures of tobacco dependence, smoking abstinence behavior, and smoking outcome and abstinence expectancies to 314 smokers (≥ 10 cigarettes/day, 32% female, M age=44 years). The ASI Mental Concerns subscale was most clearly associated with greater difficulty maintaining abstinence and stronger expectations of smoking-related negative reinforcement and withdrawal (βs=.21-.31, ps ≤ .005); the ASI Social Concerns was most clearly associated with stronger positive reinforcement smoking expectancies (β=.20, p=.0009); and ASI Physical Concerns subscale was most clearly associated with stronger tobacco withdrawal symptoms experienced in prior quit attempts (β=.20, p=.002). Based on these findings of patterns of associations with smoking-related characteristics across distinct components of AS, we speculate that (1) mindfulness training may be useful for treating tobacco addiction in smokers high in AS mental concerns, and (2) smokers high in AS physical and social concerns may benefit from smoking cessation treatment that incorporates interoceptive exposure and cognitive-behavioral therapy for social anxiety, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nucleus Accumbens AMPA Receptors Are Necessary for Morphine-Withdrawal-Induced Negative-Affective States in Rats

PubMed Central

Russell, Shayla E.; Puttick, Daniel J.; Sawyer, Allison M.; Potter, David N.; Mague, Stephen; Carlezon, William A.

2016-01-01

Dependence is a hallmark feature of opiate addiction and is defined by the emergence of somatic and affective withdrawal signs. The nucleus accumbens (NAc) integrates dopaminergic and glutamatergic inputs to mediate rewarding and aversive properties of opiates. Evidence suggests that AMPA glutamate-receptor-dependent synaptic plasticity within the NAc underlies aspects of addiction. However, the degree to which NAc AMPA receptors (AMPARs) contribute to somatic and affective signs of opiate withdrawal is not fully understood. Here, we show that microinjection of the AMPAR antagonist NBQX into the NAc shell of morphine-dependent rats prevented naloxone-induced conditioned place aversions and decreases in sensitivity to brain stimulation reward, but had no effect on somatic withdrawal signs. Using a protein cross-linking approach, we found that the surface/intracellular ratio of NAc GluA1, but not GluA2, increased with morphine treatment, suggesting postsynaptic insertion of GluA2-lacking AMPARs. Consistent with this, 1-naphthylacetyl spermine trihydrochloride (NASPM), an antagonist of GluA2-lacking AMPARs, attenuated naloxone-induced decreases in sensitivity to brain stimulation reward. Naloxone decreased the surface/intracellular ratio and synaptosomal membrane levels of NAc GluA1 in morphine-dependent rats, suggesting a compensatory removal of AMPARs from synaptic zones. Together, these findings indicate that chronic morphine increases synaptic availability of GluA1-containing AMPARs in the NAc, which is necessary for triggering negative-affective states in response to naloxone. This is broadly consistent with the hypothesis that activation of NAc neurons produces acute aversive states and raises the possibility that inhibiting AMPA transmission selectively in the NAc may have therapeutic value in the treatment of addiction. SIGNIFICANCE STATEMENT Morphine dependence and withdrawal result in profound negative-affective states that play a major role in the maintenance of addiction. However, the underlying neurobiological mechanisms are not fully understood. We use a rat model of morphine dependence to show that GluA1 subunits of AMPA glutamate receptors in the nucleus accumbens (NAc), a brain region critical for modulating affective states, are necessary for aversive effects of morphine withdrawal. Using biochemical methods in NAc tissue, we show that morphine dependence increases cell surface expression of GluA1, suggesting that neurons in this area are primed for increased AMPA receptor activation upon withdrawal. This work is important because it suggests that targeting AMPA receptor trafficking and activation could provide novel targets for addiction treatment. PMID:27225765

29 CFR 4219.12 - Employers liable upon mass withdrawal.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this subpart...

29 CFR 4219.12 - Employers liable upon mass withdrawal.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Employers liable upon mass withdrawal. 4219.12 Section 4219... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.12 Employers liable upon mass withdrawal. (a... experiences successive mass withdrawals, an employer that has been determined to be liable under this subpart...

Evaluation of the groundwater flow model for southern Utah and Goshen Valleys, Utah, updated to conditions through 2011, with new projections and groundwater management simulations

USGS Publications Warehouse

Brooks, Lynette E.

2013-01-01

The U.S. Geological Survey (USGS), in cooperation with the Southern Utah Valley Municipal Water Association, updated an existing USGS model of southern Utah and Goshen Valleys for hydrologic and climatic conditions from 1991 to 2011 and used the model for projection and groundwater management simulations. All model files used in the transient model were updated to be compatible with MODFLOW-2005 and with the additional stress periods. The well and recharge files had the most extensive changes. Discharge to pumping wells in southern Utah and Goshen Valleys was estimated and simulated on an annual basis from 1991 to 2011. Recharge estimates for 1991 to 2011 were included in the updated model by using precipitation, streamflow, canal diversions, and irrigation groundwater withdrawals for each year. The model was evaluated to determine how well it simulates groundwater conditions during recent increased withdrawals and drought, and to determine if the model is adequate for use in future planning. In southern Utah Valley, the magnitude and direction of annual water-level fluctuation simulated by the updated model reasonably match measured water-level changes, but they do not simulate as much decline as was measured in some locations from 2000 to 2002. Both the rapid increase in groundwater withdrawals and the total groundwater withdrawals in southern Utah Valley during this period exceed the variations and magnitudes simulated during the 1949 to 1990 calibration period. It is possible that hydraulic properties may be locally incorrect or that changes, such as land use or irrigation diversions, occurred that are not simulated. In the northern part of Goshen Valley, simulated water-level changes reasonably match measured changes. Farther south, however, simulated declines are much less than measured declines. Land-use changes indicate that groundwater withdrawals in Goshen Valley are possibly greater than estimated and simulated. It is also possible that irrigation methods, amount of diversions, or other factors have changed that are not simulated or that aquifer properties are incorrectly simulated. The model can be used for projections about the effects of future groundwater withdrawals and managed aquifer recharge in southern Utah Valley, but rapid changes in withdrawals and increasing withdrawals dramatically may reduce the accuracy of the predicted water-level and groundwater-budget changes. The model should not be used for projections in Goshen Valley until additional withdrawal and discharge data are collected and the model is recalibrated if necessary. Model projections indicate large drawdowns of up to 400 feet and complete cessation of natural discharge in some areas with potential future increases in water use. Simulated managed aquifer recharge counteracts those effects. Groundwater management examples indicate that drawdown could be less, and discharge at selected springs could be greater, with optimized groundwater withdrawals and managed aquifer recharge than without optimization. Recalibration to more recent stresses and seasonal stress periods, and collection of new withdrawal, stream, land-use, and discharge data could improve the model fit to water-level changes and the accuracy of predictions.

WMD Forecasting in Historical and Contemporary Perspective

DTIC Science & Technology

2010-03-01

a nuclear weapon; Use of a nuclear weapon; Withdrawal from the NPT; Emergence of a nuclear-exports grey market; Widespread dissemination of...Many studies saw technology diffusion and the globalization of commerce as ineluctable forces that contribute to the spread of nuclear (and other...engineering diffuses , the spread of biological weapon capabilities among state actors can be expected to expand in advanced and developing states. This

78 FR 23149 - Air Quality: Revision to Definition of Volatile Organic Compounds-Exclusion of trans 1-chloro-3,3...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... contribution to tropospheric ozone formation. Because EPA received one adverse comment, we are withdrawing the... air quality standards (NAAQS) for ozone under title I of the Clean Air Act (CAA). The direct final... of preparing SIPs to attain the NAAQS for ozone under title I of the CAA. If it had become effective...

Estimated Withdrawals and Other Elements of Water Use in the Great Lakes Basin of the United States in 2005

USGS Publications Warehouse

Mills, Patrick C.; Sharpe, Jennifer B.

2010-01-01

Estimates of water withdrawals in the United States part of the Great Lakes Basin and 107 of its watersheds designated by the 8-digit hydrologic unit code (HUCs) indicate that about 30.3 billion gallons per day (Bgal/d) were withdrawn for practically all categories of use in 2005. Virtually all water withdrawn was freshwater. Surface-water withdrawals totaled 28.8 Bgal/d, or 95 percent of total withdrawals; about 24 Bgal/d was withdrawn from the Great Lakes or their connecting channels. Total withdrawals, and total surface-water withdrawals, decreased 7 percent from 1995 to 2005, generally following the withdrawal trends of industrial use and that of the largest use-thermoelectric power. Groundwater withdrawals increased 3 percent from 1995 to 2005 and 33 percent during 1985-2005. The substantial increase since 1985 results primarily from increases in irrigation and self-supplied domestic withdrawals. In 2005, withdrawals for public supply, domestic, and irrigation use accounted for 81 percent of groundwater withdrawals. About 21.9 Bgal/d, or 72 percent of total withdrawals for 2005, was used for thermoelectric power. Virtually all of this water was derived from surface water and used for once-through cooling at powerplants. As such, the reuse potential of this water in the basin is high, with the majority of the withdrawn water returned to its surface-water source. Public-supply withdrawals were 3.81 Bgal/d (13 percent), with withdrawals declining by about 13 percent from 1995 to 2005. In 2005, about 77 percent of the population in the Great Lakes Basin obtained drinking water from public suppliers, compared to about 78 percent in 1995 and 83 percent in 1985. Surface water consistently provided about 88 percent of the total withdrawals for public supply since 1985. Self-supplied industrial withdrawals in 2005 totaled 2.93 Bgal/d (10 percent), possibly as much as 30 percent less than in 1995. Surface water was the source for 95 percent of industrial withdrawals. Combined withdrawals for mining, irrigation, domestic, aquaculture, and livestock use (in order of decreasing rate) were 1.63 Bgal/d, or only 5 percent of total withdrawals; the withdrawals were distributed almost equally between surface-water and groundwater sources. Withdrawals for each of these uses, except livestock, increased almost continuously during 1985-2005. Withdrawals for mining increased 103 percent and for irrigation 94 percent during 1985-2005; livestock withdrawals decreased 25 percent from their peak in 1990. The number of irrigated acres increased 56 percent since 1985, totaling 750,000 acres in 2005. No use of reclaimed wastewater for industrial or irrigation applications was reported; however, sources of information regarding its use were sparse. Within the basin, the Lake Michigan watershed accounted for 15.0 Bgal/d, or 49 percent, of total water withdrawals for 2005; an estimated 12.3 Bgal/d was withdrawn directly from Lake Michigan. The State of Michigan accounted for 38 percent of total water withdrawals, representing the largest surface-water withdrawals (primarily for thermoelectric power use) and groundwater withdrawals (primarily for public supply and self-supplied domestic use). A disproportionately large percentage of surface-water withdrawals (6 percent, 1.80 Bgal/d) were in Illinois, given this state represents less than 1 percent of the land area of the basin. Ninety percent of the Illinois population served by the water withdrawn from Lake Michigan for public supply resides outside the basin. Within land-based HUCs, the Lower Maumee (04100009) of Ohio accounted for the largest total withdrawal and total surface-water withdrawal (about 0.75 Bgal/d). The St. Joseph (04050001) of Michigan and Indiana accounted for the largest total groundwater withdrawal (0.25 Bgal/d).

Group affiliation in self-management: support or threat to identity?

PubMed

Bossy, Dagmara; Knutsen, Ingrid Ruud; Rogers, Anne; Foss, Christina

2017-02-01

Self-management is considered important in chronic illness, and contemporary health policy recommends participation in support groups for individuals with chronic conditions. Although withdrawal from or non-participation in support groups is an important problem, there is limited knowledge about individuals' own motivation for participation in or withdrawal from self-management support groups. To investigate how individuals with type 2 diabetes perceive participation in group-based self-management support. This is a qualitative focus group study using a semi-structured interview guide. Sixteen participants diagnosed with type 2 diabetes were included in the study. Individuals with and without group affiliations were mixed in three focus groups to trigger discussions. In the analysis, reoccurring themes of engagement and discussions between participants were focused within a theoretical frame of institutional logic. The focus groups are seen as social spaces where participants construct identity. Both participation and non-participation in group-based self-management support are associated with dealing with the stigma of having type 2 diabetes. Negotiations contribute to constructing an illness dignity as a response to the logic of moral responsibility for the disease. Contemporary policy contributes to societal understandings of individuals with type 2 diabetes as morally inadequate. Our study shows that group-based self-management support may counteract blame and contribute in negotiations of identity for individuals with type 2 diabetes. This mechanism makes participation in groups beneficial for some but stigma inducing for others. © 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

Effects of alcohol on the membrane excitability and synaptic transmission of medium spiny neurons in the nucleus accumbens

PubMed Central

Marty, Vincent N.; Spigelman, Igor

2013-01-01

Chronic and excessive alcohol drinking lead to alcohol dependence and loss of control over alcohol consumption, with serious detrimental health consequences. Chronic alcohol exposure followed by protracted withdrawal causes profound alterations in the brain reward system that leads to marked changes in reinforcement mechanisms and motivational state. These long-lasting neuroadaptations are thought to contribute to the development of cravings and relapse. The nucleus accumbens (NAcc), a central component of the brain reward system, plays a critical role in alcohol-induced neuroadaptive changes underlying alcohol-seeking behaviors. Here we review the findings that chronic alcohol exposure produces long-lasting neuroadaptive changes in various ion channels that govern intrinsic membrane properties and neuronal excitability, as well as excitatory and inhibitory synaptic transmission in the NAcc that underlie alcohol-seeking behavior during protracted withdrawal. PMID:22445807

Inducible transgenics. New lessons on events governing the induction and commitment in mammary tumorigenesis.

PubMed

Hulit, J; Di Vizio, D; Pestell, R G

2001-01-01

Breast cancer arises from multiple genetic events that together contribute to the established, irreversible malignant phenotype. The development of inducible tissue-specific transgenics has allowed a careful dissection of the events required for induction and subsequent maintenance of tumorigenesis. Mammary gland targeted expression of oncogenic Ras or c-Myc is sufficient for the induction of mammary gland tumorigenesis in the rodent, and when overexpressed together the rate of tumor onset is substantially enhanced. In an exciting recent finding, D'Cruz et al discovered tetracycline-regulated c-Myc overexpression in the mammary gland induced invasive mammary tumors that regressed upon withdrawal of c-Myc expression. Almost one-half of the c-Myc-induced tumors harbored K-ras or N-ras gene point mutations, correlating with tumor persistence on withdrawal of c-Myc transgene expression. These findings suggest maintenance of tumorigenesis may involve a second mutation within the Ras pathway.

Factors associated with smoking cessation

PubMed Central

França, Samires Avelino de Souza; Neves, Ana Ligian Feitosa das; de Souza, Tatiane Andressa Santos; Martins, Nandara Celana Negreiros; Carneiro, Saul Rassy; Sarges, Edilene do Socorro Nascimento Falcão; de Souza, Maria de Fátima Amine Houat

2015-01-01

OBJECTIVE To analyze the prevalence and factors associated with smoking abstinence among patients who were treated in a reference unit for smoking cessation. METHODS This cross-sectional study examined the medical records of 532 patients treated in a reference unit for smoking cessation in Belém, PA, Northern Brazil, between January 2010 and June 2012. Sociodemographic variables and those related to smoking history and treatment were analyzed. Statistical significance was set at p < 0.05. RESULTS The mean age of the participants was 50 years; 57.0% of the patients were women. The mean tobacco load was 30 packs/year, and the mean smoking duration was approximately 32 years. Most patients remained in treatment for four months. The rate of smoking abstinence was 75.0%. Regression analysis indicated that maintenance therapy, absence of relapse triggers, and lower chemical dependence were significantly associated with smoking cessation. CONCLUSIONS The smoking abstinence rate observed was 75.0%. The cessation process was associated with several aspects, including the degree of chemical dependence, symptoms of withdrawal, and period of patient follow-up in a multidisciplinary treatment program. Studies of this nature contribute to the collection of consistent epidemiological data and are essential for the implementation of effective smoking prevention and cessation strategies. PMID:25741649

FACTORIAL VALIDITY OF THE KOREAN VERSION OF THE EXERCISE DEPENDENCE SCALE-REVISED.

PubMed

Shin, Kyulee; You, Sukkyung

2015-12-01

This study evaluated the psychometric properties of the Korean version of the 21-item Exercise Dependence Scale-Revised (EDS-R). The EDS-R was designed to measure the multidimensional aspects of exercise dependence symptoms such as withdrawal, continuance, tolerance, lack of control, reductions, time, and intention. Although the EDS-R has demonstrated sound psychometric properties, it has only been validated in Western samples. Cross-cultural validations of the instrument may increase the knowledge of exercise dependence. Therefore, this study aimed to contribute to the file by investigating the validity and utility of the construct of the EDS-R, using a non-Western sample. 402 adult participants who were over 18 years of age and who reported exercising at least once a week were asked to complete the EDS-R. The results from factor analyses supported that the seven-factor model of exercise dependence symptoms showed an adequate fit for both men and women. The EDS-R scores differentiated between samples, with varying amounts of exercise; 15.4% of the sample was classified as being at risk for exercise dependence. In sum, the results indicated that the EDS-R is a psychometrically reliable assessment tool for exercise dependence symptoms in Korea.

SSRI and SNRI withdrawal symptoms reported on an internet forum.

PubMed

Stockmann, Tom; Odegbaro, Dolapo; Timimi, Sami; Moncrieff, Joanna

2018-05-09

Antidepressant withdrawal symptoms are well-recognised, but their potential duration remains uncertain. We aimed to describe the characteristics of withdrawal associated with two popular classes of antidepressants, including duration. We analysed the content of a sample of posts on an antidepressant withdrawal website. We compared the characteristics of withdrawal associated with SSRIs and SNRIs, including time of onset, duration and nature of symptoms. 110 posts about SSRI withdrawal, and 63 concerning SNRI withdrawal, were analysed. The mean duration of withdrawal symptoms was significantly longer with SSRIs than SNRIs: 90.5 weeks (standard deviation, SD, 150.0) and 50.8 weeks (SD 76.0) respectively; p = 0.043). Neurological symptoms, such as 'brain zaps,' were more common among SNRI users (p = 0.023). Psychosexual/genitourinary symptoms may be more common among SSRI users (p = 0.054). The website aims to help people with antidepressant withdrawal, and is therefore likely to attract people who have difficulties. Length of prior use of antidepressants was long, with a mean of 252.2 weeks (SD 250.8). People accessing antidepressant withdrawal websites report experiencing protracted withdrawal symptoms. There are some differences in the characteristics of withdrawal associated with different classes of antidepressants.

Novel Roles for Hypoxia and Prostaglandin E2 in the Regulation of IL-8 During Endometrial Repair

PubMed Central

Maybin, Jacqueline A.; Hirani, Nikhil; Jabbour, Henry N.; Critchley, Hilary O.D.

2011-01-01

The endometrium has a remarkable capacity for efficient repair; however, factors involved remain undefined. Premenstrual progesterone withdrawal leads to increased prostaglandin (PG) production and local hypoxia. Here we determined human endometrial expression of interleukin-8 (IL-8) and the roles of PGE2 and hypoxia in its regulation. Endometrial biopsy specimens (n = 51) were collected. Endometrial cells and explants were exposed to 100 nmol/L of PGE2 or 0.5% O2. The endometrial IL-8 concentration peaked during menstruation (P < 0.001) and had a significant proangiogenic effect. IL-8 was increased by PGE2 and hypoxia in secretory but not proliferative explants, which suggests that exposure to progesterone is essential. In vitro progesterone withdrawal induced significant IL-8 up-regulation in proliferative explants primed with progestins, but only in the presence of hypoxia. Epithelial cells treated simultaneously with PGE2 and hypoxia demonstrated synergistic increases in IL-8. Inhibition of HIF-1 by short hairpin RNA abolished hypoxic IL-8 induction, and inhibition of NF-κB by an adenoviral dominant negative inhibitor decreased PGE2-induced IL-8 expression (P > 0.05). Increased menstrual IL-8 is consistent with a role in repair. Progesterone withdrawal, hypoxia, and PGE2 regulate endometrial IL-8 by acting via HIF-1 and NF-κB. Hence, progesterone withdrawal may activate two distinct pathways to initiate endometrial repair. PMID:21356375

Effect of electron withdrawing unit for dye-sensitized solar cell based on D-A-π-A organic dyes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Dong Yuel; Chang, Dong Min; Kim, Young Sik, E-mail: youngkim@hongik.ac.kr

2014-10-15

Highlights: • To gain the red-shifted absorption spectra, withdrawing unit was substituted in dye. • By the introduction of additional withdrawing unit, LUMOs level of dye are decreased. • Decreasing LUMOs level of dye caused the red-shifted absorption spectra of dye. • Novel acceptor, DCRD, showed better photovoltaic properties than cyanoacetic acid. - Abstract: In this work, two novel D-A-π-A dye sensitizers with triarylamine as an electron donor, isoindigo and cyano group as electron withdrawing units and cyanoacetic acid and 2-(1,1-dicyanomethylene) rhodanine as an electron acceptor for an anchoring group (TICC, TICR) were designed and investigated with the ID6 dyemore » as the reference. The difference in HOMO and LUMO levels were compared according to the presence or absence of isoindigo in ID6 (TC and ID6). To gain insight into the factors responsible for photovoltaic performance, we used density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations. Owing to different LUMO levels for each acceptor, the absorption band and molar extinction coefficient of each dye was different. Among the dyes, TICR showed more red-shifted and broader absorption spectra than other dyes and had a higher molar extinction coefficient than the reference. It is expected that TICR would show better photovoltaic properties than the other dyes, including the reference dye.« less

The effect of the ecstasy 'come-down' on the diagnosis of ecstasy dependence.

PubMed

McKetin, Rebecca; Copeland, Jan; Norberg, Melissa M; Bruno, Raimondo; Hides, Leanne; Khawar, Laila

2014-06-01

The existence of an ecstasy-dependence syndrome is controversial. We examined whether the acute after-effects of ecstasy use (i.e. the 'come-down') falsely lead to the identification of ecstasy withdrawal and the subsequent diagnosis of ecstasy dependence. The Structured Clinical Interview for DSM-IV-TR Disorders: Research Version (SCID-RV) was administered to 214 Australian ecstasy users. Ecstasy withdrawal was operationalised in three contrasting ways: (i) as per DSM-IV criteria; (ii) as the expected after-effects of ecstasy (a regular come-down); or (iii) as a substantially greater or longer come-down than on first use (intense come-down). These definitions were validated against frequency of ecstasy use, readiness to change and ability to resist the urge to use ecstasy. Confirmatory factor analyses were used to see how they aligned with the overall dependence syndrome. Come-down symptoms increased the prevalence of withdrawal from 1% (DSM-IV criterion) to 11% (intense come-downs) and 75% (regular come-downs). Past year ecstasy dependence remained at 31% when including the DSM-IV withdrawal criteria and was 32% with intense come-downs, but increased to 45% with regular come-downs. Intense come-downs were associated with lower ability to resist ecstasy use and loaded positively on the dependence syndrome. Regular come-downs did not load positively on the ecstasy-dependence syndrome and were not related to other indices of dependence. The acute after-effects of ecstasy should be excluded when assessing ecstasy withdrawal as they can lead to a false diagnosis of ecstasy dependence. Worsening of the ecstasy come-down may be a marker for dependence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Withholding or withdrawing of life-sustaining therapy in older adults (≥ 80 years) admitted to the intensive care unit.

PubMed

Guidet, Bertrand; Flaatten, Hans; Boumendil, Ariane; Morandi, Alessandro; Andersen, Finn H; Artigas, Antonio; Bertolini, Guido; Cecconi, Maurizio; Christensen, Steffen; Faraldi, Loredana; Fjølner, Jesper; Jung, Christian; Marsh, Brian; Moreno, Rui; Oeyen, Sandra; Öhman, Christina Agwald; Pinto, Bernardo Bollen; Soliman, Ivo W; Szczeklik, Wojciech; Valentin, Andreas; Watson, Ximena; Zafeiridis, Tilemachos; De Lange, Dylan W

2018-05-17

To document and analyse the decision to withhold or withdraw life-sustaining treatment (LST) in a population of very old patients admitted to the ICU. This prospective study included intensive care patients aged ≥ 80 years in 309 ICUs from 21 European countries with 30-day mortality follow-up. LST limitation was identified in 1356/5021 (27.2%) of patients: 15% had a withholding decision and 12.2% a withdrawal decision (including those with a previous withholding decision). Patients with LST limitation were older, more frail, more severely ill and less frequently electively admitted. Patients with withdrawal of LST were more frequently male and had a longer ICU length of stay. The ICU and 30-day mortality were, respectively, 29.1 and 53.1% in the withholding group and 82.2% and 93.1% in the withdrawal group. LST was less frequently limited in eastern and southern European countries than in northern Europe. The patient-independent factors associated with LST limitation were: acute ICU admission (OR 5.77, 95% CI 4.32-7.7), Clinical Frailty Scale (CFS) score (OR 2.08, 95% CI 1.78-2.42), increased age (each 5 years of increase in age had a OR of 1.22 (95% CI 1.12-1.34) and SOFA score [OR of 1.07 (95% CI 1.05-1.09 per point)]. The frequency of LST limitation was higher in countries with high GDP and was lower in religious countries. The most important patient variables associated with the instigation of LST limitation were acute admission, frailty, age, admission SOFA score and country. ClinicalTrials.gov (ID: NTC03134807).

Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

PubMed Central

Lominac, Kevin D; Sacramento, Arianne D; Szumlinski, Karen K; Kippin, Tod E

2012-01-01

Methamphetamine is a highly addictive psychomotor stimulant yet the neurobiological consequences of methamphetamine self-administration remain under-characterized. Thus, we employed microdialysis in rats trained to self-administer intravenous (IV) infusions of methamphetamine (METH-SA) or saline (SAL) and a group of rats receiving non-contingent IV infusions of methamphetamine (METH-NC) at 1 or 21 days withdrawal to determine the dopamine and glutamate responses in the nucleus accumbens (NAC) to a 2 mg/kg methamphetamine intraperitoneal challenge. Furthermore, basal NAC extracellular glutamate content was assessed employing no net-flux procedures in these three groups at both time points. At both 1- and 21-day withdrawal points, methamphetamine elicited a rise in extracellular dopamine in SAL animals and this effect was sensitized in METH-NC rats. However, METH-SA animals showed a much greater sensitized dopamine response to the drug challenge compared with the other groups. Additionally, acute methamphetamine decreased extracellular glutamate in both SAL and METH-NC animals at both time-points. In contrast, METH-SA rats exhibited a modest and delayed rise in glutamate at 1-day withdrawal and this rise was sensitized at 21 days withdrawal. Finally, no net-flux microdialysis revealed elevated basal glutamate and increased extraction fraction at both withdrawal time-points in METH-SA rats. Although METH-NC rats exhibited no change in the glutamate extraction fraction, they exhibited a time-dependent elevation in basal glutamate levels. These data illustrate for the first time that a history of methamphetamine self-administration produces enduring changes in NAC neurotransmission and that non-pharmacological factors have a critical role in the expression of these methamphetamine-induced neurochemical adaptations. PMID:22030712

Smoking history, nicotine dependence, and changes in craving and mood during short-term smoking abstinence in alcohol dependent vs. control smokers.

PubMed

Heffner, Jaimee L; Mingione, Carolyn; Blom, Thomas J; Anthenelli, Robert M

2011-03-01

The goal of this study was to compare lifetime cigarette smoking, severity of nicotine dependence, and subjective effects of short-term tobacco abstinence in abstinent alcohol dependent (AD) and control smokers. AD (n=119) and control (n=55) ever-smokers were compared on tobacco use history and nicotine dependence. Negative affect and craving to smoke were examined in a subsample of currently smoking AD (N=34) and control (N=19) participants during a 6-h period of tobacco abstinence using the Profile of Mood States (POMS) and the Questionnaire on Smoking Urges-Brief (QSU-B). Although AD smokers did not differ from controls on heaviness of smoking, they were more likely to meet lifetime criteria for nicotine dependence. AD smokers also reported more withdrawal symptoms and were more likely to endorse withdrawal-related depressed mood during past smoking reduction or abstinence periods. During short-term abstinence, AD smokers were more likely to report high craving to smoke for negative affect relief within the first 150 min of tobacco abstinence, but did not differ from controls on overall craving to smoke or withdrawal-related negative affect on the POMS. Results support previous findings that AD smokers have a greater prevalence of nicotine dependence and more severe nicotine withdrawal, with a greater propensity toward withdrawal-related depressed mood. These results, along with our novel finding that greater craving to smoke in abstaining smokers with AD is specific to negative affect-related craving, suggest that negative reinforcement may be a particularly salient factor in the maintenance of tobacco use among individuals with AD. Copyright © 2010 Elsevier Ltd. All rights reserved.

Changes in Expression of Dopamine, Its Receptor, and Transporter in Nucleus Accumbens of Heroin-Addicted Rats with Brain-Derived Neurotrophic Factor (BDNF) Overexpression.

PubMed

Li, Yixin; Xia, Baijuan; Li, Rongrong; Yin, Dan; Liang, Wenmei

2017-06-09

BACKGROUND The aim of this study was to explore how changes in the expression of BDNF in MLDS change the effect of BDNF on dopamine (DA) neurons, which may have therapeutic implications for heroin addiction. MATERIAL AND METHODS We established a rat model of heroin addiction and observed changes in the expression of BDNF, DA, dopamine receptor (DRD), dopamine transporter (DAT), and other relevant pathways in NAc. We also assessed the effect of BDNF overexpression in the NAc, behavioral changes of heroin-conditioned place preference (CPP), and naloxone withdrawal in rats with high levels of BDNF. We established 5 adult male rat groups: heroin addiction, lentivirus transfection, blank virus, sham operation, and control. The PCR gene chip was used to study gene expression changes. BDNF lentivirus transfection was used for BDNF overexpression. A heroin CPP model and a naloxone withdrawal model of rats were established. RESULTS Expression changes were found in 20 of the 84 DA-associated genes in the NAc of heroin-addicted rats. Weight loss and withdrawal symptoms in the lentivirus group for naloxone withdrawal was less than in the blank virus and the sham operation group. These 2 latter groups also showed significant behavioral changes, but such changes were not observed in the BDNF lentivirus group before or after training. DRD3 and DAT increased in the NAc of the lentivirus group. CONCLUSIONS BDNF and DA in the NAc are involved in heroin addiction. BDNF overexpression in NAc reduces withdrawal symptoms and craving behavior for medicine induced by environmental cues for heroin-addicted rats. BDNF participates in the regulation of the dopamine system by acting on DRD3 and DAT.

Determining Regional Sensitivity to Energy-Related Water Withdrawals in Minnesota

NASA Astrophysics Data System (ADS)

McCulloch, A.; Brauman, K. A.

2015-12-01

Minnesota has abundant freshwater resources, yet concerns about water-impacts of energy and mining development are increasing. Statewide, total annual water withdrawals have increased, and, in some watersheds, withdrawals make up a large fraction of available water. The energy and mining sectors play a critical role in determining water availability, as water is used to irrigate biofuel feedstock crops, cool thermoelectric plants, and process and transport fuels and iron ore. We evaluated the Minnesota Department of Natural Resources (DNR) Water and Reporting System (MPARS) dataset (1988-2014) to identify regions where energy and mining-related water withdrawals are high or where they are increasing. The energy and mining sectors account for over 65 percent of total water extractions in Minnesota, but this percentage is greater in some regions. In certain southern and northeastern Minnesota watersheds, these extractions account for 90 percent of total water demand. Sensitivity to these demands is not dependent on total water demand alone, and is also not uniform among watersheds. We identified and evaluated factors influencing sensitivity, including population, extraction type (surface water or groundwater), percentage of increased demand, and whether withdrawals are consumptive or not. We determined that southern Minnesota is particularly sensitive to increased water demands, because of growing biofuel and sand extraction industries (the products of which are used in hydraulic fracturing). In the last ten years, ethanol production in Minnesota has increased by 440 percent, and over fifteen refineries (each with a capacity over 1.1 billion gallons), have been built. These users primarily extract from surface water bodies within a few watersheds, compromising local supplies. As these energy-related industries continue to grow, so will the demand for freshwater resources. Determining regional sensitivity to increased demands will allow policy-makers to manage the increased competition for Minnesota's future water supplies.

Social withdrawal in children moderates the association between parenting styles and the children's own socioemotional development.

PubMed

Zarra-Nezhad, Maryam; Kiuru, Noona; Aunola, Kaisa; Zarra-Nezhad, Mansour; Ahonen, Timo; Poikkeus, Anna-Maija; Lerkkanen, Marja-Kristiina; Nurmi, Jari-Erik

2014-11-01

Social withdrawal in early childhood is a risk factor for later socioemotional difficulties. This study examined the joint effects of children's social withdrawal and mothers' and fathers' parenting styles on children's socioemotional development. Based on diatheses-stress, vantage sensitivity, and differential susceptibility models, socially withdrawn children were assumed to be more prone to parental influences than others. Teachers rated 314 children on prosocial skills, and internalizing and externalizing behaviors at three points in time between grades 1-3. Mothers (n = 279) and fathers (n = 182) filled in questionnaires measuring their affection, and their behavioral and psychological control at the same points in time. Teacher reports on children's level of social withdrawal were obtained at the end of kindergarten. Panel analysis showed that particularly those children who showed signs of social withdrawal were vulnerable to the negative effects of low maternal affection in terms of externalizing behavior. Moreover, among these children, mothers' and fathers' psychological control predicted high levels of internalizing problem but, at the same time, mothers' psychological control predicted also a high level of prosocial behavior and low levels of externalizing problem. The results supported the diathesis-stress model more than the differential susceptibility model. For example, socially withdrawn children were found to be particularly vulnerable to the negative effects of low maternal affection. Although maternal psychological control had positive effects on the prosocial skills of socially withdrawn children, and reduced the amount of externalizing problems, it was at the same time associated with an increase in their internalizing problems. In this way, socially withdrawn children seem to be at risk of pleasing their mothers at the cost of their own well-being. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Family factors affect clinician attitudes in pediatric end-of-life decision making: a randomized vignette study.

PubMed

Ruppe, Michael D; Feudtner, Chris; Hexem, Kari R; Morrison, Wynne E

2013-05-01

Conflicts between families and clinicians in pediatric end-of-life (EOL) care cause distress for providers, dissatisfaction for patients' families, and potential suffering for terminally ill children. We hypothesized that family factors might influence clinician decision making in these circumstances. We presented vignettes concerning difficult EOL decision making, randomized for religious objection to therapy withdrawal and perceived level of family involvement, to clinicians working in three Children's Hospital intensive care units. Additionally, attitudes about EOL care were assessed. Three hundred sixty-four respondents completed the questionnaire, for an overall response rate of 54%. Respondents receiving the "involved family" vignette were more likely to agree to continue medical care indefinitely (P<0.0005). Respondents were marginally more likely to pursue a court-appointed guardian for those patients whose families had nonreligious objections to withdrawal (P=0.05). Respondents who thought that a fear of being sued affected decisions were less likely to pursue unilateral withdrawal (odds ratio 0.8, 95% CI=0.6-0.9). Those who felt personal distress as a result of difficult EOL decision making, thought they often provided "futile" care, or those who felt EOL care was effectively addressed at the institution were less likely to want to defer to the parents' wishes (range of odds ratios 0.7-1). In this randomized vignette study, we have shown that family factors, particularly how involved a family seems to be in a child's life, affect what clinicians think is ethically appropriate in challenging EOL cases. Knowledge of how a family's degree of involvement may affect clinicians should be helpful to the clinical ethics consultants and offer some degree of insight to the clinicians themselves. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: evidence from a long-access self-administration model in the rat.

PubMed

Cadet, Jean Lud; Brannock, Christie; Jayanthi, Subramaniam; Krasnova, Irina N

2015-04-01

Methamphetamine use disorder is a chronic neuropsychiatric disorder characterized by recurrent binge episodes, intervals of abstinence, and relapses to drug use. Humans addicted to methamphetamine experience various degrees of cognitive deficits and other neurological abnormalities that complicate their activities of daily living and their participation in treatment programs. Importantly, models of methamphetamine addiction in rodents have shown that animals will readily learn to give themselves methamphetamine. Rats also accelerate their intake over time. Microarray studies have also shown that methamphetamine taking is associated with major transcriptional changes in the striatum measured within a short or longer time after cessation of drug taking. After a 2-h withdrawal time, there was increased expression of genes that participate in transcription regulation. These included cyclic AMP response element binding (CREB), ETS domain-containing protein (ELK1), and members of the FOS family of transcription factors. Other genes of interest include brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor, type 2 (TrkB), and synaptophysin. Methamphetamine-induced transcription was found to be regulated via phosphorylated CREB-dependent events. After a 30-day withdrawal from methamphetamine self-administration, however, there was mostly decreased expression of transcription factors including junD. There was also downregulation of genes whose protein products are constituents of chromatin-remodeling complexes. Altogether, these genome-wide results show that methamphetamine abuse might be associated with altered regulation of a diversity of gene networks that impact cellular and synaptic functions. These transcriptional changes might serve as triggers for the neuropsychiatric presentations of humans who abuse this drug. Better understanding of the way that gene products interact to cause methamphetamine addiction will help to develop better pharmacological treatment of methamphetamine addicts.

Time-course of the DSM-5 cannabis withdrawal symptoms in poly-substance abusers

PubMed Central

2013-01-01

Background Evidence is accumulating that a cannabis withdrawal syndrome is common, of clinical significance, and has a clear time course. Up till now, very limited data exist on the cannabis withdrawal symptoms in patients with co-morbid substance use disorders, other than cannabis use and tobacco use. Methods Symptoms of withdrawal were assessed through patient self-reports during detoxification in Danish residential rehabilitation centers. Patients (n = 90) completed booklets three times during their first month at the treatment centre. Self-reported withdrawal symptoms was rated using the DSM-5 Withdrawal Symptom Check List with withdrawal symptoms from all classes of substances, with no indication that the described symptoms should be attributed to withdrawal. Self-reported time since last use of cannabis was used as a predictor of cannabis withdrawal severity. Results With the exception of loss of appetite, time since last use of cannabis was associated with all types of withdrawal symptoms listed in the DSM-5. Only four of 19 symptoms intended to measure withdrawal from other substances were related to time since last use of cannabis, including vivid, unpleasant dreams. Conclusions The findings yield strong support to the notion of a cannabis withdrawal syndrome, and gives further evidence for the inclusion of the criterion of vivid, unpleasant dreams. Further, the findings speak against the significance of demand characteristics in determining the course of the symptoms of cannabis withdrawal. PMID:24118963

20 CFR 408.355 - Can you withdraw your application?

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 408.355 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Filing Applications Withdrawal of Application § 408.355 Can you withdraw your application? (a) Request for withdrawal filed before a determination is made. You may withdraw your application...

Conjunctive-use optimization model of the Mississippi River Valley alluvial aquifer of northeastern Arkansas

USGS Publications Warehouse

Czarnecki, John B.; Clark, Brian R.; Reed, Thomas B.

2003-01-01

The Mississippi River Valley alluvial aquifer is a water-bearing assemblage of gravels and sands that underlies about 32,000 square miles of Missouri, Kentucky, Tennessee, Mississippi, Louisiana, and Arkansas. Because of the heavy demands placed on the aquifer, several large cones of depression over 100 feet deep have formed in the potentiometric surface, resulting in lower well yields and degraded water quality in some areas. A ground-water flow model of the alluvial aquifer was previously developed for an area covering 14,104 square miles, extending northeast from the Arkansas River into the northeast corner of Arkansas and parts of southeastern Missouri. The flow model showed that continued ground-water withdrawals at rates commensurate with those of 1997 could not be sustained indefinitely without causing water levels to decline below half the original saturated thickness of the aquifer. To develop estimates of withdrawal rates that could be sustained in compliance with the constraints of critical ground-water area designation, conjunctive-use optimization modeling was applied to the flow model of the alluvial aquifer in northeastern Arkansas. Ground-water withdrawal rates form the basis for estimates of sustainable yield from the alluvial aquifer and from rivers specified within the alluvial aquifer model. A management problem was formulated as one of maximizing the sustainable yield from all ground-water and surface-water withdrawal cells within limits imposed by plausible withdrawal rates, and within specified constraints involving hydraulic head and streamflow. Steady-state flow conditions were selected because the maximized withdrawals are intended to represent sustainable yield of the system (a rate that can be maintained indefinitely). Within the optimization model, 11 rivers are specified. Surface-water diversion rates that occurred in 2000 were subtracted from specified overland flow at the appropriate river cells. Included in these diversions were the planned diversions of 63,339,248 ft3/d for the Bayou Meto project area and 55,078,367 ft3/d for the Grand Prairie project area, which factor in an additional 30 and 40 percent transmission loss, respectively. Streamflow constraints were specified at all 1,165 river cells based on average 7-day minimum flows for 10 years. Sustainable yield for all rivers ranged from 0 (Current, Little Red, and Bayou Meto Rivers) to almost 5 billion cubic feet per day for the Arkansas River. Total sustainable yield from all rivers combined was 12.8 billion cubic feet per day, which represents a substantial source for supplementing ground water to meet the total water demand. Sustainable-yield estimates are affected by the allowable upper limit on withdrawals from wells specified in the optimization model. Ground-water withdrawal rates were allowed to vary as much as 200 percent of the withdrawal rate in 1997. As the overall upper limit on withdrawals is increased, the sustainable yield generally increases. Tests with the optimization model show that without limits on pumping, wells adjacent to sources of water would have optimized withdrawal rates that were orders of magnitude larger than rates corresponding to those of 1997. The sustainable yield from ground water for the entire study area while setting the maximum upper limit as the amount withdrawn in 1997 is 360 million cubic feet per day, which is only about 57 percent of the amount withdrawn in 1997 (635.6 million cubic feet per day). Optimal sustainable yields from within the Bayou Meto irrigation project area and within the Grand Prairie irrigation project area are 18.1 and 9.1 million cubic feet per day, respectively, assuming a maximum allowable withdrawal rate equal to 1997 rates. These values of sustainable yield represent 35 and 30 percent respectively of the amount pumped from these project areas in 1997. Unmet demand (defined as the difference between the optimized withdrawal rate or sustainable yield, a

Water levels and groundwater and surface-water exchanges in lakes of the northeast Twin Cities Metropolitan Area, Minnesota, 2002 through 2015

USGS Publications Warehouse

Jones, Perry M.; Trost, Jared J.; Erickson, Melinda L.

2016-10-19

OverviewThis study assessed lake-water levels and regional and local groundwater and surface-water exchanges near northeast Twin Cities Metropolitan Area lakes applying three approaches: statistical analysis, field study, and groundwater-flow modeling.  Statistical analyses of lake levels were completed to assess the effect of physical setting and climate on lake-level fluctuations of selected lakes. A field study of groundwater and surface-water interactions in selected lakes was completed to (1) estimate potential percentages of surface-water contributions to well water across the northeast Twin Cities Metropolitan Area, (2) estimate general ages for waters extracted from the wells, and (3) assess groundwater inflow to lakes and lake-water outflow to aquifers downgradient from White Bear Lake.  Groundwater flow was simulated using a steady-state, groundwater-flow model to assess regional groundwater and surface-water exchanges and the effects of groundwater withdrawals, climate, and other factors on water levels of northeast Twin Cities Metropolitan Area lakes.

Severe Henoch-Schönlein purpura with infliximab for ulcerative colitis.

PubMed

Song, Yang; Shi, Yan-Hong; He, Chong; Liu, Chang-Qin; Wang, Jun-Shan; Zhao, Yu-Jie; Guo, Yan-Min; Wu, Rui-Jin; Feng, Xiao-Yue; Liu, Zhan-Ju

2015-05-21

Infliximab (IFX) is an anti-tumor necrosis factor chimeric antibody that is effective for treatment of autoimmune disorders such as Crohn's disease and ulcerative colitis (UC). IFX is well tolerated with a low incidence of adverse effects such as infections, skin reactions, autoimmunity, and malignancy. Dermatological manifestations can appear as infusion reaction, vasculitis, cutaneous infections, psoriasis, eczema, and skin cancer. Here, we present an unusual case of extensive and sporadic subcutaneous ecchymosis in a 69-year-old woman with severe UC, partial colectomy and cecostomy, following her initial dose of IFX. The reaction occurred during infliximab infusion, and withdrawal of IFX led to gradual alleviation of her symptoms. We concluded that Henoch-Schönlein purpura, a kind of leukocytoclastic vasculitis, might have contributed to the development of the bruising. Although the precise mechanisms of the vasculitis are still controversial, such a case highlights the importance of subcutaneous adverse effects in the management of UC with IFX.

How and why to study autophagy in Drosophila: it's more than just a garbage chute.

PubMed

Nagy, Péter; Varga, Ágnes; Kovács, Attila L; Takáts, Szabolcs; Juhász, Gábor

2015-03-01

During the catabolic process of autophagy, cytoplasmic material is transported to the lysosome for degradation and recycling. This way, autophagy contributes to the homeodynamic turnover of proteins, lipids, nucleic acids, glycogen, and even whole organelles. Autophagic activity is increased by adverse conditions such as nutrient limitation, growth factor withdrawal and oxidative stress, and it generally protects cells and organisms to promote their survival. Misregulation of autophagy is likely involved in numerous human pathologies including aging, cancer, infections and neurodegeneration, so its biomedical relevance explains the still growing interest in this field. Here we discuss the different microscopy-based, biochemical and genetic methods currently available to study autophagy in various tissues of the popular model Drosophila. We show examples for results obtained in different assays, explain how to interpret these with regard to autophagic activity, and how to find out which step of autophagy a given gene product is involved in. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Fatalities temporally associated with the ingestion of ibogaine.

PubMed

Alper, Kenneth R; Stajić, Marina; Gill, James R

2012-03-01

Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical and nonmedical settings for opioid detoxification and other substance use indications. All available autopsy, toxicological, and investigative reports were systematically reviewed for the consecutive series of all known fatalities outside of West Central Africa temporally related to the use of ibogaine from 1990 through 2008. Nineteen individuals (15 men, four women between 24 and 54 years old) are known to have died within 1.5-76 h of taking ibogaine. The clinical and postmortem evidence did not suggest a characteristic syndrome of neurotoxicity. Advanced preexisting medical comorbidities, which were mainly cardiovascular, and/or one or more commonly abused substances explained or contributed to the death in 12 of the 14 cases for which adequate postmortem data were available. Other apparent risk factors include seizures associated with withdrawal from alcohol and benzodiazepines and the uninformed use of ethnopharmacological forms of ibogaine. © 2012 American Academy of Forensic Sciences.

Impact of smoking on the course of Graves' disease after withdrawal of antithyroid drugs.

PubMed

Quadbeck, B; Roggenbuck, U; Janssen, O E; Hahn, S; Mann, K; Hoermann, R

2006-09-01

Cigarette smoking has been reported to alter relapse rate in patients with Graves' disease (GD). However, the predictive effect of smoking in GD patients after withdrawal of antithyroid drug treatment (ATDT) is still controversial. A prospective multicenter trial has previously identified smoking as an independent risk factor for relapse. Based on this study, the present paper gives a more detailed analysis of the impact of smoking on the long-term course of GD after ATDT withdrawal. To this end, 86 smokers and 177 non-smokers were followed during two years after ATDT cessation. At the end of ATDT (visit 1) and four weeks later (visit 2) smokers had significant higher TSH receptor antibody (TRAb) levels than non-smokers (10.0 IU/L+/-1.6; mean+/-SEM vs. 6.4 IU/L+/-0.9; 11.0 IU/L+/-1.8 vs. 6.8 IU/L+/-0.8, p < 0.01, respectively). During follow-up, Kaplan Meier analysis showed a significantly higher relapse rate in smokers than non-smokers. A subset of GD patients with TRAb levels >10 IU/L had the highest risk to develop relapse during follow-up. Among them, smokers more often relapsed than non-smokers irrespective of TRAb levels, p < 0.01. Thus, in smokers with TRAb levels > or =10 IU/L the predictive values of a positive and negative test for relapse was 68% and 73%, respectively (specificity 95%). In conclusion, we identified two effects by which smoking alters the course of GD. First, smoking is implicated to elevate TRAb levels and therefore increase the risk for relapse during follow-up. Second, smoking is an independent risk factor to worsen the clinical course of both, GD patients with low and high immunological risk to experience relapse after a successful outcome of ATDT. Thus, our data suggest that smoking has modifying immunological consequences and an adverse impact on the course of GD after withdrawal of ATDT. Therefore, patients should be encouraged to stop smoking.

Water for Energy: Quantifying Water Use in the United States Energy Economy as of 2014

NASA Astrophysics Data System (ADS)

Grubert, E.; Sanders, K.

2016-12-01

The US energy economy requires significant quantities of water for primary energy extraction, processing and refining, conversion to secondary forms, waste disposal and site remediation. Major shifts in the energy sector have affected the water requirements of the US energy system in ways that are widely acknowledged but poorly quantified. For example, hydraulic fracturing represents a new demand for water, but wind turbines and solar photovoltaics require essentially no water. Further, many water intensity factors commonly used in energy studies are several decades old. This work updates water intensity factors for the US energy system based on recent data and thermodynamic principles, with a near comprehensive treatment of 16 energy fuel cycles from resource capture through post-conversion waste management. For the first time, we also provide absolute estimates of water withdrawn and consumed for energy, differentiated by water source (surface, ground, or reclaimed) and quality (fresh, brackish, saline, and brine). We find that as of 2014, the US consumed approximately 19 billion cubic meters (m3) and withdrew 210 billion m3 of water for the energy system. Most of this water was freshwater (76% of consumption and 86% of withdrawal). Essentially all withdrawals (excluding flow through hydroelectric facilities) are for thermoelectric power plant cooling, accounting for about 38% of total US water withdrawals. Water consumption for energy is estimated at about 12% of total US water consumption, of which an estimated 37% and 17% is for thermoelectric cooling and evaporation from hydroelectric reservoirs, respectively. Withdrawals and consumption for life cycle stages other than thermoelectric cooling are reported in detail, with locally relevant findings like basin-specific water use for coal mining. This work provides a new baseline understanding of water use for the changing US energy economy that can guide decision makers integrating water and energy decisions.

Withdrawal of anticancer therapy in advanced disease: a systematic literature review.

PubMed

Clarke, G; Johnston, S; Corrie, P; Kuhn, I; Barclay, S

2015-11-11

Current guidelines set out when to start anticancer treatments, but not when to stop as the end of life approaches. Conventional cytotoxic agents are administered intravenously and have major life-threatening toxicities. Newer drugs include molecular targeted agents (MTAs), in particular, small molecule kinase-inhibitors (KIs), which are administered orally. These have fewer life-threatening toxicities, and are increasingly used to palliate advanced cancer, generally offering additional months of survival benefit. MTAs are substantially more expensive, between £2-8 K per month, and perceived as easier to start than stop. A systematic review of decision-making concerning the withdrawal of anticancer drugs towards the end of life within clinical practice, with a particular focus on MTAs. Nine electronic databases searched. PRISMA guidelines followed. Forty-two studies included. How are decisions made? Decision-making was shared and ongoing, including stopping, starting and trying different treatments. Oncologists often experienced 'professional role dissonance' between their self-perception as 'treaters', and talking about end of life care. Why are decisions made? Clinical factors: disease progression, worsening functional status, treatment side-effects. Non-clinical factors: physicians' personal experience, values, emotions. Some patients continued treatment to maintain 'hope', often reflecting limited understanding of palliative goals. When are decisions made? Limited evidence reveals patients' decisions based upon quality of life benefits. Clinicians found timing withdrawal particularly challenging. Who makes the decisions? Decisions were based within physician-patient interaction. Oncologists report that decisions around stopping chemotherapy treatment are challenging, with limited evidence-based guidance outside of clinical trial protocols. The increasing availability of oral MTAs is transforming the management of incurable cancer; blurring boundaries between active treatment and palliative care. No studies specifically addressing decision-making around stopping MTAs in clinical practice were identified. There is a need to develop an evidence base to support physicians and patients with decision-making around the withdrawal of these high cost treatments.

Extinction of aversive memories associated with morphine withdrawal requires ERK-mediated epigenetic regulation of brain-derived neurotrophic factor transcription in the rat ventromedial prefrontal cortex.

PubMed

Wang, Wei-Sheng; Kang, Shuo; Liu, Wen-Tao; Li, Mu; Liu, Yao; Yu, Chuan; Chen, Jie; Chi, Zhi-Qiang; He, Ling; Liu, Jing-Gen

2012-10-03

Recent evidence suggests that histone deacetylase (HDAC) inhibitors facilitate extinction of rewarding memory of drug taking. However, little is known about the role of chromatin modification in the extinction of aversive memory of drug withdrawal. In this study, we used conditioned place aversion (CPA), a highly sensitive model for measuring aversive memory of drug withdrawal, to investigate the role of epigenetic regulation of brain-derived neurotrophic factor (BDNF) gene expression in extinction of aversive memory. We found that CPA extinction training induced an increase in recruiting cAMP response element-binding protein (CREB) to and acetylation of histone H3 at the promoters of BDNF exon I transcript and increased BDNF mRNA and protein expression in the ventromedial prefrontal cortex (vmPFC) of acute morphine-dependent rats and that such epigenetic regulation of BDNF gene transcription could be facilitated or diminished by intra-vmPFC infusion of HDAC inhibitor trichostatin A or extracellular signal-regulated kinase (ERK) inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene) before extinction training. Correspondingly, disruption of the epigenetic regulation of BDNF gene transcription with U0126 or suppression of BDNF signaling with Trk receptor antagonist K252a or BDNF scavenger tyrosine kinase receptor B (TrkB)-Fc blocked extinction of CPA behavior. We also found that extinction training-induced activation of ERK and CREB and extinction of CPA behavior could be potentiated or suppressed by intra-vmPFC infusion of d-cycloserine, a NMDA receptor partial agonist or aminophosphonopentanoic acid, a NMDA receptor antagonist. We conclude that extinction of aversive memory of morphine withdrawal requires epigenetic regulation of BDNF gene transcription in the vmPFC through activation of the ERK-CREB signaling pathway perhaps in a NMDA receptor-dependent manner.

Effects of Acute Withdrawal on Ethanol-Induced Conditioned Place Preference in DBA/2J mice

PubMed Central

Dreumont, Sarah E.; Cunningham, Christopher L.

2013-01-01

Rationale Re-exposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol. Objective The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal. Methods DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0 or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The Withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The No Withdrawal (NW) group did not experience acute withdrawal during conditioning trials, but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal. Results All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity. Conclusions Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism. PMID:24096534

A genetic perspective on the proposed inclusion of cannabis withdrawal in DSM-5.

PubMed

Verweij, K J H; Agrawal, A; Nat, N O; Creemers, H E; Huizink, A C; Martin, N G; Lynskey, M T

2013-08-01

Various studies support the inclusion of cannabis withdrawal in the diagnosis of cannabis use disorder (CUD) in the upcoming DSM-5. The aims of the current study were to (1) estimate the prevalence of DSM-5 cannabis withdrawal (criterion B), (2) estimate the role of genetic and environmental influences on individual differences in cannabis withdrawal and (3) determine the extent to which genetic and environmental influences on cannabis withdrawal overlap with those on DSM-IV-defined abuse/dependence. The sample included 2276 lifetime cannabis-using adult Australian twins. Cannabis withdrawal was defined in accordance with criterion B of the proposed DSM-5 revisions. Cannabis abuse/dependence was defined as endorsing one or more DSM-IV criteria of abuse or three or more dependence criteria. The classical twin model was used to estimate the genetic and environmental influences on variation in cannabis withdrawal, along with its covariation with abuse/dependence. Of all the cannabis users, 11.9% met criteria for cannabis withdrawal. Around 50% of between-individual variation in withdrawal could be attributed to additive genetic variation, and the rest of the variation was mostly due to non-shared environmental influences. Importantly, the genetic influences on cannabis withdrawal almost completely (99%) overlapped with those on abuse/dependence. We have shown that cannabis withdrawal symptoms exist among cannabis users, and that cannabis withdrawal is moderately heritable. Genetic influences on cannabis withdrawal are the same as those affecting abuse/dependence. These results add to the wealth of literature that recommends the addition of cannabis withdrawal to the diagnosis of DSM-5 CUD.

Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

PubMed

Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

2016-07-01

We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

A genetic perspective on the proposed inclusion of cannabis withdrawal in the DSM-5

PubMed Central

Verweij, K.J.H.; Agrawal, A.; Nat, N.O.; Creemers, H.E.; Huizink, A.C.; Martin, N.G.; Lynskey, M.T.

2013-01-01

Background Various studies support the inclusion of cannabis withdrawal to the diagnosis of cannabis use disorders in the upcoming DSM-5. The aims of the current study were to (1) estimate the prevalence of DSM-5 cannabis withdrawal (Criterion B), (2) estimate the role of genetic and environmental influences on individual differences in cannabis withdrawal, and (3) determine the extent to which genetic and environmental influences on cannabis withdrawal overlap with those on DSM-IV defined abuse/dependence. Methods The sample included 2276 lifetime cannabis-using adult Australian twins. Cannabis withdrawal was defined in accordance with Criterion B of the proposed DSM-5 revisions. Cannabis abuse/dependence was defined as endorsing one or more DSM-IV criteria of abuse or three or more dependence criteria. The classical twin model was used to estimate the genetic and environmental influences on variation in cannabis withdrawal, as well as its covariation with abuse/dependence. Results Of all cannabis users 11.9% met criteria for cannabis withdrawal. Around 50% of between-individual variation in withdrawal could be attributed to additive genetic variation, and the rest of the variation was mostly due to non-shared environmental influences. Importantly, the genetic influences on cannabis withdrawal almost completely (99%) overlapped with those on abuse/dependence. Conclusions We showed that cannabis withdrawal symptoms exist among cannabis users, and that cannabis withdrawal is moderately heritable. Genetic influences on cannabis withdrawal are the same as those influencing abuse/dependence. These results add to the wealth of literature that recommends the addition of cannabis withdrawal to the diagnosis of DSM-5 cannabis use disorders. PMID:23194657