Impacts of stigma and discrimination in the workplace on people living with psychosis.

BACKGROUND: Employment holds many benefits for people living with psychosis. However, significant barriers to employment for this cohort appear to exist, notably stigma and discrimination against people living with serious mental health conditions. We asked: Would a qualitative sample including multiple stakeholder groups reveal similar results and if so, what would be the main impacts of such stigma and discrimination? METHOD: This analysis used data from a qualitative study that had employed focus groups and interviews to investigate the employment barriers and support needs of people living with psychosis, including views of the multiple stakeholders (those living with mental health conditions, health professionals, care-givers, employments consultants and community members and employers). RESULTS: The impacts of workplace stigma and discrimination on people living with psychosis included work avoidance, reluctance to disclose mental health conditions to employers, work-related stress, and reduced longevity of employment. CONCLUSIONS: Significant impacts from such stigma and discrimination were found in this study. The findings indicate a need to provide support mechanisms and to change the culture of workplaces to improve employment opportunities and outcomes for people living with psychosis.

Effect of alternative on-site wastewater treatment on the viability and culturability of Salmonella choleraesuis.

The objective of this study was to determine how alternative on-site wastewater treatment systems (i.e. subsurface flow constructed wetlands, intermittent sand filters and intermittent peat filters) affect the viability and culturability of Salmonella choleraesuis (serotype typhimurium, ATCC 23567). Influent was a high strength septic tank effluent (BOD5 240-344 mgL(-1), TN approximately 100 mgL(-1), TP approximately 15 mgL(-1)) at the Natural Resources Research Institute's (NRRI) alternative treatment system test facility in northern Minnesota. Treatment systems were inoculated with cultures of S. choleraesuis for 5-7 consecutive days in summer and winter during 1998-99. After the seeding, outflow samples were taken until Salmonella counts were sustained at background levels. In addition to culture-based enumeration, S. choleraesuis abundances were also measured using fluorescent in situ hybridization (FISH) alone and in combination with the direct viable count method (DVC) to determine if plate counts underestimated total and viable Salmonella abundances and if the Salmonella cell viability changed after passing through the treatment systems. In most cases, total and viable cell abundances in treatment system effluents were several orders of magnitude higher than cultured cell abundances. Our results indicate that the culture-based method underestimated viable concentrations of the model pathogen, S. choleraesuis. Salmonella cell viability decreased in effluents during the summer but increased during the winter. Using a culture-based enumeration method alone to determine removal efficiencies of bacterial indicators and pathogens for wastewater treatment systems may result in artificially high estimates of effective treatment.

Archaeal nucleic acids in picoplankton from great lakes on three continents.

Phylogenetic analysis of PCR-amplified 16S rRNA genes revealed the presence of archaea in picoplankton collected from the Laurentian Great Lakes in North America, Africa's Lake Victoria, and Lakes Ladoga and Onega in northeastern Eurasia. From 1 to 10% of the rRNA extracted from size-fractionated picoplankton (>0.2 microm but <1.2 microm) collected in the epilimnion and hypolimnion of these lakes was specific to the Archaea, whereas the majority of rRNA was derived from Bacteria. Analysis of the 16S rRNA genes cloned from these samples indicated they were closely related to crenarchaeal sequences that have been widely characterized from marine environments. The presence of nearly identical 16S rDNA clones in several of these geographically disparate lakes suggests a cosmopolitan distribution of specific subgroups of these Archaea in freshwater environments. Despite their abundance in the water column of freshwater lakes, we have no representatives of these crenarchaea in pure culture, and so their physiological characteristics and ecological role remain unknown.

Specifying the relations between affect and heavy alcohol use among young adults.

Current reformulations of the tension reduction hypothesis posit that only a subset of vulnerable individuals are at risk for drinking in response to negative affect. To further specify this model, this study examined the types of mood and social contexts under which affect and alcohol use are associated. Participants were 74 college students who completed repeated assessments of mood, alcohol use, friendship quality, and social support. A complex pattern of findings supported the moderating influences of gender, friendship factors, and the timing of behavior (i.e., weekends vs. weekdays) on the relation between affect and alcohol use. Young adults with less intimate and supportive friendships, as compared with their peers, showed risk for greater drinking following relative elevations in sadness and hostility. Such drinking episodes, in turn, predicted subsequent elevations in these same negative moods the following week. Gender differences in such a cyclical pattern of affect and alcohol use were found to vary across differing emotional experiences. Recommendations for a more refined theory of affect and alcohol use are discussed.

Ethanol, monoamines, and affect.

Evidence suggests that ethanol self-administration is directly related to central norepinephrine (NE) activity and inversely related to central serotonin (5-HT) activity. Normal male volunteers participated in a placebo controlled crossover design to assess the effects of 1-tyrosine (TY) and 1-tryptophan (TP) (precursors of catecholamines and 5-HT, respectively) in combination with ethanol, on several neurobehavioral measures. Ethanol by itself produced negative effects on several dimensions of mood. Dysphoria was potentiated by TP in combination with ethanol and either unchanged or attenuated by the combination of TY and ethanol. Ethanol impaired verbal recall, and neither TP nor TY in combination with ethanol altered that impairment. The results are consistent with the hypothesis that 5-HT mediates some of the negative mood effects produced by ethanol or antagonizes some of its positive effects, while NE at least partly mediates ethanol's positive effects on mood. Ethanol's impairment of verbal memory appears to be mediated by mechanisms outside the monoamine systems.

Removal of contaminants from soils by electric fields.

Application of a direct-current electric field in soils that contain contaminated liquid is expected to produce an important in situ means of environmental restoration. The electric field induces a motion of the liquid and dissolved ions that transports the contaminant to wells for removal. Electrode chemistry plays an important role, and reagents can be introduced at the electrodes to enhance contaminant removal rates. Experiments and modeling demonstrate high degrees of contaminant removal, propagation of sharp acid and base wave fronts from the electrodes, and a "focusing" effect by which metals accumulate in regions of the soil.

Interaction between ethanol and calcium channel blockers in humans.

The purpose of this study was to test the hypothesis that pretreatment with Ca2+ channel blockers would antagonize the effects of ethanol intoxication in humans. The Ca2+ channel blockers verapamil and nifedipine were chosen because preclinical research has shown them to decrease certain behavioral effects of ethanol in animals. Sixteen healthy, male, paid volunteers, moderate users of ethanol, participated in the study (six in the verapamil and 10 in the nifedipine paradigms). Gelatin capsules containing verapamil (80 mg, 160 mg, or placebo) were administered orally 90 min before ethanol ingestion; whereas, gelatin capsules containing nifedipine (10 mg, 20 mg, or placebo) were administered 30 min before ethanol ingestion. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Subjects were tested in a single-blind, latin-square, cross-over design with each of the following six conditions: placebo ethanol-placebo blocker, placebo ethanol-low dose blocker, placebo ethanol-high dose blocker, ethanol-placebo blocker, ethanol-low dose blocker, and ethanol-high dose blocker. The variables measured in this study were subjective rating of ethanol intoxication, Addiction Research Center Inventory alcohol scale, heart rate, blood pressure, short-term memory, accuracy and latency of response in the Simulator Evaluation of Drug Impairment task, and blood ethanol concentrations by breath analyzer. Results indicate that pretreatment with either verapamil or nifedipine failed to antagonize the inebriating effects of ethanol including its decremental effects on short-term memory and psychomotor performance.

Dual staining of natural bacterioplankton with 4',6-diamidino-2-phenylindole and fluorescent oligonucleotide probes targeting kingdom-level 16S rRNA sequences.

A method for quantifying eubacterial cell densities in dilute communities of small bacterioplankton is presented. Cells in water samples were stained with 4',6-diamidino-2-phenylindole (DAPI), transferred to gelatin-coated slides, and hybridized with rhodamine-labeled oligonucleotide probes specific for kingdom-level 16S rRNA sequences. Between 48 and 69% of the cells captured on membrane filters were transferred to gelatin-coated slides. The number of DAPI-stained cells that were visualized with eubacterial probes varied from 35 to 67%. Only 2 to 4% of these cells also fluoresced following hybridization with a probe designed to target a eukaryotic 16S rRNA sequence. Between 0.1 and 6% of the bacterioplankton in these samples were autofluorescent and may have been mistaken as cells that hybridized with fluorescent oligonucleotide probes. Dual staining allows precise estimates of the efficiency of transfers of cells to gelatin films and can be used to measure the percentage of the total bacterioplankton that also hybridize with fluorescent oligonucleotide probes, indicating specific phylogenetic groups.

Interaction between ethanol and dextroamphetamine: effects on psychomotor performance.

The objective of this study was to investigate the interaction between ethanol and dextroamphetamine with regard to psychomotor performance. Twelve healthy, male, paid volunteers, moderate users of ethanol and amphetamines, participated in this study. Ethanol (0.85 g/kg or placebo) was administered over a 30-min interval. Five minutes before the termination of ethanol or placebo ingestion, dextroamphetamine elixir (0.09 mg/kg, 0.18 mg/kg or placebo) diluted in 50 ml of orange juice was administered. Subjects were tested in a single-blind, latin-square, crossover design with each of the following six conditions: placebo ethanol/placebo dextroamphetamine; placebo ethanol/low-dose dextroamphetamine; placebo ethanol/high-dose dextroamphetamine; ethanol/placebo dextroamphetamine; ethanol/low-dose dextroamphetamine; and ethanol/high-dose dextroamphetamine. The variables measured in this study were: subjective rating of ethanol and dextroamphetamine intoxication, accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI task), blood ethanol concentration by breath analyzer, and plasma concentrations of dextroamphetamine by gas chromatography. Results indicate ethanol induced decrements in performance of the skills necessary to drive an automobile were significantly decreased by dextroamphetamine in a dose-response fashion. The administration of dextroamphetamine did not decrease the subjective ratings of ethanol intoxication.

Behavioral and endocrine interactions between thyrotropin-releasing hormone and ethanol in normal human subjects.

Thyrotropin-releasing hormone (TRH) has been shown to antagonize the depressant effects of ethanol in animals, but conflicting findings have been reported in humans. To test whether TRH counteracts any of a variety of ethanol-sensitive behavioral measures in normal human subjects and for an effect of ethanol on TRH-induced thyrotropin (TSH) and prolactin (PRL) response, we administered TRH (500 micrograms) or placebo over 1 min intravenously, 30 min after subjects had ingested 0.8 g/kg of ethanol or a placebo drink. Blood samples for TSH and PRL were drawn prior to and 15 and 30 min after injection. Eight male subjects were studied in a balanced, crossover design with each subject receiving placebo-placebo, TRH-placebo, placebo-ethanol, and TRH-ethanol. Whereas ethanol had significant and expected effects on subjective measures, memory, disinhibition, reaction time and time perception, TRH failed to counteract any ethanol effect, except for a small effect in one memory task. Similarly, no effect of ethanol on TRH-induced TSH or PRL response was found. Though the behavioral findings could be interpreted to indicate that TRH does not alter ethanol sensitive behaviors in humans it will be necessary to utilize higher dosages of TRH and/or TRH analogues before firmly drawing this conclusion.

The pharmacologic effects of daily marijuana smoking in humans.

Six healthy male, paid volunteers smoked one NIDA cigarette containing 1.0% THC each day for 13 consecutive days. They were tested before and after the period of drug administration by the following procedure: the subjects smoked one NIDA marijuana cigarette containing 1.0% THC followed 15 minutes later by the intravenous infusion of 52 micrograms/min of deuterated THC for 50 minutes. The THC plasma concentrations, ratings of "high" and heart rate effects produced by the combined drug administration were measured, and absolute bioavailability of smoked THC was calculated on Days 1 and 22. Statistical analyses indicate that the only significant changes induced by daily marijuana exposure were in cardioacceleration.

Clinical effects of daily methamphetamine administration.

This study investigated alterations in the disposition and pharmacodynamics of methamphetamine HCl after daily administration. Six male paid volunteers familiar with the use of amphetamines participated. Each subject was administered 10 mg of methamphetamine HCl as a slow-release preparation (Desoxyn Gradumets) at 9 a.m. for 13 consecutive days (days 2-14 of the study). On days 1 and 15 the subjects were challenged with 10 mg of oral deuterated methamphetamine HCl. Deuterated drug was used to differentiate plasma concentrations of challenge doses from those of daily doses. The heart rate, subjective perception of "high," and plasma concentrations of methamphetamine were examined on days 1 and 15. Repeated ANOVA measures indicate that a significant decrease in heart-rate acceleration in response to methamphetamine challenge occurred on day 15 [F(1,5) = 8.26, p less than or equal to 0.035]. However, no significant change in either the subjective ratings of "high" or the plasma concentrations of deuterated methamphetamine occurred. These findings indicate that the disposition of methamphetamine and its subjective effects were not altered by this period of daily exposure to a low dose of the drug. In contrast, tolerance to the heart-rate accelerating effect was observed.

Dose-response studies with thyrotropin-releasing hormone (TRH) in abstinent male alcoholics: evidence for selective thyrotroph dysfunction?

A reduced thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) has been reported in subjects with a history of alcoholism whereas prolactin (PRL) responses have generally been normal. One hypothesis proposed to explain the reduced TSH response is down-regulation of pituitary TRH receptors. If this is correct, PRL response should also be diminished. To account for the different dose-response characteristics of TSH/PRL we have given four dosages of TRH (25, 100, 500 and 800 micrograms) to eight noncirrhotic, male alcoholics abstinent from ethanol a minimum of 28 days and to seven male control subjects. Across the TRH dose range the alcoholic subjects exhibited reduced basal TSH (p = .01) and a reduced TSH response (p = .0023) but no differences in basal and stimulated PRL levels. Alcoholic subjects had higher basal T4, T3 and FT4I values than did control subjects but covarying for T4, T3 and FT4I did not change the significance of either TSH or PRL findings. No significant differences in estradiol, estrone, testosterone, cortisol or glucose were noted between groups. The present study confirms the observation of a lower TSH response to TRH in abstinent alcoholics and indicates that the lower response cannot be overcome by increasing TRH dosage. The similar PRL response between groups suggests normal lactotroph function in noncirrhotic abstinent alcoholics and argues against the pituitary TRH receptor down-regulation hypothesis.

Ethanol inhibits NMDA-evoked electrophysiological activity in vivo.

Recent studies have demonstrated that ethanol blocks N-methyl-D-aspartate (NMDA) responses in vitro. In the present study, evidence is provided that ethanol, when administered by the systemic route to rats, also inhibits NMDA-evoked electrophysiological activity in vivo at behaviorally relevant doses. Ethanol, at doses in rats ranging from those producing minimal changes in spontaneous behavioral activity (0.75 g/kg) to those producing marked suppression of behavioral activity (2.5 g/kg), produced a dose-dependent inhibition of the ability of NMDA, when iontophoresed onto neurons of the medial septum (MS), to activate MS neurons. However, at all doses of ethanol tested, a proportion of MS neurons responded to ethanol with essentially complete inhibition of NMDA-evoked activity, whereas other MS neurons responded to ethanol with little or no inhibition of NMDA-evoked activity. By way of comparison, MK-801, a non-competitive NMDA antagonist, antagonized NMDA-evoked activity in all MS neurons tested. In contrast to the actions of ethanol, MK-801 increased, rather than decreased, behavioral activity even at doses that completely inhibited NMDA-evoked activity in all MS neurons tested. These latter findings provide evidence that inhibition of NMDA-evoked activity cannot account for all of the behavioral effects of ethanol. In conclusion, while the present results demonstrate for the first time that ethanol can inhibit NMDA-evoked neuronal activity in vivo, they also indicate that additional neural actions must contribute to ethanol's pharmacological profile.

Antagonism of marihuana effects by indomethacin in humans.

To investigate whether the nonsteroidal anti-inflammatory drug (NSAID) indomethacin antagonized the effects of marihuana, an exploratory single-blind, placebo-controlled study was conducted. Subjects (n = 4) smoked marihuana after pre-treatment with placebo and indomethacin. The subjective rating of marihuana "high", heart rate, word recall, time estimation/production, and plasma concentrations of THC and PGE2 were measured. It was found that: 1) indomethacin pre-treatment decreased the elevation of prostaglandins induced by THC; 2) indomethacin significantly attenuated the subjective "high" and the heart rate accelerating effects of THC, although the magnitude of this effect was modest; 3) indomethacin abolished the profound effect of THC on time estimation and production; and 4) indomethacin pretreatment did not affect the decremental effects of THC on word recall. We conclude that prostaglandins are involved in the neurophysiologic mechanisms that mediate some of the typical clinical effects of THC, particularly the distortion of time perception.

Oxidation of monohalogenated ethanes and n-chlorinated alkanes by whole cells of Nitrosomonas europaea.

We have investigated the substrate specificity of ammonia monooxygenase in whole cells of the nitrifying bacterium Nitrosomonas europaea for a number of aliphatic halogenated hydrocarbons. To determine the effect of the halogen substituent and carbon chain length on substrate reactivity, we measured the rates of oxidation of the monohalogenated ethanes (fluoroethane, chloroethane, bromoethane, and iodoethane) and n-chlorinated C1 to C4 alkanes by whole cells of N. europaea. For monohalogenated ethanes, acetaldehyde was the major organic product and little or none of any of the alternate predicted products (2-halogenated alcohols) were detected. The maximum rate of haloethane oxidation increased with decreasing halogen molecular weight from iodoethane to chloroethane (19 to 221 nmol/min per mg of protein). In addition, the amount of substrate required for the highest rate of haloethane oxidation increased with decreasing halogen molecular weight. For the n-chlorinated alkanes, the rate of dechlorination, as measured by the appearance of the corresponding aldehyde product, was greatest for chloroethane and decreased dramatically for chloropropane and chlorobutane (118, 4, and 8 nmol of aldehyde formed per min per mg of protein, respectively). The concentration profiles for halocarbon oxidation by ammonia monooxygenase showed apparent substrate inhibition when ammonia was used as the reductant source. When hydrazine was used as the electron donor, no substrate inhibition was observed, suggesting that the inhibition resulted from reductant limitation.

Differential psychopharmacology of methylphenidate and the neuropsychology of childhood hyperactivity.

The principle of rate-dependency has been proposed to explain the therapeutic effects of stimulant drugs in hyperactive children (HAC). This paper is a critical discussion of the salience of rate-dependency to childhood hyperactivity, on mathematical, theoretical and clinical levels. The results of a stimulant drug trial in 55 HAC are presented; the data are analyzed using analysis of variance to describe main drug effects, and these are compared to results derived from a traditional rate dependency analysis. The latter are found to have little salience to the actual clinical effects of stimulant drugs on a wide variety of behavioral, physiological and laboratory measures. The weakness of the rate dependency hypothesis, however, is not necessarily fatal to the idea that the state of the organism prior to drug administration influences the response profile of the drug. The heterogeneity of stimulant effects, and the relationship between stimulant effects and the predrug state of the organism, especially in electrophysiological paradigms, are clear. A hypothesis is presented to suggest that HAC may be characterized by a trait of excessive variability. Homeostatic stimulant effects in reducing response variability may be central to the therapeutic action of the drug. A neural substrate for the abnormal oscillations which characterize HAC, the correction of which is germane to therapeutic stimulant effects, is presented in terms of the regulatory functions of the frontal lobe. A neuroanatomic locus of childhood hyperactivity is proposed in terms of disorder or dysmaturation of frontal striatal systems.

Interaction between marihuana and ethanol: effects on psychomotor performance.

This is a report of the results of a placebo-controlled study in which the effects of the interaction between ethanol and marihuana on drug plasma concentrations, subjective ratings of intoxication, heart rate acceleration, and psychomotor performance were investigated. Six healthy, male, paid volunteers, moderate users of ethanol and marihuana, participated in the study. Ethanol (0.42 g/kg, 0.85 g/kg, or placebo) was administered over a 30-min interval. Fifteen minutes later the subjects smoked, in their customary manner, NIDA cigarettes containing 2.4% or 0.0004% (placebo) delta-9-tetrahydrocannabinol (THC). Each subject was tested in a single-blind, latin-square crossover design with the following six conditions: placebo ethanol/placebo marihuana; low dose ethanol/placebo marihuana; high dose ethanol/placebo marihuana; placebo ethanol/marihuana; low dose ethanol/marihuana; and high dose ethanol/marihuana. The variables measured in the study were: (a) subjective rating of ethanol and/or marihuana intoxication; (b) heart rate; (c) accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI) task; (d) blood ethanol concentration by gas chromatography; and (e) plasma concentration of THC by radioimmunoassay. The results indicate that the decrements due to ethanol in performance of skills necessary to drive an automobile were significantly enhanced by marihuana in an additive and perhaps synergistic manner. The administration of ethanol prior to marihuana smoking did not produce significant effects on the subjective rating of "high," heart rate acceleration, or THC plasma concentration.