Holistic pedestrian safety assessment for average males and females.

Objective: An integrated assessment framework that enables holistic safety evaluations addressing vulnerable road users (VRU) is introduced and applied in the current study. The developed method enables consideration of both active and passive safety measures and distributions of real-world crash scenario parameters. Methods: The likelihood of a specific virtual testing scenario occurring in real life has been derived from accident databases scaled to European level. Based on pre-crash simulations, it is determined how likely it is that scenarios could be avoided by a specific Autonomous Emergency Braking (AEB) system. For the unavoidable cases, probabilities for specific collision scenarios are determined, and the injury risk for these is determined, subsequently, from in-crash simulations with the VIVA+ Human Body Models combined with the created metamodel for an average male and female model. The integrated assessment framework was applied for the holistic assessment of car-related pedestrian protection using a generic car model to assess the safety benefits of a generic AEB system combined with current passive safety structures. Results: In total, 61,914 virtual testing scenarios have been derived from the different car-pedestrian cases based on real-world crash scenario parameters. Considering the occurrence probability of the virtual testing scenarios, by implementing an AEB, a total crash risk reduction of 81.70% was achieved based on pre-crash simulations. It was shown that 50 in-crash simulations per load case are sufficient to create a metamodel for injury prediction. For the in-crash simulations with the generic vehicle, it was also shown that the injury risk can be reduced by implementing an AEB, as compared to the baseline scenarios. Moreover, as seen in the unavoidable cases, the injury risk for the average male and female is the same for brain injuries and femoral shaft fractures. The average male has a higher risk of skull fractures and fractures of more than three ribs compared to the average female. The average female has a higher risk of proximal femoral fractures than the average male. Conclusions: A novel methodology was developed which allows for movement away from the exclusive use of standard-load case assessments, thus helping to bridge the gap between active and passive safety evaluations.

Perfluorinated chemicals (PFOA) can, by interacting with highly brominated diphenyl ethers (PBDE 209) during a defined period of neonatal brain development, exacerbate neurobehavioural defects.

Perfluorinated compounds (PFCs) and polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent environmental compounds, present in humans and at higher levels in infants/children than in adults. This study shows that co-exposure to pentadecafluorooctanoic acid (PFOA) and 2,2',3,3',4,4',5,5',6,6'-decaBDE (PBDE 209) can significantly exacerbate developmental neurobehavioural defects. Neonatal male NMRI mice, 3 and 10 days old, were exposed perorally to PBDE 209 (1.4 or 8.0 µmol/kg bw), PFOA (1.4 or 14 µmol/kg bw), co-exposed to PBDE 209 and PFOA (at the given doses), or a vehicle (20% fat emulsion) and observed for spontaneous behaviour in a novel home environment when 2 and 4 months old. The behavioural defects observed included hyperactivity and reduced habituation indicating cognitive defects. This interaction appears most likely dependent on the presence of PBDE 209 and/or its metabolites together with PFOA, during a defined critical period of neonatal brain development, corresponding to the perinatal and newborn period in humans.

Developmental effects of neonatal fractionated co-exposure to low-dose gamma radiation and paraquat on behaviour in adult mice.

Radiological methods for screening, diagnostics and therapy are often used in healthcare; however, it has recently been reported that developmental exposure to low-dose ionizing radiation (IR) causes neurotoxicity. Environmental chemicals also have the potential to affect the developing brain and the concomitant effects caused by IR and chemicals are of high interest today. We therefore aim to investigate if low-dose IR can interact with the known neurotoxicant paraquat to induce neurotoxicity in the neonatal mouse model. Using the same model, we also aim to investigate if fractionated low-dose IR can be as neurotoxic as higher acute doses. Male mice were exposed to a single dose of paraquat (0.2 or 0.02 mg/kg) on postnatal day 10 and 11. Two hours following paraquat exposure, mice were whole body irradiated with 100 or 300 mGy gamma radiation (137 Cs). Behavioural observations were performed at 2 and 3 months of age. Following behavioural testing, we evaluated striatal dopaminergic gene transcription. Animals co-exposed to IR and paraquat generally displayed altered spontaneous behaviour compared to controls and single agent exposed mice. Stronger effects by combined exposure were also observed on adult memory and learning. However, dopaminergic gene transcript levels remained unchanged by treatment. Co-exposure to low-dose IR and paraquat can interact to exacerbate neurotoxic effects and to impair cognitive function. Furthermore, fractionation of the radiation dose was observed to be as potent as higher acute exposure for induction of developmental neurotoxicity.

A Cannabinoid Receptor Type 1 (CB1R) Agonist Enhances the Developmental Neurotoxicity of Acetaminophen (Paracetamol).

Acetaminophen (AAP; also known as paracetamol) is the most used and only recommended analgesic and antipyretic among pregnant women and young children. However, recent findings in both humans and rodents suggest a link between developmental exposure to AAP and adverse neurobehavioral effects later in life. We hypothesized that the cannabinoid receptor type 1 (CB1R) may be involved in the developmental neurotoxicity of AAP, owing to its interaction with the endocannabinoid system. Here we test if CB1R agonist WIN 55 212-2 (WIN) and AAP can interact when exposure occurs during a neurodevelopmental stage known for increased growth rate and for its vulnerability to AAP exposure. We exposed male NMRI mice on postnatal day 10 to different combinations of AAP and WIN. Adult mice, neonatally co-exposed to AAP and WIN, displayed a significant lack of habituation in the spontaneous behavior test, when compared with controls and single agent exposed mice. These adult adverse effects may at least in part be explained by a reduction of transcript levels of hippocampal synaptophysin (Syp) and tropomyosin receptor kinase B (Trkb), and cerebral cortical fatty acid amide hydroxylase (Faah), 24 h after exposure. These findings are consistent with our hypothesis that AAP and WIN can interact when exposure occurs during early postnatal brain development in mice. Assuming our results are relevant for humans, they raise concerns on AAP safety because it is the only recommended analgesic and antipyretic during pregnancy and early life.

Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period.

Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg-1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice. Copyright © 2017 John Wiley & Sons, Ltd.

Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice.

PURPOSE: To investigate whether neonatal exposure to fractionated external gamma radiation and co-exposure to radiation and nicotine can affect/exacerbate developmental neurotoxic effects, including altered behavior/cognitive function and the susceptibility of the cholinergic system in adult male mice. MATERIALS AND METHODS: Neonatal male Naval Medical Research Institute (NMRI) mice were irradiated with one 200 mGy fraction/day and/or exposed to nicotine (66 µg/kg b.w.) twice daily on postnatal day (PND) 10, 10-11, 10-12 or 10-13 (nicotine only). At 2 months of age the animals were tested for spontaneous behavior in a novel home environment, habituation capacity and nicotine-induced behavior. RESULTS: Fractionated irradiation and co-exposure to radiation and nicotine on three consecutive days disrupted behavior and habituation and altered susceptibility of the cholinergic system. All observed effects were significantly more pronounced in mice co-exposed to both radiation and nicotine. CONCLUSIONS: The fractionated irradiation regime affects behavior/cognitive function in a similar manner as has previously been observed for single-dose exposures. Neonatal co-exposure to radiation and nicotine, during a critical period of brain development in general and cholinergic system development in particular, enhance these behavioral defects suggesting that the cholinergic system can be a target system for this type of developmental neurotoxic effects.

Short-term exposure and long-term consequences of neonatal exposure to Δ(9)-tetrahydrocannabinol (THC) and ibuprofen in mice.

Both Δ(9)-tetrahydrocannabinol (THC) and ibuprofen have analgesic properties by interacting with the cannabinoid receptor type 1 (CB1R) and the cyclooxygenase (COX) systems, respectively. Evaluation of these analgesics is important not only clinically, since they are commonly used during pregnancy and lactation, but also to compare them with acetaminophen, with a known interaction with both CB1R and the COX systems. Short-term exposure of neonatal rodents to acetaminophen during the first weeks of postnatal life, which is comparable with a period from the third trimester of pregnancy to the first years of postnatal life in humans, induces long-term behavioral disturbances. This period, called the brain growth spurt (BGS) and is characterized by series of rapid and fundamental changes and increased vulnerability, peaks around postnatal day (PND) 10 in mice. We therefore exposed male NMRI mice to either THC or ibuprofen on PND 10. At 2 months of age, the mice were subjected to a spontaneous behavior test, consisting of a 60min recording of the variables locomotion, rearing and total activity. Mice exposed to THC, but not ibuprofen, exhibited altered adult spontaneous behavior and habituation capability in a dose-dependent manner. This highlights the potency of THC as a developmental neurotoxicant, since a single neonatal dose of THC was enough to affect adult cognitive function. The lack of effect from ibuprofen also indicates that the previously seen developmental neurotoxicity of acetaminophen is non-COX-mediated. These results might be of importance in future research as well as in the ongoing risk/benefit assessment of THC.

Neurocognitive functioning and outcome of the Illness Management and Recovery Program for clients with schizophrenia and schizoaffective disorder.

The relationship between psychosocial programming and neurocognition has been established in previous research, but has not been explored in the context of the Illness Management and Recovery Program (IMR). This study examined associations between neurocognition and illness self-management skills acquisition, based on two previous trials of IMR. Neurocognitive functioning was assessed at baseline and post-treatment in 53 participants with schizophrenia or schizoaffective disorder who completed the IMR. Illness self-management was measured by the client and clinician versions of the Illness Management and Recovery Scale. Statistical analyses investigated improvements in neurocognitive functioning and possible association between illness self-management skills acquisition and neurocognitive functioning. Speed of processing as measured by the Trail Making Test A, was related to client-reported acquisition of illness self-management skills, before and after controlling for psychiatric symptoms and medication, but did not predict improvement in clinician ratings of client illness self-management skills. However, when controlling for client session attendance rates, the association between speed of processing and client-reported illness self-management skills acquisition ceased to be statistically significant, which suggests that compromised neurocognitive functioning does not reduce response to training in illness self-management in itself. The association between the frequency of attended IMR sessions and outcome of the IMR seems to decrease the negative impact of compromised neurocognition on illness self-management skills acquisition. Also, clients with slower speed of processing may experience less benefit from the IMR and may attend fewer sessions.

Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose--response effects and strain and sex comparison.

Development of the brain includes periods which can be critical for its normal maturation. The present study investigates specifically vulnerable peri-/postnatal periods in mice which are essential for understanding the etiology behind radiation induced neurotoxicity and functional defects, including evaluation of neurotoxicity between sexes or commonly used laboratory mouse strains following low/moderate doses of ionizing radiation (IR). Male Naval Medical Research Institute (NMRI) mice, whole body irradiated to a single 500 mGy IR dose, on postnatal day (PND) 3 or PND 10 showed an altered adult spontaneous behaviour and impaired habituation capacity, whereas irradiation on PND 19 did not have any impact on the studied variables. Both NMRI and C57bl/6 male and female mice showed an altered adult spontaneous behaviour and impaired habituation following a single whole body irradiation of 500 or 1000 mGy, but not after 20 or 100 mGy, on PND 10. The present study shows that exposure to low/moderate doses of IR during critical life stages might be involved in the induction of neurological/neurodegenerative disorder/disease. A specifically vulnerable period for radiation induced neurotoxicity seems to be around PND 3-10 in mice. Further studies are needed to investigate mechanisms involved in induction of developmental neurotoxicity following low-dose irradiation.

Developmental neurotoxic effects of two pesticides: Behavior and biomolecular studies on chlorpyrifos and carbaryl.

In recent times, an increased occurrence of neurodevelopmental disorders, such as neurodevelopmental delays and cognitive abnormalities has been recognized. Exposure to pesticides has been suspected to be a possible cause of these disorders, as these compounds target the nervous system of pests. Due to the similarities of brain development and composition, these pesticides may also be neurotoxic to humans. We studied two different pesticides, chlorpyrifos and carbaryl, which specifically inhibit acetylcholinesterase (AChE) in the nervous system. The aim of the study was to investigate if the pesticides can induce neurotoxic effects, when exposure occurs during a period of rapid brain growth and maturation. The results from the present study show that both compounds can affect protein levels in the developing brain and induce persistent adult behavior and cognitive impairments, in mice neonatally exposed to a single oral dose of chlorpyrifos (0.1, 1.0 or 5mg/kg body weight) or carbaryl (0.5, 5.0 or 20.0mg/kg body weight) on postnatal day 10. The results also indicate that the developmental neurotoxic effects induced are not related to the classical mechanism of acute cholinergic hyperstimulation, as the AChE inhibition level (8-12%) remained below the threshold for causing systemic toxicity. The neurotoxic effects are more likely caused by a disturbed neurodevelopment, as similar behavioral neurotoxic effects have been reported in studies with pesticides such as organochlorines, organophosphates, pyrethroids and POPs, when exposed during a critical window of neonatal brain development.

More signs of neurotoxicity of surfactants and flame retardants - Neonatal PFOS and PBDE 99 cause transcriptional alterations in cholinergic genes in the mouse CNS.

Maternally and lactionally transferred persistent organic pollutants may interfere with CNS development. Here, 10-day-old male mice were exposed to single oral doses of PFOS (perflourooctanosulphonate) or PBDE 99 (2,2',4,4',5-penta-bromodiphenyl ether), and examined for changes in cholinergic gene transcription in the CNS 24h and 7 weeks later. 24h after exposure qPCR analyses revealed decreased transcription of nAChR-ß2 and AChE in cortex, and increased mAChR-5 in hippocampus of PFOS treated mice. Neonatal PFOS treatment altered spontaneous behaviour at 2 months of age but did not affect gene transcription in adults. At 2 months of age neonatally PBDE 99 treated mice had altered spontaneous behaviour, and cortical transcription of AChE, nAChR-α4, nAChR-ß2 and mAChR-5 were elevated. Our results indicate that PFOS and PBDE 99 affects the developing central cholinergic system by altering gene transcription in cortex and hippocampus, which may in part account for mechanisms causing changes in spontaneous behaviour.

Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin.

Developmental neurotoxicity of industrial chemicals and pharmaceuticals have been of growing interest in recent years due to the increasing reports of neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD) and autism. Exposure to these substances during early development may lead to adverse behavior effects manifested at a later phase of life. Pesticides are a wide group of chemicals which are still actively used and residues are found in the environment and in food products. The present study investigated the potential developmental neurotoxic effects of two different types of pesticides, endosulfan and cypermethrin, after a single neonatal exposure during a critical period of brain development. Ten-day-old male NMRI mice were administrated an oral dose of endosulfan or cypermethrin (0.1 or 0.5 mg/kg body weight, respectively). Levels of proteins were measured in the neonatal and adult brain, and adult behavioral testing was performed. The results indicate that both pesticides may induce altered levels of neuroproteins, important for normal brain development, and neurobehavioral abnormalities manifested as altered adult spontaneous behavior and ability to habituate to a novel home environment. The neurotoxic behavioral effects were also presentseveral months after the initial testing, indicating long-lasting or even persistent irreversible effects. Also, the present study suggests a possible link between the altered levels of neuroprotein and changes in behavior when exposed during a critical period of brain development.

Restoration of MPTP-induced deficits by exercise and Milmed(®) co-treatment.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces permanent neurochemical and functional deficits. Following the administration of either two or four injections of the dopamine neurotoxin, MPTP, at a dose of 40 mg/kg, C57/BL6 mice were given access to running-wheels (30-min sessions, four times/week, Monday-Thursday) and treatment with the treated yeast, Milmed(®) (four times/week, Monday-Thursday), or simply running-wheel exercise by itself, over ten weeks. It was observed that the combination of physical exercise and Milmed(®) treatment, the MPTP + Exercise + Yeast (MC) group [MPTP + Exercise + Milmed(®) (MC)], restored spontaneous motor activity markedly by test day 10, restored completely subthreshold L-Dopa-induced activity, and dopamine concentration to 76% of control values, in the condition wherein two administrations of MPTP (2 × 40 mg/kg) were given prior to initiation of exercise and/or Milmed(®) treatment. Physical exercise by itself, MPTP + Exercise (MC) group, attenuated these deficits only partially. Administration of MPTP four times (i.e., 40 mg/kg, s.c., once weekly over four weeks for a total of 160 mg/kg, MPTP + Exercise + Yeast (MC) group [MPTP + Exercise + Milmed(®) (SC)] and MPTP + Exercise (SC), induced a lesioning effect that was far too severe for either exercise alone or the exercise + Milmed(®) combination to ameliorate. Nevertheless, these findings indicate a powerful effect of physical exercise reinforced by Milmed(®) treatment in restoring MPTP-induced deficits of motor function and dopamine neurochemistry in mice.

Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice.

Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, but procedures as computerized tomography (CT) may deliver a significant radiation dose to the patient. Recently, awareness has been raised about possible non-cancer consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. In the present study neonatal NMRI mice were whole body irradiated with a single dose of gamma radiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of both sexes were observed for spontaneous behaviour in a novel home environment. The neuroproteins CaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus were analysed 24h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10. A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old mice was observed, where both males and females displayed a modified habituation, indicating reduced cognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male mice showed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined critical period of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, an elevation of tau protein was observed in male mice displaying reduced cognitive function.

Developmental exposure to the polybrominated diphenyl ether PBDE 209: Neurobehavioural and neuroprotein analysis in adult male and female mice.

Polybrominated diphenyl ethers (PBDEs), used as flame retardants in polymer products, are reported to cause developmental neurotoxic effects in mammals. The present study have investigated neurotoxic effects arising from neonatal exposure to PBDE 209, including alterations in sex differences, spontaneous behaviour, learning and memory, neuroproteins and altered susceptibility of the cholinergic system in adults. Three-day-old NMRI mice, of both sexes, were exposed to PBDE 209 (2,2',3,3',4,4',5,5',6,6'-decaBDE at 0, 1.4, 6.0 and 14.0µmol/kg b.w.). At adult age (2-7 months) a similar developmental neurotoxic effects in both male and female mice were seen, including lack of or reduced habituation to a novel home environment, learning and memory defects, modified response to the cholinergic agent's paraoxon (males) and nicotine (females) indicating increased susceptibility of the cholinergic system. The behavioural defects were dose-response related and persistent. In mice of both sexes and showing behavioural defects, neuroprotein tau was increased.

Propofol promotes blood-brain barrier breakdown and heat shock protein (HSP 72 kd) activation in the developing mouse brain.

Anesthetic agents induce cellular stress that may affect blood-brain barrier (BBB) permeability permeability in the developing brain causing brain dysfunction. In this investigation, effects of Propofol on cellualr stress using inducible heat shock protein (HSP72) and BBB breakdown employing albumin immunoreactivity in the mouse brain were examined. Propofol was administered to in mice on the postnatal day 10 once (10 mg/kg or 60 mg/kg subcutaneously). On the 75th day, HSP72 and albumin immunostaining were examined on 3-µm thick paraffin sections in the midbrain areas using standard protocol. Saline-treated and age-matched mice served as controls. Propofol dose-dependently produced a significant increase in the number of HSP72 and albumin-positive cells in cortex, hippocampus, thalamus and hypothalamus, a feature not seen in the saline-treated group. HSP72 and albumin activity in the propofol-treated group was largely confined to neurons and often localized to their cell cytoplasm and/or nucleus. HSP72 and albumin expression was the most prominent in cerebral cortex and in hippocampus, followed by hypothalamus and thalamus. These novel observations suggest that anesthetic agents, by inducing cellular stress in the developing brain may disrupt the BBB permeability that may have long lasting effects on adult brain function.

Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

The yeast product Milmed enhances the effect of physical exercise on motor performance and dopamine neurochemistry recovery in MPTP-lesioned mice.

Both clinical and laboratory studies have demonstrated that different types of physical exercise may alleviate Parkinsonism yet evidence for complete restoration of motor function and biomarker integrity are difficult to identify. MPTP (1 × 30 mg/kg, s.c., 4 groups) or saline (vehicle 1 × 5 ml/kg, s.c., 1 group) were administered in a single dose regime over three consecutive weeks on Fridays. Three MPTP groups were given four 30-min periods/week (Mondays to Thursdays), of these two groups, MPTP + Exer + M(i) and MPTP + Exer + M(ii); the former were introduced to exercise and Milmed (oral injection) on the week following the 1st MPTP injection and the latter on the Monday prior to the 1st injection of MPTP onwards. One MPTP group, MPTP + Exer, was given access to exercise (running wheels) from the week following the 1st MPTP injection onwards. The fourth MPTP group, MPTP-NoEx, and the Vehicle group were only given access to exercise on a single day each week (Wednesdays, exercise test) from the week following the 1st MPTP injection onwards. The exercise/exercise + Milmed regime was maintained for a further 9 weeks. It was observed that exercise by itself ameliorated MPTP-induced deficits regarding motor function and dopamine loss only partially whereas in the groups combining exercise with twice weekly dosages of Milmed the MPTP-induced deficits were abolished by the 10th week of the intervention. The three main conclusions that were drawn from correlational analyses of individual mice were: (i) that DA integrity was observed to be a direct function of ability to express running exercise in a treadmill wheel-running arrangement, and (ii) that DA integrity was observed to be a direct function of the capacity for motor performance as measured by spontaneous motor activity and subthreshold L-Dopa (5 mg/kg) induced activity in the motor activity test chambers, and (iii) that the extent to which running exercise in a running wheel was predictive of later motor performance in the activity test chambers was highly convincing.

Alcohol and drug use, smoking, and gambling among psychiatric outpatients: a 1-year prevalence study.

BACKGROUND AND AIMS: Studies of alcohol habits in general psychiatric populations are scarce. The objective was to investigate alcohol and drug use, smoking, and gambling in a clinical sample of psychiatric outpatients. A further aim was to study age and gender differences in the rates of these habits. METHODS: Data were collected among psychiatric outpatients with mainly mood (47%) and anxiety (35%) disorders. A questionnaire package was distributed, including AUDIT (Alcohol Use Disorders Identification Test), DUDIT (Drug Use Disorders Identification Test), tobacco items, and gambling items. Two major drinking categories were formed: "Nonhazardous alcohol use" (NH) and "Alcohol use above hazardous levels" (AH). RESULTS: In total, 2160 patients (65% females) responded to the questionnaire package. The AH rate was high among psychiatric outpatients (28.4%), particularly among young females (46.6%). Young female patients also reported a high prevalence of problematic drug use (13.8%). Problematic drug use, daily smoking, and problematic gambling were frequent. The unhealthy habits were linked to AH. CONCLUSIONS: Alcohol and drug use, smoking, and gambling are all highly prevalent among psychiatric outpatients. Young females are in particular need of attention. Interventions should be tailored for co-occurring psychiatric disorders and applied within routine psychiatric care.

Brief alcohol intervention in a psychiatric outpatient setting: a randomized controlled study.

BACKGROUND: Although brief alcohol intervention (BI) is widely studied, studies from psychiatric outpatient settings are rare. The aim of this study was to investigate the effects of two variants of BI in psychiatric outpatients. By using clinical psychiatric staff to perform the interventions, we sought to collect information of the usefulness of BI in the clinical setting. METHODS: Psychiatric outpatients with Alcohol Use Disorders Identification Test (AUDIT) scores indicating hazardous or harmful drinking were invited to participate in the study. The outpatients were randomized to minimal (assessment, feedback, and an informational leaflet) or BI (personalized advice added). Measurements were performed at baseline and at six and 12 months after the intervention. The primary outcome was change in AUDIT score at the 12-month follow-up. RESULTS: In all, 150 patients were enrolled and received either a minimal intervention (n = 68) or BI (n = 82). At 12 months, there was a small reduction in AUDIT score in both groups, with no significant differences in outcome between groups. At 12-month follow-up, 21% of participants had improved from a hazardous AUDIT score level to a nonhazardous level, and 8% had improved from a harmful level to a hazardous level (8%). CONCLUSIONS: Brief alcohol interventions may result in a reduction of AUDIT score to a small extent in psychiatric patients with hazardous or harmful alcohol use. Results suggest that BI may be of some value in the psychiatric outpatient setting. Still, more profound forms of alcohol interventions with risky-drinking psychiatric patients need elaboration.