Acceptance and commitment therapy as an adjunct to the MOVE! programme: a randomized controlled trial.

OBJECTIVE: The current study tested the efficacy of an acceptance and commitment therapy (ACT) group intervention for disinhibited eating behaviour as an adjunct to the Veterans Affairs MOVE!© weight management programme. METHODS: Veterans (N = 88) with overweight or obesity who completed the MOVE! weight management programme and self-identified as having problems with 'stress-related eating' were randomized to four 2-h weekly ACT sessions or a continued behavioural weight-loss (BWL) intervention. Assessments were completed at baseline, post-treatment and 3- and 6-month follow-up on outcomes of interest including measures of disinhibited eating patterns, obesity-related quality of life, weight-related experiential avoidance and weight. RESULTS: The BWL group exhibited significantly greater reductions in binge eating behaviour at post-treatment compared with the ACT group. Significant improvements in other outcomes were found with minimal differences between groups. In both groups, decreases in weight-related experiential avoidance were related to improvements in binge eating behaviour. CONCLUSIONS: Taken together, the continued BWL intervention resulted in larger improvements in binge eating behaviour than the ACT intervention. The two groups showed similar improvements in other disinhibited eating outcomes. Future studies are encouraged to determine if more integrated or longer duration of ACT treatment may maximize eating outcomes in MOVE.Trial Registration Number: This trial was registered with ClinicalTrials.gov database (NCT01757847).

Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit.

Anxiety, depression and disability across the lifespan.

The authors examined the relationship between anxiety, depression and physical disability, after controlling for demographic and health variables, in a sample of 374 adults aged 18-94. Results indicate that anxiety, depression and comorbid anxiety and depression are associated with higher levels of disability, after controlling for factors such as age, gender, income, self-rated health, number of medical conditions and number of physician visits in the past year. Furthermore, anxiety, depression and comorbid anxiety and depression have a differential effect on disability according to age, with older adults with any of these symptoms reporting higher levels of disability than younger adults. These findings suggest that physicians working with older adults should assess for and treat anxiety as well as depressive symptoms.

Inhibition, reactivation and aging kinetics of highly toxic organophosphorus compounds: pig versus minipig acetylcholinesterase.

Organophosphorus compound-based (OP) chemical warfare agents (nerve agents) represent a continuing threat to military forces and the civilian population. OPs act primarily by inhibiting acetylcholinesterase (AChE), the standard treatment for which includes AChE reactivators (oximes) in combination with antimuscarinic drugs. In the last decades, the efficacy of oximes has been investigated mostly in small animal models. In order to increase the predictive value of animal studies it is desirable to measure numerous physiological and biochemical parameters. This is difficult in small animals. Large animal models fulfil these requirements and swine are increasingly being used in toxicology studies. Swine breeds generally show considerable variability in different characteristics which may be minimised by the use of specially bred minipigs which have a known genetic background and health status. A comparative study was, therefore, initiated to investigate the kinetic properties of the White Landrace pig and Göttingen minipig AChE in respect of inhibition by the pesticide paraoxon; the nerve agents cyclosarin, VX and VR; the reactivation of inhibited AChE by oximes (obidoxime, pralidoxime and HI 6); and the aging and spontaneous reactivation of inhibited AChE. The determination of the respective kinetic constants found similarities between pig and minipig AChE which showed marked differences in comparison with human AChE values. This has to be considered in designing meaningful models for the investigation of oxime efficacy in pig or minipig experiments. The generated data indicate comparable kinetic properties of pig and minipig AChE and may provide a kinetic basis for extrapolation of data from pig studies to humans.

Guinea-pig heart acetylcholinesterase after continuous physostigmine administration.

G1 and G4 acetylcholinesterase (AChE) molecular forms were separated in different regions of guinea-pig heart. The activities of both were highest in the left side of the left ventricle (LV(L)). The reversible anticholinesterase physostigmine, or saline, was administered continuously for six days. In saline-treated animals the activity of both molecular forms was markedly increased in both atria, G1 activity was increased on the left side of the right ventricle (LV(R)), and G4 activity was increased on both sides of the right ventricle compared to untreated animals. However, G1 activity was significantly decreased on the left side of the left ventricle. Physostigmine administration caused a significant reduction in G4 activity in the left atrium (LA), the left side of the right ventricle, and the left side of the left ventricle, and a significant increase in G1 activity on the right side of the right ventricle compared to saline-treated animals. The distribution of AChE indicates a role for parasympathetic nerves in the control of both ventricles and atria. The changes in AChE in saline-treated animals could have been due to the anaesthesia or stress of the surgical procedures. Physostigmine caused delayed changes in the enzyme in some regions, consistent with an effect on its expression.

A simple method for measuring EEG in freely moving guinea pigs.

This paper describes a method of measuring EEG in guinea pigs by means of temporarily attached superficial electrodes with radiotelemetry equipment. This represents an alternative approach to more conventional methods of monitoring EEG in animals, which necessitate surgical implantation of electrodes. The novel approach of using superficial electrodes was compared with the cortical screw electrode technique, in a nerve agent-induced seizure model. In both cases, radiotelemetry techniques were used for data capture to facilitate monitoring of nerve agent-induced seizures in freely moving non-tethered guinea pigs. The advantages and disadvantages of the technique are discussed, for example the saving in resources and the benefits to animal welfare.

A longitudinal analysis of anxiety and depressive symptoms.

The authors modeled depressive and anxiety symptom data from 1,391 participants in a longitudinal study of middle-aged and older Swedish twins (M age = 60.9 years, SD = 13.3). Although anxiety and depression were highly correlated, a model with distinct Anxiety and Depression factors fit the data better than models with Positive and Negative Affect factors or a single Mental Health factor. Lack of well-being was associated with anxiety rather than depression. Over two 3-year intervals, anxiety symptoms led to depressive symptoms, but the relationship was not reciprocal. Anxiety symptoms were more stable than depression. These findings provide additional support for the idea that anxiety symptoms may reflect a personality trait such as neuroticism more than do depressive symptoms and suggest that low positive affect may not be as specific to depression among older adults as in younger people.

The effect of continuous pyridostigmine administration on functional (A12) acetylcholinesterase activity in guinea-pig muscles.

Pyridostigmine which causes a reversible inhibition of acetylcholinesterase (AChE), was administered continuously for 6 days to guinea-pigs, via a subcutaneously implanted osmotic pump. This produced 40-50% inhibition of red cell acetylcholinesterase (AChE). Controls were animals treated with saline via pumps, and untreated animals. The activities of the functional A12 molecular form of AChE were compared in diaphragm, extensor digitorum longus (EDL) and soleus muscles in the three animal groups at 6 days. The pumps were removed at 6 days and the A12 AChE activities were determined at various times thereafter As the enzyme separation procedure was lengthy, drug-induced inhibition was no longer present when the enzyme activity was measured. At 6 days, the activity was significantly higher in EDL (over 50% higher) and soleus (over two-fold higher) in pyridostigmine-treated animals than saline-treated animals. In the diaphragm, the activities in pyridostigmine and saline-treated animals were similar but both were significantly (over two-fold) higher than in untreated animals. At 1 day after pump removal (day 7) the activity had declined in all three muscles of the pyridostigmine-treated animals and in the diaphragm of saline-treated animals. Thereafter, in the diaphragm (but not the EDL or soleus) in pyridostigmine-treated animals, there were marked variations in the enzyme activity up to day 20. In saline-treated animals there was a marked transient increase in activity at day 13 in all muscles. The results indicate that the homeostatic control offunctional AChE had been affected in both the pyridostigmine and saline treatment groups.

Effect of halothane administration on acetylcholinesterase activity in guinea-pig muscle and brain.

The effect of halothane administration on the activity of acetylcholinesterase molecular forms was studied in diaphragm, extensor digitorum longus (EDL), and soleus muscles, and six regions of the brain (striatum, cerebellum, cortex, hippocampus, medulla-pons, midbrain) of guinea-pigs. Six days after the anaesthetic, the activity of the G4 form was significantly increased in all three muscles and the A12 form was significantly increased in EDL. The G1 precursor form was significantly decreased in soleus. The G4 form was significantly increased in medulla-pons, and the G1 form was significantly decreased in hippocampus and midbrain. These findings show that halothane can have prolonged effects on acetylcholinesterase activity in both muscle and brain, and may have important implications for the use of halothane and other volatile anaesthetics in studies of the cholinergic system.

Review of bonded amalgam restorations, and assessment in a general practice over five years.

This study reviewed the literature on bonded amalgam restorations and assessed the failure, marginal fracture and marginal staining behavior of 366 Permite C amalgam restorations lined with five dentin bonding resins (Scotchbond 2, Panavia Ex, Amalgambond, Amalgambond Plus, Geristore) and a polyamide cavity varnish (Barrier). The restorations were placed in the posterior permanent teeth of 190 adult patients and examined at intervals over periods of up to five years. There were five restoration failures (1.4%), usually from tooth fracture, involving Class II preparations in molar teeth. No instances of persistent pulpal sensitivity or recurrent caries were reported. The marginal deterioration of the restorations was assessed indirectly using photographs for comparison with two standard sets of enlarged color transparencies. Most of the marginal fracture and marginal staining scores were low, with little difference between the six lining materials at any period.

Introducing Adelaide dental students to a problem-based learning curriculum.

A course designed to introduce new students to a problem-based learning (PBL) curriculum in dentistry at the University of Adelaide is described. Australian students are admitted to the Adelaide dental course either directly from school (SL) or after one or more years of tertiary education (TT). The admissions process is designed to select academically able students who will flourish in a problem-based environment. Some international students (INT) are also selected through a modified admissions process. A 9-item questionnaire derived from frequently-asked questions from previous years was administered to the new students at the beginning and at the end of the introductory course, and each individual's responses before and after the course were compared. There was an increased number of positive responses (significant at P < 0.05 to 7 of the 9 items) after the course. Although the course appeared to be effective in familiarising new students with a PBL curriculum, many students were still uncertain about two items which commonly provoke anxiety, namely how to decide when to stop researching a topic, and how to balance group and solo learning.

History of depression and other psychiatric illness as risk factors for Alzheimer disease in a twin sample.

Although case-control studies have found elevated risk for Alzheimer disease (AD) associated with a prior psychiatric history, most of the previous research had inadequate controls for familial risk factors. Putative psychiatric risk factors were evaluated for a registry-based sample of 65 twin pairs discordant for AD. Risk ratios were calculated for psychiatric illness at any time and for episodes more than 10 years before dementia onset. Prior psychiatric illness was significantly associated with elevated risk. Most of these cases represented depressive episodes. When analyses were restricted to individuals whose mental illness commenced more than 10 years before dementia onset, the magnitude of the odds ratio decreased markedly. These findings suggest that a history of psychiatric illness, especially depression, may be associated with an elevated risk for AD. In particular, these results are consistent with an interpretation that symptoms of depression and similar complaints represent prodromal phases of dementia.

Self-assessment in a problem-based learning curriculum in dentistry.

The creation of sound self-judgement for students is an integral goal in any educational sphere. Student clinicians in dentistry must learn sufficient skills to be able to self-assess their performance very accurately, because after graduation, the nature of dental procedures means that others are seldom in a position to evaluate the quality of their work. Over recent years, the Department of Dentistry at the University of Adelaide has been developing a self-assessment procedure, initially as a pilot study in the subject oral diagnosis, and currently in all years of the course. This paper describes how self-assessment has been demonstrated to work initially in the pilot subject, and currently across the whole course. The paper also describes how the criteria for assessment and the levels of performance expected for each grade are established and how student performance is monitored. Finally, evidence is presented to indicate acceptance by the students of self-assessment as a valuable and integral part of their learning in dentistry.

Self-perceived competency at graduation: a comparison of dental graduates from the Adelaide PBL curriculum and the Toronto traditional curriculum.

The first class to complete the new Adelaide problem-based learning curriculum graduated in 1997. Their self-perceived competence at graduation was assessed using a revised version of a questionnaire recently compiled and used in Toronto, and based on the global competencies for dental practice accepted in 1995 by all Canadian Faculties of Dentistry. 38 of the 45 Adelaide class members (84%) completed the survey, compared with 93/129 (72%) in Toronto, and their responses were largely similar to those of the Toronto students. At least 67% of the Adelaide and Toronto students felt well-prepared in 34 of the 55 competencies. Most felt well-prepared for the basic everyday items such as diagnosis, local anaesthesia and basic restorative, but less so for items that are not encountered as often in dental school, such as business matters, practice management, soft tissue biopsies and dentofacial trauma. Items showing significant differences between the 2 schools are discussed with reference to curricular and other dissimilarities in the schools, and some inferences are drawn about the importance of context to learning and feelings of competence.

Neuroimaging findings in twins discordant for Alzheimer's disease.

Data from computed tomography (CT) scans of 12 twin pairs in which one partner had Azheimer's disease (AD) and the other partner is cognitively intact were analyzed to study structural brain features associated with AD while controlling for familial factors. Visual ratings and analysis of quantified areas and volumes indicated that AD twins showed more dilation of temporal horns, lateral ventricles and third ventricle, and more atrophy of temporal lobes, particularly in the anterior temporal/perisylvian area, than their healthy cotwins. Demented twins did not have smaller intracranial areas or overall brain volumes than their intact partners. The apolipoprotein sigma-4 allele was associated with greater dilation of lateral ventricles and ventricular volume. Significant intrapair correlations were found for total intracranial area and volume, cerebellar area and white matter lesions.

Differential recovery of acetylcholinesterase in guinea pig muscle and brain regions after soman treatment.

1. In brain areas of untreated guinea-pigs the highest activity of acetylcholinesterase was seen in the striatum and cerebellum, followed by the midbrain, medulla-pons and cortex, and the lowest in the hippocampus. The activity in diaphragm was seven-fold lower than in the hippocampus. 2. At 1 h after soman (27 micrograms/kg) administration the activity of the enzyme was dramatically reduced in all tissues studied. In muscle the three major molecular forms (A12, G4 and G1) showed a similar degree of inhibition and a similar rate of recovery and the activity had returned to normal by 7 days. 3. In the brain soman inhibited the G4 form more than the G1 form. The hippocampus, cortex and midbrain showed the greatest reductions in enzyme activity. At 7 days the activity in the cortex, medulla pons and striatum had recovered but in the hippocampus, midbrain and cerebellum it was still inhibited. 4. Thus the effects of soman administration varied in severity and time course in the different tissues studied. However the enzyme activity was still reduced in all tissues at 24 h when the overt signs of poisoning had disappeared.

Effects of excitatory amino acid antagonists on dendrotoxin-induced increases in neurotransmitter release and epileptiform bursting in rat hippocampus in vitro.

Alpha-dendrotoxin (alpha-DTx), a snake venom toxin which blocks several types of fast-activating voltage-dependent potassium channels, induces limbic seizures and neuronal damage when injected into the brain. The mechanisms underlying these convulsant and neuropathological actions are not fully understood. We have studied the effects of alpha-DTx on neurotransmitter release and electrical activity in rat hippocampal brain slices and the role of excitatory amino acid receptors in mediating these actions of the toxin. alpha-DTx increased the basal release of acetylcholine, glutamate, aspartate, and GABA in a concentration-dependent manner and induced epileptiform bursting in the CA1 and CA3 regions of the slice. The increase in neurotransmitter release was evident during the first 4 min after toxin addition, whereas the bursting appeared after a concentration-dependent delay (20-40 min with 250 nM toxin). The N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and MK-801 had no effect on the frequency or amplitude of dendrotoxin-induced epileptiform bursts, but the non-NMDA antagonists CNQX and DNQX abolished bursting in both CA1 and CA3 within 4-6 min. In contrast, the toxin-induced increases in neurotransmitter release were not blocked by DNQX. This study has demonstrated that, following exposure to alpha-DTx, there is a rapid increase in the release of neurotransmitters which precedes the onset of epileptiform bursting in the hippocampus. Since DNQX abolished the bursting but had no effect on the increase in neurotransmitter release, these results suggest that DNQX blocks alpha-DTx-induced epileptiform activity by antagonism of postsynaptic non-NMDA receptors.

First-year responses to a new problem-based curriculum in dentistry.

The first year of a new Bachelor of Dental Surgery curriculum was introduced at the University of Adelaide in 1993. Four integrated streams replaced the previous large number of separate subjects, with an overall reduction in formal contact hours, more exposure to clinical practise, and an emphasis on problem-based learning and student self-directed learning. This report compares students attitudes to the new programme with their attitudes to the previous course. Evaluation forms were completed by 30 of 53 first-year students in 1992 and 38 of 47 first-year students in 1993. Comparisons between years, made using the Student's that, indicated significant differences for several questions. For example, the workload in the previous course was considered to be significantly heavier, with too much theory and too many topics. It was felt that the aims and objectives of the new course were significantly clearer; there was more time to understand material; more opportunities to choose areas to study; students were encouraged more to think for themselves; and staff were more understanding and supportive. The authors conclude that the new problem-based Adelaide dental curriculum has facilitated a more contextual and better-balanced learning environment for students.

The use of student journals in problem-based learning.

This paper describes several examples of the use of journals in a Bachelor of Dental Surgery course. The examples cover: the use of journals in first year subjects and in later-year clinical subjects; the effect of changes in policy and practise as a result of experience with journals; and student views on their experiences with journals. The use of journals offers a means of achieving some of the more important goals of problem-based learning (PBL), particularly those requiring students to reflect upon and evaluate their experiences. When effectively integrated in a PBL course, journals have several functions: to formalize reflection; an outlet for personal feeling; an opportunity for feedback about a student's progress and about the course; to provide the student with a summary of the year's work; and a means whereby students and teachers gain insight into the learning process. However, our experience in Dentistry raises several contentious issues, especially with regard to confidentiality and assessment. We make several recommendations for the effective use of journals based on the need for frequent communication between students and staff, the development of an environment of trust, and the need for staff and student education in journal use.