Peroxisome proliferator-activated receptor-(gamma) receptor ligand partially prevents the development of endometrial explants in baboons: a prospective, randomized, placebo-controlled study

A prospective, randomized, placebo-controlled study was conducted in a baboon model to determine if a thiazolidinedione agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone, can impede the development of endometriosis. Endometriosis was induced using laparoscopic, intrapelvic injection of eutopic menstrual endometrium, previously incubated with placebo or pioglitazone for 30 min, in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. At this point, the 12 baboons were randomized into two groups and treated from the day of induction. They received either PBS tablets (n = 6, placebo control, placebo tablets once a day by mouth) or pioglitazone (n = 6, test drug, 7.5 mg by mouth each day). A second and final laparoscopy was performed in the baboons to record the extent of endometriotic lesions between 24 and 42 d after induction (no difference in length of treatment between the two groups, P = 0.38). A videolaparoscopy was performed to document the number and surface area of endometriotic lesions. The surface area and volume of endometriotic lesions were significantly lower in pioglitazone treated baboons than the placebo group (surface area, 48.6 vs. 159.0 mm(2), respectively, P = 0.049; vol, 23.7 vs. 131.8 mm(3), respectively, P = 0.041). The surface area (3.5 vs. 17.8 mm(2), P = 0.017, pioglizatone vs. placebo) and overall number (1.5 vs. 9.5, P = 0.007, pioglizatone vs. placebo) of red lesions were lower in the pioglitazone group. A peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, effectively reduced the initiation of endometriotic disease in the baboon endometriosis model. Using this animal model, we have shown that thiazolidinedione is a promising drug for preventive treatment of endometriosis.

Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease

BACKGROUND Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disease Initiative Study Group). One-hundred and eighty patients were evaluated using the Unified Huntington Disease Rating Scale over 36 months. A placebo effect was defined as an improvement of at least 50% over baseline scores in the Unified Huntington Disease Rating Scale, and clinically relevant when at least 10% of the population met it. RESULTS Only behavior showed a significant placebo effect, and the proportion of the patients with placebo effect ranged from 16% (first visit) to 41% (last visit). Nondepressed patients with better functional status were most likely to be placebo-responders over time. CONCLUSIONS In Huntington's disease, behavior seems to be more vulnerable to placebo than overall motor function, cognition, and function

Evidence for a cognitive control network for goal-directed attention in simple sustained attention

The deterioration of performance over time is characteristic for sustained attention tasks. This so-called "performance decrement" is measured by the increase of reaction time (RT) over time. Some behavioural and neurobiological mechanisms of this phenomenon are not yet fully understood. Behaviourally, we examined the increase of RT over time and the inter-individual differences of this performance decrement. On the neurophysiological level, we investigated the task-relevant brain areas where neural activity was modulated by RT and searched for brain areas involved in good performance (i.e. participants with no or moderate performance decrement) as compared to poor performance (i.e. participants with a steep performance decrement). For this purpose, 20 healthy, young subjects performed a carefully designed task for simple sustained attention, namely a low-demanding version of the Rapid Visual Information Processing task. We employed a rapid event-related functional magnetic resonance imaging (fMRI) design. The behavioural results showed a significant increase of RT over time in the whole group, and also revealed that some participants were not as prone to the performance decrement as others. The latter was statistically significant comparing good versus poor performers. Moreover, high BOLD-responses were linked to longer RTs in a task-relevant bilateral fronto-cingulate-insular-parietal network. Among these regions, good performance was associated with significantly higher RT-BOLD correlations in the pre-supplementary motor area (pre-SMA). We concluded that the task-relevant bilateral fronto-cingulate-insular-parietal network was a cognitive control network responsible for goal-directed attention. The pre-SMA in particular might be associated with the performance decrement insofar that good performers could sustain activity in this brain region in order to monitor performance declines and adjust behavioural output.

First clinical trial of tomographic neurofeedback in attention-deficit/hyperactivity disorder: evaluation of voluntary cortical control

Tomographic neurofeedback (tNF) training was evaluated as a treatment for attention-deficit/hyperactivity disorder (ADHD). To investigate the specificity of the treatment, outcomes were related to learning during tNF.

Altered response control and anterior cingulate function in attention-deficit/hyperactivity disorder boys

To investigate mechanisms and structures underlying prefrontal response control and inhibition in boys suffering from attention-deficit/hyperactivity disorder (ADHD).

Ego depletion and attention regulation under pressure: Is a temporary loss of self-control strength indeed related to impaired attention regulation?

In the current study we investigated whether ego depletion negatively affects attention regulation under pressure in sports by assessing participants' dart throwing performance and accompanying gaze behavior. According to the strength model of self-control, the most important aspect of self-control is attention regulation. Because higher levels of state anxiety are associated with impaired attention regulation, we chose a mixed design with ego depletion (yes vs. no) as between-subjects and anxiety level (high vs. low) as within-subjects factor. Participants performed a perceptual-motor task requiring selective attention, namely, dart throwing. In line with our expectations, depleted participants in the high-anxiety condition performed worse and displayed a shorter final fixation on bull's eye, demonstrating that when one's self-control strength is depleted, attention regulation under pressure cannot be maintained. This is the first study that directly supports the general assumption that ego depletion is a major factor in influencing attention regulation under pressure.

Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study.

OBJECTIVE Vitamin D (D₃) status is reported to correlate negatively with insulin production and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, few placebo-controlled intervention data are available. We aimed to assess the effect of large doses of parenteral D3 on glycosylated haemoglobin (HbA(₁c)) and estimates of insulin action (homeostasis model assessment insulin resistance: HOMA-IR) in patients with stable T2DM. MATERIALS AND METHODS We performed a prospective, randomised, double-blind, placebo-controlled pilot study at a single university care setting in Switzerland. Fifty-five patients of both genders with T2DM of more than 10 years were enrolled and randomised to either 300,000 IU D₃ or placebo, intramuscularly. The primary endpoint was the intergroup difference in HbA(₁c) levels. Secondary endpoints were: changes in insulin sensitivity, albuminuria, calcium/phosphate metabolism, activity of the renin-aldosterone axis and changes in 24-hour ambulatory blood pressure values. RESULTS After 6 months of D₃ supply, there was a significant intergroup difference in the change in HbA(₁c) levels (relative change [mean ± standard deviation] +2.9% ± 1.5% in the D₃ group vs +6.9% ± 2.1% the in placebo group, p = 0.041) as HOMA-IR decreased by 12.8% ± 5.6% in the D₃ group and increased by 10% ± 5.4% in the placebo group (intergroup difference, p = 0.032). Twenty-four-hour urinary albumin excretion decreased in the D₃ group from 200 ± 41 to 126 ± 39, p = 0.021). There was no significant intergroup difference for the other secondary endpoints. CONCLUSIONS D₃ improved insulin sensitivity (based on HOMA-IR) and affected the course of HbA(₁c) positively compared with placebo in patients with T2DM.

Ego depletion and attention regulation under pressure: Is a temporary loss of self-control strength indeed related to impaired attention regulation?

In the present study we investigated whether ego depletion negatively affects attention regulation under pressure in sports by assessing participants’ dart throwing performance and accompanying gaze behavior. According to the strength model of self-control the most important aspect of self-control is attention regulation (Schmeichel & Baumeister, 2010). As higher levels of state anxiety are associated with impaired attention regulation (Nieuwenhuys & Oudejans, 2012) we chose a mixed design with ego depletion (yes vs. no) as between-subjects and anxiety level (high vs. low) as within-subjects factor. A total of 28 right-handed students participated in our study (Mage = 23.4, SDage = 2.5; 10 female; no professional dart experience). Participants performed a perceptual-motor task requiring selective attention, namely, dart throwing. The task was performed while participants were positioned high and low on a climbing wall (i.e., with high and low levels of anxiety). In line with our expectations, a mixed-design ANOVA revealed that depleted participants in the high anxiety condition performed worse (p < .001) and displayed a shorter final fixation on bull’s eye (p < .01) than in the low anxiety condition, demonstrating that when one is depleted attention regulation under pressure cannot be maintained. This is the first study that directly supports the general assumption that ego depletion is a major factor in influencing attention regulation under pressure.

Time-referenced effects of an internal vs. external focus of attention on muscular activity and compensatory variability

The paralysis-by-analysis phenomenon, i.e., attending to the execution of one's movement impairs performance, has gathered a lot of attention over recent years (see Wulf, 2007, for a review). Explanations of this phenomenon, e.g., the hypotheses of constrained action (Wulf et al., 2001) or of step-by-step execution (Masters, 1992; Beilock et al., 2002), however, do not refer to the level of underlying mechanisms on the level of sensorimotor control. For this purpose, a “nodal-point hypothesis” is presented here with the core assumption that skilled motor behavior is internally based on sensorimotor chains of nodal points, that attending to intermediate nodal points leads to a muscular re-freezing of the motor system at exactly and exclusively these points in time, and that this re-freezing is accompanied by the disruption of compensatory processes, resulting in an overall decrease of motor performance. Two experiments, on lever sequencing and basketball free throws, respectively, are reported that successfully tested these time-referenced predictions, i.e., showing that muscular activity is selectively increased and compensatory variability selectively decreased at movement-related nodal points if these points are in the focus of attention.

Homeopathic Preparations to Control the Rosy Apple Aphid (Dysaphis plantaginea Pass.)

A laboratory model system with the rosy apple aphid (Dysaphis plantaginea Pass.) on apple seedlings was developed to study the effects of homeopathic preparations on this apple pest. The assessment included the substance Lycopodium clavatum and a nosode of the rosy apple aphid. Each preparation was applied on the substrate surface as aqueous solution of granules (6c, 15c, or 30c). Controls were aqueous solutions of placebo granules or pure water. In eight independent, randomized, and blinded experiments under standardized conditions in growth chambers, the development of aphids on treated and untreated apple seedlings was observed over 17 days, each. Six experiments were determined to assess the effects of a strict therapeutic treatment; two experiments were designed to determine the effects of a combined preventative and therapeutic treatment. After application of the preparations, the number of juvenile offspring and the damage on apple seedlings were assessed after 7 and 17 days, respectively. In addition, after 17 days, the seedling weight was measured. In the final evaluation of the six strictly therapeutic trials after 17 days, the number of juvenile offspring was reduced after application of L. clavatum 15c (-17%, p = 0.002) and nosode 6c (-14%, p = 0.02) compared to the pure water control. No significant effects were observed for leaf damage or fresh weight for any application. In the two experiments with combined preventative and therapeutic treatment, no significant effects were observed in any measured parameter. Homeopathic remedies may be effective in plant-pest systems. The magnitude of observed effects seems to be larger than in models with healthy plants, which renders plant-pest systems promising candidates for homeopathic basic research. For successful application in agriculture, however, the effect is not yet sufficient. This calls for further optimization concerning homeopathic remedy selection, potency level, dosage, and application routes.

Genome-wide association study in German patients with attention deficit/hyperactivity disorder

The heritability of attention deficit hyperactivity disorder (ADHD) is approximately 0.8. Despite several larger scale attempts, genome-wide association studies (GWAS) have not led to the identification of significant results. We performed a GWAS based on 495 German young patients with ADHD (according to DSM-IV criteria; Human660W-Quadv1; Illumina, San Diego, CA) and on 1,300 population-based adult controls (HumanHap550v3; Illumina). Some genes neighboring the single nucleotide polymorphisms (SNPs) with the lowest P-values (best P-value: 8.38 × 10(-7)) have potential relevance for ADHD (e.g., glutamate receptor, metabotropic 5 gene, GRM5). After quality control, the 30 independent SNPs with the lowest P-values (P-values ≤ 7.57 × 10(-5) ) were chosen for confirmation. Genotyping of these SNPs in up to 320 independent German families comprising at least one child with ADHD revealed directionally consistent effect-size point estimates for 19 (10 not consistent) of the SNPs. In silico analyses of the 30 SNPs in the largest meta-analysis so far (2,064 trios, 896 cases, and 2,455 controls) revealed directionally consistent effect-size point estimates for 16 SNPs (11 not consistent). None of the combined analyses revealed a genome-wide significant result. SNPs in previously described autosomal candidate genes did not show significantly lower P-values compared to SNPs within random sets of genes of the same size. We did not find genome-wide significant results in a GWAS of German children with ADHD compared to controls. The second best SNP is located in an intron of GRM5, a gene located within a recently described region with an infrequent copy number variation in patients with ADHD.

Mindfulness meditation counteracts self-control depletion

Mindfulness meditation describes a set of different mental techniques to train attention and awareness. Trait mindfulness and extended mindfulness interventions can benefit self-control. The present study investigated the short-term consequences of mindfulness meditation under conditions of limited self-control resources. Specifically, we hypothesized that a brief period of mindfulness meditation would counteract the deleterious effect that the exertion of self-control has on subsequent self-control performance. Participants who had been depleted of self-control resources by an emotion suppression task showed decrements in self-control performance as compared to participants who had not suppressed emotions. However, participants who had meditated after emotion suppression performed equally well on the subsequent self-control task as participants who had not exerted self-control previously. This finding suggests that a brief period of mindfulness meditation may serve as a quick and efficient strategy to foster self-control under conditions of low resources.

Effectiveness of integrated psychological therapy (IPT) for schizophrenia patients: a research update

Standardized recovery criteria go beyond symptom remission and put special emphasis on personal and social functioning in residence, work, and leisure. Against this background, evidence-based integrated approaches combining cognitive remediation with social skills therapy show promise for improving functional recovery of schizophrenia patients. Over the past 30 years, research groups in 12 countries have evaluated integrated psychological therapy (IPT) in 36 independent studies. IPT is a group therapy program for schizophrenia patients. It combines neurocognitive and social cognitive interventions with social skills and problem-solving approaches. The aim of the present study was to update and integrate the growing amount of research data on the effectiveness of IPT. We quantitatively reviewed the results of these 36 studies, including 1601 schizophrenia patients, by means of a meta-analytic procedure. Patients undergoing IPT showed significantly greater improvement in all outcome variables (neurocognition, social cognition, psychosocial functioning, and negative symptoms) than those in the control groups (placebo-attention conditions and standard care). IPT patients maintained their mean positive effects during an average follow-up period of 8.1 months. They showed better effects on distal outcome measures when all 5 subprograms were integrated. This analysis summarizes the broad empirical evidence indicating that IPT is an effective rehabilitation approach for schizophrenia patients and is robust across a wide range of sample characteristics as well as treatment conditions. Moreover, the cognitive and social subprograms of IPT may work in a synergistic manner, thereby enhancing the transfer of therapy effects over time and improving functional recovery.