Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression - 1. Impact on maternal mood!

Background: Psychological interventions for postnatal depression can be beneficial in the short term but their longer-term impact is unknown, Aims To evaluate the long-term effect on maternal mood of three psychological treatments in relation to routine primary care. Method: Women with post-partum depression (n=193)were assigned randomly to one of four conditions: routine primary care, non-directive counselling, cognitive-behavioural therapy or psychodynamic therapy. They were assessed immediately after the treatment phase (at 4.5 months) and at 18 and 60 months post-partum. Results: Compared with the control, ail three treatments had a significant impact at 4.5 months on maternal mood (Edinburgh Postnatal Depression Scale, EPDS). Only psychodynamic therapy produced a rate of reduction in depression (Structured Clinical interview for DSM III-R) significantly superior to that of the control. The benefit of treatment was no longer apparent by 9 months postpartum, treatment did not reduce subsequent episodes of post-partum depression. Conclusions: Psychological intervention for post-partum depression improves maternal mood (EPDS) in the short term. However, this benefit is not superior to spontaneous remission in the long term.

A systematic review of controlled trials of interventions to prevent childhood obesity and overweight: realistic synthesis of the evidence

Background: Preventing childhood overweight and obesity has become a major public health issue in developed and developing countries. Systematic reviews of this topic have not provided practice-relevant guidance because of the generally low quality of research and the heterogeneity of reported effectiveness. Aim: To present practice-relevant guidance on interventions to reduce at least one measure of adiposity in child populations that do or do not contain overweight or obese children. Design: Systematic review of eligible randomized, controlled trials or controlled trials using a novel approach to synthesizing the trial results through application of descriptive epidemiological and realistic evaluation concepts. Eligible trials involved at least 30 participants, lasted at least 12 weeks and involved non-clinical child populations. Results: Twenty-eight eligible trials were identified to 30 April 2006. Eleven trials were effective and 17 were ineffective in reducing adiposity. Blind to outcome, the main factor distinguishing effective from ineffective trials was the provision of moderate to vigorous aerobic physical activity in the former on a relatively 'compulsory' rather than 'voluntary' basis. Conclusions: By using a novel approach to synthesizing trials, a decisive role for the 'compulsory' provision of aerobic physical activity has been demonstrated. Further research is required to identify how such activity can be sustained and transformed into a personally chosen behaviour by children and over the life course. (C) 2007 The Royal Institute of Public Health. Published by Elsevier Ltd. All rights reserved.

A double-blind, placebo controlled human study investigating the effects of coffee derived manno-oligosaccharides on the faecal microbiota of a healthy adult population.

The aims of this study were to assess the impact of coffee derived mannooligosaccharides on the faecal microbiota of a healthy UK based population. Methods and Results: A double-blind, placebo-controlled, crossover human intervention study was conducted. Volunteers were assigned, 3g MOS, 5g MOS and placebo coffee preparations, to consume daily over a 3 wks, followed by a 2 wk washout period. Faecal samples were collected, and microbial population characterised using fluorescence in situ hybridization. Short-chain and branched-chain fatty acid profiles were obtained by gas chromatography. All treatments led to significant lactobacilli increases (placebo, p < 0.001; 3g, p = 0.04; 5g, p=0.04). The 3g treatment led to a significant bifidobacteria increase (p=0.001). Significantly less iso-valerate was found in faeces following 3g MOS daily (p=0.05). Conclusions: The 3g dose of MOS led to a potentially beneficial shift in the faecal microbiota. MOS was therefore confirmed to be a prebiotic at 3g dose. Significance and Impact of Study: This study provides confirmation of a new novel prebiotic, that can be considered for incorporation into a wider variety of food products, to provide different selective and nutritional properties.

Sterically controlled recognition of macromolecular sequence information by molecular tweezers

Sequence-specific binding is demonstrated between pyrene-based tweezer molecules and soluble, high molar mass copolyimides. The binding involves complementary pi - pi stacking interactions, polymer chain-folding, and hydrogen bonding and is extremely sensitive to the steric environment around the pyromellitimide binding-site. A detailed picture of the intermolecular interactions involved has been obtained through single-crystal X-ray studies of tweezer complexes with model diimides. Ring-current magnetic shielding of polyimide protons by the pyrene '' arms '' of the tweezer molecule induces large complexation shifts of the corresponding H-1 NMR resonances, enabling specific triplet sequences to be identified by their complexation shifts. Extended comonomer sequences (triplets of triplets in which the monomer residues differ only by the presence or absence of a methyl group) can be '' read '' by a mechanism which involves multiple binding of tweezer molecules to adjacent diimide residues within the copolymer chain. The adjacent-binding model for sequence recognition has been validated by two conceptually different sets of tweezer binding experiments. One approach compares sequence-recognition events for copolyimides having either restricted or unrestricted triple-triplet sequences, and the other makes use of copolymers containing both strongly binding and completely nonbinding diimide residues. In all cases the nature and relative proportions of triple-triplet sequences predicted by the adjacent-binding model are fully consistent with the observed H-1 NMR data.

Integrated motivational interviewing and cognitive behavioural therapy for people with psychosis and comorbid substance misuse: randomised controlled trial

Objectives To evaluate the effectiveness of integrated motivational interviewing and cognitive behaviour therapy in addition to standard care for patients with psychosis and a co-morbid substance use problem. Design Two-centre, open, rater-blind randomised controlled trial Setting UK Secondary Care Participants 327 patients with clinical diagnoses of schizophrenia, schizophreniform or schizoaffective disorder and DSM-IV diagnoses of drug and/or alcohol dependence or abuse Interventions Participants were randomly allocated to integrated motivational interviewing and cognitive behaviour therapy or standard care. Therapy has two phases. Phase one – “motivation building” – concerns engaging the patient, then exploring and resolving ambivalence for change in substance use. Phase two –“Action” – supports and facilitates change using cognitive behavioural approaches. Up to 26 therapy sessions were delivered over one year. Main outcomes The primary outcome was death from any cause or admission to hospital in the 12 months after therapy. Secondary outcomes were frequency and amount of substance use (Timeline Followback), readiness to change, perceived negative consequences of use, psychotic symptom ratings, number and duration of relapses, global assessment of functioning and deliberate self harm, at 12 and 24 months, with additional Timeline Followback assessments at 6 and 18 months. Analysis was by intention-to-treat with robust treatment effect estimates. Results 327 participants were randomised. 326 (99.7%) were assessed on the primary outcome, 246 (75.2%) on main secondary outcomes at 24 months. Regarding the primary outcome, there was no beneficial treatment effect on hospital admissions/ death during follow-up, with 20.2% (33/163) of controls and 23.3% (38/163) of the therapy group deceased or admitted (adjusted odds-ratio 1.16; P= 0.579; 95% confidence interval 0.68 to 1.99). For secondary outcomes there was no treatment effect on frequency of substance use or perceived negative consequences, but a statistically significant effect of therapy on amount used per substance-using day (adjusted odds-ratios: (a) for main substance 1.50; P=0.016; 1.08 to 2.09, (b) all substances 1.48; P=0.017; 1.07 to 2.05). There was a statistically significant treatment effect on readiness to change use at 12 months (adjusted odds-ratio 2.05; P=0.004; 1.26 to 3.31), not maintained at 24 months. There were no treatment effects on assessed clinical outcomes. Conclusions Integrated motivational interviewing and cognitive behaviour therapy for people with psychosis and substance misuse does not improve outcome in terms of hospitalisation, symptom outcomes or functioning. It does result in a reduction in amount of substance use which is maintained over the year’s follow up. Trial registration Current Controlled Trials: ISRCTN14404480

Luminescence of a new Ru(II) polypyridine complex controlled by a redox-responsive protonable anthra[1,10]phenanthrolinequinone

Redox-controlled luminescence quenching is presented for a new Ru(II)-bipyridine complex [Ru(bpy)(2)(1)](2+) where ligand 1 is an anthra[1,10] phenanthrolinequinone. The complex emits from a short-lived metal-to-ligand charge transfer, (MLCT)-M-3 state (tau = 5.5 ns in deaerated acetonitrile) with a low luminescence quantum yield (5 x 10(-4)). The emission intensity becomes significantly enhanced when the switchable anthraquinone unit is reduced to corresponding hydroquinone. On the contrary, chemical one-electron reduction of the anthraquinone moiety to semiquinone in aprotic tetrahydrofuran results in total quenching of the emission.

A double-blind, placebo-controlled, crossover-designed probiotic feeding study in children diagnosed with autistic spectrum disorders

There is growing interest in the role of gastrointestinal (GI) pathology and clinical expression of autism. Recent studies have demonstrated differences in the faecal clostridial populations harboured by autistic and non-autistic children. The potential of Lactobacillus plantarum WCSF1 (a probiotic) to modulate the gut microbiota of autistic subjects was investigated during a double-blind, placebo-controlled, crossover-designed feeding study. The faecal microbiota, gut function and behaviour scores of subjects were examined throughout the 12-week study. Lactobacillus plantarum WCFS1 feeding significantly increased Lab158 counts (lactobacilli and enterococci group) and significantly reduced Erec482 counts (Clostridium cluster XIVa) compared to placebo. Probiotic feeding also resulted in significant differences in the stool consistency compared to placebo and behaviour scores (total score and scores for some subscales) compared to baseline. The major finding of this work was the importance of study protocol in relation to the specific considerations of this subject population, with an extremely high dropout rate seen (predominantly during the baseline period). Furthermore, the relatively high inter-individual variability observed suggests that subsequent studies should use defined subgroups of autistic spectrum disorders, such as regressive or late-onset autism. In summary, the current study has highlighted the potential benefit of L. plantarum WCFS1 probiotic feeding in autistic individuals.

A double-blind, placebo-controlled, randomized human study assessing the capacity of a novel galacto-oligosaccharide mixture in reducing travellers' diarrhoea.

Background/Objectives: Prebiotics have attracted interest for their ability to positively affect the colonic microbiota composition, thus increasing resistance to infection and diarrhoeal disease. This study assessed the effectiveness of a prebiotic galacto-oligosaccharide mixture (B-GOS) on the severity and/or incidence of travellers' diarrhoea (TD) in healthy subjects. Subjects/Methods: The study was a placebo-controlled, randomized, double blind of parallel design in 159 healthy volunteers, who travelled for minimum of 2 weeks to a country of low or high risk for TD. The investigational product was the B-GOS and the placebo was maltodextrin. Volunteers were randomized into groups with an equal probability of receiving either the prebiotic or placebo. The protocol comprised of a 1 week pre-holiday period recording bowel habit, while receiving intervention and the holiday period. Bowel habit included the number of bowel movements and average consistency of the stools as well as occurrence of abdominal discomfort, flatulence, bloating or vomiting. A clinical report was completed in the case of diarrhoeal incidence. A post-study questionnaire was also completed by all subjects on their return. Results: Results showed significant differences between the B-GOS and the placebo group in the incidence (P<0.05) and duration (P<0.05) of TD. Similar findings occurred on abdominal pain (P<0.05) and the overall quality of life assessment (P<0.05). Conclusions: Consumption of the tested galacto-oligosaccharide mixture showed significant potential in preventing the incidence and symptoms of TD.

A double-blind, placebo-controlled, cross-over study to establish the bifidogenic effect of a very-long-chain inulin extracted from globe artichoke (Cynara scolymus) in healthy human subjects

There is growing interest in the use of inulins as substrates for the selective growth of beneficial gut bacteria such as bifidobacteria and lactobacilli because recent studies have established that their prebiotic effect is linked to several health benefits. In the present study, the impact of a very-long-chain inulin (VLCI), derived from globe artichoke (Cynara scolymus), on the human intestinal microbiota compared with maltodextrin was determined. A double-blind, cross-over study was carried out in thirty-two healthy adults who were randomised into two groups and consumed 10 g/d of either VLCI or maltodextrin, for two 3-week study periods, separated by a 3-week washout period. Numbers of faecal bifidobacteria and lactobacilli were significantly higher upon VLCI ingestion compared with the placebo. Additionally, levels of Atopobium group significantly increased, while Bacteroides–Prevotella numbers were significantly reduced. No significant changes in faecal SCFA concentrations were observed. There were no adverse gastrointestinal symptoms apart from a significant increase in mild and moderate bloating upon VLCI ingestion. These observations were also confirmed by in vitro gas production measurements. In conclusion, daily consumption of VLCI extracted from globe artichoke exerted a pronounced prebiotic effect on the human faecal microbiota composition and was well tolerated by all volunteers.

Cognitive tests used in chronic adult human randomised controlled trial micronutrient and phytochemical intervention studies

In recent years there has been a rapid growth of interest in exploring the relationship between nutritional therapies and the maintenance of cognitive function in adulthood. Emerging evidence reveals an increasingly complex picture with respect to the benefits of various food constituents on learning, memory and psychomotor function in adults. However, to date, there has been little consensus in human studies on the range of cognitive domains to be tested or the particular tests to be employed. To illustrate the potential difficulties that this poses, we conducted a systematic review of existing human adult randomised controlled trial (RCT) studies that have investigated the effects of 24 d to 36 months of supplementation with flavonoids and micronutrients on cognitive performance. There were thirty-nine studies employing a total of 121 different cognitive tasks that met the criteria for inclusion. Results showed that less than half of these studies reported positive effects of treatment, with some important cognitive domains either under-represented or not explored at all. Although there was some evidence of sensitivity to nutritional supplementation in a number of domains (for example, executive function, spatial working memory), interpretation is currently difficult given the prevailing 'scattergun approach' for selecting cognitive tests. Specifically, the practice means that it is often difficult to distinguish between a boundary condition for a particular nutrient and a lack of task sensitivity. We argue that for significant future progress to be made, researchers need to pay much closer attention to existing human RCT and animal data, as well as to more basic issues surrounding task sensitivity, statistical power and type I error.

Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

Translationally controlled tumour protein (TCTP) is a highly conserved protein present in all eukaryotic organisms. Various cellular functions and molecular interactions have been ascribed to this protein, many related to its growth-promoting and antiapoptotic properties. TCTP levels are highly regulated in response to various cellular stimuli and stresses. We have shown recently that the double-stranded RNA-dependent protein kinase, PKR, is involved in translational regulation of TCTP. Here we extend these studies by demonstrating that TCTP is downregulated in response to various proapoptotic treatments, in particular agents that induce Ca++ stress, in a PKR-dependent manner. This regulation requires phosphorylation of protein synthesis factor eIF2α. Since TCTP has been characterized as an antiapoptotic and Ca++-binding protein, we asked whether it is involved in protecting cells from Ca++-stress-induced apoptosis. Overexpression of TCTP partially protects cells against thapsigargin-induced apoptosis, as measured using caspase-3 activation assays, a nuclear fragmentation assay, using fluorescence-activated cell sorting analysis, and time-lapse video microscopy. TCTP also protects cells against the proapoptotic effects of tunicamycin and etoposide, but not against those of arsenite. Our results imply that cellular TCTP levels influence sensitivity to apoptosis and that PKR may exert its proapoptotic effects at least in part through downregulation of TCTP via eIF2α phosphorylation.

A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents

Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings.

Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study

BACKGROUND: The absorption of cocoa flavanols in the small intestine is limited, and the majority of the flavanols reach the large intestine where they may be metabolized by resident microbiota. OBJECTIVE: We assessed the prebiotic potential of cocoa flavanols in a randomized, double-blind, crossover, controlled intervention study. DESIGN: Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF) group (494 mg cocoa flavanols/d) or a low-cocoa flavanol (LCF) group (23 mg cocoa flavanols/d) for 4 wk. This was followed by a 4-wk washout period before volunteers crossed to the alternant arm. Fecal samples were recovered before and after each intervention, and bacterial numbers were measured by fluorescence in situ hybridization. A number of other biochemical and physiologic markers were measured. RESULTS: Compared with the consumption of the LCF drink, the daily consumption of the HCF drink for 4 wk significantly increased the bifidobacterial (P < 0.01) and lactobacilli (P < 0.001) populations but significantly decreased clostridia counts (P < 0.001). These microbial changes were paralleled by significant reductions in plasma triacylglycerol (P < 0.05) and C-reactive protein (P < 0.05) concentrations. Furthermore, changes in C-reactive protein concentrations were linked to changes in lactobacilli counts (P < 0.05, R(2) = -0.33 for the model). These in vivo changes were closely paralleled by cocoa flavanol-induced bacterial changes in mixed-batch culture experiments. CONCLUSION: This study shows, for the first time to our knowledge, that consumption of cocoa flavanols can significantly affect the growth of select gut microflora in humans, which suggests the potential prebiotic benefits associated with the dietary inclusion of flavanol-rich foods. This trial was registered at clinicaltrials.gov as NCT01091922.

Operator performance evaluation of controlled depth of field in a stereographically displayed virtual environment

Retinal blurring resulting from the human eye's depth of focus has been shown to assist visual perception. Infinite focal depth within stereoscopically displayed virtual environments may cause undesirable effects, for instance, objects positioned at a distance in front of or behind the observer's fixation point will be perceived in sharp focus with large disparities thereby causing diplopia. Although published research on incorporation of synthetically generated Depth of Field (DoF) suggests that this might act as an enhancement to perceived image quality, no quantitative testimonies of perceptional performance gains exist. This may be due to the difficulty of dynamic generation of synthetic DoF where focal distance is actively linked to fixation distance. In this paper, such a system is described. A desktop stereographic display is used to project a virtual scene in which synthetically generated DoF is actively controlled from vergence-derived distance. A performance evaluation experiment on this system which involved subjects carrying out observations in a spatially complex virtual environment was undertaken. The virtual environment consisted of components interconnected by pipes on a distractive background. The subject was tasked with making an observation based on the connectivity of the components. The effects of focal depth variation in static and actively controlled focal distance conditions were investigated. The results and analysis are presented which show that performance gains may be achieved by addition of synthetic DoF. The merits of the application of synthetic DoF are discussed.

Head-controlled assistive telerobot with extended physiological proprioception capability

People with disabilities such as quadriplegia can use mouth-sticks and head-sticks as extension devices to perform desired manipulations. These extensions provide extended proprioception which allows users to directly feel forces and other perceptual cues such as texture present at the tip of the mouth-stick. Such devices are effective for two principle reasons: because of their close contact with the user's tactile and proprioceptive sensing abilities; and because they tend to be lightweight and very stiff, and can thus convey tactile and kinesthetic information with high-bandwidth. Unfortunately, traditional mouth-sticks and head-sticks are limited in workspace and in the mechanical power that can be transferred because of user mobility and strength limitations. We describe an alternative implementation of the head-stick device using the idea of a virtual head-stick: a head-controlled bilateral force-reflecting telerobot. In this system the end-effector of the slave robot moves as if it were at the tip of an imaginary extension of the user's head. The design goal is for the system is to have the same intuitive operation and extended proprioception as a regular mouth-stick effector but with augmentation of workspace volume and mechanical power. The input is through a specially modified six DOF master robot (a PerForceTM hand-controller) whose joints can be back-driven to apply forces at the user's head. The manipulation tasks in the environment are performed by a six degree-of-freedom slave robot (the Zebra-ZEROTM) with a built-in force sensor. We describe the prototype hardware/software implementation of the system, control system design, safety/disability issues, and initial evaluation tasks.