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Epidemiological and clinical evidence highlight the benefit of dietary fibre consumption on body weight. This benefit is partly attributed to the interaction of dietary fibre with the gut microbiota. Dietary fibre possesses a complex food structure which resists digestion in the upper gut and therefore reaches the distal gut where it becomes available for bacterial fermentation. This process yields SCFA which stimulate the release of appetite-suppressing hormones glucagon-like peptide-1 and peptide YY. Food structures can further enhance the delivery of fermentable substrates to the distal gut by protecting the intracellular nutrients during upper gastrointestinal digestion. Domestic and industrial processing can disturb these food structures that act like barriers towards digestive enzymes. This leads to more digestible products that are better absorbed in the upper gut. As a result, less resistant material (fibre) and intracellular nutrients may reach the distal gut, thus reducing substrates for bacterial fermentation and its subsequent benefits on the host metabolism including appetite suppression. Understanding this link is essential for the design of diets and food products that can promote appetite suppression and act as a successful strategy towards obesity management. This article reviews the current evidence in the interplay between food structure, bacterial fermentation and appetite control.
Varenicline is an α4β2 partial nicotinic agonist approved for smoking cessation. There have been spontaneous postmarketing reports of neuropsychiatric adverse events (NPAEs) in smokers without a history of psychiatric illness quitting with varenicline.
110 smokers without history of psychiatric illness (screened by Structured Clinical Interview for DSM) were randomized to 12 weeks of varenicline (n=55) (1mg bid) or placebo. Adverse events were solicited systematically. Depressive symptoms, anxiety symptoms, aggression and irritability were measured at baseline and weekly using the Montgomery-Asberg Depression-rating scale (MADRS), the Hamilton Anxiety scale (HAM-A), and the Overt Aggression scale-modified (OAS-m). The Profile of Mood States (POMS) was administered daily. Mixed Model analysis of repeated measures was conducted to compare mean changes in scores between groups across the study period.
Smokers had a mean age of 33; smoked on average 22 cigarettes/day with mean Fagerstrom score for Nicotine Dependence >7 at baseline. Reported NPAEs were similar between groups. No suicidal events were reported. There were no significant differences between groups for the MADRS (treatment difference vs. placebo [TD] = 0.03, 95% CI: -0.68, 0.73; NS), HAM-A (TD = 0.14, 95% CI: -0.62, 0.90; NS), OAS-m irritability subscale (TD = 0.08, 95% CI: -0.17, 0.34; NS), OAS-m aggression subscale (TD = 0.5, 95% CI: -1.18, 2.18, NS) and the POMS total scores (TD = 0.5, 95% CI: -0.52, 1.53; NS).
There were no significant differences between groups on measures of depressive symptoms, anxiety and aggression/hostility. Systematically solicited NPAEs were similar between varenicline and placebo.
Aripiprazole and quetiapine are the two most recent second generation antipsychotics available in the UK. We aimed to study patients who were prescribed aripiprazole and quetiapine in routine clinical practice, to identify and compare patients who had a good clinical response.
From a data set of 22,000 electronic patient records (from 2002 to 2007), we retrospectively identified all secondary care psychiatric patients started on aripiprazole and quetiapine for schizophrenia and other psychotic disorders. We retrospectively assigned a severity and an improvement score of Clinical Global Impression (CGI) to records, to measure the effectiveness of both drugs.
89 patients were newly prescribed aripiprazole and 132 patients prescribed quetiapine, for schizophrenia and other psychotic conditions. Patients on aripiprazole had a lower initial severity of illness, CGI (Severity) 3.9 versus 4.4, p=0.0003. After excluding treatment resistant patients, a CGI (Improvement) score 1-4 (minimally to very much improved) was achieved with aripiprazole in 69% and quetiapine in 71% of patients. There were no statistical differences in overall discontinuation rates (aripiprazole 40%, quetiapine 41.5%). There were differences in mean time to discontinuation, aripiprazole,165 days, quetiapine, 267 days (p=0.017)
This study is an independent comparison of aripiprazole and quetiapine in schizophrenia and psychoses. Both aripiprazole and quetiapine were clinically effective in the majority of patients. CGI improvement scores were similar for both drugs as were overall discontinuation rates. Patients on aripiprazole, however, discontinued earlier than those discontinuing from quetiapine.
To compare Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (1H-MRS) between people with Alzheimer's disease (AD) and mild cognitive impairment (MCI).
AD is characterised by cognitive impairment. 10-15% of people with MCI progress to dementia each year. The hippocampus is involved in memory functioning and is one of the brain regions first affected by AD. MRI based hippocampal volumetric measurement enables accurate quantification of atrophy. In addition, 1H-MRS can be used to measure concentrations of brain metabolites including myoinositol (mI) and N-acetylaspartate (NAA). NAA is a proxy measure of neuronal density.
Subjects with AD (n=46), MCI (n=28) and controls (n=39) were scanned using a 1.5 Tesla MR system. Manual tracing of hippocampal volumes was undertaken using Measure software. 1H-MRS voxels of interest were defined in the left and right hippocampi. A point-resolved spectroscopy pulse sequence produced spectra from each voxel and clearly resolved NAA and mI peaks. Statistical analysis was undertaken using SPSS15.
Hippocampal volumes were significantly reduced between AD and controls (p=0.003) and between AD and MCI (p=0.001). Compared to controls, individuals with AD and MCI had a significant reduction in [NAA]. MCI showed a non-significant increase in [mI]. A positive relationship was found between hippocampal volume and [NAA] and between hippocampal volume and [mI] for MCI.
AD is associated with decreased viable neuronal density/function (as measured by NAA) and a reduction in hippocampal volume associated with impaired cognitive functioning. The elevated [mI] in MCI may be a “tipping point” into dementia.
NICE guidelines indicate one in five people will suffer from depression at some point in their lives with relapse rates of 50–80% in those who have experienced one or more episodes of depression (National Institute for Health and Clinical Excellence [NICE], 2007). By 2020, depression is predicted to be the second largest cause of death or disability and consequently there is a need to explore and develop the ways of working with depression. Mindfulness based cognitive therapy (MBCT) is a group psycho-educational treatment designed to reduce the risk of recurrent depression by integrating mindfulness based meditation practices with cognitive therapy techniques (Segal, Williams, & Teasdale, 2002). MBCT comprises eight weekly two-hour group sessions with additional time for meditative homework practice. As yet, little is known about how patients experience meditative homework assignments in a UK public health setting. This study examines subjective accounts of the meaning of carrying out meditative homework assignments in terms of impact on the self as well as an exploration of barriers and facilitating factors from a participant's perspective. Six Individual in-depth interviews were conducted, transcribed verbatim and an Interpretative Phenomenological Approach was used to analyse the data. Results focus on perceived facilitating factors and difficulties experienced in carrying out meditative homework as well as implications for clinical practice in the prevention of recurrent depression. Transformation of participant’s experience of the self and social relatedness as a consequence of meditative homework is discussed in relation to existing psychological literature and the practise of MBCT.
Bipolar disorder is frequently misdiagnosed or diagnosed late.
We aimed to improve the diagnosis of bipolar disorder in our team.
Using an excel database, an audit of the diagnoses of all patients in a CMHT in Bedford was carried out.
It was noted that few patients were diagnosed as having bipolar II disorder, while there was a large number of Bipolar I patients, and a larger number of patients with recurrent depressive disorder, mixed anxiety and depression, unipolar depression, and psychotic depression.
All patients with recurrent depressive disorder, anxiety and depression, unipolar depression and psychotic depression are being reassessed in the outpatient clinic, using a longitudinal history, a family history, and, when these tests are positive, the ‘mood disorder questionnaire’.
The new diagnoses are recorded in the Database.
This poster represents work in progress. Increased awareness of bipolar disorder is leading to a more frequent diagnosis or re-diagnosis of Bipolar II disorder, as well as a consequent change in the proportions of each diagnosis in the sample.
The frequent misdiagnosis of Bipolar II disorder frequently leads to the treatment of these patients with anti-depressants only.
This leads to the possibility of patients becoming elated, or going into mixed states, with increased suicidality.
Appropriate diagnosis of bipolar II disorder requires skills at present found in secondary care. Such patients should therefore be referred to secondary care. Both Primary and Secondary care should be more aware of this diagnosis and its consequences.
Post hoc analysis of occupational attainment and performance on a standard neurocognitive battery suggests that performance on letter-number sequencing is strongly associated with work attainment. Letter-number sequencing may warrant further investigation as a clinically useful tool to inform decisions around vocational rehabilitation.
To assess gender differences in the clinical presentation of GAD and response to pregabalin (PGB) treatment.
Data were pooled from 6 randomized, double-blind, placebo-controlled, 4- to 6-week trials of outpatients who met DSM-IV criteria for GAD with a minimum HAM-A total score >18. Response was evaluated for 3 fixed-dosage groups: 150 mg/d, 300-450 mg/d, and 600 mg/d.
Baseline presentation of GAD was similar for women and men, respectively, for mean (±SD) age (38.6±12.3 vs 39.4±11.5 y) and severity of concurrent depressive symptoms (HAM-D score, 13.7±4.4 vs 13.4±4.3). However, women had a modest but significantly higher mean HAM-A somatic factor score (11.5±3.2 vs 10.8±3.1; P<0.01). For both sexes, treatment with PGB resulted in significantly higher LOCF-endpoint improvement in HAM-A total score: Women: PGB-150 mg, -10.7±0.82; PGB-300/450 mg, -11.8±0.68; PGB-600 mg, -12.4±0.59 vs. placebo, -9.5±0.51; P<0.0001 for all comparisons; Men: PGB-150 mg, -10.8±0.81; PGB-300/450 mg, -12.6±0.59; PGB-600 mg, -11.6±0.51 vs placebo, -8.7±0.47; P<0.0001 for all comparisons. CGI-I responder rates were significantly higher (P<0.001) on PGB (combined doses) vs. placebo for both women (50% vs 35%) and men (53% vs 38%). There were no gender differences in attrition due to adverse events, or in proportion of severe adverse events.
Women and men with GAD showed similar clinical presentations, with women reporting somewhat more somatic symptoms. Pregabalin was an effective and well-tolerated treatment for GAD for both sexes.
There are high rates of psychiatric morbidity associated with refractory epilepsy. It is unclear whether seizure frequency or comorbid psychiatric illness impacts more upon patients’ quality of life in epilepsy. The objective of this study was to establish which of these two factors impacted more upon patients.
Patients with medically refractory epilepsy who were admitted to the National Neurological Centre in Beaumont Hospital were recruited to the study. Structural Clinical Interview for DSM IV (Axis I) (SCID I) and SCID II (Axis II) were the objective measures and HADS, and QOLIE-89 were the subjective measures utilized.
A total of 138 patients had SCIDs conducted over the four year study. 75 patients (54.4%) had an Axis I disorder. Of these 30 patients (21.7%) had a mood disorder, 18 patients (13%) had an anxiety disorder and 49 patients (35.5%) were diagnosed with a psychotic disorder. There was no relationship between patient seizure frequency and HADS (p=0.94) or QOLIE-89 (p=0.93) scores. Patients having a high number of seizures were not more likely to have a SCID Axis I diagnosis than patients with a low number of seizures (p=0.246). Patients with a mood disorder were more likely to have a lower QOLIE-89 score than patients without a mood disorder (p=0.0001).
Patients with medically refractory epilepsy have high rates of psychopathology. Seizure frequency is not correlated with the presence, severity of psychiatric symptoms or quality of life. The presence of a psychiatric disorder and its severity is strongly correlated with quality of life.
Schizophrenia is associated with an increased risk of violence. The successful identification of the illness specific factors that contribute to that risk could lead to the development of novel therapeutic risk management strategies.
To identify cognitive and emotion processing deficits that are linked to violence risk in schizophrenia.
Fifty male patients with DSM-IV schizophrenia and thirty-nine healthy controls were assessed across a range of intellectual, executive, emotion and social processing domains. Lifetime propensity to violence was quantified in terms of frequency, severity and victim outcome.
General intellectual ability and memory were not significantly associated with violence propensity. Violent patients showed significantly poorer response inhibition, after accounting for relevant clinical variables. A greater lifetime propensity to violence was associated with an attentional bias towards anger, a heightened sensitivity to the recognition of fear, with poorer complex Theory of Mind performance.
Our results allow us to propose a hypothetical model of the risk of violence in schizophrenia. We suggest that heightened sensitivity to environmental negative emotional cues and poorer understanding of complex social situations, combined with a poorer ability both to quickly process but also inhibit pre-potent responses, results in a greater propensity to violence in schizophrenia. We propose that this model sits alongside risk associated with other factors such as illicit drug use. These findings need replication but could have implications for more effective treatment and management of patients with schizophrenia.
Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.
The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.
There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.
Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.
Remission and recovery rates for people who have had a first episode psychosis (FEP) remain uncertain.
We conducted a systematic review and meta-analysis to assess pooled prevalence rates of remission and recovery in FEP in longitudinal studies and conducted meta regression analyses to investigate potential moderators.
A systematic literature search of major electronic databases without language restrictions was conducted from database inception until July 1, 2016. Longitudinal studies with follow up greater than 1 year reporting data on remission or recovery rates in FEP were included.
Seventy-nine studies were included representing 19,072 FEP patients (mean age = 26.9 years, male = 59.5%). The pooled rate of remission among 12,301 individuals with FEP was 57.9% (95%CI: 52.7–62.9, Q = 1536.3, P< 0.001, n = 60 studies, mean follow up = 5.5 years). Restricting the analysis to studies, which used the remission in schizophrenia working group (RSWG) criteria (n = 25 studies, n = 6909 patients), the pooled remission rate was 56.9% (95%CI: 48.9–64.5, Q = 656.9). Higher remission rates were moderated by studies from more recent years. The pooled prevalence of recovery among 9642 individuals with FEP was 37.9% (95%CI: 30.0–46.5, Q = 1450.8, studies = 35, P = 0.006, average follow up = 7.2 years). Recovery rates were higher (P< 0.05) in North America compared to other regions.
Our data suggest that remission and recovery rates in FEP may be more favorable than previously thought. We observed stability of recovery rates after the first two years, suggesting that a progressive deteriorating course of illness is not typical. While remission rates have improved over time, recovery rates have not, raising questions about the effectiveness of specialist early intervention services in achieving improved recovery.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The history of religious migration and experience of exile in the early modern period has received a great deal of attention in recent years. Neglected within this scholarship, however, is sustained discussion of linguistic encounter within these often fraught transcultural and transnational interactions. This article breaks new ground by exploring the linguistic experiences of religious exiles in English convents founded in the Low Countries. Most women within English communities in exile were linguistically challenged; focusing on the creative ways these women subsequently negotiated language barriers sheds new light on female language acquisition and encounter during this period.
Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18–75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism–tHcy association (β standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype–hypertension association was confined to adults aged ≤50 years.
During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S rRNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/day) and fibre (g/day) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.
Preliminary evidence has suggested that high-fat diets (HFD) enriched with SFA, but not MUFA, promote hyperinsulinaemia and pancreatic hypertrophy with insulin resistance. The objective of this study was to determine whether the substitution of dietary MUFA within a HFD could attenuate the progression of pancreatic islet dysfunction seen with prolonged SFA-HFD. For 32 weeks, C57BL/6J mice were fed either: (1) low-fat diet, (2) SFA-HFD or (3) SFA-HFD for 16 weeks, then switched to MUFA-HFD for 16 weeks (SFA-to-MUFA-HFD). Fasting insulin was assessed throughout the study; islets were isolated following the intervention. Substituting SFA with MUFA-HFD prevented the progression of hyperinsulinaemia observed in SFA-HFD mice (P < 0·001). Glucose-stimulated insulin secretion from isolated islets was reduced by SFA-HFD, yet not fully affected by SFA-to-MUFA-HFD. Markers of β-cell identity (Ins2, Nkx6.1, Ngn3, Rfx6, Pdx1 and Pax6) were reduced, and islet inflammation was increased (IL-1β, 3·0-fold, P = 0·007; CD68, 2·9-fold, P = 0·001; Il-6, 1·1-fold, P = 0·437) in SFA-HFD – effects not seen with SFA-to-MUFA-HFD. Switching to MUFA-HFD can partly attenuate the progression of SFA-HFD-induced hyperinsulinaemia, pancreatic inflammation and impairments in β-cell function. While further work is required from a mechanistic perspective, dietary fat may mediate its effect in an IL-1β–AMP-activated protein kinase α1-dependent fashion. Future work should assess the potential translation of the modulation of metabolic inflammation in man.
Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the ‘Fiebig staging system’ has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying ‘sensitivity’. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define ‘stages’ of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.
Computational modeling is an important aspect of the research on nuclear waste materials. In particular, atomistic simulations, when used complementary to experimental efforts, contribute to the scientific basis of safety case for nuclear waste repositories. Here we discuss the state-of-the-art and perspectives of atomistic modeling for nuclear waste management on a few cases of successful synergy of atomistic simulations and experiments. In particular, we discuss here: (1) the potential of atomistic simulations to investigate the uranium oxidation state in mixed-valence uranium oxides and (2) the ability of cementitious barrier materials to retain radionuclides such as 226Ra and 90Sr, and of studtite/metastudtite secondary peroxide phases to incorporate actinides such as Np and Am. The new contribution we make here is the computation of the incorporation of Sr by C-S-H (calcium silicate hydrate) phases.