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Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
Purposeful qualitative modelling of embodiment function relations is a challenge in embodiment design. This contribution investigates the applicability and usefulness of the Contact and Channel Approach as a qualitative modelling approach in a survey study. From 23 development and research projects, advantages and challenges regarding applicability and usefulness are identified. A further result is that many different models are used additionally to the Contact and Channel Approach. Based on the findings, research potential for optimization and development of links to other models emerges.
Surface based MRI methods are a promising approach for the identification of cerebral shape alterations in schizophrenia . In particular, investigating gyrification might offer important evidence for disturbed neurodevelopmental mechanisms in schizophrenia.
The present study is the first to compare on a vertex - wise basis mean curvature as a sensitive parameter for the identification of local gyrification changes in first episode schizophrenia.
54 patients with first-episode schizophrenia and 54 healthy control subjects underwent high-resolution T1-weighted MRI scans. Surface extraction and mean curvature calculation was performed using the Freesurfer Software package. Statistical cortical maps were created to estimate gyrification differences between groups.
A significantly increased gyrification was detected in patients relative to controls in a large right parahippocampal-lingual cortex area. A further analysis of cortical thickness of this cluster revealed concurrent significant reduced cortical thickness in patients.
This is the first study to reveal an aberrant gyrification of the medial surface in first episode schizophrenia on basis of a vertex - wise analysis of local gyrification changes of the entire cortex. Both affected areas, the parahippocampal and the lingual cortex, are of high pathophysiological relevance for schizophrenia. Thus, our data provided new in vivo evidence for an early maturational deficit of these cortical areas in schizophrenia .
The aim of this study was to detect longitudinal differences in white matter brain structures in adults with schizophrenia compared to healthy controls.
Twenty adult patients with multi-episode schizophrenia under stable antipsychotic medication and twenty-two age- and sex-matched healthy subjects were included in the study. Diffusion Tensor Imaging (DTI) was applied at baseline (t1), after 6weeks (t2) and after 3months (t3) and data processing was done with tract-based spatial statistics (p<0.05, corrected). Two subjects in the schizophrenic sample dropped out at t2 and one healthy subject at t3. Clinical and neuropsychological variables were measured and correlated with the most significant DTI findings.
Compared with healthy age- and sex-matched controls schizophrenic patients showed widespread decreases in mean fractional anisotropy values (p<0.05, corrected). The most obvious FA decrease in the long-term was found in the anterior part of the corpus callosum (p<0.005, corrected), the left temporal lobe (p<0.004, corr.) and the mid-cingulate gyrus bilateral (p<0.004, corr.). Correlations to demographic variables, clinical rating scales (PANSS, CGI and GAF), verbal learning and memory and working memory will be presented.
Magnetic resonance imaging was able to detect altered structural connectivity in patients with multi-episode schizophrenia in a longitudinal design.
Gene × environment (G × E) interactions in eating pathology have been increasingly investigated, however studies have been limited by sample size due to the difficulty of obtaining genetic data.
To synthesize existing G × E research in the eating disorders (ED) field and provide a clear picture of the current state of knowledge with analyses of larger samples.
Complete data from seven studies investigating community (n = 1750, 64.5% female) and clinical (n = 426, 100% female) populations, identified via systematic review, were included. Data were combined to perform five analyses: 5-HTTLPR × Traumatic Life Events (0–17 events) to predict ED status (n = 909), 5-HTTLPR × Sexual and Physical Abuse (n = 1097) to predict bulimic symptoms, 5-HTLPR × Depression to predict bulimic symptoms (n = 1256), and 5-HTTLPR × Impulsivity to predict disordered eating (n = 1149).
The low function (s) allele of 5-HTTLPR interacted with number of traumatic life events (P < .01) and sexual and physical abuse (P < .05) to predict increased likelihood of an ED in females but not males (Fig. 1). No other G × E interactions were significant, possibly due to the medium to low compatibility between datasets (Fig. 1).
Early promising results suggest that increased knowledge of G × E interactions could be achieved if studies increased uniformity of measuring ED and environmental variables, allowing for continued collaboration to overcome the restrictions of obtaining genetic samples.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Excessive mobilization of body reserves during the transition from pregnancy to lactation imposes a risk for metabolic diseases on dairy cows. We aimed to establish an experimental model for high v. normal mobilization and herein characterized performance, metabolic and endocrine changes from 7 weeks antepartum (a.p.) to 12 weeks postpartum (p.p.). Fifteen weeks a.p., 38 pregnant multiparous Holstein cows were allocated to two groups that were fed differently to reach either high or normal body condition scores (HBCS: 7.2 NEL MJ/kg dry matter (DM); NBCS: 6.8 NEL MJ/kg DM) at dry-off. Allocation was also based on differences in body condition score (BCS) in the previous and the ongoing lactation that was further promoted by feeding to reach the targeted BCS and back fat thickness (BFT) at dry-off (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). Thereafter, both groups were fed identical diets. Blood samples were drawn weekly from 7 weeks a.p. to 12 weeks p.p. to assess the serum concentrations of metabolites and hormones. The HBCS cows had greater BCS, BFT and BW than the NBCS cows throughout the study and lost more than twice as much BFT during the first 7 weeks p.p. compared with NCBS. Milk yield and composition were not different between groups, except that lactose concentrations were greater in NBSC than in HBCS. Feed intake was also greater in NBCS, and NBCS also reached a positive energy balance earlier than HBCS. The greater reduction in body mass in HBCS was accompanied by greater concentrations of non-esterified fatty acids, and β-hydroxybutyrate in serum after calving than in NBCS, indicating increased lipomobilization and ketogenesis. The mean concentrations of insulin across all time-points were greater in HBCS than in NBCS. In both groups, insulin and IGF-1 concentrations were lower p.p than in a.p. Greater free thyroxine (fT4) concentrations and a lower free 3-3′-5-triiodothyronine (fT3)/fT4 ratio were observed in HBCS than in NBCS a.p., whereas p.p. fT3/fT4 ratio followed a reverse pattern. The variables indicative for oxidative status had characteristic time courses; group differences were limited to greater plasma ferric reducing ability values in NBSC. The results demonstrate that the combination of pre-selection according to BCS and differential feeding before dry-off to promote the difference was successful in obtaining cows that differ in the intensity of mobilizing body reserves. The HBCS cows were metabolically challenged due to intense mobilization of body fat, associated with reduced early lactation dry matter intake and compromised antioxidative capacity.
Identifying the transmission sources and reservoirs of Streptococcus pneumoniae (SP) is a long-standing question for pneumococcal epidemiology, transmission dynamics, and vaccine policy. Here we use serotype to identify SP transmission and examine acquisitions (in the same household, local community, and county, or of unidentified origin) in a longitudinal cohort of children and adults from the Navajo Nation and the White Mountain Apache American Indian Tribes. We found that adults acquire SP relatively more in the household than other age groups, and children 2–8 years old typically acquire in their own or surrounding communities. Age-specific transmission probability matrices show that transmissions within household were mostly seen from older to younger siblings. Outside the household, children most often transmit to other children in the same age group, showing age-assortative mixing behavior. We find toddlers and older children to be most involved in SP transmission and acquisition, indicating their role as key drivers of SP epidemiology. Although infants have high carriage prevalence, they do not play a central role in transmission of SP compared with toddlers and older children. Our results are relevant to inform alternative pneumococcal conjugate vaccine dosing strategies and analytic efforts to inform optimization of vaccine programs, as well as assessing the transmission dynamics of pathogens transmitted by close contact in general.
Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40–60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.
Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.
Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).
In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls.
This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.
Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years).
Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment.
An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ⩾70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41–12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries.
Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.
Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred.
To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive–behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS.
A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up.
A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019).
Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.
The significance of the potential impacts of microbial activity on the transport properties of host rocks for geological repositories is an area of active research. Most recent work has focused on granitic environments. This paper describes pilot studies investigating changes in transport properties that are produced by microbial activity in sedimentary rock environments in northern Japan. For the first time, these short experiments (39 days maximum) have shown that the denitrifying bacteria, Pseudomonas denitrificans, can survive and thrive when injected into flow-through column experiments containing fractured diatomaceous mudstone and synthetic groundwater under pressurized conditions. Although there were few significant changes in the fluid chemistry, changes in the permeability of the biotic column, which can be explained by the observed biofilm formation, were quantitatively monitored. These same methodologies could also be adapted to obtain information from cores originating from a variety of geological environments including oil reservoirs, aquifers and toxic waste disposal sites to provide an understanding of the impact of microbial activity on the transport of a range of solutes, such as groundwater contaminants and gases (e.g. injected carbon dioxide).
With modern undulators generating light of an arbitrary polarization state, experiments exploiting this feature in the soft X-ray region are becoming increasingly widespread. Circularly polarized light in the soft X-ray region is of particular interest to investigate of magnetic metals such as Fe, Co and Ni, and the rare earths. A versatile multilayer polarimeter has been designed and developed to characterize the polarization state of the soft X-ray beam. A W/B4C multilayer transmission phase retarder and reflection analyser has been used for polarimetry measurements on the beamline (I06) at Diamond Light Source. The design details of the polarimeter and preliminary polarimetry results are presented.
With regard to current neurobiological theories, the aim of our study was to examine possible alterations of temporal and frontal lobe volume in panic disorder (PD).
Seventeen in-patients with PD and a group of healthy control subjects (HC) matched for age and gender were investigated by quantitative volumetric magnetic resonance imaging (MRI). Structures of interest were: the temporal lobe, the amygdala–hippocampus complex (AHC) and the frontal lobe. In addition, a voxel-based morphometry (VBM) analysis implemented in Statistical Parametric Mapping 5 (SPM5) was used for a more detailed assessment of possible volume alterations. Modulated grey matter (GM) images were used to test our a priori hypotheses and to present the volumetric results.
Quantitative volumetric MRI revealed a bilateral reduction in temporal lobe volume in patients with PD compared to HC subjects. The AHC was normal. The right frontal lobe volume was also decreased. Using VBM we detected a significant GM volume reduction in the right middle temporal gyrus [Brodmann area (BA) 21] in patients with PD. In addition, there was a reduction in GM volume in the medial part of the orbitofrontal cortex (BA 11).
Our results of reduced temporal and frontal lobe volume in PD are in agreement with prior studies. By using a recent VBM approach we were able to assess the abnormalities more precisely. The location of GM volume reduction in the right middle temporal gyrus and medial orbitofrontal cortex lends further support to recent aetiological models of PD.
There is increasing evidence that the frequently reported working memory impairments in schizophrenia might be partly due to an alteration in the functional connectivity between task-relevant areas. However, little is known about the functional connectivity patterns in schizophrenia patients during learning processes. In a previous study, Koch et al. [Neuroscience (2007) 146, 1474–1483] have demonstrated stronger exponential activation decreases in schizophrenia patients during overlearning of short-term memory material. The question arises whether these differential temporal patterns of activation in schizophrenia patients and controls are going along with changes in task-related functional connectivity.
Therefore, in the current study, 13 patients with schizophrenia and 13 controls were studied while performing a short-term memory task associated with increasing overlearning of verbal stimulus material. Functional connectivity was investigated by analyses of psychophysiological interactions (PPI).
Results revealed significant task-related modulation of functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and a network including the right DLPFC, left ventrolateral prefrontal cortex, premotor cortex, right inferior parietal cortex, left and right cerebellum as well as the left occipital lobe in patients during the course of overlearning and practice. No significant PPI results were detectable in controls.
Activation changes with practice were associated with high functional connectivity between task-relevant areas in schizophrenia patients. This could be interpreted as a compensatory resource allocation and network integration in the context of cortical inefficiency and may be a specific neurophysiological signature underlying the pathophysiology of schizophrenia.