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All human tissues are in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates. It has been well-established that protein ingestion stimulates skeletal muscle and whole-body protein synthesis. Stable isotope-labelled amino acid methodologies are commonly applied to assess the various aspects of protein metabolism in vivo in human subjects. However, to achieve a more comprehensive assessment of post-prandial protein handling in vivo in human subjects, intravenous stable isotope-labelled amino acid infusions can be combined with the ingestion of intrinsically labelled protein and the collection of blood and muscle tissue samples. The combined application of ingesting intrinsically labelled protein with continuous intravenous stable isotope-labelled amino acid infusion allows the simultaneous assessment of protein digestion and amino acid absorption kinetics (e.g. release of dietary protein-derived amino acids into the circulation), whole-body protein metabolism (whole-body protein synthesis, breakdown and oxidation rates and net protein balance) and skeletal muscle metabolism (muscle protein fractional synthesis rates and dietary protein-derived amino acid incorporation into muscle protein). The purpose of this review is to provide an overview of the various aspects of post-prandial protein handling and metabolism with a focus on insights obtained from studies that have applied intrinsically labelled protein under a variety of conditions in different populations.
Liquid-phase transmission electron microscopy is a technique for simultaneous imaging of the structure and dynamics of specimens in a liquid environment. The conventional sample geometry consists of a liquid layer tightly sandwiched between two Si3N4 windows with a nominal spacing on the order of 0.5 μm. We describe a variation of the conventional approach, wherein the Si3N4 windows are separated by a 10-μm-thick spacer, thus providing room for gas flow inside the liquid specimen enclosure. Adjusting the pressure and flow speed of humid air inside this environmental liquid cell (ELC) creates a stable liquid layer of controllable thickness on the bottom window, thus facilitating high-resolution observations of low mass-thickness contrast objects at low electron doses. We demonstrate controllable liquid thicknesses in the range 160 ± 34 to 340 ± 71 nm resulting in corresponding edge resolutions of 0.8 ± 0.06 to 1.7 ± 0.8 nm as measured for immersed gold nanoparticles. Liquid layer thickness 40 ± 8 nm allowed imaging of low-contrast polystyrene particles. Hydration effects in the ELC have been studied using poly-N-isopropylacrylamide nanogels with a silica core. Therefore, ELC can be a suitable tool for in situ investigations of liquid specimens.
We assessed the relation between social pension benefits and health among poor older individuals in Colombia based on a qualitative case study (N = 51) using in-depth semi-structured interviews. Participants were beneficiaries of the Colombia Mayor social pension programme, recruited through snowball sampling in one rural and one urban area. Participants reported using cash benefits mainly for purchasing essential foods and medicines, as well as for paying for household utilities and satisfying personal needs. Beneficiaries of the programme view the latter as being positively associated with their health as it not only satisfies material needs but also increases their sense of autonomy, emotional wellbeing and also promotes a positive and cheerful attitude. Despite most beneficiaries perceiving the programme as positively associated with their health and wellbeing, results also highlight the importance of the various individual- as well as contextual-level factors in determining the relation between social pensions and health.
This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.
Methods
Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.
Results
JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.
Conclusions
These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
In this prospective cohort of 1,012 Swiss hospital employees, 3 different assays were used to screen serum for SARS-CoV-2 antibodies. Seropositivity was 1%; the positive predictive values of the lateral-flow immunoassay were 64% (IgG) and 13% (IgM). History of fever and myalgia most effectively differentiated seropositive and seronegative participants.
Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50–59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.
In Pervasive Developmental Disorders, visual perception deficits, such as impaired face and object recognition, have been previously described. More particularly, Kracke (1994) as well as Pietz and colleagues (2003) reported prosopagnosia in individuals fulfilling criteria for Asperger Syndrome (AS). Moreover, anatomical or functional anomalies in the temporo-occipital areas have been observed in neuroimaging studies in autistic patients. Besides, this region is known to underlie visuo-attentional functions. Yet, the examination of such cognitive functions in autistic disorders is scarce, even in clinical practice.
This poster presents the case study of a teenager (male, 14 years) diagnosed with AS on the basis of his developmental history and current presentation: marked social abnormalities, lack of ocular contact, good language although with verbal and non-verbal communication difficulties, circumscribed special interests and motor impairments.
A neuropsychological and neuroophtalmological assessment of visuo-attentional cognitive functions revealed a visual field concentric reduction, signs of left unilateral spatial neglect, impaired visual pursuit, visuo-constructive apraxia and visual extinction. The anatomical MRI showed a mild enlargement of the left posterior ventricular horn (facing the occipital lobe), probably consecutive to a cortical atrophy (in the occipito-parietal parenchyma).
This case study emphasizes that visuo-attentional cognitive difficulties such as visual recognition deficit, visual field defect and attentional bias may be associated to behavioural signs of AS. In addition to previous descriptions in the literature, our case study leads us to consider that neuropsychological assessments of visuo-attentional functions in children with autistic symptoms may provide invaluable clinical and theoretical information.
Clinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.
Objectives
To test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).
Methods
18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.
Results
Single dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.
Conclusions
In this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.
The serotonergic system modulates brain functions that are considered to underlie affective states, emotion and cognition. Several lines of evidence point towards a strong lateralization of these mental processes, indicating similar asymmetries in associated neurotransmitter systems.
Objectives
To investigate a potential brain asymmetry of the serotonin transporter (SERT) distribution using Positron Emission Tomography (PET).
Aims
As brain asymmetries differ between sexes, we aimed to compare serotonin transporter asymmetry between females, males and male-to-female transsexuals whose brains are considered to be partly feminized.
Methods
36 subjects aged 19-54 years (9 female controls, 13 male controls and 14 male-to-female transsexuals) were measured with PET and [11C]DASB. Whole-brain voxel-wise SERT binding potential (BPND) maps were computed using a tracer-specific symmetric template. Statistics comprised repeated measures ANOVA with group as the between subjects factor, voxel-wise SERT asymmetry as repeated factor and group*asymmetry as interaction term.
Results
SERT binding in all groups showed both strong left and rightward asymmetries in several cortical and subcortical structures including temporal and frontal cortices, anterior cingulate, hippocampus, caudate and thalamus (p< 0.05 FDRcorrected). Further, male controls showed a rightward asymmetry in the midcingulate cortex (p>0.05 FDR-corrected) which was absent in females and male-to-female transsexuals.
Conclusions
Our data support the notion of a lateralized serotonergic system, which is in line with previous findings of asymmetric serotonin-1A receptor distributions, extracellular serotonin concentrations, serotonin turnover and uptake. The absence of serotonin transporter asymmetry in the midcingulate in male-to-female transsexuals may be attributed to an absence of brain masculinization in this region.
Evidence suggests a relationship between exposure to trauma and higher levels of symptoms and poorer functional outcomes in early psychotic patients (EPP). However, the impact of the age at the time of exposure to trauma in this association is as yet unknown.
Objectives
To examine the potential differential impact of trauma, according to age at the time of exposure, on the level of functioning and on the psychopathological profile of EPP followed-up prospectively.
Methods
Two hundred and fifty-five EPP aged 18–35 were followed-up prospectively over 36 months. Patients who had faced at least one experience of abuse or neglect were classified according to age at the time of first exposure (early-trauma: before age 12; late-trauma: between age 12 and 16), and then compared with unexposed patients (non-trauma). The level of symptoms was assessed using the Positive and Negative Syndrome Scale. The Young Mania Rating Scale, and the Montgomery-Asberg Depression Rating Scale. The level of functioning was assessed with the global assessment of functioning.
Results
Comparisons over the 3 years of treatment with non-trauma patients revealed that:
– late-trauma patients only showed more negative symptoms (P = 0.029) as compared to non-trauma patients.
Conclusions
The age at the time of exposure to trauma has a modulating effect on its impact on symptoms and functional outcome in EPP and it should be systematically examined in clinical and experimental settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The mechanism linking childhood trauma (CT) to the functional deficits observed in early psychosis (EP) patients is as yet unknown.
Objectives
To examine the potential mediating effect of depressive symptoms in this well-established association.
Methods
Two hundred nine EP subjects aged 18-35 were assessed for functioning and psychopathology after 2, 6, 12, 18, 24, 30, and 36 months of treatment. Patients were classified into early-trauma if they had faced at least one experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) before age 12, and late-trauma if the exposure had occurred between ages 12 and 16. Psychopathology was assessed with the Positive and Negative Syndrome Scale and the Montgomery-Asberg Depression Rating Scale. Functioning was measured with the Global Assessment of Functioning (GAF) and the Social and Occupational Functioning Assessment Scale (SOFAS). Mediation analyses were performed in order to study whether the relationship between CT and functioning was mediated by depressive symptoms.
Results
When compared with nonexposed patients, early but not late trauma patients showed lower levels of GAF and SOFAS scores over all the time points, excepting after the first assessment. After 30 and 36 months, the effect of early trauma on functioning was completely mediated by depressive symptoms. No mediating effect of positive or negative symptoms was highlighted at those time points.
Conclusion
Mild depressive symptoms mediated the impact of early trauma on long-term functional outcome. Intensifying pharmacologic and/or psychotherapeutic treatment, focused on the depressive dimension, may help traumatized EP patients to improve their functioning.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
It has been shown that patients with schizophrenia are super-sensitive towards dopamine-releasing agents such as amphetamine. Here, we studied the effects of amphetamine sensitization on amphetamine-induced dopamine release in healthy subjects.
Objectives
To measure d-amphetamine-induced dopamine release as measured with the D2,3 agonist radioligand [11C]-(+)-PHNO-PET via change in non-displacable binding potential (BPND) and behavioral measures of d-amphetamine effects with drug effects questionnaire (DEQ) and subjective states questionnaire (SSQ).
Aims
To study d-amphetamine-induced sensitization in healthy subjects on a behavioral and neurochemical level with [11C]-(+)-PHNO-PET in order to gain more knowledge on sensitization-induced changes in the dopaminergic system.
Methods
Twelve stimulant-naïve healthy male subjects underwent three 90-min [11C]-(+)-PHNO-PET-scans and four oral administrations of d-amphetamine. After a naïve baseline scan, subjects underwent a PET scan with previous ingestion of 0.4 mg/kg bodyweight of d-amphetamine 90–120 minutes before scanning. Subsequently, subjects were sensitized to d-amphetamine with the same dose on two separate days. Thereafter, they underwent another PET scan with previous d-amphetamine ingestion. DEQ and SSQ were administered before, 60 min, 90–120 min, and 210 min after amphetamine ingestion.
Results
We found significant sensitization effects on a behavioral level and on a neurochemical level after four administrations of amphetamine. Items of the SSQ, which showed significant sensitization effects were “outgoing”, “energetic”, “lively”, “alert” and “focused”.
Conclusions
We were able to induce significant behavioral and neurochemical sensitization in healthy humans, which were measured with [11C]-(+)-PHNO-PET for the first time. This sensitization model will be useful for studying the neurobiology of schizophrenia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
New δ13Ccarb and microfacies data from Hereford–Worcestershire and the West Midlands allow for a detailed examination of variations in the Homerian carbon isotope excursion (Silurian) and depositional environment within the Much Wenlock Limestone Formation of the Midland Platform (Avalonia), UK. These comparisons have been aided by a detailed sequence-stratigraphic and bentonite correlation framework. Microfacies analysis has identified regional differences in relative sea-level change and indicates an overall shallowing of the carbonate platform interior from Hereford–Worcestershire to the West Midlands. Based upon the maximum δ13Ccarb values for the lower and upper peaks of the Homerian carbon isotope excursion (CIE), the shallower depositional setting of the West Midlands is associated with values that are 0.7 ‰ and 0.8 ‰ higher than in Hereford–Worcestershire. At the scale of parasequences the effect of depositional environment upon δ13Ccarb values can also be observed, with a conspicuous offset in the position of the trough in δ13Ccarb values between the peaks of the Homerian CIE. This offset can be accounted for by differences in relative sea-level change and carbonate production rates. While such differences complicate the use of CIEs as a means of high-resolution correlation, and caution against correlations based purely upon the isotopic signature, it is clear that a careful analysis of the depositional environment can account for such differences and thereby improve the use of carbon isotopic curves as a means of correlation.
The Weaklaw vent in SE Scotland (East Lothian coast), inferred to be Namurian, produced lava spatter and volcanic bombs. The latter commonly contained ultramafic xenoliths. All were metasomatised by carbonic fluids rich in incompatible elements. The lavas and xenoliths are inferred to have been basanites and lherzolites prior to metasomatism. The abundance and size of (carbonated) peridotite xenoliths at Weaklaw denotes unusual rapidity of magma ascent and high-energy eruption making Weaklaw exceptional in the British Isles. The lavas and xenoliths were altered subsequently by low-temperature (<200°C) carbo-hydrous fluids to carbonate, clay and quartz assemblages. A small irregular tuffisite ‘dyke’ that transects the ejecta is also composed dominantly of carbonates and clays. The peridotitic xenoliths are typically foliated, interpreted as originating as pre-entrainment mantle shear-planes.
Analyses of the relic spinels shows them to be compositionally similar to spinels in local unaltered lherzolites from near-by basanitic occurrences. Chromium showed neither significant loss nor gain but was concentrated in a di-octahedral smectite allied to volkonskoite. It is in the complex association of smectite with other clays, chlorite and possibly fuchsite that the diverse incompatible elements are concentrated.
We conclude that late Palaeozoic trans-tensional fault movement caused mantle shearing. Rapid ascent of basanite magma entrained large quantities of sheared lithospheric mantle. This was followed by ascent of an aggressive carbonate-/ hydroxyl-rich fluid causing pervasive metasomatism. The vent is unique in several ways: in its remarkable clay mineralogy and in displaying such high Cr-clays in a continental intra-plate setting; in being more productive in terms of its ‘cargo’ of peridotite xenoliths; in presenting an essentially un-eroded sequence of Namurian extrusives; and, not least, for giving evidence for post-eruptive, surface release of small-melt, deep-source fluids.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
The X-Shooter Spectral Library (XSL) contains more than 800 spectra of stars across the color-magnitude diagram, that extend from near-UV to near-IR wavelengths (320-2450 nm). We summarize properties of the spectra of O-rich Long Period Variables in the XSL, such as phase-related features, and we confront the data with synthetic spectra based on static and dynamical stellar atmosphere models. We discuss successes and remaining discrepancies, keeping in mind the applications to population synthesis modeling that XSL is designed for.