142 research outputs found

    Nesfatin-130−59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions

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    Nesfatin-1 is well-established to induce an anorexigenic effect. Recently, nesfatin-130−59, was identified as active core of full length nesfatin-11−82 in mice, while its role in rats remains unclear. Therefore, we investigated the effects of nesfatin-130−59 injected intracerebroventricularly (icv) on the food intake microstructure in rats. To assess whether the effect was also mediated peripherally we injected nesfatin-130−59 intraperitoneally (ip). Since obesity affects the signaling of various food intake-regulatory peptides we investigated the effects of nesfatin-130−59 under conditions of diet- induced obesity (DIO). Male Sprague–Dawley rats fed ad libitum with standard diet were icv cannulated and injected with vehicle (5 μl ddH2O) or nesfatin-130−59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food intake microstructure assessed using a food intake monitoring system. Next, naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130−59 (8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or vehicle (5 μl ddH2O) was injected icv and the food intake microstructure assessed. In rats fed standard diet, nesfatin-130−59 caused a dose-dependent reduction of dark phase food intake reaching significance at 0.9 nmol/rat in the period of 4–8 h post injection (−29%) with the strongest reduction during the fifth hour (−75%), an effect detectable for 24 h (−12%, p < 0.05 vs. vehicle). The anorexigenic effect of nesfatin-130−59 was due to a reduction in meal size (−44%, p < 0.05), while meal frequency was not altered compared to vehicle. In contrast to icv injection, nesfatin-130−59 injected ip in up to 30-fold higher doses did not alter food intake. In DIO rats fed high fat diet, nesfatin-130−59 injected icv reduced food intake in the third hour post injection (−71%), an effect due to a reduced meal frequency (−27%, p < 0.05), while meal size was not altered. Taken together, nesfatin-130−59 is the active core of nesfatin-11−82 and acts centrally to reduce food intake in rats. The anorexigenic effect depends on the metabolic condition with increased satiation (reduction in meal size) under normal weight conditions, while in DIO rats satiety (reduction in meal frequency) is induced

    Epidemiology of Pathogenic Retroviruses and Domestic Cat Hepadnavirus in Community and Client-Owned Cats in Hong Kong

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    Understanding the local epidemiology of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in Hong Kong will inform retrovirus prevention strategies. Domestic cat hepadnavirus (DCH), a novel hepatitis-B-like virus, is commonly detected among client-owned cats in Hong Kong, but community cats have not been studied. The aims of this study were to investigate the frequency and potential risk factors for (i) FeLV and FIV among community and client-owned cats and (ii) perform molecular detection of DCH among community cats in Hong Kong. Blood samples from 713 cats were obtained from client-owned (n = 415, residual diagnostic) and community cats (n = 298, at trap-neuter-return). Point-of-care (POC) testing for FeLV antigen and feline immunodeficiency virus (FIV) anti-p15 and p24 antibodies was performed. FeLV-positive samples were progressed to p27 sandwich enzyme-linked immunosorbent assay. Whole blood DNA was tested with qPCRs for FeLV U3 and gag, and nested PCRs where additional information was required. DCH qPCR was performed on a subset of community cats (n = 193). A single, regressive, FeLV infection was detected in a client-owned cat (1/415 FeLV U3 qPCR positive, 0.2%, 95% CI 0.0–1.3%). Five/415 client-owned cats tested presumably false FeLV-antigen positive (qPCR negative). No markers of FeLV infection were detected in community cats (0/298; 0%). FIV seroprevalence was much higher in community cats (46/298, 15.4%) than in client-owned cats (13/415, 3.1%) (p < 0.001). Mixed breed was a risk factor for FIV infection in client-owned cats. Neither sex nor age were associated with FIV infection. DCH DNA was detected in 34/193 (17.6%) community cats (median viral load 6.32 × 103 copies/reaction). FeLV infection is rare in Hong Kong, negatively impacting the positive predictive value of diagnostic tests. FeLV-antigen testing remains the screening test of choice, but confirmation of a positive result using FeLV qPCR is essential. FIV infection is common in community cats and the absence of a sex predisposition, seen previously in cats managed similarly, raises questions about virus-transmission dynamics in these groups. DCH infection is very common in Hong Kong, both in client-owned and community cats, highlighting the importance of understanding the pathogenic potential of this virus for cats

    Enhanced stimulation of antigen-specific immune responses against nucleophosmin 1 mutated acute myeloid leukaemia by an anti-programmed death 1 antibody

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    Nucleophosmin1 (NPM1) is one of the most commonly mutated genes in AML and is often associated with a favourable prognosis. Immune responses play an increasing role in AML treatment decisions; however, the role of immune checkpoint inhibition is still not clear. To address this, we investigated specific immune responses against NPM1, and three other leukaemia-associated antigens (LAA), PRAME, Wilms' tumour 1 and RHAMM in AML patients. We investigated T cell responses against leukaemic progenitor/stem cells (LPC/LSC) using colony-forming immunoassays and flow cytometry. We examined whether immune checkpoint inhibition with the anti-programmed death 1 antibody increases the immune response against stem cell-like cells, comparing cells from NPM1 mutated and NPM1 wild-type AML patients. We found that the anti-PD-1 antibody, nivolumab, increases LAA stimulated cytotoxic T lymphocytes and the cytotoxic effect against LPC/LSC. The effect was strongest against NPM1mut cells when the immunogenic epitope was derived from the mutated region of NPM1 and these effects were enhanced through the addition of anti-PD-1. The data suggest that patients with NPM1 mutated AML could be treated with the immune checkpoint inhibitor anti-PD-1 and that this treatment combined with NPM1-mutation specific directed immunotherapy could be even more effective for this unique group of patients

    Relationship Between Time of Admission, Help-Seeking Behavior, and Psychiatric Outcomes: “From Dusk Till Dawn”

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    Introduction: Day and time of admission influence treatment outcomes and prognosis in several medical specialties; this seems related to resources' ability. It is largely unknown whether this also applies to mental health services. We investigate the relationship between time of admission, patients' demographic and clinical profile, and treatment outcomes. Methods: Demographic and clinical profiles of admitted and discharged patients to a general psychiatric ward between January 1st, 2013 and December 31st, 2020, were analyzed. In addition, we used the last year (i.e., 2020) to monitor rehospitalization. Time of admission was defined as weekdays (working day, weekend) and dayshifts (daytime, dusk, and dawn). Results: During the study period, 12,449 patient admissions occurred. The mean age of the sample was 48.05 ± 20.90 years, with 49.32% (n = 6,140) females. Most admissions (n = 10,542, 84%) occurred on working days. Two-fifths of admissions (39.7%, n = 4,950) were compulsory, with a higher rate outside daytime hours. Patients had slight differences in the clinical profile, resulting from evaluating the different items of the Health of Nation Outcome Scale (HoNOS). Patients admitted on night shifts, weekends, and holidays showed a shorter length of stay; patients compulsorily admitted during daytime (disregarding the day of the week) had a longer length of stay. All patient groups achieved a robust clinical improvement (i.e., an HoNOS score reduction of around 50%), with similar readmission rates. Discussion: The main finding of our study is the relationship between "daytime hours" and fewer compulsory admissions, a result of the interplay between demographics, clinical characteristics, and out-of-clinic service availability (such as ambulatory psychiatric- psychological praxis; day-clinic; home-treatment). The differing clinical profile, in turn, determines differences in treatment selection, with patients admitted after office hours experiencing a higher rate of coercive measures. The shorter length of stay for out-of-office admissions might result from the hospitalization as an intervention. These results should encourage the implementation of outpatient crisis-intervention services, available from dusk till dawn. Keywords: coercive measures; day and time of admission; help-seeking behavior; psychiatric outcomes; service use

    Utility and validity of the Brief Psychiatric Rating Scale (BPRS) as a transdiagnostic scale

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    The Brief Psychiatric Rating Scale (BPRS) was originally conceived to assess psychopathology in several psychiatric disorders, making it an appropriate candidate to be used as a transdiagnostic instrument. We analyzed the utility and validity of the BPRS in a diagnostically heterogeneous sample of 600 psychiatric inpatients. As a comparator, we chose the mini-ICF-APP, a scale used to measure functioning and impairment across the diagnostic spectrum. Both scales had good internal consistency. The BPRS and the mini-ICF-APP showed a moderate correlation, with good levels of agreement. We were able to identify general symptoms present across the diagnostic spectrum, influencing severity and a cluster of symptoms specific for each diagnosis. Our results show the utility and validity of the BPRS as a transdiagnostic assessment tool that could easily be introduced in routine clinical work

    Immuno-histochemical correlation of fibrosis-related markers with the desmoplastic reaction of the mesentery in small intestine neuroendocrine neoplasms

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    INTRODUCTION Small intestine neuroendocrine neoplasms (siNENs) will attain more importance due to their increasing incidence. Moreover, siNENs might lead to a desmoplastic reaction (DR) of the mesentery causing severe complications and deteriorating prognosis. The expression of fibrosis-related proteins appears to be the key mechanisms for the development of this desmoplastic reaction. Therefore, this study aimed to investigate the association of the desmoplastic mesentery with specific fibrosis-related protein expression levels. MATERIALS AND METHODS By immunohistochemistry, the protein expression levels of four fibrosis-related markers (APLP2, BNIP3L, CD59, DKK3) were investigated in primary tumors of 128 siNENs. The expression levels were correlated with the presence of a desmoplastic reaction and clinico-pathological parameters. RESULTS In the primary tumor, APLP2, BNIP3L, CD59 and DKK3 were highly expressed in 29.7% (n = 38), 64.9% (n = 83), 92.2% (n = 118) and 80.5% (n = 103), respectively. There was no significant correlation of a single marker or the complete marker panel to the manifestation of a desmoplastic mesentery. The desmoplastic mesentery was significantly associated with clinical symptoms, such as flushing and diarrhea. However, neither the fibrosis-related marker panel nor single marker expressions were associated with clinical symptoms. DISCUSSION The expression rates of four fibrosis-related markers in the primary tumor display a distinct pattern. However, the expression patterns are not associated with desmoplastic altered mesenteric lymph node metastases and the expression patterns did not correlate with prognosis. These findings suggest alternative mechanisms being responsible for the desmoplastic reaction

    High contrast imaging at the LBT: the LEECH exoplanet imaging survey

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    In Spring 2013, the LEECH (LBTI Exozodi Exoplanet Common Hunt) survey began its \sim130-night campaign from the Large Binocular Telescope (LBT) atop Mt Graham, Arizona. This survey benefits from the many technological achievements of the LBT, including two 8.4-meter mirrors on a single fixed mount, dual adaptive secondary mirrors for high Strehl performance, and a cold beam combiner to dramatically reduce the telescope's overall background emissivity. LEECH neatly complements other high-contrast planet imaging efforts by observing stars at L' (3.8 μ\mum), as opposed to the shorter wavelength near-infrared bands (1-2.4 μ\mum) of other surveys. This portion of the spectrum offers deep mass sensitivity, especially around nearby adolescent (\sim0.1-1 Gyr) stars. LEECH's contrast is competitive with other extreme adaptive optics systems, while providing an alternative survey strategy. Additionally, LEECH is characterizing known exoplanetary systems with observations from 3-5μ\mum in preparation for JWST.Comment: 12 pages, 5 figures. Proceedings of the SPIE, 9148-2

    The LEECH Exoplanet Imaging Survey: Limits on Planet Occurrence Rates Under Conservative Assumptions

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    We present the results of the largest LL^{\prime} (3.8 μ3.8~\mum) direct imaging survey for exoplanets to date, the Large Binocular Telescope Interferometer (LBTI) Exozodi Exoplanet Common Hunt (LEECH). We observed 98 stars with spectral types from B to M. Cool planets emit a larger share of their flux in LL^{\prime} compared to shorter wavelengths, affording LEECH an advantage in detecting low-mass, old, and cold-start giant planets. We emphasize proximity over youth in our target selection, probing physical separations smaller than other direct imaging surveys. For FGK stars, LEECH outperforms many previous studies, placing tighter constraints on the hot-start planet occurrence frequency interior to 20\sim20 au. For less luminous, cold-start planets, LEECH provides the best constraints on giant-planet frequency interior to 20\sim20 au around FGK stars. Direct imaging survey results depend sensitively on both the choice of evolutionary model (e.g., hot- or cold-start) and assumptions (explicit or implicit) about the shape of the underlying planet distribution, in particular its radial extent. Artificially low limits on the planet occurrence frequency can be derived when the shape of the planet distribution is assumed to extend to very large separations, well beyond typical protoplanetary dust-disk radii (50\lesssim50 au), and when hot-start models are used exclusively. We place a conservative upper limit on the planet occurrence frequency using cold-start models and planetary population distributions that do not extend beyond typical protoplanetary dust-disk radii. We find that 90%\lesssim90\% of FGK systems can host a 7 to 10 MJupM_{\mathrm{Jup}} planet from 5 to 50 au. This limit leaves open the possibility that planets in this range are common.Comment: 31 pages, 13 figures, accepted to A

    Two inhibitory control training interventions designed to improve eating behaviour and determine mechanisms of change

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    Inhibitory control training has been shown to influence eating behaviour in the laboratory; however, the reliability of these effects is not yet established outside the laboratory, nor are the mechanisms responsible for change in behaviour. Two online Stop-Signal Task training interventions were conducted to address these points. In Study 1, 72 participants completed baseline and follow-up measures of inhibitory control, self-regulatory depletion, fat intake and body-mass index. Participants were randomly assigned to complete one of three Stop-Signal Tasks daily for ten days: food-specific inhibition - inhibition in response to unhealthy food stimuli only, general inhibition - inhibition was not contingent on type of stimuli, and control - no inhibition. While fat intake did not decrease, body-mass index decreased in the food-specific condition and change in this outcome was mediated by changes in vulnerability to depletion. In Study 2, the reliability and longevity of these effects were tested by replicating the intervention with a third measurement time-point. Seventy participants completed baseline, post-intervention and follow-up measures. While inhibitory control and vulnerability to depletion improved in both training conditions post-intervention, eating behaviour and body-mass index did not. Further, improvements in self-regulatory outcomes were not maintained at follow-up. It appears that while the training paradigm employed in the current studies may improve self-regulatory outcomes, it may not necessarily improve health outcomes. It is suggested that this may be due to the task parameters, and that a training paradigm that utilises a higher proportion of stop-signals may be necessary to change behaviour. In addition, improvements in self-regulation do not appear to persist over time. These findings further current conceptualisations of the nature of self-regulation and have implications for the efficacy of online interventions designed to improve eating behaviour
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