A 12-month follow-up study of treating overweight schizophrenic patients with aripiprazole

Objective: To investigate the feasibility of switching overweight schizophrenic patients to aripiprazole and to assess the impact of 12 months of aripiprazole treatment on weight in routine practice. Method: This was a non-controlled cohort study in overweight schizophrenic patients. Data were collected before treatment with aripiprazole was started and at 12-month follow-up. Results: A total of 53 patients were included; of these 55% continued using aripiprazole for 12 months. Aripiprazole treatment for 12 months (P = 0.027) and stopping clozapine or olanzapine treatment (P = 0.038) predicted weight loss (>= 3 kg). Patients receiving aripiprazole monotherapy (n = 16, mean -3.0 kg) had similar weight loss than patients receiving aripiprazole in addition to another antipsychotic drug (n = 13, mean -4.4 kg). Conclusion: In routine practice once aripiprazole treatment was started, more than half of the patients remained on aripiprazole and most of them lost weight. Adding aripiprazole to clozapine gave similar weight loss as monotherapy with aripiprazole

Visualization of the thymus by substance P receptor scintigraphy in man

Substance P, an 11-amino acid neuropeptide, has an important role in modulating pain transmission through neurokinin 1 and 2 receptors. Substance P and other tachykinins may also play a role in the pathogenesis of inflammatory diseases. In this study we present the results concerning the metabolism of the substance P analogue [111In-DTPA-Arg1]-substance P in man, as well as the visualization of the thymus in patients with immune-mediated diseases. Twelve selected patients were investigated, comprising five with inflammatory bowel disease, one with ophthalmic Graves' disease, one with sclerosing cholangitis, one with Sjogren's syndrome, one with rheumatoid arthritis, one with systemic lupus erythematosus and two with myasthenia gravis. During and after intravenous administration of 150-250 MBq (2.5-5.0 μg) [111In-DTPA-Arg1]-substance P, blood pressure, heart rate and oxygen saturation were monitored. Radioactivity was measured in blood, urine and faeces during the 48 h after injection. Planar and single-photon emission tomographic images were obtained 4 and 24 h after injection. After administration of [111In-DTPA-Arg1]-substance P a transient flush was observed in all patients. Degradation of [111In-DTPA-Arg1] -substance P started in the first minutes after administration, resulting in a half-life of 10 min for the total plasma radioactivity, and of 4 min for the intact radiopharmaceutical, as identified with high-performance liquid chromatography. Urinary excretion accounted for &gt;95% of the radioactivity within 24 h post injection, and up to 0.05% was found in the faeces up to 60 h. In all patients uptake of radioactivity was found in the areolae mammae (in women), liver, spleen, kidneys and urinary bladder. In eight patients a high uptake of [111In-DTPA-Arg1]-substance P was observed in the thymus. We conclude that, despite its short half-life. [111In-DTPA-Arg1]-substance P, a new radiopharmaceutical, can be used to visualize the thymus. This may contribute to the investigation of the role of thymus in immune-mediated diseases. In addition, inflammatory sites in various diseases could be visualized.</p

Visualization of the thymus by substance P receptor scintigraphy in man

Substance P, an 11-amino acid neuropeptide, has an important role in modulating pain transmission through neurokinin 1 and 2 receptors. Substance P and other tachykinins may also play a role in the pathogenesis of inflammatory diseases. In this study we present the results concerning the metabolism of the substance P analogue [111In-DTPA-Arg1]-substance P in man, as well as the visualization of the thymus in patients with immune-mediated diseases. Twelve selected patients were investigated, comprising five with inflammatory bowel disease, one with ophthalmic Graves' disease, one with sclerosing cholangitis, one with Sjogren's syndrome, one with rheumatoid arthritis, one with systemic lupus erythematosus and two with myasthenia gravis. During and after intravenous administration of 150-250 MBq (2.5-5.0 μg) [111In-DTPA-Arg1]-substance P, blood pressure, heart rate and oxygen saturation were monitored. Radioactivity was measured in blood, urine and faeces during the 48 h after injection. Planar and single-photon emission tomographic images were obtained 4 and 24 h after injection. After administration of [111In-DTPA-Arg1]-substance P a transient flush was observed in all patients. Degradation of [111In-DTPA-Arg1] -substance P started in the first minutes after administration, resulting in a half-life of 10 min for the total plasma radioactivity, and of 4 min for the intact radiopharmaceutical, as identified with high-performance liquid chromatography. Urinary excretion accounted for &gt;95% of the radioactivity within 24 h post injection, and up to 0.05% was found in the faeces up to 60 h. In all patients uptake of radioactivity was found in the areolae mammae (in women), liver, spleen, kidneys and urinary bladder. In eight patients a high uptake of [111In-DTPA-Arg1]-substance P was observed in the thymus. We conclude that, despite its short half-life. [111In-DTPA-Arg1]-substance P, a new radiopharmaceutical, can be used to visualize the thymus. This may contribute to the investigation of the role of thymus in immune-mediated diseases. In addition, inflammatory sites in various diseases could be visualized.</p

Small Nuclear RNAs Encoded by Herpesvirus saimiri Upregulate the Expression of Genes Linked to T Cell Activation in Virally Transformed T Cells

SummarySeven small nuclear RNAs of the Sm class are encoded by Herpesvirus saimiri (HVS), a γ Herpesvirus that causes aggressive T cell leukemias and lymphomas in New World primates and efficiently transforms T cells in vitro [1–4]. The Herpesvirus saimiri U RNAs (HSURs) are the most abundant viral transcripts in HVS-transformed, latently infected T cells but are not required for viral replication or transformation in vitro [5]. We have compared marmoset T cells transformed with wild-type or a mutant HVS lacking the most highly conserved HSURs, HSURs 1 and 2. Microarray and Northern analyses reveal that HSUR 1 and 2 expression correlates with significant increases in a small number of host mRNAs, including the T cell-receptor β and γ chains, the T cell and natural killer (NK) cell-surface receptors CD52 and DAP10, and intracellular proteins—SKAP55, granulysin, and NKG7—linked to T cell and NK cell activation. Upregulation of three of these transcripts was rescued after transduction of deletion-mutant-HVS-transformed cells with a lentiviral vector carrying HSURs 1 and 2. These changes indicate an unexpected role for the HSURs in regulating a remarkably defined and physiologically relevant set of host targets involved in the activation of virally transformed T cells during latency

What's in a score:A longitudinal investigation of scores based on item response theory and classical test theory for the Amsterdam Instrumental Activities of Daily Living Questionnaire in cognitively normal and impaired older adults

OBJECTIVE:We aimed to investigate whether item response theory (IRT)-based scoring allows for a more accurate, responsive, and less biased assessment of everyday functioning than traditional classical test theory (CTT)-based scoring, as measured with the Amsterdam Instrumental Activities of Daily Living Questionnaire. METHOD: In this longitudinal multicenter study including cognitively normal and impaired individuals, we examined IRT-based and CTT-based score distributions and differences between diagnostic groups using linear regressions, and investigated scale attenuation. We compared change over time between scoring methods using linear mixed models with random intercepts and slopes for time.RESULTS: Two thousand two hundred ninety-four participants were included (66.6 ± 7.7 years, 54% female): n = 2,032 (89%) with normal cognition, n = 93 (4%) with subjective cognitive decline, n = 79 (3%) with mild cognitive impairment, and n = 91 (4%) with dementia. At baseline, IRT-based and CTT-based scores were highly correlated (r = -0.92). IRT-based scores showed less scale attenuation than CTT-based scores. In a subsample of n = 1,145 (62%) who were followed for a mean of 1.3 (SD = 0.6) years, IRT-based scores declined significantly among cognitively normal individuals (unstandardized coefficient [B] = -0.15, 95% confidence interval, 95% CI [-0.28, -0.03], effect size = -0.02), whereas CTT-based scores did not (B = 0.20, 95% CI [-0.02, 0.41], effect size = 0.02). In the other diagnostic groups, effect sizes of change over time were similar. CONCLUSIONS: IRT-based scores were less affected by scale attenuation than CTT-based scores. With regard to responsiveness, IRT-based scores showed more signal than CTT-based scores in early disease stages, highlighting the IRT-based scores' superior suitability for use in preclinical populations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).</p

An overview of the design, construction and performance of large area triple-GEM prototypes for future upgrades of the CMS forward muon system

GEM detectors are used in high energy physics experiments given their good spatial resolution, high rate capability and radiation hardness. An international collaboration is investigating the possibility of covering the 1.6 < vertical bar eta vertical bar < 2.4 region of the CMS muon endcaps with large-area triple-GEM detectors. The CMS high-eta area is actually not fully instrumented, only Cathode Strip Chamber (CSC) are installed. The vacant area presents an opportunity for a detector technology able to to cope with the harsh radiation environment; these micropattern gas detectors are an appealing option to simultaneously enhance muon tracking and triggering capabilities in a future upgrade of the CMS detector. A general overview of this feasibility study is presented. Design and construction of small (10cm x 10cm) and full-size trapezoidal (1m x 0.5m) triple-GEM prototypes is described. Results from measurements with x-rays and from test beam campaigns at the CERN SPS is shown for the small and large prototypes. Preliminary simulation studies on the expected muon reconstruction and trigger performances of this proposed upgraded muon system are reported

Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project

To codify the use of multiparametric magnetic resonance imaging (mpMRI) for the interrogation of prostate neoplasia (PCa) in clinical practice and focal therapy (FT). An international collaborative consensus project was undertaken using the Delphi method among experts in the field of PCa. An online questionnaire was presented in three consecutive rounds and modified each round based on the comments provided by the experts. Subsequently, a face-to-face meeting was held to discuss and finalize the consensus results. mpMRI should be performed in patients with prior negative biopsies if clinical suspicion remains, but not instead of the PSA test, nor as a stand-alone diagnostic tool or mpMRI-targeted biopsies only. It is not recommended to use a 1.5 Tesla MRI scanner without an endorectal or pelvic phased-array coil. mpMRI should be performed following standard biopsy-based PCa diagnosis in both the planning and follow-up of FT. If a lesion is seen, MRI-TRUS fusion biopsies should be performed for FT planning. Systematic biopsies are still required for FT planning in biopsy-naïve patients and for patients with residual PCa after FT. Standard repeat biopsies should be taken during the follow-up of FT. The final decision to perform FT should be based on histopathology. However, these consensus statements may differ for expert centers versus non-expert centers. The mpMRI is an important tool for characterizing and targeting PCa in clinical practice and FT. Standardization of acquisition and reading should be the main priority to guarantee consistent mpMRI quality throughout the urological communit

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Search for Heavy Isosinglet Neutrino in e+e- Annihilation at LEP

We report on a search for the first generation heavy neutrino that is an isosinglet under the standard SU(2)_L gauge group. The data collected with the L3 detector at center-of-mass energies between 130 GeV and 208 GeV are used.The decay channel N_e --> eW is investigated and no evidence is found for a heavy neutrino, N_e, in a mass range between 80 GeV and 205 GeV. Upper limits on the mixing parameter between the heavy and light neutrino are derived