ITI-007 demonstrates brain occupancy at serotonin 5-HT2A and dopamine D2 receptors and serotonin transporters using positron emission tomography in healthy volunteers

© 2015 Springer-Verlag Berlin Heidelberg.Rationale: Central modulation of serotonin and dopamine underlies efficacy for a variety of psychiatric therapeutics. ITI-007 is an investigational new drug in development for treatment of schizophrenia, mood disorders, and other neuropsychiatric disorders. Objectives: The purpose of this study was to determine brain occupancy of ITI-007 at serotonin 5-HT2A receptors, dopamine D2 receptors, and serotonin transporters using positron emission tomography (PET) in 16 healthy volunteers. Methods: Carbon-11-MDL100907, carbon-11-raclopride, and carbon-11-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) (carbon-11-DASB) were used as the radiotracers for imaging 5-HT2A receptors, D2 receptors, and serotonin transporters, respectively. Brain regions of interest were outlined using magnetic resonance tomography (MRT) with cerebellum as the reference region. Binding potentials were estimated by fitting a simplified reference tissue model to the measured tissue-time activity curves. Target occupancy was expressed as percent change in the binding potentials before and after ITI-007 administration. Results: Oral ITI-007 (10-40 mg) was safe and well tolerated. ITI-007 rapidly entered the brain with long-lasting and dose-related occupancy. ITI-007 (10 mg) demonstrated high occupancy (>80 %) of cortical 5-HT2A receptors and low occupancy of striatal D2 receptors (~12 %). D2 receptor occupancy increased with dose and significantly correlated with plasma concentrations (r 2∈=∈0.68, p∈=∈0.002). ITI-007 (40 mg) resulted in peak occupancy up to 39 % of striatal D2 receptors and 33 % of striatal serotonin transporters. Conclusions: The results provide evidence for a central mechanism of action via dopaminergic and serotonergic pathways for ITI-007 in living human brain and valuable information to aid dose selection for future clinical trials

Milkfish hatchery operations

The manual is intended primarily for practicing prawn hatchery operators who would like to diversify their operations to include larval rearing of milkfish (Chanos chanos). Only those procedures important in the daily operations of a milkfish hatchery are described in detail, under the following headings: Essential facilities - tanks and equipment; Production of natural food - Chlorella culture and Brachionus culture; Production of milkfish fry - preparation of hatching and larval rearing tanks, hatching of milkfish eggs, stocking of larvae, larval rearing, and harvesting

Nursery culture of grouper (Epinephelus fuscoguttatus Forsskal) and sea bass (Lates calcarifer Bloch) in brackish water ponds: Co-feeding of zooplankton and formulated diets containing L-tryptophan

This study compared co-feeding zooplankton (ZP, mixed copepods and mysids) and formulated diets (FD) supplemented with L-tryptophan (TRP) on the survival and growth of grouper and sea bass fry nursed in brackish water ponds. Grouper (84 fry m−3) and sea bass (150 fry m−3) were reared for 30 days and 60 days, respectively, in net cages within two separate 743 m2 nursery ponds. Five treatments (with three replicates each) were compared (P < 0.05): FD-1 = ZP + basal FD (no added TRP, but containing 0.29% endogenous TRP); FD-2 = ZP + (FD 0.58% TRP); FD-3 = ZP + (FD 1.22% TRP); FD-4 = ZP + (FD 2.50% TRP); and FD-5 = minced fish (Sardinella sp.) + basal FD (no additional TRP). TRP supplementation in grouper diets produced no significant affect on growth but increased survival at rates of 0.58% and above. TRP supplementation at 2.5% (FD-4) produced significantly better sea bass growth than other diets but had no affect on survival. Zooplankton improved both survival and growth in both grouper and sea bass juveniles compared to the minced fish diet, and may be a practical and lower cost alternative to indoor nursing

Women Scientists and Managers in Agricultural Research in the Philippines

This case study investigates the entry, retention, and achievement of women in agricultural science in the Philippines. It is intended to help research managers and their organizations in developing countries meet the challenges of changing work-force characteristics. It was carried out in four public-sector institutes with a total of almost 300 scientists, 54% of whom are women. The study used survey data, interviews and discussions with 100 staff, and records from two universities. Women are replacing men who have left the public sector for career opportunities in the private sector. Family responsibilities are an important factor leading to retention of women in public-sector jobs, which offer stability, flexibility, and supportive policies. Although women constitute a majority of the workforce, they are underrepresented in top-level positions. Seniority and research output did not explain the discrepancy since men and women have comparable length-of-service and publication records. Data suggest that women’s careers are affected more than men’s by their status in dual-career families. Women cited delays in training, relocation to follow husbands, and lack of mobility as career constraints. Cultural stereotypes of men’s and women’s roles within the household continue to color and affect working relationships and appear to limit women’s opportunities for advancement into senior positions. We are likely to see increasing participation of women in research organizations in developing countries. Constraints to women’s career attainment may persist primarily due to cultural barriers. The study discusses management practices from the Philippines that can assist the effective incorporation of women into a scientific work force

Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial.

IMPORTANCE: Psilocybin shows promise as a treatment for major depressive disorder (MDD). OBJECTIVE: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. DESIGN, SETTING, AND PARTICIPANTS: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days\u27 duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. INTERVENTIONS: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. MAIN OUTCOMES AND MEASURES: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. RESULTS: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P CONCLUSIONS AND RELEVANCE: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03866174