Goethite dissolution by acidophilic bacteria.

Previous studies have reported the role of some species of acidophilic bacteria in accelerating the dissolution of goethite under aerobic and anaerobic conditions. This has relevance for environments impacted by acid mine drainage and for the potential bioleaching of limonitic laterite ores. In this study, natural well-characterized goethite mineral samples and synthetic goethite were used in aerobic and anaerobic laboratory batch culture incubation experiments with ferric iron-reducing, acidophilic bacteria, including the lithoautotrophic species Acidithiobacillus (At.) thiooxidans, At. ferrooxidans, and At. caldus, as well as two strains of the organoheterotrophic species Acidiphilium cryptum. All bacteria remained alive throughout the experiments and efficiently reduced soluble ferric iron in solution in positive control assays. However, goethite dissolution was low to negligible in all experimental assays with natural goethite, while some dissolution occurred with synthetic goethite in agreement with previous publications. The results indicate that ferric iron-reducing microbial activity at low pH is less relevant for goethite dissolution than the oxidation of elemental sulfur to sulfuric acid. Microbial ferric iron reduction enhances but does not initiate goethite dissolution in very acidic liquors.

Comparison of bioleaching of a sulfidic copper ore (chalcopyrite) in column percolators and in stirred-tank bioreactors including microbial community analysis.

Chalcopyrite is the most abundant Cu-sulfide and economically the most important copper mineral in the world. It is known to be recalcitrant in hydrometallurgical processing and therefore chalcopyrite bioleaching has been thoroughly studied for improvement of processing. In this study, the microbial diversity in 22 samples from the Sarcheshmeh copper mine in Iran was investigated via 16S rRNA gene sequencing. In total, 1063 species were recognized after metagenomic analysis including the ferrous iron- and sulfur-oxidizing acidophilic genera Acidithiobacillus, Leptospirillum, Sulfobacillus and Ferroplasma. Mesophilic as well as moderately thermophilic acidophilic ferrous iron- and sulfur-oxidizing microorganisms were enriched from these samples and bioleaching was studied in shake flask experiments using a chalcopyrite-containing ore sample from the same mine. These enrichment cultures were further used as inoculum for bioleaching experiments in percolation columns for simulating heap bioleaching. Addition of 100 mM NaCl to the bioleaching medium was assessed to improve the dissolution rate of chalcopyrite. For comparison, bioleaching in stirred tank reactors with a defined microbial consortium was carried out as well. While just maximal 32% copper could be extracted in the flask bioleaching experiments, 73% and 76% of copper recovery was recorded after 30 and 10 days bioleaching in columns and bioreactors, respectively. Based on the results, both, the application of moderately thermophilic acidophilic bacteria in stirred tank bioreactors, and natural enrichment cultures of mesoacidophiles, with addition of 100 mM NaCl in column percolators with agglomerated ore allowed for a robust chalcopyrite dissolution and copper recovery from Sarcheshmeh copper ore via bioleaching.

Pimavanserin for psychosis in Parkinson's disease dementia: Subgroup analysis of the HARMONY Trial.

INTRODUCTION: Pimavanserin is FDA-approved to treat Parkinson's disease (PD) psychosis. We analyzed the effect of pimavanserin on psychosis in the PD dementia (PDD) subgroup from the phase 3 HARMONY trial. METHODS: This subgroup analysis included PDD patients enrolled in an international, multicenter, randomized discontinuation study of pimavanserin for dementia-related psychosis. PDD patients with moderate-to-severe psychosis, age 50-90 years, received pimavanserin 34 mg/day for 12 weeks (open-label period). Those with a sustained psychosis response to pimavanserin at weeks 8 and 12 were randomized during the double-blind period to continue pimavanserin or receive placebo. Primary efficacy endpoint was time to psychosis relapse as measured by the SAPS-H + D and CGI-I. Safety was assessed, as were effects on motor symptoms and cognitive abilities using the ESRS-A and MMSE. RESULTS: 392 patients were enrolled in HARMONY (mean age: 72.6 years; 38.8 % female): 59 had PDD; 49/59 remained on pimavanserin during the open-label period (safety analysis set), and 36/49 were randomized to pimavanserin (n = 16) or placebo (n = 20) in the double-blind phase (intent-to-treat analysis set). Risk of psychosis relapse was lower with pimavanserin 34 mg compared with placebo in the double-blind phase (HR = 0.052; 95 % CI 0.016-0.166; 1-sided nominal p < 0.001). During the open-label period, 46.9 % experienced a treatment-emergent adverse event; event incidence was similar across arms in the double-blind period. Pimavanserin did not adversely affect motor or cognitive function in either treatment phase. CONCLUSIONS: Pimavanserin significantly reduced risk of psychosis relapse in patients with PDD, was well tolerated, and did not worsen motor or cognitive function.

ENHANCE: Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin for Schizophrenia in Patients With an Inadequate Response to Antipsychotic Treatment.

Inadequate response to antipsychotic treatment is common in patients with schizophrenia. This study evaluated pimavanserin, a 5-HT 2A receptor inverse agonist/antagonist, as adjunctive treatment in patients with inadequate response. This was a 6-week, randomized, double-blind, placebo-controlled, study conducted in North America and Europe. Adult outpatients with schizophrenia and inadequate response to current antipsychotic were enrolled. Inclusion criteria included Positive and Negative Syndrome Scale (PANSS) total score ≥65 and ≤110 and retrospective antipsychotic treatment stability of 8 weeks. Pimavanserin 20 mg/day or placebo added to ongoing antipsychotic was tested in a flexible-dose paradigm with dose adjustments allowed during the first 3 weeks. The primary efficacy endpoint, PANSS total score change from baseline to week 6, was not met, although improvement was greater with pimavanserin than placebo (LS mean difference: -2.1, [95% CI: -4.5, 0.4]; P = .094). As a hierarchical testing procedure was used, additional efficacy analyses were exploratory. Clear separation from placebo was observed with pimavanserin at week 6 for the PANSS Negative Symptoms subscale (LS mean difference: -0.7, [95% CI: -1.5, 0.0]) and Marder Negative Symptom Factor score (-0.9, [-1.7, -0.1]). Analysis of European sites (81.5% of patients) revealed a difference for pimavanserin versus placebo on PANSS total score (LS mean difference: -3.1, [95% CI: -5.8, -0.4]) and Clinical Global Impressions-Severity score (-0.2, [-0.4, -0.0]). Treatment-emergent adverse events occurred in 39.9% with pimavanserin and 36.4% with placebo. Although statistical significance for the primary endpoint was not met, a trend toward improvement in negative symptoms was observed with pimavanserin, warranting further study.