Discharge from secondary care services to primary care for adults with serious mental illness: a scoping review.

BACKGROUND: Effective transitions of patients from Secondary Care Services (SCSs) to primary care are necessary for optimization of resources and care. Factors that enable or restrict smooth transitions of individuals with Serious Mental Illness (SMI) to primary care from SCSs have not been comprehensively synthesized. METHODS: A scoping review was conducted to answer the questions (1) "What are the barriers and facilitators to discharge from SCSs to primary care for adults with SMI?" and (2) "What programs have been developed to support these transitions?". RESULTS: Barriers and facilitators of discharge included patient-, primary care capacity-, and transition Process/Support-related factors. Patient-related barriers and facilitators were most frequently reported. 11 discharge programs were reported across the evidence sources. The most frequently reported program components were the provision of additional mental health supports for the transition and development of care plans with relapse signatures and intervention plans. CONCLUSIONS: Established discharge programs should be comprehensively evaluated to determine their relative benefits. Furthermore, research should be expanded to evaluate barriers and facilitators to discharge and discharge programs in different national contexts and models of care. TRIAL REGISTRATION: The protocol for this scoping review is registered with the Open Science Framework ( https://doi.org/10.17605/OSF.IO/NBTMZ ).

Expression of Histophilus somni IbpA DR2 protective antigen in the diatom Thalassiosira pseudonana.

Increasing demand for the low-cost production of valuable proteins has stimulated development of novel expression systems. Many challenges faced by existing technology may be overcome by using unicellular microalgae as an expression platform due to their ability to be cultivated rapidly, inexpensively, and in large scale. Diatoms are a particularly productive type of unicellular algae showing promise as production organisms. Here, we report the development of an expression system in the diatom Thalassiosira pseudonana by expressing the protective IbpA DR2 antigen from Histophilus somni for the production of a vaccine against bovine respiratory disease. The utilization of diatoms with their typically silicified cell walls permitted development of silicon-responsive transcription elements to induce protein expression. Specifically, we demonstrate that transcription elements from the silicon transporter gene SIT1 are sufficient to drive high levels of IbpA DR2 expression during silicon limitation and growth arrest. These culture conditions eliminate the flux of cellular resources into cell division processes, yet do not limit protein expression. In addition to improving protein expression levels by molecular manipulations, yield was dramatically increased through cultivation enhancement including elevated light and CO2 supplementation. We substantially increased recombinant protein production over starting levels to 1.2% of the total sodium dodecyl sulfate-extractable protein in T. pseudonana, which was sufficient to conduct preliminary immunization trials in mice. Mice exposed to 5 µg of diatom-expressed DR2 in whole or sonicated cells (without protein purification) exhibited a modest immune response without the addition of adjuvant.

Transcript level coordination of carbon pathways during silicon starvation-induced lipid accumulation in the diatom Thalassiosira pseudonana.

Diatoms are one of the most productive and successful photosynthetic taxa on Earth and possess attributes such as rapid growth rates and production of lipids, making them candidate sources of renewable fuels. Despite their significance, few details of the mechanisms used to regulate growth and carbon metabolism are currently known, hindering metabolic engineering approaches to enhance productivity. To characterize the transcript level component of metabolic regulation, genome-wide changes in transcript abundance were documented in the model diatom Thalassiosira pseudonana on a time-course of silicon starvation. Growth, cell cycle progression, chloroplast replication, fatty acid composition, pigmentation, and photosynthetic parameters were characterized alongside lipid accumulation. Extensive coordination of large suites of genes was observed, highlighting the existence of clusters of coregulated genes as a key feature of global gene regulation in T. pseudonana. The identity of key enzymes for carbon metabolic pathway inputs (photosynthesis) and outputs (growth and storage) reveals these clusters are organized to synchronize these processes. Coordinated transcript level responses to silicon starvation are probably driven by signals linked to cell cycle progression and shifts in photophysiology. A mechanistic understanding of how this is accomplished will aid efforts to engineer metabolism for development of algal-derived biofuels.

Characterization of a novel strain of Tribonema minus demonstrating high biomass productivity in outdoor raceway ponds.

Photosynthetic algae represent a large, diverse bioresource potential. Yellow-green algae of the genus Tribonema are candidates for production of biofuels and other bioproducts. We report on a filamentous isolate from an outdoor raceway polyculture growing on municipal reclaimed wastewater which we classified as T. minus. Over one year of cultivation in 3.5 m2 raceway ponds fed by reclaimed municipal wastewater, T. minus cultures were more productive than the native algal polycultures, with annual average productivities of 15.9 ± 0.3 and 13.4 ± 0.4 g/m2/day, respectively. The biochemical composition of T. minus biomass grown outdoors was constant year-round, with 28.3 ± 0.4% carbohydrates, 37.6 ± 0.7% proteins, and 6.1 ± 0.3% fatty acids (measured as methyl esters), with up to 4.0% of the valuable omega-3 eicosapentaenoic acid, on an ash-free dry-weight basis. In summary, T. minus was more productive, easier to harvest and produced higher quality biomass than the native polycultures.

Annotated Genome Sequence of the High-Biomass-Producing Yellow-Green Alga Tribonema minus.

Here, we report the annotated genome sequence for a heterokont alga from the class Xanthophyceae. This high-biomass-producing strain, Tribonema minus UTEX B 3156, was isolated from a wastewater treatment plant in California. It is stable in outdoor raceway ponds and is a promising industrial feedstock for biofuels and bioproducts.

Characterization of a modular, cell-surface protein and identification of a new gene family in the diatom Thalassiosira pseudonana.

We report the characterization of a cell-surface protein isolated from copper-stressed cells of the centric diatom Thalassiosira pseudonana Hasle and Heimdal (CCMP 1335). This protein has an apparent molecular weight of 100kDa and is highly acidic. The 100kDa protein (p100) sequence is comprised almost entirely of a novel domain termed TpRCR for T. pseudonana repetitive cysteine-rich domain, that is repeated 8 times and that contains conserved aromatic, acidic, and potential metal-binding amino acids. The analysis of the T. pseudonana genome suggests that p100 belongs to a large family of modular proteins that consist of a variable number of TpRCR domain repeats. Based on cell surface biotinylation and antibody data, p100 appears to migrate more rapidly with SDS-PAGE when extracted from cells exposed to high levels of copper; however, the discovery of a large family of TpRCR domain-containing proteins leaves open the possibility that the antibody may be cross-reacting with members of this protein family that are responding differently to copper. The response of the gene encoding p100 at the mRNA level during synchronized progression through the normal cell cycle is similar to previously characterized genes in T. pseudonana encoding cell wall proteins called silaffins.

A self-propagating system for Ge incorporation into nanostructured silica.

Technologically-relevant levels of Ge can be incorporated into cell wall silica of the diatom Thalassiosira pseudonana with no aberration in structure at low levels, whereas higher levels alter structure.

Clarification of Photorespiratory Processes and the Role of Malic Enzyme in Diatoms.

Evidence suggests that diatom photorespiratory metabolism is distinct from other photosynthetic eukaryotes in that there may be at least two routes for the metabolism of the photorespiratory metabolite glycolate. One occurs primarily in the mitochondria and is similar to the C2 photorespiratory pathway, and the other processes glycolate through the peroxisomal glyoxylate cycle. Genomic analysis has identified the presence of key genes required for glycolate oxidation, the glyoxylate cycle, and malate metabolism, however, predictions of intracellular localization can be ambiguous and require verification. This knowledge gap leads to uncertainties surrounding how these individual pathways operate, either together or independently, to process photorespiratory intermediates under different environmental conditions. Here, we combine in silico sequence analysis, in vivo protein localization techniques and gene expression patterns to investigate key enzymes potentially involved in photorespiratory metabolism in the model diatom Thalassiosira pseudonana. We demonstrate the peroxisomal localization of isocitrate lyase and the mitochondrial localization of malic enzyme and a glycolate oxidase. Based on these analyses, we propose an updated model for photorespiratory metabolism in T. pseudonana, as well as a mechanism by which C2 photorespiratory metabolism and its associated pathways may operate during silicon starvation and growth arrest.

Applications of Imaging Flow Cytometry for Microalgae.

The ability to image large numbers of cells at high resolution enhances flow cytometric analysis of cells and cell populations. In particular, the ability to image intracellular features adds a unique aspect to analyses, and can enable correlation between molecular phenomena resulting in alterations in cellular phenotype. Unicellular microalgae are amenable to high-throughput analysis to capture the diversity of cell types in natural samples, or diverse cellular responses in clonal populations, especially using imaging cytometry. Using examples from our laboratory, we review applications of imaging cytometry, specifically using an Amnis(®) ImageStream(®)X instrument, to characterize photosynthetic microalgae. Some of these examples highlight advantages of imaging flow cytometry for certain research objectives, but we also include examples that would not necessarily require imaging and could be performed on a conventional cytometer to demonstrate other concepts in cytometric evaluation of microalgae. We demonstrate the value of these approaches for (1) analysis of populations, (2) documentation of cellular features, and (3) analysis of gene expression.

Metabolic and cellular organization in evolutionarily diverse microalgae as related to biofuels production.

Microalgae are among the most diverse organisms on the planet, and as a result of symbioses and evolutionary selection, the configuration of core metabolic networks is highly varied across distinct algal classes. The differences in photosynthesis, carbon fixation and processing, carbon storage, and the compartmentation of cellular and metabolic processes are substantial and likely to transcend into the efficiency of various steps involved in biofuel molecule production. By highlighting these differences, we hope to provide a framework for comparative analyses to determine the efficiency of the different arrangements or processes. This sets the stage for optimization on the based on information derived from evolutionary selection to diverse algal classes and to synthetic systems.

Gene expression induced by copper stress in the diatom Thalassiosira pseudonana.

Utilizing a PCR-based subtractive cDNA approach, we demonstrated that the marine diatom Thalassiosira pseudonana exhibits a rapid response at the gene level to elevated concentrations of copper and that this response attenuates over 24 h of continuous exposure. A total of 16 copper-induced genes were identified, 11 of which were completely novel; however, many of the predicted amino acid sequences had characteristics suggestive of roles in ameliorating copper toxicity. Most of the novel genes were not equivalently induced by H2O2- or Cd-induced stress, indicating specificity in response. Two genes that could be assigned functions based on homology were also induced under conditions of general cellular stress. Half of the identified genes were located within two inverted repeats in the genome, and novel genes in one inverted repeat had mRNA levels induced by approximately 500- to 2,000-fold by exposure to copper for 1 h. Additionally, some of the inverted repeat genes demonstrated a dose-dependent response to Cu, but not Cd, and appear to belong to a multigene family. This multigene family may be the diatom functional homolog of metallothioneins.

The genome of the diatom Thalassiosira pseudonana: ecology, evolution, and metabolism.

Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for approximately 20% of global carbon fixation. We report the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, use of a range of nitrogenous compounds, and a complete urea cycle, all attributes that allow diatoms to prosper in aquatic environments.