Delirium in psychiatric settings: risk factors and assessment tools in patients with psychiatric illness: a scoping review.

BACKGROUND: Delirium is a common disorder affecting patients' psychiatric illness, characterized by a high rate of underdiagnosis, misdiagnosis, and high risks. However, previous studies frequently excluded patients with psychiatric illness, leading to limited knowledge about risk factors and optimal assessment tools for delirium in psychiatric settings. OBJECTIVES: The scoping review was carried out to (1) identify the risk factors associated with delirium in patients with psychiatric illness; (2) synthesize the performance of assessment tools for detecting delirium in patients with psychiatric illness in psychiatric settings. DESIGN: Scoping review. DATA SOURCES: PubMed, Web of Science, and Embase were searched to identify primary studies on delirium in psychiatric settings from inception to Dec 2023 inclusive. Two independent reviewers screened eligible studies against inclusion criteria. A narrative synthesis of the included studies was conducted. RESULTS: A final set of 36 articles meeting the inclusion criteria, two main themes were extracted: risk factors associated with delirium in patients with psychiatric illness and assessment tools for detecting delirium in psychiatric settings. The risk factors associated with delirium primarily included advanced age, physical comorbid, types of psychiatric illness, antipsychotics, anticholinergic drug, Electroconvulsive therapy, and the combination of lithium and Electroconvulsive therapy. Delirium Rating Scale-Revised-98, Memorial Delirium Assessment Scale, and Delirium Diagnostic Tool-Provisional might be valuable for delirium assessment in patients with psychiatric illness in psychiatric settings. CONCLUSIONS: Delirium diagnosis in psychiatric settings is complex due to the overlapping clinical manifestations between psychiatric illness and delirium, as well as their potential co-occurrence. It is imperative to understand the risk factors and assessment methods related to delirium in this population to address diagnostic delays, establish effective prevention and screening strategies. Future research should focus on designing, implementing, and evaluating interventions that target modifiable risk factors, to prevent and manage delirium in patients with psychiatric illness.

Bifidobacterium longum subsp. infantis regulates Th1/Th2 balance through the JAK-STAT pathway in growing mice.

Objectives: Bifidobacterium longum subsp. infantis is a dominant bacterium in infant gut, which plays a critical role in maintaining the health and development of infants. This study investigated the abilities of eight different strains of B. longum subsp. infantis to regulate the T helper (Th)1/Th2 balance. Methods: Eight B. longum subsp. infantis strains, including I2MI (FJSWXI2MIM1), I4MI [FJSWXI4MI (CCFM1270)], I4MNI (FJSWXI4MNIM1), I5TI (FJSWXI5TIM1), I6TI (FJSWXI6TIM1), I8TI [FJSWXI8TI (CCFM1271)], I10TI [FJSWXI10TI (CCFM1272)], and B6MNI [BJSWXB6MNIM1 (CCFM1269)], were gavaged to BALB/C pups in both female (n = 8) and male (n = 8) mice starting from 1 to 3 weeks old (1 × 109 CFU/day/mice). Selected immune cells were assessed by immunofluorescence and flow cytometry. Cytokines and immunoglobulins were determined by ELISA. Bacterial and bifidobacterial communities were determined by 16S rRNA gene sequencing and bifidobacterial groEL sequencing. Results: B. longum subsp. infantis I4MI and I8TI were shown to increase the ration of colonic IgG2a/IgE in male mice (P < 0.05). B6MNI was demonstrated to significantly increase the levels of colonic IFN-γ and IgG2a, as well as the ratio of IgG2a/IgE in female mice (P < 0.05). It was also shown to significantly increase the ratio of colonic IgG2a/IgE (P < 0.05) and reduce the level of colonic IL-4 in male mice (P < 0.05). Furthermore, B6MNI was demonstrated to regulate colonic JAK/STAT pathway in both male and female mice. I4MI, I5TI, and B6MNI were shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in both male and female mice, whereas I8TI was only shown to increase the relative abundance of Bifidobacterium and B. longum subsp. infantis in male mice (P < 0.05). Conclusion: These results indicated supplementation with B. longum subsp. infantis in early infancy may regulate the Th1/Th2 immune balance, which may prevent the development of related diseases.

Biomolecular investigations into BBI reveal an enzymatic mechanism for PUFA isomerisation in bifidobacterium CFA bioconversion strains.

Multiple species of Bifidobacterium exhibit the ability to bioconvert conjugated fatty acids (CFAs), which is considered an important pathway for these strains to promote host health. However, there has been limited progress in understanding the enzymatic mechanism of CFA bioconversion by bifidobacteria, despite the increasing number of studies identifying CFA-producing strains. The protein responsible for polyunsaturated fatty acid (PUFA) isomerization in B. breve CCFM683 has recently been discovered and named BBI, providing a starting point for exploring Bifidobacterium isomerases (BIs). This study presents the sequence classification of membrane-bound isomerases from four common Bifidobacterium species that produce CFA. Heterologous expression, purification, and enzymatic studies of the typical sequences revealed that all possess a single c9, t11 isomer as the product and share common features in terms of enzymatic properties and catalytic kinetics. Using molecular docking and alanine scanning, Lys84, Tyr198, Asn202, and Leu245 located in the binding pocket were identified as critical to the catalytic activity, a finding further confirmed by site-directed mutagenesis-based screening assays. Overall, these findings provide insightful knowledge concerning the molecular mechanisms of BIs. This will open up additional opportunities for the use of bifidobacteria and CFAs in probiotic foods and precision nutrition.

Isolation and Characterisation of Streptococcus spp. with Human Milk Oligosaccharides Utilization Capacity from Human Milk.

Human milk oligosaccharides (HMO) that promote the growth of beneficial gut microbes in infants are abundant in human milk. Streptococcus, one of the dominant genera in human milk microbiota, is also highly prevalent in the infant gut microbiota, possibly due to its adeptness at utilizing HMOs. While previous studies have mainly focused on HMO interactions with gut bacteria like Bifidobacterium and Bacteroides spp., the interaction with Streptococcus spp. has not been fully explored. In this study, Streptococcus spp. was isolated from human milk and identified to exhibit extensive capabilities in utilizing HMOs. Their consumption rates of 2'-fucosyllactose (2'-FL), 6'-sialyllactose (6'-SL), and lacto-N-tetraose (LNT) closely matched those of Bifidobacterium longum subsp. infantis ATCC 15697. Furthermore, we assessed the safety-related genes in the genomes of the Streptococcus species capable of utilizing HMOs, revealing potential virulence and resistance genes. In addition, no haemolytic activity was observed. These findings expand the knowledge of metabolic interactions and networks within the microbiota of human milk and the early life human gut.

Bifidobacterium longum Subsp. infantis Promotes IgA Level of Growing Mice in a Strain-Specific and Intestinal Niche-Dependent Manner.

Throughout infancy, IgA is crucial for maintaining gut mucosal immunity. This study aims to determine whether supplementing newborn mice with eight different strains of Bifidobacterium longum subsp. infantis might regulate their IgA levels. The strains were gavaged to BALB/C female (n = 8) and male (n = 8) dams at 1-3 weeks old. Eight strains of B. longum subsp. infantis had strain-specific effects in the regulation of intestinal mucosal barriers. B6MNI, I4MI, and I10TI can increase the colonic IgA level in females and males. I8TI can increase the colonic IgA level in males. B6MNI was also able to significantly increase the colonic sIgA level in females. B6MNI, I4MI, I8TI, and I10TI regulated colonic and Peyer's patch IgA synthesis genes but had no significant effect on IgA synthesis pathway genes in the jejunum and ileum. Moreover, the variety of sIgA-coated bacteria in male mice was changed by I4MI, I5TI, I8TI, and B6MNI. These strains also can decrease the relative abundance of Escherichia coli. These results indicate that B. longum subsp. infantis can promote IgA levels but show strain specificity. Different dietary habits with different strains of Bifidobacterium may have varying effects on IgA levels when supplemented in early infancy.

Structural identification and antioxidant activity of trans-9, trans-11, cis-15-conjugated linolenic acid converted by probiotics.

The study aimed to determine the chemical structures of octadecatrienoic acid isomers produced by probiotics through the bioconversion of α-linolenic acid and to assess their antioxidant capacities. The chemical structures were identified using nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), while the antioxidant capacities were evaluated in vitro and in cellular. The NMR signals obtained allowed for definitive characterization, with the main ion fragments detected being m/z 58.0062, 59.0140, 71.0141, 113.0616, 127.0777, and 181.5833. Compounds at concentrations below 40 µM maintained the antioxidant capacity of HepG2 cells by protecting endogenous antioxidative enzymes and mitochondrial membrane potential. However, doses higher than 40 µM increase oxidative damage and mitochondrial dysfunction. These results confirmed the structure of the probiotic-derived compound as trans9, trans11, cis15-conjugated linolenic acid. Additionally, appropriate doses of CLNA can alleviate oxidative stress induced by AAPH, while high doses aggravate cellular damage. These findings provide foundational information for the further exploration of probiotic-derived edible lipids.

Characterization of Three Types of Elongases from Different Fungi and Site-Directed Mutagenesis.

Fatty acid elongases play crucial roles in synthesizing long-chain polyunsaturated fatty acids. Identifying more efficient elongases is essential for enhancing oleaginous microorganisms to produce high yields of target products. We characterized three elongases that were identified with distinct specificities: McELO from Mucor circinelloides, PrELO from Phytophthora ramorum, and PsELO from Phytophthora sojae. Heterologous expression in Saccharomyces cerevisiae showed that McELO preferentially elongates C16 to C18 fatty acids, PrELO targets Δ6 polyunsaturated fatty acids, and PsELO uses long chain saturated fatty acids as substrates. McELO and PrELO exhibited more homology, potentially enabling fatty acid composition remodeling and enhanced LC-PUFAs production in oleaginous microorganisms. Site-directed mutagenesis of conserved amino acids across elongase types identified residues essential for activity, supported by molecular docking. Alanine substitution of conserved polar residues led to enzyme inactivation, underscoring their importance in the condensation reaction. Our findings offer promising elongase candidates for polyunsaturated fatty acid production, contributing to the bioindustry's sustainable development.

Harnessing the endogenous Type I-C CRISPR-Cas system for genome editing in Bifidobacterium breve.

Bifidobacterium breve, one of the main bifidobacterial species colonizing the human gastrointestinal tract in early life, has received extensive attention for its purported beneficial effects on human health. However, exploration of the mode of action of such beneficial effects exerted by B. breve is cumbersome due to the lack of effective genetic tools, which limits its synthetic biology application. The widespread presence of CRISPR-Cas systems in the B. breve genome makes endogenous CRISPR-based gene editing toolkits a promising tool. This study revealed that Type I-C CRISPR-Cas systems in B. breve can be divided into two groups based on the amino acid sequences encoded by cas gene clusters. Deletion of the gene coding uracil phosphoribosyl-transferase (upp) was achieved in five B. breve strains from both groups using this system. In addition, translational termination of uracil phosphoribosyl-transferase was successfully achieved in B. breve FJSWX38M7 by single-base substitution of the upp gene and insertion of three stop codons. The gene encoding linoleic acid isomerase (bbi) in B. breve, being a characteristic trait, was deleted after plasmid curing, which rendered it unable to convert linoleic acid into conjugated linoleic acid, demonstrating the feasibility of successive editing. This study expands the toolkit for gene manipulation in B. breve and provides a new approach toward functional genome editing and analysis of B. breve strains.IMPORTANCEThe lack of effective genetic tools for Bifidobacterium breve is an obstacle to studying the molecular mechanisms of its health-promoting effects, hindering the development of next-generation probiotics. Here, we introduce a gene editing method based on the endogenous CRISPR-Cas system, which can achieve gene deletion, single-base substitution, gene insertion, and successive gene editing in B. breve. This study will facilitate discovery of functional genes and elucidation of molecular mechanisms of B. breve pertaining to health-associated benefits.

Human breastmilk-derived Bifidobacterium longum subsp. infantis CCFM1269 regulates bone formation by the GH/IGF axis through PI3K/AKT pathway.

Bifidobacterium longum subsp. infantis is a prevalent member of the gut microbiota of breastfed infants. In this study, the effects of human breastmilk-derived B.longum subsp. infantis CCFM1269 on bone formation in developing BALB/c mice were investigated. Newborn female and male mice were assigned to control group (administered saline), CCFM11269 group (administered B. longum subsp. infantis CCFM1269, 1 × 109 CFU/mouse/day) and I5TI group (administered B. longum subsp. infantis I5TI, 1 × 109 CFU/mouse/day) from 1-week-old to 3-, 4- and 5-week old. B. longum subsp. infantis I5TI served as a negative control in this study. The results demonstrated that B. longum subsp. infantis CCFM1269 promoted bone formation in growing mice by modulating the composition of the gut microbiota and metabolites. The expression of genes and proteins in the PI3K/AKT pathway was stimulated by B. longum subsp. infantis CCFM1269 through the GH/IGF-1 axis in growing mice. This finding suggests B. longum subsp. infantis CCFM1269 may be useful for modulating bone metabolism during growth.