Exposure to psychotropic medications and mortality in schizophrenia: a 5-year national cohort study.

BACKGROUND: Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia. METHODS: We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted. RESULTS: A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07-1.27; HR in moderate dose: 1.32, 95% CI 1.21-1.44; HR in high dose: 1.83, 95% CI 1.67-2.01)]. CONCLUSIONS: The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study.

Overexpressing Ferredoxins in Chlamydomonas reinhardtii Increase Starch and Oil Yields and Enhance Electric Power Production in a Photo Microbial Fuel Cell.

Ferredoxins (FDX) are final electron carrier proteins in the plant photosynthetic pathway, and function as major electron donors in diverse redox-driven metabolic pathways. We previously showed that overexpression of a major constitutively expressed ferredoxin gene PETF in Chlamydomonas decreased the reactive oxygen species (ROS) level and enhanced tolerance to heat stress. In addition to PETF, an endogenous anaerobic induced FDX5 was overexpressed in transgenic Chlamydomonas lines here to address the possible functions of FDX5. All the independent FDX transgenic lines showed decreased cellular ROS levels and enhanced tolerance to heat and salt stresses. The transgenic Chlamydomonas lines accumulated more starch than the wild-type line and this effect increased almost three-fold in conditions of nitrogen depletion. Furthermore, the lipid content was higher in the transgenic lines than in the wild-type line, both with and without nitrogen depletion. Two FDX-overexpressing Chlamydomonas lines were assessed in a photo microbial fuel cell (PMFC); power density production by the transgenic lines was higher than that of the wild-type cells. These findings suggest that overexpression of either PETF or FDX5 can confer tolerance against heat and salt stresses, increase starch and oil production, and raise electric power density in a PMFC.

Medication Dosage Impact on Mortality in Old-Age Individuals with Schizophrenia: A National Cohort Study.

As the prevalence of old-age individuals with schizophrenia (OAS) increases in a society undergoing demographic aging, the exploration of medication choices becomes increasingly crucial. Due to the current scarcity of literature on OAS, this study seeks to examine how the utilization and cumulative dosages of psychotropic medications influence both overall and cause-specific mortality risks within this population. A national cohort of 6433 individuals diagnosed with OAS was followed up for 5 years. This study involved comparing the mortality rates associated with low, moderate, and high dosages of antipsychotics, antidepressants, mood stabilizers, and sedative/hypnotic drugs against the 'no exposure' category, based on individual dosages. Cox regression was employed for survival analyses to compare overall mortality and specific-cause mortality across various dosage groups. The exposure variable examined was the dosage of a specific psychotropic medication. Covariates were adjusted accordingly. The analysis revealed that patients on low/moderate antipsychotic doses had improved survival compared to non-exposed individuals. Moderate antipsychotic use corresponded to reduced cardiovascular disease mortality risk. Similarly, those exposed to antidepressants had enhanced survival in low and moderate doses. Sedative-hypnotic exposure was linked to decreased mortality risk in low doses. This study observed that low/moderate antipsychotic doses in older adults with schizophrenia were associated with decreased all-cause mortality, emphasizing the significance of precise medication selection and dosing. It underscores the need for vigilant polypharmacy management and tailored medication strategies in addressing the complexities of treating OAS.

Promoting chondrocyte cell clustering through tuning of a poly(ethylene glycol)-poly(peptide) thermosensitive hydrogel with distinctive microarchitecture.

Hydrogels are considered to be attractive cell-matrix for chondrocytes due to their similarity in properties to the natural cartilage. However, the formation of chondrocyte cell clusters in hydrogels has been mostly limited to naturally-derived or relatively fast degrading materials. In this study, a series of diblock copolymer poly(ethylene glycol)-poly(alanine) (mPEG-PA) was synthesized and investigated as injectable biomimic hydrogels for the culturing of chondrocytes. Depending on the poly(alanine) chain length, afforded hydrogels exhibited variable mechanical property and microarchitecture due to difference in secondary structure arrangement. After 21days of culture, cell clusters were observed in all hydrogels with longer PA chains and these hydrogels supported more homogenous and established clustering as well as significantly higher glycosaminoglycan and collagen deposition. Interestingly, scanning electron microscopy revealed a distinct micron range fibrillar-like microarchitecture that may be responsible for maintaining chondrocyte phenotype and matrix production. In addition, micrographs revealed the presence of collagen fibrils and an extensive extracellular matrix network. Therefore, it is reasonable to conclude that mPEG-PA hydrogels possess the desirable properties for chondrocyte cluster formation and serve as potential candidate in cartilage tissue engineering.

A cell-compatible PEO-PPO-PEO (Pluronic®)-based hydrogel stabilized through secondary structures.

Pluronic F-127 (PF127) is a thermosensitive polymer that has been widely recognized as a potential candidate for various bio-applications. However, in hydrogel form, its rapid disintegration and inhospitality toward cells have significantly limited its usage. As a means to increase the integrity and cell compatibility of a PF127 hydrogel, we propose the introduction of stabilizing secondary structures to the gel network by the addition of secondary structure-forming oligo-alanine and oligo-phenylalanine. Results indicate that increasing the oligo(peptides) attached to PF127 led to a significant decrease in the gelation concentration and temperature. A selected oligo(peptide)-modified PF127 was capable of forming a stable hydrogel network at 5% and suffered only 20% weight loss after 7days of incubation in media. Scanning electron microscopy (SEM) revealed comparably more interconnected morphology in modified hydrogels which may be attributed to the presence of secondary structures, as verified by circular dichroism (CD) and Fourier-transformed infrared (FT-IR) spectroscopy. Nuclear magnetic resonance (NMR) provided insights into the extensive interactions at the micelle core, which is the key to altered gelation behavior. Furthermore, modified hydrogels maintained structural integrity within culturing media and supported the proliferation of encapsulated chondrocytes. In addition, in vivo residence time was extended to well beyond 2weeks after oligo(peptide) modification, thereby broadening the application scope of the PF127 hydrogel to encompass long-term drug delivery and cell culturing.