Selective 5HT3 antagonists and sensory processing: A systematic review

Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson’s disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications

Block length-dependent protein fouling on Poly(2-oxazoline)-based polymersomes: influence on macrophage association and circulation behavior

Polymersomes are vesicular structures self-assembled from amphiphilic block copolymers and are considered an alternative to liposomes for applications in drug delivery, immunotherapy, biosensing, and as nanoreactors and artificial organelles. However, the limited availability of systematic stability, protein fouling (protein corona formation), and blood circulation studies hampers their clinical translation. Poly(2-oxazoline)s (POx) are valuable antifouling hydrophilic polymers that can replace the current gold-standard, poly(ethylene glycol) (PEG), yet investigations of POx functionality on nanoparticles are relatively sparse. Herein, a systematic study is reported of the structural, dynamic and antifouling properties of polymersomes made of poly(2-methyl-2-oxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) (PMOXA-b-PDMS-b-PMOXA). The study relates in vitro antifouling performance of the polymersomes to atomistic molecular dynamics simulations of polymersome membrane hydration behavior. These observations support the experimentally demonstrated benefit of maximizing the length of PMOXA (degree of polymerization (DP) > 6) while keeping PDMS at a minimal length that still provides sufficient membrane stability (DP > 19). In vitro macrophage association and in vivo blood circulation evaluation of polymersomes in zebrafish embryos corroborate these findings. They further suggest that single copolymer presentation on polymersomes is outperformed by blends of varied copolymer lengths. This study helps to rationalize design rules for stable and low-fouling polymersomes for future medical applications

A cross-sectional study of potentially modifiable risk factors for dementia and cognitive function in India: a secondary analysis of 10/66, LASI, and SAGE data

OBJECTIVES: Dementia is rising globally, particularly in low-and-middle-income countries. India has almost four million people living with dementia, set to double by 2050. Targeting nine potentially modifiable risk factors (less education, hearing impairment, depression, physical inactivity, hypertension, obesity, smoking, diabetes, and social isolation) could possibly prevent or delay many dementias. We aimed for the first time to examine risk factors for dementia in India and their link with cognitive status and dementia, to inform prioritisation of public health interventions that could prevent or delay dementia. METHODS: We conducted a cross-sectional analysis using three studies: 10/66 Dementia Study (n= 2,004), Longitudinal Aging Study of India (n= 386), and Study of Global Ageing (n= 2,441). Our exposures were the nine risk factors above. We calculated a cognitive z-score within each study and used dementia diagnosis in 10/66. We adjusted for socioeconomic factors, age, and sex using multivariable linear for cognition and logistic regression for dementia. RESULTS: Less education, hearing impairment, depression, and physical inactivity were associated with lower z-scores and increased odds of dementia. Obesity was associated with higher z-score and lower odds of dementia. Social isolation was associated with lower z-scores and decreased odds of dementia. Results for smoking, diabetes, and hypertension were inconsistent. CONCLUSION: Our risk estimates were larger for less education, hearing impairment and physical inactivity compared to global estimates and should be intervention priorities. This study highlights the need for longitudinal studies to clarify the relationship between these potentially modifiable risk factors and dementia in India. This article is protected by copyright. All rights reserved

Scales for assessing patient satisfaction with mental health care: A systematic review

BACKGROUND: Patient satisfaction with mental health care has become an important construct in research and routine care. Both as a process measure and as an outcome criterion in its own right, it needs to be assessed with appropriate scales. PURPOSE: To provide a review of scales for assessing patient satisfaction in different settings, their characteristics and the content of care that they cover. METHOD: A systematic search of electronic databases was conducted to identify studies that used a scale to assess patient satisfaction with care in mental health services. Peer reviewed articles were screened by two independent reviewers and included when they met predetermined criteria. Data on the characteristics of scales found in at least two studies were extracted and a qualitative analysis was performed to identify the contents of included scales. RESULTS: Twenty-eight scales were identified. They vary substantially in terms of structure, length, focus and quality. The qualitative analyses identified a total of 19 contents of care that were covered in the scales. The most consistent contents across scales were overall satisfaction, followed by relationship with staff and staff skills. DISCUSSION: A wide range of scales have been used to assess patient satisfaction with mental health care in different settings. Whilst some scales have been frequently used, there is no consensus on a gold standard one. The choice of the most appropriate scale depends on the aim of the assessment, the setting, the content that should be covered, and the time available for the assessment

STING agonist delivery by tumour-penetrating PEG-lipid nanodiscs primes robust anticancer immunity

Activation of the innate immune STimulator of INterferon Genes (STING) pathway potentiates antitumour immunity, but systemic delivery of STING agonists to tumours is challenging. We conjugated STING-activating cyclic dinucleotides (CDNs) to PEGylated lipids (CDN-PEG-lipids; PEG, polyethylene glycol) via a cleavable linker and incorporated them into lipid nanodiscs (LNDs), which are discoid nanoparticles formed by self-assembly. Compared to state-of-the-art liposomes, intravenously administered LNDs carrying CDN-PEG-lipid (LND-CDNs) exhibited more efficient penetration of tumours, exposing the majority of tumour cells to STING agonist. A single dose of LND-CDNs induced rejection of established tumours, coincident with immune memory against tumour rechallenge. Although CDNs were not directly tumoricidal, LND-CDN uptake by cancer cells correlated with robust T-cell activation by promoting CDN and tumour antigen co-localization in dendritic cells. LNDs thus appear promising as a vehicle for robust delivery of compounds throughout solid tumours, which can be exploited for enhanced immunotherapy