A Critical Evaluation of Dynamical Systems Models of Bipolar Disorder

Bipolar disorder (BD) is a mood disorder involving recurring (hypo)manic and depressive episodes. The inherently temporal nature of BD has inspired its conceptualization using dynamical systems theory, which is a mathematical framework for understanding systems that evolve over time. In this paper we provide a critical review of dynamical systems models of BD. Owing to heterogeneity of methodologies and experimental designs in computational modeling, we designed a structured approach to guide our review in a fashion that parallels the appraisal of animal models by their Face, Predictive, and Construct Validity. This tool, the Validity Appraisal Guide for Computational Models (VAG-CM) is not an absolute estimate of validity, but rather a guide for more objective appraisal of models in this review. We identified 26 studies published before November 18, 2021 that proposed generative dynamical systems models of time-varying signals in BD. Two raters independently applied the VAG-CM to included studies, obtaining a mean Cohen's kappa of 0.55 (95% CI [0.45, 0.64]) prior to establishing consensus ratings. Consensus VAG-CM ratings revealed three model/study clusters: data-driven models with face validity, theory-driven models with predictive validity, and theory-driven models lacking all forms of validity. We conclude that future models should be developed using a hybrid approach that first operationalizes BD features of interest using empirical data (a data-driven approach), followed by explanations of those features using generative models with components that are homologous to physiological or psychological systems involved in BD (a theory-driven approach).

The Potential Role of Microbial Biostimulants in the Amelioration of Climate Change-Associated Abiotic Stresses on Crops

Crop plants are more often exposed to abiotic stresses in the current age of fast-evolving climate change. This includes exposure to extreme and unpredictable changes in climatic conditions, phytosanitary hazards, and cultivation conditions, which results in drastic losses in worldwide agricultural productions. Plants coexist with microbial symbionts, some of which play key roles in the ecosystem and plant processes. The application of microbial biostimulants, which take advantage of symbiotic relationships, is a long-term strategy for improving plant productivity and performance, even in the face of climate change-associated stresses. Beneficial filamentous fungi, yeasts, and bacteria are examples of microbial biostimulants, which can boost the growth, yield, nutrition and stress tolerance in plants. This paper highlights recent information about the role of microbial biostimulants and their potential application in mitigating the abiotic stresses occurring on crop plants due to climate change. A critical evaluation for their efficient use under diverse climatic conditions is also made. Currently, accessible products generally improve cultural conditions, but their action mechanisms are mostly unknown, and their benefits are frequently inconsistent. Thus, further studies that could lead to the more precisely targeted products are discussed.

Composite Bioinks With Mesoporous Bioactive Glasses—A Critical Evaluation of Results Obtained by In Vitro Experiments

Besides osteoconductivity and a high degradation rate, mesoporous bioactive glasses (MBGs) are specific for their highly ordered channel structure and high specific surface area, making them suitable as drug and/or growth factor delivery systems. On the other hand, the mesoporous channel structure and MBG composition can have an effect on common cell evaluation assays, leading to inconclusive results. This effect is especially important when MBG is mixed in composite bioinks, together with cells. Additionally, the hydrogel component of the ink can influence the degradation of MBG, leading to different ion releases, which can additionally affect the analyses. Hence, our aim here was to show how the MBG structure and composition influence common cell viability and differentiation assays when calcium (Ca)- or magnesium (Mg)-containing glass is part of an alginate-based composite bioink. We suggested pre-labeling of cells with DiI prior to bioprinting and staining with calcein-AM to allow identification of metabolically active cells expressing signals in both green and red channels, allowing the use of fluorescence imaging for cell viability evaluations in the presence of high amounts (7 wt %) of MBGs. The release and uptake of ions during degradation of CaMBG and MgMBG were significantly changed by alginate in the composite bioinks, as confirmed by higher release and uptake from bulk glasses. Additionally, we detected a burst release of Mg2+ from composites only after 24 h of incubation. Furthermore, we demonstrated that released ions and the mesoporous channel structure affect the measurement of lactate dehydrogenase (LDH) and alkaline phosphatase activity (ALP) in bioprinted composite scaffolds. Measured LDH activity was significantly decreased in the presence of CaMBG. On the other hand, the presence of MgMBG induced increased signal measured for the ALP. Taken together, our findings show how composite bioinks containing MBGs can interfere with common analyses, obtaining misleading results.

DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain

While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summary and critical evaluation of two epigenetic mechanisms, DNA methylation and non-coding RNA expression, on transcriptional modulation in nociceptive pathways during the development of tissue injury-associated pain. We assess the pre-clinical data and their translational implication and evaluate the potential of controlling DNA methylation and non-coding RNA expression as novel analgesic approaches and/or biomarkers of persistent pain.