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Parkinson's Disease (PD) is a prevalent and escalating neurodegenerative disorder with significant societal implications. Despite being considered a proteinopathy, in which the aggregation of α-synuclein is the main pathological change, the intricacies of PD initiation remain elusive. Recent evidence suggests a potential link between gut microbiota and PD initiation, emphasizing the need to explore the effects of microbiota-derived molecules on neuronal cells. In this study, we exposed dopaminergic-differentiated SH-SY5Y cells to microbial molecules such as lipopolysaccharide (LPS), rhamnolipid, curli CsgA and phenol soluble modulin α-1 (PSMα1). We assessed cellular viability, cytotoxicity, growth curves and α-synuclein levels by performing MTS, LDH, real-time impedance readings, qRT-PCR and Western Blot assays respectively. Statistical analysis revealed that rhamnolipid exhibited concentration-dependent effects, reducing viability and inducing cytotoxicity at higher concentrations, increasing α-synuclein mRNA and protein levels with negative effects on cell morphology and adhesion. Furthermore, LPS exposure also increased α-synuclein levels. Curli CsgA and PSMα-1 showed minimal or no changes. Our findings suggest that microbiota-derived molecules, particularly rhamnolipid and LPS, impact dopaminergic neurons by increasing α-synuclein levels. This study highlights the potential involvement of gut microbiota in initiating the upregulation of α-synuclein that may further initiate PD, indicating the complex interplay between microbiota and neuronal cells., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Well integrity is currently defined through the concept of well barriers, in which one or more barriers are used to prevent unwanted fluid flow. Many papers have highlighted that the casing-cement interfacial bonding is critical for well integrity, but many discrepancies between laboratory experiments and field data have been noticed. The use of finite element analysis is now established as an alternative to complex in situ tests, but these simulations are sensitive to the input parameters, which results in many discrepancies across published works. Currently, the cohesive zone material (CZM) method is considered to offer good results if the correct parameters are selected or experimentally determined. The novelty of this paper lies in the development of a better workflow that enables the simulation of three processes that are acting on the laboratory-scale casing-cement system: temperature changes, debonding, and post-debonding behavior. The aim of this paper is to fully understand the debonding process within laboratory-scale samples, and thus to eventually enable upscaling in the near future. The paper presents a new workflow generated using FEM that allows us to determine the contact stresses at the casing-cement interface during temperature changes at the moment of debonding and post-debonding. The results presented within this paper show that temperature samples tested according to the push-down setup will provide similar interfacial bonding shear strength values; however, post-debonding, there is a remaining frictional force slightly higher than that of the room-temperature samples. In this case, the results are within a 5% error of the average field data, which is slightly higher than in our previous experiments, where only room temperature data were considered. A major outcome of our paper is the demonstration of the existence of friction forces after debonding, which are a result of radial stresses induced during the debonding process.

Although they are considered rare disorders, muscular dystrophies have a strong impact on people's health. Increased disease severity with age, frequently accompanied by the loss of ability to walk in some people, and the lack of treatment, have directed the researchers towards the development of more effective therapeutic strategies aimed to improve the quality of life and life expectancy, slow down the progression, and delay the onset or convert a severe phenotype into a milder one. Improved understanding of the complex pathology of these diseases together with the tremendous advances in molecular biology technologies has led to personalized therapeutic procedures. Different approaches that are currently under extensive investigation require more efficient, sensitive, and less invasive methods. Due to its remarkable analytical sensitivity, droplet digital PCR has become a promising tool for accurate measurement of biomarkers that monitor disease progression and quantification of various therapeutic efficiency and can be considered a tool for non-invasive prenatal diagnosis and newborn screening. Here, we summarize the recent applications of droplet digital PCR in muscular dystrophy research and discuss the factors that should be considered to get the best performance with this technology.