The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets

Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. Albeit the molecular mechanisms responsible for the therapeutic effects of CBD have yet to be fully elucidated, many efforts have been devoted in the last decades to shed light on its complex pharmacological profile. In particular, an ever-increasing number of molecular targets linked to those disorders have been identified for this phytocannabinoid, along with the modulatory effects of CBD on their cascade signaling. In this view, here we will try to provide a comprehensive and up-to-date overview of the molecular basis underlying the therapeutic effects of CBD involved in the treatment of neurological and neuropsychiatric disorders.     

A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C₇₀@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C₇₀@lysozyme are confirmed using UV-visible and 2D ¹H, ¹⁵N NMR spectroscopy. The excellent imaging contrast of C₇₀@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C₇₀@lysozyme and its ability to initiate cell death by means of singlet oxygen (¹O₂) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C₇₀@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.     

Current advances concerning the most cited metal ions doped bioceramics and silicate-based bioactive glasses for bone tissue engineering

Studies related to biomaterials that stimulate the repair of living tissue have increased considerably, improving the quality of many people's lives that require surgery due to traumatic accidents, bone diseases, bone defects, and reconstructions. Among these biomaterials, bioceramics and bioactive glasses (BGs) have proved to be suitable for coating materials, cement, scaffolds, and nanoparticles, once they present good biocompatibility and degradability, able to generate osteoconduction on the surrounding tissue. However, the role of biomaterials in hard tissue engineering is not restricted to a structural replacement or for guiding tissue regeneration. Nowadays, it is expected that biomaterials develop a multifunctional role when implanted, orchestrating the process of tissue regeneration and providing to the body the capacity to heal itself. In this way, the incorporation of specific metal ions in bioceramics and BGs structure, including magnesium, silver, strontium, lithium, copper, iron, zinc, cobalt, and manganese are currently receiving enhanced interest as biomaterials for biomedical applications. When an ion is incorporated into the bioceramic structure, a new category of material is created, which has several unique properties that overcome the disadvantages of primitive material and favors its use in different biomedical applications. The doping can enhance handling properties, angiogenic and osteogenic performance, and antimicrobial activity. Therefore, this review aims to summarize the effect of selected metal ion dopants into bioceramics and silicate-based BGs in bone tissue engineering. Furthermore, new applications for doped bioceramics and BGs are highlighted, including cancer treatment and drug delivery.     

Workers’ rest allowance and smoothing of the workload in assembly lines

Ergonomic aspects have a crucial role in manual assembly systems. They impact on the workers’ health, final product quality and productivity. For these reasons, there is the necessity to integrate them into the assembly line balancing phase as, whereas, only time and cost variables are considered. In this study, human energy expenditures are considered as ergonomic aspects and we integrate them, for the first time, into the assembly line balancing problem type 2 through the rest allowance evaluation. We consider as an objective function the minimization of the smoothness index. Firstly, a new optimal method based on mixed integer linear programming and a new linearization methodology are proposed. Then, a heuristic approach is introduced. To complete the study, a computational experimentation is presented to validate the mathematical model and to compare the methodologies proposed in terms of computational time, complexity and solution. Additionally, we provide a detailed analysis of the impact that rest allowance evaluation can have on productivity comparing the results obtained, taking into account the rest allowance integration before, during and after the assembly balancing process.     

Ageing workforce management in manufacturing systems: state of the art and future research agenda

The workforce ageing phenomenon is recently affecting most of the Organisation for Economic Co-operation and Development (OECD) member countries, due to a general ageing of their populations and a higher average retirement age of the workforce. In this paper, the topic of ageing workforce management is addressed from a production research standpoint, with the aim of understanding how older workers can be supported and involved in a manufacturing system. First, the current state of the art related to the ageing workforce in production systems is presented. This is structured according to four main topics: (1) analysis and evaluation of ageing workers’ functional capacities, (2) consideration of ageing workers’ capacities in industrial system modelling and management, (3) analysis and exploitation of ageing workers’ expertise, (4) acknowledgement, analysis, design and integration of supporting technologies. Next, the discussion on the impact of the ageing workforce on manufacturing systems’ performances leads to the comparison of some technological advances that are related to the Industry 4.0 paradigms. Finally, a future research agenda on this topic is proposed, based on the same topics classification proposed for the literature analysis. Five different research areas are derived, suggesting future directions for appropriate research concerning the employ of older workers in production environments.     

Biodegradation of poly(lactic acid)—cassava bagasse composites produced by injection molding

Neat poly (lactic acid) (PLA) and PLA/cassava bagasse (CB) composites were used to produce seedling tubes by extrusion and injection molding. The tubes were buried in simulated soil, and their biodegradation was investigated by weight loss, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). After 180 days, the composites' biodegradation was higher than neat PLA material, and the higher the CB content, the higher the biodegradation, which caused fissures and voids in the material. The biodegradation of PLA/CB composites increased the phosphorus content in the soil after 180 days. Composites of PLA with CB, an abundant agro-industrial residue in Brazil, are promising because they can reduce the environmental impact due to CB's proper destination, and the composites' costs and biodegradation are faster than pure PLA material. Both the faster biodegradation of the tube and the higher P content are advantageous for seedling tubes.     

Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.