Three-dimensional (3D) and four-dimensional (4D) printing have emerged as the next-generation fabrication technologies, covering a broad spectrum of areas, including construction, medicine, transportation, and textiles. 3D printing, also known as additive manufacturing (AM), allows the fabrication of complex structures with high precision via a layer-by-layer addition of various materials. On the other hand, 4D printing technology enables printing smart materials that can alter their shape, properties, and functions upon a stimulus, such as solvent, radiation, heat, pH, magnetism, current, pressure, and relative humidity (RH). Myriad of biomedical materials (BMMs) currently serve in many biomedical engineering fields aiding patients’ needs and expanding their life-span. 3D printing of BMMs provides geometries that are impossible via conventional processing techniques, while 4D printing yields dynamic BMMs, which are intended to be in long-term contact with biological systems owing to their time-dependent stimuli responsiveness. This review comprehensively covers the most recent technological advances in 3D and 4D printing towards fabricating BMMs for tissue engineering, drug delivery, surgical and diagnostic tools, and implants and prosthetics. In addition, the challenges and gaps of 3D and 4D printed BMMs, along with their future outlook, are also extensively discussed. The current review also addresses the scarcity in the literature on the composition, properties, and performances of 3D and 4D printed BMMs in medical applications and their pros and cons. Moreover, the content presented would be immensely beneficial for material scientists, chemists, and engineers engaged in AM manufacturing and clinicians in the biomedical field.

Aim: Cannabis use for sleep-related problems is on the rise; however, little is known about the cannabis products people are using for sleep or the perceived effects of cannabis in comparison to more conventional sleep aids. Therefore, the aim of this study was to examine the products cannabis users prefer to use for sleep as well as their experiences with cannabis relative to more conventional sleep aids. Methods: De-identified archival data from a Strainprint® survey of 1,216 individuals who use cannabis for sleep were analyzed. Results: Participants predominantly reported smoking joints or vaping flower as their methods of administration, and seeking tetrahydrocannabinol (THC), cannabidiol (CBD), and the terpene myrcene in the cannabis they use for sleep. Only a small minority reported using cannabis in conjunction with conventional sleep aids. Comparisons of the self-reported effects of cannabis to conventional sleep aids revealed that participants reported feeling more refreshed, focused, better able to function, fewer headaches, and less nausea the morning after using cannabis for sleep than after using more conventional sleep aids or no sleep aids. However, they indicated they were more sleepy, anxious, and irritable in the mornings following the use of cannabis relative to other sleep aids. Participants were more likely to report red eyes and thirst and less likely to report nausea, anxiety, paranoia, and racing heart as side effects of cannabis relative to other sleep aids. Conclusions: Knowledge gained from this survey will provide health professionals with a better understanding of why people are using cannabis for sleep and may help guide future more controlled research.

The pathophysiological mechanisms underlying the close relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are multiple, complex and only partially known. The purpose of this paper was to review the current knowledge of these mechanisms in a unified manner. Subjects with NAFLD and T2DM have established insulin resistance (IR), which exacerbates the two comorbidities. IR worsens NAFLD by increasing the accumulation of free fatty acids (FFAs) in the liver. This occurs due to an increase in the influx of FFAs from peripheral adipose tissue by the activation of hormone-sensitive lipase. In addition, there is de novo increased lipogenesis, a transcription factor, the sterols regulatory element-binding transcription factor 1c (SREBP-1c), which activates the expression of several genes strongly promotes lipogenesis by the liver and facilitate storage of triglycerides. Lipids accumulation in the liver induces a chronic stress in the endoplasmic reticulum of the hepatocytes. Genome-wide association studies have identified genetic variants associated with NAFLD severity, but unrelated to IR. In particular, the alteration of patatin-like phospholipase domain-containing protein 3 contributes to the susceptibility to NAFLD. Furthermore, the lipotoxicity of ceramides and diacylglycerol, well known in T2DM, triggers a chronic inflammatory process favoring the progression from hepatic steatosis to steatohepatitis. Reactive oxygen species produced by mitochondrial dysfunction trigger both liver inflammation and beta-cells damage, promoting the progression of both NAFLD and T2DM. The close association between NAFLD and T2DM is bidirectional, as T2DM may trigger both NAFLD onset and its progression, but NAFLD itself may contribute to the development of IR and T2DM. Future studies on the mechanisms will have to deepen the knowledge of the interaction between the two pathologies and should allow the identification of new therapeutic targets for the treatment of NAFLD, currently substantially absent.