• Yildiz Han posted an update a month ago

    Age of first use of cannabis influenced trajectories of young cannabis users with later onset leading to higher increase, whereas the frequency of psychotic-like experiences was not associated with a change in cannabis use. The observed association between perceived stress and psychotic-like experiences at age 22 emphasizes the importance of stress experiences in developing psychosis independent of cannabis use.

    Age of first use of cannabis influenced trajectories of young cannabis users with later onset leading to higher increase, whereas the frequency of psychotic-like experiences was not associated with a change in cannabis use. The observed association between perceived stress and psychotic-like experiences at age 22 emphasizes the importance of stress experiences in developing psychosis independent of cannabis use.Auditory hallucinations are a debilitating symptom of schizophrenia. Effective treatment is limited because the underlying neural mechanisms remain unknown. Our study investigates how local and long-range functional connectivity is associated with auditory perceptual disturbances (APD) in schizophrenia. APD was assessed using the Auditory Perceptual Trait and State Scale. Resting state fMRI data were collected for N=99 patients with schizophrenia. Local functional connectivity was estimated using regional homogeneity (ReHo) analysis; long-range connectivity was estimated using resting state functional connectivity (rsFC) analysis. Mediation analyses tested whether local (ReHo) connectivity significantly mediated associations between long-distance rsFC and APD. Severity of APD was significantly associated with reduced ReHo in left and right putamen, left temporoparietal junction (TPJ), and right hippocampus-pallidum. Higher APD was also associated with reduced rsFC between the right putamen and the contralateral putamen and auditory cortex. Local and long-distance connectivity measures together explained 40.3% of variance in APD (P less then 0.001), with the strongest predictor being the left TPJ ReHo (P less then 0.001). Additionally, TPJ ReHo significantly mediated the relationship between right putamen – left putamen rsFC and APD (Sobel test, P = 0.001). Our findings suggest that both local and long-range functional connectivity deficits contribute to APD, emphasizing the role of striatum and auditory cortex. Considering the translational impact of these circuit-based findings within the context of prior clinical trials to treat auditory hallucinations, we propose a model in which correction of both local and long-distance functional connectivity deficits may be necessary to treat auditory hallucinations.Dimensionally stable vertical bone regeneration outside of the existing bony envelope is a major challenge in the field of orofacial surgery. In this study, we demonstrate that a highly porous, resorbable scaffold fabricated using additive manufacturing techniques enables reproducible extra-skeletal bone formation and prevents bone resorption. An additively manufactured medical grade polycaprolactone (mPCL) biphasic scaffold mimicking the architecture of the jaw bone, consisting of a 3D-printed outer shell overlying an inner highly porous melt electrowritten scaffold, was assessed for its ability to support dimensionally stable bone regeneration in an extraskeletal ovine calvarial model. To investigate bone formation capacity (stage 1), 7 different constructs placed under a protective dome were assessed 8 weeks post-implantation Empty control, Biphasic scaffold with hydrogel (PCL-Gel), PCL-Gel with 75 or 150 μg of BMP-2 (PCL-BMP-75 and PCL-BMP-150), hydrogel only (Gel), Gel containing 75 or 150 μg of BMP-2 (Ghe space maintenance properties and dimensional stability of the biphasic scaffold. Titanium implants osseointegrated into the newly formed bone within the biphasic scaffolds. In conclusion, additively manufactured biphasic scaffolds functionalized with BMP-2 facilitated dimensionally stable bone regeneration that supported dental implant osseointegration.Space experimentation of cardiomyocyte differentiation from human induced pluripotent stem cells offers an exciting opportunity to explore the potential of these cells for disease modeling, drug discovery and regenerative medicine. Previous studies on the International Space Station were done with 2D non-cryopreserved cultures of cardiomyocytes being loaded and cultivated in spaceflight culture modules with CO2. Here we report the development of methods of cryopreservation and CO2-independent culture of 3D cardiac progenitors. The cryopreservation allows preparation and pretesting of the cells before spaceflight, makes it easier to transport the cell culture, reduces the impact of strong gravitational force exerted on the cells during the launch of spaceflight, and accommodates a more flexible working schedule for the astronauts. The use of CO2-independent medium with supplements supports cell growth and differentiation without a CO2 incubator. With these methods, we conducted a spaceflight experiment through the SpaceX-20 mission to evaluate the effect of microgravity on the survival and differentiation of 3D cardiac progenitors. Our cryopreserved cardiac progenitor spheres were successfully cultivated in a spaceflight culture module without CO2 for 3 weeks aboard the International Space Station. Beating cardiomyocytes were generated and returned to the earth for further study.Historically, the field of regenerative medicine has aimed to heal damaged tissue through the use of biomaterials scaffolds or delivery of foreign progenitor cells. Despite 30 years of research, however, translation and commercialization of these techniques has been limited. Proteases inhibitor To enable mammalian regeneration, a more practical approach may instead be to develop therapies that evoke endogenous processes reminiscent of those seen in innate regenerators. Recently, investigations into tadpole tail regrowth, zebrafish limb restoration, and the super-healing Murphy Roths Large (MRL) mouse strain, have identified ancient oxygen-sensing pathways as a possible target to achieve this goal. Specifically, upregulation of the transcription factor, hypoxia-inducible factor one alpha (HIF-1α) has been shown to modulate cell metabolism and plasticity, as well as inflammation and tissue remodeling, possibly priming injuries for regeneration. Since HIF-1α signaling is conserved across species, environmental or pharmacological manipulation of oxygen-dependent pathways may elicit a regenerative response in non-healing mammals.

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