Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue.

Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key inflammatory pathways, mitigate the pathological effects of inflammation, and offer new avenues for therapeutic interventions in IBD. This study investigates the anti-inflammatory effects of 5-HT2A ligands, including psilocybin, 4-AcO-DMT, and ketanserin, in combination with TRP channel ligands, including capsaicin, curcumin, and eugenol, on the inflammatory response induced by tumor necrosis factor (TNF)-α and interferon (IFN)-γ in human 3D EpiIntestinal tissue. Enzyme-linked immunosorbent assay was used to assess the expression of pro-inflammatory markers TNF-α, IFN-γ, IL-6, IL-8, MCP-1, and GM-CSF. Our results show that psilocybin, 4-AcO-DMT, and eugenol significantly reduce TNF-α and IFN-γ levels, while capsaicin and curcumin decrease these markers to a lesser extent. Psilocybin effectively lowers IL-6 and IL-8 levels, but curcumin, capsaicin, and 4-AcO-DMT have limited effects on these markers. In addition, psilocybin can significantly decrease MCP-1 and GM-CSF levels. While ketanserin lowers IL-6 and GM-CSF levels, there are no effects seen on TNF-α, IFN-γ, IL-8, or MCP-1. Although synergistic effects between 5-HT2A and TRP channel ligands are minimal in this study, the results provide further evidence of the anti-inflammatory effects of psilocybin and eugenol. Further research is needed to understand the mechanisms of action and the feasibility of using these compounds as anti-inflammatory therapies for conditions like IBD.

Anti-Inflammatory Effects of Serotonin Receptor and Transient Receptor Potential Channel Ligands in Human Small Intestinal Epithelial Cells.

Intestinal inflammation and dysbiosis can lead to inflammatory bowel diseases (IBD) and systemic inflammation, affecting multiple organs. Developing novel anti-inflammatory therapeutics is crucial for preventing IBD progression. Serotonin receptor type 2A (5-HT2A) ligands, including psilocybin (Psi), 4-Acetoxy-N,N-dimethyltryptamine (4-AcO-DMT), and ketanserin (Ket), along with transient receptor potential (TRP) channel ligands like capsaicin (Cap), curcumin (Cur), and eugenol (Eug), show promise as anti-inflammatory agents. In this study, we investigated the cytotoxic and anti-inflammatory effects of Psi, 4-AcO-DMT, Ket, Cap, Cur, and Eug on human small intestinal epithelial cells (HSEIC). HSEIC were exposed to tumor necrosis factor (TNF)-α and interferon (IFN)-γ for 24 h to induce an inflammatory response, followed by treatment with each compound at varying doses (0-800 µM) for 24 to 96 h. The cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and protein expression by Western blot (WB) analysis. As single treatments, Psi (40 µM), Cur (0.5 µM), and Eug (50 µM) significantly reduced COX-2 levels without cytotoxic effects. When combined, Psi (40 µM) and Cur (0.5 µM) exhibited synergy, resulting in a substantial decrease in COX-2 protein levels (-28× fold change), although the reduction in IL-6 was less pronounced (-1.6× fold change). Psi (20 µM) and Eug (25 µM) demonstrated the most favorable outcomes, with significant decreases in COX-2 (-19× fold change) and IL-6 (-10× fold change) protein levels. Moreover, the combination of Psi and Eug did not induce cytotoxic effects in vitro at any tested doses. This study is the first to explore the anti-inflammatory potential of psilocybin and 4-AcO-DMT in the intestines while highlighting the potential for synergy between the 5-HT2A and TRP channel ligands, specifically Psi and Eug, in alleviating the TNF-α/IFN-γ-induced inflammatory response in HSEIC. Further investigations should evaluate if the Psi and Eug combination has the therapeutic potential to treat IBD in vivo.

Interdisciplinary consensus statements on imaging of DRUJ instability and TFCC injuries.

OBJECTIVES: The purpose of this agreement was to establish evidence-based consensus statements on imaging of distal radioulnar joint (DRUJ) instability and triangular fibrocartilage complex (TFCC) injuries by an expert group using the Delphi technique. METHODS: Nineteen hand surgeons developed a preliminary list of questions on DRUJ instability and TFCC injuries. Radiologists created statements based on the literature and the authors' clinical experience. Questions and statements were revised during three iterative Delphi rounds. Delphi panelists consisted of twenty-seven musculoskeletal radiologists. The panelists scored their degree of agreement to each statement on an 11-item numeric scale. Scores of "0," "5," and "10" reflected complete disagreement, indeterminate agreement, and complete agreement, respectively. Group consensus was defined as a score of "8" or higher for 80% or more of the panelists. RESULTS: Three of fourteen statements achieved group consensus in the first Delphi round and ten statements achieved group consensus in the second Delphi round. The third and final Delphi round was limited to the one question that did not achieve group consensus in the previous rounds. CONCLUSIONS: Delphi-based agreements suggest that CT with static axial slices in neutral rotation, pronation, and supination is the most useful and accurate imaging technique for the work-up of DRUJ instability. MRI is the most valuable technique in the diagnosis of TFCC lesions. The main indication for MR arthrography and CT arthrography are Palmer 1B foveal lesions of the TFCC. CLINICAL RELEVANCE STATEMENT: MRI is the method of choice for assessing TFCC lesions, with higher accuracy for central than peripheral abnormalities. The main indication for MR arthrography is the evaluation of TFCC foveal insertion lesions and peripheral non-Palmer injuries. KEY POINTS: • Conventional radiography should be the initial imaging technique in the assessment of DRUJ instability. CT with static axial slices in neutral rotation, pronation, and supination is the most accurate method for evaluating DRUJ instability. • MRI is the most useful technique in diagnosing soft-tissue injuries causing DRUJ instability, especially TFCC lesions. • The main indications for MR arthrography and CT arthrography are foveal lesions of the TFCC.

The Effect of Combined Treatment of Psilocybin and Eugenol on Lipopolysaccharide-Induced Brain Inflammation in Mice.

Inflammation is an organism's biological defense mechanism. Acute and chronic inflammation of the body triggers the production of pro- and anti-inflammatory pathways that can affect the content of cytokines in the brain and thus cause brain inflammation. Disorders such as depression and posttraumatic stress disorder (PTSD) are often associated with elevated inflammation. Recently, positive and promising clinical results of psilocybin for the treatment of depression and PTSD were reported. Thus, we decided to test whether psilocybin alone or in combination with eugenol, an anti-inflammatory and antioxidant agent, would prevent the increase in or decrease the content of cytokines in the brain of C57BL/6J mice injected with lipopolysaccharides (LPS). Two experiments were performed, one with pre-treatment of mice through gavage with psilocybin (0.88 mg/kg), eugenol (17.6 mg/kg), or combinations of psilocybin and eugenol (1:10, 1:20, or 1:50), followed by intraperitoneal injection of LPS, and the second, post-treatment, with initial injection with LPS, followed by treatment with psilocybin, eugenol, or their combination. Brain tissues were collected, and cytokines were analyzed by qRT-PCR, Western blot, and ELISA. Data were analyzed with a one-way ANOVA followed by Tukey's post hoc test or with multiple unpaired t-tests. LPS upregulated mRNA expression of COX-2, TNF-α, IL-1ß, and IL-6. All pre-treatments decreased the expression of COX-2 and TNF-α, with psilocybin alone and in 1:50 combination, with eugenol being the most effective. In the post-treatment, all combinations of psilocybin and eugenol were effective in reducing inflammation, with the 1:50 ratio displaying the most prominent results in reducing the mRNA content of tested cytokines. Western blot analysis confirmed the effect on COX-2 and IL-1ß proteins. Finally, the ELISA showed that post-treatment with psilocybin + eugenol (1:50) demonstrated the best results, decreasing the expression of multiple markers including IL-6 and IL-8. This demonstrates the anti-inflammatory effects of a combination of psilocybin and eugenol in the brain of animals with systemically induced inflammation.

Scaphoid kinematics in scapholunate instability: a dynamic CT study.

OBJECTIVE: The scaphoid is proposed to be driven by the distal carpal row in scapholunate instability (SLI) as it is dissociated from the proximal row. The aim of this study was to describe the 6 degrees of freedom kinematics of the scaphoid using dynamic CT in the normal and SLI wrists. We hypothesised that the SLI scaphoid would demonstrate kinematic evidence conforming to distal row motion. MATERIALS AND METHODS: We studied dynamic CT scans of 17 SLI and 17 normal wrists during ulnar to radial deviation and extension to flexion. The radio-scaphoid angles in three anatomic planes were calculated in the wrist neutral position and during wrist motion. The centroid position was also calculated in the wrist neutral position and during wrist motion. The scapho-capitate motion index (SCI) was calculated as a ratio between the scaphoid and the capitate motion. RESULTS: In the neutral position of the wrist, the SLI scaphoid was flexed, internally rotated, and radially translated compared to the normal scaphoid. During wrist motion, the SLI scaphoid had more 'in-plane' motion and less 'out-of-plane' motion with a higher SCI during wrist neutral to radial deviation and extension to neutral. CONCLUSION: We have described the malalignment of the SLI scaphoid in the neutral position of the wrist and 6 degrees of freedom kinematics during wrist motion of the SLI scaphoid compared to the normal. The SLI scaphoid conformed more to the distal row motion than the normal scaphoid. This information may help define the surgical reconstruction techniques for SLI.

Survival after lipiodol escape at embolization for lung transplant chylothorax.

We present imaging of lipiodil escape after thoracic duct embolization for transplant associated chylothorax leading to transient impairment, then resolution.

Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts.

In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation. Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin fibroblasts, the effects of pCBs on cellular viability, functional activity, metabolic function, and nuclear architecture were tested. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) within the range of 0.5 µM to 2.0 µM increased cell growth in a dose-dependent manner while significantly decreasing senescence as measured by beta-galactosidase activity. Utilizing a scratch assay, both THC and CBD (2.0 µM) significantly improved wound healing in both healthy and SIPS fibroblasts. THC and CBD altered nuclear architecture and mRNA levels of cell cycle regulators and genes involved in ECM production. Subsequently, we found ELN, Cyclin D1, PCNA, and BID protein levels altered by SIPS but ameliorated after pCBs exposure in human dermal fibroblasts. Lastly, we compared the efficacy of THC and CBD with common anti-aging nutrient signaling regulators in replicative senescent adult human dermal fibroblasts, CCD-1135Sk. Both THC and CBD were found to improve wound healing better than metformin, rapamycin, and triacetylresveratrol in replicative senescent CCD-1135Sk fibroblasts. Therefore, pCBs can be a valuable source of biologically active substances used in cosmetics, and more studies using clinical trials should be performed to confirm the efficacy of phytocannabinoids.

Genetic Markers of Atopic Dermatitis Risk for Screening Aviation Applicants.

INTRODUCTION: Atopic dermatitis (AD) is a skin condition with many genetic risk factors. In this review, we summarize the different genetic variants for AD from the perspective of screening purposes within the U.S. Air Force aviation community. Using a PRISMA-informed systematic review approach, we found 13 papers reporting genetic associations with AD. We report 98 genetic associations with AD, of which 4 had a greater than twofold increased odds of developing the condition when present. These 98 variants were found in 45 associated genes, including LRRC32, OVOL1, and IL13, which were each replicated in 3 studies; as well as RTEL1 and ZNF365, which were each replicated in 2 studies. A polygenic risk model created based upon these variants or genes could contribute to a risk screening protocol for military aviation candidates, potentially helping minimize risk for candidates at increased genetic risk for AD or other atopic diseases (e.g., asthma, allergic rhinitis).Gregory ID, Collie J, Chapleau RR. Genetic markers of atopic dermatitis risk for screening aviation applicants. Aerosp Med Hum Perform. 2022; 93(11):806-810.

Static allometries do not reflect evolutionary allometry in exaggerated weaponry of male New Zealand sheetweb spiders (Cambridgea spp.).

Across the animal kingdom, exaggerated weaponry is frequently used by one sex to contest access for potential mates. Within species, if disproportionate investment in weaponry confers an advantage to larger individuals, this may result in positive static allometry. It is predicted that the same selective pressures may also lead to positive evolutionary allometry, where larger species bear disproportionately large weapons on average, compared with smaller species. Furthermore, in species with stronger sexual selection, the static allometries of those weapons are expected to steepen. All adult males across the New Zealand sheetweb spider genus Cambridgea bear exaggerated chelicerae, which are used to compete for control of females' webs. Here, we characterize the distribution of chelicera lengths within each sex of 12 Cambridgea species to show that chelicerae almost always exhibit positive static allometry in males while female chelicera lengths are consistently isometric. We use comparative phylogenetic methods to demonstrate that the slopes of static allometries steepen in males of larger species but that the ratio of average chelicera length to cephalothorax width is tightly conserved across taxa, leading to an isometric evolutionary allometry. While static allometries indeed steepen in larger species, possibly due to stronger sexual selection, this conservation of relative trait size suggests that chelicera length is subject to other stabilizing selective pressures. Changes to species body plans might be constrained, while still allowing for disproportionate investment in weapon traits in the upper range of intraspecific body sizes.

The Effects of Nutrient Signaling Regulators in Combination with Phytocannabinoids on the Senescence-Associated Phenotype in Human Dermal Fibroblasts.

Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin aging is controversial. In light of the increasing appearance of phytocannabinoids in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of phytocannabinoids in combination with nutrient signaling regulators in skin rejuvenation. Utilizing CCD-1064Sk skin fibroblasts, the effect of metformin, triacetylresveratrol, and rapamycin combined with phytocannabinoids on cellular viability, functional activity, metabolic function, and nuclear architecture was tested. We found triacetylresveratrol combined with cannabidiol increased the viability of skin fibroblasts (p < 0.0001), restored wound-healing functional activity (p < 0.001), reduced metabolic dysfunction, and ameliorated nuclear eccentricity and circularity in senescent fibroblasts (p < 0.01). Conversely, metformin with or without phytocannabinoids did not show any beneficial effects on functional activity, while rapamycin inhibited cell viability (p < 0.01) and the speed of wound healing (p < 0.001). Therefore, triacetylresveratrol and cannabidiol can be a valuable source of biologically active substances used in aging and more studies using animals to confirm the efficacy of cannabidiol combined with triacetylresveratrol should be performed.

Modeling of the Senescence-Associated Phenotype in Human Skin Fibroblasts.

Modern understanding of aging is based on the accumulation of cellular damage during one's life span due to the gradual deterioration of regenerative mechanisms in response to the continuous effect of stress, lifestyle, and environmental factors, followed by increased morbidity and mortality. Simultaneously, the number of senescent cells accumulate exponentially as organisms age. Cell culture models are valuable tools to investigate the mechanisms of aging by inducing cellular senescence in stress-induced premature senescence (SIPS) models. Here, we explain the three-step and one-step H2O2-induced senescence models of SIPS designed and reproduced on different human dermal fibroblast cell lines (CCD-1064Sk, CCD-1135Sk, and BJ-5ta). In both SIPS models, it was evident that the fibroblasts developed similar aging characteristics as cells with replicative senescence. Among the most noticeable senescent biomarkers were increased ß-Gal expression, high levels of the p21 protein, altered levels of cell-cycle regulators (i.e., CDK2 and c-Jun), compromised extracellular matrix (ECM) composition, reduced cellular viability, and delayed wound healing properties. Based on the significant increase in senescence biomarkers in fibroblast cultures, reduced functional activity, and metabolic dysfunction, the one-step senescence model was chosen as a feasible and reliable method for future testing of anti-aging compounds.

Volar Marginal Rim Fractures of the Distal Radius Have a Higher Rate of Associated Carpal Injuries-A Comparative Cohort Study.

Background Volar marginal rim distal radius fractures can be challenging due to volar instability of the carpus. The associated carpal injuries, however, have not previously been reported. Purpose The aim of this study was to compare volar marginal rim fractures to other distal radius fractures to determine if there is any association with other carpal injuries. If so, do these injuries lead to further instability and fixation failure? Materials and Methods A retrospective radiological review of 25 volar marginal rim fractures was conducted. This was compared with a comparison cohort of 25 consecutive intra-articular distal radius fractures not involving the volar marginal rim. All radiographs were reviewed for associated carpal injuries, including carpal and ulnar styloid fractures, scapholunate instability, and carpal translocation. Results Volar marginal rim fractures had a significantly higher incidence of associated carpal injuries per patient (2.52 vs. 1.64), scapholunate diastasis (36 vs. 12%), and carpal dislocation (80 vs. 48%). The fixation chosen was more likely to involve a volar rim-specific plate (44 vs. 0%). Following surgical fixation, the volar marginal rim fractures had a significantly higher incidence of carpal instability (56 vs. 24%), failure of fixation (24 vs. 0%), and revision surgery (12 vs. 0%). Conclusions Volar marginal rim fractures have significantly more carpal injuries, scapholunate instability, and volar carpal instability, compared with other distal radius fractures. Despite the use of volar rim-specific plating, volar marginal rim fractures have a significantly higher incidence of persistent carpal instability, including scapholunate instability, ulnar translocation, volar subluxation, failure of fixation, and revision surgery. Level of Evidence This is a level III, retrospective review.

Endoscopic cubital tunnel decompression: state of the art.

Cubital tunnel syndrome is a common compressive neuropathy of the upper limb. Surgical decompression is indicated for patients who failed conservative therapy. Decompression in situ has shown to achieve comparable outcomes as decompression with anterior transposition in idiopathic cubital tunnel syndrome. Endoscopic cubital tunnel decompression has gained popularity in recent years, as surgeons can attain decompression of the ulnar nerve along its course using a small incision. Results from randomised controlled studies and systematic reviews, comparing endoscopic with open decompression in situ, are promising. Cases in which anterior transposition of the ulnar nerve is needed, an endoscopic technique can still be used by creating an additional volar portal, for the mobilisation of ulnar nerve. Early short-term results are encouraging. Further adequately powered, prospective, preferably double-blinded, randomised study are needed.

Irradiation-induced sterility in an egg parasitoid and possible implications for the use of biological control in insect eradication.

Classical biological control is a pest control tool involving the release of imported natural enemies. The Sterile Insect Technique (SIT) comprises releasing sexually sterile insects of a pest into the wild population for suppression or eradication. Both these approaches are environmentally friendly and their combination can result in a synergistic impact on pest populations and improve eradication. However, stringent regulation surrounding the introduction of biological control agents limits their use in eradication owing to the perceived risk of effects on non-target organisms. We investigated the irradiation biology of the egg parasitoid Trissolcus basalis to ascertain whether sterile parasitoids could mitigate the risk of potential sustained non-target impacts. Mated female T. basalis were gamma-irradiated at doses between 120 and 150 Gy and exposed to egg masses of their host Nezara viridula throughout their lifespans. This resulted in host mortality, despite a substantial reduction in developing parasitoid offspring, which followed a negative dose-response. There was no emergence of parasitoid offspring at 140 Gy and above. Irradiation did not affect oviposition behaviour but caused an increase in longevity. Consequently, sterile parasitoids could possibly alleviate concerns regarding the irreversibility of biological control release, which promotes further investigation of their potential role in eradication.

Interdisciplinary consensus statements on imaging of scapholunate joint instability.

OBJECTIVES: The purpose of this agreement was to establish evidence-based consensus statements on imaging of scapholunate joint (SLJ) instability by an expert group using the Delphi technique. METHODS: Nineteen hand surgeons developed a preliminary list of questions on SLJ instability. Radiologists created statements based on the literature and the authors' clinical experience. Questions and statements were revised during three iterative Delphi rounds. Delphi panellists consisted of twenty-seven musculoskeletal radiologists. The panellists scored their degree of agreement to each statement on an eleven-item numeric scale. Scores of '0', '5' and '10' reflected complete disagreement, indeterminate agreement and complete agreement, respectively. Group consensus was defined as a score of '8' or higher for 80% or more of the panellists. RESULTS: Ten of fifteen statements achieved group consensus in the second Delphi round. The remaining five statements achieved group consensus in the third Delphi round. It was agreed that dorsopalmar and lateral radiographs should be acquired as routine imaging work-up in patients with suspected SLJ instability. Radiographic stress views and dynamic fluoroscopy allow accurate diagnosis of dynamic SLJ instability. MR arthrography and CT arthrography are accurate for detecting scapholunate interosseous ligament tears and articular cartilage defects. Ultrasonography and MRI can delineate most extrinsic carpal ligaments, although validated scientific evidence on accurate differentiation between partially or completely torn or incompetent ligaments is not available. CONCLUSIONS: Delphi-based agreements suggest that standardized radiographs, radiographic stress views, dynamic fluoroscopy, MR arthrography and CT arthrography are the most useful and accurate imaging techniques for the work-up of SLJ instability. KEY POINTS: • Dorsopalmar and lateral wrist radiographs remain the basic imaging modality for routine imaging work-up in patients with suspected scapholunate joint instability. • Radiographic stress views and dynamic fluoroscopy of the wrist allow accurate diagnosis of dynamic scapholunate joint instability. • Wrist MR arthrography and CT arthrography are accurate for determination of scapholunate interosseous ligament tears and cartilage defects.

Treatment of elbow instability: state of the art.

The elbow is a congruent joint with a high degree of inherent stability, provided by osseous and soft-tissue constraints; however, when substantial lesions of these stabilising structures happen, instability of the elbow occurs. Significant improvements in surgical elbow instability diagnosis and treatment have been recently introduced both for acute and chronic cases. Specific stress tests, recently introduced in the clinical practice, and different imaging techniques, both static and dynamic, allow assessment of the elbow stabilisers and detection of the instability direction and mechanism even in subtle forms. Many surgical techniques have been standardised and surgical instruments and devices, specifically dedicated to elbow instability treatment, have been developed. Specific rehabilitation protocols have been designed to protect the healing of the elbow stabilisers while minimising elbow stiffness. However, despite the progress, surgical treatments can be challenging even for expert surgeons and the rate of persistent instability, post-traumatic arthritis, stiffness and pain can be still high especially in most demanding cases. The biology of the soft-tissue healing remains one of the most important aspects for future investigation. If future research will help to understand, correct or modulate the biological response of soft-tissue healing, our confidence in elbow instability management and the reproducibility of our treatment will tremendously improve. In this paper, the state of the art of the current knowledge of elbow instability is presented, specifically focusing on modern surgical techniques used to solve instability, with repair or reconstruction of the damaged elbow stabilisers.