We have previously shown that histamine (2-(1H-imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic (H2R-TG) mice that overexpress the human H2 histamine receptor (H2R) in the heart; however, the effects were not seen in their wild-type (WT) littermates. Amitriptyline, which is still a highly prescribed antidepressant drug, was reported to act as antagonist on H2Rs. Here, we wanted to determine whether the histamine effects in H2R-TG were antagonized by amitriptyline. Contractile studies were performed on isolated left and right atrial preparations, isolated perfused hearts from H2R-TG and WT mice and human atrial preparations. Amitriptyline shifted the concentration-dependent PIE of histamine (1 nM-10 μM) to higher concentrations (rightward shift) in left atrial preparations from H2R-TG. Similarly, in isolated perfused hearts from H2R-TG and WT mice, histamine increased the contractile parameters and the phosphorylation state of phospholamban (PLB) at serine 16 in the H2R-TG mice, but not in the WT mice. However, the increases in contractility and PLB phosphorylation were attenuated by the addition of amitriptyline in perfused hearts from H2R-TG. In isolated electrically stimulated human atria, the PIE of histamine that was applied in increasing concentrations from 1 nM to 10 μM was reduced by 10-μM amitriptyline. In summary, we present functional evidence that amitriptyline also acts as an antagonist of contractility at H2Rs in H2R-TG mouse hearts and in the human heart which might in part explain the side effects of amitriptyline. Middle meningeal artery (MMA) embolization is emerging as apotential treatment of chronic subdural hematomas (CSDHs). The purpose of this study is to describe MMA angiographic anatomy in relation to CSDH embolization. This retrospective monocentric study was performed on imaging data of MMA embolization procedures for CSDH treatment performed between March15, 2018 and April30, 2020. Imaging data, including digital subtraction angiography (DSA) were reviewed independently by two physicians. Discrepancies were resolved by consensus. The MMA bifurcation pattern was analyzed according to an extended Adachi classification. Relations of the MMA with the ophthalmic artery (OA) were also analyzed. In this study, 140 MMAs were analyzed. Dominance of the anterior branch (typeI) was observed in only 57/140 (41%) MMAs with amoderate interobserver agreement for classifying MMA into typeI against all other (κ = 0.53, 95% confidence interval, CI 0.39-0.67). The posterior branch presented aproximal origin (typeA), at the point of emergence of the MMA from the foramen spinosum or its immediate vicinity, in 48/135 (36%) MMAs with avery good interobserver agreement for classifying MMAs into typeA against all other (κ = 0.82, 95% CI 0.72-0.92). An angiographic relationship with the OA was observed in 26MMAs (19%). In the majority of CSDH patients both anterior and posterior branches of the MMA should be targeted to achieve extensive convexity devascularization. Frequent anatomical variations of the MMA with respect to emergence of the posterior branch and MMA orbital branches are expected to impact CSDH embolization strategy. In the majority of CSDH patients both anterior and posterior branches of the MMA should be targeted to achieve extensive convexity devascularization. Frequent anatomical variations of the MMA with respect to emergence of the posterior branch and MMA orbital branches are expected to impact CSDH embolization strategy. Results of surgical or endovascular treatment of intracranial aneurysms are often assessed using angiography. A reliable method to report results irrespective of treatment modality is needed to enable comparisons. Our goals were to systematically review existing classification systems, and to propose a 3-point classification applicable to both treatments and assess its reliability. We conducted two systematic reviews on classification systems of angiographic results after clipping or coiling to select a simple 3-category scale that could apply to both treatments. We then circulated an electronic portfolio of angiograms of clipped (n=30) or coiled (n=30) aneurysms, and asked raters to evaluate the degree of occlusion using this scale. Raters were also asked to choose an appropriate follow-up management for each patient based on the degree of occlusion. Agreement was assessed using Krippendorff's α statistics (α ), and relationship between occlusion grade and clinical management was analyzed using Fisher's exact and Cramer's V tests. The systematic reviews found 70 different grading scales with heterogeneous reliability (kappa values from 0.12 to 1.00). https://www.selleckchem.com/products/defactinib.html The 60-patient portfolio was independently evaluated by 19 raters of diverse backgrounds (neurosurgery, radiology, and neurology) and experience. There was substantial agreement (α =0.76, 95%CI, 0.67-0.83) between raters, regardless of background, experience, or treatment used. Intra-rater agreement ranged from moderate to almost perfect. A strong relationship was found between angiographic grades and management decisions (Cramer's V 0.80±0.12). A simple 3-point scale demonstrated sufficient reliability to be used in reporting aneurysm treatments or in evaluating treatment results in comparative randomized trials. A simple 3-point scale demonstrated sufficient reliability to be used in reporting aneurysm treatments or in evaluating treatment results in comparative randomized trials.The strong genetic and clinical overlaps between spondyloarthritis (SpA) and inflammatory bowel disease (IBD) have placed much needed focus on the gut-joint axis of inflammation in SpA, leading to three key hypotheses that attempt to unravel this complex relationship. The arthritogenic peptide hypothesis and the aberrant cellular trafficking hypothesis have been put forth to rationalize the manner by which the innate and adaptive immune systems cooperate and converge during SpA pathogenesis. The bacterial dysbiosis hypothesis discusses how changes in the microbiome lead to architectural and immunological consequences in SpA. These theories are not mutually exclusive, but can provide an explanation as to why subclinical gut inflammation may sometimes precede joint inflammation in SpA patients, thereby implying a causal relationship. Such investigations will be important in informing therapeutic decisions which may be common to both SpA and IBD. However, these hypotheses can also offer insights for a coincident inflammatory relationship between the gut and the joint, particularly when assessing the immunological players involved.