Currently there is no consensus regarding the aetiology of the excessive ocular volume that characterizes high myopia. Thus, we aimed to test whether the gene pathways identified by gene set enrichment analysis of RNA-seq transcriptomics refutes the predictions of the Retinal Ion Driven Efflux (RIDE) hypothesis when applied to the induction of form-deprivation myopia (FDM) and subsequent recovery (post-occluder removal). We found that the induction of profound FDM led to significant suppression in the ligand-gated chloride ion channel transport pathway via suppression of glycine, GABAA and GABAC ionotropic receptors. Post-occluder removal for short term recovery from FDM of 6 h and 24 h, induced significant upregulation of the gene families linked to cone receptor phototransduction, mitochondrial energy, and complement pathways. These findings support a model of form deprivation myopia as a Cl- ion driven adaptive fluid response to the modulation of the visual signal cascade by form deprivation that in turn affects the resultant ionic environment of the outer and inner retinal tissues, axial and vitreal elongation as predicted by the RIDE model. Occluder removal and return to normal light conditions led to return to more normal upregulation of phototransduction, slowed growth rate, refractive recovery and apparent return towards physiological homeostasis.Although beneficial effects of an early goal directed therapy (EGDT) after cardiac arrest and successful return of spontaneous circulation (ROSC) have been described, clinical implementation in this period seems rather difficult. The aim of the present study was to investigate the feasibility and the impact of EGDT on myocardial damage and function after cardiac resuscitation. A translational pig model which has been carefully adapted to the clinical setting was employed. After 8 min of cardiac arrest and successful ROSC, pigs were randomized to receive either EGDT (EGDT group) or therapy by random computer-controlled hemodynamic thresholds (noEGDT group). Therapeutic algorithms included blood gas analysis, conductance catheter method, thermodilution cardiac output and transesophageal echocardiography. Twenty-one animals achieved successful ROSC of which 13 pigs survived the whole experimental period and could be included into final analysis. cTnT and LDH concentrations were lower in the EGDT group without reaching statistical significance. buy Valproic acid Comparison of lactate concentrations between 1 and 8 h after ROSC exhibited a decrease to nearly baseline levels within the EGDT group (1 h vs 8 h 7.9 vs. 1.7 mmol/l, P  less then  0.01), while in the noEGDT group lactate concentrations did not significantly decrease. The EGDT group revealed a higher initial need for fluids (P  less then  0.05) and less epinephrine administration (P  less then  0.05) post ROSC. Conductance method determined significant higher values for preload recruitable stroke work, ejection fraction and maximum rate of pressure change in the ventricle for the EGDT group. EGDT after cardiac arrest is associated with a significant decrease of lactate levels to nearly baseline and is able to improve systolic myocardial function. Although the results of our study suggest that implementation of an EGDT algorithm for post cardiac arrest care seems feasible, the impact and implementation of EGDT algorithms after cardiac arrest need to be further investigated.FGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.Detailed understanding of the innervation of the hip capsule (HC) helps inform surgeons' and anaesthetists' clinical practice. Post-interventional pain following radiofrequency nerve ablation (RFA) and dislocation following total hip arthroplasty (THA) remain poorly understood, highlighting the need for more knowledge on the topic. This systematic review and meta-analysis focuses on gross anatomical studies investigating HC innervation. The main outcomes were defined as the prevalence, course, density and distribution of the nerves innervating the HC and changes according to demographic variables. HC innervation is highly variable; its primary nerve supply seems to be from the nerve to quadratus femoris and obturator nerve. Many articular branches originated from muscular branches of the lumbosacral plexus. It remains unclear whether demographic or anthropometric variables may help predict potential differences in HC innervation. Consequently, primary targets for RFA should be the anterior inferomedial aspect of the HC. For THA performed on non-risk patients, the posterior approach with capsular repair appears to be most appropriate with the lowest risk of articular nerve damage. Care should also be taken to avoid damaging vessels and muscles of the hip joint. Further investigation is required to form a coherent map of HC innervation, utilizing combined gross and histological investigation.