Porphyrinogenic compounds are known to induce porphyria-mediated hepatocellular injury and subsequent regenerative proliferation in rodents, ultimately leading to hepatocellular tumor induction. read more However, an appropriate in vivo experimental model to evaluate an effect of porphyrinogenic compounds on human liver has not been fully established. Recently, the chimeric mouse with humanized liver (PXB mice) became widely used as a humanized model in which human hepatocytes are transplanted. In the present study, we examined the utility of PXB mice as an in vivo experimental model to evaluate the key events of the porphyria-mediated cytotoxicity mode of action (MOA) in humans. The treatment of PXB mice with 5-aminolevulinic acid, a representative porphyrinogenic compound, for 28 days caused protoporphyrin IX accumulation, followed by hepatocyte necrosis, increased mitosis, and an increase in replicative DNA synthesis in human hepatocytes, indicative of cellular injury and regenerative proliferation, similar to findings in patients with porphyria or experimental porphyria models and corresponding to the key events of the MOA for porphyria-mediated hepatocellular carcinogenesis. We conclude that the PXB mouse is a useful model to evaluate the key events of the porphyria-mediated cytotoxicity MOA in humans and suggest the utility of PXB mice for clarifying the human relevancy of findings in mice.Acute respiratory distress syndrome is a life-threatening complication of scrub typhus; we sought to describe its mortality and associated factors, namely eschar, hepatomegaly and severe thrombocytopenia, in a retrospective study in India of 65 children.Intracellular inclusions were observed in urinary bladder epithelium of male Wistar rats, following oral treatment with high doses of the α2A-adrenoceptor agonist tasipimidine for 28 days. No cell death or inflammation was associated with the brightly eosinophilic inclusions. Electron microscopy (EM) studies showed that the inclusions represented intact or fragmented red blood cells (RBC) resulting from erythrophagocytosis, further supported by the presence of iron in urothelial cells. In addition, scattered iron-positive macrophages were observed in the submucosa and muscle layer, indicating microvascular leakage, as no major hemorrhage was evident. Despite the presence of inclusions, the urothelium showed normal uroplakin III distribution, normal cell turnover, and an absence of α-2u-globulin. It is, therefore, concluded that the inclusions were not associated with urothelial damage or increased renewal of the epithelium. This finding shows also that urothelial cells have the capability to phagocytize and break down RBCs originating from submucosal microvascular leakage. Similar changes were not observed in tasipimidine-treated beagle dogs (28 days), suggesting these findings were rat specific. The leakage of RBCs into the urothelium is suggested to be a consequence of exaggerated pharmacology leading to vasoconstriction of submucosal blood vessels in combination with transient increased bladder distension and pressure.Parental factors in internet and computer game addiction in adolescence An overview Abstract. Objective Internet-related disorders (IRD) in adolescents and young adults are closely linked to family factors. However, few research and review articles include the family. To this end, N = 87 scientific papers were integrated into the literature review. Method The present work gives an overview of parental factors that can be involved in the development, maintenance, and reduction of symptoms. Results The literature provides clear connections between the parent-child relationship and IRD in adolescents and young adults. The quality of parent-child communication appears to be a promising approach for influencing IRD symptoms. There are indications that, at least for some families, encouraging the time spent together could be helpful. Regarding educational aspects, a distinction should be made between different areas. Parental knowledge and control of internet use seem to be protective factors. The effect of rules and restrictions, however, is unclear. Conclusions To change IRD symptoms, it makes sense to improve the parent-child relationship. However, the ways to achieve that have hardly been explored. Recommendations regarding parenting strategies (e. g., rules and restrictions) should be formulated very carefully, as the effects are still unclear. The integration of parents in prevention and intervention efforts is advocated by many researchers, but there only individual studies have considered parents in the context of interventions.Introduction & Objective As life expectancy continues to rise, the prevalence of frailty is also increasing. The idea of frailty and its effect on the operative patient has been previously studied, but not regularly incorporated into routine practice. We present a review on frailty metrics in the literature, validated assessment methods, and simplified screening tools, to better predict and optimize patient outcomes. Methods An online Pubmed search was conducted by 3 authors (TA, TB, MM) for all frailty, frailty assessment, and pre-operative risk assessment. Only English publications were included in the analysis. Full text analysis was then conducted by all three authors to validate the data. Results An abundance of literature was found on frailty. Even though some methods are validated as very effective for assessing frailty, they may be time consuming and require a specialist. various quick screening methods are also present, many already validated, and should be utilized by urologist more regularly. Conclusions Multiple studies demonstrate the relationship between frailty and surgical patients’ outcome. Many quick, office based, validated tools to screen for frailty are described, and should be incorporated into our practice in appropriate patients. Future research is now focused on the concept of “prehabilitation” to improve patient frailty status in the pre-operative setting, and consequently operative outcomes.This study aimed to examine whether the ratio of vessel-specific coronary arterial lumen volume to the fraction of myocardial mass (VR/MR) affects myocardial ischemia. We proposed a calculation method for VR/MR, and compared the ratio of total epicardial coronary arterial lumen volume to left ventricular myocardial mass (V/M) with VR/MR in predicting myocardial ischemia. VR/MR and V/M were computed using data from 205 patients with 241 stenosis vessel who underwent coronary computed tomography angiography (CTA), quantitative coronary angiography, and fractional flow reserve. The vessel-specific coronary arterial lumen volume (VR) was obtained from CTA by segmenting the coronary arterial lumen volume, while the vessel-specific fraction of myocardial mass (MR) was obtained by allometric scaling. The VR/MR was then calculated. The cut-off values of V/M (23.55 mm3/g) and VR/MR (12.98 mm3/g) were used to define equal groups of ischemic and non-ischemic patients, respectively. Using these cut-off values, the accuracy, specificity, sensitivity, positive predictive value, and negative predictive value of V/M were 60%, 76%, 45%, 57%, and 66%, and of VR/MR were 87%, 92%, 77%, 89%, and 83%, respectively.