Transcriptome analysis showed that genes involved in various cell proliferative pathways, such as the RAS/RAF/MAP and PIP3/AKT signaling pathways, were downregulated by RBMY overexpression in HuH-7 cells. Furthermore, in vivo analyses in a mouse liver cancer model using hydrodynamic tail vein injection of constitutively active AKT and RAS oncogenes showed that RBMY abolished HCC development. These findings support the notion that Y-linked RBMY could serve dual tumor-suppressing and tumor-promoting functions, depending on the spatiotemporal and magnitude of its expression during oncogenic processes, thereby contributing to sexual dimorphisms in liver cancer.Background Surgical approaches to the kidneys and perirenal structures are uncommonly performed in horses and several complications have been described with the current procedures. Objective To describe the anatomy of the retroperitoneal perirenal space and investigate a retroperitoneal minimally invasive approach to access the kidney and perirenal structures in horses. Study design Descriptive, cadaveric study. Methods Anatomical description of the retroperitoneal space was performed on three equine cadavers and the surgical approach was developed based on these dissections. Ten cadaveric horses underwent a retroperitoneoscopy. Five horses were placed in a right lateral recumbency position to explore the left retroperitoneal space and five horses were placed in a standing position to explore both left and right sides. Anatomical landmarks, working space and access to the renal hilus and perirenal structures were evaluated. Results Dissections revealed that kidneys are surrounded by a renal fascia which delimits two spaces a perirenal space between the kidney and the renal fascia, and a pararenal space between the renal fascia and psoas muscles or peritoneum. The retroperitoneoscopic portal was placed at the level of the dorsal aspect of the tuber coxae, 3 cm caudal to the last rib for the left side and 2 cm caudal to the last rib for the right side. Retroperitoneal access and working space were successfully established in all horses. The standing position allowed an easier dissection than lateral recumbency. Division of the perirenal fat allowed access to the kidney and adrenal glands as well as individualisation of renal vessels and ureter in the renal hilus. Main limitations Study of cadavers precluded appreciation of haemorrhage or use the pulsating vessels as landmarks. Conclusions This study provides a description of the retroperitoneal perirenal space and describes a new surgical approach to access kidneys and perirenal structures in horses.Purpose To calculate in- and out-of-field neutron spectra and dose equivalent, using Monte Carlo (MC) simulation, for a Mevion gantry-mounted passively scattered proton system in craniospinal irradiation. An analytical model based on the MC calculations that estimates in- and out-of-field neutron dose equivalent from proton Craniospinal irradiation (CSI) was also developed. Methods The MCNPX MC code was used to simulate a Mevion S250 proton therapy system. The simulated proton depth doses and profiles for pristine and spread-out Bragg peaks were benchmarked against the measured data. Previous measurements using extended-range Bonner spheres were used to verify the calculated neutron spectra and dose equivalent. Using the benchmarked results as a reference condition, a correction-based analytical model was reconstructed by fitting the data to derive model parameters at 95% confidence interval. Sensitivity analysis of brass aperture opening, thickness of the Lucite (PMMA) range compensator, and modulation width was performed to obtain correction parameters for nonreference conditions. Results For the neutron dose equivalent per therapeutic proton dose, the MCNPX calculated dose equivalent matched the measured values to within 8%. The benchmarked neutron dose equivalent at the isocenter was 41.2 and 20.8 mSv/Gy, for cranial and spinal fields, respectively. For in- and out-of-field neutron dose calculations, the correction-based analytical model showed up to 17% discrepancy compared to the MC calculations. The correction factors may provide a conservative estimation of neutron dose, especially for depth ≤ 5 cm and regions underneath the brass aperture. Conclusion The proposed analytical model can be used to estimate the contribution of the neutron dose to the overall CSI treatment dose. Moreover, the model can be employed to estimate the neutron dose to the implantable cardiac electronic devices.Clear cell carcinoma of the ovary is thought to arise from endometriosis. In addition, retrograde menstruation of shed endometrium is considered the origin of endometriosis. However, little evidence supports cellular continuity from uterine endometrium to clear cell carcinoma through endometriosis at the genomic level. Here, we performed multiregional whole-exome sequencing to clarify clonal relationships among uterine endometrium, ovarian endometriosis and ovarian clear cell carcinoma in a 56-year-old patient. Many somatic mutations including cancer-associated gene mutations in ARID1A, ATM, CDH4, NRAS and PIK3CA were shared among epithelium samples from uterine endometrium, endometriotic lesions distant from and adjacent to the carcinoma, and the carcinoma. The mutant allele frequencies of shared mutations increased from uterine endometrium to distant endometriosis, adjacent endometriosis, and carcinoma. Although a splice site mutation of ARID1A was shared among the four epithelium samples, a frameshift insertion in ARID1A was shared by adjacent endometriosis and carcinoma samples, suggesting that the biallelic mutations triggered malignant transformation. Somatic copy number alterations, including loss of heterozygosity events at PIK3CA and ATM, were identified only in adjacent endometriosis and carcinoma, suggesting that mutant allele-specific imbalance is another key factor driving malignant transformation. By reconstructing a clonal evolution tree based on the somatic mutations, we showed that the epithelium samples were derived from a single ancestral clone. Although the study was limited to a single patient, the results from this illustrative case could suggest the possibility that epithelial cells of ovarian endometriosis and clear cell carcinoma were descendants of uterine endometrial epithelium.Increased reactive oxygen species (ROS) generation may disrupt the oocytes function and their competence. In this study, we introduced BTZO-1, a new supplement that can regulate the oxidative stress. Addition of BTZO-1 during IVM of bovine oocytes improved their developmental competence in the term of improvement of blastocyst rates. In addition, the quality of the produced embryos was improved by decreasing the apoptosis level by showing a decreased number of TUNNEL positive cells.Epilepsy is a major neurological condition that affects millions of people globally. While a number of interventions have been developed to mitigate this condition, a significant number of patients are refractory to these treatments. Consequently, other avenues of research are needed. One such avenue is modulation of the immune system response to this condition, which has mostly focused on microglia, the resident immune cells of the central nervous system (CNS). However, other immune cells can impact neurological conditions, principally blood-borne monocytes that can infiltrate into brain parenchyma after seizures. As such, this review will first discuss how monocytes can be recruited to the CNS and how they can be distinguished from there immunological cousins, microglia. Then, we will explore what is known about the role monocytes have within seizure pathogenesis and epilepsy. Considering how little is known about monocyte function in seizure- and epilepsy-related pathologies, further studies are warranted that investigate infiltrated blood-borne monocytes as a potential therapeutic target for epilepsy treatment.Children with multiple exposures to anesthesia and surgery may be more likely to develop the learning disability. Coenzyme Q10 (CoQ10) was reported to reduce the multiple sevoflurane treatment-induced cognitive deficiency in 6-day-old young mice. However, its specific mechanisms have not yet been found. This research aimed to reveal the role of ApoE in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia and the protective mechanism of CoQ10 in a multiple sevoflurane treatment model of young mice. The mice were randomly divided into four groups Control + corn oil, Sevoflurane + corn oil, Control + CoQ10, and Sevoflurane + CoQ10. Sevoflurane group mice were anesthetized with 3% sevoflurane and 60% oxygen 2 hr a day for 3 days, while control group mice received only 60% oxygen. https://www.selleckchem.com/products/SNS-032.html Mice received an intraperitoneal injection of 50 mg/kg CoQ10 or the same volume of corn oil 30 min before the inhalation of oxygen or sevoflurane for 3 days. Mice received sevoflurane anesthesia or control treatment from the 6th to 8th day after birth. The cortex and hippocampus were harvested on the 8th day. The ATP, MMP, ApoE mRNA, total ApoE, ApoE fragments, Aβ1-40, Aβ1-42, Tau5, AT8, and PHF levels were detected. The Morris water maze (MWM) tests were performed from P30 to p36 after anesthesia or control treatment. The results indicated that the injection of CoQ10 ahead of sevoflurane treatment could reverse the anesthesia-induced energy deficiency, mitochondrial dysfunction, ApoE, and its fragments expression, Aβ1-42 generation, Tau phosphorylation, and cognitive impairment in young mice. These data reveal that the ApoE and its fragments enhancement may play an important role in the pathogenesis of cognitive deficiency caused by sevoflurane anesthesia. CoQ10 could reduce ApoE expression by improving energy replenishment and mitochondrial functions, thereby alleviating sevoflurane-induced brain damage and cognitive impairment.Background & aims Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury manifested by increased liver enzymes in reports worldwide. Prevalence of liver injury and associated clinical characteristics are not well-defined. We aim to identify the prevalence of and risk factors for development of COVID-19 associated acute liver injury in a large cohort in the United States. Approach & results In this retrospective cohort study, all patients who underwent SARS-CoV-2 testing at three hospitals in the NewYork-Presbyterian network were assessed. Of 3381 patients, 2273 tested positive and had higher initial and peak ALT than those who tested negative. Acute liver injury was categorized as mild if alanine aminotransferase (ALT) was > upper limit of normal (ULN) but five times ULN. link2 Among patients who tested positive, 45% had mild, 21% moderate, and 6.4% severe liver injury. In multivariable analysis, severe acute liver injury was significantly associated with elevated inflammatory markers including ferritin (OR 2.40, p less then 0.001) and IL-6 (OR 1.45, p=0.009). Patients with severe liver injury had a more severe clinical course, including higher rates of ICU admission (69%), intubation (65%), renal replacement therapy (33%), and mortality (42%). In multivariable analysis, peak ALT was significantly associated with death or discharge to hospice (OR 1.14, p=0.044), controlling for age, body mass index, diabetes, hypertension, intubation, and renal replacement therapy. link3 Conclusion Acute liver injury is common in patients who test positive for SARS-CoV-2, but is most often mild. However, among the 6.4% of patients with severe liver injury, a severe disease course should be anticipated.