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Objective The objective of the present study was to evaluate the effect of low-dose of ketamine, in short-term, on behavioral impairment and acute neuronal death in the cerebral cortex during the acute phase in a model of epileptic mouse induced by pilocarpine.MethodsKetamine was administrated (10 mg/kg) intraperitoneally, 30 min before pilocarpine injection (100 mg/kg) in the first group. The second group received the same dose of ketamine 30 min after pilocarpine injection. The effect of ketamine on behavioral disorders and cerebral neuronal integrity in epileptic mice was evaluated.ResultsClinical observations and behavioural tests relate a reduction in behavioural dysfunctions in mice treated with ketamine. Interestingly, treatment of mice with low dose of ketamine decreased the clinical symptoms (movements of the vibrios, nods of the head, and movements of the whiskers), especially when administered before epilepsy induction. Furthermore, the administration of ketamine limits oedema in the hippocampus, neuronal degeneration and gliosis in the different cortical layers. These results could be explained by NMDA receptors inhibition by ketamine.ConclusionTherefore, it appears that ketamine is endowed with a potential neuroprotective effect and can reduce the severity of neurodegeneration, especially when administrated before Status Epilepticus (SE) installation.Objectives To investigate VEGF and Ang-2 level changes in the systemic circulation after laser photocoagulation in premature infants with ROP. Methods Eleven infants (4 girls and 7 boys) had serum levels determined for VEGF and Ang-2, collected 1 day prior to and 7 days after ROP laser therapy. Serum levels of VEGF and Ang-2 were quantified by enzyme-linked immunosorbent assay (ELISA). Results Serum VEGF levels were significantly lower at 7 days after laser therapy compared to that at 1 day prior to laser therapy (p = 0.045). Serum Ang-2 levels increased significantly at 7 days after laser therapy compared with that at 1 day prior to laser therapy (p = 0.046). Conclusions Serum VEGF levels in patients with ROP were suppressed and Ang-2 levels elevated significantly after laser therapy. The results suggest that changes in VEGF and Ang-2 serum levels may reflect regression and treatment of ROP.Achieving remission after induction therapy in high-risk neuroblastoma (HR-NB) is of significant prognostic importance. This study investigated remission after induction-chemotherapy using three standard neuroblastoma protocols in the South African (SA) setting. Retrospective data of 261 patients with HR-NB diagnosed between January 2000 and December 2016, who completed induction chemotherapy with standard treatment protocols were evaluated. The treatment protocols were either OPEC/OJEC or the St Jude NB84 protocol (NB84) or rapid COJEC (rCOJEC). The postinduction metastatic complete remission (mCR) rate, 2-year overall survival (OS) and 2-year event free survival (EFS) were determined as comparative denominators. The majority (48.3%; n = 126) received OPEC/OJEC, while 70 patients received (26.8%) rCOJEC and 65 (24.9%) NB84. Treatment with NB84 had the best mCR rate (36.9%), followed by OPEC/OJEC (32.5%) and rCOJEC (21.4%). The 2-year OS of treatment with NB84 was 41% compared to OPEC/OJEC (35%) and rCOJEC (24%) (p = 0.010). The 2-year EFS of treatment with NB84 was 37% compared to OPEC/OJEC (35%) and rCOJEC (18%) (p = 0.008). OPEC/OJEC had the least treatment-related deaths (1.6%) compared to rCOJEC (7.1%) and NB84 (7.5%) (p = 0.037). On multivariate analysis LDH (p = 0.023), ferritin (p = 0.002) and INSS stage (p = 0.006) were identified as significant prognostic factors for OS. The induction chemotherapy was not significant for OS (p = 0.18), but significant for EFS (p = 0.08) Treatment with NB84 achieved better mCR, OS and EFS, while OPEC/OJEC had the least treatment-related deaths. In resource-constrained settings, OPEC/OJEC is advised as induction chemotherapy in HR-NB due to less toxicity as reflected in less treatment-related deaths.Background Fibrocystic change in the breast is one of the entities under the spectrum of benign breast disease. It occurs primarily in females of the reproductive age group. Though the exact etiology is unknown, estrogen-progesterone imbalance is possibly one of the causative factors. Its occurrence in the pediatric age group is infrequent and is hitherto unreported in the pre-pubertal age group. Case report We present the case of a 2-year-old female presenting with an ill -defined lump approximately 4 cm in diameter, with an unremarkable hormonal status for the age. Histopathology revealed fibrocystic change in the resected tissue. Conclusion Fibrocystic breast change in children may represent an exaggeration of the normal developmental involution process.Immune cells are characterized by diversity, specificity, plasticity, and adaptability-properties that enable them to contribute to homeostasis and respond specifically and dynamically to the many threats encountered by the body. Single-cell technologies, including the assessment of transcriptomics, genomics, and proteomics at the level of individual cells, are ideally suited to studying these properties of immune cells. In this review we discuss the benefits of adopting single-cell approaches in studying underappreciated qualities of immune cells and highlight examples where these technologies have been critical to advancing our understanding of the immune system in health and disease. Expected final online publication date for the Annual Review of Immunology, Volume 38 is April 26, 2020. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Objectives. The criteria for "active surveillance" depend in part on quantification of tumor extent and grade on prostate biopsies. It is known that false-negative biopsies may occur from incomplete sectioning of cores within the paraffin blocks. Methods. We retrospectively analyzed a prostate biopsy series, which were subjected to a second round of sections, in order to determine the rate of missed cancers. Results. Of 1324 sets of prostate biopsies, 4.5% (60) showed additional involved cores or higher grade tumor on recut sections. SRI-011381 In 27 patients (2.0%), the changed diagnosis resulted in a potential mild increase in National Comprehensive Cancer Network (NCCN) risk, from negative to very low (12), very low to low (12), and low to favorable intermediate (3). In 3 patients (0.2%), the changed diagnosis resulted in a significant increase in NCCN risk. Comparison of the initial sets of slides to the recuts demonstrated areas of absent tissue in many of the cases in which tumor segments were missed. In 2/3 cases with the significant grade increase, gaps were present in one that should have alerted the pathologist to incomplete sections, and the tumor was fragmented at the edge of the core appearing incompletely sampled. Conclusions. A significant increase in risk was seen in this study in 0.2% of patients when blocks were recut for further sampling, with minor increases in 2%. While embedding issues only rarely resulted in clinically significant sampling error, the 3 significantly underdiagnosed cases underscore the need for pathologists to be alert to incomplete sections of prostate cores.Objective To investigate the validation and reliability of Istanbul Low Back Pain Disability Index (ILBPDI) in axial spondyloarthritis (Ax-SpA).Methods Patients with Ax-SpA according to The Assessment of SpondyloArthritis International Society criteria were recruited. The validation was assessed by face, content, and construct (convergent and divergent) validities, whereas the reliability was assessed by internal consistency and test-retest reliability. Factor analysis was performed. Convergent validity was assessed by correlations of ILBPDI with functional parameters (The Bath Ankylosing Spondylitis Functional Index, The Dougados Functional Index, and The Health Assessment Questionnaire). Divergent validity was assessed by correlations of ILBPDI with non-functional parameters.Results Two hundred forty patients were recruited. Cognitive debriefing showed ILBPDI to be clear, relevant, and comprehensive. Cronbach's alpha coefficient was 0.953. The test-retest reliability was good with the intraclass correlation coefficient of 0.870. ILBPDI was represented by three-factor groups of activity axial bending, sitting/rest, and standing activities. ILBPDI had good correlations with the functional parameters (rho changes between 0.809 and 0.580), and it had poor or non-significant correlations with the non-functional parameters (absolute rho changes between 0.669 and 0.001).Conclusion ILBPDI is a practical, accurate, and non-time-consuming scale which is valid and reliable to evaluate the functional disability in patients with Ax-SpA.Background While perioperative red blood cell transfusion has been widely associated with poor surgical outcomes, few studies have focused specifically on the preoperative transfusional risk-benefit ratio. The aim of the present study was to evaluate the effects of preoperative red blood cell transfusion on short-term surgical outcomes in a cohort of anemic colon cancer patients.Methods Moderate and severe anemic patients undergoing colectomy for cancer were divided into two groups based upon the receipt of preoperative transfusion and compared in terms of short-term outcomes.Results A total of 271 patients with moderate or severe anemia were identified, 93 (34.3%) of whom were preoperatively transfused with a median of two units of packed red blood cells per patient (interquartile range 2-4 units). The overall morbidity rate did not differ significantly between the two groups (35.5% vs. 36.2%; p = 0.63), while an increased incidence of major morbidity (Clavien-Dindo grade > 3a) observed in transfused patients [14% vs. 6.2% respectively; odds ratio (OR) 2.47, 95% confidence interval (CI) 1.06-5.75; p = 0.03]. The increase in major morbidity was confirmed by multivariate analysis, adjusted for potential confounders (OR 3.45; 95% CI 1.32-9.04; p = 0.01).Conclusions Preoperative blood transfusion is associated with severe postoperative complications following colectomy in moderate and severe anemic cancer patients. Further studies are needed to establish an optimal preoperative transfusional cutoff value to optimize postoperative outcomes and balance clinical costs.Resistance to anticancer agents has been an obstacle to developing therapeutics and reducing medical costs. Whereas sorafenib is used for the treatment of human hepatocellular carcinoma (HCC), resistance limits its efficacy. p62, a multifunctional protein, is overexpressed in several HCC cell lines, such as Huh-1 cells. Phosphorylated p62 (p-p62) inhibits the protein-protein interaction (PPI) between Keap1 and Nrf2, resulting in the Nrf2 overactivation that causes drug resistance. We have found a unique Nrf2 inactivator, named K67, that inhibited the PPI between Keap1 and p-p62 and attenuated sorafenib resistance in Huh-1 cells. Herein, we designed and synthesized novel K67 derivatives by modification of the substituent at the 4-position of the two benzenesulfonyl groups of K67. Although these new derivatives inhibited the Keap1-p-p62 PPI to a level comparable to or weaker than that of K67, the isopropoxy derivative enhanced the sensitivity of Huh-1 cells to sorafenib to a greater extent than K67 without any influence on the viability of Huh-7 cells, which is a nonresistant HCC cell line.
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