Tamoxifen induces eryptosis through calcium accumulation and oxidative stress.

Chemotherapy-related anemia is a major obstacle in anticancer therapy. Tamoxifen (TAM) is an antiestrogen prescribed for breast cancer patients with hemolytic potential and apoptotic properties in nucleated cells. However, the eryptotic activity of TAM has hitherto escaped the efforts of investigators. RBCs from apparently healthy volunteers were treated with 1-50 µM of TAM for 24 h at 37 °C. Hemoglobin leakage and LDH, AST, and AChE activities were photometrically determined while K+, Na+, and Mg2+ were detected by ion-selective electrode. Flow cytometry was used to identify eryptotic cells by annexin-V-FITC, intracellular Ca2+ by Fluo4/AM, sell size and morphology by FSC and SSC signals, respectively, and oxidative stress by H2DCFDA. Whole blood was also exposed to 30 µM of TAM for 24 h at 37 °C to examine the toxicity of TAM to WBCs and platelets. TAM caused Ca2+-independent, dose-responsive hemolysis accompanied by K+, LDH, and AST leakage without improving the mechanical stability of RBCs in hypotonic environments. TAM treatment also increased the proportion of cells positive for annexin-V-FITC, Fluo4, and DCF, along with diminished FSC and SSC signals and AChE activity. Notably, TAM toxicity was aggravated by sucrose but abrogated by vitamin C, PEG 8000, and urea. Moreover, TAM exhibited distinct cytotoxic profiles against leukocytes and platelets. TAM-induced eryptosis is characterized by breakdown of membrane asymmetry, inhibition of AChE activity, Ca2+ accumulation, cell shrinkage, and oxidative stress. Vitamin C, PEG 8000, and urea may hold promise to subvert the undesirable toxic effects of TAM on RBCs.

Comparative Metabolic Characterization of Extraintestinal Pathogenic Escherichia coli Blood Isolates from Saudi Arabia.

Background: The prevalence of bloodstream infections caused by extraintestinal pathogenic Escherichia coli (ExPEC) has increased substantially. E. coli ST131 is one of the dominant ExPEC clones among E. coli bacteremia population. Metabolism can trigger the pathogenesis of some bacterial isolates, and here we evaluated and compared the metabolic traits of E. coli bacteremia isolates including ß-lactamase (BL)/extended-spectrum ß-lactamase (ESBL)-positive and ESBL-negative isolates and ST131 and non-ST131 isolates. Methods: The metabolic profiles of thirty E. coli isolates, obtained from blood samples for hospitalized individuals at a tertiary healthcare facility in Riyadh, were determined using HiMedia carbohydrate test strips. The difference in the utilization ability between isolate groups was then statistically assessed. Results: Our data found that non-BL/ESBL producers were of low metabolic capacity compared with ESBL-positive isolates although the difference remained insignificant. Higher levels of utilization for some carbohydrates, such as fructose and trehalose, were detected among ST131 isolates when compared with non-ST131, and ST131 was also significantly associated with metabolizing rhamnose. The mean bio-score of both isolate groups was insignificant. We showed no link between metabolism and antimicrobial susceptibility profiles among tested blood isolates. Conclusion: ST131 blood isolates were slightly higher in their carbohydrate utilization activity than non-ST131. More importantly, ST131 isolates were significantly capable of metabolizing rhamnose. Future research should focus on the factors that might drive the success of major ExPEC clones such as ST131.

Findings of a Multidisciplinary Assessment of Children Referred for Possible Neurodevelopmental Disorders: Insights from a Retrospective Chart Review Study.

Children with ASD have a wide spectrum of functional deficits in multiple neurodevelopmental domains. A multidisciplinary team assessment (MDT) is required to assess those deficits to help construct a multimodal intervention plan. This is a retrospective chart review of the assessment for children who were referred for an assessment of potential neurodevelopmental disorders. We reviewed 221 participants' charts from January 2019 to January 2020. The mean age of the children was 7.95 ± 3.69, while the mean age of the fathers and mothers was 37.31 ± 8.57 and 31.95 ± 6.93, respectively. Consanguinity was as high as 37.9% for the referred children with developmental delay who were first-degree related, and 13.2% of the parents were second-degree relatives. Approximately 26.6% of children had a family history of mental illness in first-degree relatives. ASD was the most commonly reported diagnosis post-assessment, and ADHD was the most common reported comorbidity at 64.3% and 88.5%, respectively. The MDT findings showed that 58% of children required moderate or higher assistance with toileting, 79.2% were unable to answer yes/no questions, and 86.8% were unable to understand "wh" questions. Only 26% of the nonverbal children had average IQ testing results, and 31% of verbal children did. In conclusion, the mean age of the children when assessed was above that recommended for early screening and intervention. An increased paternal and maternal age was noticeable. Consanguinity and a family history of mental disorders in first-degree relatives were high, attesting to a possible genetic risk.