The determination of LC50 of diazinon and it's sub-lettal effect on haematological indices of beluga (Huso huso)

The acute toxicity and effects of diazinon on some hematological indices of Beluga (Huso huso) juveniles weighting 4.1±0.12 grams was assessed following the 0.E.C.D. direction in a static temperature in the range 20.27±2.05°C. The 96h LC50 value of diazinon for beluga juveniles was 5.821. Also, the maximum allowable concentration of diazinon in natural waters for beluga was determined to be 0.5821mg/L. Based on the toxicity table of insecticides, diazinon was listed as toxic for beluga .The clinical symptoms that were observed in this study consisted of lordosis and neural paralytic syndrome in fish exposed to the pesticide. Some abnormal reactions such as losing the balance when swimming and swimming in a half circle; expressive pigmentation mainly on the dorsal part were seen in the juveniles. Examination of hematological indices was performed on control and experimental specimens of beluga weighting 16.08 grams on average that were treated with 96h exposure to diazinon in a concentration lower than LC50 96h. The experimental group of beluga showed significantly lower value (P<0.05) of ,erythrocyte (RBC) and leukocyte count, hemoglobin content (Hb), and haematocrite (PCV), MCV, MCH and relative lymphocyte and eosinophil counts compared to the control group In comparison, the relative heterophil count in the juveniles of the experimental group was significantly higher than the control group. By observing a decrease in the amount of leukocyte profile specially lymphocytes which are important in non-specific immunity of the fish, it can be said that diazinon may cause a decrease in the non-specific immunity of beluga

Epigenetic changes in FOXO3 and CHEK2 genes and their correlation with clinicopathological findings in myelodysplastic syndromes

Objectives/background: Myelodysplastic syndromes (MDSs) are a heterogeneous disease in terms of clinical course and response to therapy. Epigenetic changes are the primary mechanism of MDS pathogenesis. FOXO3 and CHEK2 genes play significant roles in normal cellular mechanisms and are also known as tumor suppressor genes. We aimed to clarify the correlation of epigenetic changes in these genes with clinicopathologic findings in MDS. Methods: A total of 54 newly diagnosed MDS patients referred to Shariati and Firouzgar Hospitals (Tehran, Iran) were included in the study from 2013 to 2015, comprising the following cases: 26 with refractory cytopenia with unilineage dysplasia, 10 with refractory cytopenia with multilineage dysplasia, four refractory anemia with excess blasts-1 (RAEB-1), 11 refractory anemia with excess blasts-2 (RAEB-2), and three MDS associated with isolated deletion (5q-). Risk groups were determined according to the Revised International Prognostic Scoring System (IPSS-R). The methylation status of CHEK2 and FOXO3 promoters were determined by methylation-sensitive high-resolution melting analysis of sodium bisulfite-converted DNA. Expressions of CHEK2, FOXO3, and GAPDH were measured by quantitative real-time polymerase chain reaction and fold changes were calculated using the ��CT method. Results: Statistical analysis revealed no promoter methylation of CHEK2 and FOXO3 in healthy control specimens. FOXO3 promoter methylation was associated with high-risk World Health Organization subgroups (p = .017), high-risk IPSS-R (p = .007), high-risk cytogenetics (p = .045), and more than 5 blasts in bone marrow (p = .001). CHEK2 promoter methylation was correlated with more than 5 blasts in bone marrow (p = .009). Conclusions: Promoter methylation of CHEK2 and especially FOXO3 is associated with adverse clinicopathological findings and disease progression in MDS. © 2020 King Faisal Specialist Hospital & Research Centr

Individual Radiosensitivity Assessment of the Families of Ataxia-Telangiectasia Patients by G2-Checkpoint Abrogation

Objectives: Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder characterised by cerebellar degeneration, telangiectasia, radiation sensitivity, immunodeficiency, oxidative stress and cancer susceptibility. Epidemiological research has shown that carriers of the heterozygous ataxia-telangiectasia mutated (ATM) gene mutation are radiosensitive to ionising irradiation and have a higher risk of cancers, type 2 diabetes and atherosclerosis. However, there is currently no fast and reliable laboratory-based method to detect heterozygous ATM carriers for family screening and planning purposes. This study therefore aimed to evaluate the ability of a modified G2-assay to identify heterozygous ATM carriers in the families of A-T patients. Methods: This study took place at the Tehran University of Medical Sciences, Tehran, Iran, between February and December 2017 and included 16 A-T patients, their parents (obligate heterozygotes) and 30 healthy controls. All of the subjects underwent individual radiosensitivity (IRS) assessment using a modified caffeine-treated G2-assay with G2-checkpoint abrogation. Results: The mean IRS of the obligate ATM heterozygotes was significantly higher than the healthy controls (55.13% ± 5.84% versus 39.03% ± 6.95%; P <0.001), but significantly lower than the A-T patients (55.13% ± 5.84% versus 87.39% ± 8.29%; P = 0.001). A receiver operating characteristic (ROC) curve analysis of the G2-assay values indicated high sensitivity and specificity, with an area under the ROC curve of 0.97 (95% confidence interval: 0.95–1.00). Conclusion: The modified G2-assay demonstrated adequate precision and relatively high sensitivity and specificity in detecting heterozygous ATM carriers. Keywords: Ataxia-Telangiectasia; Chromosome Breakage; Genetic Carrier Screening; Heterozygote; Radiation Sensitivity; Sensitivity and Specificity

Frequencies of BCR-ABL1 fusion transcripts among Sudanese chronic myeloid leukaemia patients

The incidence of one or other rearrangement in chronic myeloid leukemia (CML) patients varies in different reported series. In this study we report the frequencies of BCR-ABL1 fusion transcript variants studied in 43 CML patients from Sudan. The study includes 46 Sudanese patients, three of which negative for the BCR-ABL1 fusion transcript. More than half of 43 positive patients showed b2a2 fusion transcript (53.5%), while (41.9%) showed b3a2 transcript and the remaining (4.6%) coexpression of b3a2/ b2a2 and b3a2/b2a2/e19a2. We detected neither coexpression of p210/p190 nor e1a2 alone. Male patients showed a tendency to express b2a2, while female tende to express b3a2 (p = 0.017). Moreover, a single nucleotide polymorphism was detected in BCR exon 13 in one out of four patients and this patient showed only b2a2 expression. In conclusion, we observed a significant correlation between sex and type of BCR-ABL1 transcript, an observation that deserves further investigation

Resilience as the predictor of quality of life in the infertile couples as the most neglected and silent minorities

Background: It has been demonstrated that infertility can affect quality of life (QoL) in infertile couples. Resilience is considered a protective factor against the distress caused by infertility and the quality of life status. There is a new definition for Fertility Quality of Life that evaluates particularly the impact of infertility on various aspects of life. Material and methods: In this couple-based study, the main objective was investigating the quality of life based on the gender and resilience of infertile couples. Measurement tools were three questionnaires including a demographic one, a quality of life of infertile couples questionnaire and the Connor�Davidson Resilience Scale. Data analysis was done through paired t-test and linear multiple regressions test. Results: Overall the difference of mean score for QoL is statistically significant (P > 0.001) between men and women (69.48 vs 58.87), which means that QoL status was positive in men and neutral in women. In addition, the mean score of male resilience was more than female resilience (P = 0.009). The results showed there was a significant and positive correlation between the QoL status and resilience score (P = 0.008, r = 0.13) (P < 0.1), and resilience (β = 0.04 and P = 0.04) had a significant protective effect on the quality of life. Conclusion: Low resilience status in infertile couples is better to be considered as a risk factor compromising the quality of life and infertility consolers should keep in mind this issue and provide a comprehensive and holistic approach for a better outcome of infertility treatment. Abbreviations: QoLICQ: Quality of Life in Infertile Couple Questionnaire; CD-RISC: Connor�Davidson Resilience Scale; IVF: in vitro fertilisation; ART: assisted reproductive technique; PTSD: posttraumatic stress disorder; IUI: intrauterine insemination; ICSI: intracytoplasmic sperm injection. ©, Society for Reproductive and Infant Psychology

A Comparison of Dexamethasone plus Vincristine versus Standard Regimen in Induction Therapy of Adult Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplantation

Background: Current treatment options of acute lymphoblastic leukemia(ALL) include chemotherapy alone or hematopoietic stem cell transplantation (HSCT) following induction chemotherapy both along with CNS prophylaxis. The usual and standard induction regimens currently administered could have severe complications and mortality. Materials and Methods: To lessen induction regimen complications in ALL patients who undergo HSCT, we used a cytoreduction induction regimen including dexamethasone (8 mg, IV, three times a day, for 28 days) and vincristine(1.4 mg/m2, IV, on days 1,8,15 and 22) for 49 newly diagnosed adult ALL patients followed by an early sibling donor HSCT within two months. The results were matched with outcomes of HSCT in 172 ALL patients inducted by standard induction regimen. Results: Median follow-up time was 5.41 years in the standard group and 5.27 years in the other. All patients of the case group (100) achieved complete remission. Landmark analyses were performed to scrutinize the effect of treatments on different time intervals: first two years and 2nd to end years. Type of treatment had no significant effect on the hazard of death in the first landmark (HR=0.87, P=0.64). Cytoreduction regimen amplified the hazard of death 3.43 times more than the standard regimen in the second landmark (HR=3.43 P=0.035). Multivariate analysis showed that the cytoreduction regimen reduced the hazard of relapse about 22, but not statistically significant (HR=0.78, P-value=0.24). Conclusion: Overall, it seems despite achieving complete remission in induction therapy, depth of response is a critical predictor for long-term outcomes of HSCT in ALL patients, and the use of multiple agents may be necessary to decrease tumor cell burden and minimal residual disease(MRD). © 2021 Tehran University of Medical Sciences