Kokakhtar8485

Standardization of the detection and quantification of leukocyte differentiation markers by the EuroFlow Consortium has led to a major step forward in the integration of flow cytometry into classification of leukemia and lymphoma. In our opinion, this now enables introduction of markers for more dynamic parameters, such as proliferative and (anti)apoptotic markers, which have proven their value in the field of histopathology in the diagnostic process of solid tumors and lymphoma. Although use of proliferative and (anti)apoptotic markers as objective parameters in the diagnostic process of myeloid malignancies was studied in the past decades, this did not result in the incorporation of these biomarkers into clinical diagnosis. This review addresses the potential of these markers for implementation in the current, state-of-the-art multiparameter analysis of myeloid malignancies. The reviewed studies clearly recognize the importance of proliferation and apoptotic mechanisms in the pathogenesis of bone marrow (BM) malignancies. The literature is, however, contradictory on the role of these processes in myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasms, and acute myeloid leukemia. learn more Furthermore, several studies underline the need for the analysis of the proliferative and apoptotic rates in subsets of hematopoietic BM cell lineages and argue that these results can have diagnostic and prognostic value in patients with myeloid malignancies. Recent developments in multiparameter flow cytometry now allow quantification of proliferative and (anti)apoptotic indicators in myeloid cells during their different maturation stages of separate hematopoietic cell lineages. This will lead to a better understanding of the biology and pathogenesis of these malignancies.From 1948 to 1954, the Atomic Bomb Casualty Commission conducted a study of pregnancy outcomes of children of atomic bomb survivors who had received radiation doses from zero to near-lethal levels. Past reports (1956, 1981, and 1990) on the cohort did not identify significant associations of radiation exposure with untoward pregnancy outcomes such as major congenital malformations, stillbirths, or neonatal deaths, individually or in aggregate. We have re-examined the risk of major congenital malformations and perinatal deaths in the children of the atomic bomb survivors (N=71,603) using fully reconstructed data to minimize the potential for bias, with refined estimates of the gonadal dose from the Dosimetry System 2002 and refined analytical methods for characterizing dose-response relationships. The analyses show that parental exposure is associated with increased risk for major congenital malformations and perinatal deaths, but the estimates are imprecise for direct radiation effects and most are not statistically significant. Nonetheless, the uniformly positive estimates for untoward pregnancy outcomes among children of both maternal and paternal survivors are useful for risk assessment purposes, although extending them to circumstances other than atomic bomb survivors comes with uncertainty as to the generalizability of the Hiroshima and Nagasaki populations.We assessed the teratogenicity of tenofovir, a human immunodeficiency virus (HIV) drug similar to remdesivir currently being evaluated for the treatment of coronavirus disease 2019 (COVID-19). Using US Medicaid Analytic Extract (MAX) claims data (2000-2014), we identified a population-based pregnancy cohort of women with HIV who filled ≥1 prescription for antiretroviral therapies (ART) during the first trimester. Women on tenofovir disoproxil fumarate (TDF) were compared with women receiving ART without TDF. Major malformations were identified by ICD-9 codes using validated algorithms. Relative risks (RR) and 95% confidence intervals (CI) were estimated using propensity score (PS) stratification to control for potential confounders. We incorporated the results into prior knowledge by conducting a systematic literature review and a meta-analysis. Major congenital malformations were diagnosed in 37 out of 866 (4.27%) infants exposed to TDF and 38 out of 1,020 (3.73%) infants exposed to ART other than TDF; the adjusted RR was 1.21 (95% CI 0.77 to 1.90). Estimates for specific malformations were imprecise. The pooled RR from the meta-analysis with six prior studies was 0.88 (0.75 to 1.03). Based on evidence accumulated in patients with HIV, first trimester TDF use does not increase the risk of major congenital malformations overall in the newborn compared to other ART.The evidence of styrene as a human lung carcinogen has been inconclusive. Occupational cohorts within the reinforced plastics industry are an ideal population to study this association due to relatively high levels of exposure to styrene and lack of concomitant exposures to other known carcinogens. However, healthy worker survivor bias (HWSB), where healthier workers stay employed longer and thus have higher exposure potential, is a likely source of confounding bias for exposure-response associations, in part due to styrene's acute effects. We studied a cohort of 5163 boatbuilders exposed to styrene in Washington state employed between 1959 and 1978; prior regression analyses demonstrated little evidence for an exposure-response between styrene exposure and lung cancer mortality. Based on estimates of necessary components of HWSB, we found evidence for a potentially large HWSB. Using g-estimation of a structural nested model to account for HWSB we estimated that one year of exposure >30 ppm accelerates time to lung cancer death by 2.3 years (95% Confidence intervals=1.53, 2.94). Our results suggest possibly strong HWSB in our small cohort and indicate that large, influential studies of styrene exposed workers may suffer similar biases, warranting a re-assessment of the evidence of long-term health effects of styrene exposure.The two main phases of the mammalian cardiac cycle are contraction and relaxation; however, whether there is a connection between them in humans is not well understood. Routine exercise has been shown to improve cardiac function, morphology, and molecular signatures. Likewise, the acute and chronic changes that occur in the heart in response to injury, disease, and stress are well characterized, albeit not fully understood. In this study, we investigated how exercise and myocardial injury affect contraction-relaxation coupling. We retrospectively analyzed the correlation between the maximal speed of contraction and the maximal speed of relaxation of canine myocardium after receiving surgically induced myocardial infarction, followed by either sedentary recovery or exercise training for 10-12 wk. We used isolated right ventricular trabeculae, which were electrically paced at different lengths, frequencies, and with increasing β-adrenoceptor stimulation. In all conditions, contraction and relaxation were linearly correlated, irrespective of injury or training history.