Integration of automated morphological features resolves a distinct group of atypical chronic lymphocytic leukemias with chromosomal aberrations

Automated morphological assessment of peripheral blood slides has become an important modality facilitating characterization and quantification of cells in a uniform, fast and robust manner. In this study, we evaluated the morphological diversity in peripheral blood films of 94 chronic lymphocytic leukemia (CLL) patients using the DM1200 CellaVision automated microscopy system. Aberrant lymphocytes and smudge cells were enumerated and correlated with CLL immunophenotype, chromosomal aberrations and prognostic parameters. Herein, we show that the percentages of aberrant and smudge cells was highly variable between patients and did not correlate with each other. Increased aberrant lymphocytes and fewer smudge cells were associated with an atypical immunophenotype including low expression of CD23, higher levels of FMC7 and bright surface levels of CD20. High fraction of aberrant lymphocytes also was associated with trisomy 12. These cells were predominantly of small/medium size, sometimes with cleft nuclei. No correlation was noted between aberrant or smudge cells and clinical stage, CD38, ZA70 or time to first treatment. Taken together, automated morphological analysis of peripheral blood leukocytes emerged as a powerful and robust tool for the quantitative morphological stratification of CLL. Integration of the automated morphological features discriminates between different CLL phenotypes and distinct chromosomal aberrations.     

Diffuse excessive high signal intensity in low-risk preterm infants at term-equivalent age does not predict outcome at 1 year: a prospective study

Introduction

The outcome of premature infants with only diffuse excessive high signal intensity (DEHSI) is not clear. We explored the relationship between DEHSI, white matter (WM) diffusion characteristics, perinatal characteristics, and neurobehavioral outcome at 1 year in a homogenous group of preterm infants without major brain abnormalities.

Methods

Fifty-eight preterm infants, gestational age 29?±?2.6 weeks, underwent an MRI at term-equivalent age (TEA). Griffiths Mental Developmental Scales, neurological assessment, and Parental Stress Index (PSI) were performed at 1 year corrected age. These measures were compared between preterm infants according to DEHSI classification (none, mild, moderate). Diffusion tensor imaging was used in major WM volumes of interest to objectively measure the degree of WM maturation.

Results

No significant differences were detected in the perinatal risk characteristics, neurobehavioral outcome, and PSI at 1 year between infants with different DEHSI classifications. In infants with DEHSI, increased axial and radial diffusivities were detected in the optic radiations, centrum semiovale, and posterior limb of the internal capsule, indicating less advanced maturation of the WM. Significant correlations were detected between the time interval from birth to MRI and the WM microstructure in infants without DEHSI.

Conclusion

DEHSI in premature infants is neither a predictive measure for short-term adverse neurobehavioral outcome nor related to perinatal risk characteristics. Extrauterine exposure time had a differential effect on WM maturational trajectories in infants with DEHSI compared to those without. We suggest DEHSI may represent an alteration in WM maturational characteristics. Further follow-up studies may verify later consequences of DEHSI in premature infants.     

Modulated expression of WFDC1 during carcinogenesis and cellular senescence

Fibroblasts located adjacent to the tumor [cancer-associated fibroblasts (CAFs)] that constitute a large proportion of the cancer-associated stroma facilitate the transformation process. In this study, we compared the biological behavior of CAFs that were isolated from a prostate tumor to their normal-associated fibroblast (NAF) counterparts. CAFs formed more colonies when seeded at low cell density, exhibited a higher proliferation rate and were less prone to contact inhibition. In contrast to the general notion that high levels of alpha-smooth muscle actin serve as a marker for CAFs, we found that prostate CAFs express it at a lower level compared with prostate NAFs. Microarray analysis revealed a set of 161 genes that were altered in CAFs compared with NAFs. We focused on whey acidic protein four-disulfide core domain 1 (WFDC1), a known secreted protease inhibitor, and found it to be downregulated in the CAFs. WFDC1 expression was also dramatically downregulated in highly prolific mesenchymal cells and in various cancers including fibrosarcomas and in tumors of the lung, bladder and brain. Overexpression of WFDC1 inhibited the growth rate of the fibrosarcoma HT1080 cell line. Furthermore, WFDC1 level was upregulated in senescent fibroblasts. Taken together, our data suggest an important role for WFDC1 in inhibiting proliferation of both tumors and senescent cells. Finally, we suggest that the downregulation of WFDC1 might serve as a biomarker for cellular transformation.     

Engraftment of human blood malignancies to the turkey embryo: A robust new in vivo model

Xenografting of human blood malignancies to immunodeficient SCID mice is a powerful research tool. We evaluate here whether the immunodeficient turkey embryo can also serve as a xenograft host for human blood malignancies. Human leukemia, lymphoma and myeloma lines engrafted robustly into medullary and extramedullary tissues of turkey embryos as detected by PCR, FACS and histology in 8–10 days. Four of eleven patient AML samples also engrafted the bone marrow. Grafts of two lines responded to chemotherapy with doxorubicin. The turkey embryo therefore has the potential to be a complementary xenograft model for the study of human blood malignancies.     

Hormonal contraception,sexual behaviour and HIV prevalence among women in Cameroon

Background  

Data on the effect of contraceptive methods, other than the condom, on HIV acquisition is not clear. The aim of this study was to describe hormonal contraceptive use, sexual behaviour and HIV prevalence among women in Cameroon in order to provide baseline information for future analytical studies.     

Socioeconomic status and health behaviors as predictors of changes in self-rated health among older persons in Israel

There is a considerable body of scientific knowledge about factors associated with self-rated health (SRH), a common measure of health status. However, less is known about the factors associated with changes in SRH over time. In order to fill this gap, the aim of the current study was to examine a combination of socioeconomic, psychosocial, and health behaviour variables in explaining changes in SRH among older adults. The study used data from two time periods in Israel of the Survey of Health, Aging and Retirement in Europe (SHARE) to analyse the predictive contribution of Time 1 socioeconomic, psychosocial and behavioural variables and changes in these variables over time to changes in SHR. The sample included 1,549 older persons interviewed at baseline (years 2009–2010) and four years later (year 2013). Using bivariate and multivariate regression models, the findings show that 26 percent and 23 percent of the participants reported either improvement or a deterioration in their SRH, respectively. Decline in SRH was predicted by a combination of Time 1 socioeconomic (subjective assessment of a household's ability to make ends meet), psychosocial (QoL and in trust in people), and behavioural factors (moderate physical activity) and decline in these factors over time. The findings demonstrate that changes in those variables make an additional significant contribution for explaining changes in SRH. The findings suggest that in addition to identification of low SES, poor psychosocial and behavioural factors as risk factors to poor SRH changes in these factors should be monitored among older populations.     

Exploring the capacity of community-based organisations to absorb health system patient referrals for unmet social needs

This study examines the perspectives, resources, role and services provided by community-based organisations (CBOs) in response to the integration of health and social services to address individual unmet social needs, as well as the impact on organisational carrying capacity related to the ability to receive referrals from health system partners. Mixed methods combining qualitative interviews with 24 organisations and Social Network Analysis with 75 organisations were completed in 2018 in two communities (Denton, TX and Sarasota, FL) with robust examples of health and social systems alignment. Findings suggest that while community organisations are embedded in robust cross-sector networks, the potential increase in referrals from clinical settings is not something they are fully aware of, or prepared for, as evidenced by inadequate funding models, misalignment between capacity and capability, and a lack of coordination on screening and referral activities. Misalignment between clinical and CBO understanding of demand, needs and capacity present a potential risk in building strategies that integrate health and social services to address unmet social need. Failing to build a strong cross-sector screening and referral infrastructure that considers CBO capacity from the start could undermine the goal of improving population health through the integration of clinical and social care.