Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release

Ploidy could be the key to understanding megakaryocyte (MK) biologyand platelet production. Human CD34⁺ cells purified fromumbilical cord blood (CB) and peripheral blood (PB) were investigatedon their capability to give rise, in a serum-free medium containingthrombopoietin, to MKs and platelets. CB-MKs showed reducedpolyploidization and platelet number compared with PB-MKs, but asimilar membrane phenotype. Most CB-MKs showed a 2N content of DNA(~80%) and only 2.6% had 8N, whereas 40% of the PB cells had 8N ormore. Platelets were substantially released in PB culture from day 12;at day 14 the CB-derived MKs were able to release platelets although ata reduced level (~35%), correlating with their reduced size. Adirect correlation was demonstrated by sorting polyploid cells fromPB-MKs and evaluating the platelets released in the supernatant.Furthermore, the study analyzed the expression and distribution ofcyclin D3 and cyclin B1. Cyclin D3 protein was increased in PB incomparison to CB-MKs; in PB culture most cells rapidly became positive,whereas in CB-derived cells cyclin D3 expression was evident only fromday 9 and in a reduced percentage. Cyclin B1 was essentially localizedat the nuclear level in the CB and was expressed during the wholeculture. In PB-MKs, at day 9, a reduction was observed, correlatingwith an advanced ploidy state. The data indicate the inability of the CB-MKs to progress in the endomitotic process and a direct correlation between DNA content and platelet production.     

Varying sun protection of young children by migrant and Australian‐born mothers

Objective: To compare sun protection by Australian‐born and migrant mothers of three‐year‐old children. Methods: Australian‐born and migrant mothers taking part in the Environments for Healthy Living prospective birth‐cohort study were asked standard questions about their child's sun protection. Children were given a skin cancer susceptibility score based on grandparents' ethnic origin. Logistic regression was used to estimate odds ratios (ORs) to measure the association of sun protection of children according to mothers' migrant status adjusted for socio‐demographic characteristics. Results: A total of 613 Australian‐born and 224 migrant mothers of three‐year‐old children were studied. Mothers who had migrated less than four years ago were more likely to allow their three‐year‐old to spend more than two hours outdoors between 10 am and 3 pm compared to Australian‐born mothers (OR=2.80, 95%CI 1.20–6.57). Mothers from high latitude countries (>45 degrees) were more likely to apply sunscreen to their child than those from lower latitude countries (OR=3.15, 95%CI 1.03–9.61). Conclusions and implications: Strategies should aim to increase general awareness about the need for sun protection of young children, and recent migrants should be alerted to the harms of excessive sun exposure.     

Comparison of a Low,Fixed Dose and a High,Weight-Based Dose of Recombinant Factor VIIa in the Treatment of Warfarin-Associated Intracranial Hemorrhage

Background

Recombinant activated Factor VII (rFVIIa) can be used for rapid INR normalization in patients with warfarin-associated intracranial hemorrhage (WA-ICH); however, the optimal dose to normalize INR has not been established.

Methods

This is a retrospective review comparing two rFVIIa hospital protocols for WA-ICH [weight-based dose (80 mcg/kg) or fixed dose (2 mg)]. Primary endpoint was the percentage of patients with INR reversal (INR <1.3) at the next INR draw and the need for further doses of rFVIIa. Secondary endpoints included time to documented INR reversal and sustained INR normalization, morbidity, mortality, change in hematoma size, cost, and adverse drug reactions.

Results

Twenty-nine patients were included in each group. The weight-based group received a mean dose of 78.9 ± 21 mcg/kg versus 26.6 ± 8 mcg/kg in the fixed dose group. More patients in the fixed dose protocol achieved documented INR reversal than those in the weight-based group (92.6 vs 72.4 %, p = 0.19). The weight-based group achieved INR normalization in 229.5 [102, 331] minutes versus 165 [83, 447] minutes in the fixed dose group (p=0.02). Time to sustained INR normalization was similar in both groups. Four patients in the fixed dose group received an additional dose of 1 mg per hospital protocol. With the exception of medication acquisition cost savings of about $4,300 per patient who received fixed dose protocol, all other endpoints were similar between groups.

Conclusions

A low, fixed dose of rFVIIa appears to be as effective as a high, weight-based dose in achieving INR normalization in patients with WA-ICH.     

The Relation Between Health Insurance and Health Care Disparities Among Adults With Disabilities

Objectives. We examined disparities among US adults with disabilities and the degree to which health insurance attenuates disparities by race, ethnicity, and socioeconomic status (SES).Methods. We pooled data from the 2001–2007 Medical Expenditure Panel Survey on individuals with disabilities aged 18 to 64 years. We modeled measures of access and use as functions of predisposing, enabling, need, and contextual factors. We then included health insurance and examined the extent to which it reduced observed differences by race, ethnicity, and SES.Results. We found evidence of disparities in access and use among adults with disabilities. Adjusting for health insurance reduced these disparities most consistently for emergency department use. Uninsured individuals experienced substantially poorer access across most measures, including reporting a usual source of care and experiencing delays in or being unable to obtain care.Conclusions. Although health insurance is an important enabling resource among adults with disabilities, its effect on reducing differences by race, ethnicity, and SES on health care access and use was limited. Research exploring the effects of factors such as patient–provider interactions is warranted.Continuing its emphasis on reductions in health care disparities, Healthy People 2020 identifies the elimination of health disparities as 1 of 4 overarching goals.1 Congress has charged the Agency for Healthcare Research and Quality (AHRQ) with tracking disparities in health care access and quality among racial, ethnic, and socioeconomic groups, as well as for priority populations. In April 2012, AHRQ released its ninth report, finding that, although there was evidence of improvements in quality of care, health care access and quality are suboptimal, particularly for individuals who are racial/ethnic minorities or of lower socioeconomic status (SES).2An estimated 1 in 5 noninstitutionalized individuals in the United States experiences a disability.3 Although individuals with disabilities have been identified as a priority population by Congress,2 examining disparities among those with disabilities has garnered less attention. There is evidence that individuals with disabilities receive fewer preventive and treatment services than individuals without disabilities.4–7 Individuals with disabilities are more likely to report cost as a barrier to care,4,8 to report higher out-of-pocket costs,9 and to report unmet need for medical care.8Individuals with disabilities are disproportionately racial/ethnic minority and of lower SES. Rates of disability are higher for Blacks (22.2%) than for Hispanics (17.8%) and Whites (17.4%).3 Using data from the American Community Survey, Erickson and Lee10 found prevalence of disability to decline with increasing income. Disability is also associated with educational attainment. Substantially more people without a disability (30.8%) had a bachelor’s degree or higher than people with a disability (12.5%). Limited work has focused on disparities by race and SES on health care access and use among individuals with disabilities.11Health insurance provides an essential link to health services and outcomes,12,13 attenuating but not eliminating disparities by race and SES in the general population.14 Data from the 2010 American Community Survey indicate that, nationally, 82.1% of working-age individuals with disabilities had health insurance, compared with 78.2% among working-age individuals without disabilities.15 Nationally, 17.9% of working-age adults with disabilities were uninsured, but there was substantial state variability. Adults with disabilities are much more likely to have public, relative to private, coverage—50.5% public and 43% private coverage nationally in 2010 (some individuals have both public and private coverage). Research has rarely examined the extent to which health insurance coverage reduces potential disparities by race, ethnicity, and SES among individuals with disabilities. Thus, we extended the research on disparities among individuals with disabilities by examining whether minority and lower-SES adults with disabilities experience disparate access to and use of health care services.     

“I have got something positive out of this situation”: psychological benefits of caregiving in relatives of young people with muscular dystrophy

This paper focuses on the psychological benefits of caregiving in key relatives of patients with muscular dystrophies (MD), a group of rare diseases characterized by progressive weakness and restriction of the patient’s functional abilities. We describe whether relatives perceived caregiving to be a positive experience and test whether relatives’ perceptions vary in relation to their view of the patient as a valued person, the degree of involvement in care, and the level of support provided by social network and professionals. The study sample included 502 key relatives of patients aged 4–25 years, suffering from Duchenne, Becker, or limb-girdle MD, in treatment for at least 6 months to one of the eight participating centers, living with at least one relative aged 18–80 years. Of key relatives, 88 % stated that they had gotten something positive out of the situation, 96 % considered their patients to be sensitive, and 94 % viewed their patients as talented. Positive aspects of caregiving were more recognized by key relatives who were more convinced that the patient was sensitive and who perceived that they received higher level of professional help and psychological social support. These results suggest that most key relatives consider that their caregiving experience has had a positive impact on their lives, despite the practical difficulties of caring for patients with MD. Professionals should help relatives to identify the benefits of caregiving without denying its difficulties. Clinicians themselves should develop positive attitudes towards family involvement in the care of patients with long-term diseases.     

Association of a de novo 16q copy number variant with a phenotype that overlaps with Lenz microphthalmia and Townes-Brocks syndromes

Background  

Anophthalmia and microphthalmia are etiologically and clinically heterogeneous. Lenz microphthalmia is a syndromic form that is typically inherited in an X-linked pattern, though the causative gene mutation is unknown. Townes-Brocks syndrome manifests thumb anomalies, imperforate anus, and ear anomalies. We present a 13-year-old boy with a syndromic microphthalmia phenotype and a clinical diagnosis of Lenz microphthalmia syndrome.     

High resolution analysis of follicular lymphoma genomes reveals somatic recurrent sites of copy‐neutral loss of heterozygosity and copy number alterations that target single genes

A multiplatform approach, including conventional cytogenetic techniques, BAC array comparative genomic hybridization, and Affymetrix 500K SNP arrays, was applied to the study of the tumor genomes of 25 follicular lymphoma biopsy samples with paired normal DNA samples to characterize balanced translocations, copy number imbalances, and copy‐neutral loss of heterozygosity (cnLOH). In addition to the t(14;18), eight unique balanced translocations were found. Commonly reported FL‐associated copy number regions were revealed including losses of 1p32‐36, 6q, and 10q, and gains of 1q, 6p, 7, 12, 18, and X. The most frequent regions affected by copy‐neutral loss of heterozygosity were 1p36.33 (28%), 6p21.3 (20%), 12q21.2‐q24.33 (16%), and 16p13.3 (24%). We also identified by SNP analysis, 45 aberrant regions that each affected one gene, including CDKN2A, CDKN2B, FHIT, KIT, PEX14, and PTPRD, which were associated with canonical pathways involved in tumor development. This study illustrates the power of using complementary high‐resolution platforms on paired tumor/normal specimens and computational analysis to provide potential insights into the significance of single‐gene somatic aberrations in FL tumorigenesis. © 2010 Wiley‐Liss,Inc.