Silent cerebral infarction,income, and grade retention among students with sickle cell anemia

Children with sickle cell anemia have a higher‐than‐expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross‐sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5–15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia. Am. J. Hematol. 89:E188–E192, 2014. © 2014 Wiley Periodicals, Inc.     

Outcome of deceased donor renal transplantation in patients with an ileal conduit

Renal transplantation in recipients with an ileal conduit is uncommon and occasionally controversial as it has been associated with high morbidity and mortality rates. We report on 17 patients with an ileal conduit who received a deceased donor renal transplant at our institution between January 1986 and December 2012. We retrospectively reviewed their allograft and surgical outcome. There were four mortalities at five, five, 39, and 66 months post‐transplant. Sixteen of 17 grafts functioned immediately; one patient had primary non‐function secondary to vascular thrombosis. Thirteen of 17 (76.5%) grafts were functioning at a mean follow‐up period of 105 months. The mean serum creatinine at follow‐up was 111 μM (±38.62). Five patients had seven episodes of urosepsis requiring hospital admission, and five patients received treatment for renal stone disease. We conclude that given improvements in immunosuppression, surgical technique, infection treatment, and selection criteria, we believe that renal transplantation in the patient with an ileal conduit yields excellent graft survival, although there is a high morbidity rate in this cohort of patients in the long term.     

The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cells

Neonates and infants are susceptible to infection due to distinct immune responses in early life. Therefore, development of vaccine formulation and delivery systems capable of activating human newborn leukocytes is of global health importance. Poly[di(carboxylatophenoxy)phosphazene] (PCPP) belongs to a family of ionic synthetic polyphosphazene polyelectrolyte compounds that can form non-covalent interactions with protein antigens and demonstrate adjuvant activity in animals and in human clinical trials. However, little is known about their ability to activate human immune cells. In this study, we characterized the effects of PCPP alone or in combination with a model antigen (recombinant HIV-Gag (Gag)), on the maturation, activation and antigen presentation by human adult and newborn dendritic cells (DCs) in vitro. PCPP treatment induced DC activation as assessed by upregulation of co-stimulatory molecules and cytokine production. Studies benchmarking PCPP to Alum, the most commonly used vaccine adjuvant, demonstrated that both triggered cell death and release of danger signals in adult and newborn DCs. When complexed with Gag antigen, PCPP maintained its immunostimulatory characteristics while permitting internalization and presentation of Gag by DCs to HIV-Gag-specific CD4⁺ T cell clones. The PCPP vaccine formulation outlined here has intrinsic adjuvant activity, can facilitate effective delivery of antigen to DCs, and may be advantageous for induction of beneficial T cell-mediated immunity. Moreover, polyphosphazenes can further reduce cost of vaccine production and distribution through their dose-sparing and antigen-stabilizing properties, thus potentially eliminating the need for cold chain distribution.     

Supporting women with learning disabilities in infant feeding decisions: A scoping review

Mothers with learning disabilities face many challenges during the perinatal period including preparing for and establishing infant feeding. Evidence shows that women with learning disabilities are less likely to breastfeed than other mothers. A scoping review was undertaken using Arksey and O''Malley''s methodology to understand what is known about how women with learning disabilities can be supported to make infant feeding decisions, particularly in relation to the use of appropriate and accessible images. An additional aim was to understand what further research is needed to achieve sustainable improvements to policy and practice in this area. A comprehensive search of fourteen electronic databases was undertaken to look for both published and grey literature. Initial searches, after removal of duplicates, resulted in 467 primary research articles plus 22 items of grey literature. Following a systematic process, three published papers and six items of grey literature were identified which met inclusion and exclusion criteria, five of which were resources. Little is known about the acceptability of existing resources, specifically in relation to the use of visual images. A synthesis of the grey literature and a thematic analysis of published literature was conducted and confirmed that women with learning disabilities need tailored support with infant feeding, including accessible resources and that there is a need for more in‐depth research in this area. There is a high level of agreement about the importance of using easily read visual images within these resources, but little evaluation of the types of imagery used or their aesthetic histories.     

Microtubule-associated protein 2: monoclonal antibodies demonstrate the selective incorporation of certain epitopes into Alzheimer neurofibrillary tangles.

Neurofibrillary tangles (NFT) are the principal structural alteration of neuronal cell bodies in Alzheimer disease as well as in normal aging of the human brain. While the ultrastructure of these intraneuronal lesions has been extensively studied, the biochemical composition of the fibers comprising the NFT is unknown. We report the production of three monoclonal antibodies against the microtubule-associated protein 2 (MAP-2), one of which intensely labels Alzheimer NFT. All three antibodies specifically recognize MAP-2 on immunoblots and stain brain tissue in a characteristic dendritic pattern. The three antibodies are directed against at least two different antigenic sites on the MAP-2 molecule, and one appears to recognize a phosphorylation site on MAP-2. That only one of the three antibodies immunolabels NFT suggests that the formation of the tangle involves some modification of the MAP-2 molecule. Our findings suggest that one aspect of Alzheimer-type neurofibrillary pathology is an aggregation of MAP-2 or MAP-2 fragments with altered neurofilamentous elements present in NFT. Normal interactive function, which putatively occurs between neurofilaments and MAP-2, may thus be disrupted in Alzheimer disease.     

Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFkappaB pathway

Dysfunctional endothelial cell activation and cytokines are implicated in preterm labor, a condition commonly treated with the tocolytic agent, magnesium sulfate (MgSO(4)). Based on recent findings showing the inflammatory effects of magnesium deficiency, we examined the effect of MgSO(4) on human umbilical vein endothelial cell (HuVEC) inflammatory responses in vitro. HuVECs isolated from term umbilical cords were incubated with MgSO(4) prior to stimulation with lipopolysaccharide (LPS) and then assessed for endothelial cell activation. Endothelial cell supernatants were assayed for inflammatory mediator production (interleukin-8; IL-8), and endothelial cell-associated intercellular adhesion molecule (ICAM-1) expression was determined. In the absence of LPS stimulation, MgSO(4) had no effect on HuVEC responses. Treatment of HuVECs with MgSO(4) prior to LPS stimulation inhibited inflammatory mediator production (p<0.05) and cell adhesion molecule expression (p<0.05) in a dose-dependent manner. Mechanistic studies showed that MgSO(4) reduced NFkappaB nuclear translocation and protected cytoplasmic IkappaBalpha from degradation in LPS-treated HuVECs. In conclusion, MgSO(4) inhibits endothelial cell activation, as measured by levels of IL-8 and ICAM-1 expression, via NFkappaB. Our results support the hypothesis that MgSO(4) treatment may function as an anti-inflammatory agent during preterm labor.     

Objective cervical portio length measurements: consistency and efficacy of screening for a short cervix

OBJECTIVE: To determine the consistency of 4-quadrant cervical portio length measurements with an objective cervical measuring device and to identify patients who may benefit from transvaginal ultrasound. STUDY DESIGN: Prenatal patients (12-34 weeks) derwent 4-quadrant cervical portio measurements and transvaginal ultrasound by different, blinded examiners. Cervical portio quadrant measures were analyzed by correlation analysis, and the predictive ability of cervical portio length measurements to identify short cervices with transvaginal ultrasound was assessed. RESULTS: The right and left lateral cervical portio measurements were consistently available and correlated highly with each other. Cervical portio length had excellent sensitivity (88%), specificity (92%) and negative predictive value (99%) in identifying patients with a short cervix (< 30 mm) by transvaginal ultrasound. CONCLUSION: Right and left lateral cervical portio length measurements are highly consistent and provide an effective screen for patients with short cervixes who may benefit from transvaginal ultrasound.