Diabetic-associated stillbirth: incidence, pathophysiology, and prevention

All forms of diabetes during pregnancy are associated with an increased risk for stillbirth, defined as fetal death at greater than 20 weeks. The incidence of stillbirth in women who have diabetes has decreased dramatically with improved diabetes care. Diabetic-associated stillbirth is associated with hyperglycemia, resulting in fetal anaerobic metabolism with hypoxia and acidosis. Prevention of stillbirth in women who have diabetes hinges on intensive multidisciplinary prenatal care with control of blood sugars and appropriate fetal surveillance.     

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its therapeutic potential in breast and gynecologic cancers

OBJECTIVE: The relationship between the apoptotic pathway and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising area of scientific interest for cancer researchers. TRAIL-receptor-activating agents have demonstrated favorable in vitro and in vivo activity for the treatment of several malignancies including breast and gynecologic cancers. METHODS: This article reviews the available peer-reviewed literature and our own institution's experience with specific TRAIL-receptor-activating agents. Emphasis was placed on the apoptotic/TRAIL mechanism, preclinical evaluation, and phase I studies in various malignancies. RESULTS: Preclinical and early phase I studies indicate that these novel agents are safe with enhanced target specificity for malignancy. When these targeted agents are combined with conventional chemotherapy drugs or radiation therapy, they appear to increase cell death over single-agent modalities. CONCLUSIONS: TRAIL-receptor-activating agents represent an exciting new class of targeted therapies that hold promise to improve the treatment of women with breast and gynecologic malignancies.     

The effect of certification and preparation on teacher quality

To improve the quality of the teacher workforce, some states have tightened teacher preparation and certification requirements while others have eased requirements and introduced "alternative" ways of being certified to attract more people to teaching. Donald Boyd, Daniel Goldhaber, Hamilton Lankford, and James Wyckoff evaluate these seemingly contradictory strategies by examining how preparation and certification requirements affect student achivement. If strong requirements improve student outcomes and deter relatively few potential teachers, the authors say, then they may well be good policy. But if they have little effect on student achievement, if they seriously deter potential teachers, or if schools are able to identify applicants who will produce good student outcomes, then easing requirements becomes a more attractive policy. In reviewing research on these issues, the authors find that evidence is often insufficient to draw conclusions. They do find that highly selective alternative route programs can produce effective teachers who perform about the same as teachers from traditional routes after two years on the job. And they find that teachers who score well on certification exams can improve student outcomes somewhat. Limited evidence suggests that certification requirements can diminish the pool of applicants, but there is no evidence on how they affect student outcomes. And the authors find that schools have a limited ability to identify attributes in prospective teachers that allow them to improve student achievement. The authors conclude that the research evidence is simply too thin to have serious implications for policy. Given the enormous investment in teacher preparation and certification and given the possibility that these requirements may worsen student outcomes, the lack of convincing evidence is disturbing. The authors urge researchers and policymakers to work together to move to a more informed position where good resource decisions can be made.     

Plasma protein adsorption to surfaces grafted with dense homopolymer and copolymer brushes containing poly(N-isopropylacrylamide)

Growing polymer chains from surface initiators in principle allows much more dense polymer surface layers to be created than can be produced by grafting of whole (self-excluding) chains. We have utilized aqueous atom transfer radical polymerization to graft a series of cleavable hydrophilic poly(N-isopropylacrylamide) (PNIPAM) homopolymers and block copolymers of substituted acrylamides from polystyrene latex to give brushes of controlled MW and surface density. Average chain separations much less than their free solution radii of gyration have been achieved. Exposure to radiolabeled single proteins or to whole plasma and subsequent analysis by SDS-PAGE shows that PNIPAM brushes decrease protein adsorption relative to the latex surface or other substituted polyacrylamides. The PNIPAM brushes exhibit a second-order phase transition around 30 degrees C as reflected by a decrease in the hydrodynamic thickness of the brush at higher temperatures. Total plasma protein adsorption is increased at 40 degrees C compared to 20 degrees C but there is significant differential adsorption behavior among the proteins detected by gel-electrophoresis analysis.     

Modifier effect of the Toll-like receptor 4 D299G polymorphism in children with cystic fibrosis

Introduction Clinical phenotype varies amongst cystic fibrosis (CF) patients with identical CF transmembrane regulator (CFTR) genotype, suggesting genetic modifiers exist. One potential modifier is the Toll-like receptor 4 (TLR4) gene. TLR4 binds lipopolysaccharide (LPS), a constituent of Pseudomonas aeruginosa (PA), activating innate immunity and promoting inflammation. TLR4 polymorphisms are associated with LPS-hyporesponsiveness and may be protective in CF due to decreased inflammation. Materials and Methods DNA was extracted from blood of recruited CF subjects, and PCR performed to establish TLR4 D299G genotype. Case-notes were reviewed to obtain clinical data. Subjects possessing the TLR4 299G allele were compared with age, sex, and CFTR genotype-matched wild-type (299DD) subjects and also with all controls. Results 100 subjects (mean age 8.9 years) were studied, with 11 299DG heterozygotes identified. On case-matched analyses, no statistically significant differences between groups were found for mean ± SEM rates of change of %predicted FEV₁/year (0.9 ± 2.3 (DD) vs. − 3.9 ± 2.8 (DG), p = 0.22), %predicted FEV₁ (76 ± 8 vs. 74 ± 11), p = 0.91), or z scores for height ( − 0.47 ± 0.26 vs. − 0.24 ± 0.19, p = 0.48) and weight ( − 0.01 ± 0.22 vs. − 0.29 ± 0.27, p = 0.44). Median ± SE survival age at first PA isolation was also not significantly different (3.5 ± 2.1 vs. 6.5 ± 2.4 years, p = 0.29). No statistically significant differences were noted when 299DG heterozygotes were compared with all controls. Conclusions Potential reasons for absence of modifier effect include the basolateral location of TLR4 receptors on respiratory epithelium, or because inflammatory response to PA in the CF airway is so overwhelming that even a blunted response (as suggested for the 299G allele) results in increased inflammation and lung damage.     

Contributions of the Transplant Registry: The 2006 Annual Report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS)

This summary of the NAPRTCS 2006 Annual Report of the Transplant Registry highlights the significant impact the registry has had in advancing knowledge in pediatric renal transplantation worldwide. This cooperative group has collected clinical information on children undergoing a renal transplantation since 1987 and now includes over 150 participating medical centers in the USA, Canada, Mexico, and Costa Rica. Currently, the NAPRTCS transplant registry includes information on 9837 renal transplants in 8990 patients (NAPRTCS 2006 Annual Report). Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in outcome after renal transplantation in addition to identifying factors associated with both favorable and poor outcomes. The registry has served to document and influence practice patterns, clinical outcomes, and changing trends in renal transplantation.     

Is it a safe practice to administer oxygen during uncomplicated delivery: A randomized controlled trial?

Background

Newborns exposed to oxygen suffer from an oxidative stress with significant alterations in the concentrations of superoxide dismutase (SOD) and glutathione (GSSG).

Objective

To investigate the biological and clinical effects of oxygen administration to delivering mothers.

Methods

We conducted a randomized, double-blinded, controlled trial on a cohort of delivering women (n = 56) with an uncomplicated term pregnancy. Women were randomly assigned to one of two groups: Oxygen group or Room Air group. The Oxygen group received 100% oxygen (2 l/min) via nasal cannula for at least 30 min before delivery. Subjects in the Room Air group were connected to a nasal cannula while on room air. Concentrations of SOD (μg/g of Hb) and GSSG (μM/ml) were measured in maternal and umbilical cord blood. Bivariate and multivariate analyses were used to compare the two groups using the SAS system.

Results

Maternal SOD and GSSG did not differ between the two groups at baseline or after delivery. Concentrations of SOD and GSSG in umbilical cord blood did not differ between groups. More infants in Oxygen Group required delivery room resuscitation (20% vs. 0%, P = 0.03). This difference could not be explained by mode of delivery, infant sex, or other confounders.

Conclusions

Maternal exposure to oxygen during delivery is not associated with changes in umbilical cord SOD or GSSG. Further studies are needed to explore mechanisms responsible for the need of resuscitation in the oxygen group.     

Issues in febrile urinary tract infection management

Urinary tract infections are common occurrences in the pediatric age group and are a cause of significant morbidity and expense. The understanding of the consequences and sequelae of febrile urinary tract infections led to revision of standard protocols initiated by the American Academy of Pediatrics (AAP) in 1999. A less invasive protocol of radiologic evaluation has been the major outcome of the revised AAP guidelines. Emphasis on prevention of recurrent febrile urinary tract infections has also led to therapeutic programs that are centered less around the use of prophylactic antibiotics than has previously been the practice.