Variations in Prkdc and susceptibility to benzene-induced toxicity in mice.

Benzene, a carcinogen that induces chromosomal breaks, is strongly associated with leukemias in humans. Possible genetic determinants of benzene susceptibility include proteins involved in repair of benzene-induced DNA damage. The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), encoded by Prkdc, is one such protein. DNA-PKcs is involved in the nonhomologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here we compared the toxic effects of benzene on mice (C57BL/6 and 129/Sv) homozygous for the wild-type Prkdc allele and mice (129/SvJ) homozygous for a Prkdc functional polymorphism that leads to diminished DNA-PK activity and enhanced apoptosis in response to radiation-induced damage. Male and female mice were exposed to 0, 10, 50, or 100 ppm benzene for 6 h/d, 5 d/week for 2 weeks. Male mice were more susceptible to benzene toxicity compared with females. Hematotoxicity was evident in all male mice but was not seen in female mice. We observed similar, large increases in both micronucleated erythrocyte populations in all male mice. Female mice had smaller but significant increases in micronucleated cells. The p53-dependent response was induced in all strains and genders of mice following benzene exposure, as indicated by an increase in p21 mRNA levels in bone marrow that frequently corresponded with cell cycle arrest in G2/M. Prkdc does not appear to be a significant genetic susceptibility factor for acute benzene toxicity. Moreover, the role of NHEJ, mediated by DNA-PK, in restoring genomic integrity following benzene-induced DSB remains equivocal.     

Changes in the expression of the type-2 but not the type-1 cyclo-oxygenase enzyme in chorion-decidua with the onset of labour

Objective To determine the relative expression of cyclo-oxygenase (COX)-1 and COX-2 in the chorion-decidual part of human fetal membranes following delivery at term and to identify any changes in expression associated with labour.
Methods Fetal membranes were collected from 12 term pregnancies before labour following elective caesarean section and from 12 spontaneous vaginal deliveries. Expression of COX-1 and COX-2 mRNA was measured using a previously validated quantitative RT-PCR assay.
Results COX-2 expression exceeded that of COX-1 by approximately eight-fold. COX1 expression did not change but COX-2 expression was found to increase four-fold with labour.
Conclusions Chorion-decidua has the capacity to contribute to the increase in prostaglandin synthesis within the uterus associated with labour. As in the amnion, it is COX-2 and not COX-1 which is upregulated with labour. COX-2 selective anti-prostaglandins should therefore be as effective as nonselective drugs in inhibition of fetal membrane prostaglandin synthesis.     

Patterns and predictors of inpatient falls and fall-related injuries in a large academic hospital.

OBJECTIVES: Most research on hospital falls has focused on predictors of falling, whereas less is known about predictors of serious fall-related injury. Our objectives were to characterize inpatients who fall and to determine predictors of serious fall-related injury. METHODS: We performed a retrospective observational study of 1,082 patients who fell (1,235 falls) during January 2001 to June 2002 at an urban academic hospital. Multivariate analysis of potential risk factors for serious fall-related injury (vs no or minor injury) included in the hospital's adverse event reporting database was conducted with logistic regression to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CI95) RESULTS: The median age of patients who fell was 62 years (interquartile range, 49-77 years), 50% were women, and 20% were confused. The hospital fall rate was 3.1 falls per 1,000 patient-days, which varied by service from 0.86 (women and infants) to 6.36 (oncology). Some (6.1%) of the falls resulted in serious injury, ranging by service from 3.1% (women and infants) to 10.9% (psychiatry). The most common serious fall-related injuries were bleeding or laceration (53.6%), fracture or dislocation (15.9%), and hematoma or contusion (13%). Patients 75 years or older (aOR, 3.2; CI95, 1.3-8.1) and those on the geriatric psychiatry floor (aOR, 2.8; CI95, 1.3-6.0) were more likely to sustain serious fall-related injuries. CONCLUSIONS: There is considerable variation in fall rates and fall-related injury percentages by service. More detailed studies should be conducted by floor or service to identify predictors of serious fall-related injury so that targeted interventions can be developed to reduce them.     

Preservice early childhood students' perceptions of written feedback on their essays

Lecturer feedback on students' essays is important to the quality of the experience students have at university (Norton & Norton, 2001). The aim of the present study was to investigate whether early childhood students at one university actually read lecturer feedback on their essays and, if they did, what they found helpful and not helpful to their learning. Feedback was defined as 'giving students information on how well or how poorly they are doing in their academic work' (Hounsell, 1987, p. 109). Using the Vygotskian concept of learning as a socially shared activity, qualitative data were collected from second-year students from a four-year early childhood degree programme via an anonymous survey and four focus groups. Major findings were that, in contrast with studies of students in other programmes, early childhood students read lecturer feedback on their essays and used feedback that was detailed and explanatory as a learning tool. Types of feedback students found to be most and least useful were identified.     

What do pediatric primary care providers think are important research questions? A perspective from PROS providers.

OBJECTIVE: To describe what pediatric primary care providers involved in the Pediatric Research in Office Settings (PROS) research network think are important yet inadequately addressed questions in pediatric primary care research. METHODS: A total of 1785 pediatric primary care providers in the PROS network were asked what they thought were important yet inadequately addressed areas of primary care research. We used a single, open-ended question in a mail survey. Written answers to this question were analyzed by qualitative methods to determine the main themes of interest to pediatric primary care providers. RESULTS: Overall survey response rate was 48.7%; the open-ended question yielded 1109 individual answers. Six lines of inquiry were identified as being important to these providers: (1) effective counseling techniques to use in anticipatory guidance; (2) strategies to prevent and treat obesity; (3) the effectiveness of well-child care; (4) ongoing management of patients with attention-deficit/hyperactivity disorder; (5) the role of the primary care provider in caring for children with mental health needs; and (6) optimal organization of office practices. CONCLUSIONS: The translation of research into practice may be improved by a better understanding of the needs and interests of those who see pediatric patients in the primary care setting.     

Hepatic resections

Hepatic resection is the treatment of choice for many secondary and primary hepatic tumors. With improvement in surgical techniques and earlier recognition of hepatic tumors, there has been a renewed interest in performing hepatic resections. In this operative review, we will describe the techniques for performing right-sided and left-side hepatic resections. A major hepatic resection can be performed with less than 5% mortality and approximately a 5% to 15% morbidity. Special mention will be made of performing a hepatic resection without vascular inflow occlusion. This is necessary in performing a hepatic resection for use in live donor liver transplantation.     

Environmental risk factors and colorectal neoplasia: Recent developments

The vast majority of new cases of colorectal cancer, the second most common cause of death in men and women in the United States, are attributable to environmental rather than genetic causes. Recent research has clarified inconsistencies in the literature and has explored new pathways through which risk factors may act. This review discusses newly published, selected interesting and important findings in colorectal cancer etiology; these include postmenopausal hormone use, nonsteroidal anti-inflammatory drug use, obesity, physical activity, diet, and other confirmed epidemiologic associations. This research provides insight into mechanisms and offers opportunities for prevention.     

Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Effective and tolerable palliative treatments are needed for patients with incurable squamous cell carcinoma of the head and neck (SCCHN). Single-agent targeted therapies have limited activity in this setting. The feasibility of adding celecoxib to gefitinib for the treatment of incurable SCCHN is unknown. PATIENTS AND METHODS: Nineteen patients with unresectable recurrent locoregional and/or distant metastatic SCCHN with progressive disease after at least one prior chemotherapy or chemoradiotherapy regimen were enrolled onto this single-institution phase I study. Three dose levels were explored: (1) celecoxib 200 mg twice daily plus gefitinib 250 mg daily; (2) celecoxib 400 mg twice daily plus gefitinib 250 mg daily; and (3) celecoxib 400 mg twice daily plus gefitinib 500 mg daily. RESULTS: No dose-limiting toxicities were encountered at any dose level. The most common toxicities were acneiform rash, diarrhea, hand reaction, dyspepsia, and anemia. Four of 18 patients assessable for response (22%; 95% CI, 2% to 42%) achieved a confirmed partial response. CONCLUSION: The combination of gefitinib 500 mg daily plus celecoxib 400 mg twice daily is well-tolerated. The encouraging responses seen in this early study suggest further evaluation of epidermal growth factor receptor and cyclooxygenase-2 inhibitors in SCCHN is warranted.     

A realist qualitative study to explore how low‐income pregnant women use Healthy Start food vouchers

Healthy Start is the UK government's food voucher programme for low‐income pregnant women and young children. It was introduced in 2006, but the impact of the programme on nutritional outcomes remains understudied. This study sought to explore potential outcomes of the Healthy Start programme (including intended and unintended outcomes) and develop explanations for how and why these outcomes might occur. A realist review preceded this study, in which programme theories were developed and tested using existing evidence. This qualitative study aimed to further refine and consolidate the programme theories from the realist review while remaining open to new and emerging theories (or hypotheses) about how low‐income pregnant women use Healthy Start vouchers. Semistructured interviews were conducted with 11 low‐income women from North West England, who received Healthy Start vouchers during pregnancy. A realist logic of analysis was applied to generate clear and transparent linkages between outcomes and explanations. The findings suggested that some women used the vouchers to improve their diets during pregnancy (intended outcome), whereas some women were diverted towards alternative or unintended outcomes. Women's circumstances, values, beliefs, and motivations influenced how they perceived and responded to the vouchers. This paper presents four evidence‐based programme theories to explain four contrasting (and potentially overlapping) outcomes: dietary improvements (theory refined from review), shared benefits (new theory), financial assistance (theory refined from review), and stockpiling formula (new theory). It considers how the Healthy Start programme could be improved, to increase the possibilities for low‐income women to experience the intended outcome of dietary improvements.