Publications

Provision of language services is central to the delivery of equitable, safe, high-quality health care for patients with limited English proficiency. However, there are many barriers to ensuring access to such services. We analyzed the experience of a model language service program at a public hospital to develop recommendations applicable to all hospitals that wish to create an effective language service program. Our case study demonstrates that with organizational commitment, early information technology involvement, attention to clinical needs, active engagement of stakeholders, and coordinated project management, it is possible to provide high-quality language services in a setting of financial constraints.

1,25 dihydroxyvitamin D(3) (1,25 (OH)2 D) and its less hypercalcemic analogues have been shown to inhibit the proliferation of vascular smooth muscle cells (VSMC) in culture. However, the mechanism(s) underlying this suppression is not well understood. Here we have shown that 1,25 (OH)2 D and its analogues (RO-25-6760 and RO-23-7553) inhibit endothelin (ET)-dependent DNA synthesis and cell proliferation in neonatal rat aortic VSMC. While ET stimulation of mitogenic activity requires activation of the MEK/ERK signal transduction cascade, 1,25 (OH)2 D neither affected the ET-dependent activation of ERK nor synergized with the MEK inhibitor PD98059 in reducing DNA synthesis in these cultures, implying that the locus of 1,25 (OH)2 D actions lies between ERK and the cell cycle machinery. 1,25 (OH)2 D suppressed ET-induced activation of cyclin-dependent kinase 2 (Cdk2), a key cell cycle kinase, but had no effect on the expression of this protein. Collectively, the data identify Cdk2 as the target of 1,25 (OH)2 D in the cell cycle machinery and imply a potential role for 1,25 (OH)2 D, or its less hypercalcemic analogues, in the treatment of disorders of VSMC proliferation involving the vascular wall.

Interstitial lung disease (ILD) is a common manifestation of systemic autoimmunity characterized by progressive inflammation or scarring of the lungs. Patients who develop these complications can exhibit significantly impaired gas exchange that may result in hypoxemia, pulmonary hypertension, and even death. Unfortunately, little is understood about how these diseases arise, including the role of specific defects in immune tolerance. Another key question is whether autoimmune responses targeting the lung parenchyma are critical to ILD pathogenesis, including that of isolated idiopathic forms. We show that a specific defect in central tolerance brought about by mutations in the autoimmune regulator gene (Aire) leads to an autoreactive T cell response to a lung antigen named vomeromodulin and the development of ILD. We found that a human patient and mice with defects in Aire develop similar lung pathology, demonstrating that the AIRE-deficient model of autoimmunity is a suitable translational system in which to unravel fundamental mechanisms of ILD pathogenesis.

Gene editing mediated by oligonucleotides has been shown to induce stable single base alterations in genomic DNA in both prokaryotic and eukaryotic organisms. However, the low frequencies of gene repair have limited its applicability for both basic manipulation of genomic sequences and for the development of therapeutic approaches for genetic disorders. Here, we show that single-stranded oligodeoxynucleotides (ssODNs) containing a methyl-CpG modification and capable of binding to the methyl-CpG binding domain protein 4 (MBD4) are able to induce >10-fold higher levels of gene correction than ssODNs lacking the specific modification. Correction was stably inherited through cell division and was confirmed at the protein, transcript and genomic levels. Downregulation of MBD4 expression using RNAi prevented the enhancement of gene correction efficacy obtained using the methyl-CpG-modified ssODN, demonstrating the specificity of the repair mechanism being recruited. Our data demonstrate that efficient manipulation of genomic targets can be achieved and controlled by the type of ssODN used and by modulation of the repair mechanism involved in the correction process. This new generation of ssODNs represents an important technological advance that is likely to have an impact on multiple applications, especially for gene therapy where permanent correction of the genetic defect has clear advantages over viral and other nonviral approaches currently being tested.

CONTEXT

Traditional measures of pregnancy intentions that are dichotomous and retrospective do not fully capture the complexity surrounding women's plans to become pregnant.

METHODS

During January-June 2008, 249 women aged 15-44 awaiting pregnancy test results at family planning clinics in Pittsburgh completed a survey containing both single- and multi-item measures of pregnancy intentions. Chi-square analyses were used to assess differences between subgroups of women.

RESULTS

Few women were trying to become or planning for pregnancy (11% on the single-item measure; 20% on the multi-item measure), while approximately one-third of the sample were not trying to become or planning for pregnancy (31% on the single-item and 36% on the multi-item measure). The single-item measure categorized more women as ambivalent about pregnancy (58%) than did the multi-item measure (44%). Of women categorized as ambivalent by the single-item measure, 62% were also categorized as ambivalent by the multi-item measure. Overall, 68% of responses to the two measures were concordant. With both measures, women who were not planning or trying for pregnancy were more likely than those who were planning for pregnancy or who were ambivalent to indicate that they planned to have an abortion if their test was positive (27-29% vs. 0-2%).

CONCLUSIONS

Prospective assessment of pregnancy intention with either a single- or a multi-item measure may allow for a more nuanced assessment of pregnancy intention than current measures. The multi-item measure may reduce the number of women categorized as ambivalent and aid the development of targeted contraceptive and preconception counseling interventions.