Publications

Bacterial binding to human platelets is an important step in the pathogenesis of infective endocarditis. Streptococcus gordonii can mediate its platelet attachment through a cell wall glycoprotein termed GspB ('gordonii surface protein B'). GspB export is mediated by a seven-component accessory Sec system, containing two homologues of the general secretory pathway (SecA2 and SecY2) and five accessory Sec proteins (Asps1-5). Here we show that the Asps are required for optimal export of GspB independent of the glycosylation process. Furthermore, yeast two-hybrid screening of the accessory Sec system revealed interactions occurring between Asp3 and the other components of the system. Asp3 was shown to bind SecA2, Asp1, Asp2 and itself. Mutagenesis of Asp3 identified N- and C-terminal regions that are essential for GspB transport, and conserved residues within the C-terminal domain mediated Asp3 binding to other accessory Sec components. The loss of binding by Asp3 also resulted in an impaired ability of S. gordonii to secrete GspB. These studies indicate that Asp3 is a central element mediating multiple interactions among accessory Sec components that are essential for GspB transport to the cell surface.

BACKGROUND

Certain medications increase the risk of birth defects whether used during pregnancy or immediately preconception.

OBJECTIVES

To describe dispensing of potentially teratogenic medications (Food and Drug Administration classes D or X) to female Veterans treated by the Veterans Affairs (VA) Healthcare System, and assess whether documented provision of family planning services is more common when potentially teratogenic medications are prescribed.

RESEARCH DESIGN

We examined all 2,634,441 prescriptions filled in fiscal year 2007 or 2008 by 78,232 female Veterans, aged 18 to 45, who made >or=2 visits to VA clinics within the year prior to medication dispensing from VA pharmacies.

MEASURES

: Medications dispensed, contraceptive counseling, and pregnancy testing.

RESULTS

Prescriptions for potentially teratogenic medications were filled by 48.8% of female Veterans who received medications from a VA pharmacy. Women who filled prescriptions for potentially teratogenic medications were only slightly more likely to have documented family planning services (eg, contraception, contraceptive counseling, or pregnancy testing) than women who filled class C, but not class D or X, prescriptions (55.7% vs. 51.8%). Women filling only class A or B prescriptions were least likely to have documented family planning services (35.9%). Among women dispensed potentially teratogenic medications, family planning services were significantly more likely to be documented for women who were >or=25 years (odds ratio [OR], 2.82; 95% confidence interval [CI], 2.57-3.11), unmarried (OR, 1.30; 95% CI, 1.23-1.35), non-White (OR, 1.17; 95% CI, 1.09-1.26), seen at a women's clinic (OR, 1.96; 95% CI, 1.88-2.05), received a retinoid medication (OR, 7.72; 95% CI, 3.02-19.7), or had serious mental illness (OR, 1.26; 95% CI, 1.18-1.34).

CONCLUSIONS

Medications that may cause birth defects if used during pregnancy are dispensed frequently to female Veterans by VA pharmacies without documented receipt of contraceptive counseling or pregnancy testing.

BACKGROUND

Lactation has been associated with improvements in maternal glucose metabolism.

METHODS

We explored the relationships between lactation and risk of type 2 diabetes in a well-characterized, population-representative cohort of women, aged 40-78 years, who were members of a large integrated health care delivery organization in California and enrolled in the Reproductive Risk factors for Incontinence Study at Kaiser (RRISK), between 2003 and 2008. Multivariable logistic regression was used to control for age, parity, race, education, hysterectomy, physical activity, tobacco and alcohol use, family history of diabetes, and body mass index while examining the impact of duration, exclusivity, and consistency of lactation on risk of having developed type 2 diabetes.

RESULTS

Of 2233 women studied, 1828 were mothers; 56% had breastfed an infant for > or =1 month. In fully adjusted models, the risk of type 2 diabetes among women who consistently breastfed all of their children for > or =1 month remained similar to that of women who had never given birth (odds ratio [OR] 1.01; 95% confidence interval [CI], 0.56-1.81). In contrast, mothers who had never breastfed an infant were more likely to have developed type 2 diabetes than nulliparous women (OR 1.93; 95% CI, 1.14-3.27) [corrected]. Mothers who never exclusively breastfed were more likely to have developed type 2 diabetes than mothers who exclusively breastfed for 1-3 months (OR 1.52; 95% CI, 1.11-2.10).

CONCLUSIONS

Risk of type 2 diabetes increases when term pregnancy is followed by <1 month of lactation, independent of physical activity and body mass index in later life. Mothers should be encouraged to exclusively breastfeed all of their infants for at least 1 month.