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.

CONTEXT

Parent-adolescent communication is associated with increased adolescent contraceptive use. However, studies of this association are limited by their lack of examination of the communication process, reliance on cross-sectional designs and infrequent comparison of parent and adolescent perspectives. Examining communication in black families is particularly important, given the high pregnancy rate among black adolescents.

METHODS

Between December 2007 and March 2008, a total of 21 focus groups were conducted with 53 black families (68 parents and 57 adolescents) in Pennsylvania. Separate groups were held for males and females, and for parents and adolescents. The discussion guide explored family communication about sexual health topics, including contraception, family planning and abortion. Sessions were audio-recorded; data were transcribed and analyzed using a grounded theory approach to content analysis and the constant comparison method.

RESULTS

Five key themes emerged among both parents and adolescents. First, discussions about contraception were indirect and framed in terms of the need to avoid negative consequences of sex. Second, contraceptive knowledge was low. Third, parents more often reported helping male adolescents get condoms than helping females get contraceptives. Fourth, discussions emphasized planning for the future over contraception. Finally, negative attitudes toward abortion were prevalent.

CONCLUSIONS

Parent-adolescent communication interventions should improve contraceptive knowledge, help parents understand the harmful effects of gender biases in information dissemination, and provide mothers and fathers with communication skills tailored to enhance the role they play in their adolescents' sexual development.

PURPOSE

Initial weight loss improves urinary incontinence in overweight and obese women. In this study we examined the longer term effects of a weight loss intervention on urinary incontinence.

MATERIALS AND METHODS

Overweight and obese women (mean +/- SD age 53 +/- 10 years) with 10 or more urinary incontinence episodes weekly were randomized to an 18-month behavioral weight loss intervention (226) or control group (112). Outcome measures were collected at 12 and 18 months.

RESULTS

At baseline women had a mean body mass index of 36 +/- 6 kg/m(2) and reported a mean of 24 +/- 18 incontinence episodes weekly. Of the patients 86% completed 18-month measurements. The percent weight loss in the intervention group averaged 8.0%, 7.5% and 5.5% at 6, 12 and 18 months, respectively, vs approximately 1.5% in the control group (all values p <0.001). Compared with controls at 12 months the intervention group reported a greater percent reduction in weekly stress urinary incontinence episodes (65% vs 47%, p <0.001), and a greater proportion achieved at least a 70% decrease in weekly total and stress urinary incontinence episodes. At 18 months a greater proportion of women in the weight loss intervention group had more than 70% improvement in urge incontinence episodes but there were no significant differences between the groups for stress or total urinary incontinence. The intervention group also reported greater satisfaction with changes in urinary incontinence than the control group at 6, 12 and 18 months.

CONCLUSIONS

Weight loss intervention reduced the frequency of stress incontinence episodes through 12 months and improved patient satisfaction with changes in incontinence through 18 months. Improving weight loss maintenance may provide longer term benefits for urinary incontinence.

OBJECTIVE

Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure.

RESEARCH DESIGN AND METHODS

We evaluated the association of diabetes and A1C with incident heart failure in outpatients with stable CAD and no history of heart failure (average follow-up 4.1 years).

RESULTS

Of 839 participants, 200 had diabetes (23.8%). Compared with patients who did not have diabetes, those with diabetes had an increased risk of heart failure (hazard ratio [HR] 2.17 [95% CI 1.37-3.44]). Adjustment for risk factors for CAD (age, sex, race, smoking, physical inactivity, obesity, blood pressure, and LDL cholesterol), interim myocardial infarction, and myocardial ischemia did not alter the strength of the association between diabetes and heart failure. After inclusion also of other risk factors for heart failure (left ventricular ejection fraction, diastolic dysfunction, and C-reactive protein) and medication use, diabetes remained an independent predictor of heart failure (HR 3.34 [95% CI 1.65-6.76]; P = 0.001). Each 1% increase in A1C concentration was associated with a 36% increased HR of heart failure hospitalization (HR 1.36 [95% CI 1.17-1.58]).

CONCLUSIONS

In patients with stable CAD who are free from heart failure at baseline, diabetes and glycemic control are independent risk factors for new-onset heart failure. The mechanisms by which diabetes and hyperglycemia lead to heart failure deserve further study, as the association is independent of baseline functional assessment of ischemia, systolic and diastolic function, and interim myocardial infarction.