Role of the Funder/Sponsor: The Robert Wood Johnson Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Breastfeeding has been shown to improve maternal and child health. In Nicaragua, the primary risk of death and disability-adjusted life years among children under 5 years of age is suboptimal breastfeeding. Although the Nicaraguan Ministry of Health promotes exclusive breastfeeding from within the first half hour through the first 6 months of life, less than a third of children in the country under 6 months of age are exclusively breastfed. As part of a larger, mixed-methods study, 21 semi-structured, in-depth interviews were conducted with new mothers recruited from three primary health centers between June and August 2015 in order to identify the social, cultural, and structural factors that contribute to infant feeding practices and the discrepancy between recommendations and practices among mothers who delivered at an urban public hospital in León, Nicaragua. Audio recordings were transcribed verbatim, and interview transcripts were coded and analyzed by a three-member team using a grounded theory approach. Findings highlight a widespread perception of insufficient milk among mothers that influenced early cessation of exclusive breastfeeding and other infant feeding practices. This perception stemmed from anxiety about meeting infant nutritional needs and infant satiety, anxiety about maternal nutrition, advice from and role modeling of family members about mixed feeding, and perceived infant feeding norms. Results suggest that support modeled after the 10 steps of the Baby-friendly Hospital Initiative as well as strengthened policy-level support are needed. Community interventions that address cultural and structural barriers to improve breastfeeding practices may also help to increase breastfeeding rates.

Breastfeeding has been shown to benefit infants and mothers. Women who have caesarean deliveries (C-sections) are expected to be less likely to initiate and continue breastfeeding than those who have vaginal deliveries. Given the high rate of C-sections in Nicaragua, the importance of breastfeeding, and the centrality of culture in choices about breastfeeding, this study sought to examine if mode of delivery relates with breastfeeding initiation and exclusivity in Nicaragua.Two hundred fifty mothers were surveyed about birth experiences and breastfeeding behaviour

Vibrio cholerae, the causative agent of the human diarrheal disease cholera, exports numerous enzymes that facilitate its adaptation to both intestinal and aquatic niches. These secreted enzymes can mediate nutrient acquisition, biofilm assembly, and V. cholerae interactions with its host. We recently identified a V. cholerae-secreted serine protease, IvaP, that is active in V. cholerae-infected rabbits and human choleric stool. IvaP alters the activity of several host and pathogen enzymes in the gut and, along with other secreted V. cholerae proteases, decreases binding of intelectin, an intestinal carbohydrate-binding protein, to V. cholerae in vivo. IvaP bears homology to subtilisin-like enzymes, a large family of serine proteases primarily comprised of secreted endopeptidases. Following secretion, IvaP is cleaved at least three times to yield a truncated enzyme with serine hydrolase activity, yet little is known about the mechanism of extracellular maturation. Here, we show that IvaP maturation requires a series of sequential N- and C-terminal cleavage events congruent with the enzyme's mosaic protein domain structure. Using a catalytically inactive reporter protein, we determined that IvaP can be partially processed in trans, but intramolecular proteolysis is most likely required to generate the mature enzyme. Unlike many other subtilisin-like enzymes, the IvaP cleavage pattern is consistent with stepwise processing of the N-terminal propeptide, which could temporarily inhibit, and be cleaved by, the purified enzyme. Furthermore, IvaP was able to cleave purified intelectin, which inhibited intelectin binding to V. cholerae. These results suggest that IvaP plays a role in modulating intelectin–V. cholerae interactions.

Insulin is an essential medicine for people with diabetes (DM), but increasing prices have threatened its affordability. We examined the prevalence of and factors associated with cost-related insulin underuse. We administered a cross-sectional survey to patients with DM prescribed insulin at Yale Diabetes Center (YDC). Our primary outcome was cost-related underuse in the past 12 months, defined by a positive response to any 1 of 6 questions: Did you ⋯ 1) Use less insulin than prescribed 2) Try to stretch out your insulin 3) Take smaller doses of insulin than prescribed 4) Stop insulin 5) Not fill an insulin prescription 6) Not start insulin ⋯ because of cost? We examined the association of cost-related underuse with HbA1c >9% using logistic regression controlling for age, sex, age, DM duration, and income. Out of 354 patients prescribed insulin who had YDC visit in July 2017, 199 (56.2%) completed the survey (50.8% female, 60.8% white, 41.7% type 1). Of these patients, 51 (25.5%) reported cost-related insulin underuse. Patients with cost-related underuse had lower income levels, variable drug coverage and employment (Figure), and 3-fold higher odds of HbA1c >9% (p = 0.03) than patients who did not report underuse. One in four patients at our urban diabetes center reported cost-related insulin underuse, and this was associated with poor glycemic control. These results highlight an urgent need to address high insulin prices in the U.S. Disclosure D.M. Herkert: None. P. Vijayakumar: None. J. Luo: Consultant; Self; Alosa Health, Inc.. J. Schwartz: None. T.L. Rabin: None. E.M. DeFilippo: None. K.J. Lipska: Other Relationship; Self; Centers for Medicare and Medicaid Services. Research Support; Self; National Institutes of Health.