Purpose: Within a family medicine residency, an outpatient buprenorphine treatment program was provided for pregnant women who were dependent on opioids. The purpose of this study was to investigate the outcomes of infants who were exposed to a range of doses of buprenorphine in utero and to determine how closely observed maternal/fetal outcomes (eg, method of delivery and infants requiring treatment for neonatal abstinence syndrome [NAS]) match those previously reported in the literature.Methods: This study consists of a retrospective case series of 23 infants born to 22 pregnant women who were dependent on opioids and who were treated with buprenorphine during a 31-month period.Results: Thirty-five percent of infants (8 of 23) required treatment for NAS. There was no significant relationship between maternal dose of buprenorphine and birth weight, NAS severity (ie, peak NAS score), or time to first peak NAS score. Infants born to tobacco users had a significantly lower birth weight (P ؍ .0136) than infants born to nonusers. Seventy percent of infants (16 of 23) were breastfeeding at the time of discharge from the hospital.Conclusions: The observations made in this case series are consistent with data previously reported in the literature. Infants in this study were more likely to be breastfed than those previously described by others, but further analysis is necessary to determine whether this finding is significant. Estimates of illicit substance use during pregnancy are highly variable and range from 0.4% to 27% among all pregnant women in the United States.
Phosphoinositide 3-kinase (PI3K) family members are involved in diverse cellular fates including cell growth, proliferation, and survival. While many molecular details are known about the Class I and III PI3Ks, less is known about the Class II PI3Ks. To explore the function of all eight PI3K isoforms in autophagy, we knock down each gene individually and measure autophagy. We find a significant decrease in autophagy following siRNA-mediated PIK3C2A (encoding the Class 2 PI3K, PI3K-C2α) knockdown. This defective autophagy is rescued by exogenous PI3K-C2α, but not kinase-dead PI3K-C2α. Using confocal microscopy, we probe for markers of endocytosis and autophagy, revealing that PI3K-C2α colocalizes with markers of endocytosis. Though endocytic uptake is intact, as demonstrated by transferrin labeling, PIK3C2A knockdown results in vesicle accumulation at the recycling endosome. We isolate distinct membrane sources and observe that PI3K-C2α interacts with markers of endocytosis and autophagy, notably ATG9. Knockdown of either PIK3C2A or ATG9A/B, but not PI3KC3, results in an accumulation of transferrin-positive clathrin coated vesicles and RAB11-positive vesicles at the recycling endosome. Taken together, these results support a role for PI3K-C2α in the proper maturation of endosomes, and suggest that PI3K-C2α may be a critical node connecting the endocytic and autophagic pathways.
Porphyria cutanea tarda (PCT) is characterized by a skin blistering eruption that develops in sun exposed areas of the skin. It is the most common cutaneous porphyria world-wide, and classically associated with hepatic injury but also estrogen use, cigarette smoking, and HIV. In any case of photodistributed persistent blistering skin condition, PCT must be high on the differential. This case of a carpenter diagnosed with PCT not only illustrates a classic case but also the opportunity to achieve significant response to therapy in a motivated patient particularly with improved access to direct-acting antivirals (DAA) for hepatitis C treatment.
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