SUMMARY Microphthalmia-associated transcription factor (MITF) is a survival factor in melanocytes and melanoma cells. MITF regulates expression of anti-apoptotic genes and promotes lineage specific survival in response to ultraviolet (UV) radiation and to chemotherapeutics. SWI/SNF chromatin remodeling enzymes interact with MITF to regulate MITF target gene expression. We determined that the catalytic subunit, BRG1, of the SWI/SNF complex protects melanoma cells against UV-induced death. BRG1 prevents apoptosis in UV- irradiated melanoma cells by activating expression of the melanoma inhibitor of apoptosis (ML-IAP). Down-regulation of ML-IAP compromises BRG1 mediated survival of melanoma cells in response to UV-radiation. BRG1 regulates ML-IAP expression by cooperating with MITF to promote transcriptionally permissive chromatin structure on the ML-IAP promoter. The alternative catalytic subunit, BRM and the BRG1 associated factor, BAF180 were found to be dispensable for elevated expression of ML-IAP in melanoma cells. Thus, we illuminate a lineage-specific mechanism by which a specific SWI/SNF subunit, BRG1, modulates the cellular response to DNA damage by regulating an anti-apoptotic gene and implicate this subunit of the SWI/SNF complex in mediating the pro-survival function of MITF. SIGNIFICANCE SWI/SNF enzymes interact with the Microphthalmia-associated transcription factor (MITF) a lineage addiction oncogene, to promote MITF target gene expression in melanoma cells. In this study we determined that the SWI/SNF component, BRG1, promotes melanoma survival in response to UV-radiation, by activating expression of the melanoma inhibitor of apoptosis, ML-IAP gene. Our data show that BRG1 and MITF co-operate to establish permissive chromatin structure on the ML-IAP promoter and alter the association of other epigenetic regulators. Thus, we have elucidated a mechanism by which a component of the SWI/SNF complex promotes the pro-survival function of MITF. We further demonstrate that the BRG1 associated factor, BAF180, is not required for the activation of ML-IAP, suggesting that a specific configuration of the SWI/SNF complex mediates distinct activities. These results provide insight into how SWI/SNF function is deregulated in melanoma.

ability to estimate blood loss. All data were analyzed using chi square test.RESULTS: Underestimation was significantly higher at cesarean, occurring 65% versus 39% of the time at vaginal delivery (P5.002). Contrary to our hypothesis, overestimation was significantly higher at vaginal delivery, occurring 51% versus 33% of the time at cesarean (P5.007). Differences in resident versus attending ability to estimate blood loss did not reach statistical significance.CONCLUSION: Physicians significantly overestimated blood loss at vaginal delivery, and significantly underestimated blood loss at cesarean delivery. There was no difference in resident versus attending ability to estimate blood loss.

Purpose of review Maternal and congenital syphilis infection is on the rise in the United States and worldwide. Without adequate testing or provider recognition of infection, treatment can be neglected resulting in significant perinatal morbidity and mortality. This review article discusses the epidemiology of T. pallidum, describes novel diagnostic tests, and considers the need to expand therapeutic options. Recent findings A new chemiluminescence immunoassay for use in the reverse-sequence algorithm is more sensitive and specific in pregnant women than previously noted and is helpful for identifying pregnant women at highest risk for neonatal congenital syphilis. Point-of-care testing may be used to detect early syphilitic disease and provide same-day testing and treatment. Randomized control trials of oral cefixime for treatment of syphilis are paving the way for potential use in pregnant women. Penicillin skin testing, challenge, and desensitization in pregnancy can be done safely. Summary Congenital syphilis is a preventable disease and treatable infection in the modern world, but we are still met with challenges in its eradication. We should proceed with advancing efficient laboratory testing, expanding medical therapy, and implementing public health measures to curb the rise of the disease.

INTRODUCTION: Hospitals have been adapting quantitative blood loss (QBL) techniques over traditionally estimated blood loss (EBL), which has been shown to underestimate large volumes of blood loss. Our purpose was to determine the milliliters of blood loss where QBL better approximates EBL in vaginal deliveries. METHODS: Retrospective cohort study was conducted at a tertiary center examining blood loss from singleton term vaginal births. EBL and QBL groups each contained 6 separate months of deliveries and compared to a standard: calculated blood loss (CBL), determined by maternal size and hematocrit decrease. Absolute differences between calculated and recorded blood loss were computed and modeled against CBL. Multiple linear regression was used to control for confounders. RESULTS: CBL between EBL (n=1085) and QBL (n=1076) groups were not significantly different (P=.051), with a median of 685 (interquartile range 426-948) mL vs 697 (457-967) mL. Absolute difference between CBL and recorded blood loss was smaller in the EBL group [402 (178-644) mL] than QBL group [497 (268-716) mL]. Absolute differences were plotted: EBL (r^2 .84, P<.001) and QBL (r^2 .63, P<.001) groups exhibited linear relationships. Intersection of the linear models corresponded to 370 mL; beyond this value, QBL group demonstrated a smaller difference in comparison to EBL group. CONCLUSION: QBL measurements are not more accurate than EBL for uncomplicated vaginal deliveries with little blood loss. However, when blood loss measures greater than 370 mL, QBL is a better approximate. Further studies need to be done to validate role of CBL in determining blood loss for all delivery types.

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