A multidrug ABC transporter with a taste for salt.

BACKGROUND: LmrA is a multidrug ATP-binding cassette (ABC) transporter from Lactococcus lactis with no known physiological substrate, which can transport a wide range of chemotherapeutic agents and toxins from the cell. The protein can functionally replace the human homologue ABCB1 (also termed multidrug resistance P-glycoprotein MDR1) in lung fibroblast cells. Even though LmrA mediates ATP-dependent transport, it can use the proton-motive force to transport substrates, such as ethidium bromide, across the membrane by a reversible, H(+)-dependent, secondary-active transport reaction. The mechanism and physiological context of this reaction are not known. METHODOLOGY/PRINCIPAL FINDINGS: We examined ion transport by LmrA in electrophysiological experiments and in transport studies using radioactive ions and fluorescent ion-selective probes. Here we show that LmrA itself can transport NaCl by a similar secondary-active mechanism as observed for ethidium bromide, by mediating apparent H(+)-Na(+)-Cl(-) symport. Remarkably, LmrA activity significantly enhances survival of high-salt adapted lactococcal cells during ionic downshift. CONCLUSIONS/SIGNIFICANCE: The observations on H(+)-Na(+)-Cl(-) co-transport substantiate earlier suggestions of H(+)-coupled transport by LmrA, and indicate a novel link between the activity of LmrA and salt stress. Our findings demonstrate the relevance of investigations into the bioenergetics of substrate translocation by ABC transporters for our understanding of fundamental mechanisms in this superfamily. This study represents the first use of electrophysiological techniques to analyze substrate transport by a purified multidrug transporter

A multidrug ABC transporter with a taste for salt.

BACKGROUND: LmrA is a multidrug ATP-binding cassette (ABC) transporter from Lactococcus lactis with no known physiological substrate, which can transport a wide range of chemotherapeutic agents and toxins from the cell. The protein can functionally replace the human homologue ABCB1 (also termed multidrug resistance P-glycoprotein MDR1) in lung fibroblast cells. Even though LmrA mediates ATP-dependent transport, it can use the proton-motive force to transport substrates, such as ethidium bromide, across the membrane by a reversible, H(+)-dependent, secondary-active transport reaction. The mechanism and physiological context of this reaction are not known. METHODOLOGY/PRINCIPAL FINDINGS: We examined ion transport by LmrA in electrophysiological experiments and in transport studies using radioactive ions and fluorescent ion-selective probes. Here we show that LmrA itself can transport NaCl by a similar secondary-active mechanism as observed for ethidium bromide, by mediating apparent H(+)-Na(+)-Cl(-) symport. Remarkably, LmrA activity significantly enhances survival of high-salt adapted lactococcal cells during ionic downshift. CONCLUSIONS/SIGNIFICANCE: The observations on H(+)-Na(+)-Cl(-) co-transport substantiate earlier suggestions of H(+)-coupled transport by LmrA, and indicate a novel link between the activity of LmrA and salt stress. Our findings demonstrate the relevance of investigations into the bioenergetics of substrate translocation by ABC transporters for our understanding of fundamental mechanisms in this superfamily. This study represents the first use of electrophysiological techniques to analyze substrate transport by a purified multidrug transporter

Determinants of stillbirths in Ghana: does quality of antenatal care matter?

BACKGROUND: Each year, over two million babies die before they are born. Like maternal deaths, the great majority of these stillbirths occur in developing countries, with about a third of all cases worldwide in sub-Saharan Africa (SSA). Few studies have, however, examined the determinants of stillbirths in SSA. In addition, the emphases on promoting deliveries by skilled birth attendants and/or in health facilities to prevent maternal deaths, though important, may have undermined efforts to provide good quality antenatal care (ANC), which may have an additional role in preventing stillbirths. This study examines the factors associated with stillbirths in Ghana, focusing on the role of ANC quality. METHODS: Data are from the Ghana Maternal Health Survey (N = 4,868)—a national survey of women of reproductive age. The main analysis includes women who had a pregnancy ending in a live birth or stillbirth in the five years preceding the survey and who received ANC at least once. ANC quality is measured by an index based on receipt (or otherwise) of nine antenatal services during the last pregnancy, including education about pregnancy complications; with receipt of at least of eight services classified as higher quality ANC. Stillbirths refer to babies born dead at seven or more months of pregnancy. Analytic techniques include multilevel logistic regression, with moderation and mediation analysis to examine conditional and intervening effects respectively. RESULTS: Higher quality ANC decreases the odds of a stillbirth by almost half after accounting for other factors, including the type of delivery provider and facility. Educating pregnant women about pregnancy complications contributes significantly to this difference by ANC quality. The type of delivery facility and provider account for a small proportion (14 %) of the ANC quality effect on stillbirths and a larger proportion of the rural/urban difference (27 %) in stillbirths. Completing the recommended four antenatal visits decreases the odds of a stillbirth. Having a pregnancy complication, a multiple gestation, a past stillbirth, or a sister who died from pregnancy complications increases the odds of a stillbirth. CONCLUSIONS: Good quality ANC can improve birth outcomes in two ways: directly through preventative measures, and indirectly through promoting deliveries in health facilities where complications can be better managed. Targeted programs and policies to increase ANC quality, including adequately educating women on pregnancy complications, will help improve birth outcomes in Ghana, and in SSA as a whole. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12884-016-0925-9) contains supplementary material, which is available to authorized users

Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic.

BACKGROUND: Surgical services are preparing to scale up in areas affected by COVID-19. This study aimed to evaluate the association between preoperative SARS-CoV-2 testing and postoperative pulmonary complications in patients undergoing elective cancer surgery. METHODS: This international cohort study included adult patients undergoing elective surgery for cancer in areas affected by SARS-CoV-2 up to 19 April 2020. Patients suspected of SARS-CoV-2 infection before operation were excluded. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery. Preoperative testing strategies were adjusted for confounding using mixed-effects models. RESULTS: Of 8784 patients (432 hospitals, 53 countries), 2303 patients (26.2 per cent) underwent preoperative testing: 1458 (16.6 per cent) had a swab test, 521 (5.9 per cent) CT only, and 324 (3.7 per cent) swab and CT. Pulmonary complications occurred in 3.9 per cent, whereas SARS-CoV-2 infection was confirmed in 2.6 per cent. After risk adjustment, having at least one negative preoperative nasopharyngeal swab test (adjusted odds ratio 0.68, 95 per cent confidence interval 0.68 to 0.98; P = 0.040) was associated with a lower rate of pulmonary complications. Swab testing was beneficial before major surgery and in areas with a high 14-day SARS-CoV-2 case notification rate, but not before minor surgery or in low-risk areas. To prevent one pulmonary complication, the number needed to swab test before major or minor surgery was 18 and 48 respectively in high-risk areas, and 73 and 387 in low-risk areas. CONCLUSION: Preoperative nasopharyngeal swab testing was beneficial before major surgery and in high SARS-CoV-2 risk areas. There was no proven benefit of swab testing before minor surgery in low-risk areas