Molecular mechanism of choline and ethanolamine transport in humans.

Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome2-7. Earlier studies concluded that FLVCR1 may function as a haem exporter8-12, whereas FLVCR2 was suggested to act as a haem importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14-16. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation-π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.

Seek and ye shall find: The utility of perioperative VTE screening in high-risk oncologic patients undergoing abdominopelvic surgery.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors associated with perioperative venous thromboembolism (VTE) in patients undergoing major oncologic surgery using an epidural catheter (EC) for postoperative analgesia with mechanical prophylaxis and without chemoprophylaxis. METHODS: Six hundred and twenty-six patients undergoing major oncologic surgery from 2009 to 2023 were evaluated. VTE was defined as deep vein thrombosis above the level of the knee. Lower extremity venous duplexes (LEVDs) were done preoperatively and postoperatively after the EC was removed. All patients received mechanical thromboprophylaxis, but not chemical prophylaxis, while the EC was in place. A generalized linear multivariable model was constructed to identify risk factors that predict pre and postoperative VTE. RESULTS: 29/626 patients (4.6%) were found to have preoperative VTE. 16/626 (2.6%) were found to have a postoperative VTE when their preoperative LEVD was negative. In comparison to patients without preoperative VTE, those with VTE were more likely to be male, anticoagulated, and have a history of coronary artery disease. Patients in the postoperative VTE group were older, male, anticoagulated, and had a history of VTE. On multivariable analysis, previous history of VTE was the risk factor most strongly associated with both pre and postoperative VTE. CONCLUSION: Oncologic patients undergoing elective abdominopelvic surgery with epidural analgesia should be screened in the perioperative setting with LEVD to identify VTE and possibly prevent PE.

Prediction of neonatal outcomes using gestational age vs ACOG definitions of maternal disease severity in hypertensive disorders of pregnancy.

PURPOSE: Hypertensive disorders of pregnancy cause significant neonatal complications. Disease severity is often used to predict neonatal outcomes, however gestational age (GA) at delivery may be a better predictor. We aimed to assess whether disease severity or GA was more predictive of adverse neonatal outcomes. METHODS: We included 165 participants with confirmed HELLP syndrome or severe preeclampsia (sPE). Two predictive models were constructed to assess the ability of disease severity compared to GA to predict a composite adverse neonatal outcome. The composite outcome included low birth weight, SGA, IUGR, Apgar score, and neonatal death. RESULTS: Using severity as a predictor of binary neonatal outcome had an AUC of 0.73 (0.65-0.81), with a sensitivity (SE) of 70.3% and a specificity (SP) of 64.4%. For GA, we observed an AUC of 0.82 (0.75-0.89), with a SE of 75.7% and a SP of 76.7%. CONCLUSION: For the composite neonatal outcome, GA was a better predictor than ACOG diagnosis (severity). This observation underscores the need for further research to validate these findings in larger cohorts and to determine their applicability to maternal outcomes.

The Association of Alcohol Outlet Density With Alcohol Intake: The Multiethnic Cohort.

OBJECTIVE: Neighborhood characteristics have been shown to influence lifestyle behaviors. Here we characterized alcohol outlet density in Los Angeles County, CA, and Hawaii and assessed the association of alcohol outlet density with self-reported alcohol intake in the Multiethnic Cohort. METHOD: Participants (n = 178,977) had their addresses geocoded at cohort entry (1993-1996) and appended to block group-level alcohol outlet densities (on- and off-premises). Multinomial logistic regression was performed to assess the association between self-reported alcohol intake and on- and off-premise alcohol outlet densities by each state. Stratified analysis was conducted by sex, race, and ethnicity. RESULTS: Overall, we did not find associations between alcohol outlet density and self-reported alcohol intake in Los Angeles County, but we found that on-premise alcohol outlets were associated with 59% (odds ratio [OR] = 1.59, 95% CI [1.29, 1.96]) increased odds of consuming more than two drinks per day in Hawaii. Women living in neighborhoods with a high density of on-premise alcohol outlets (Los Angeles County: OR = 1.15, 95% CI [0.95, 1.40]; Hawaii: OR = 2.07, 95% CI [1.43, 3.01]) had an increased odds of more than two drinks per day. CONCLUSIONS: This study suggests that neighborhood factors are associated with individual-level behaviors and that multilevel interventions may be needed.