Search

Membrane-bound O -acyltransferases (MBOATs) are membrane-embedded enzymes that catalyze acyl chain transfer to a diverse group of substrates, including lipids, small molecules, and proteins. MBOATs share a conserved structural core, despite wide-ranging functional specificity across both prokaryotes and eukaryotes. The structural basis of catalytic specificity, regulation and interactions with the surrounding environment remain uncertain. Here, we combine comparative molecular dynamics (MD) simulations with bioinformatics to assess molecular and interactional divergence across the family. In simulations, MBOATs differentially distort the bilayer depending on their substrate type. Additionally, we identify lipid binding sites surrounding reactant gates in the surrounding membrane. Complementary bioinformatic analyses reveal a conserved role for re-entrant loop-2 in MBOAT fold stabilization and a key hydrogen bond bridging DGAT1 dimerization. Finally, we predict differences in MBOAT solvation and water gating properties. These data are pertinent to the design of MBOAT-specific inhibitors that encompass dynamic information within cellular mimetic environments. [Display omitted] • MBOAT subfamilies differentially distort the surrounding bilayer • Conserved residue pairs on re-entrant loop-2 stabilize the MBOAT fold • A conserved hydrogen bond interconnects the DGAT1 dimer • Solvent gating and hydration properties differ across the family Ansell et al. use molecular dynamics simulations and bioinformatic analyses to compare interactions across the MBOAT family. MBOAT subfamilies differentially interact with themselves, the surrounding membrane, and solvent environments. These data are pertinent to the design of MBOAT-specific inhibitors and family classification. [ABSTRACT FROM AUTHOR]

1. Recognize the uniqueness of the early-phase clinical trial (EP-CT) patient population 2. Apply the concept of early intervention of supportive care services for patients with advanced cancer in EP-CTs Early-phase clinical trials (EP-CTs) investigate novel therapeutic approaches for people with cancer. Little is known about the use of supportive care (SC) services and timing of goals-of-care (GOC) discussions in EP-CTs. Analyze utilization of supportive care services and documentation of advance care planning by EP-CT participants. Retrospective review of electronic health records of consecutive patients enrolled in EP-CTs at Massachusetts General Hospital from 2017 to 2019. We collected information via electronic medical record to obtain baseline characteristics, receipt of SC services (palliative care [PC], social work [SW], physical therapy [PT], and nutrition), and documentation of GOC and code status discussions (before/during EP-CT vs after/never). Among 425 patients (median age 63.0; 56.0% female; 97.4% metastatic cancer, 22.1% gastrointestinal cancer), less than half received SC services before or during the trial (PC: 33.2% before/during, 66.8% post/never; SW: 41.9% before/during, 58.1% post/never; PT: 38.4% before/during, 61.6% post/never; and nutrition: 33.2% before/during, 62.1% post/never). Patients with gastrointestinal cancer were more likely to receive PC and SW before/during EP-CT (PC: 29.8% vs 18.3%, p = 0.009; SW: 27.5% vs 18.2%, p = 0.025), Earlier PC was associated with earlier hospice referral (HR = 1.95, p = 0.014) and shorter survival (HR = 1.54, p < 0.001). Patients receiving earlier SC services were more likely to have GOC discussions documented earlier (PC: 65.2% vs 13.0%, p < 0.001; SW: 41.0% vs 22.7%, p < 0.001; PT: 38.7% vs 25.2%, p = 0.005; nutrition: 39.1% vs 25.0%, p = 0.002). Patients with earlier PC were more likely to have earlier documented code status (46.8% vs 24.3%, p < 0.001) but not for any other service. Less than half of patients received SC services before or during their participation in EP-CTs. Those who received earlier SC services were more likely to have earlier documentation of GOC discussions. PC before or during EP-CT was associated with earlier code status, earlier hospice use, and shorter survival. Findings underscore the utility of supportive care services in EP-CTs. [ABSTRACT FROM AUTHOR]

Background: Maternal resuscitation in the emergency department requires planning and special consideration of the physiologic changes of pregnancy. Perimortem cesarean delivery (PMCD) is a rare but potentially life-saving procedure for both mother and fetus. Emergency physicians should be aware of the procedure's indications and steps because it needs to be performed rapidly for the best possible outcomes.Objective: We sought to review the approach to the critically ill pregnant patient in light of new expert guidelines, including indications for PMCD and procedural techniques.Discussion: The prevalence of maternal cardiac arrest and survival outcomes of PMCD in the emergency department setting are difficult to estimate. Advanced cardiovascular life support protocols should be followed in maternal arrest with special considerations made based on the physiologic changes of pregnancy. The latest recommendations for maternal resuscitation are reviewed, including advance planning, rapid determination of gestational age, emergent delivery, and postprocedure considerations for PMCD.Conclusions: Maternal resuscitation requires knowledge of physiologic changes and evidence-based recommendations. PMCD outcomes are best for both mother and fetus when the procedure is performed rapidly and efficiently in the appropriate setting. Emergency physicians should be familiar with this unique clinical scenario so they are adequately prepared to intervene in order to improve maternal and fetal morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Death from opioid abuse is a major public health issue. The death rate associated with opioid overdose nearly quadrupled from 1999 to 2008. Acute care settings are a major source of opioid prescriptions, often for minor conditions and chronic noncancer pain.Objective: Our aim was to determine whether a voluntary opioid prescribing guideline reduces the proportion of patients prescribed opioids for minor and chronic conditions.Methods: A retrospective chart review was performed on records of adult emergency department visits from January 2012 to July 2014 for dental, neck, back, or unspecified chronic pain, and the proportion of patients receiving opioid prescriptions at discharge was compared before and after the guideline. Attending emergency physicians were surveyed on their perceptions regarding the impact of the guideline on prescribing patterns, patient satisfaction, and physician-patient interactions.Results: In our sample of 13,187 patient visits, there was a significant (p < 0.001) and sustained decrease in rates of opioid prescriptions for dental, neck, back, or unspecified chronic pain. The rate of opioid prescribing decreased from 52.7% before the guideline to 29.8% immediately after its introduction, and to 33.8% at an interval of 12 to 18 months later. The decrease in opioid prescriptions was observed in all of these diagnosis groups and in all age groups. All 31 eligible prescribing physicians completed a survey. The opioid prescribing guideline was supported by 100% of survey respondents.Conclusions: An opioid prescribing guideline significantly decreased the rates at which opioids were prescribed for minor and chronic complaints in an acute care setting. [ABSTRACT FROM AUTHOR]

Expanding the Safety Net: Emergency Department-Based Gun Lock Distribution for Violence Prevention. [Extracted from the article]