The fatty acyl composition of phospholipids determines the biophysical character of membranes and impacts the function of membrane proteins. Here, we define a nuclear receptor pathway for the dynamic ...modulation of membrane composition in response to changes in cellular lipid metabolism. Ligand activation of liver X receptors (LXRs) preferentially drives the incorporation of polyunsaturated fatty acids into phospholipids through induction of the remodeling enzyme Lpcat3. Promotion of Lpcat3 activity ameliorates endoplasmic reticulum (ER) stress induced by saturated free fatty acids in vitro or by hepatic lipid accumulation in vivo. Conversely, Lpcat3 knockdown in liver exacerbates ER stress and inflammation. Mechanistically, Lpcat3 modulates inflammation both by regulating inflammatory kinase activation through changes in membrane composition and by affecting substrate availability for inflammatory mediator production. These results outline an endogenous mechanism for the preservation of membrane homeostasis during lipid stress and identify Lpcat3 as an important mediator of LXR effects on metabolism.
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•Induction of Lpcat3 expression by LXRs promotes phospholipid remodeling•LXR-Lpcat3 activation drives unsaturated fatty acid incorporation into phospholipids•Lpcat3 activity in liver modulates lipid-induced ER stress and inflammation•Lpcat3 affects inflammation through regulation of membrane c-Src activity
Past climates inform our future Tierney, Jessica E; Poulsen, Christopher J; Montañez, Isabel P ...
Science,
11/2020, Letnik:
370, Številka:
6517
Journal Article
Recenzirano
Odprti dostop
As the world warms, there is a profound need to improve projections of climate change. Although the latest Earth system models offer an unprecedented number of features, fundamental uncertainties ...continue to cloud our view of the future. Past climates provide the only opportunity to observe how the Earth system responds to high carbon dioxide, underlining a fundamental role for paleoclimatology in constraining future climate change. Here, we review the relevancy of paleoclimate information for climate prediction and discuss the prospects for emerging methodologies to further insights gained from past climates. Advances in proxy methods and interpretations pave the way for the use of past climates for model evaluation-a practice that we argue should be widely adopted.
The purpose of this study was to use a large claims database to determine if there is a difference in opioid use after operative intervention for proximal humerus fractures in patients with known ...cannabis use compared with those who do not report cannabis use. The PearlDiver database was queried to find all patients who underwent proximal humerus open reduction and internal fixation. A group of patients with reported cannabis use or dependence was matched to a cohort without known cannabis use. Between the two groups, differences in the number of opioid prescriptions filled in the postoperative period (within 3 days), the morphine milligram equivalents (MMEs) prescribed in total and per day, and the number of opioid prescription refills were explored. There were 66,445 potential control patients compared with 1260 potential study patients. After conducting the propensity score match, a total of 1245 patients were included in each group. The patients in the cannabis group filled fewer opioid prescriptions (
=.045) and were prescribed fewer total MMEs (
=.044) in the first 3 days postoperatively. Results of this study indicate that patients who use cannabis products may use fewer opioids after proximal humerus open reduction and internal fixation.
. 2024;47(3):147-151..
Abstract
Background
It is unclear whether chronic use of immunosuppressive drugs worsens or improves the severity of coronavirus disease 2019 (COVID-19), with plausible mechanisms for both.
Methods
...Retrospective cohort study in 2121 consecutive adults with acute inpatient hospital admission between 4 March and 29 August 2020 with confirmed or suspected COVID-19 in a large academic health system, with adjustment for confounding with propensity score–derived stabilized inverse probability of treatment weights. Chronic immunosuppression was defined as prescriptions for immunosuppressive drugs current at the time of admission. Outcomes included mechanical ventilation, in-hospital mortality, and length of stay.
Results
There were 2121 patients admitted with laboratory-confirmed (1967, 93%) or suspected (154, 7%) COVID-19 during the study period, with a median age of 55 years (interquartile range, 40–67). Of these, 108 (5%) were classified as immunosuppressed before COVID-19, primarily with prednisone (>7.5 mg/day), tacrolimus, or mycophenolate mofetil. Among the entire cohort, 311 (15%) received mechanical ventilation; the median (interquartile range) length of stay was 5.2 (2.5–10.6) days, and 1927 (91%) survived to discharge. After adjustment, there were no significant differences in the risk of mechanical ventilation (hazard ratio HR, .79; 95% confidence interval CI, .46–1.35), in-hospital mortality (HR, .66; 95% CI, .28–1.55), or length of stay (HR, 1.16; 95% CI, .92–1.47) among individuals with immunosuppression and counterparts.
Conclusions
Chronic use of immunosuppressive drugs was neither associated with worse nor better clinical outcomes among adults hospitalized with COVID-19 in one US health system.
Among adults with confirmed or suspected coronavirus disease 2019 (COVID-19), chronic use of immunosuppressive drugs was neither associated with worse nor better clinical outcomes such as mechanical ventilation, in-hospital mortality, or length of stay.
A central goal of precision education (PE) is efficiently delivering the right educational intervention to the right learner at the right time. This can be achieved through a PE cycle that involves ...gathering inputs, using analytics to generate insights, planning and implementing interventions, learning and assessing outcomes, and then using lessons learned to inform modifications to the cycle. In this paper, the authors describe 3 PE initiatives utilizing this cycle. The Graduate Medical Education Laboratory (GEL) uses longitudinal data on graduate trainee behavior, clinical skills, and wellness to improve clinical performance and professional fulfillment. The Transition to Residency Advantage (TRA) program uses learner data from medical school coupled with individualized coaching to improve the transition to residency. The Anesthesia Research Group for Educational Technology (TARGET) is developing an automated tool to deliver individualized education to anesthesia residents based on a longitudinal digital representation of the learner. The authors discuss strengths of the PE cycle and transferrable learnings for future PE innovations. Common challenges are identified, including related to data (e.g., volume, variety, sharing across institutions, using the electronic health record), analytics (e.g., validating augmented intelligence models), and interventions (e.g., scaling up learner assessments with limited resources). PE developers need to share their experiences in order to overcome these challenges, develop best practices, and ensure ethical development of future systems. Adapting a common framework to develop and assess PE initiatives will lead to a clearer understanding of their impact, help to mitigate potential risks, and allow deployment of successful practices on a larger scale.
Intra-articular distal humerus fractures frequently require olecranon osteotomies for adequate exposure, but fixation of olecranon osteotomies is associated with high rates of hardware-related ...complications requiring subsequent reoperation for removal. Intramedullary screw fixation is an attractive option to attempt to minimize hardware prominence. The purpose of this biomechanical study is to directly compare intramedullary screw fixation (IMSF) with plate fixation (PF) of chevron olecranon osteotomies. It was hypothesized that PF would be biomechanically superior to IMSF.
Chevron olecranon osteotomies of 12 matched pairs of fresh-frozen human cadaveric elbows were repaired with either precontoured proximal ulna locking plates or cannulated screws with a washer. Displacement and amplitude of displacement at the dorsal and medial aspects of the osteotomies under cyclic loading conditions were measured. Finally, the specimens were loaded to failure.
The IMSF group had significantly greater medial displacement (P = .034) and dorsal amplitude (P = .029) than the PF group. Medial displacement was negatively correlated with bone mineral density in the IMSF group (r = −0.66, P = .035) but not in the PF group (r = .160, P = .64). Mean load to failure between groups, however, was not statistically significant (P = .183).
While there was no statistically significant difference in the load to failure between the two groups, IMSF repair resulted in significantly greater displacement of the medial osteotomy site during cyclic loading and greater amplitude of displacement dorsally with loading force. Decreased bone mineral density was associated with an increased displacement of the medial repair site. These results suggest that IMSF of olecranon osteotomies may result in increased fracture site displacement when compared to PF; this displacement may be greater in patients with poor bone quality.
Barrett's esophagus is thought to be a disease occurring predominantly in White Caucasian males of higher socioeconomic status. There are no published studies simultaneously examining risk of ...Barrett's esophagus according to ethnicity, gender, and socioeconomic status within a single data set. The authors conducted a retrospective case-control analysis within a cross-sectional study to determine risk of Barrett's esophagus in relation to sociodemographic variables in a large United Kingdom population. All patients undergoing upper gastrointestinal endoscopy at two clinical centers between January 2000 and January 2003 were evaluated. Data on ethnicity, age, gender, socioeconomic status, and the presence of Barrett's esophagus and esophagitis at endoscopy were collected. A total of 20,310 patients were analyzed. Barrett's esophagus was more common in White Caucasians (401/14,095 (2.8%)) than in South Asians (16/5,190 (0.3%)) (adjusted odds ratio (OR) = 6.03, 95% confidence interval (CI): 3.56, 10.22), as was esophagitis (2,500/14,095 (17.7%) vs. 557/5,190 (10.7%); adjusted OR = 1.76, 95% CI: 1.57, 1.97). Patients with Barrett's esophagus were also more likely to be male (adjusted OR = 2.70, 95% CI: 2.18, 3.35) and of higher socioeconomic status (adjusted OR = 1.58, 95% CI: 1.16, 2.15 (top tertile vs. bottom tertile)). White Caucasian ethnicity, male gender, and higher socioeconomic status are independent risk factors for Barrett's esophagus.
We tested the efficacy of a simple, visual cue to increase hand washing with soap and water. Automated towel dispensers in 8 public bathrooms were set to present a towel either with or without ...activation by users. We set the 2 modes to operate alternately for 10 weeks. Wireless sensors were used to record entry into bathrooms. Towel and soap consumption rates were checked weekly. There were 97,351 hand-washing opportunities across all restrooms. Towel use was 22.6% higher (P=.05) and soap use was 13.3% higher (P=.003) when the dispenser presented the towel without user activation than when activation was required. Results showed that a visual cue can increase hand-washing compliance in public facilities.
To examine the relationship between arthritis and fracture.
Women were classified into 3 self-reported groups at baseline: no arthritis (n = 83,295), osteoarthritis (OA; n = 63,402), and rheumatoid ...arthritis (RA; n = 960). Incident fractures were self-reported throughout followup. Age-adjusted fracture rates by arthritis category were generated, and the Cox proportional hazards model was used to test the association between arthritis and fracture.
After an average of 7.80 years, 24,137 total fractures were reported including 2559 self-reported clinical spinal fractures and 1698 adjudicated hip fractures. For each fracture type, age-adjusted fracture rates were highest in the RA group and lowest in the nonarthritic group. After adjustment for several covariates, report of arthritis was associated with increased risk for spine, hip, and any clinical fractures. Compared to the nonarthritis group, the risk of sustaining any clinical fracture in the OA group was HR 1.09 (95% CI 1.05, 1.13; p < 0.001) and HR 1.49 (95% CI 1.26, 1.75; p < 0.001) in the RA group. The risk of sustaining a hip fracture was not statistically increased in the OA group (HR 1.11; 95% CI 0.98, 1.25; p = 0.122) compared to the nonarthritis group; however, the risk of hip fracture increased significantly (HR 3.03; 95% CI 2.03, 4.51; p < 0.001) in the RA group compared to the nonarthritis group.
The increase in fracture risk confirms the importance of fracture prevention in patients with RA and OA.
The purpose of this study was to assess the maternal morbidity associated with attempted vaginal birth after cesarean (VBAC) in twin gestations using a large, nationwide sample of deliveries.
Data ...for this study were obtained from an administrative dataset, the Nationwide Inpatient Sample, a representative sample of discharges from non-Federal hospitals, for the years 1993 to 2002. Patients admitted nonemergently for the delivery of twin gestations who had a history of previous cesarean delivery were selected. Patients that either delivered vaginally or who had discharge codes that indicated labor before cesarean delivery were defined as the trial of labor group, while patients who had a cesarean delivery without discharge codes that indicated labor were defined as the elective cesarean group. Various complications of delivery were analyzed for each group.
We identified 4705 women who underwent an elective cesarean delivery and 1850 women who underwent a trial of labor. For women who had a trial of labor, 836 (45.2%) delivered vaginally. The rate of uterine rupture was higher in the trial of labor group than in the elective cesarean group (0.9% vs 0.1%,
P < .001), and the rate of wound complications was lower (0.6% vs 1.3%,
P < .02). The rates of other complications including hysterectomy, transfusion, major postpartum infection, thromboembolism, uterine dehiscence, and pelvic hematoma were not significantly different between the 2 groups.
Our study showed a significantly higher rate of uterine rupture in the trial of labor group that is similar to the rates reported for trial of labor after cesarean in singleton pregnancies.
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