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Evidence indicates hypervitaminosis A may be attributed to overconsumption of natural preformed vitamin A (VA) and overlapping VA intervention strategies. Hypervitaminosis A can disrupt metabolic processes; however, the extent and mechanisms of these impacts are not well understood. This study aims to assess metabolic differences related to hypervitaminosis A and VA supplementation by performing metabolomics analysis. A subsample of South African preschoolers participating in the country’s VA supplementation programme was selected. Participants were divided into two groups: adequate VA (n 15; 0·59–0·99 µmol/g total liver reserve and high VA (n 15; ≥ 1·0 µmol/g total liver reserve). Serum samples were collected at baseline and 28 d after consuming a 200 000 IU VA supplement. Lipidomics and oxylipins assays were conducted using ultraperformance LC-MS. At baseline, unsaturated lysophosphatidylcholines and unsaturated phosphatidylcholines were significantly lower in the high VA group (P < 0·05). A group-by-time interaction with VA supplementation was observed for polyunsaturated lysophosphatidylcholines and polyunsaturated phosphatidylcholines (P < 0·05). Additionally, a group effect was noted for oxylipins, and a time effect in response to VA supplementation was seen with decreased arachidonic acid and lipoxygenase- and non-enzymatically derived oxylipins (P < 0·05). Hypervitaminosis A is associated with modifications in lipids involved in cell structure and signalling, particularly unsaturated lysophosphatidylcholines and phosphatidylcholines. Further research is needed to identify the mechanisms behind these modifications, their physiological effects and their potential as biomarkers of elevated vitamin A status.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
Numerous studies have shown longer pre-hospital and in-hospital workflow times and poorer outcomes in women after acute ischemic stroke (AIS) in general and after endovascular treatment (EVT) in particular. We investigated sex differences in acute stroke care of EVT patients over 5 years in a comprehensive Canadian provincial registry.
Methods:
Clinical data of all AIS patients who underwent EVT between January 2017 and December 2022 in the province of Saskatchewan were captured in the Canadian OPTIMISE registry and supplemented with patient data from administrative data sources. Patient baseline characteristics, transport time metrics, and technical EVT outcomes between female and male EVT patients were compared.
Results:
Three-hundred-three patients underwent EVT between 2017 and 2022: 144 (47.5%) women and 159 (52.5%) men. Women were significantly older (median age 77.5 [interquartile range: 66–85] vs.71 [59–78], p < 0.001), while men had more intracranial internal carotid artery occlusions (48/159 [30.2%] vs. 26/142 [18.3%], p = 0.03). Last-known-well to comprehensive stroke center (CSC)-arrival time (median 232 min [interquartile range 90–432] in women vs. 230 min [90–352] in men), CSC-arrival-to-reperfusion time (median 108 min [88–149] in women vs. 102 min [77–141] in men), reperfusion status (successful reperfusion 106/142 [74.7%] in women vs. 117/158 [74.1%] in men) as well as modified Rankin score at 90 days did not differ significantly. This held true after adjusting for baseline variables in multivariable analyses.
Conclusion:
While women undergoing EVT in the province of Saskatchewan were on average older than men, they were treated just as fast and achieved similar technical and clinical outcomes compared to men.
New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.
To examine differences in surgical practices between salaried and fee-for-service (FFS) surgeons for two common degenerative spine conditions. Surgeons may offer different treatments for similar conditions on the basis of their compensation mechanism.
Methods:
The study assessed the practices of 63 spine surgeons across eight Canadian provinces (39 FFS surgeons and 24 salaried) who performed surgery for two lumbar conditions: stable spinal stenosis and degenerative spondylolisthesis. The study included a multicenter, ambispective review of consecutive spine surgery patients enrolled in the Canadian Spine Outcomes and Research Network registry between October 2012 and July 2018. The primary outcome was the difference in type of procedures performed between the two groups. Secondary study variables included surgical characteristics, baseline patient factors, and patient-reported outcome.
Results:
For stable spinal stenosis (n = 2234), salaried surgeons performed statistically fewer uninstrumented fusion (p < 0.05) than FFS surgeons. For degenerative spondylolisthesis (n = 1292), salaried surgeons performed significantly more instrumentation plus interbody fusions (p < 0.05). There were no statistical differences in patient-reported outcomes between the two groups.
Conclusions:
Surgeon compensation was associated with different approaches to stable lumbar spinal stenosis and degenerative lumbar spondylolisthesis. Salaried surgeons chose a more conservative approach to spinal stenosis and a more aggressive approach to degenerative spondylolisthesis, which highlights that remuneration is likely a minor determinant in the differences in practice of spinal surgery in Canada. Further research is needed to further elucidate which variables, other than patient demographics and financial incentives, influence surgical decision-making.
The purpose of this document is to highlight practical recommendations to assist acute care hospitals to prioritize and implement strategies to prevent ventilator-associated pneumonia (VAP), ventilator-associated events (VAE), and non-ventilator hospital-acquired pneumonia (NV-HAP) in adults, children, and neonates. This document updates the Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA), and is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the American Hospital Association, the Association for Professionals in Infection Control and Epidemiology, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.
Eggs contain important compounds related to enhanced cognition, but it is not clear if egg consumption, as a whole, has a direct impact on memory decline in older adults. This study aimed to determine whether egg intake levels predict the rate of memory decline in healthy older adults after sociodemographic and dietary controls. We conducted a secondary analysis of data from 470 participants, age 50 and over, from the Biospsychosocial Religion and Health Study. Participants completed a food frequency questionnaire, which was used to calculate egg intake and divide participants into Low (<23 g/week, about half an egg), Intermediate (24–63 g/week, half to 1½ eggs) and High (≥63 g/week, about two or more eggs) tertiles. Participants were administered the California Verbal Learning Test – 2nd Edition (CVLT-II) Short Form in 2006–2007, and 294 of them were again tested in 2010–2011. Using linear mixed model analysis, no significant cross-sectional differences were observed in CVLT-II performance between egg intake levels after controlling for age, sex, race, education, body mass index, cardiovascular risk, depression and intake of meat, fish, dairy and fruits/vegetables. Longitudinally, the Intermediate egg group exhibited significantly slower rates of decline on the CVLT-II compared to the Low egg group. The High egg group also exhibited slower rates of decline, but not statistically significant. Thus, limited consumption of eggs (about 1 egg/week) was associated with slower memory decline in late life compared to consuming little to no eggs, but a dose-response effect was not clearly evident. This study may help explain discrepancies in previous research that did not control for other dietary intakes and risk factors.
Skin is the parchment upon which identity is written; class, race, ethnicity, and gender are all legible upon the human surface. Removing skin tears away identity, and leaves a blank slate upon whichlaw, punishment, sanctity, or monstrosity can be inscribed; whether as an act of penal brutality, as a comic device, or as a sign of spiritual sacrifice, it leaves a lasting impression about the qualities and nature of humanity. Flaying often functioned as an imaginative resource for medieval and early modern artists and writers, even though it seems to have been rarely practiced in reality. From images of Saint Bartholomew holding his skin in his arms, to scenes of execution in Havelok the Dane, to laws that prescribed it as a punishment for treason, this volume explores the ideaand the reality of skin removal - flaying - in the Middle Ages. It interrogates the connection between reality and imagination in depictions of literal skin removal, rather than figurative or theoretical interpretations of flaying, and offers a multilayered view of medieval and early modern perceptions of flaying and its representations in European culture. Its two parts consider practice and representation, capturing the evolution of flaying as both an idea and a practice in the premodern world.
Larissa Tracy is Associate Professor, Longwood University.
Contributors: Frederika Bain, Peter Dent, Kelly DeVries, Valerie Gramling, Perry Neil Harrison, Jack Hartnell, Emily Leverett, Michael Livingston, Sherry C.M. Lindquist, Asa Mittman, Mary Rambaran-Olm, William Sayers, Christina Sciacca, Susan Small, Larissa Tracy, Renée Ward
An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown.
Methods
Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA).
Results
BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). Neither the change in KynA/QA, nor baseline KynA/QA were associated with response to BA therapy.
Conclusion
The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.
Conventional longitudinal behavioral genetic models estimate the relative contribution of genetic and environmental factors to stability and change of traits and behaviors. Longitudinal models rarely explain the processes that generate observed differences between genetically and socially related individuals. We propose that exchanges between individuals and their environments (i.e., phenotype–environment effects) can explain the emergence of observed differences over time. Phenotype–environment models, however, would require violation of the independence assumption of standard behavioral genetic models; that is, uncorrelated genetic and environmental factors. We review how specification of phenotype–environment effects contributes to understanding observed changes in genetic variability over time and longitudinal correlations among nonshared environmental factors. We then provide an example using 30 days of positive and negative affect scores from an all-female sample of twins. Results demonstrate that the phenotype–environment effects explain how heritability estimates fluctuate as well as how nonshared environmental factors persist over time. We discuss possible mechanisms underlying change in gene–environment correlation over time, the advantages and challenges of including gene–environment correlation in longitudinal twin models, and recommendations for future research.
Background: Surgical site infections (SSIs) among cardiothoracic (CT) patients are associated with high rates of morbidity and mortality. Data are limited regarding SSI incidence among pediatric patients undergoing primary reparative procedures for congenital cardiac disease. Published evidence on targeted interventions to prevent pediatric CT-surgery SSI is lacking. We aimed to establish standard metrics for measuring CT-surgery SSI incidence and to implement bundled interventions for SSI prevention. Methods: A dedicated CT-surgery SSI prevention workgroup was established, consisting of hospital leadership, CT surgeons, cardiac critical care unit staff, anesthesia, perfusion, environmental services, instrument sterile processing, risk management, infection prevention and antibiotic stewardship. We created a standard definition for CT-surgery SSI and calculated retrospective SSI rates over a 24-month period (2017–2019). The outcome measured was incidence of CT-surgery SSI per 100 primary cardiac procedures with delayed ( 3 days after primary surgery) or non-delayed chest closure. The difference in proportion of SSI was reported separately for delayed closure and non-delayed closure; statistical significance was tested using a Fisher’s Exact test. We identified many potential improvement opportunities, including gaps in SSI surveillance, poor compliance with daily bathing, inconsistent perioperative antimicrobial prophylaxis, lack of controlled environment for bedside chest closures, and lapses in environmental cleaning. These issues informed the enhanced SSI prevention bundle, which included education on sterility with the operating room (OR) staff. Protocols for care of cardiac patients with delayed chest closures focused on universal daily and preoperative chlorhexidine baths. In addition, the bundle incorporated stringent environmental cleaning interventions including scheduled decluttering of patient rooms and clinical spaces, terminal cleaning of patient rooms prior to returning from the OR, and use of adjunctive ultraviolet light for the daily cleaning of operating rooms and patient rooms at discharge. Results: Surveillance definition of microbiological growth from a clinical sample obtained within 30 days of primary cardiac procedure sufficiently captured all CT-surgery SSIs. Of 551 CT-surgery procedures prior to intervention, 91 (17%) had delayed final operative closures. Prior to the intervention, 16 SSIs were identified from July 2017 – May 2019 for a rate of 2.90 per /100 procedures, and was higher among patients with delayed chest closure 6.59 per /100 procedures (6 SSIs/91 procedures) versus those with primary chest closure 2.17 per /100 procedures (10 SSIs/460 procedures; P = 0.034). Gram-positive organisms, including coagulase coagulase-negative Staphylococci, were most frequently identified as the causative organisms for SSIs. Compliance with bundled intervention, rolled out over a 2-month period, was associated with an immediate decrease in the number of SSIs for primary and delayed chest closures 6SSIs /185 procedures in the initial quarters (August – December 2019) of the post-intervention period. However, this decrease was not reflected in the overall rate (3.24 per /100 procedures) due to fewer procedures performed. Data collection to measure sustainability is ongoing. Conclusions: Bundled interventions targeting skin antisepsis and environmental cleaning may be associated with a decrease in SSIs among pediatric CT-surgery patients. Ongoing surveillance is required to determine sustainability of these interventions.
Carbapenem-resistant Enterobacterales (CRE) are common causes of healthcare-associated infections and are often multidrug resistant with limited therapeutic options. Additionally, CRE can spread within and between healthcare facilities, amplifying potential harms.
Objective:
To better understand the burden, risk factors, and source of acquisition of carbapenemase genes in clinical Escherichia coli and Klebsiella spp isolates from patients in Washington to guide prevention efforts.
Design:
Multicenter prospective surveillance study.
Methods:
Escherichia coli and Klebsiella spp isolates meeting the Washington state CRE surveillance case definition were solicited from clinical laboratories and tested at Washington Public Health Laboratories using polymerase chain reaction (PCR) for the 5 most common carbapenemase genes: blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48. Case patients positive by PCR were investigated by the public health department.
Results:
From October 2012 through December 2017, 363 carbapenem-resistant E. coli and Klebsiella spp isolates were tested. Overall, 45 of 115 carbapenem-resistant K. pneumoniae (39%), 1 of 8 K. oxytoca (12.5%), and 28 of 239 carbapenem-resistant E. coli (11.7%) were carbapenemase positive. Of 74 carbapenemase-positive isolates, blaKPC was most common (47%), followed by blaNDM (30%), blaOXA-48 (22%), and blaIMP (1%). Although all cases had healthcare exposure, blaKPC acquisition was associated with US health care, whereas non-blaKPC acquisition was associated with international health care or travel.
Conclusions:
We report that blaKPC, the most prevalent carbapenemase in the United States, accounts for nearly half of carbapenemase cases in Washington state and that most KPC-cases are likely acquired through in-state health care.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Trauma bypass has been introduced successfully worldwide with sustained reductions in mortality/morbidity. Analyzing structure, process, and outcome individually and collectively in systems has been found to focus improvement efforts in the audit cycle. The second Irish report on Major Trauma Audit (MTA) was published in December 2017. The median age of trauma patients in Ireland was 59, indicating an aging trauma population. 28% of patients required secondary transfer to complete their care. The mortality rate for 2016 was only 4%.
Aim:
To determine the ability of a road-based EMS system to bring patients from areas of Wexford County to proposed receiving centers within 60-90 minutes.
Methods:
Analysis took population centers in Wexford County, used Google Maps to estimate travel times at 3pm on a weekday, and proposed new trauma units and centers in Dublin, Cork, and Waterford.
Results:
In Wexford County urban centers, >95% of patients will not reach a trauma unit in less than 60 minutes with current prehospital medical service capabilities. This even excludes response/on-scene time by prehospital practitioners in land-based EMS vehicles.
Discussion:
The proposed introduction of trauma bypass systems in Ireland should not disenfranchise patients with respect to the standards they are currently receiving. Gap analysis suggests considerable work is required within the ambulance service to increase critical skill levels of paramedics to support critical patients in the golden hour of their transfer. An increase in vehicles/resources will be required to ensure adequate staffing to meet Health Information and Quality Authority (HIQA) targets of 8 and 19 minutes for response acuity, and for longer durations of transport allied to dynamic resource deployment model as used by National Emergency Operations Centre (NEOC). Unintended consequences of system changes will need to be monitored carefully to avoid further adversely impacting recruitment of staff to bypassed Model 3 hospitals.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.