Unusual presentation of Lisfranc fracture dislocation associated with high-velocity sledding injury: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Lisfranc fracture dislocations of the foot are rare injuries. A recent literature search revealed no reported cases of injury to the tarsometatarsal (Lisfranc) joint associated with sledding.</p> <p>Case presentation</p> <p>A 19-year-old male college student presented to the emergency department with a Lisfranc fracture dislocation of the foot as a result of a high-velocity sledding injury. The patient underwent an immediate open reduction and internal fixation.</p> <p>Conclusion</p> <p>Lisfranc injuries are often caused by high-velocity, high-energy traumas. Careful examination and thorough testing are required to identify the injury properly. Computed tomography imaging is often recommended to aid in diagnosis. Treatment of severe cases may require immediate open reduction and internal fixation, especially if the risk of compartment syndrome is present, followed by a period of immobilization. Complete recovery may take up to 1 year.</p

Global, regional, and national estimates of the impact of a maternal Klebsiella pneumoniae vaccine: A Bayesian modeling analysis.

BACKGROUND: Despite significant global progress in reducing neonatal mortality, bacterial sepsis remains a major cause of neonatal deaths. Klebsiella pneumoniae (K. pneumoniae) is the leading pathogen globally underlying cases of neonatal sepsis and is frequently resistant to antibiotic treatment regimens recommended by the World Health Organization (WHO), including first-line therapy with ampicillin and gentamicin, second-line therapy with amikacin and ceftazidime, and meropenem. Maternal vaccination to prevent neonatal infection could reduce the burden of K. pneumoniae neonatal sepsis in low- and middle-income countries (LMICs), but the potential impact of vaccination remains poorly quantified. We estimated the potential impact of such vaccination on cases and deaths of K. pneumoniae neonatal sepsis and project the global effects of routine immunization of pregnant women with the K. pneumoniae vaccine as antimicrobial resistance (AMR) increases. METHODS AND FINDINGS: We developed a Bayesian mixture-modeling framework to estimate the effects of a hypothetical K. pneumoniae maternal vaccine with 70% efficacy administered with coverage equivalent to that of the maternal tetanus vaccine on neonatal sepsis infections and mortality. To parameterize our model, we used data from 3 global studies of neonatal sepsis and/or mortality-with 2,330 neonates who died with sepsis surveilled from 2016 to 2020 undertaken in 18 mainly LMICs across all WHO regions (Ethiopia, Kenya, Mali, Mozambique, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, Brazil, Italy, Greece, Pakistan, Bangladesh, India, Thailand, China, and Vietnam). Within these studies, 26.95% of fatal neonatal sepsis cases were culture-positive for K. pneumoniae. We analyzed 9,070 K. pneumoniae genomes from human isolates gathered globally from 2001 to 2020 to quantify the temporal rate of acquisition of AMR genes in K. pneumoniae isolates to predict the future number of drug-resistant cases and deaths that could be averted by vaccination. Resistance rates to carbapenems are increasing most rapidly and 22.43% [95th percentile Bayesian credible interval (CrI): 5.24 to 41.42] of neonatal sepsis deaths are caused by meropenem-resistant K. pneumoniae. Globally, we estimate that maternal vaccination could avert 80,258 [CrI: 18,084 to 189,040] neonatal deaths and 399,015 [CrI: 334,523 to 485,442] neonatal sepsis cases yearly worldwide, accounting for more than 3.40% [CrI: 0.75 to 8.01] of all neonatal deaths. The largest relative benefits are in Africa (Sierra Leone, Mali, Niger) and South-East Asia (Bangladesh) where vaccination could avert over 6% of all neonatal deaths. Nevertheless, our modeling only considers country-level trends in K. pneumoniae neonatal sepsis deaths and is unable to consider within-country variability in bacterial prevalence that may impact the projected burden of sepsis. CONCLUSIONS: A K. pneumoniae maternal vaccine could have widespread, sustained global benefits as AMR in K. pneumoniae continues to increase

Comparison of phenomics and cfDNA in a large breast screening population: the Breast Screening and Monitoring Study (BSMS)

To assess their roles in breast cancer diagnostics, we aimed to compare plasma cell-free DNA (cfDNA) levels with the circulating metabolome in a large breast screening cohort of women recalled for mammography, including healthy women and women with mammographically detected breast diseases, ductal carcinoma in situ and invasive breast cancer: the Breast Screening and Monitoring Study (BSMS). In 999 women, plasma was analyzed by nuclear magnetic resonance (NMR) and Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) and then processed to isolate and quantify total cfDNA. NMR and UPLC-MS results were compared with data for 186 healthy women derived from the AIRWAVE cohort. Results showed no significant differences between groups for all metabolites, whereas invasive cancers had significantly higher plasma cfDNA levels than all other groups. When stratified the supervised OPLS-DA analysis and total cfDNA concentration showed high discrimination accuracy between invasive cancers and the disease/medication-free subjects. Furthermore, comparison of OPLS-DA data for invasive breast cancers with the AIRWAVE cohort showed similar discrimination between breast cancers and healthy controls. This is the first report of agreement between metabolomics and plasma cfDNA levels for discriminating breast cancer from healthy subjects in a true screening population. It also emphasizes the importance of sample standardization. Follow on studies will involve analysis of candidate features in a larger validation series as well as comparing results with serial plasma samples taken at the next routine screening mammography appointment. The findings here help establish the role of plasma analysis in the diagnosis of breast cancer in a large real-world cohort

Set Pseudophasors to Stun for Flow Cytometry

Study of signal transduction in live cells benefits from the ability to visualize and quantify light emitted by fluorescent proteins (XFPs) fused to different signaling proteins. However, because cell signaling proteins are often present in small numbers, and because the XFPs themselves are poor fluorophores, the amount of emitted light, and the observable signal in these studies, is often small. An XFP's fluorescence lifetime contains additional information about the immediate environment of the fluorophore that can augment the information from its weak light signal. Here, we constructed and expressed in Saccharomyces cerevisiae variants of Teal Fluorescent Protein (TFP) and Citrine that were isospectral but had shorter fluorescence lifetimes, ∼ 1.5 ns vs ∼ 3 ns. We modified microscopic and flow cytometric instruments to measure fluorescence lifetimes in live cells. We developed digital hardware and a measure of lifetime called a "pseudophasor" that we could compute quickly enough to permit sorting by lifetime in flow. We used these abilities to sort mixtures of cells expressing TFP and the short-lifetime TFP variant into subpopulations that were respectively 97% and 94% pure. This work demonstrates the feasibility of using information about fluorescence lifetime to help quantify cell signaling in living cells at the high throughput provided by flow cytometry. Moreover, it demonstrates the feasibility of isolating and recovering subpopulations of cells with different XFP lifetimes for subsequent experimentation

Conformational Changes and Slow Dynamics through Microsecond Polarized Atomistic Molecular Simulation of an Integral Kv1.2 Ion Channel

Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins—not to mention numerous applications in drug design. Here, we present a full 1 µs atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120° rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation (∼35°) of the extracellular end of all S4 segments is present also in a reference 0.5 µs simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 310 helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4–lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5–1 µs). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations

Association of blood lead concentrations with mortality in older women: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Blood lead concentrations have been associated with increased risk of cardiovascular, cancer, and all-cause mortality in adults in general population and occupational cohorts. We aimed to determine the association between blood lead, all cause and cause specific mortality in elderly, community residing women.</p> <p>Methods</p> <p>Prospective cohort study of 533 women aged 65–87 years enrolled in the Study of Osteoporotic Fractures at 2 US research centers (Baltimore, MD; Monongahela Valley, PA) from 1986–1988. Blood lead concentrations were determined by atomic absorption spectrometry. Using blood lead concentration categorized as < 8 μg/dL (0.384 μmol/L), and ≥ 8 μg/dL (0.384 μmol/L), we determined the relative risk of mortality from all cause, and cause-specific mortality, through Cox proportional hazards regression analysis.</p> <p>Results</p> <p>Mean blood lead concentration was 5.3 ± 2.3 μg/dL (range 1–21) [0.25 ± 0.11 μmol/L (range 0.05–1.008)]. After 12.0 ± 3 years of > 95% complete follow-up, 123 (23%) women who died had slightly higher mean (± SD) blood lead 5.56 (± 3) μg/dL [0.27(± 0.14) μmol/L] than survivors: 5.17(± 2.0) [0.25(± 0.1) μmol/L] (<it>p </it>= 0.09). Women with blood lead concentrations ≥ 8 μg/dL (0.384 μmol/L), had 59% increased risk of multivariate adjusted all cause mortality (Hazard Ratio [HR], 1.59; 95% confidence interval [CI], 1.02–2.49) (p = 0.041) especially coronary heart disease (CHD) mortality (HR = 3.08 [CI], (1.23–7.70)(p = 0.016), compared to women with blood lead concentrations < 8 μg/dL(< 0.384 μmol/L). There was no association of blood lead with stroke, cancer, or non cardiovascular deaths.</p> <p>Conclusion</p> <p>Women with blood lead concentrations of ≥ 8 μg/dL (0.384 μmol/L), experienced increased mortality, in particular from CHD as compared to those with lower blood lead concentrations.</p

Comparing administrative and survey data for ascertaining cases of irritable bowel syndrome: a population-based investigation

<p>Abstract</p> <p>Background</p> <p>Administrative and survey data are two key data sources for population-based research about chronic disease. The objectives of this methodological paper are to: (1) estimate agreement between the two data sources for irritable bowel syndrome (IBS) and compare the results to those for inflammatory bowel disease (IBD); (2) compare the frequency of IBS-related diagnoses in administrative data for survey respondents with and without self-reported IBS, and (3) estimate IBS prevalence from both sources.</p> <p>Methods</p> <p>This retrospective cohort study used linked administrative and health survey data for 5,134 adults from the province of Manitoba, Canada. Diagnoses in hospital and physician administrative data were investigated for respondents with self-reported IBS, IBD, and no bowel disorder. Agreement between survey and administrative data was estimated using the κ statistic. The χ²statistic tested the association between the frequency of IBS-related diagnoses and self-reported IBS. Crude, sex-specific, and age-specific IBS prevalence estimates were calculated from both sources.</p> <p>Results</p> <p>Overall, 3.0% of the cohort had self-reported IBS, 0.8% had self-reported IBD, and 95.3% reported no bowel disorder. Agreement was poor to fair for IBS and substantially higher for IBD. The most frequent IBS-related diagnoses among the cohort were anxiety disorders (34.4%), symptoms of the abdomen and pelvis (26.9%), and diverticulitis of the intestine (10.6%). Crude IBS prevalence estimates from both sources were lower than those reported previously.</p> <p>Conclusions</p> <p>Poor agreement between administrative and survey data for IBS may account for differences in the results of health services and outcomes research using these sources. Further research is needed to identify the optimal method(s) to ascertain IBS cases in both data sources.</p

Basin-scale transport of hydrothermal dissolved metals across the South Pacific Ocean

Hydrothermal venting along mid-ocean ridges exerts an important control on the chemical composition of sea water by serving as a major source or sink for a number of trace elements in the ocean(1-3). Of these, iron has received considerable attention because of its role as an essential and often limiting nutrient for primary production in regions of the ocean that are of critical importance for the global carbon cycle(4). It has been thought that most of the dissolved iron discharged by hydrothermal vents is lost from solution close to ridge-axis sources(2,5) and is thus of limited importance for ocean biogeochemistry(6). This long-standing view is challenged by recent studies which suggest that stabilization of hydrothermal dissolved iron may facilitate its longrange oceanic transport(7-10). Such transport has been subsequently inferred from spatially limited oceanographic observations(11-13). Here we report data from the US GEOTRACES Eastern Pacific Zonal Transect (EPZT) that demonstrate lateral transport of hydrothermal dissolved iron, manganese, and aluminium from the southern East Pacific Rise (SEPR) several thousand kilometres westward across the South Pacific Ocean. Dissolved iron exhibits nearly conservative (that is, no loss from solution during transport and mixing) behaviour in this hydrothermal plume, implying a greater longevity in the deep ocean than previously assumed(6,14). Based on our observations, we estimate a global hydrothermal dissolved iron input of three to four gigamoles per year to the ocean interior, which is more than fourfold higher than previous estimates(7,11,14). Complementary simulations with a global-scale ocean biogeochemical model suggest that the observed transport of hydrothermal dissolved iron requires some means of physicochemical stabilization and indicate that hydrothermally derived iron sustains a large fraction of Southern Ocean export productio