Neighborhood-scale lead (Pb) speciation in Akron, Ohio (USA) soils: primary sources, post-deposition diagenesis, and high concentrations of labile Pb.

Lead (Pb) poses a significant risk to infants and children through exposure to contaminated soil and dust. However, there is a lack of information on Pb speciation and distribution at the neighborhood-scale. This work aimed to determine: (1) the distribution of acid-extractable (labile) Pb and other metals ([M]AE) in two neighborhoods in Akron, Ohio (USA) (Summit Lake and West Akron; n = 82 samples); and (2) Pb speciation and potential sources. Total metal concentration ([M]T) and [M]AE was strongly correlated for Pb and Zn (R2 of 0.66 and 0.55, respectively), corresponding to 35% and 33% acid-extractability. Lead and Zn exhibited a strong positive correlation with each other (R2 = 0.56 for MT and 0.68 for MAE). Three types of Pb-bearing phases were observed by electron microscopy: (1) galena (PbS)-like (5-10 µm); (2) paint chip residuals (10-20 µm); and (3) Pb-bearing Fe-oxides (20 µm). Isotope ratio values for PbAE were 1.159 to 1.245 for 206Pb/207Pb, and 1.999 to 2.098 for 208Pb/206Pb, and there was a statistically significant difference between the two neighborhoods (p = 0.010 for 206Pb/207Pb and p = 0.009 for 208Pb/206Pb). Paint and petrol are the dominant sources of Pb, with some from coal and fly ash. Lead speciation and distribution is variable and reflects a complex relationship between the input of primary sources and post-deposition transformations. This work highlights the importance of community science collaborations to expand the reach of soil sampling and establish areas most at risk based on neighborhood-dependent Pb speciation and distribution for targeted remediation.

Inhibiting anti-angiogenic VEGF165b activates a miR-17-20a-Calcipressin-3 pathway that revascularizes ischemic muscle in peripheral artery disease.

BACKGROUND: VEGF165a increases the expression of the microRNA-17-92 cluster, promoting developmental, retinal, and tumor angiogenesis. We have previously shown that VEGF165b, an alternatively spliced anti-angiogenic VEGF-A isoform, inhibits the VEGFR-STAT3 pathway in ischemic endothelial cells (ECs) to decrease their angiogenic capacity. In ischemic macrophages (Møs), VEGF165b inhibits VEGFR1 to induce S100A8/A9 expression, which drives M1-like polarization. Our current study aims to determine whether VEGF165b inhibition promotes perfusion recovery by regulating the microRNA(miR)-17-92 cluster in preclinical PAD. METHODS: Femoral artery ligation and resection was used as a preclinical PAD model. Hypoxia serum starvation (HSS) was used as an in vitro PAD model. VEGF165b was inhibited/neutralized by an isoform-specific VEGF165b antibody. RESULTS: Here, we show that VEGF165b-inhibition induces the expression of miR-17-20a (within miR-17-92 (miR-17-18a-19a-19b-20a-92) cluster) in HSS-ECs and HSS-Møs vs. respective normal and/or isotype-matched IgG controls to enhance perfusion recovery. Consistent with the bioinformatics analysis that revealed RCAN3 as a common target of miR-17 and miR-20a, Argonaute-2 pull-down assays showed decreased miR-17-20a expression and higher RCAN3 expression in the RNA-induced silencing complex of HSS-ECs and HSS-Møs vs. respective controls. Inhibiting miR-17-20a induced RCAN3 levels to decrease ischemic angiogenesis and promoted M1-like polarization to impair perfusion recovery. Finally, using STAT3 inhibitors, S100A8/A9 silencers, and VEGFR1-deficient ECs and Møs, we show that VEGF165b-inhibition activates the miR-17-20a-RCAN3 pathway independent of VEGFR1-STAT3 or VEGFR1-S100A8/A9 in ischemic-ECs and ischemic-Møs respectively. CONCLUSIONS: Our data revealed a hereunto unrecognized therapeutic 'miR-17-20a-RCAN3' pathway in the ischemic vasculature that is VEGFR1-STAT3/S100A8/A9 independent and is activated only upon VEGF165b-inhibition in PAD.

Therapies that can grow new blood vessels in the ischemic muscle are necessary to restore blood flow and provide relief to patients with peripheral artery disease (PAD). We have previously shown that blocking VEGF₁₆₅b, a small protein involved in the regulation of regenerating blood vessels, promotes the growth of new blood vessels in the ischemic muscle. However, the mechanism by which this occurs is not clear. Here, we build on this existing knowledge and show the complex processes driving the growth of new blood vessels, which will help to supply blood to the ischemic muscle and provide therapeutic relief from PAD.

Pharmacy stewardship to reduce recurrent hypoglycemia.

BACKGROUND: Inpatient hypoglycemia is associated with increased morbidity and mortality. After a hypoglycemic event, the likelihood of additional episodes increases. The Joint Commission recommends evaluating all episodes of hypoglycemia for root-cause analysis. Studies have shown that pharmacists' involvement with glycemic control protocols can prevent hypoglycemia. OBJECTIVES: This study aimed to assess whether the implementation of pharmacists' real-time assessment of hypoglycemic events using an electronic alert messaging system contributes to the reduction of the number of recurrent hypoglycemia during hospitalization. PRACTICE DESCRIPTION: A community hospital that provides a wide range of health care services. The pharmacy department provides fully decentralized clinical services and team-based specialist services. PRACTICE INNOVATION: The pharmacist-led hypoglycemia stewardship initiative included a comprehensive review of hypoglycemic alerts received via an automated message. The alerts generated in the electronic health record (EHR) every time a patient's blood glucose resulted in less than 70 mg/dL if there was a documented administration of a hypoglycemic agent 48 hours before the hypoglycemia event. Once the alert was received by the pharmacists via an EHR in-basket, a real-time review was conducted to identify the potential causes of the event and opportunities for therapy modification. EVALUATION METHODS: A single-center retrospective observational study including a pre- and post-implementation phase from January 1 to June 3, 2020, and January 1 to June 30, 2021, respectively. Continuous data were analyzed using paired and equal variance t test. Noncontinuous data were analyzed using Fisher exact and chi-square test. Descriptive statistics were used to describe distribution and frequency of data. RESULTS: There was a 5.1% absolute reduction in recurrent hypoglycemic events (P < 0.001) and a 0.6% reduction of severe hypoglycemic days (P = 0.269) in the postimplementation group. The average time to pharmacist intervention was 4 (± 3.5) hours with a 92% acceptance rate. CONCLUSION: This study demonstrated the utility of pharmacist-led hypoglycemia reviews in the reduction of recurrent hypoglycemic events in the inpatient setting.

Altmetric analysis of the most mentioned articles online in the orthopaedic literature.

Social media has become a valuable tool for the distribution of scientific content. This investigation examined the most mentioned articles in orthopaedics and identified factors concurrent with greater dissemination. Altmetric Attention Score (AAS), which measures the online attention of an article, was examined for 88,683 publications in the top 50 orthopaedic journals by 2021 impact factor. Comparative and correlational analyses were completed. Overall, average AAS and citation count of the 100 most mentioned articles were 606.7 (SD ± 272.0) and 67.55 (SD ± 98.01), respectively. These articles had primarily male first authors (75%), were produced predominantly in the United States (60%), concerned the subspecialty of sports medicine (28%), and were cross-sectional analyses (22%). There were significant differences in AAS between publications (p < 0.05) by the degree of collaboration and the type of article. Such insights can guide authors when considering avenues to increase the impact of their research.

Global Quaternary Carbonate Burial: Proxy- and Model-Based Reconstructions and Persisting Uncertainties.

Constraining rates of marine carbonate burial through geologic time is critical for interpreting reconstructed changes in ocean chemistry and understanding feedbacks and interactions between Earth's carbon cycle and climate. The Quaternary Period (the past 2.6 million years) is of particular interest due to dramatic variations in sea level that periodically exposed and flooded areas of carbonate accumulation on the continental shelf, likely impacting the global carbonate budget and atmospheric carbon dioxide. These important effects remain poorly quantified. Here, we summarize the importance of carbonate burial in the ocean-climate system, review methods for quantifying carbonate burial across depositional environments, discuss advances in reconstructing Quaternary carbonate burial over the past three decades, and identify gaps and challenges in reconciling the existing records. Emerging paleoceanographic proxies such as the stable strontium and calcium isotope systems, as well as innovative modeling approaches, are highlighted as new opportunities to produce continuous records of global carbonate burial.

Does Construct Type Matter? A Retrospective Review Comparing Outcomes of Distal Radius Fractures Treated with Standard Volar Plating versus Fragment-Specific Fixation.

Background Treatment of intra-articular distal radius fractures (DRFs) rests on anatomic internal fixation. Fragment-specific fixation (FSF) is applied when fracture pattern is too complex for standard volar plating (SVP), oftentimes with potential increased risk of complications. We hypothesized that patients undergoing FSF would achieve less wrist range of motion (ROM) with higher risk of complications compared with SVP. Methods We conducted a retrospective review of 159 consecutive patients undergoing DRF fixation from 2017 to 2020. Patients < 18 years old, < 8 weeks' follow-up, open fractures, ipsilateral trauma, and fractures requiring dorsal spanning plate were excluded. Patient demographics, specific construct type, AO fracture classification, ROM, and complications were assessed. ROM was calculated using average flexion, extension, supination, and pronation. t -Tests were used to determine differences in ROM among construct types. Results Ninety-two patients met all inclusion criteria: 59 underwent SVP and 33 underwent FSF. Average wrist ROM for patients undergoing SVP was 57 degrees/50 degrees flexion-extension and 87 degrees/88 degrees supination-pronation; average ROM for patients undergoing FSF was 55 degrees/49 degrees flexion-extension and 88 degrees/89 degrees supination-pronation. No significant differences were identified when comparing final wrist flexion ( p = 0.08), extension ( p = 0.33), supination ( p = 0.35), or pronation ( p = 0.21). Overall reoperation rate was 5% and higher for FSF (12%) versus SVP (2%). Highest reoperation rate was observed in the double volar hook cohort (80%; N = 4). Conclusion Construct type does not appear to affect final ROM if stable internal fixation is achieved. SVP and FSF had similar complication rates; however, double volar hook constructs resulted in increased reoperations likely from fixation failure and plate prominence. Level of Evidence Level IV, retrospective review.

Effects of Autoclaving, EtOH, and UV Sterilization on the Chemical, Mechanical, Printability, and Biocompatibility Characteristics of Alginate.

Sterilization is a necessary step during the processing of biomaterials, but it can affect the materials' functional characteristics. This study characterizes the effects of three commonly used sterilization processes-autoclaving (heat-based), ethanol (EtOH; chemical-based), and ultraviolet (UV; radiation-based)-on the chemical, mechanical, printability, and biocompatibility properties of alginate, a widely used biopolymer for drug delivery, tissue engineering, and other biomedical applications. Sterility assessment tests showed that autoclaving was effective against Gram-positive and Gram-negative bacteria at loads up to 108 CFU/mL, while EtOH was the least effective. Nuclear magnetic-resonance spectroscopy showed that the sterilization processes did not affect the monomeric content in the alginate solutions. The differences in compressive stiffness of the three sterilized hydrogels were also not significant. However, autoclaving significantly reduced the molecular weight and polydispersity index, as determined via gel permeation chromatography, as well as the dynamic viscosity of alginate. Printability analyses showed that the sterilization process as well as the extrusion pressure and speed affected the number of discontinuities and spreading ratio in printed and cross-linked strands. Finally, human adipose-derived stem cells demonstrated over 90% viability in all sterilized hydrogels over 7 days, but the differences in cellular metabolic activity in the three groups were significant. Taken together, the autoclaving process, while demonstrating broad spectrum sterility effectiveness, also resulted in most notable changes in alginate's key properties. In addition to the specific results with the three sterilization processes and alginate, this study serves as a roadmap to characterize the interrelationships between sterilization processes, fundamental chemical properties, and resulting functional characteristics and processability of hydrogels.

Factors affecting sedimentational separation of bacteria from blood.

Rapid diagnosis of blood infections requires fast and efficient separation of bacteria from blood. We have developed spinning hollow disks that separate bacteria from blood cells via the differences in sedimentation velocities of these particles. Factors affecting separation included the spinning speed and duration, and disk size. These factors were varied in dozens of experiments for which the volume of separated plasma, and the concentration of bacteria and red blood cells (RBCs) in separated plasma were measured. Data were correlated by a parameter of characteristic sedimentation length, which is the distance that an idealized RBC would travel during the entire spin. Results show that characteristic sedimentation length of 20 to 25 mm produces an optimal separation and collection of bacteria in plasma. This corresponds to spinning a 12-cm-diameter disk at 3,000 rpm for 13 s. Following the spin, a careful deceleration preserves the separation of cells from plasma and provides a bacterial recovery of about 61 ± 5%.

Genome Sequences of Nine Erwinia amylovora Bacteriophages.

Erwinia amylovora is a plant pathogen belonging to the Enterobacteriaceae family, a family containing many plant and animal pathogens. Herein, we announce nine genome sequences of E. amylovora bacteriophages isolated from infected apple trees along the Wasatch Front in Utah.

Rapid separation of very low concentrations of bacteria from blood.

A rapid and accurate diagnosis of the species and antibiotic resistance of bacteria in septic blood is vital to increase survival rates of patients with bloodstream infections, particularly those with carbapenem-resistant enterobacteriaceae (CRE) infections. The extremely low levels in blood (1 to 100CFU/ml) make rapid diagnosis difficult. In this study, very low concentrations of bacteria (6 to 200CFU/ml) were separated from 7ml of whole blood using rapid sedimentation in a spinning hollow disk that separated plasma from red and white cells, leaving most of the bacteria suspended in the plasma. Following less than a minute of spinning, the disk was slowed, the plasma was recovered, and the bacteria were isolated by vacuum filtration. The filters were grown on nutrient plates to determine the number of bacteria recovered from the blood. Experiments were done without red blood cell (RBC) lysis and with RBC lysis in the recovered plasma. While there was scatter in the data from blood with low bacterial concentrations, the mean average recovery was 69%. The gender of the blood donor made no statistical difference in bacterial recovery. These results show that this rapid technique recovers a significant amount of bacteria from blood containing clinically relevant low levels of bacteria, producing the bacteria in minutes. These bacteria could subsequently be identified by molecular techniques to quickly identify the infectious organism and its resistance profile, thus greatly reducing the time needed to correctly diagnose and treat a blood infection.

Rapid separation of bacteria from blood - Chemical aspects.

To rapidly diagnose infectious organisms causing blood sepsis, bacteria must be rapidly separated from blood, a very difficult process considering that concentrations of bacteria are many orders of magnitude lower than concentrations of blood cells. We have successfully separated bacteria from red and white blood cells using a sedimentation process in which the separation is driven by differences in density and size. Seven mL of whole human blood spiked with bacteria is placed in a 12-cm hollow disk and spun at 3000rpm for 1min. The red and white cells sediment more than 30-fold faster than bacteria, leaving much of the bacteria in the plasma. When the disk is slowly decelerated, the plasma flows to a collection site and the red and white cells are trapped in the disk. Analysis of the recovered plasma shows that about 36% of the bacteria is recovered in the plasma. The plasma is not perfectly clear of red blood cells, but about 94% have been removed. This paper describes the effects of various chemical aspects of this process, including the influence of anticoagulant chemistry on the separation efficiency and the use of wetting agents and platelet aggregators that may influence the bacterial recovery. In a clinical scenario, the recovered bacteria can be subsequently analyzed to determine their species and resistance to various antibiotics.