Evaluation of the Safety of Uninterrupted Warfarin Anticoagulation With Tranexamic Acid in Total Joint Arthroplasty.

BACKGROUND: The continuation of long-term warfarin therapy is gaining acceptance in minor surgeries but maintaining therapeutic international normalized ratio (INR) values among patients during major orthopedic procedures raises concern. While bridging therapy with low-molecular-weight heparin is currently recommended for patients receiving anticoagulation, few studies have evaluated the safety of continuing warfarin during total joint arthroplasty. This study evaluated the safety and efficacy of continuous warfarin anticoagulation through total joint arthroplasty with and without prophylactic tranexamic acid (TXA). MATERIALS AND METHODS: We conducted a retrospective, matched-pair analysis of two experimental groups of patients who underwent primary total hip arthroplasty or total knee arthroplasty performed by a single surgeon. Our first experimental group, warfarin plus TXA (warfarin+TXA), consisted of 21 patients who underwent arthroplasty while receiving therapeutic anticoagulation with warfarin (INR, 2.0-3.0) and who received prophylactic TXA. Our second experimental group, warfarin without TXA (warfarin-TXA), consisted of 40 patients who underwent arthroplasty while receiving therapeutic anticoagulation with warfarin (INR, 2.0-3.0) without prophylactic TXA. RESULTS: The percent change in hemoglobin value after surgery, red blood cells transfused, surgical site infections, bleeding complications, and thrombotic complications were similar between both experimental and control groups. When comparing the historical group with the warfarin+TXA group, the addition of TXA resulted in a statistical decrease in mean red blood cells transfused and estimated blood loss, with no statistically significant increase in complications. CONCLUSION: Many factors must be considered when choosing perioperative thromboembolic prophylaxis for arthroplasty candidates with medical comorbidities requiring long-term anticoagulation. This study presents data indicating that it could be safe and effective to continue therapeutic warfarin while using prophylactic TXA. [Orthopedics. 202x;4x(x):xx-xx.].

The Joint Awareness Score: A Shortened, Simplified, Improved Alternative to the Forgotten Joint Score.

Background: The Forgotten Joint Score (FJS) is a 12-question patient-reported outcomes measure created to measure a patient's awareness of their artificial joint. The FJS has attained wide usage, though it is not without weaknesses. Our patients report that the semantics of the English translation are flawed and that the 5 answer options for each question are poorly differentiated. Additionally, the FJS will result in no score if 3 or more questions are unanswered. This prompted the development of an alternative patient-reported outcomes measure, the Joint Awareness Score (JAS), that builds upon the core concept of joint awareness underlying the FJS, but that is easier to understand and shorter to complete. We completed an exploratory, pilot study to evaluate this outcomes instrument. Our hypothesis is that the JAS will correlate strongly with the FJS and could be used as a substitute. Methods: Knee arthroplasty patients in a prospective registry were administered the FJS and the JAS. Internal consistency and correlation were calculated with Cronbach's alpha and Pearson's correlation coefficient, respectively. Results: This study included 174 patients. Cronbach's alpha for FJS was 0.97 for 6 months and 0.97 for 12 months, whereas JAS was 0.89 at 6 months and 0.85 at 12 months. Pearson correlation comparing FJS and JAS at 6 months was 0.88 (95% confidence interval: 0.83, 0.92) and 0.86 (95% confidence interval: 0.78, 0.92) at 12 months. Conclusions: The Joint Awareness Score is a new patient-reported outcomes measure that is a substitute for the FJS, with half the number of questions, improved semantics, and simplified answers.

Efficacy and Safety of Pairing iStent Inject Trabecular Micro-Bypass and iAccess Precision Blade Goniotomy in Patients with Open-Angle Glaucoma.

INTRODUCTION: This study evaluated efficacy and safety of implanting two second-generation trabecular micro-bypass stents (iStent inject/iStent inject W) with phacoemulsification, either with or without iAccess Precision Blade goniotomy, in patients with mild-to-moderate open-angle glaucoma (OAG). METHODS: This retrospective, non-randomized, unmasked, dual-arm, single-site, multi-surgeon, consecutive case series evaluated all OAG eyes that underwent phacoemulsification and iStent inject implantation either as a dual procedure (group A) or paired with iAccess goniotomy (group B) from July 2020 to May 2022. Effectiveness outcomes analyzed from 1 month onward included intraocular pressure (IOP), proportions of eyes with IOP ≤ 12/≤ 15/≤ 18, proportion medication-free, and medication number. Safety outcomes at all timepoints included adverse events and secondary surgeries. RESULTS: In group A, mean IOP reduced from 14.9 ± 3.2 mmHg on 1.22 ± 1.31 mean medications preoperatively (n = 63) to 13.5 ± 2.5 mmHg on 0.24 ± 0.61 medications at month 3 (n = 34; p = 0.048 IOP, p < 0.001 medications). In group B, mean IOP reduced from 16.0 ± 4.2 mmHg on 1.12 ± 1.07 medications preoperatively (n = 93) to 12.2 ± 2.3 mmHg on 0.57 ± 1.27 medications at month 3 (n = 23; p < 0.001 IOP, p = 0.003 medications). From preoperative to 3 months, the percent of eyes with IOP ≤ 12 mmHg remained at 32.4% in group A (p = 1.0) and rose from 21.7% to 60.9% in group B (p = 0.0177); eyes with IOP ≤ 15 mmHg rose from 52.9% to 76.5% in group A (p = 0.0963) and from 43.5% to 91.3% in group B (p = 0.0034). Adjusting for baseline between-group differences, group B had significantly greater postoperative IOP reduction than group A (p = 0.043); medication reductions were similar. Safety was favorable in both groups. CONCLUSIONS: Phacoemulsification and iStent inject with or without iAccess Precision Blade goniotomy produced clinically meaningful and safe IOP and medication reductions. The paired iStent inject + iAccess + phacoemulsification procedure enabled greater IOP reduction and lower IOP thresholds than iStent inject + phacoemulsification. The study provides some of the first data on this paired approach and on the novel iAccess Precision Blade.

Comparison of Clinical Outcomes Following Gel Stent Implantation via Ab-Externo and Ab-Interno Approaches in Patients with Refractory Glaucoma.

Purpose: To compare clinical outcomes following gel stent implantation via ab externo and ab interno approaches in patients with refractory glaucoma. Patients and Methods: This retrospective study included 203 eyes of 185 patients aged ≥45 years who underwent Xen gel stent implantation as a standalone procedure for medically uncontrolled glaucoma (intraocular pressure (IOP) ≥18 mmHg) despite maximum tolerable IOP-lowering medications. One hundred and five eyes underwent gel stent implantation via ab interno approach and 98 via ab externo. Patients with prior conjunctival-incisional glaucoma or cataract surgery were also included. Study parameters were reduction in IOP and number of IOP-lowering medications from baseline to 3, 6, 9 and 12 months postoperatively. Results: There were no statistically significant differences in the age, sex, preoperative IOP, number of IOP-lowering medications or cup-disc ratio between the ab interno and ab externo groups at baseline (p > 0.05). At all postoperative time points, mean IOP and percentage reduction from baseline were comparable in both groups (p > 0.05) except at postoperative 6 months when the outcomes were significantly better (p < 0.05) in the ab externo group. The rate of postoperative procedures (5-Fluorouracil injections and bleb needling), the incidence of numerical or clinical hypotony and adverse events were comparable in both groups (p > 0.05). The mean number of IOP-lowering medications was comparable in both groups at all time points. Conclusion: The Xen gel stent, whether implanted ab interno or ab externo, is effective in reducing IOP and dependence on topical medications in eyes with refractory glaucoma. The stent may be used in both phakic and pseudophakic patients and is a reasonable option for patients with prior failed trabeculectomy.

Complete Genome Sequences of Five SO-1-Like Siphoviridae Bacteriophages That Infect Enterobacteriales.

The Enterobacteriales order is composed of Gram-negative bacteria that range from harmless symbionts to well-studied pathogens. We announce complete genome sequences of five related SO-1-like Enterobacteriales bacteriophages (also known as the Dhillonvirus genus) isolated from wastewater that infect Escherichia coli (Opt-212, Over9000, Pubbukkers, and Teewinot) or Shigella boydii (StarDew).

Optimizing performance and yield of vertical GaN diodes using wafer scale optical techniques.

To improve the manufacturing of vertical GaN devices for power electronics applications, the effects of defects in GaN substrates need to be better understood. Many non-destructive techniques including photoluminescence, Raman spectroscopy and optical profilometry, can be used to detect defects in the substrate and epitaxial layers. Raman spectroscopy was used to identify points of high crystal stress and non-uniform conductivity in a substrate, while optical profilometry was used to identify bumps and pits in a substrate which could cause catastrophic device failures. The effect of the defects was studied using vertical P-i-N diodes with a single zone junction termination extention (JTE) edge termination and isolation, which were formed via nitrogen implantation. Diodes were fabricated on and off of sample abnormalities to study their effects. From electrical measurements, it was discovered that the devices could consistently block voltages over 1000 V (near the theoretical value of the epitaxial layer design), and the forward bias behavior could consistently produce on-resistance below 2 mΩ cm2, which is an excellent value considering DC biasing was used and no substrate thinning was performed. It was found that high crystal stress increased the probability of device failure from 6 to 20%, while an inhomogeneous carrier concentration had little effect on reverse bias behavior, and slightly (~ 3%) increased the on-resistance (Ron). Optical profilometry was able to detect regions of high surface roughness, bumps, and pits; in which, the majority of the defects detected were benign. However a large bump in the termination region of the JTE or a deep pit can induce a low voltage catastrophic failure, and increased crystal stress detected by the Raman correlated to the optical profilometry with associated surface topography.

Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro).

Starting from the MLPCN probe compound ML300, a structure-based optimization campaign was initiated against the recent severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (3CLpro). X-ray structures of SARS-CoV-1 and SARS-CoV-2 3CLpro enzymes in complex with multiple ML300-based inhibitors, including the original probe ML300, were obtained and proved instrumental in guiding chemistry toward probe compound 41 (CCF0058981). The disclosed inhibitors utilize a noncovalent mode of action and complex in a noncanonical binding mode not observed by peptidic 3CLpro inhibitors. In vitro DMPK profiling highlights key areas where further optimization in the series is required to obtain useful in vivo probes. Antiviral activity was established using a SARS-CoV-2-infected Vero E6 cell viability assay and a plaque formation assay. Compound 41 demonstrates nanomolar activity in these respective assays, comparable in potency to remdesivir. These findings have implications for antiviral development to combat current and future SARS-like zoonotic coronavirus outbreaks.

Enhanced Affinity for 3-Amino-Chromane-Derived σ1 Receptor Ligands.

The σ1 receptor is implicated in regulating a diverse range of physiology and is a target for developing therapies for cancer, pain management, neural degradation, and COVID-19. This report describes 36 phenethylamine-containing 3-amino-chromane ligands, which bind to σ1 with low nM affinities. The family consists of 18 distinct compounds and each enantiomer was independently assayed. Three compounds with the greatest affinity bind in the 2 nM K i range (∼8.7 pK i). Furthermore, ligands with the (3R,4R) absolute stereochemistry on the 3-amino-chromane core have a higher affinity and greater σ1 versus TMEM97 selectivity. The most promising ligands were assayed in 661W cells, which did not show significant protective effects.

Excisional Goniotomy in Latino Patients with Open-Angle Glaucoma: Outcomes Through 24 Months.

PURPOSE: To characterize the efficacy of combined phacoemulsification and excisional goniotomy with the Kahook Dual Blade (KDB-phaco) in eyes of Latino adults with cataract and open-angle glaucoma (OAG). METHODS: Health records of consecutive Latino patients undergoing KDB-phaco were retrospectively reviewed. Intraocular pressure (IOP) and IOP-lowering medication use were recorded at baseline and each postoperative visit through up to 24 months. Primary outcomes were reductions in IOP and medication use from baseline; secondary outcomes were the proportions of eyes achieving IOP reductions of ≥20% and medication reductions ≥1 medication from baseline. Subgroup analysis was conducted in eyes with high and low baseline IOP. RESULTS: Data from 44 eyes of 32 Latino patients with OAG were analyzed. Mean IOP was 17.8 (0.7) mmHg at baseline and postoperatively ranged from 12.4 to 13.8 mmHg (p≥0.0003), representing mean IOP reductions of 4.2-4.6 mmHg (19.7-23.1%). Mean medication was 1.5 (0.2) medications per eye at baseline and postoperatively ranged from 0.2 to 1.0 (p≥0.0061), representing mean medication reductions of 0.7-1.2 medications per eye (47.1-87.2%). In the low baseline IOP group (<18 mmHg), mean IOP was significantly reduced through Month 24 and medications through Month 12; in the high baseline IOP group (≥18 mmHg), IOP and medications were significantly reduced through Month 24. From Months 1-24, IOP reductions of ≥20% were achieved by 48.4-56.2% of eyes in the full cohort, by 20.0-33.3% in the low IOP group, and by 66.7-100% in the high IOP group; medication reductions of ≥1 medication were achieved by 72.0-95.6%, 64.7-94.2%, and 87.5-100% of eyes, respectively. CONCLUSION: Combined KDB-phaco in eyes of Latino patients with glaucoma and cataract significantly lowers IOP and the need for IOP-lowering medications for up to 24 months and should be considered for such patients who warrant IOP reduction, medication reduction, or both.

Impact of Current and Temperature on Extremely Low Loading Epoxy-CNT Conductive Composites.

Carbon nanotube (CNT) conductive composites have attracted significant attention for their potential use in applications such as electrostatic dissipation and/or electromagnetic interference shielding. The focus of this work is to evaluate resistivity trends of extremely low loading (<0.1 wt%) epoxy-CNT composites that lack a connected CNT network, but still present electrical conductivity values appropriate for those uses. The impact of current, temperature, and cycle life on electrical properties are here identified and tied to possible performance limits. At extremely low loadings, the CNT content is not sufficient to form a completely interconnected grid, thus, electrons must travel through insulating media. While still in the semi-conductor range, resistivity values are observed to decrease with increasing direct current and demonstrate a non-ohmic behavior. CNT epoxy composites were subjected to elevated currents and/or temperatures over diverse periods of time to examine impacts on resistivity. Microstructural analyses of composite samples were conducted to observe signs of damage for specimens taken to extreme temperatures/currents. An understanding of the electrical conductivity characteristics of extremely low loading epoxy-CNT composites and their failure mechanisms will aid in understanding risks associated with their use in challenging environments that may include high temperatures, high currents, and/or high frequencies.

3-Amino-chromanes and Tetrahydroquinolines as Selective 5-HT2B, 5-HT7, or σ1 Receptor Ligands.

The phenethylamine backbone is a privileged substructure found in a wide variety of G protein-coupled receptor (GPCR) ligands. This includes both endogenous neurotransmitters and active pharmaceutical agents. More than 20 structurally unique heterocyclic phenethylamine derivatives were broadly evaluated for GPCR affinity. Selective ligands for the 5-HT2B, 5-HT7, and σ1 receptors were identified, each with low nanomolar binding affinities. The σ1 receptor affinity was supported in a cellular assay that provided evidence for increased cell survival under oxidative stress.

"It's a (Kinetic) Trap!" - Selectively Differentiating Allylic Azide Isomers.

Allylic azides are known to undergo the Winstein rearrangement and are often isolated as an equilibrating mixture of isomers. While this process has been known for almost 60 years, very few synthetic applications of this process have been reported. The absence of methods exploiting these intermediates likely stems from a paucity of approaches for gaining the required selectivity to differentiate the isomers. Our lab has made some progress in leveraging this unusual reaction into practical synthetic methodology. Presented herein is a summary of our lab's recent accomplishments in selectively trapping allylic azides.

The collaborative effect of scientific meetings: A study of the International Milk Genomics Consortium.

Collaboration among scientists has a major influence on scientific progress. Such collaboration often results from scientific meetings, where scientists gather to present and discuss their research and to meet potential collaborators. However, most scientific meetings have inherent biases, such as the availability of research funding or the selection bias of professional societies that make it difficult to study the effect of the meeting per se on scientific productivity. To evaluate the effects of scientific meetings on collaboration and progress independent of these biases, we conducted a study of the annual symposia held by the International Milk Genomics Consortium (IMGC) over a 12-year period. In our study, we conducted permutation testing to analyze the effectiveness of the IMGC in facilitating collaboration and productivity in a community of milk scientists who were meeting attendees relative to non-attendees. Using the number of co-authorships on published papers as a measure of collaboration, our analysis revealed that scientists who attended the symposium were associated with more collaboration than were scientists who did not attend. Furthermore, we evaluated the scientific progress of consortium attendees by analyzing publication rate and article impact. We found that IMGC attendees, in addition to being more collaborative, were also more productive and influential than were non-attendees who published in the same field. The results of our study suggest that the annual symposium encouraged interactions among disparate scientists and increased research productivity, exemplifying the positive effect of scientific meetings on both collaboration and progress.

Stereoselective Dynamic Cyclization of Allylic Azides: Synthesis of Tetralins, Chromanes, and Tetrahydroquinolines.

This report describes the stereoselective synthesis of 3-azido-tetralins, -chromanes, and -tetrahydroquinolines via a tandem allylic azide rearrangement/Friedel-Crafts alkylation. Exposure of allylic azides with a pendant trichloroacetimidate to catalytic quantities of AgSbF6 proved optimal for this transformation. This cascade successfully differentiates the equilibrating azide isomers, providing products in excellent yield and selectivity (>25 examples, up to 94% yield and >25:1 dr). In many cases, the reactive isomer is only a trace fraction of the equilibrium mixture, keenly illustrating the dynamic nature of these systems. We demonstrate the utility of this process via a synthesis of hasubanan.

Seasonal Patterns in Microbial Community Composition in Denitrifying Bioreactors Treating Subsurface Agricultural Drainage.

Denitrifying bioreactors, consisting of water flow control structures and a woodchip-filled trench, are a promising approach for removing nitrate from agricultural subsurface or tile drainage systems. To better understand the seasonal dynamics and the ecological drivers of the microbial communities responsible for denitrification in these bioreactors, we employed microbial community "fingerprinting" techniques in a time-series examination of three denitrifying bioreactors over 2 years, looking at bacteria, fungi, and the denitrifier functional group responsible for the final step of complete denitrification. Our analysis revealed that microbial community composition responds to depth and seasonal variation in moisture content and inundation of the bioreactor media, as well as temperature. Using a geostatistical analysis approach, we observed recurring temporal patterns in bacterial and denitrifying bacterial community composition in these bioreactors, consistent with annual cycling. The fungal communities were more stable, having longer temporal autocorrelations, and did not show significant annual cycling. These results suggest a recurring seasonal cycle in the denitrifying bioreactor microbial community, likely due to seasonal variation in moisture content.

Gas-phase reactions of alcohols with hexamethylene triperoxide diamine (HMTD) under atmospheric pressure chemical ionization conditions.

RATIONALE: Hexamethylene triperoxide diamine (HMTD) is a sensitive peroxide explosive first synthesized in 1885. HMTD exhibits an unusual gas-phase phenomenon in the presence of alcohols that has been previously observed, but incorrectly resolved. We are attempting to determine this specific mechanism. METHODS: We used positive ion mode atmospheric pressure chemical ionization (APCI) as the interface to the mass spectrometer. HMTD was infused with various solvents including (18) O- and (2) H-labeled methanol in order to determine gas-phase reaction mechanisms. RESULTS: Based on these labeled experiments, it was determined that, under APCI conditions, the alcohol oxygen attacks a methylene carbon of HMTD and releases H2 O2 . This was attempted with nine different alcohols and, in each case, the alcohol is fully incorporated into the molecule with the peroxide release. A mechanism for this reaction has been proposed. CONCLUSIONS: This work appears to have confirmed the gas-phase reaction mechanism of HMTD with alcohols. As we continue efforts to characterize this unusual molecule, the information may prove useful in determining formation and degradation mechanism(s). In addition, this property of HMTD may find use in other fields of science.

Intestinal epithelial barrier disruption through altered mucosal microRNA expression in human immunodeficiency virus and simian immunodeficiency virus infections.

UNLABELLED: Epithelial barrier dysfunction during human immunodeficiency virus (HIV) infection has largely been attributed to the rapid and severe depletion of CD4(+) T cells in the gastrointestinal (GI) tract. Although it is known that changes in mucosal gene expression contribute to intestinal enteropathy, the role of small noncoding RNAs, specifically microRNA (miRNA), has not been investigated. Using the simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV pathogenesis, we investigated the effect of viral infection on miRNA expression in intestinal mucosa. SIV infection led to a striking decrease in the expression of mucosal miRNA compared to that in uninfected controls. This decrease coincided with an increase in 5'-3'-exoribonuclease 2 protein and alterations in DICER1 and Argonaute 2 expression. Targets of depleted miRNA belonged to molecular pathways involved in epithelial proliferation, differentiation, and immune response. Decreased expression of several miRNA involved in maintaining epithelial homeostasis in the gut was localized to the proliferative crypt region of the intestinal epithelium. Our findings suggest that SIV-induced decreased expression of miRNA involved in epithelial homeostasis, disrupted expression of miRNA biogenesis machinery, and increased expression of XRN2 are involved in the development of epithelial barrier dysfunction and gastroenteropathy. IMPORTANCE: MicroRNA (miRNA) regulate the development and function of intestinal epithelial cells, and many viruses disrupt normal host miRNA expression. In this study, we demonstrate that SIV and HIV disrupt expression of miRNA in the small intestine during infection. The depletion of several key miRNA is localized to the proliferative crypt region of the gut epithelium. These miRNA are known to control expression of genes involved in inflammation, cell death, and epithelial maturation. Our data indicate that this disruption might be caused by altered expression of miRNA biogenesis machinery during infection. These findings suggest that the disruption of miRNA in the small intestine likely plays a role in intestinal enteropathy during HIV infection.

Spatial variation in the bacterial and denitrifying bacterial community in a biofilter treating subsurface agricultural drainage.

Denitrifying biofilters can remove agricultural nitrates from subsurface drainage, reducing nitrate pollution that contributes to coastal hypoxic zones. The performance and reliability of natural and engineered systems dependent upon microbially mediated processes, such as the denitrifying biofilters, can be affected by the spatial structure of their microbial communities. Furthermore, our understanding of the relationship between microbial community composition and function is influenced by the spatial distribution of samples.In this study we characterized the spatial structure of bacterial communities in a denitrifying biofilter in central Illinois. Bacterial communities were assessed using automated ribosomal intergenic spacer analysis for bacteria and terminal restriction fragment length polymorphism of nosZ for denitrifying bacteria.Non-metric multidimensional scaling and analysis of similarity (ANOSIM) analyses indicated that bacteria showed statistically significant spatial structure by depth and transect,while denitrifying bacteria did not exhibit significant spatial structure. For determination of spatial patterns, we developed a package of automated functions for the R statistical environment that allows directional analysis of microbial community composition data using either ANOSIM or Mantel statistics.Applying this package to the biofilter data, the flow path correlation range for the bacterial community was 6.4 m at the shallower, periodically in undated depth and 10.7 m at the deeper, continually submerged depth. These spatial structures suggest a strong influence of hydrology on the microbial community composition in these denitrifying biofilters. Understanding such spatial structure can also guide optimal sample collection strategies for microbial community analyses.