An overview of mineralocorticoid receptor antagonists as a treatment option for patients with heart failure: the current state-of-the-art and future outlook.

INTRODUCTION: Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in patients with heart failure. These benefits of MRAs vary in different heart failure populations based on left ventricular ejection fraction and associated comorbidities. AREAS COVERED: We define the pharmacologic properties of MRAs and the pathophysiological rationale for their utility in heart failure. We outline the current literature on the use of MRAs in different heart failure populations, including reduced and preserved ejection fraction (HFrEF/HFpEF) and acute heart failure decompensation. Finally, we describe the limitations of currently available data and propose future directions of study. EXPERT OPINION: While there is strong evidence supporting the use of MRAs in HFrEF, evidence in patients with HFpEF or acute heart failure is less definitive. Comorbidities such as obesity or atrial fibrillation could be clinical modifiers of the response to MRAs and potentially alter the risk/benefit ratio in these subpopulations. Emerging evidence for new non-steroidal MRAs reveal promising preliminary results that, if confirmed in large randomized clinical trials, could favor a change in clinical practice.

Authorship Gender Composition in Urology Literature From 2015 Through 2020.

OBJECTIVE: To describe the current landscape of first and last female authorship in urology journals relative to the journals' impact factor. We hypothesized that women would have a smaller proportion of publications in journals with higher impact factors. METHODS: Eighteen urology journals were divided into groups based on impact factor accordingly: from 33.2 to 6.2 were classified as high (European Urology, Nature Reviews Urology, The Journal of Urology, BJU International, Prostate Cancer and Prostatic Diseases, and The Journal of Sexual Medicine), from 5.8 to 5.0 as medium (Asian Journal of Andrology, European Urology Focus, Sexual Medicine Reviews, Bladder Cancer, Prostate and World Journal of Urology), and from 4.8 to 2.2 as low (Urologic Oncology, Journal of Endourology, Neurourology and Urodynamics, Urology, Journal of Pediatric Urology and Female Pelvic Medicine & Reconstructive Surgery). A computer script was designed using Python to search PubMed and record first and last author of publications between 2015 and 2020. Gender was determined by Gender-Api (https://gender-api.com). Names with an accuracy of <90% were excluded. Type of peer-review and scope of each journal were also analyzed. Statistical analysis was performed using Matlab. RESULTS: A total of 37,413 first and 28,414 last authors were identified during the study period. Overall, women represented 21% (8,029/37,413) of first and 15% (4,232/28,414) of last authors. Women were significantly less published in high impact journals compared to both medium and low impact journals (P <.001 in all). Among all journals, articles with female first authors were more likely to have a female last author (OR: 2.72, CI: 2.5-2.9, P <.001). Subspecialty journals had more female last authors than general journals (P <.05), and female representation increased if reviews were double-blinded (P <.001). Over the last 6 years, there has been a significant increase in female senior authorship among all journals (P = .045). CONCLUSION: The proportion of female authorship was significantly lower in higher impact urology journals. While the underlying cause is likely multifactorial, this finding highlights a gender discrepancy that may impact women's ability to achieve career goals in academic medicine when compared to their male counterparts.

Outcomes of transulnar and transradial percutaneous coronary intervention using ultrasound guided access in patients selected based on an ultrasound algorithm.

We performed a prospective observational study of 215 patients (58 ± 11 years) and compared the outcomes of ultrasound guided ulnar (n = 98, 45.6%) vs. radial (n = 117, 54.4%) cardiac catheterization and percutaneous coronary intervention (PCI) in patients selected by an ultrasound based algorithm. Primary endpoints included the number of access attempts and conversion to femoral access. Secondary endpoints included all-cause mortality, cardiac mortality, myocardial infarction, stroke, repeat revascularization, stent thrombosis, in-stent restenosis, and access site complications. No significant difference was found in the primary endpoints between radial or ulnar. Ulnar access showed no significant hematomas. Therefore, ulnar PCI is a feasible alternative.

Patterns of video-based motion analysis use among sports physical therapists.

OBJECTIVE: Examine video-based motion analysis (VBMA) use among sports physical therapists. DESIGN: Cross-sectional observation. SETTING: Survey, online-platform. PARTICIPANTS: American Academy of Sports Physical Therapy members (n = 261). MAIN OUTCOME MEASURES: VBMA use frequency, reasons for use, facilitators/barriers, tools used, factors associated with use. RESULTS: 194 (74.3%) used VBMA but 163 (84%) use it for ≤ 25% of their caseload. Most (57.7%) used their personal device to capture VBMA. Commonly cited reasons for use were movement analysis (93.8%) and patient education (87.6%). Barriers to use included time (30.7%), unfamiliarity with device/equipment (19.2%), and lack of device/equipment (18.4%). Younger age, advanced training, and greater time spent with return patients were each associated with use. For every 5-year increase of age, there was a 12% reduced likelihood of VBMA use (OR = 0.88; 95% CI = 0.77-1.00). Board-certified sports clinical specialists were more likely to use vs. those without additional certifications/degrees (OR = 3.27; 95% CI = 1.33-8.02). Spending 30-59 (vs. <30) minutes with return patients increased the odds of use (ORs range: 2.71 to 3.85). CONCLUSION: Most respondents used VBMA, albeit infrequently. Those younger, with advanced training, and spending ≥30 min with return patients were more likely to use VBMA. Future research should investigate whether VBMA use enhances patient outcomes.

Outcomes of Dorsal Distal Radial, Radial, and Ulnar Artery Percutaneous Coronary Intervention With Ultrasound Guidance in Acute Myocardial Infarction.

Ultrasound utilization during access enables precise vessel cannulation. We sought to evaluate the outcomes of ultrasound guided dorsal distal radial artery (DDRA), radial, and ulnar cardiac catheterization (CC) and percutaneous coronary intervention (PCI). We performed a prospective observational study of 224 patients (58 ± 12 years) at an academic medical center from October 2016 to March 2020 (median follow-up of 13 months) and compared the outcomes of ultrasound guided DDRA, ulnar, or radial artery CC and PCI. Groups were divided into DDRA (n = 18, 8.0%), ulnar (n = 94, 42.0%) and radial access (n = 112, 50.0%). Primary endpoints included the number of access attempts and conversion to femoral access. Secondary endpoints included all-cause mortality, cardiac mortality, acute myocardial infarction (AMI), stroke, repeat revascularization, stent thrombosis, in-stent restenosis, and access site complications. In the primary endpoints, no significant difference was found amongst groups in the number of access attempts (P = 0.272) or conversion to femoral access (P = 0.381). In the radial group (59 ± 11 years, median follow-up of 16 months), 2 cardiac mortalities (1 lymphocytic myocarditis, 1 AMI) and 2 noncardiac mortalities occurred. None of the secondary endpoints occurred in the DDRA (66 ± 17 years, median follow-up of 13 months) or ulnar group (56 ± 11 years, median follow-up of 14 months). DDRA and ulnar PCI was safe and efficacious with no complications. Femoral conversion or the number of access attempts was not different between DDRA, ulnar, or radial. Therefore, DDRA and ulnar are viable alternatives for PCI, which can preserve radial for future use.

Psychosis and Catatonia in Fragile X Syndrome.

Fragile X syndrome is an inherited disorder with an X-linked dominant inheritance pattern that is the most commonly inherited cause of intellectual developmental disorder and has a strong association with autism spectrum disorder. This report describes the case of an 18-year-old male with fragile X syndrome and multiple psychiatric comorbidities who presented with new onset psychosis and catatonia.

Acute Circulatory Collapse and Advanced Therapies in Patients with COVID-19 Infection.

In the current era of the COVID-19 pandemic, intensive care patients with COVID-19 often develop respiratory failure and acute respiratory distress syndrome. While less frequent, acute circulatory collapse, with or without respiratory failure, has its own management challenges and nuances. Early identification of acute circulatory collapse requires appropriate imaging, particularly echocardiography, and precise diagnosis of cardiogenic shock using a Swan-Ganz catheter. Escalation to mechanical circulatory support (MCS), such as an intra-aortic balloon pump, Impella, and extracorporeal membrane oxygenation, has been useful in patients with acute circulatory collapse from COVID-19. This condition is associated with high morbidity and mortality, but early recognition of appropriate candidates for specific treatment strategies and escalation to MCS might improve outcomes.

IL-26 mediated human cell activation and antimicrobial activity against Borrelia burgdorferi.

Lyme disease is an inflammatory disease caused by infection with Borrelia burgdorferi (Bb). Inflammatory sequelae of Bb infection appear to be refractory to antibiotics. An antimicrobial peptide with the ability to bind the DNA in the tissue could serve as a viable option of treatment for chronic complications of Lyme borreliosis. DNA of Bb can remain in tissues causing a prolonged inflammatory response that lead to chronic joint pain. Here we examined the effect of IL-26, a newly reported antimicrobial protein, against Bb DNA. An antimicrobial effect of IL-26 on the spirochete was observed. In human macrophages, IL-26 treated cells showed an increase in IRF activation upon Bb stimulation. Moreover, IL-26 treated macrophages showed an increased in phagocytic activity compared to untreated cells. Although no Bb DNA degradation was observed using a TUNEL assay run in an agarose gel, a Comet assay on whole bacteria showed cellular and Bb DNA degradation by IL-26. Our results showed that IL-26 (monomer and dimer) has not only the potential to control Bb growth in vitro, but it also enhances the anti-borrelial response of human macrophages. Further research aiming to characterize the role of IL-26 in controlling other aspects of the inflammatory response that could provide insight of its potential therapeutic applications are needed.

Actuation of shape-memory colloidal fibres of Janus ellipsoids.

Many natural micrometre-scale assemblies can be actuated to control their optical, transport and mechanical properties, yet such functionality is lacking in colloidal structures synthesized thus far. Here, we show with experiments and computer simulations that Janus ellipsoids can self-assemble into self-limiting one-dimensional fibres with shape-memory properties, and that the fibrillar assemblies can be actuated on application of an external alternating-current electric field. Actuation of the fibres occurs through a sliding mechanism that permits the rapid and reversible elongation and contraction of the Janus-ellipsoid chains by ~36% and that on long timescales leads to the generation of long, uniform self-assembled fibres. Colloidal-scale actuation might be useful in microrobotics and in applications of shape-memory materials.

Direct current electric field assembly of colloidal crystals displaying reversible structural color.

We report the application of low-voltage direct current (dc) electric fields to self-assemble close-packed colloidal crystals in nonaqueous solvents from colloidal spheres that vary in size from as large as 1.2 µm to as small as 0.1 µm. The assemblies are created rapidly (∼2 min) from an initially low volume fraction colloidal particle suspension using a simple capacitor-like electric field device that applies a steady dc electric voltage. Confocal microscopy is used to observe the ordering that is produced by the assembly method. This spatial evidence for ordering is consistent with the 6-fold diffraction patterns identified by light scattering. Red, green, and blue structural color is observed for the ordered assemblies of colloids with diameters of 0.50, 0.40, and 0.29 µm, respectively, consistent with spectroscopic measurements of reflectance. The diffraction and spectrophotometry results were found to be consistent with the theoretical Bragg's scattering expected for closed-packed crystals. By switching the dc electric field from on to off, we demonstrate reversibility of the structural color response on times scales ∼60 s. The dc electric field assembly method therefore represents a simple method to produce reversible structural color in colloidal soft matter.

Spatially and temporally reconfigurable assembly of colloidal crystals.

The self-assembly of colloidal crystals is important to the production of materials with functional optical, mechanical and conductive properties. Yet, self-assembly methods are limited by their slow kinetics and lack of structural control in space and time. Refinements such as templating and directed assembly partially address the problem, albeit by introducing fixed surface features such as templates or electrodes. A template-free method to reconfigure colloidal crystals simultaneously in three-dimensional space and time would better align work in colloidal assembly with materials applications. Here, we report a photo-induced assembly method that yields regions either filled with colloidal crystals or completely devoid of colloids. The origin of the effect is found to be electrophoresis of colloids generated by photochemistry at an indium tin oxide-coated substrate. Simple optical manipulations are applied to reconfigure these assembly and depletion regions. Thus, the method represents a new kind of template-free, reconfigurable three-dimensional photolithography.

Synthesis, assembly, and image analysis of spheroidal patchy particles.

We report a method to synthesize and image Janus spheroid and "kayak" shaped patchy particles that combine both shape and interaction anisotropy. These particles are fabricated by sequentially combining evaporative deposition of chrome and gold with the uniaxial deformation of the colloidal particles into spheroids. We introduce combined reflection and fluorescence confocal microscopy to image each component of the patchy particle. Image analysis algorithms that resolve patch orientation from these image volumes are described and used to characterize self-assembly behavior. Assemblies of the Janus spheroid and kayak particles produced at different salt concentrations demonstrate the functional nature of the patch-to-patch interactions between the particles. Selective gold-to-gold patch bonding is observed at intermediate salt concentrations, while higher salt concentrations yield gel-like structures with nonselective patch-to-patch bonding. At intermediate salt concentrations, differences in the orientational order of the assemblies indicate that both the preferential gold-to-gold patch bonding and the particles' shape anisotropy influence the self-assembled structure.

Liquid crystal order in colloidal suspensions of spheroidal particles by direct current electric field assembly.

DC electric fields are used to produce colloidal assemblies with orientational and layered positional order from a dilute suspension of spheroidal particles. These 3D assemblies, which can be visualized in situ by confocal microscopy, are achieved in short time spans (t < 1 h) by the application of a constant voltage across the capacitor-like device. This method yields denser and more ordered assemblies than had been previously reported with other assembly methods. Structures with a high degree of orientational order as well as layered positional order normal to the electrode surface are observed. These colloidal structures are explained as a consequence of electrophoretic deposition and field-assisted assembly. The interplay between the deposition rate and the rotational Brownian motion is found to be critical for the optimal ordering, which occurs when these rates, as quantified by the Peclet number, are of order one. The results suggest that the mechanism leading to ordering is equilibrium self-assembly but with kinetics dramatically accelerated by the application of the DC electric field. Finally, the crystalline symmetry of the densest structure formed is determined and compared with previously studied spheroidal assemblies.

Contribution of the Klebsiella pneumoniae capsule to bacterial aggregate and biofilm microstructures.

We studied the interaction between capsule production and hydrodynamic growth conditions on the internal and macroscopic structure of biofilms and spontaneously formed aggregates of Klebsiella pneumoniae. Wild-type and capsule-deficient strains were studied as biofilms and under strong and mild hydrodynamic conditions. Internal organization of multicellular structures was determined with a novel image-processing algorithm for feature extraction from high-resolution confocal microscopy. Measures included interbacterial spacing and local angular alignment of individual bacteria. Macroscopic organization was measured via the size distribution of aggregate populations forming under various conditions. Compared with wild-type organisms, unencapsulated mutant organisms formed more organized aggregates with less variability in interbacterial spacing and greater interbacterial angular alignment. Internal aggregate structure was not detectably affected by the severity of hydrodynamic growth conditions. However, hydrodynamic conditions affected both wild-type and mutant aggregate size distributions. Bacteria grown under high-speed shaking conditions (i.e., at Reynolds' numbers beyond the laminar-turbulent transition) formed few multicellular aggregates while clumpy growth was common in bacteria grown under milder conditions. Our results indicate that both capsule and environment contribute to the structure of communities of K. pneumoniae, with capsule exerting influence at an interbacterial length scale and fluid dynamic forces affecting overall particle size.

Toward Assembly of Non-close-packed Colloidal Structures from Anisotropic Pentamer Particles.

Particles combining multiple anisotropy dimensions offer possibilities for self-assembly that have not been extensively explored to date. The scope for assembly of microparticles in which the anisotropy dimensions of internal bond angle and chemical ordering have been varied is investigated. Colloidal assemblies with interesting open (i.e., non-close-packed) structures can be assembled from these building blocks. The structure of the assemblies formed is linked to the building block anisotropy because the steric constraints introduced induce deviations from close packing. Key challenges addressed in pursuit of these structures are parallelization of microfluidic synthesis methods, simulation to efficiently search the available anisotropy space, and methods that characterize the properties of the resulting assemblies. This combined program of synthesis, simulation, assembly, and characterization may be applied to develop design rules that guide efforts to fabricate microparticle building blocks and their assemblies.