Spectrophotometric properties of commercially available blue blockers across multiple lighting conditions.

Lenses that filter short-wavelength ("blue") light are commercially marketed to improve sleep and circadian health. Despite their widespread use, minimal data are available regarding their comparative efficacy in curtailing blue light exposure while maintaining visibility. Fifty commercial lenses were evaluated using five light sources: a blue LED array, a computer tablet display, an incandescent lamp, a fluorescent overhead luminaire, and sunlight. Absolute irradiance was measured at baseline and for each lens across the visual spectrum (380-780 nm), which allowed calculation of percent transmission. Transmission specificity was also calculated to determine whether light transmission was predominantly circadian-proficient (455-560 nm) or non-proficient (380-454 nm and 561-780 nm). Lenses were grouped by tint and metrics were compared between groups. Red-tinted lenses exhibited the lowest transmission of circadian-proficient light, while reflective blue lenses had the highest transmission. Orange-tinted lenses transmitted similar circadian-proficient light as red-tinted lenses but transmitted more non-circadian-proficient light, resulting in higher transmission specificity. Orange-tinted lenses had the highest transmission specificity while limiting biologically active light exposure in ordinary lighting conditions. Glasses incorporating these lenses currently have the greatest potential to support circadian sleep-wake rhythms.

Frequency of Urinary Tract Infections, Gonorrhea, and Chlamydia in Emergency Department Patients With Acute Scrotal Pain.

BACKGROUND: Acute scrotal pain has many causes. According to the American Urological Association recommendations: history, physical examination, and ultrasound are key in diagnosing acute scrotal pain. OBJECTIVE: The primary objective of this study was to evaluate the frequency of urinary tract infections (UTI) on routine Urinalysis (UA) in patients presenting with acute scrotal pain to the emergency department (ED). METHODS: We conducted a multicentered retrospective chart review of patients who presented to the ED with acute scrotal pain. Patient visits from February 1, 2018 to November 1, 2019 from 13 EDs were analyzed. Demographic data, UA interpretation, urine culture, gonorrhea and chlamydia (GC) testing, clinical findings, treatment outcomes, and ultrasounds were recorded. Patients who did not have a UA and scrotal ultrasound performed or who had a diagnosis of scrotal cellulitis or soft tissue infection were excluded. RESULTS: There were 2,392 patients included in the study. A UTI was present in 173 (7.2%) patients. Of the patients who were found to have a UTI, 100/173 (57.8%) had a concomitant ultrasound diagnosis of epididymitis/orchitis. Also, 731 patients underwent GC testing in addition to standard UA collection, and ultrasound, seven were positive for gonorrhea (0.95%), and 30 were positive for chlamydia (4.10%). CONCLUSIONS: Routine UA collection of patients presenting to the ED with acute scrotal pain should be considered, especially in patients with a concomitant ultrasound diagnosis of epididymo-orchitis. GC testing has limited yield without symptoms suggestive of sexually transmitted infections and a normal ultrasound.

Environmental Impacts from Photovoltaic Solar Cells Made with Single Walled Carbon Nanotubes.

An ex-ante life cycle inventory was developed for single walled carbon nanotube (SWCNT) PV cells, including a laboratory-made 1% efficient device and an aspirational 28% efficient four-cell tandem device. The environmental impact of unit energy generation from the mono-Si PV technology was used as a reference point. Compared to monocrystalline Si (mono-Si), the environmental impacts from 1% SWCNT was ∼18 times higher due mainly to the short lifetime of three years. However, even with the same short lifetime, the 28% cell had lower environmental impacts than mono-Si. The effects of lifetime and efficiency on the environmental impacts were further examined. This analysis showed that if the SWCNT device efficiency had the same value as the best efficiency of the material under comparison, to match the total normalized impacts of the mono- and poly-Si, CIGS, CdTe, and a-Si devices, the SWCNT devices would need a lifetime of 2.8, 3.5, 5.3, 5.1, and 10.8 years, respectively. It was also found that if the SWCNT PV has an efficiency of 4.5% or higher, its energy payback time would be lower than other existing and emerging PV technologies. The major impacts of SWCNT PV came from the cell's materials synthesis.

Matrix stiffening promotes a tumor vasculature phenotype.

Tumor microvasculature tends to be malformed, more permeable, and more tortuous than vessels in healthy tissue, effects that have been largely attributed to up-regulated VEGF expression. However, tumor tissue tends to stiffen during solid tumor progression, and tissue stiffness is known to alter cell behaviors including proliferation, migration, and cell-cell adhesion, which are all requisite for angiogenesis. Using in vitro, in vivo, and ex ovo models, we investigated the effects of matrix stiffness on vessel growth and integrity during angiogenesis. Our data indicate that angiogenic outgrowth, invasion, and neovessel branching increase with matrix cross-linking. These effects are caused by increased matrix stiffness independent of matrix density, because increased matrix density results in decreased angiogenesis. Notably, matrix stiffness up-regulates matrix metalloproteinase (MMP) activity, and inhibiting MMPs significantly reduces angiogenic outgrowth in stiffer cross-linked gels. To investigate the functional significance of altered endothelial cell behavior in response to matrix stiffness, we measured endothelial cell barrier function on substrates mimicking the stiffness of healthy and tumor tissue. Our data indicate that barrier function is impaired and the localization of vascular endothelial cadherin is altered as function of matrix stiffness. These results demonstrate that matrix stiffness, separately from matrix density, can alter vascular growth and integrity, mimicking the changes that exist in tumor vasculature. These data suggest that therapeutically targeting tumor stiffness or the endothelial cell response to tumor stiffening may help restore vessel structure, minimize metastasis, and aid in drug delivery.

3D Bioprinting of Spatially Heterogeneous Collagen Constructs for Cartilage Tissue Engineering.

3D printing of biological tissues has been of increasing interest to the biomaterials community in part because of its potential to produce spatially heterogeneous constructs. Such technology is particularly promising for orthopedic applications, which require the generation of complex geometries to match patient anatomy and complex microstructures to produce spatial heterogeneity and anisotropy. Prior research has demonstrated the capacity to create precisely shaped 3D printed constructs using biocompatible alginate hydrogels. However, alginate is extremely compliant and brittle, and high-density collagen hydrogels could be a preferable option for load-bearing applications. This research focused on developing and evaluating a method of printing soft tissue implants with high-density collagen hydrogels using a commercially available 3D printer, modified for tissue-engineering purposes. The tissue constructs, seeded with primary meniscal fibrochondrocytes, were evaluated using measures of geometric fidelity, cell viability, mechanical properties, and fiber microstructure. The constructs were found to be mechanically stable and were able to support and maintain cell growth. Furthermore, heterogeneous 3D-printed constructs were generated, consisting of discrete domains with distinct mechanical properties.

Tissue stiffness regulates serine/arginine-rich protein-mediated splicing of the extra domain B-fibronectin isoform in tumors.

Alternative splicing of proteins gives rise to different isoforms that play a crucial role in regulating several cellular processes. Notably, splicing profiles are altered in several cancer types, and these profiles are believed to be involved in driving the oncogenic process. Although the importance of alternative splicing alterations occurring during cancer is increasingly appreciated, the underlying regulatory mechanisms remain poorly understood. In this study, we use both biochemical and physical tools coupled with engineered models, patient samples, and a murine model to investigate the role of the mechanical properties of the tumor microenvironment in regulating the production of the extra domain-B (EDB) splice variant of fibronectin (FN), a hallmark of tumor angiogenesis. Specifically, we show that the amount of EDB-FN produced by endothelial cells increases with matrix stiffness both in vitro and within mouse mammary tumors. Matrix stiffness regulates splicing through the activation of serine/arginine rich (SR) proteins, the splicing factors involved in the production of FN isoforms. Activation of the SR proteins by matrix stiffness and the subsequent production of EDB-FN are dependent on intracellular contractility and PI3K-AKT signaling. Notably, matrix stiffness-mediated splicing is not limited to EDB-FN, but also affects splicing in the production of PKC ßII and the VEGF 165b splice variant. Together, these results demonstrate that the mechanical properties of the microenvironment regulate alternative splicing and establish a previously unidentified mechanism by which cells can adapt to their microenvironment.

Biophysical induction of vascular smooth muscle cell podosomes.

Vascular smooth muscle cell (VSMC) migration and matrix degradation occurs with intimal hyperplasia associated with atherosclerosis, vascular injury, and restenosis. One proposed mechanism by which VSMCs degrade matrix is through the use of podosomes, transient actin-based structures that are thought to play a role in extracellular matrix degradation by creating localized sites of matrix metalloproteinase (MMP) secretion. To date, podosomes in VSMCs have largely been studied by stimulating cells with phorbol esters, such as phorbol 12,13-dibutyrate (PDBu), however little is known about the physiological cues that drive podosome formation. We present the first evidence that physiological, physical stimuli mimicking cues present within the microenvironment of diseased arteries can induce podosome formation in VSMCs. Both microtopographical cues and imposed pressure mimicking stage II hypertension induce podosome formation in A7R5 rat aortic smooth muscle cells. Moreover, wounding using a scratch assay induces podosomes at the leading edge of VSMCs. Notably the effect of each of these biophysical stimuli on podosome stimulation can be inhibited using a Src inhibitor. Together, these data indicate that physical cues can induce podosome formation in VSMCs.

Cooperative effects of matrix stiffness and fluid shear stress on endothelial cell behavior.

Arterial hemodynamic shear stress and blood vessel stiffening both significantly influence the arterial endothelial cell (EC) phenotype and atherosclerosis progression, and both have been shown to signal through cell-matrix adhesions. However, the cooperative effects of fluid shear stress and matrix stiffness on ECs remain unknown. To investigate these cooperative effects, we cultured bovine aortic ECs on hydrogels matching the elasticity of the intima of compliant, young, or stiff, aging arteries. The cells were then exposed to laminar fluid shear stress of 12 dyn/cm(2). Cells grown on more compliant matrices displayed increased elongation and tighter EC-cell junctions. Notably, cells cultured on more compliant substrates also showed decreased RhoA activation under laminar shear stress. Additionally, endothelial nitric oxide synthase and extracellular signal-regulated kinase phosphorylation in response to fluid shear stress occurred more rapidly in ECs cultured on more compliant substrates, and nitric oxide production was enhanced. Together, our results demonstrate that a signaling cross talk between stiffness and fluid shear stress exists within the vascular microenvironment, and, importantly, matrices mimicking young and healthy blood vessels can promote and augment the atheroprotective signals induced by fluid shear stress. These data suggest that targeting intimal stiffening and/or the EC response to intima stiffening clinically may improve vascular health.

A quality improvement project to improve compliance with the joint commission children's asthma care-3 measure.

BACKGROUND AND OBJECTIVE: Since the initiation of the Children's Asthma Care (CAC) core measures in 2008, hospitals have struggled to achieve a high rate of compliance with the CAC-3 measure of the Home Management Plan of Care (HMPC). At inception of this project in 2009, the national average was 65% compliance, which has now increased to 80%. These rates are below the Hospital Corporation of America's goal of 90% compliance. Our objective was to identify potential pitfalls that interfere with compliance on CAC-3 at our institution and to devise solutions to increase compliance to >90%. METHODS: Inpatient pediatric patients at a community teaching hospital in a predominantly rural state were included in our interrupted time-series quality improvement project from 2008 to 2011. Patients were between 2 and 17 years of age with an International Classification of Diseases, Ninth Revision (ICD-9), primary diagnosis code of asthma at time of discharge. We identified potential stumbling blocks that interfered with compliance of CAC measures and then implemented repeated Plan-Do-Study-Act (PDSA) cycles to improve processes, including redesign of the HMPC form, education, and electronic documentation tied to the discharge medication reconciliation form, which is also required by The Joint Commission. RESULTS: We started with an average quarterly compliance of 43% with CAC-3 before our PDSA cycles. We have improved our compliance after the 2 PDSA cycles to an average of 97%. CONCLUSIONS: By linking the HMPC form to the discharge medication reconciliation form, we were able to achieve and maintain >90% compliance with CAC-3.

Controlling the mechanical properties of three-dimensional matrices via non-enzymatic collagen glycation.

The mechanical properties of the extracellular matrix play an important role in maintaining cellular function and overall tissue homeostasis. Recently, a number of hydrogel systems have been developed to investigate the role of matrix mechanics in mediating cell behavior within three-dimensional environments. However, many of the techniques used to modify the stiffness of the matrix also alter properties that are important to cellular function including matrix density, porosity and binding site frequency, or rely on amorphous synthetic materials. In a recent publication, we described the fabrication, characterization and utilization of collagen gels that have been non-enzymatically glycated in their unpolymerized form to produce matrices of varying stiffness. Using these scaffolds, we showed that the mechanical properties of the resulting collagen gels could be increased 3-fold without significantly altering the collagen fiber architecture. Using these matrices, we found that endothelial cell spreading and outgrowth from multi-cellular spheroids changes as a function of the stiffness of the matrix. Our results demonstrate that non-enzymatic collagen glycation is a tractable technique that can be used to study the role of 3D stiffness in mediating cellular function. This commentary will review some of the current methods that are being used to modulate matrix mechanics and discuss how our recent work using non-enzymatic collagen glycation can contribute to this field.

Improving safe sleep environments for well newborns in the hospital setting.

OBJECTIVE: Following the "Back to Sleep" campaign, deaths from sudden infant death syndrome (SIDS) were reduced. However, SIDS and sleep-related deaths continue to occur. Studies demonstrate that modeling by health care workers influences parents to place infants supine for sleep. Recently, additional emphasis has been placed on environment. The purpose of this study was to improve sleep position and environment in the hospital. METHODS: A Plan-Do-Study-Act cycle was initiated. Sleeping infants were observed at baseline. A bundled intervention was implemented; infants were again observed. Parents were surveyed. RESULTS: At baseline, 25% (36/144) of sleeping infants were safe; the majority of unsafe sleep was a result of environment. Postintervention, significantly more (58%; 145/249) had safe sleep (P < .0001). Most parents planned to use the supine position (95%; 96/101); none planned to cosleep. Many intended to adjust their infants' home sleep environment. CONCLUSION: Using a multifaceted approach significantly improved infant safe sleep practice in the hospital setting.

Tuning three-dimensional collagen matrix stiffness independently of collagen concentration modulates endothelial cell behavior.

Numerous studies have described the effects of matrix stiffening on cell behavior using two-dimensional synthetic surfaces; however, less is known about the effects of matrix stiffening on cells embedded in three-dimensional in vivo-like matrices. A primary limitation in investigating the effects of matrix stiffness in three dimensions is the lack of materials that can be tuned to control stiffness independently of matrix density. Here, we use collagen-based scaffolds where the mechanical properties are tuned using non-enzymatic glycation of the collagen in solution, prior to polymerization. Collagen solutions glycated prior to polymerization result in collagen gels with a threefold increase in compressive modulus without significant changes to the collagen architecture. Using these scaffolds, we show that endothelial cell spreading increases with matrix stiffness, as does the number and length of angiogenic sprouts and the overall spheroid outgrowth. Differences in sprout length are maintained even when the receptor for advanced glycation end products is inhibited. Our results demonstrate the ability to de-couple matrix stiffness from matrix density and structure in collagen gels, and that increased matrix stiffness results in increased sprouting and outgrowth.