Extreme γ' fibrinogen levels in COVID-19 patients.

COVID-19 disease progression can be accompanied by a "cytokine storm" that leads to secondary sequelae such as acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 disease progression, but have high daily intra-individual variability. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (GPF) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. COVID-19 patients were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using a commercial ELISA. We found that COVID-19 patients can develop extraordinarily high levels of GPF. Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients.

One-Step Synthesis of Biphasic, Cavity-forming Polymer Particles via Dispersion Copolymerization of Styrene and Sulfobetaine Methacrylate.

A one-step dispersion copolymerization technique is demonstrated to fabricate biphasic particles as an approach to streamline the production of particles with complex morphology. The model system studies a monomer feed of hydrophobic styrene and hydrophilic, zwitterionic sulfobetaine methacrylate (SBMA) in a water/isopropanol cosolvent mixture. The resulting particles have a core-shell morphology that can be transformed, simply by washing the particles with water, into particles with a single surface opening connected to an interior cavity. Results indicate that particle morphology is dependent on the presence of nanoscopic SBMA-rich aggregates in the initial reaction mixture to act as nucleation sites, forming an SBMA-rich core encased in a styrene-rich shell. Systematic study of the morphology evolution reveals that the difference in monomer solubility profile can be exploited to control compositional drift of the particle composition during copolymerization yielding copolymer with sufficiently different composition to form phase-separated particle morphology. When SBMA is replaced with various ionic comonomers, the cavity-forming morphology is observed when reaction conditions result in low solubility of the comonomer in the cosolvent mixture. Based on these results, design guidelines are developed that may be applied to a variety of systems requiring complex and responsive particles made from chemically distinct comonomer pairings.

Relationship Between Age and Running Kinematics in Female Recreational Runners.

Sex-based analyses are important when studying running kinematics. Females experience a unique aging process and demonstrate differences in running biomechanics from males. The purpose was to determine the relationship between age and running kinematics in female runners. Forty-six female runners (18-65 y) ran at self-selected jogging and maximal speed on a treadmill. Lower-extremity joint kinematics were calculated, and 2 principal component analyses (jogging speed and maximal speed) were performed from kinematic variables. Regression was used to examine the relationship between age and identified components, and between age and the variables with the highest loadings within these components. For jogging speed, there was a positive relationship between age and ankle varus at initial contact and a negative relationship between age and peak eversion, hip adduction, knee flexion, dorsiflexion, and hip adduction at initial contact (Ps < .05). For maximal speed, initial contact ankle frontal plane angle became more positive with age, and there was a negative relationship with age and peak eversion, dorsiflexion and knee flexion, and knee flexion and hip adduction at initial contact (Ps < .05). Primarily distal joint angles decreased with increasing age in female recreational runners at self-selected running speeds.

No Difference in Psychotropic Medication Use in Cosmetic and General Dermatology Patients.

BACKGROUND: Patients presenting for appearance-related concerns are often perceived as being more difficult (ie, more needy, more difficult to satisfy) than patients presenting for medical dermatologic problems. While the reasons for this perception are many, some hypothesize that this may be related to a higher rate of anxiety, depression, or body image issues among these patients.
OBJECTIVE: To determine the prevalence of psychotropic medication use in cosmetic dermatology patients compared to the prevalence of such medication use in general dermatology patients.
METHODS & MATERIALS: The study was a retrospective chart review of female patients, 18 or older, new to a private practice. Exclusion criteria included dermatologic disorders with known psychosocial comorbidity. Psychotropic medication use was recorded.
RESULTS: The percentage of subjects in the medical group (n=156) who reported using psychotropic medications was 22.2% compared to 26.8% in the cosmetic group (n=154; P=0.09).
CONCLUSION: The prevalence of psychotropic medication use among all dermatology patients in our practice was relatively high, but there was no statistically significant difference in the rate of psychotropic medication use in cosmetic dermatology patients compared to general dermatology patients.

J Drugs Dermatol. 2016;15(7):858-861.

Engineering the surface patchiness and topography of polystyrene colloids: From spheres to ellipsoids.

HYPOTHESIS: Colloidal surface morphology determines suspension properties and applications. While existing methods are effective at generating specific features on spherical particles, an approach extending this to non-spherical particles is currently missing. Synthesizing un-crosslinked polymer microspheres with controlled chemical patchiness would allow subsequent thermomechanical stretching to translate surface topographical features to ellipsoidal particles. EXPERIMENTS: A systematic study using seeded emulsion polymerization to create polystyrene (PS) microspheres with controlled surface patches of poly(tert-butyl acrylate) (PtBA) was performed with different polymerization parameters such as concentration of tBA monomer, co-swelling agent, and initiator. Thermomechanical stretching converted seed spheres to microellipsoids. Acid catalyzed hydrolysis (ACH) was performed to remove the patch domains. Roughness was characterized before and after ACH using atomic force microscopy. FINDINGS: PS spheres with controlled chemical patchiness were synthesized. A balance between two factors, domain coalescence from reduced viscosity and domain growth via monomer absorption, dictates the final PtBA) patch features. ACH mediated removal of patch domains produced either golf ball-like porous particles or multicavity particles, depending on the size of the precursor patches. Patchy microspheres were successfully stretched into microellipsoids while retaining their surface characteristics. Particle roughness is governed by the patch geometry and increases after ACH. Overall, this study provides a facile yet controllable platform for creating colloids with highly adjustable surface patterns.

Nanoscale Porosity in Microellipsoids Cloaks Interparticle Capillary Attraction at Fluid Interfaces.

Anisotropic particles pinned at fluid interfaces tend toward disordered multiparticle configurations due to large, orientationally dependent, capillary forces, which is a significant barrier to exploiting these particles to create functional self-assembled materials. Therefore, current interfacial assembly methods typically focus on isotropic spheres, which have minimal capillary attraction and no dependence on orientation in the plane of the interface. In order to create long-range ordered structures with complex configurations via interfacially trapped anisotropic particles, control over the interparticle interaction energy via external fields and/or particle engineering is necessary. Here, we synthesize colloidal ellipsoids with nanoscale porosity and show that their interparticle capillary attraction at a water-air interface is reduced by an order of magnitude compared to their smooth counterparts. This is accomplished by comparing the behavior of smooth, rough, and porous ellipsoids at a water-air interface. By monitoring the dynamics of two particles approaching one another, we show that the porous particles exhibit a much shorter-range capillary interaction potential, with scaling intriguingly different than theory describing the behavior of smooth ellipsoids. Further, interferometry measurements of the fluid deformation surrounding a single particle shows that the interface around porous ellipsoids does not possess the characteristic quadrupolar symmetry of smooth ellipsoids, and quantitatively confirms the decrease in capillary interaction energy. By engineering nanostructured surface features in this fashion, the interfacial capillary interactions between particles may be controlled, informing an approach for the self-assembly of complex two-dimensional microstructures composed of anisotropic particles.

Treatment of peristomal pyoderma gangrenosum with topical crushed dapsone.

A 27-year-old male with a history of Crohn's disease was treated for chronic pyoderma gangrenosum at his stoma site. Treatment with topical application of crushed dapsone resulted in improvement of his pyoderma gangrenosum. Crushed dapsone may be an efficacious treatment with minimal systemic side effects. This appears to be the first case of pyoderma gangrenosum treated with crushed dapsone.

A Multilevel Approach to Understand the Context and Potential Solutions for Low Colorectal Cancer (CRC) Screening Rates in Rural Appalachia Clinics.

PURPOSE: To explore system/staff- and patient-level opportunities to improve colorectal cancer (CRC) screening within an 11-clinic Federally Qualified Health Center (FQHC) in rural Appalachia with CRC screening rates around 22%-30%. METHODS: Using a convergent parallel mixed-methods design, staff (n = 26) and patients (n = 60, age 50-75, 67% female, 83%

Increased shedding of HU177 correlates with worse prognosis in primary melanoma.

BACKGROUND: Increased levels of cryptic collagen epitope HU177 in the sera of melanoma patients have been shown to be associated with thicker primary melanomas and with the nodular histologic subtype. In this study, we investigate the association between HU177 shedding in the sera and clinical outcome in terms of disease-free survival (DFS) and overall survival (OS). METHODS: Serum samples from 209 patients with primary melanoma prospectively enrolled in the Interdisciplinary Melanoma Cooperative Group at the New York University Langone Medical Center (mean age = 58, mean thickness = 2.09 mm, stage I = 136, stage II = 41, stage III = 32, median follow-up = 54.9 months) were analyzed for HU177 concentration using a validated ELISA assay. HU177 serum levels at the time of diagnosis were used to divide the study cohort into two groups: low and high HU177. DFS and OS were estimated by Kaplan-Meier survival analysis, and the log-rank test was used to compare DFS and OS between the two HU177 groups. Multivariate Cox proportional hazards regression models were employed to examine the independent effect of HU177 category on DFS and OS. RESULTS: HU177 sera concentrations ranged from 0-139.8 ng/ml (mean and median of 6.2 ng/ml and 3.7 ng/ml, respectively). Thirty-eight of the 209 (18%) patients developed recurrences, and 34 of the 209 (16%) patients died during follow-up. Higher HU177 serum level was associated with an increased rate of melanoma recurrence (p = 0.04) and with increasing mortality (p = 0.01). The association with overall survival remained statistically significant after controlling for thickness and histologic subtype in a multivariate model (p = 0.035). CONCLUSIONS: Increased shedding of HU177 in the serum of primary melanoma patients is associated with poor prognosis. Further studies are warranted to determine the clinical utility of HU177 in risk stratification compared to the current standard of care.

Design of an entrustable professional activity for adult extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation supports severe cardiac or pulmonary failure. There are currently no competency-based standards for extracorporeal membrane oxygenation training. METHODS: Extracorporeal membrane oxygenation experts were interviewed using a structured interview. Responses were audio recorded, transcribed, and validated by respondents. Interviews were coded using grounded theory with a constant comparison method. Themes were developed and used to construct the entrustable professional activity, which was reviewed by the extracorporeal membrane oxygenation experts. RESULTS: Nine experts were interviewed; all had experience with trainees. Interview themes identified include patient selection, circuit and medical management, multidisciplinary communication, problem-based learning and simulation, and entrustment decisions. Essential functions of the entrustable professional activity were patient selection, circuit management, cannula selection, responding to circuit emergencies/complications, anticoagulation management, weaning, and family/team communication. CONCLUSIONS: Essential functions of an extracorporeal membrane oxygenation entrustable professional activity were defined using data from structured interviews. The resultant entrustable professional activity could be implemented by critical-care programs as a scaffolding for competency-based fellow training.

End-of-Life Nursing Knowledge Among Nursing Students.

BACKGROUND: The U.S. health care system is poorly designed to meet the needs of patients at the end of life (EOL) and their families. Nursing students often have reported feeling inadequate to provide EOL care. METHOD: Following an EOL simulation, reflective journals were collected from junior and senior nursing students and analyzed for themes using qualitative content analysis. The condensed meaning units were abstracted into codes based on Carper's fundamental patterns of knowing. RESULTS: Thirty-one junior and senior nursing students (mean age, 21.04 ± 0.52 years, 96.2% female) in a baccalaureate program participated in the study. The broad themes of student reflections included empirics (theoretical or natural historical) aesthetics (transformative nursing action), personal (interpersonal process of nurse-patient interaction), and ethics (emotion influences actions). CONCLUSION: Student perception and participation in all roles contributes to the gestalt of the experience of a highly emotional EOL simulation for both students and faculty. [J Nurs Educ. 2020;59(3):154-157.].

Functional Interrogation of a Depression-Related Serotonergic Single Nucleotide Polymorphism, rs6295, Using a Humanized Mouse Model.

The serotonin 1A receptor (5-HT1A) system has been extensively implicated in modulating mood and behavior. Notably, 5-HT1A levels in humans display remarkable variation, and differences in receptor levels have been linked with a variety of psychiatric disorders. Further, reduction of receptor levels by 30-50% in mice suggests that changes in receptor levels that model existing human variation are sufficient to drive behavioral alterations. As a result, genetic mechanisms that modulate human 5-HT1A levels may be important for explaining individual differences in mood and behavior, representing a potential source of psychiatric disease risk. One common genetic variant implicated in differential 5-HT1A levels is the G/C single nucleotide polymorphism (SNP) rs6295, located upstream of the human 5-HT1A gene. This SNP differentially binds the transcription factor, NUDR/Deaf1, leading to cell-type specific effects on transcription in vitro. To investigate the direct effects of this SNP in the heterogeneous cellular context of the brain, we generated humanized transgenic mice using a design that maximized the local transcriptional landscape of the human HTR1A gene while also controlling for effects of genomic insertion location. We integrated a 180 kb human bacteria artificial chromosome (BAC) transgene containing G- and C-alleles of rs6295 flanked by FRT or loxP sites. Subsequent deletion of each allele by Cre- or Flp-recombinase resulted in rs6295G and C alleles in the same genomic location. These alleles were bred onto a 5-HT1A null mouse such that the human BAC was the sole source of 5-HT1A in these mice. We generated three separate lines, two of which had detectable human 5-HT1A levels in the brain, although none displayed expression in the raphe. Of these, one line exhibited rs6295-dependent differences in 5-HT1A levels and differences in behavior, even though the overall levels were considerably lower than native expression levels. The line-dependent effect of rs6295 on protein levels and behavior may depend upon differences in background genetic factors or different insertion sites across each line. This work confirms that relatively subtle differences in 5-HT1A levels can contribute to differences in behavior and highlights the challenges of modeling human noncoding genetic variation in mice.

Knowledge and Practice Discordance in Treating Urinary Tract Infections.

BACKGROUND AND OBJECTIVES: Urinary tract infections (UTIs) are a common condition in women. Guidelines have been published on the diagnosis and management of such infections with the twin goals of improved patient safety and avoiding unnecessary health care costs. In this study we evaluated both physicians' knowledge of these guidelines, and whether that knowledge translates to their clinical practice. METHODS: We performed a retrospective chart review of UTI management before and after an educational intervention in a family medicine residency. Two control sites were also included. We also assessed physicians' knowledge of current UTI management guidelines using an anonymous quiz. RESULTS: At the intervention site, guideline adherence improved following the educational session. Inappropriate culture use decreased from 88% to 68% (P<.005) while first-line antibiotic use increased from 68% to 92% (P<.005). No such benefits were seen at the control sites. The control and intervention site providers did not differ in knowledge of antibiotic choice on the quiz (86% and 88% correct respectively, P=.85), but all control providers felt routine cultures were appropriate, whereas only 38% of the intervention providers did (P<.05). CONCLUSIONS: A simple educational intervention made an impact on the management of UTI. Our results also highlighted that knowledge and practice are not always aligned.