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The sulfur dioxide (SO2) compound is a primary environmental pollutant worldwide, whereas elemental sulfur (S) is a global commodity possessing a variety of industrial as well as commercial functions. The chemical relationship between poisonous SO2 and commercially viable elemental S has motivated this investigation using the Density Functional Theory calculation of the relative transition state barriers for the two-step dehydro-sulfurization oxidation–reduction reaction. Additionally, doubly-charged nanoscale platelet molybdenum disulfide (MoS2), armchair (6,6) carbon nanotube, 28-atom graphene nanoflake (GR-28), and fullerene C-60 are utilized as catalysts. The optimal heterogeneous and homogeneous catalysis pathways of the two-step oxidation–reduction from SO2 to elemental S are further inspired by the biomimicry of the honeybee species’ multi-step bio-catalysis of pollen conversion to organic honey. Potential applications include environmental depollution, the mining of elemental sulfur, and the functionalization of novel technologies such as the recently patented aerial and amphibious LynchpinTM drones.

Adaptable degradative responses to multiple biological stimuli are of great importance for biorecognition. Here, enzymatic and ROS degradability are tuned by monomer identity and sequence in a series of sequence-defined oligomers.

Purpose Islamophobia is a growing social problem that leads to the discrimination of Muslims. Using Group Conflict Theory and the Integrated Threat Theory as the theoretical frameworks, this study aims to measure the presence of Islamophobia in the hiring practices of the most southern state of Switzerland. Design/methodology/approach An experimental formative research study was conducted with employees. Based on CVs for two positions, back-office and front-office, candidates were selected for interviews and reasons were provided. Two variables were manipulated to represent the “Muslim appearance” on the CVs: the picture and the name. A content analysis of reasons was conducted in addition to descriptive statistics of survey responses. Findings A negative perception of Muslim candidates emerged from the answers with a clear difference between the two scenarios: candidates perceived to be Muslim were not rejected from the back-office position, but they were from the front-office position. Social implications Results demonstrate that hiring practices in Ticino Switzerland are, in some cases, based on a prejudicial attitude. As long as Muslims were “not seen as Muslims to the customers,” they were judged as acceptable for the job. This has implications for social marketing research and practice aimed to change this discrimination behavior. A next step could be to understand if it is fear of Muslims or fear of what the public might think of Muslims that cause the selection difference between the two jobs. Systems-wide and macro level social marketing research is well suited to investigate such problems and test solutions, in a local context, following the methodology used in this study. Originality/value A disturbing escalation of the phenomenon of Islamophobia has emerged across the globe. This paper examines a fundamental issue in equity and prosperity, which is equal opportunity for employment. Using experimental design, the authors find that discrimination exists in hiring practices, which is a problem that social marketing is well equipped to address.

Studies show it is safe to have multiple sessions of single laser treatment over an appropriate time period, which allows for the skin to heal between treatments. Waiting to have several sessions may not be realistic for every patient. Physicians may combine laser treatments into a single session to accommodate for patient convenience and to achieve cosmetic improvement faster. Although individual laser therapies are reported to have minimal side effects, few studies explore the safety of multiple laser treatments in a single session.This study is a retrospective chart review from a single-physician patient pool. Patients who received 1 laser treatment in a single session were compared to those who received 2 or more laser treatments in a single session. Patients were evaluated for treatment type and safety, measured by the Common Terminology Criteria for Adverse Events (CTCAE). The CTCAE is a validated severity scale (1-5) where 1 represents minimal adverse events and 5 represents death. Adverse event scores were acquired from follow-up visits, messages through the electronic health record, or follow-up phone calls.Over a 12-month period, 89 patients qualified for the study with 152 sessions recorded: 116 had 1 laser treatment and 36 had 2 or more laser treatments in a single session. All but 1 patient scored a 1 on the CTCAE, the other, a 2.This study suggests there is no difference in adverse events from a single laser treatment vs 2 or more laser treatments in a single session. J Drugs Dermatol. 2022;21(11):1181-1184. doi:10.36849/JDD.6766.

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD,a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy.

Inflammation is a crucial part of wound healing and pathogen clearance. However, it can also play a role in exacerbating chronic diseases and cancer progression when not regulated properly. A subset of current innate immune engineering research is focused on how molecules such as lipids, proteins, and nucleic acids native to a healthy inflammatory response can be harnessed in the context of biomaterial design to promote healing, decrease disease severity, and prolong survival. The engineered biomaterials in this review inhibit inflammation by releasing anti-inflammatory cytokines, sequestering proinflammatory cytokines, and promoting phenotype switching of macrophages in chronic inflammatory disease models. Conversely, other biomaterials discussed here promote inflammation by mimicking pathogen invasion to inhibit tumor growth in cancer models. The form that these biomaterials take spans a spectrum from nanoparticles to large-scale hydrogels to surface coatings on medical devices. Cell-inspired molecules have been incorporated in a variety of creative ways, including loaded into or onto the surface of biomaterials or used as the biomaterials themselves. IMPACT STATEMENT: Chronic inflammatory diseases and cancers are widespread health care concerns. Treatment plans for these diseases can be complicated and the outcomes are often mixed due to off-target effects. Current research efforts in immune engineering and biomaterials are focused on utilizing the body's native immune response to return to homeostasis as a therapeutic approach. This review collects many of the most current findings in the field as a resource for future research.

PurposeThe objective of this study was to quantify inter-surgeon variation in strabismus surgery reoperation rates in a large national database of provider payments, and to explore associations of reoperation rate with practice type and volume, surgical techniques, and characteristics of the patient population.MethodsFee-for-service payments to providers for Medicare beneficiaries having strabismus surgery between 2012 and 2020 were retrospectively analyzed to identify reoperations in the same calendar year. The adjustable-suture technique was considered to be available to the patient if the patient’s surgeon billed for adjustable sutures. Predictors of the rate of reoperation for each surgeon were determined by multivariable linear regression.ResultsAmong 141 surgeons, the reoperation rate for 1-horizontal muscle surgery varied between 0.0% and 30.8%. Due to the presence of high-volume surgeons with high reoperation rates, just 11 surgeons contributed half of the reoperation events for 1-horizontal muscle surgery in this national database. Use of adjustable sutures, surgeon gender, and surgical volume were not independently associated with surgeon reoperation rate. Associations of reoperation with patient characteristics, such as age and poverty, were explored. In a multivariable model, surgeons in the South tended to have a higher reoperation rate (p=0.03). Still, the multivariable model could explain only 16.3% of the variation in surgeon reoperation rate for 1-horizontal muscle. For 1-vertical muscle surgery, patient poverty was associated with a lower surgeon reoperation rate (p=0.008).ConclusionsPatient-level analyses which ignore inter-surgeon variation will be dominated by the practices of a small number of high-volume, high-reoperation surgeons. There are order-of-magnitude variations in reoperation rates among strabismus surgeons, the cause of which remains largely unexplained.

The disintegrin and metalloproteinase 17 (ADAM17) exhibits α-secretase activity, whereby it can prevent the production of neurotoxic amyloid precursor protein-α (APP). ADAM17 is abundantly expressed in vascular endothelial cells and may act to regulate vascular homeostatic responses, including vascular growth and vasomotor function. We hypothesized that cerebrovascular ADAM17 plays a role in the pathogenesis of Alzheimer’s disease (AD). Here we found that 8-10 months old APP/PS1 mice (expressing transgenes for APP Swedish mutation and PSEN1 with L166P mutation) with significant cognitive deficits display a markedly reduced expression of ADAM17 in cerebral microvessels. Systemic delivery and AAV-mediated re-expression of ADAM17 in APP/PS1 mice improved cognitive functioning, without affecting β-amyloid plaque density. Moreover, we found that the endothelium-dependent vasodilator function of isolated and pressurized cerebral arteries in APP/PS1 mice was impaired, which was restored to normal levels by the ADAM17 re-expression. The cerebral microvascular network density in the APP/PS1 mice before or after ADAM17 re-expression was not affected. In addition, proteomic analysis identified several differentially expressed molecules involved in AD neurodegeneration and repair that were reversed by ADAM17 re-expression. Thus, we propose that a reduced ADAM17 expression in cerebral microvessels impairs vasodilator function, whereby it contributes to the development of cognitive dysfunction in APP/PS1 mice, and that ADAM17 can potentially be targeted for therapeutic intervention in AD. T32HL155011; 20PRE35211126 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

IntroductionThe disintegrin and metalloproteinase 17 (ADAM17) exhibits α-secretase activity, whereby it can prevent the production of neurotoxic amyloid precursor protein-α (APP). ADAM17 is abundantly expressed in vascular endothelial cells and may act to regulate vascular homeostatic responses, including vasomotor function, vascular wall morphology, and formation of new blood vessels. The role of vascular ADAM17 in neurodegenerative diseases remains poorly understood. Here, we hypothesized that cerebrovascular ADAM17 plays a role in the pathogenesis of Alzheimer’s disease (AD).Methods and resultsWe found that 9-10 months old APP/PS1 mice with b-amyloid accumulation and short-term memory and cognitive deficits display a markedly reduced expression of ADAM17 in cerebral microvessels. Systemic delivery and adeno-associated virus (AAV)-mediated re-expression of ADAM17 in APP/PS1 mice improved cognitive functioning, without affecting b-amyloid plaque density. In isolated and pressurized cerebral arteries of APP/PS1 mice the endothelium-dependent dilation to acetylcholine was significantly reduced, whereas the vascular smooth muscle-dependent dilation to the nitric oxide donor, sodium nitroprusside was maintained when compared to WT mice. The impaired endothelium-dependent vasodilation of cerebral arteries in APP/PS1 mice was restored to normal level by ADAM17 re-expression. The cerebral artery biomechanical properties (wall stress and elasticity) and microvascular network density was not affected by ADAM17 re-expression in the APP/PS1 mice. Additionally, proteomic analysis identified several differentially expressed molecules involved in AD neurodegeneration and neuronal repair mechanisms that were reversed by ADAM17 re-expression.DiscussionThus, we propose that a reduced ADAM17 expression in cerebral microvessels impairs vasodilator function, which may contribute to the development of cognitive dysfunction in APP/PS1 mice, and that ADAM17 can potentially be targeted for therapeutic intervention in AD.

Background: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder with cutaneous manifestations including poor wound healing and atrophic scar formation. There is evidence supporting the use of topical vitamin C and laser for scar revisions, but limited reports of using topical vitamin C in scar revisions in patients with hEDS. Objective: To present a case where topical vitamin C applied post-laser treatment resulted in improved healing and aesthetic outcomes in a patient with a connective tissue disorder. Methods: We present a case of treatment of atrophic and hypertrophic scars in a patient with hEDS with ablative fractional laser, pulsed dye laser, and post-procedural topical vitamin C. We discuss the patient’s treatments, outcomes, and previous literature on the matter. Results: This patient had markedly improved wound healing after topical application of vitamin C post-laser treatment with no complications. Additionally, the patient had improved aesthetic outcomes with topical vitamin C and laser treatment just after one session. Conclusion: This case suggests that hEDS scars may be safely treated with lasers when combined with post-procedural topical vitamin C.

We present a neutron diffraction study of NaYbO$_2$, a candidate quantum spin liquid compound hosting a geometrically frustrated triangular lattice of magnetic Yb$^{3+}$ ions. We observe diffuse magnetic scattering that persists to at least 20 K, demonstrating the presence of short-range magnetic correlations in this system up to a relatively high energy scale. Using reverse Monte Carlo and magnetic pair distribution function analysis, we confirm the predominant antiferromagnetic nature of these correlations and show that the diffuse scattering data can be well described by noninteracting layers of XY spins on the triangular lattice. We rule out Ising spins and short-range-ordered stripe or 120$^{\circ}$ phases as candidate ground states of NaYbO$_2$. These results are consistent with a possible QSL ground state in NaYbO$_2$ and showcase the benefit of combined reciprocal- and real-space analysis of materials with short-range magnetic correlations.

We aim at testing the main effects and interactions of three common categories of behavioral interventions: exposure to information (with vs. without), a social appeal (with collective action framing vs. without), and two choice architecture menu variations (meat dishes salience nudge vs. meat-free dishes salience nudge). The main outcome of interest is the climate footprint of food choices of university students in Switzerland, on a meal selection task-based scenario. Climate footprint is estimated based on a life cycle analysis of the selected meals. Secondary outcomes include intention to reduce meat consumption, support for food climate policies, and willingness to try food innovations.

Cosmetic dermatology is a key subspecialty of academic dermatology. As such, academic centers are expected to demonstrate excellence in the teaching of cosmetic dermatology skills to trainees, the clinical delivery of cosmetic dermatology services to patients, and the performance of clinical research that advances knowledge and uncovers new therapies in cosmetic dermatology. The Association of Academic Cosmetic Dermatology (AACD), a newly formed medical professional society, includes as its principal aims the support of all of these areas. AACD is comprised of group of board-certified dermatologists who teach cosmetic and laser dermatology at US dermatology residency programs. An expert panel constituted by the AACD recently convened a workshop to review gaps pertaining to academic cosmetic dermatology. This panel considered needs and potential corrective initiatives in three domains: resident education, patient experience, and clinical research. The work of the panel was used to develop a roadmap, which was adopted by consensus, and which will serve to guide the AACD moving forward.

This paper examines a method of quantifying voter preferences and behavior using a two-stage multivoting (2SMV) model. The 2SMV model gives voters an endowment of additional votes exceeding the number of policies under consideration in a direct democracy-style election. Voters may freely allocate this endowment to any of the policies up for election. Using the 2SMV mechanism, the paper provides a methodology for identifying voter preferences and voting behavior within a staged multivoting system. From this methodology, three types of voting behavior are defined: policy indifference, strictly-dominating preferences, and fixed-weight preferences. Using experimental data collected from college students, the study evaluates the performance of the two-stage multivoting system in the context of the 2020 Democratic Presidential Primaries, compared to the traditional “one-person, one-vote” (1P1V) system. Using the full sample of observations, the 1P1V system resulted in a tie between Joe Biden and Bernie Sanders, while the 2SMV system selected Joe Biden over Bernie Sanders as the nominee by a 206 net vote difference. The study finds that the 2SMV system produces more unique and distant ranks between candidates, reducing the prevalence of ties common within the 1P1V system.

BACKGROUND AND OBJECTIVES We evaluated if oxymetazoline therapy combined with 595-nm pulsed dye laser (PDL) will be more beneficial than topical oxymetazoline alone for the improvement of erythematotelangiectatic rosacea. STUDY DESIGN/MATERIALS AND METHODS This was a randomized, controlled, prospective clinical trial approved by an independent Institutional Review Board, which enrolled 34 patients with moderate to severe clinical erythema (CEA) into a two-arm study of PDL with concomitant oxymetazoline cream (Arm 1) and oxymetazoline cream alone (Arm 2). Patients in Arm 1 were treated with 3 monthly laser sessions, which were started after 1 month of topical oxymetazoline cream. Thirty subjects continued with the study, and 25 subjects (Arm 1: 14, Arm 2: 11) completed the 6-month follow-up. With photographic comparison to baseline images, efficacy endpoints were based on clinical on-site grading by both the investigator and the patient, using the grading tools for CEA, Global Aesthetic Improvement (GAI) assessment, vessel size improvement, and subject self-assessment. These scales were assessed at baseline and/or at each clinical follow-up at 1, 2, 3, and 6 months. Subject satisfaction as well as post-treatment immediate response and treatment-associated pain scores were also evaluated. RESULTS Statistically significant improvement in CEA was seen in both arms at the 1-, 2-, and 3-month post-baseline visits (P

Social determinants of health (SDOH) are circumstances in which people grow, live, work, and play. Unmet SDOH needs can adversely affect mental and physical health; however, to date, there are no comprehensive publications that highlight human services providers’ (HSPs’) role in addressing SDOH. This article defines SDOH, delineates HSPs’ role in addressing SDOH, and provides conceptual frameworks that can be used by HSPs to promote SDOH in practice. Special consideration is given for a collective approach that incorporates multiple frameworks to promote holistic practice and health equity. The article concludes with implications for HSPs, administrators, and educators.

Video detailing how the study will be conducted.

All details pertaining to materials and procedure.

Skeletal muscle regeneration after severe damage is reliant on local stem cell proliferation and differentiation, processes that are tightly regulated by macrophages. Peripheral artery disease is a globally prevalent cardiovascular disease affecting millions of people. Progression of the disease leads to intermittent claudication, subsequent critical limb ischemia and muscle injury. Tissue-derived and ex vivo-expanded mesenchymal stromal cells (MSCs) for skeletal muscle regeneration have been studied, but pre-clinical and clinical results have not been consistent. As a result, the potential therapeutic efficacy and associated repair mechanisms of MSCs remain unclear. Numerous studies have demonstrated the vulnerability of delivered MSCs, with a precipitous drop in cell viability upon transplantation. This has prompted investigation into the therapeutic benefit of apoptotic cells, microvesicles, exosomes and soluble signals that are released upon cell death.In this study, we characterized various components produced by MSCs after cell death induction under different conditions. We discovered anti-inflammatory and pro-regenerative effects produced by cell components following a freeze and thaw (FT) process on macrophage polarization in vitro. We further investigated the underlying mechanisms of macrophage polarization by those components resulting from severe cell death induction.We found potent therapeutic effects from FT-induced cell debris are dependent on the externalization of phosphatidylserine on the plasma membrane. In contrast, effects from the supernatant of FT-induced cell death primarily depends on the released protein content. We then applied the FT-induced cell supernatant to an animal model of peripheral artery disease to treat muscle injury caused by severe ischemia. Treatment with the FT supernatant but not the vulnerable MSCs resulted in significantly improved recovery of muscle function, blood flow and morphology and inflammation resolution in the affected muscles 2 weeks after injury.This study validates the therapeutic potential of FT-induced supernatant obviating the need for a viable population from vulnerable MSCs to treat injury, thus providing a roadmap for cell-free therapeutic approaches for tissue regeneration.

Many professional societies utilize travel awards programs to foster inclusion and facilitate the professional development of underrepresented minority (URM) scientists. All member societies that participate in the Alliance to Catalyze Change for Equity in STEM Success (ACCESS) do so to some degree. Members of this meta-organization recently came together to share their different approaches to URM travel award program assessment. The practices of the Biophysical Society (BPS), one of the ACCESS member societies, is used as a case study to discuss the highlights of our findings. We share and discuss a framework for URM travel award program assessment.

Background: Parkinson’s disease (PD) neuropathology is characterized by intraneuronal protein aggregates composed of misfolded α-Synuclein (α-Syn), as well as degeneration of substantia nigra dopamine neurons. Deficits in olfactory perception and aggregation of α-Syn in the olfactory bulb (OB) are observed during early stages of PD, and have been associated with the PD prodrome, before onset of the classic motor deficits. α-Syn fibrils injected into the OB of mice cause progressive propagation of α-Syn pathology throughout the olfactory system and are coupled to olfactory perceptual deficits. Objective: We hypothesized that accumulation of pathogenic α-Syn in the OB impairs neural activity in the olfactory system. Methods: To address this, we monitored spontaneous and odor-evoked local field potential dynamics in awake wild type mice simultaneously in the OB and piriform cortex (PCX) one, two, and three months following injection of pathogenic preformed α-Syn fibrils in the OB. Results: We detected α-Syn pathology in both the OB and PCX. We also observed that α-Syn fibril injections influenced odor-evoked activity in the OB. In particular, α-Syn fibril-injected mice displayed aberrantly high odor-evoked power in the beta spectral range. A similar change in activity was not detected in the PCX, despite high levels of α-Syn pathology. Conclusion: Together, this work provides evidence that synucleinopathy impacts in vivo neural activity in the olfactory system at the network-level.

Through developing the Sport Fan Sense of Community (SFSC) scale, this study examined the factors that would constitute a sense of membership in a sport fan community, the impact of these factors on behavioral and psychological outcomes of membership, and their influence on the creation and maintenance of social capital through membership in the sport fan community. Sport fans ( N = 525) were surveyed and data were analyzed through a two-step confirmatory factor analysis and subsequent structural equation model analyses. A total of 17 items under five key factors were resulted for the SFSC scale, including Collective Unity, Positivity, Inclusivity, Social Opportunities, and Knowledgeable Members. These factors significantly ( p < .05) contributed to the psychological outcomes related to cognitive and affective benefits, as well as behavioral outcomes of increased game attendance, merchandise sales, and positive word of mouth. An individual’s sense of membership in the fan community also contributed to his/her bridging and bonding of social capital. This study built on previous conceptualizations of sport fan communities and developed the SFSC scale to delineate, specify, and measure one’s sense of membership in a fan community. The findings help further the theoretical understanding of sport fan communities and also provide evidence for sport organizations to identify operational areas in which they can communicate with consumers in order to create, channel, and sustain stronger communities.

Hydrogels are a class of biomaterials used for a wide range of biomedical applications, including as a three-dimensional (3D) scaffold for cell culture that mimics the extracellular matrix (ECM) of native tissues. To understand the role of the ECM in the modulation of cardiac cell function, alginate was used to fabricate crosslinked gels with stiffness values that resembled embryonic (2.66 ± 0.84 kPa), physiologic (8.98 ± 1.29 kPa) and fibrotic (18.27 ± 3.17 kPa) cardiac tissues. The average pore diameter and hydrogel swelling were seen to decrease with increasing substrate stiffness. Cardiomyocytes cultured within soft embryonic gels demonstrated enhanced cell spreading, elongation, and network formation, while a progressive increase in gel stiffness diminished these behaviors. Cell viability decreased with increasing hydrogel stiffness. Furthermore, cells in fibrotic gels showed enhanced protein expression of the characteristic cardiac stress biomarker, Troponin-I, while reduced protein expression of the cardiac gap junction protein, Connexin-43, in comparison to cells within embryonic gels. The results from this study demonstrate the role that 3D substrate stiffness has on cardiac tissue formation and its implications in the development of complex matrix remodeling-based conditions, such as myocardial fibrosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40204-020-00137-0) contains supplementary material, which is available to authorized users.

Vagal activation usually affects both sinus and atrioventricular (AV) nodes, manifesting as sinus slowing accompanied by varying degrees of AV block. AV block accompanying sinus acceleration as during treadmill testing is usually considered pathologic. We report 2 cases of vagally mediated reflex AV block accompanied by sinus tachycardia and acceleration. (Level of Difficulty: Intermediate.), Graphical abstract, Vagal activation usually affects both sinus and atrioventricular (AV) nodes, manifesting as sinus slowing accompanied by varying degrees of AV block…

Key hallmarks of inflammation include proinflammatory (M1) macrophages and production of reactive oxygen species (ROS). Therefore, we developed a ROS-sensitive, photoacoustic (PA) nanoprobe capable of identifying M1 macrophages in vitro. The nanoprobe is a silica-coated gold nanorod (AuNR), which provides a stable PA signal, combined with an adsorbed polyelectrolyte-dye (poly-d-lysine (PDL)-IR775c) coating that exhibits ROS sensitivity. By monitoring the ratio between these two PA intensities, we can determine if ROS is present. Upon loading, then stimulating, macrophages toward an M1 phenotype, we observe a significant decrease in the ratio of dye/AuNR intensities relative to a nonstimulated control. Our nanoprobe is also applied to a mouse model of peripheral artery disease (PAD), where we demonstrate an ability to identify early signs of muscle inflammation before symptoms or histologic evidence. Taken together, our nanoprobe can be a powerful tool for monitoring macrophage phenotype and inflammation in vivo.

Macrophages play a critical role in the initiation, maintenance, and resolution of inflammation because of their diverse and plastic phenotypic responses to extracellular stimuli. Inflammatory stimuli drive the recruitment and activation of inflammatory (M1) macrophages, capable of significant cytokine production that potentiates inflammation. Local environmental signals including apoptotic cell efferocytosis drive a phenotypic transition toward pro-reparative (M2) macrophages to facilitate the resolution of inflammation. However, prolonged or dysregulated inflammatory macrophage response contributes to many disease states and tissue damage. We have developed a nanoparticle to help resolve macrophage-mediated inflammation by mimicking the anti-inflammatory effect of apoptotic cell engulfment. The nanoparticle, comprised of a poly(lactide-co-glycolide) core, is coated in phosphatidylserine (PS)-supplemented cell plasma membrane to emulate key characteristics of the apoptotic cell surface. These apoptotic body-inspired PS/membrane-coated nanoparticles (PS-MNPs) reduce inflammatory cytokine expression to promote an anti-inflammatory, phenotypic shift in macrophages in vitro, without the use of small molecule inhibitors or other drugs. Specifically, PS-MNP treatment before lipopolysaccharide (LPS)-induced inflammatory challenge resulted in a 2.5-fold reduction in secreted tumor necrosis factor α (TNFα) at 24 h, with co-treatment of PS-MNPs and LPS demonstrating a 5-fold TNFα reduction compared to LPS alone. Reduced TNFα production, as well as gene expression of several pro-inflammatory cytokines, correlated with a reduction in NFκB activation from PS-MNP treatment. The development of a nanoparticle to reduce the production of multiple inflammatory cytokines and transition away from an inflammatory macrophage phenotype, through the use of a physiologic anti-inflammatory pathway, illustrates a new potential strategy in creating anti-inflammatory therapeutics. Statement of Significance Macrophages propagate inflammation as the major source of cytokine production in the body. In inflammatory diseases, pro-inflammatory macrophages persist in the site of inflammation and exacerbate tissue destruction. Current anti-inflammatory drugs have significant drawbacks, including variable response rates and off-target effects. Here, we have developed an apoptotic-body inspired nanoparticle to modulate inflammatory macrophage phenotype. This polymeric nanoparticle is coated with phosphatidylserine-supplemented cell plasma membrane to mimic the anti-inflammatory effect of apoptotic cell engulfment. Nanoparticle delivery reduces inflammatory cytokine production and promotes an anti-inflammatory phenotypic macrophage shift. The capacity of these nanoparticles to help resolve macrophage-mediated inflammation may be a useful tool to study macrophage-apoptotic cell interactions, the role of macrophages in inflammatory diseases, and in the design of anti-inflammatory therapeutics.

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been associated with numerous pathophysiological sequelae, including large artery vasospasm and microvascular thrombosis. The focus of this review is to provide an overview of experimental animal model studies and human autopsy studies that explore the temporal-spatial characterization and mechanism of microvascular platelet aggregation and thrombosis following SAH, as well as to critically assess experimental studies and clinical trials highlighting preventative therapeutic options against this highly morbid pathophysiological process. Upon review of the literature, we discovered that microvascular platelet aggregation and thrombosis occur after experimental SAH across multiple species and SAH induction techniques in a similar time frame to other components of DCI, occurring in the cerebral cortex and hippocampus across both hemispheres. We discuss the relationship of these findings to human autopsy studies. In the final section of this review, we highlight the important therapeutic options for targeting microvascular platelet aggregation and thrombosis, and emphasize why therapeutic targeting of this neurovascular pathology may improve patient care. We encourage ongoing research into the pathophysiology of SAH and DCI, especially in regard to microvascular platelet aggregation and thrombosis and the translation to randomized clinical trials.

Background and objectives Device innovation in dermatology is increasing. Medical devices identified as "substantially equivalent" to predicate ones by the United States Food and Drug Administration (FDA) may be exempt from premarket approval through the 510(k) pathway. The 510(k) pathway has been criticized for having less stringent clinical data requirements, and implications of dermatologic device clearance via this pathway are incompletely described. The objective of this study is to characterize dermatologic device clearance via the 510(k) pathway. Study design/materials and methods We performed a retrospective review of the FDA's 510(k) database between January 1, 1996 and December 31, 2018. Dermatologic devices were included based on product code and classified by the application. Approval pathways and decision characteristics were compared among dermatologic device categories. Results Of the 76,607 records screened, 4,637 met inclusion criteria. Laser/thermal devices comprised the largest category (64.2%), followed by wound (24.0%) and light-based devices (5.8%). The majority of 510(k) pathway submissions were traditional (89.2%) compared with alternative (10.8%) submission types (P = 0.003). Devices that were deemed substantially equivalent without limitations (98.5%) were the most common among all device categories. Rates of device clearance over the study period increased for all categories except laser/thermal devices. Conclusions Dermatologic devices are increasingly cleared via the FDA's 510(k) pathway through "substantial equivalence" with minimal requirements for premarket clinical data. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

The “Zen 2” processor is designed to meet the needs of diverse markets spanning server, desktop, mobile, and workstation. The core delivers significant performance and energy-efficiency improvements over “Zen” by microarchitectural changes including a new TAGE branch predictor, a double-size op cache, and a double-width floating-point unit. Building upon the core design, a modular chiplet approach provides flexibility and scalability up to 64 cores per socket with a total of 256 MB of L3 cache.

Self-assembling peptides can be used in a bottom-up approach to build hydrogels that are similar to the extracellular matrix at both structural and functional levels. In this study, a nucleo-tripeptide library was constructed to identify molecules that form hydrogels under physiological conditions. We used both experimental and computational approaches to study these self-assembled structures. Circular dichroism spectroscopy, transmission electron microscopy, and rheometry were utilized to support and supplement molecular dynamics simulations. Our data demonstrate that nucleo-tripeptides can form nanofibrous hydrogels through Watson-Crick base pairing and π-π stacking interactions. Self-assembly conditions are mediated by nucleo-tripeptide hydrophobicity and amphiphilicity and can therefore be regulated by a rational molecular design. We have found that structures derived from specific peptide and nucleobase conjugations form hydrogels under physiologic conditions, making them promising candidates for biomedical applications.