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In an era marked by a growing demand for sustainable and high-performance materials, the convergence of additive manufacturing (AM), also known as 3D printing, and the thermal treatment, or pyrolysis, of polymers to form high surface area hierarchically structured carbon materials stands poised to catalyze transformative advancements across a spectrum of electrification and energy storage applications. Designing 3D printed polymers using low-cost resins specifically for conversion to high performance carbon structures via post-printing thermal treatments overcomes the challenges of 3D printing pure carbon directly due to the inability of pure carbon to be polymerized, melted, or sintered under ambient conditions. In this perspective, we outline the current state of AM methods that have been used in combination with pyrolysis to generate 3D carbon structures and highlight promising systems to explore further. As part of this endeavor, we discuss the effects of 3D printed polymer chemistry composition, additives, and pyrolysis conditions on resulting 3D pyrolytic carbon properties. Furthermore, we demonstrate the viability of combining continuous liquid interface production (CLIP) vat photopolymerization with pyrolysis as a promising avenue for producing 3D pyrolytic carbon lattice structures with 15 μm feature resolution, paving way for 3D carbon-based sustainable energy applications.

Purpose of Review: This review examines best practices to ensure patient and clinician safety when performing inpatient dermatology consults. Recent Findings: Inpatient settings may not be optimized for dermatologic procedures and workflows, leading to unique challenges in ensuring patient safety. During consultations, dermatologists should focus on procedural safety in the inpatient setting, communicating clearly with the primary team, and supporting the transition from inpatient to outpatient care. Summary: Best practices emphasize standardization, clear communication, and workflow optimization to minimize safety risks during inpatient dermatology consultations. Dermatologists providing consultations in the inpatient setting should focus on patient and occupational safety during the consultation, particularly biopsies and procedures; optimize workflows for processing of dermatology specimens; and clearly communicate results and management recommendations. During the consultation, dermatologists should establish clear communication with both the primary team and patient to ensure proper implementation of the care plan and timely follow-up after discharge.

This article examines the rise of Javier Milei, a political figure in Argentina who has gained popularity among his supporters. Milei is seen as a messianic figure and a folk-hero, particularly in light of the country's increasing hunger and economic stagnation. The article delves into the failures of previous administrations and intellectuals in addressing these issues, and how Milei has capitalized on popular discontent. It also explores the influence of feminism and identity politics on Argentina's political landscape. Overall, the article provides an analysis of the political climate in Argentina and the factors contributing to Milei's rise. The author of the article is a writer who has published political articles in various publications and has also written poetry and performed at poetry festivals. [Extracted from the article]

This digest, based on an extensive review of research on comprehensive school reform, presents a brief overview of the role of teachers in comprehensive schoolwide reform (CSR). CSR is most successful when schools have decision-making autonomy in administration and instruction. Teachers also prefer models that fit with the school's overall environment, staffing, and student population, and those that mesh with reforms already in progress. Teachers play a vital role in CSR implementation. Providing them with adequate resources for implementation and time for planning promotes their support. Some CSR models are very prescriptive, and provide curricula and assessments, while other models rely more on the school to develop materials that support the philosophy of the reform. Among the factors that facilitate implementation of reform efforts by teachers include provision by the designers of a structured curriculum, concrete examples of instructional practices reflecting the reform, and specific, practical mechanisms for achieving the higher standards established as a goal. (Contains 14 references.) (SLD)

Irritable bowel syndrome is a gastrointestinal disorder that affects 15%–20% of the US population. Its symptoms can have negative effects on a person's quality of life, and its treatment can be associated with high medical costs. An emerging area of irritable bowel syndrome research concerns the relationship between this condition and the gut microbiome. The purpose of this article is not only to review irritable bowel syndrome, and the role that the microbiome can play in its symptoms, but also to examine new emerging pathways that could blaze the trail for more individualized treatments. If equipped with this knowledge, gastrointestinal nurses and providers of care can be better prepared to help patients with irritable bowel syndrome in order to manage symptoms and improve their quality of life.

IMPORTANCE: In clinical trials, preoperative immune checkpoint inhibitors (ICIs) have shown clinical activity in advanced cutaneous squamous cell carcinoma (cSCC). However, these studies excluded patients with relevant comorbidities. OBJECTIVE: To evaluate radiologic and pathologic response rates to neoadjuvant-intent programed cell death protein 1 (PD-1) ICIs in a clinical population. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of patients who were treated with neoadjuvant cemiplimab or pembrolizumab for advanced cSCC from January 2018 to January 2023 was conducted at 2 academic institutions in Boston, Massachusetts. Median follow-up was 9.5 months (range, 1.2-40.5). EXPOSURES: Cemiplimab or pembrolizumab. MAIN OUTCOMES AND MEASURES: Primary outcomes were radiologic and pathologic response rates. Secondary outcomes were 1-year recurrence-free survival, progression-free survival, disease-specific survival, and overall survival. RESULTS: This cohort study included 27 patients (including 9 patients [33.3%] with a history of lymphoma). Most patients were male (18 of 27 [66.7%]), with a median age of 72 years (range, 53-87 years). Most primary tumors were located on the head/neck (21 of 27 [77.8%]). There were no unexpected delays in surgery. The median number of doses before surgery was 3.5 (range, 1.0-10.0). Five patients (18.5%) ultimately declined to undergo planned surgery due to clinical responses or stability, and 1 (3.7%) did not undergo surgery due to progressive disease. The overall pathologic response rate (pathological complete response [pCR] or major pathological response) was 47.4% (9 of 19), and the overall radiologic response rate (radiologic complete response or partial response) was 50.0% (8 of 16). The pCR rate (7 of 19 [36.8%]) was higher than the radiologic complete response rate (2 of 16 [12.5%]). The pCR rate among patients with cSCC and concomitant lymphoma was 25.0%. The 1-year recurrence-free survival rate was 90.9% (95% CI, 50.8%-98.7%), progression-free survival was 83.3% (95% CI, 27.3%-97.5%), disease-specific survival was 91.7% (95% CI, 53.9%-98.8%), and overall survival was 84.6% (95% CI, 51.2%-95.9%). CONCLUSIONS AND RELEVANCE: The results of this cohort study support the reproducibility of neoadjuvant-intent immunotherapy for cSCC in the clinical setting, including for patients with a history of lymphoma. Outside of clinical trials, it is not infrequent for patients to opt out of surgery for regressing tumors. The inclusion of higher-risk patients and preference for nonsurgical treatment are 2 factors that might explain the numerically lower pathologic response rate in this institutional experience.

This article examines the relationship between the United States and Israel, particularly in light of the recent conflict in Gaza. It raises concerns about why the US seems unable to exert influence over Israeli actions, despite its declining global standing and President Biden's decreasing popularity. The article explores conspiracy theories suggesting that Israel actually controls US policy, criticizing Biden's perceived weakness and performative condemnations of Israeli Prime Minister Netanyahu. It also discusses Biden's history of supporting regime change and disregard for civilian suffering in other countries. The article concludes by suggesting that Biden's attempts at regime change have been unsuccessful, leaving the US weaker and outdated in the eyes of the world. Additionally, the text criticizes Western elites for celebrating the removal of Hamas without considering the loss of civilian lives and argues that the US is being held hostage by Israel's nuclear capabilities. The author suggests that Biden's slow response is influenced by pressure groups, including pro-Israeli lobbyists, and criticizes the failures of his foreign policy and the lack of accountability from progressives. [Extracted from the article]

Particle fabrication has attracted recent attention owing to its diverse applications in bioengineering1,2, drug and vaccine delivery3–5, microfluidics6,7, granular systems8,9, self-assembly5,10,11, microelectronics12,13and abrasives14. Herein we introduce a scalable, high-resolution, 3D printing technique for the fabrication of shape-specific particles based on roll-to-roll continuous liquid interface production (r2rCLIP). We demonstrate r2rCLIP using single-digit, micron-resolution optics in combination with a continuous roll of film (in lieu of a static platform), enabling the rapidly permutable fabrication and harvesting of shape-specific particles from a variety of materials and with complex geometries, including geometries not possible to achieve with advanced mould-based techniques. We demonstrate r2rCLIP production of mouldable and non-mouldable shapes with voxel sizes as small as 2.0 × 2.0 µm2in the print plane and 1.1 ± 0.3 µm unsupported thickness, at speeds of up to 1,000,000 particles per day. Such microscopic particles with permutable, intricate designs enable direct integration within biomedical, analytical and advanced materials applications.

The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs). Using laminar probes, we recorded LFPs from 14 cortical areas across the cortical hierarchy in five macaque monkeys. The laminar locations of recordings were histologically identified by electrolytic lesions. Across all areas, we found a ubiquitous spectrolaminar pattern characterized by an increasing deep-to-superficial layer gradient of high-frequency power peaking in layers 2/3 and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. Laminar recordings from additional species showed that the spectrolaminar pattern is highly preserved among primates—macaque, marmoset and human—but more dissimilar in mouse. Our results suggest the existence of a canonical layer-based and frequency-based mechanism for cortical computation.

Proliferating pilar tumors are rare neoplasms that differentiate toward the outer sheath near the isthmus and can rarely undergo malignant transformation. We performed histopathologic evaluation on 26 benign proliferating pilar tumor (BPPT) and 17 malignant proliferating pilar tumor (MPPT). Ki-67 and p53 immunostains were performed on 13 BPPT and 10 MPPT. Six MPPT cases were successfully analyzed by a next-generation sequencing platform which surveyed exonic DNA sequences of 447 cancer genes and 191 regions across 60 genes for rearrangement detection. Patient demographics and clinical characteristics were similar between the BPPT and MPPT groups. Follow-up data of 16 of 17 MPPT (median, 25 mo) showed metastasis in 1 MPPT. The histologic features associated with MPPT include size >2.5 cm, adjacent desmoplastic stroma, small nests or cords of atypical epithelium in surrounding stroma, irregular infiltration or borders, abnormal keratinization, large hyperchromatic nuclei, prominent nucleoli, severe cytologic atypia, nuclear pleomorphism, necrosis, and increased mitotic figures. MPPT harbors copy number gains of 15q and losses of 6p and 6q, findings previously reported in BPPT. However, MPPT harbors frequent TP53mutations as molecular markers of progression. Different from cutaneous squamous cell carcinoma, MPPT more frequently demonstrates low tumor mutational burden and typically lacks a UV signature, suggestive of a different etiologic pathway than squamous cell carcinoma. In summary, with a median follow-up of 25 months, this study shows that MPPT is a biologically indolent carcinoma with rare metastasis. Molecular analyses suggest a non–UV-related pathogenesis with frequent TP53aberration.

RNA-guided systems, which use complementarity between a guide RNA and target nucleic acid sequences for recognition of genetic elements, have a central role in biological processes in both prokaryotes and eukaryotes. For example, the prokaryotic CRISPR–Cas systems provide adaptive immunity for bacteria and archaea against foreign genetic elements. Cas effectors such as Cas9 and Cas12 perform guide-RNA-dependent DNA cleavage1. Although a few eukaryotic RNA-guided systems have been studied, including RNA interference2and ribosomal RNA modification3, it remains unclear whether eukaryotes have RNA-guided endonucleases. Recently, a new class of prokaryotic RNA-guided systems (termed OMEGA) was reported4,5. The OMEGA effector TnpB is the putative ancestor of Cas12 and has RNA-guided endonuclease activity4,6. TnpB may also be the ancestor of the eukaryotic transposon-encoded Fanzor (Fz) proteins4,7, raising the possibility that eukaryotes are also equipped with CRISPR–Cas or OMEGA-like programmable RNA-guided endonucleases. Here we report the biochemical characterization of Fz, showing that it is an RNA-guided DNA endonuclease. We also show that Fz can be reprogrammed for human genome engineering applications. Finally, we resolve the structure of Spizellomyces punctatusFz at 2.7 Å using cryogenic electron microscopy, showing the conservation of core regions among Fz, TnpB and Cas12, despite diverse cognate RNA structures. Our results show that Fz is a eukaryotic OMEGA system, demonstrating that RNA-guided endonucleases are present in all three domains of life.

Increases in youth vaping rates and concerns of a new generation of nicotine addicts recently prompted an increase in the federal minimum legal purchase age (MLPA) for tobacco products, including e-cigarettes, to 21 years. This study presents the first regression discontinuity evidence on the effectiveness of e-cigarette MLPA laws. Using data on 12th graders from Monitoring the Future, we obtain robust evidence that federal and state age 18 MLPAs decreased underage e-cigarette use by 15–20 percent and frequent use by 20–40 percent. These findings suggest that the age 21 federal MLPA could meaningfully reduce e-cigarette use among 18- to 20-year-olds.

In the study of micro-swimmers, both artificial and biological ones, many-query problems arise naturally. Even with the use of advanced high performance computing (HPC), it is not possible to solve this kind of problems in an acceptable amount of time. Various approximations of the Stokes equation have been considered in the past to ease such computational efforts but they introduce non-negligible errors that can easily make the solution of the problem inaccurate and unreliable. Reduced order modeling solves this issue by taking advantage of a proper subdivision between a computationally expensive offline phase and a fast and efficient online stage. This work presents the coupling of Boundary Element Method (BEM) and Reduced Basis (RB) Reduced Order Modeling (ROM) in two models of practical interest, obtaining accurate and reliable solutions to different many-query problems. Comparisons of standard reduced order modeling approaches in different simulation settings and a comparison to typical approximations to Stokes equations are also shown. Different couplings between a solver based on a HPC boundary element method for micro-motility problems and reduced order models are presented in detail. The methodology is tested on two different models: a robotic-bacterium-like and an Eukaryotic-like swimmer, and in each case two resolution strategies for the swimming problem, the split and monolithic one, are used as starting points for the ROM. An efficient and accurate reconstruction of the performance of interest is achieved in both cases proving the effectiveness of our strategy.

Cutaneous myiasis is an infection most commonly caused globally by Dermatobia hominus, the human botfly, which is endemic to Central and South America. In North America, the most common cause of cutaneous myiasis is infestation with the larvae of Cuterebra, the North American botfly. The authors describe a 44-year-old man who presented with a 1-month history of intermittent, severe, boring pain along the side of his nose that progressed to swelling and redness along his right inferior orbital rim and lacrimal sac. CT imaging showed a rim-enhancing collection at the right medial canthus with surrounding phlegmonous changes communicating with the skin. Pathologic evaluation revealed curvilinear pigmented material associated with a granulomatous and eosinophil-rich inflammatory infiltrate, consistent with botfly myiasis. This case describes the pathogenesis of the botfly infestation in humans, as well as the clinical, radiographic, and histopathologic features of this rare orbital infection, with an emphasis on its treatment.This report describes a 44-year-old man with botfly myiasis with periorbital involvement and provides an update on the pathophysiology of the infectious agent, as well as the diagnostic and therapeutic modalities for this rare infection.

Background/Objectives: The aim of this study was to ascertain the use of ocular imaging and the updated screening criteria in the evaluation of choroidal nevus across the United States. Methods: Sixty ophthalmologists completed an anonymous 21-question survey addressing their use of the screening criteria for evaluating choroidal nevi, as well as their use of ultrasonography (US), optical coherence tomography (OCT), and autofluorescence (AF) in daily practice. Results: The majority of respondents were from the Northeast (55%), worked in private practice (83%), and practiced general ophthalmology (42%). The 2009 criteria TFSOM-UHHD was used by 39 (65%) respondents, while the 2019 criteria TFSOM-DIM was used by 29 (48%) respondents. Compared to anterior segment ophthalmologists, posterior segment ophthalmologists were more likely to use the TFSOM-UHHD criteria (94% vs. 53%, OR = 13.9, p= 0.014), the TFSOM-DIM criteria (88% vs. 33%, OR = 15.5, p< 0.001), fundus AF (82% vs. 19%, OR = 20.4, p< 0.001), and US (94% vs. 42%, OR = 22.2, p= 0.004) in daily practice. Conclusions: From the survey of current practice patterns, we learned that there is a general trend of underutilization of the proper imaging modalities – and thus the criteria – in evaluating choroidal nevus. More education about ocular cancer and its screening could improve patient outcomes in the future.

To describe the epidemiology and complications of platelet transfusions among hospitalized pediatric patients during 2010 to 2019.We performed a retrospective cohort study of hospitalized children within the Pediatric Health Information System database. Pediatric encounters receiving at least one platelet transfusion during hospitalization from 2010 to 2019 were identified. Data regarding demographics, diagnoses, procedures required during hospitalization, complications, and outcomes were extracted for eligible encounters.Within the Pediatric Health Information System database, 6 284 264 hospitalizations occurred from 2010 to 2019. A total of 244 464 hospitalizations required at least one platelet transfusion, yielding a prevalence of 3.89% (95% confidence interval [CI], 3.87%–3.91%). Transfusion prevalence did not change significantly across the decade (P value = .152). Two-thirds of children receiving platelet transfusions were in their first 6 years of life, and the majority identified as male (55%). Recipients most commonly had diseases of the circulatory system (21%, 52 008 of 244 979), perinatal disorders (16%, 38 054 of 244 979), or diseases of the hematologic/immune systems (15%, 37 466 of 244 979). When adjusted for age, support by extracorporeal membrane oxygenation, mechanical ventilation, surgical intervention, and diagnostic category, the odds of thrombosis, infection, and mortality increased by 2% (odds ratio [OR], 1.02; 95% CI, 1.016–1.020), 3% (OR, 1.03; 95% CI, 1.028–1.033), and 7% (OR, 1.07; 95% CI, 1.067–1.071), respectively, with each additional transfusion.The prevalence of platelet transfusions among pediatric inpatients remained consistent across the decade. Our finding that increasing numbers of transfusions may be associated with elevated morbidity and mortality is consistent with other observation and experimental studies, highlighting the need to be thoughtful in weighing risks and benefits when prescribing repeated platelet transfusions to hospitalized children.

Nanotechnology is a new emerging cutting-edge technology in the 21st century and has applications in medical, cosmetics, electronics, energy, food, agriculture, and many sectors. Nanomaterials (NMs) are the main component of nanotechnology. NMs prepared by chemical routes are very hazardous and not safe for life. Therefore, attempts are being made to prepare NMs via different green routes. It is expected that nanotechnology using green synthesized NMs will be safe. At the same time, green synthesized nanomaterials will be cost-effective. In this chapter, the applications of green synthesized NMs in agriculture have been discussed in detail.

The green synthesis of nanomaterials is nowadays gaining great attention owing to several beneficial aspects in terms of the low toxicity of reagents and by-products, low damage to the health and the environment, sustainability of energy savings and rational use of natural resources. The intrinsic complexity offered by the biological sources (plants, microorganisms, animal products) and the conditions applied in the synthetic procedures forms various nanomaterials with different sizes, morphologies and surface properties that strongly determine their functionality and applications. A deep understanding of the role of biological components, the mechanism of nanostructure formation and growth, and the effects of green synthesis conditions is of paramount importance to achieving the desired nanomaterial for the required application. In this context, this review aims to provide an overview of the structural and functional complexity of nanomaterials achieved by using green synthesis procedures, with a special focus on the role of biological sources and parameters in controlling the complexity and benefit of nanomaterial applications.

To estimate the incidence of invasive pneumococcal disease (IPD) in the pre–13-valent pneumococcal conjugate vaccine (pre-PCV13; 7-valent pneumococcal conjugate vaccine era, 2002-2010) and post-PCV13 (2011-2018) time periods.

Low doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects, but the underlying mechanisms remain unclear. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that are activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNSTGA). The majority of ovBNSTGAneurons express neurotensin receptor 1 (Ntsr1) and form circuits with brain regions known to regulate anxiety and stress responses. Optogenetic activation of ovBNSTGAor ovBNSTNtsr1neurons significantly attenuated anxiety-like behaviors in both naive animals and mice with inflammatory pain, while inhibition of these cells elevated anxiety. Activation of these neurons decreased heart rate and increased heart rate variability, suggesting that they reduce anxiety by modulating autonomic responses. Our study identifies ovBNSTGA/ovBNSTNtsr1neurons as a common neural substrate mediating the anxiolytic effect of low-dose anesthetics and a potential therapeutic target for treating anxiety-related disorders.

Background/Context: Instructional policy aims to shift the nature of teaching and learning. Decades of policy studies have highlighted the challenges inherent in these aims and the conditions necessary to support such change, including a robust infrastructure to support teacher learning. Further, teachers themselves must perceive and experience their policy environment to be supportive of calls to shift instruction.Purpose/Objective/Research Question/Focus of Study: In this study, we examine the connection between teachers’ perceptions of their policy environments and their instructional practices over time, in the context of college-and-career-readiness (CCR) standards implementation. While conducted in the context of standards implementation, our findings apply to supporting instructional change through policy more broadly.Setting: We examine implementation of CCR standards in two unique state contexts: Texas and Ohio. These states represent important differences in demographics and in their approaches to CCR standards implementation over time.Research Design: We use a convergent mixed-methods design that draws on state-representative teacher survey data at two points in time (allowing for a trend analysis to understand how teachers’ perceptions and experiences evolve), longitudinal interview data with state education leaders, and interview data with educators in one case study district in each state.Data Collection and Analysis: Surveys measured teachers’ perceptions of their policy environments, as well as their self-reported instructional practices. Interviews focused on understanding state- and district-level policies, guidance, and resources, and educators’ enactment of standards. Survey analysis included descriptive analysis of patterns over time and hierarchical linear modeling. To unpack broad-based survey patterns, we coded qualitative data and developed assertions based on emergent patterns.Findings/Results: We found that Texas teachers agreed more strongly than Ohio teachers that their policy environment had aligned, specific, and stable resources, as well as accountability mechanisms in place. Specificity of guidance and resources for standards implementation predicted teachers’ use of standards-emphasized instruction in 2019. These patterns reflected each state’s approach to policy implementation: a robust state-level infrastructure for guidance and support in Texas, compared with fewer state-developed resources in Ohio in favor of local control. Still, aspects of teachers’ local context—in particular, lack of infrastructure for ongoing, embedded professional learning—limited teachers’ ability to engage in state-developed guidance.Conclusions/Recommendations: Our study offers enduring lessons about how to establish the policy conditions necessary to support teachers to change instruction. Findings suggest a need for states to develop resources that clarify instructional shifts for teachers, and districts must balance these top-down resources with ongoing opportunities for educators to adapt resources to suit their students’ needs.

Postoperative atrial fibrillation (POAF) is one of the most common complications after cardiac surgery. POAF is associated with a longer hospital stay, higher healthcare resource utilization, and higher risk of morbidity and mortality. As a result, the American and European guidelines recommend the use of beta-blockers and amiodarone for the prevention of POAF, and in turn, avoid the complications associated with POAF.

IMPORTANCE: Given that mycosis fungoides−cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT). OBJECTIVES: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL. DESIGN, SETTINGS, AND PARTICIPANTS: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL. INTERVENTIONS: In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020. RESULTS: The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred. CONCLUSION AND RELEVANCE: The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02448381

Pulsed electric field (PEF) ablation is an emerging modality for the treatment of cardiac arrhythmias. Data regarding effects on the interventricular septum are limited, and the optimal delivery protocol and electrode configuration remain undefined.

Heart block requiring permanent pacemaker (PPM) implantation is a relatively frequent complication of transcatheter aortic valve replacement (TAVR).

Biomaterials capable of precisely controlling the delivery of agrochemicals/biologics/drugs/fragrances have significant markets in the agriscience/healthcare industries. Here, we report the development of degradable electroactive polymers and their application for the controlled delivery of a clinically relevant drug (the anti-inflammatory dexamethasone phosphate, DMP). Electroactive copolymers composed of blocks of polycaprolactone (PCL) and naturally occurring electroactive pyrrole oligomers (e.g., bilirubin, biliverdin, and hemin) were prepared and solution-processed to produce films (optionally doped with DMP). A combination of in silico/in vitro/in vivo studies demonstrated the cytocompatibility of the polymers. The release of DMP in response to the application of an electrical stimulus was observed to be enhanced by ca. 10–30% relative to the passive release from nonstimulated samples in vitro. Such stimuli-responsive biomaterials have the potential for integration devices capable of delivering a variety of molecules for technical/medical applications.

Timeliness of surgical pathology result reporting is a critical quality metric for patients and treating clinicians. Over the past several decades, studies have sought to define laboratory turnaround time (TAT) in the context of the surgical pathology workflow, investigate the various factors that influence TAT, and develop a framework to monitor, measure, and track TAT within and across laboratories. However, the complexity of health care delivery and health information technology creates barriers to tracking TAT that should be considered in the context of local environments. We seek to provide background and context as well as a framework for tracking TAT as a key quality metric in surgical pathology. We outline a roadmap to monitoring local TAT to maximize efficiency and customer satisfaction while reducing diagnostic error and near-miss safety events.

Spinal cord stimulation (SCS) is considered a minimally invasive and reversible neuromodulation therapy for various chronic pain disorders. The rates of infection following SCS surgery reported in the literature range from 2.8% to 10%. Several studies indicated no potential benefit of postoperative antibiotics (beyond 24 hours) on subsequent device infection. This study aimed to understand the characteristics of postoperative antibiotic prescriptions and subsequent infections following SCS surgery.

Coronavirus disease 2019 (COVID-19) can progress to cardiovascular complications which are linked to higher in-hospital mortality rates. Infective endocarditis (IE) can develop in patients with recent COVID-19 infections, however, characterization of IE following COVID-19 infection has been lacking. To better characterize this disease, we performed a systematic review with descriptive analysis of the clinical features and outcomes of these patients.

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The decline in retina visits during the COVID-19 pandemic was correlated with many indicators of mobility, including COVID-19 incidence, geography, and social distancing measures. Different regions variably prioritized retina visits during the pandemic.

AbstractAtrial fibrillation (AF) and cerebral amyloid angiopathy (CAA) present risks of ischemic stroke and intracerebral hemorrhage (ICH). Vitamin K antagonist use is associated with fluctuations in international normalized ratio (INR), which predispose to a higher bleeding risk. Patients with a diagnosis of AF and ICH while on a vitamin K antagonist were identified using the Rochester Epidemiology Project. Sixty patients were identified (mean age 81.3 years; 24 men). Thirty-three (55%) exhibited characteristics consistent with possible (n = 25) or probable (n = 8) CAA. Mean time in therapeutic range in the 30 days preceding ICH was 55.4%, with no difference between CAA and non-CAA patients. Mean time spent above therapeutic range (INR > 3.0) was 17.7%, with no difference between CAA and non-CAA patients. Following ICH, 21 (35%) died within 30 days, with total mortality at 76.7% after 176.4 person-years of follow-up (mean 2.9 years). Time in therapeutic range in the 30 days prior to ICH had no significant impact on 7-day mortality, nor risk of recurrent ICH or ischemic stroke. Patients with warfarin-related ICH were often outside of the therapeutic range within the month preceding hemorrhage but more frequently were subtherapeutic. Even with careful avoidance of supratherapeutic INR, vitamin K antagonist use in CAA patients is unlikely to have a major effect in preventing ICH and must be used with caution.

The extensive school closures due to the unprecedented COVID-19 pandemic resulted in prolonged water stagnation within schools' plumbing for longer durations than routine schools' holidays and summer breaks. With many of the U.S. schools suffering from problems of lead (Pb) in potable water for decades, the extended water stagnation caused by schools' closure has raised significant concerns regarding the schools' water safety. Thus, this research was conducted to evaluate the resiliency of schools' potable water plumbing toward the interruption caused by the COVID-19 pandemic. For this purpose, the impact of extended water stagnation on heavy metal release into water samples collected from fixtures with and without known lead problems in 25 schools within a school district in Tennessee was investigated. The results revealed a significant increase in the median Pb concentration due to the extended water stagnation. Furthermore, elevated levels of Fe, Zn, and Cu were released from both problematic and nonproblematic fixtures into tap water. Estimation of children's blood lead level (BLL), assuming the consumption of prolonged stagnated water, revealed an increased risk of elevated BLLs (>5 μg dL−1). To better identify the potential sources of lead release within schools, a combination of plumbing investigation and sequential water sampling was conducted. The lead-containing fixtures, connecting plumbing, and interior plumbing were found as the possible sources contributing to the lead release into water. Implementation of remediation actions reduced the lead release into tap water to less than 3.4 μg L−1in the target fixtures.

ObjectiveNon-bacterial thrombotic endocarditis (NBTE) is a syndrome characterised by cardiac valve vegetations and/or thickening due to non-infective mechanisms. Nowadays, a premortem diagnosis of NBTE is possible based on echocardiographic findings. Therefore, to better characterise this disease, we performed a contemporary review of the epidemiology, demographics, diagnosis and clinical outcomes of these patients.MethodsAdults with a diagnosis of NBTE seen within the Mayo Clinic Enterprise from December 2014 to December 2021 were included. NBTE diagnosis was identified by clinicians representing at least two specialties including cardiology, infectious diseases, rheumatology and oncology. Patients with positive blood cultures, infective endocarditis, culture-negative endocarditis and denial of research authorisation were excluded. All patients had a 1-year follow-up.ResultsForty-eight cases were identified; mean age was 60.0±13.8 years, 75% were female. The most prevalent comorbidities were malignancy (52.1%) and connective tissue disease (37.5%). Valvular abnormalities included 41 (85.4%) patients with vegetations, 43 (89.6%) patients with thickening and 26 (54.2%) with moderate to severe regurgitation. Thirty-eight (79.2%) patients had an embolic event (stroke in 26 (54.2%) patients) within 1 month of NBTE diagnosis and 16 (33.3%) patients died within 1 year of NBTE diagnosis. Metastatic tumours and lung cancer were associated with 1-year all-cause mortality (p=0.0017 and p=0.0004, respectively).ConclusionsNBTE was more prevalent in females and embolic complications were the most frequent clinical finding. Overall, patients with NBTE had a poor prognosis, particularly in those with lung cancer or metastatic tumours. Further studies in patients with NBTE are needed given its morbidity and mortality.

Histone acetylation, catalyzed by histone acetyltransferases, has emerged as a promising therapeutic strategy in Alzheimer's disease (AD). By longitudinally characterizing spatial memory at 3, 6, and 9 mo of age, we show that acute activation and inhibition of the histone acetyltransferase PCAF remediated memory impairments in 3xTG-AD mice in an age-related bidirectional manner. At 3 and 6 mo of age, PCAF activation ameliorated memory deficits. At 9 mo of age, PCAF activation had no effect on spatial memory, whereas PCAF inhibition improved memory deficits in females. This work reveals a complex potential therapeutic role for PCAF in AD, initially benefitting memory but becoming detrimental as the disease progresses.

Intravenous TTI-621 (SIRPα-IgG1 Fc) was previously shown to have activity in relapsed or refractory haematological malignancies. This phase 1 study evaluated the safety and activity of TTI-621 in patients with percutaneously accessible relapsed or refractory mycosis fungoides, Sézary syndrome, or solid tumours. Here we report the clinical and translational results among patients with mycosis fungoides or Sézary syndrome.

IMPORTANCE: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs). OBJECTIVE: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs. EVIDENCE REVIEW: Dermatologists with more than 5 years’ experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists’ rationale for their responses. FINDINGS: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage–based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC. CONCLUSIONS AND RELEVANCE: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.