Interaction of COVID-19 With Common Cardiovascular Disorders.

The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain groups appeared to be at higher risk for severe illness once infected. One such group that immediately came to the forefront and garnered international attention was patients with preexisting cardiovascular disease. Here, we examine the available literature describing the interaction of COVID-19 with a myriad of cardiovascular conditions and diseases, paying particular attention to patients diagnosed with arrythmias, heart failure, and coronary artery disease. We further discuss the association of acute COVID-19 with de novo cardiovascular disease, including myocardial infarction due to coronary thrombosis, myocarditis, and new onset arrhythmias. We will evaluate various biochemical theories to explain these findings, including possible mechanisms of direct myocardial injury caused by the severe acute respiratory syndrome coronavirus-2 virus at the cellular level. Finally, we will discuss the strategies employed by numerous groups and governing bodies within the cardiovascular disease community to address the unprecedented challenges posed to the care of our most vulnerable patients, including heart transplant recipients, end-stage heart failure patients, and patients suffering from acute coronary syndromes, during the early days and height of the COVID-19 pandemic.

Active learning narrows achievement gaps for underrepresented students in undergraduate science, technology, engineering, and math.

We tested the hypothesis that underrepresented students in active-learning classrooms experience narrower achievement gaps than underrepresented students in traditional lecturing classrooms, averaged across all science, technology, engineering, and mathematics (STEM) fields and courses. We conducted a comprehensive search for both published and unpublished studies that compared the performance of underrepresented students to their overrepresented classmates in active-learning and traditional-lecturing treatments. This search resulted in data on student examination scores from 15 studies (9,238 total students) and data on student failure rates from 26 studies (44,606 total students). Bayesian regression analyses showed that on average, active learning reduced achievement gaps in examination scores by 33% and narrowed gaps in passing rates by 45%. The reported proportion of time that students spend on in-class activities was important, as only classes that implemented high-intensity active learning narrowed achievement gaps. Sensitivity analyses showed that the conclusions are robust to sampling bias and other issues. To explain the extensive variation in efficacy observed among studies, we propose the heads-and-hearts hypothesis, which holds that meaningful reductions in achievement gaps only occur when course designs combine deliberate practice with inclusive teaching. Our results support calls to replace traditional lecturing with evidence-based, active-learning course designs across the STEM disciplines and suggest that innovations in instructional strategies can increase equity in higher education.

True Grit: Passion and persistence make an innovative course design work.

Our first two experiments on adapting a high-structure course model to an essentially open-enrollment university produced negative or null results. Our third experiment, however, proved more successful: performance improved for all students, and a large achievement gap that impacted underrepresented minority students under traditional lecturing closed. Although the successful design included preclass preparation videos, intensive active learning in class, and weekly practice exams, student self-report data indicated that total study time decreased. Faculty who have the grit to experiment and persevere in making evidence-driven changes to their teaching can reduce the inequalities induced by economic and educational disadvantage.

Aminolevulinic Acid 20% Solution Combined With Photodynamic Therapy for Treatment of Actinic Keratoses: A Review.

Actinic keratoses (AK) are lesions with potential to transform into nonmelanoma skin cancers. Numerous methods are available for treatment of AK. Here, we review clinical trial data on the use of photodynamic treatment combined with the sensitizing agent aminolevulinic acid 20% solution (ALA-PDT) for AK management. Although treatment guidelines for AK vary in their specific recommendations, efficacy of ALA-PDT is considered comparable or better relative to other FDA-approved treatments for AK. It is generally well tolerated and has a very acceptable long-term safety profile. ALA-PDT is typically recommended for patients who have multiple AKs and is associated with improved cosmetic outcomes compared with cryotherapy. Patients who undergo treatment with ALA-PDT should receive thorough education regarding the risks and benefits of treatment, the treatment regimen and the importance of adhering to it, how to manage local reactions, and signs and symptoms that warrant further evaluation. J Drugs Dermatol. 2021;20(11):1239-1244. doi:10.36849/JDD.6166.

High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

UNLABELLED: Motor affordances occur when the visual properties of an object elicit behaviorally relevant motor representations. Typically, motor affordances only produce subtle effects on response time or on motor activity indexed by neuroimaging/neuroelectrophysiology, but sometimes they can trigger action itself. This is apparent in "utilization behavior," where individuals with frontal cortex damage inappropriately grasp affording objects. This raises the possibility that, in healthy-functioning individuals, frontal cortex helps ensure that irrelevant affordance provocations remain below the threshold for actual movement. In Experiment 1, we tested this "frontal control" hypothesis by "loading" the frontal cortex with an effortful working memory (WM) task (which ostensibly consumes frontal resources) and examined whether this increased EEG measures of motor affordances to irrelevant affording objects. Under low WM load, there were typical motor affordance signatures: an event-related desynchronization in the mu frequency and an increased P300 amplitude for affording (vs nonaffording) objects over centroparietal electrodes. Contrary to our prediction, however, these affordance measures were diminished under high WM load. In Experiment 2, we tested competing mechanisms responsible for the diminished affordance in Experiment 1. We used paired-pulse transcranial magnetic stimulation over primary motor cortex to measure long-interval cortical inhibition. We found greater long-interval cortical inhibition for high versus low load both before and after the affording object, suggesting that a tonic inhibition state in primary motor cortex could prevent the affordance from provoking the motor system. Overall, our results suggest that a high WM load "sets" the motor system into a suppressed state that mitigates motor affordances. SIGNIFICANCE STATEMENT: Is an irrelevant motor affordance more likely to be triggered when you are under low or high cognitive load? We examined this using physiological measures of the motor affordance while working memory load was varied. We observed a typical motor affordance signature when working memory load was low; however, it was abolished when load was high. Further, there was increased intracortical inhibition in primary motor cortex under high working memory load. This suggests that being in a state of high cognitive load "sets" the motor system to be imperturbable to distracting motor influences. This makes a novel link between working memory load and the balance of excitatory/inhibitory activity in the motor cortex and potentially has implications for disorders of impulsivity.

Active learning increases student performance in science, engineering, and mathematics.

To test the hypothesis that lecturing maximizes learning and course performance, we metaanalyzed 225 studies that reported data on examination scores or failure rates when comparing student performance in undergraduate science, technology, engineering, and mathematics (STEM) courses under traditional lecturing versus active learning. The effect sizes indicate that on average, student performance on examinations and concept inventories increased by 0.47 SDs under active learning (n = 158 studies), and that the odds ratio for failing was 1.95 under traditional lecturing (n = 67 studies). These results indicate that average examination scores improved by about 6% in active learning sections, and that students in classes with traditional lecturing were 1.5 times more likely to fail than were students in classes with active learning. Heterogeneity analyses indicated that both results hold across the STEM disciplines, that active learning increases scores on concept inventories more than on course examinations, and that active learning appears effective across all class sizes--although the greatest effects are in small (n ≤ 50) classes. Trim and fill analyses and fail-safe n calculations suggest that the results are not due to publication bias. The results also appear robust to variation in the methodological rigor of the included studies, based on the quality of controls over student quality and instructor identity. This is the largest and most comprehensive metaanalysis of undergraduate STEM education published to date. The results raise questions about the continued use of traditional lecturing as a control in research studies, and support active learning as the preferred, empirically validated teaching practice in regular classrooms.

Withholding a Reward-driven Action: Studies of the Rise and Fall of Motor Activation and the Effect of Cognitive Depletion.

Controlling an inappropriate response tendency in the face of a reward-predicting stimulus likely depends on the strength of the reward-driven activation, the strength of a putative top-down control process, and their relative timing. We developed a rewarded go/no-go paradigm to investigate such dynamics. Participants made rapid responses (on go trials) to high versus low reward-predicting stimuli and sometimes had to withhold responding (on no-go trials) in the face of the same stimuli. Behaviorally, for high versus low reward stimuli, responses were faster on go trials, and there were more errors of commission on no-go trials. We used single-pulse TMS to map out the corticospinal excitability dynamics, especially on no-go trials where control is needed. For successful no-go trials, there was an early rise in motor activation that was then sharply reduced beneath baseline. This activation-reduction pattern was more pronounced for high- versus low-reward trials and in individuals with greater motivational drive for reward. A follow-on experiment showed that, when participants were fatigued by an effortful task, they made more errors on no-go trials for high versus low reward stimuli. Together, these studies show that, when a response is inappropriate, reward-predicting stimuli induce early motor activation, followed by a top-down effortful control process (which we interpret as response suppression) that depends on the strength of the preceding activation. Our findings provide novel information about the activation-suppression dynamics during control over reward-driven actions, and they illustrate how fatigue or depletion leads to control failures in the face of reward.

Microneedling Prior to Levulan PDT for the Treatment of Actinic Keratoses: A Split-Face, Blinded Trial.

INTRODUCTION: Photodynamic Therapy (PDT) with topical Levulan is an approved and efficacious method for treating actinic keratoses. This therapy depends on the ability of the Levulan (delta amino levulinic acid) to penetrate the stratum corneum and enter the cells of the epidermis. Microneedling is an increasing popular cosmetic therapy in which an array of tiny needles is used to make holes in the epidermis and presumably induce a wound healing cascade that leads to cosmetic improvement of the skin. We were interested to know if prior microneedling would enhance the penetration of topical Levulan and thus enhance the PDT treatment, and if a cosmetic improvement beyond the PDT alone would be seen when it is used in conjunction with microneedling.
METHODS: 20 patients each with at least 4 non hyperkeratotic AKs on each side of their face were enrolled. All patients were randomized to receive multiple passes with a microneedling device to ½ of their face, left or right, followed by application of Levulan to the entire face. The Levulan was allowed to incubate 1 hour followed by exposure to blue light (Blu U) for 1000 seconds.
RESULTS: 19 patients completed the study with 4-month follow up. The mean percentage reduction in AKs was 89.3% on the microneedling side versus 69.5% on the PDT alone side, a significant difference. A physician's global cosmetic assessment was performed based on Canfield Visia photographs: 15 of the 19 patients had a noticeable improved cosmetic appearance on one side of the face versus the other, and in 13 of these patients the improved side was the microneedled side.
DISCUSSION: Prior microneedling significantly enhances the effect of Levulan PDT. It also seems to provide a cosmetic benefit above and beyond the PDT alone. It was safe and well tolerated in this study.

J Drugs Dermatol. 2016;15(9):1072-1074.

Structural foundations of resting-state and task-based functional connectivity in the human brain.

Magnetic resonance imaging enables the noninvasive mapping of both anatomical white matter connectivity and dynamic patterns of neural activity in the human brain. We examine the relationship between the structural properties of white matter streamlines (structural connectivity) and the functional properties of correlations in neural activity (functional connectivity) within 84 healthy human subjects both at rest and during the performance of attention- and memory-demanding tasks. We show that structural properties, including the length, number, and spatial location of white matter streamlines, are indicative of and can be inferred from the strength of resting-state and task-based functional correlations between brain regions. These results, which are both representative of the entire set of subjects and consistently observed within individual subjects, uncover robust links between structural and functional connectivity in the human brain.

Multi-method approach to quantify uncertainties in the measurements of light absorption by particles.

Through technological and research advances, numerous methods and protocols have emerged to estimate spectral absorption of light by particles, ap, in an aquatic medium. However, the level of agreement among measurements remains elusive. We employed a multi-method approach to estimate the measurement precision of measuring optical density of particles on a filter pad using two common spectrophotometric methods, and the determination precision, or uncertainty, of the computational techniques for estimating ap for six ocean color wavelengths (412, 443, 490, 510, 555, 670 nm). The optical densities measured with the two methods exhibited a significant, positive correlation. Optical density measurement precision ranged from 0.061%-63% and exhibited a significant, positive correlation. Multi-method uncertainty ranged from 7.48%-119%. Values of ap at 555 nm and 670 nm exhibited the highest values of uncertainty. Poor performance of modeled ap compared to determined ap suggest uncertainties are propagated into bio-optical algorithms.

Nationally endorsed learning objectives to improve course design in introductory biology.

Introductory biology for majors is one of the most consequential courses in STEM, with annual enrollments of several hundred thousand students in the United States alone. To support increased student success and meet current and projected needs for qualified STEM professionals, it will be crucial to redesign majors biology by using explicit learning objectives (LOs) that can be aligned with assessments and active learning exercises. When a course is designed in this way, students have opportunities for the practice and support they need to learn, and instructors can collect the evidence they need to evaluate whether students have mastered key concepts and skills. Following an iterative process of review, revision, and evaluation, which included input from over 800 biology instructors around the country, we produced a nationally endorsed set of lesson-level LOs for a year-long introductory biology for major's course. These LOs are granular enough to support individual class sessions and provide instructors with a framework for course design that is directly connected to the broad themes in Vision and Change and the general statements in the BioCore and BioSkills Guides. Instructors can implement backward course design by aligning these community endorsed LOs with daily and weekly learning activities and with formative and summative assessments.

Comparative Costs to Medicare and Medicare Beneficiaries of Alternative AF Stroke Risk Reduction Strategies.

Background: As healthcare costs are increasingly being shifted from payers to patients, it is important to understand the economic consequences of therapeutic strategies to both payers and patients. Objective: To determine the relative costs to Medicare and Medicare beneficiaries (patients) of warfarin, non-vitamin K oral anticoagulants (NOACs), and left atrial appendage closure (LAAC) for stroke risk reduction in nonvalvular atrial fibrillation. Methods: An economic model was developed to assess costs at 5 and 10 years. For warfarin and NOACs, inputs were derived from published meta-analyses; for LAAC with the Watchman device, inputs were derived from pooled 5-year PROTECT AF and PREVAIL trial results. The model captured therapy costs vs clinical event costs, including procedural complications and follow-up clinical outcomes. Costs were based on 2023 Medicare reimbursement and copayment rates. Results: At 10 years, overall LAAC costs ($48,337) were lower than those of NOACs ($81,198) and warfarin ($52,359). Overall LAAC costs were lower than those of NOACs by year 5 and warfarin by year 9. At 5 years, patient LAAC costs were lowest at $4,764, compared to $7,146 and $6,453 for NOACs and warfarin, respectively. LAAC patient costs were lower than those of NOACs by year 3 and warfarin by year 4. Clinical events comprised 96% of overall warfarin costs vs 48% for LAAC and 40% for NOACs. Conclusion: LAAC yielded the lowest overall and patient costs. Warfarin costs were largely driven by clinical events, which may represent an unplanned financial burden for patients. These considerations should be incorporated into shared decision-making discussions about stroke prophylaxis strategies.

Phytoplankton optical fingerprint libraries for development of phytoplankton ocean color satellite products.

Phytoplankton respond to physical and hydrographic forcing on time and space scales up to and including those relevant to climate change. Quantifying changes in phytoplankton communities over these scales is essential for predicting ocean food resources, occurrences of harmful algal blooms, and carbon and other elemental cycles, among other predictions. However, one of the best tools for quantifying phytoplankton communities across relevant time and space scales, ocean color sensors, is constrained by its own spectral capabilities and availability of adequately vetted and relevant optical models. To address this later shortcoming, greater than fifty strains of phytoplankton, from a range of taxonomic lineages, geographic locations, and time in culture, alone and in mixtures, were grown to exponential and/or stationary phase for determination of hyperspectral UV-VIS absorption coefficients, multi-angle and multi-spectral backscatter coefficients, volume scattering functions, particle size distributions, pigment content, and fluorescence. The aim of this publication is to share these measurements to expedite their utilization in the development of new optical models for the next generation of ocean color satellites.

Prognostic value of sentinel lymph node biopsy compared with that of Breslow thickness: implications for informed consent in patients with invasive melanoma.

BACKGROUND: Sentinel lymph node (SLN) status is reportedly a powerful prognosticator of survival. Breslow thickness alone provides significant prognostic information. OBJECTIVE: To assess overall survival (OS) according to tumor depth based on SLN status. MATERIALS AND METHODS: MEDLINE, EMBASE, and the Cochrane Central Database were searched for studies. Included studies evaluated overall survival according to SLNB results and were stratified according to Breslow thickness. Meta-analysis was performed if appropriate in each category for which three or more studies reported risk estimates and variability measurement. RESULTS: Twenty-nine articles met inclusion criteria. Six met the criteria for meta-analysis. In individuals with thin melanoma (<1 mm), SLN-negative status conferred no survival advantage (sign test, p > .99). Few studies were available for intermediate depths, and most reported worse survival in SLN-positive patients, although the difference was not statistically significant (p > .05). For thick melanoma (>4 mm), SLN positivity was related to worse prognosis (sign test, p = .004). Based on the pooled results of six studies of patients with tumors 4 mm thick or thicker, SLN-positive patients had a greater likelihood of dying (hazard ratio = 2.42, 95% confidence interval = 2.00-2.92). CONCLUSIONS: Sentinel lymph node biopsy may not provide more-accurate prognostic information than Breslow thickness for most melanomas.

Cardiac tamponade-mediated generalized coronary vasospasm presenting as an inferior ST-segment elevation myocardial infarction: a case report.

Background: Coronary vasospasm is a rare cause of ST-segment elevation myocardial infarction (STEMI) and can be precipitated by numerous inciting factors including endogenous catecholamines. Differentiating coronary vasospasm from an acute atherothrombotic event is diagnostically challenging and requires a careful clinical history combined with electrocardiographic and angiographic abnormalities to make the diagnosis and guide therapy. Case Summary: We report a case of cardiogenic shock secondary to cardiac tamponade leading to an endogenous catecholamine surge resulting in profound arterial vasospasm and STEMI. The patient presented with chest pain and inferior ST segment elevations prompting emergent coronary angiography, demonstrating subtotal occlusion of the right coronary artery, severe proximal left anterior descending coronary artery stenosis, and diffusely stenosed aortoiliac vessels. Emergent transthoracic echocardiogram revealed a large pericardial effusion and hemodynamics consistent with cardiac tamponade. Pericardiocentesis resulted in dramatic hemodynamic improvement with immediate normalization of ST segments. Repeat coronary angiography performed one day later showed no angiographically significant coronary or peripheral arterial stenosis. Discussion: This is the first reported case of simultaneous coronary and peripheral arterial vasospasm presenting as inferior STEMI caused by endogenous catecholamines from cardiac tamponade. Several clues suggest coronary vasospasm including the discordant electrocardiography (ECG) and coronary angiographic findings as well as diffusely stenosed aortoiliac vessels. Diffuse vasospasm was confirmed when repeat angiography performed after pericardiocentesis demonstrated angiographic resolution of coronary and peripheral arterial stenosis. Though rare, circulating endogenous catecholamines resulting in diffuse coronary vasospasm may present as STEMI and should be considered based on the clinical history, ECG findings, and coronary angiography.

Good neighbors? Does aggregation of nests in an Arctic-breeding shorebird influence daily survival rates?

Our current understanding of the factors that influence where birds nest is incomplete, yet such information is important for accurate demographic assessments. To address questions related to spatial distributions of shorebird nests and to evaluate factors that may affect nest distribution in these species, during 2017 and 2019, we studied a small population of semipalmated sandpiper Calidris pusilla breeding in the Central Canadian Arctic, near the Karrak Lake Research Station, in Nunavut. The spatial distribution of semipalmated sandpiper nests at this site suggested loose aggregation, with median nearest neighbor distances of 73.8 m and 92.0 m in 2017 and 2019, respectively, while no nests were detected on mainland areas in the vicinity. Evidence for the influence of nesting distribution on the daily survival rate of nests, however, was mixed. Neither nearest neighbor distance nor local nest density had a significant effect on daily nest survival in 2017, but in 2019, the best approximating model included an effect of local nest density, which indicated that nests in areas of high density had reduced survival rates. Contrary to other studies assessing settlement and nest site selection in semipalmated sandpipers, the spatial distribution of nests in this population demonstrates aggregation in an otherwise territorial species, but suggests that aggregated nesting can impose a cost on nest survival under certain conditions.

Assessing how well students understand the molecular basis of evolution by natural selection.

Researchers have called for undergraduate courses to update teaching frameworks based on the Modern Synthesis with insights from molecular biology, by stressing the molecular underpinnings of variation and adaptation. To support this goal, we developed a modified version of the widely used Assessing Conceptual Reasoning of Natural Selection (ACORNS) instrument. The expanded tool, called the E-ACORNS, is explicitly designed to test student understanding of the connections among genotypes, phenotypes, and fitness. E-ACORNS comprises a slight modification to the ACORNS open-response prompts and a new scoring rubric. The rubric is based on five core concepts in evolution by natural selection, with each concept broken into elements at the novice, intermediate, and expert-level understanding. Initial tests of the E-ACORNS showed that (1) upper-level undergraduates can score responses reliably and quickly, and (2) students who were just starting an introductory biology series for majors do not yet grasp the molecular basis of phenotypic variation and its connection to fitness.

Measuring undergraduates' understanding of the culture of scientific research as an outcome variable in research on CUREs.

Researchers who work on course-based undergraduate research experiences (CUREs) and issues related to science, technology, engineering, and math (STEM) retention have begun exploring changes in student thinking about what it means to be a scientist. To support this effort, we developed rubrics to score answers to three open-response prompts: What does it mean to think like a scientist? What does it mean to do science? and Did you do real research in your coursename labs? The rubric development process was iterative and was based on input from the literature, experienced researchers, and early-career undergraduates. A post hoc analysis showed that the rubric elements map to 27 of 31 statements in the Culture of Scientific Research (CSR) framework, suggesting that scored responses to the three prompts can assess how well students understand what being a science professional entails. Scores on responses from over 400 students who were starting an introductory biology course for majors furnish baseline data from the rubrics and suggest that (i) undergraduates at this level have, as expected, a novice-level understanding of CSR, and (ii) level of understanding in novice students does not vary as a function of demography or academic preparation. Researchers and instructors are encouraged to add CSR to their list of learning objectives for CUREs and consider assessing it using the rubrics provided here.

A CURE on the Evolution of Antibiotic Resistance in Escherichia coli Improves Student Conceptual Understanding.

We developed labs on the evolution of antibiotic resistance to assess the costs and benefits of replacing traditional laboratory exercises in an introductory biology course for majors with a course-based undergraduate research experience (CURE). To assess whether participating in the CURE imposed a cost in terms of exam performance, we implemented a quasi-experiment in which four lab sections in the same term of the same course did the CURE labs, while all other students did traditional labs. To assess whether participating in the CURE impacted other aspects of student learning, we implemented a second quasi-experiment in which all students either did traditional labs over a two-quarter sequence or did CURE labs over a two-quarter sequence. Data from the first experiment showed minimal impact on CURE students' exam scores, while data from the second experiment showed that CURE students demonstrated a better understanding of the culture of scientific research and a more expert-like understanding of evolution by natural selection. We did not find disproportionate costs or benefits for CURE students from groups that are minoritized in science, technology, engineering, and mathematics.

Individual differences in shifting decision criterion: a recognition memory study.

An ability to flexibly shift a decision criterion can be advantageous. For example, a known change in the base rate of targets and distractors on a recognition memory test will lead optimal decision makers to shift their criterion accordingly. In the present study, 95 individuals participated in two recognition memory tests that included periodic changes in the base rate probability that the test stimulus had been presented during the study session. The results reveal a wide variability in the tendency to shift decision criterion in response to this probability information, with some appropriately shifting and others not shifting at all. However, participants were highly reliable in their tendency to shift criterion across tests. The goal of the present study was to explain what factors account for these individual differences. To accomplish this, over 50 variables were assessed for each individual (e.g., personality, cognitive style, state of mind). Using a regression model that incorporated different sets of factors, over 50% of the variance was accounted for. The results of the analysis describe the total, direct, and mediating effects on criterion shifting from factors that include memory strength, strategy, and inherent characteristics such as a fun-seeking personality, a negative affect, and military rank. The results are discussed with respect to understanding why participants rarely chose an optimal decision-making strategy and provide greater insight into the underlying mechanisms of recognition memory.