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Abstract Background Given the rapid deployment of telemedicine at the onset of the COVID - 19 pandemic, updated assessment methods are needed to study and characterize telemedicine programs. We developed a novel semi - structured survey instrument to systematically describe the characteristics and implementation processes of telemedicine programs in primary care. Methods In the context of a larger study aiming to describe telemedicine programs in primary care, a survey was developed in 3 iterative steps: 1) literature review to obtain a list of telemedicine features, facilitators, and barriers; 2) application of three evaluation frameworks; and 3) stakeholder engagement through a 2-stage feedback process. During survey refinement, items were tested against the evaluation frameworks while ensuring it could be completed within 20–25 min. Data reduction techniques were applied to explore opportunity for condensed variables/items. Results Sixty initially identified telemedicine features were reduced to 32 items / questions after stakeholder feedback. Per the life cycle framework, respondents are asked to report a month in which their telemedicine program reached a steady state, i.e., “maturation”. Subsequent questions on telemedicine features are then stratified by telemedicine services offered at the pandemic onset and the reported point of maturation. Several open - ended questions allow for additional telemedicine experiences to be captured. Data reduction techniques revealed no indication for data reduction. Conclusion This 32-item semi-structured survey standardizes the description of primary care telemedicine programs in terms of features as well as maturation process. This tool will facilitate evaluation of and comparisons between telemedicine programs across the United States, particularly those that were deployed at the pandemic onset.

Although there have been some advances during in recent decades, the treatment of head and neck squamous cell carcinoma (HNSCC) remains challenging. Resistance is a major issue for various treatments that are used, including both the conventional standards of care (radiotherapy and platinum-based chemotherapy) and the newer EGFR and checkpoint inhibitors. In fact, all the non-surgical treatments currently used for HNSCC are associated with intrinsic and/or acquired resistance. Herein, we explore the cellular mechanisms of resistance reported in HNSCC, including those related to epigenetic factors, DNA repair defects, and several signaling pathways. This article discusses these mechanisms and possible approaches that can be used to target different pathways to sensitize HNSCC to the existing treatments, obtain better responses to new agents, and ultimately improve the patient outcomes.

Abstract Accurate assessment of tumor margins with specific, non-invasive imaging would result in the preservation of healthy tissue and improve long-term local tumor control, thereby reducing the risk of recurrence. Overexpression of epidermal growth factor receptor (EGFR) has been used in other cancers as an imaging biomarker to identify cancerous tissue. We hypothesize that expression of EGFR in ameloblastomas may be used to specifically visualize tumors. The aims of this study are to measure the specificity of radiolabeled 89Zr-panitumumab (an EGFR antibody) in vivo using patient-derived xenograft (PDX) models of ameloblastoma and positron emission tomography/computed tomography (PET/CT) scans. In PDX of ameloblastomas from four patients (AB-36, AB-37, AB-39 AB-53), the biodistribution of 89Zr-panitumumab was measured 120 h post-injection and was reported as the injected dose per gram of tissue (%ID/g; AB-36, 40%; AB-37, 62%; AB-39 18%; AB-53, 65%). The radiolabeled %ID/g was significantly greater in tumors of 89Zr-panitumumab-treated mice that did not receive unlabeled panitumumab as a blocking control for AB-36, AB-37, and AB-53. Radiolabeled anti-EGFR demonstrates specificity for ameloblastoma PDX tumor xenografts, we believe 89Zr-panitumumab is an attractive target for pre-surgical imaging of ameloblastomas. With this technology, we could more accurately assess tumor margins for the surgical removal of ameloblastomas.

Gi/o protein-coupled receptors (Gi/o-GPCRs) limit β-cell insulin secretion by decreasing Ca2+ entry; however, the underlying mechanism has not been identified. Here, the authors show that Gi/o-GPCRs hyperpolarize mouse and human β-cell membrane potential by activating Na+/K+ATPases.

The study interrogates the contention that social entrepreneurship pedagogy plays an essential role in developing students' entrepreneurial mindset in a Covid-19 era from the perspective of the Lagos State University, Nigeria. The exploratory design was employed to harness new knowledge from existing literature. A total of 18 final-year students were purposively and conveniently for an interview, and data were analyzed with the NVivo (v.12) qualitative software. Results reveal a lack of pedagogy initiatives in delivering teachings and learning such as seminars/workshops, networking, internships and case studies, the absence of a conventional department of entrepreneurship education and a lack of appropriate entrepreneurship education curriculum for the development of students' entrepreneurship mindsets. Notably, the fallout from the Covid-19 pandemic has shown that students can revive the Nigerian economy with a positive outlook due to their entrepreneurial mindset. The study echoes the need for the constitution of appropriate pedagogy initiatives and relevant course contents and curriculum that could steer a robust students' entrepreneurial mindset for venture creation and economic development amidst the prevailing loss of jobs in this epoch of Covid-19.

Vertically transmitted (VT) microbial symbionts play a vital role in the evolution of their insect hosts. A longstanding question in symbiont research is what genes help promote long-term stability of vertically transmitted lifestyles. Symbiont success in insect hosts is due in part to expression of beneficial or manipulative phenotypes that favor symbiont persistence in host populations. In Spiroplasma, these phenotypes have been linked to toxin and virulence domains among a few related strains. However, these domains also appear frequently in phylogenetically distant Spiroplasma, and little is known about their distribution across the Spiroplasma genus. In this study, we present the complete genome sequence of the Spiroplasma symbiont of Drosophila atripex, a non-manipulating member of the Ixodetis clade of Spiroplasma, for which genomic data are still limited. We perform a genus-wide comparative analysis of toxin domains implicated in defensive and reproductive phenotypes. From 12 VT and 31 non-VT Spiroplasma genomes, ribosome-inactivating proteins (RIPs), OTU-like cysteine proteases (OTUs), ankyrins, and ETX/MTX2 domains show high propensity for VT Spiroplasma compared to non-VT Spiroplasma. Specifically, OTU and ankyrin domains can be found only in VT-Spiroplasma, and RIP domains are found in all VT Spiroplasma and three non-VT Spiroplasma. These domains are frequently associated with Spiroplasma plasmids, suggesting a possible mechanism for dispersal and maintenance among heritable strains. Searching insect genome assemblies available on public databases uncovered uncharacterized Spiroplasma genomes from which we identified several spaid-like genes encoding RIP, OTU, and ankyrin domains, suggesting functional interactions among those domain types. Our results suggest a conserved core of symbiont domains play an important role in the evolution and persistence of VT Spiroplasma in insects.

COVID-19 emerged as a worldwide pandemic in early 2020, and while the rapid development of safe and efficacious vaccines stands as an extraordinary achievement, the identification of effective therapeutics has been less successful. This process has been limited in part by a lack of human-relevant preclinical models compatible with therapeutic screening on the native virus, which requires a high-containment environment. Here, we report SARS-CoV-2 infection and robust viral replication in PREDICT96-ALI, a high-throughput, human primary cell-based organ-on-chip platform. We evaluate unique infection kinetic profiles across lung tissue from three human donors by immunofluorescence, RT-qPCR, and plaque assays over a 6-day infection period. Enabled by the 96 devices/plate throughput of PREDICT96-ALI, we also investigate the efficacy of Remdesivir and MPro61 in a proof-of-concept antiviral study. Both compounds exhibit an antiviral effect against SARS-CoV-2 in the platform. This demonstration of SARS-CoV-2 infection and antiviral dosing in a high-throughput organ-on-chip platform presents a critical capability for disease modeling and therapeutic screening applications in a human physiology-relevant in vitro system.

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin lymphoma (NHL) that can be aggressive with rapid speed, thus mandating a timely diagnosis to optimize treatment and deter progression. NHL classically presents with lymphadenopathy and constitutional symptoms. However, ALCL can present with nonspecific cutaneous manifestations with minimal or absent constitutional symptoms. The cutaneous involvement may resemble common dermatologic conditions, delaying diagnosis. We present a case of an aggressive cutaneous ALCL lesion mimicking facial cellulitis that rapidly progressed from a small comedone to a large, exophytic mass over the course of 1 month. Prior to presentation at our institution, the patient was previously diagnosed and treated for suspected bacterial infection with no response to therapy. Core needle biopsy of the forehead lesion confirmed the diagnosis of anaplastic lymphoma kinase-negative ALCL. Chemotherapy with brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone was planned for a total of 6–8 cycles with curative intent. By cycle 5, positron emission tomography and computed tomography demonstrated response to therapy with no enlarged or metabolically active lymph nodes appreciated. Our case report highlights the importance of developing a broad differential diagnosis for ulcerative facial masses, particularly when unresponsive to antimicrobial therapies. Lymphomas should be included in the differential diagnosis of patients with rapidly growing facial lesions.

Value-based care initiatives require accurate quantification of resource utilization. This study explores hospital resource documentation performance for total knee and hip arthroplasty (TKA, THA) implants and how this may differ between hospitals. This retrospective study utilized the Premier discharge database, years 2006 to 2020. TKA/THA cases were categorized into 5 tiers based upon the completeness of implant component documentation: Platinum, Gold, Silver, Bronze, Poor. Correlation between TKA and THA documentation performance (per-hospital percentage of Platinum cases) was assessed. Logistic regression analyses measured the association between hospital characteristics (region, teaching status, bed size, urban/rural) and satisfactory documentation. TKA/THA implant documentation performance was compared to documentation for endovascular stent procedures. Individual hospitals tended to have very complete (Platinum) or very incomplete (Poor) documentation for both TKA and THA. TKA and THA documentation performance were correlated (correlation coefficient = .70). Teaching hospitals were less likely to have satisfactory documentation for both TKA ( P = .002) and THA ( P = .029). Documentation for endovascular stent procedures was superior compared to TKA/THA. Hospitals’ TKA and THA-related implant documentation performance is generally either very proficient or very poor, in contrast with often well-documented endovascular stent procedures. Hospital characteristics, other than teaching status, do not appear to impact TKA/THA documentation completeness.

Esophageal intramural pseudodiverticulosis is a benign disease characterized by numerous, small outpouchings from the esophageal epithelium. Esophageal intramural pseudodiverticulosis has scarcely been reported with only 200–300 cases worldwide. The etiology of esophageal intramural pseudodiverticulosis is also unclear; however, there is an associated increased risk with diabetes mellitus, gastroesophageal reflux disease, esophageal candidiasis, and chronic alcohol and tobacco abuse. Esophageal intramural pseudodiverticulosis has a characteristic appearance on esophagogastroduodenoscopy. Treatment of esophageal intramural pseudodiverticulosis has historically been limited to symptom management with acid suppression, anti-fungal therapy, and endoscopic dilation in areas of stricture. This report is a case of a 52-year-old female status post two esophageal stricture repairs with dilation over prior 2 years, who presented with non-remitting solid food dysphagia and food impaction found to have esophageal intramural pseudodiverticulosis with concomitant jackhammer esophagus and esophageal candidiasis.

Abstract Premise Plant disease severity assessments are used to quantify plant–pathogen interactions and identify disease‐resistant lines. One common method for disease assessment involves scoring tissue manually using a semi‐quantitative scale. Automating assessments would provide fast, unbiased, and quantitative measurements of root disease severity, allowing for improved consistency within and across large data sets. However, using traditional Root System Markup Language (RSML) software in the study of root responses to pathogens presents additional challenges; these include the removal of necrotic tissue during the thresholding process, which results in inaccurate image analysis. Methods Using PlantCV, we developed a Python‐based pipeline, herein called RootDS, with two main objectives: (1) improving disease severity phenotyping and (2) generating binary images as inputs for RSML software. We tested the pipeline in common bean inoculated with Fusarium root rot. Results Quantitative disease scores and root area generated by this pipeline had a strong correlation with manually curated values (R2 = 0.92 and 0.90, respectively) and provided a broader capture of variation than manual disease scores. Compared to traditional manual thresholding, images generated using our pipeline did not affect RSML output. Discussion Overall, the RootDS pipeline provides greater functionality in disease score data sets and provides an alternative method for generating image sets for use in available RSML software.

Introduction. Telemedicine was rapidly deployed at the onset of the COVID-19 pandemic. Little has been published on telemedicine in musculoskeletal care prior to the COVID-19 pandemic. This study is aimed at characterizing trends in telemedicine for musculoskeletal care preceding the COVID-19 pandemic. Methods. This retrospective study used insurance claims from the Truven MarketScan database. Musculoskeletal-specific outpatient visits from 2014 to 2018 were identified using the musculoskeletal major diagnostic category ICD-10 codes. Telemedicine visits were categorized using CPT codes and Healthcare Common Procedure Coding Systems. We described annual trends in telemedicine in the overall dataset and by diagnosis grouping. Multivariable logistic regression modeling estimated the association between patient-specific and telemedicine visit variables and telemedicine utilization. Results. There were 36,672 musculoskeletal-specific telemedicine visits identified (0.020% of all musculoskeletal visits). Overall, telemedicine utilization increased over the study period (0% in 2014 to 0.05% in 2018). Orthopedic surgeons had fewer telemedicine visits than primary care providers (OR 0.57, 95% CI 0.55-0.59). The proportion of unique patients utilizing telemedicine in 2018 was higher in the south (OR 2.28, 95% CI 2.19-2.38) and west (OR 5.58, 95% CI 5.36-5.81) compared to the northeast. Those with increased comorbidities and lower incomes and living in rural areas had lower rates of telemedicine utilization. Conclusions. From 2014 to 2018, there was an increase in telemedicine utilization for musculoskeletal visits, in part due to insurance reimbursement and telemedicine regulation. Despite this increase, the rates of telemedicine utilization are still lowest in some of the groups that could derive the most benefit from these services. Establishing this baseline is important for assessing how the roll-out of telemedicine during the pandemic impacted how/which patients and providers are utilizing telemedicine today.

Mycosis fungoides is the most common cutaneous T-cell lymphoma. It presents a diagnostic challenge due to resemblance with many other dermatologic conditions. The disease typically follows a progression from patches to plaques to skin-based tumors with potential for visceral involvement. Diagnosis is made by clinical presentation and histology. When early diagnosis is made, there is an estimated 88% five-year survival. This report details a 60-year-old Black man diagnosed with stage IIIA mycosis fungoides with a severe degree of cutaneous involvement. This case is unique due to the aggressive large cell transformation and rapid progression to death within 18 months of diagnosis. We highlight the challenge of diagnosing, treating, and monitoring the therapeutic response of mycosis fungoides. Finally, this case calls for a multi-disciplinary approach to treatment and to include mycosis fungoides on the differential diagnosis for patients presenting with a variety of vague, recurrent cutaneous symptoms, especially with patchy dyspigmentation or plaques.

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counterintuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfvén waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, α = 2 as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed >600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: preflare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that α = 1.63 ± 0.03. This is below the critical threshold, suggesting that Alfvén waves are an important driver of coronal heating.

Summary: Cytoplasmic incompatibility (CI) is a form of reproductive manipulation caused by maternally inherited endosymbionts infecting arthropods, like Wolbachia, whereby matings between infected males and uninfected females produce few or no offspring. We report the discovery of a new CI symbiont, a strain of Spiroplasma causing CI in the parasitoid wasp Lariophagus distinguendus. Its extracellular occurrence enabled us to establish CI in uninfected adult insects by transferring Spiroplasma-infected hemolymph. We sequenced the CI-Spiroplasma genome and did not find any homologues of any of the cif genes discovered to cause CI in Wolbachia, suggesting independent evolution of CI. Instead, the genome contains other potential CI-causing candidate genes, such as homologues of high-mobility group (HMG) box proteins that are crucial in eukaryotic development but rare in bacterial genomes. Spiroplasma’s extracellular nature and broad host range encompassing medically and agriculturally important arthropods make it a promising tool to study CI and its applications.

Introduction. Solid organ transplant increases the risk for muscle-invasive bladder cancer (MIBC). Although a common tumor, urothelial cell carcinoma (UCC) of the bladder in patients with kidney-pancreas transplants is scarcely reported. Case Presentation. A 65-year-old male with history of type 1 diabetes and a 14-year status post deceased donor pancreas-kidney transplant presented with 3 weeks of gross hematuria. CT scan showed multiple bladder masses. Transurethral resection of bladder tumor (TURBT) showed papillary UCC. 5 months later, the patient reported new-onset gross hematuria. TURBT showed MIBC. The patient elected for bladder-preserving TMT. On cystoscopy there was no gross evidence of carcinoma at 3.5 years of follow up. Discussion. Currently, no specific management guidelines target this population with MIBC. The first-line treatment for MIBC is radical cystectomy (RC) with neoadjuvant chemotherapy. For patients that are medically unfit or unwilling to undergo RC, trimodal therapy (TMT) is an alternative. TMT for bladder cancer consists of complete tumor resection with chemotherapy and radiation. This report demonstrates a unique case of a patient with kidney-pancreas transplant diagnosed with MIBC treated with TMT that has no evidence of gross tumorigenesis at 3.5 years after diagnosis. Our findings suggest that trimodal therapy should be considered for treatment of MIBC in patients with kidney-pancreatic transplants to preserve the donated allografts.

Introduction: A systematic analysis of clinical trials was performed in order to assess the effectiveness and risks of bilateral renal denervation (RDN) in patients with chronic heart failure with reduced ejection fraction (HFrEF). Methods: A systematic review was conducted of all clinical trials exploring the effectiveness of RDN in patients with HF who had reduced (

Objective: The aim of this study was to evaluate and define paw placement patterns for canines completing the weave pole obstacle during canine agility trials. The secondary objectives were to determine the most efficient running style and completion percentages and provide a basis for future studies to evaluate the long-term implications of variants in weave style and predisposition to injury. We hypothesized that dogs would display definitive gait patterns and that a single stepping pattern would yield faster run times compared to double stepping patterns.Animals: A total of 1,377 video recordings of dogs completing weaves poles at the American Kennel Club 2019 National Agility Championship were viewed.Procedures: Competition videos were reviewed as dogs attempted completion of the weave pole obstacle. Data collected included front limb and rear limb paw placement styles, time to complete the obstacle, and demographic data.Results: Attempts could be classified into one of five styles based on front and rear paw placement, with no one style dominant. Weave style differed by height and breed, with taller dogs and Border Collies preferring a single stepping style. Weave times were significantly faster for competitors using a single stepping style vs. other gaits.Conclusions and Clinical Relevance: This study found five identifiable gait styles used by dogs running weave pole obstacles, with front feet single stepping yielding significantly faster run times compared to other gaits. A clear classification of running styles will allow future studies to evaluate different stresses on joints, such as the shoulder, between varying gait styles, which could lead to recommendations for injury prevention.

Summary: Chronic low-grade inflammation is a subclinical condition directly and indirectly linked to the development of a wide range of diseases responsible for the vast majority of morbidity. To examine mechanisms coupled to chronic disease, a group of overweight and obese human subjects without known inflammatory diseases participated in a high-fat meal challenge as an acute inflammation stimulus. Analysis of serum metabolites grouped by baseline cytokine levels revealed that single samples had little power in differentiating groups. However, an analysis that incorporated temporal response separated inflammatory response phenotypes and allowed us to create a metabolic signature of inflammation which revealed metabolic components that are crucial to a cytokine-mediated inflammation response. The use of temporal response, rather than a single time point, improved metabolomic prediction of high postprandial inflammation responses and led to the development of a dynamic biosignature as a potential tool for stratifying risk to a wide range of diseases.

Rising anthropogenic CO2 levels in the atmosphere are resulting in ocean acidification which may impact coral growth rates. Here, the authors quantify the relationship between water depth and δ13C compositions of South Pacific corals from the pre-industrial era, and their results should lead to improvements in the precision of sea level reconstructions using fossil corals.

Abstract Background and Purpose: Intracerebral hemorrhage (ICH) accounts for around 10% of stroke, but carries 50% of stroke mortality. ICH characteristics and prognostic factors specific to the Stroke Belt are not well defined by race. Methods: Records of patients admitted to the University of Alabama Hospital with ICH from 2017 to 2019 were reviewed. We examined the association of demographics; clinical and radiographic features including stroke severity, hematoma volume, and ICH score; and transfer status with in-hospital mortality and discharge functional status for a biracial population including Black and White patients. Independent predictors of in-hospital mortality and functional outcome were examined using logistic regression. Results: Among the 275 ICH cases included in this biracial analysis, Black patients (n = 114) compared to White patients (n = 161) were younger (60.6 vs. 71.4 years, P < 0.0001), more often urban (81% vs. 64%, P < 0.01), more likely to have a history of hypertension (87% vs. 71%, P < 0.01), less often transferred (44% vs. 74%, P < 0.01), and had smaller median initial hematoma volumes (9.1 vs. 12.6 mL, P = 0.041). On multivariable analysis, Glasgow Coma Scale (GCS) for White patients (OR 13.0, P < 0.0001), hyperlipidemia for Black patients (OR 13.9, P = 0.019), and ICH volume for either race (Black patients: OR 1.05, P = 0.03 and White patients: OR 1.04, P < 0.01) were independent predictors of in-hospital mortality. Conclusions: Hypertension is more prevalent among Black ICH patients in the Stroke Belt. The addition of hyperlipidemia to the ICH score model improved the prediction of mortality for Black ICH patients. No differences in in-hospital mortality or poor functional outcome were observed by race.

Objective: In recognition of the mixed associations between traditionally scored slow wave sleep and memory, we sought to explore the relationships between slow wave sleep, electroencephalographic (EEG) power spectra during sleep and overnight verbal memory retention in older adults.Design, Setting, Participants, and Measurements: Participants were 101 adults without dementia (52% female, mean age 70.3 years). Delayed verbal memory was first tested in the evening prior to overnight polysomnography (PSG). The following morning, subjects were asked to recall as many items as possible from the same List (overnight memory retention; OMR). Partial correlation analyses examined the associations of delayed verbal memory and OMR with slow wave sleep (SWS) and two physiologic EEG slow wave activity (SWA) power spectral bands (0.5–1 Hz slow oscillations vs. 1–4 Hz delta activity).Results: In subjects displaying SWS, SWS was associated with enhanced delayed verbal memory, but not with OMR. Interestingly, among participants that did not show SWS, OMR was significantly associated with a higher slow oscillation relative power, during NREM sleep in the first ultradian cycle, with medium effect size.Conclusions: These findings suggest a complex relationship between SWS and memory and illustrate that even in the absence of scorable SWS, older adults demonstrate substantial slow wave activity. Further, these slow oscillations (0.5–1 Hz), in the first ultradian cycle, are positively associated with OMR, but only in those without SWS. Our findings raise the possibility that precise features of slow wave activity play key roles in maintaining memory function in healthy aging. Further, our results underscore that conventional methods of sleep evaluation may not be sufficiently sensitive to detect associations between SWA and memory in older adults.

Abstract Increases in impervious surfaces and land‐use changes associated with urbanization have long been the focus of urban hydrological research. However, studies and calculations that consider impervious surfaces alone do not encompass all factors that influence urban hydrologic response, as alternative urban structures may have a substantial effect on stormflow. This study examines several descriptors to improve estimations of hydrologic impacts of urbanization in small watersheds. Configurations of drainage densities that include storm sewers were computed for the highly urbanized Rocky Branch Watershed. Storm sewer configurations resulted in an approximate tripling of the drainage density. In addition, rainfall and stormflow data were analyzed to compare the hydrologic response of two subcatchments with varying percentages of impervious areas and drainage densities. The subcatchment with a higher percentage of impervious area produced significantly (p

Over the past few decades, medical education has seen increased interest in the use of active learning formats to engage learners and promote knowledge application over knowledge acquisition. The field of psychiatry, in particular, has pioneered a host of novel active learning paradigms. These have contributed to our understanding of the role of andragogy along the continuum of medical education, from undergraduate to continuing medical education. In an effort to frame the successes and failures of various attempts at integrating active learning into healthcare curricula, a group of educators from the A. B. Baker Section on Neurological Education from the American Academy of Neurology reviewed the state of the field in its partner field of medical neuroscience. Herein we provide a narrative review of the literature, outlining the basis for implementing active learning, the novel formats that have been used, and the lessons learned from qualitative and quantitative analysis of the research that has been done to date. While preparation time seems to present the greatest obstacle to acceptance from learners and educators, there is generally positive reception to the new educational formats. Additionally, most assessments of trainee performance have suggested non-inferiority (if not superiority). However, occasional mixed findings point to a need for better assessments of the type of learning that these new formats engender: knowledge application rather than acquisition. Moreover, this field is relatively nascent and, in order to ascertain how best to integrate active learning into psychiatry education, a framework for quantitative outcome assessments is needed going forward.

We report a teenager with childhood onset focal seizures associated with the chapeau de gendarme sign or ictal pouting of anterior insular lobe origin. The chapeau de gendarme sign has been associated with frontal lobe seizures in patients with focal epilepsy. However, in this case, stereo-electroencephalography (SEEG) localized seizures to the anterior insular cortex prior to her typical clinical manifestations. Surgical resection of the insular and frontal-lobe network resulted in seizure freedom. We propose that the anterior insular cortex should be a site of investigation during pre-surgical phase 2 evaluation in patients exhibiting the chapeau de gendarme sign during focal seizures. Keywords: Epilepsy, Chapeau de gendarme, Ictal pouting, Insula, Focal, SEEG

Yb14ZnSb11 is one of the newest additions to the high-performance Yb14MSb11 (M = Mn, Mg, and Zn) family of p-type high-temperature thermoelectric materials and shows promise for forming passivating oxide coatings. Work on the oxidation of rare earth (RE)-substituted Yb14-xRExMnSb11 single crystals suggested that substituting late RE elements may form more stable passivation oxide coatings. Yb14-xLuxZnSb11 (x = 0.1, 0.2, 0.3, 0.4, 0.5, and 0.7) samples were synthesized, and Lu-substitution's effects on thermoelectric and oxidation properties are investigated. The solubility of Lu within the system was found to be quite low with xmax ∼ 0.3; samples with x > 0.3 contained impurities of LuSb. Goldsmid-Sharp band gap estimations show that introducing Lu reduces the apparent band gap. Because of this, the Lu-substituted samples show a reduction in the maximum Seebeck coefficient, decreasing the high-temperature zT. This contrasts with the impact of Lu3+ substitution in Yb14MnSb11, where the addition of Lu3+ for Yb2+ results in increases in both resistivity and the Seebeck coefficient. Oxidation of the x = 0.3 solid solution was studied by thermogravimetric- differential scanning calorimetry , powder X-ray diffraction, scanning electron microscopy-energy-dispersive spectroscopy, and optical images. The samples show no mass gain before 785 K, and ensuing oxidation reactions are proposed. At the highest temperatures, significant amounts of Yb14-xLuxZnSb11 remained beneath an oxide coating, suggesting that passivation may be achievable in oxygen environments.

The original version of the Source Data associated with this Article included an error, in which the ‘Fiji AB d13C-Suess’ data point and the ‘TNI2 d13C-Suess Effect’ data point for the year ‘1950.5’ where incorrectly omitted from the Figure 3 tab. The missing values are ‘−0.24’ and ‘−0.64’, respectively. The HTML has been updated to include a corrected version of Source Data.

Study objectivesPeriodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects.MethodsThe MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization.ResultsWe found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 × 10-12, β = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p = 3.06 × 10-22, β = 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS.ConclusionsBecause PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.

Enzymes stabilize transition states of reactions while limiting binding to ground states, as is generally required for any catalyst. Alkaline Phosphatase (AP) and other nonspecific phosphatases are some of Nature's most impressive catalysts, achieving preferential transition state over ground state stabilization of more than 10²²-fold while utilizing interactions with only the five atoms attached to the transferred phosphorus. We tested a model that AP achieves a portion of this preference by destabilizing ground state binding via charge repulsion between the anionic active site nucleophile, Ser102, and the negatively charged phosphate monoester substrate. Removal of the Ser102 alkoxide by mutation to glycine or alanine increases the observed Pi affinity by orders of magnitude at pH 8.0. To allow precise and quantitative comparisons, the ionic form of bound P(i) was determined from pH dependencies of the binding of Pi and tungstate, a P(i) analog lacking titratable protons over the pH range of 5-11, and from the ³¹P chemical shift of bound P(i). The results show that the Pi trianion binds with an exceptionally strong femtomolar affinity in the absence of Ser102, show that its binding is destabilized by ≥10⁸-fold by the Ser102 alkoxide, and provide direct evidence for ground state destabilization. Comparisons of X-ray crystal structures of AP with and without Ser102 reveal the same active site and P(i) binding geometry upon removal of Ser102, suggesting that the destabilization does not result from a major structural rearrangement upon mutation of Ser102. Analogous Pi binding measurements with a protein tyrosine phosphatase suggest the generality of this ground state destabilization mechanism. Our results have uncovered an important contribution of anionic nucleophiles to phosphoryl transfer catalysis via ground state electrostatic destabilization and an enormous capacity of the AP active site for specific and strong recognition of the phosphoryl group in the transition state.

Loneliness is an important predictor of physical and mental health in the general population and in individuals across the psychosis spectrum, including those experiencing subclinical psychotic-like experiences (PLEs). However, the mechanisms underlying loneliness in the psychosis spectrum are not well understood. Emotion processing deficits are well described across the psychosis spectrum, and socioemotional processing biases are critical for the development and maintenance of loneliness through altered social appraisal, including judgements of rejection. Therefore, we propose that PLEs are associated with increased loneliness, and the relationship is mediated by alterations in socioemotional processing. We also explored how this pathway may be affected by mood and anxiety symptoms, which have been associated with loneliness across the psychosis spectrum. As part of the Human Connectome Project, generally healthy adults (n = 1180) reported symptomatology and social functioning and completed the Penn Emotion Recognition Task to assess efficiency in identifying emotions. We found that higher reported PLEs were associated with elevated levels of loneliness and perceived rejection and that these factors were linked by multiple independent pathways. First, anxiety/depression and emotion processing efficiency independently mediated the PLE-loneliness relationship. Second, we found that the association between PLEs and loneliness was serially mediated through inefficient emotion recognition then higher levels of perceived rejection. These separable mechanisms of increased loneliness in subclinical psychosis have implications for treatment and continued study of social functioning in the psychosis spectrum.

PURPOSE The need to rapidly implement telemedicine in primary care during the coronavirus disease 2019 (COVID-19) pandemic was addressed differently by various practices. Using qualitative data from semistructured interviews with primary care practice leaders, we aimed to report commonly shared experiences and unique perspectives regarding telemedicine implementation and evolution/maturation since March 2020. METHODS We administered a semistructured, 25-minute, virtual interview with 25 primary care practice leaders from 2 health systems in 2 states (New York and Florida) included in PCORnet, the Patient-Centered Outcomes Research Institute clinical research network. Questions were guided by 3 frameworks (health information technology evaluation, access to care, and health information technology life cycle) and involved practice leaders' perspectives on the process of telemedicine implementation in their practice, with a specific focus on the process of maturation and facilitators/barriers. Two researchers conducted inductive coding of qualitative data open-ended questions to identify common themes. Transcripts were electronically generated by virtual platform software. RESULTS Twenty-five interviews were administered for practice leaders representing 87 primary care practices in 2 states. We identified the following 4 major themes: (1) the ease of telemedicine adoption depended on both patients' and clinicians' prior experience using virtual health platforms, (2) regulation of telemedicine varied across states and differentially affected the rollout processes, (3) visit triage rules were unclear, and (4) there were positive and negative effects of telemedicine on clinicians and patients. CONCLUSIONS Practice leaders identified several challenges to telemedicine implementation and highlighted 2 areas, including telemedicine visit triage guidelines and telemedicine-specific staffing and scheduling protocols, for improvement. Key words: telemedicine; primary care; COVID-19 pandemic; East Coast; primary health care; https://doi.org/10.1370/afm.2967, INTRODUCTION The abrupt onset of the coronavirus disease 2019 (COVID-19) pandemic required a rapid implementation of telemedicine--the synchronous delivery of health care in an audio-plus-video or audio-only modality--in primary care. [...]

Adolescence is characterized by significant changes in several domains, including brain structure and function, puberty, and social and environmental factors. Some of these changes serve to increase the likelihood of psychosis onset during this period, while others may buffer this risk. This review characterizes our current knowledge regarding the unique aspects of adolescence that may serve as risk factors for schizophrenia spectrum disorders. In addition, we provide potential future directions for research into adolescent-specific developmental mechanisms that impart vulnerability to psychosis and the possibility of interventions that capitalize on adolescents' unique characteristics. Specifically, we explore the ways in which gray and white matter develop throughout adolescence in typically developing youth as well as in those with psychosis spectrum disorders. We also discuss current views on the function that social support and demands, as well as role expectations, play in risk for psychosis. We further highlight the importance of considering biological factors such as puberty and hormonal changes as areas of unique vulnerability for adolescents. Finally, we discuss cannabis use as a factor that may have a unique impact during adolescent neurodevelopment, and subsequently potentially impact psychosis onset. Throughout, we include discussion of resilience factors that may provide unique opportunities for intervention during this dynamic life stage.