Risk of Recurrent Stroke and Mortality Among Black and White Patients With Poststroke Depression.

BACKGROUND: Poststroke depression (PSD) is a treatable and common complication of stroke that is underdiagnosed and undertreated in minority populations. We compared outcomes of Black and White patients with PSD in the United States to assess whether race is independently associated with the risk of recurrent stroke and mortality. METHODS: We used deidentified Medicare data from inpatient, outpatient, and subacute nursing facilities for Black and White US patients from January 1, 2016, to December 31, 2019, to perform this retrospective cohort analysis. International Classification of Diseases, Tenth Revision codes were used to identify patients diagnosed with depression within 6 months of index stroke with no depression diagnosis 1-year preceding index stroke. We performed an unadjusted Kaplan-Meier analysis of the cumulative risk of recurrent stroke up to 3 years after index acute ischemic stroke admission and all-cause mortality following acute ischemic stroke stratified by Black and White race. We performed adjusted and reduced Cox regression to calculate hazard ratios for the main predictor of race (Black versus White), for recurrent stroke and all-cause mortality, adjusting for sociodemographic characteristics, comorbidities, characteristics of the hospitalization, and acute stroke interventions. RESULTS: Of 474 770 Medicare patients admitted with acute index stroke, 443 486 were categorized as either Black or White race and 35 604 fulfilled our criteria for PSD. Within the PSD cohort, 25 451 (71.5%) had no death or recurrent stroke within 6 months and 5592 (15.7%) had no death or readmission of any cause within 6 months. Black patients with PSD had a persistently elevated cumulative risk of recurrent stroke compared with White patients with PSD up to 3 years following acute ischemic stroke (log-rank P=0.0011). In our reduced multivariable model, Black patients had a 19.8% (hazard ratio, 1.198 [95% CI, 1.022-1.405]; P=0.0259) greater risk of recurrent stroke than White patients. The unadjusted cumulative risk of all-cause mortality was higher in this cohort of older White patients with PSD compared with Black patients; however, this difference disappeared with adjustment for age and other cofactors. CONCLUSIONS: Black patients with PSD face a persistently elevated risk of recurrent stroke compared with White patients but a similar risk of all-cause mortality. Our findings support that black race is an independent predictor of recurrent stroke in patients with PSD and highlight the need to address social determinants of health and systemic racism that impact poststroke outcomes among racial minorities.

National Institutes of Health Stroke Scale Reporting in Medicare Claims Data: Reporting in the First 3 Years.

BACKGROUND: Since 2016, hospitals have been able to document International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for the National Institutes of Health Stroke Scale (NIHSS). As of 2023, the Centers for Medicare & Medicaid Services uses NIHSS as a risk adjustment variable. We assessed associations between patient- and hospital-level variables and contemporary NIHSS reporting. METHODS: We performed a retrospective cross-sectional analysis of 2019 acute ischemic stroke admissions using deidentified, national 100% inpatient Medicare Fee-For-Service data sets. We identified index acute ischemic stroke admissions using the ICD-10-CM code I63.x and abstracted demographic information, medical comorbidities, hospital characteristics, and NIHSS. We linked Medicare and Mount Sinai Health System (New York, NY) registry data from 2016 to 2019. We calculated NIHSS documentation at the patient and hospital levels, predictors of documentation, change over time, and concordance with local data. RESULTS: There were 231 383 index acute ischemic stroke admissions in 2019. NIHSS was documented in 44.4% of admissions and by 66.5% of hospitals. Hospitals that documented ≥1 NIHSS were more commonly teaching hospitals (39.0% versus 5.5%; standardized mean difference score, 0.88), stroke certified (37.2% versus 8.0%; standardized mean difference score, 0.75), higher volume (mean, 80.8 [SD, 92.6] versus 6.33 [SD, 14.1]; standardized mean difference score, 1.12), and had intensive care unit availability (84.9% versus 23.2%; standardized mean difference score, 1.57). Adjusted odds of documentation were lower for patients with inpatient mortality (odds ratio, 0.64 [95% CI, 0.61-0.68]; P<0.0001), in nonmetropolitan areas (odds ratio, 0.49 [95% CI, 0.40-0.61]; P<0.0001), and male sex (odds ratio, 0.95 [95% CI, 0.93-0.97]; P<0.0001). NIHSS was documented for 52.9% of Medicare cases versus 93.1% of registry cases, and 74.7% of Medicare NIHSS scores equaled registry admission NIHSS. CONCLUSIONS: Missing ICD-10-CM NIHSS data remain widespread 3 years after the introduction of the ICD-10-CM NIHSS code, and there are systematic differences in reporting at the patient and hospital levels. These findings support continued assessment of NIHSS reporting and caution in its application to risk adjustment models.

The Development and Feasibility of a Novel Group Intervention to Support Helping Professionals in Metabolizing Suffering and Engaging Strengths: The CHRYSALIS Program.

This feasibility study reports on the development and initial evaluation of a novel online intervention for helping professionals (HPs; i.e. mental health professionals, chaplains, clergy) designed to (a) address occupational hazards, such as burnout and vicarious traumatization, and (b) promote well-being and flourishing at work. In contrast with competency and self-care focused models, the CHRYSALIS (Catalyzing Helping Professionals' Resilience, VitalitY, Spirituality, Authentic Living, and Inner Strength) intervention centers the self of the provider, explores cultural and spiritual contexts, and attends to systemic challenges. As part of a larger randomized controlled trial evaluating two program formats, the group format entails eight online sessions exploring strengths that can promote well-being, including processing, relational, vitalizing, orienting, and agentic capacities. To pilot test this framework and establish proof of concept, this study analyzed data from 41 HPs who had been randomly assigned to the group condition and completed surveys at four time points. Quantitative results indicated significant reductions in vicarious traumatization and burnout as well as increased well-being and meaning in work. Qualitative results suggest the intervention fostered relational support, cultivated new perspectives, and increased engagement with strengths, positively impacting participants' work and navigation of caregiving systems. Feedback about cohesion and group dynamic challenges in an online format informed further program development. This study provides initial support for the feasibility and efficacy of the group format of the CHRYSALIS intervention as a creative means to address HPs' risk for occupational hazards and promote holistic formation in a relational context.

Human Macrophages Activate Bystander Neutrophils' Metabolism and Effector Functions When Challenged with Mycobacterium tuberculosis.

Neutrophils are dynamic cells, playing a critical role in pathogen clearance; however, neutrophil infiltration into the tissue can act as a double-edged sword. They are one of the primary sources of excessive inflammation during infection, which has been observed in many infectious diseases including pneumonia and active tuberculosis (TB). Neutrophil function is influenced by interactions with other immune cells within the inflammatory lung milieu; however, how these interactions affect neutrophil function is unclear. Our study examined the macrophage-neutrophil axis by assessing the effects of conditioned medium (MΦ-CM) from primary human monocyte-derived macrophages (hMDMs) stimulated with LPS or a whole bacterium (Mycobacterium tuberculosis) on neutrophil function. Stimulated hMDM-derived MΦ-CM boosts neutrophil activation, heightening oxidative and glycolytic metabolism, but diminishes migratory potential. These neutrophils exhibit increased ROS production, elevated NET formation, and heightened CXCL8, IL-13, and IL-6 compared to untreated or unstimulated hMDM-treated neutrophils. Collectively, these data show that MΦ-CM from stimulated hMDMs activates neutrophils, bolsters their energetic profile, increase effector and inflammatory functions, and sequester them at sites of infection by decreasing their migratory capacity. These data may aid in the design of novel immunotherapies for severe pneumonia, active tuberculosis and other diseases driven by pathological inflammation mediated by the macrophage-neutrophil axis.

Cinnamic Acid and Caffeic Acid Effects on Gastric Tight Junction Proteins Analyzed in Xenopus laevis Oocytes.

Analysis of secondary plant compounds for the development of novel therapies is a common focus of experimental biomedicine. Currently, multiple health-supporting properties of plant-derived molecules are known but still information on many mechanisms is scarce. Cinnamic acid and caffeic acid are two of the most abundant polyphenols in human dietary fruits and vegetables. In this study, we investigated cinnamic acid and caffeic acid effects on the gastric barrier, which is primarily provided by members of the transmembrane tight junction protein family of claudins. The Xenopus laevis oocyte has been established, in recent years, as a heterologous expression system for analysis of transmembrane tight junction protein interactions, by performing paired oocyte experiments to identify an effect on protein-protein interactions, in vitro. In our current study, human gastric claudin-4, -5, and -18.2. were expressed and detected in the oocyte plasma membrane by freeze fracture electron microscopy and immunoblotting. Oocytes were paired and incubated with 100 µM or 200 µM cinnamic acid or caffeic acid, or Ringer's solution, respectively. Caffeic acid showed no effect on the contact area strength of paired oocytes but led to an increased contact area size. In contrast, cinnamic acid-incubated paired oocytes revealed a reduced contact area and a strengthening effect on the contact area was identified. These results may indicate that caffeic acid and cinnamic acid both show an effect on gastric barrier integrity via direct effects on tight junction proteins.

Cannabidiol Strengthening of Gastric Tight Junction Complexes Analyzed in an Improved Xenopus Oocyte Assay.

Cannabidiol (CBD), the non-psychoactive compound derived from the cannabis plant, has gained attention in recent years as a remedy against gastrointestinal disorders ranging from nausea and inflammation to abdominal pain. Recent advances demonstrated an effect on inflammatory pathways and barrier proteins. However, information on possible direct effects is scarce and needs to be addressed, as applications are currently increasing in popularity. To accomplish this, we have employed Xenopus laevis oocytes as a heterologous expression system for analysis of the direct effects on stomach-specific claudins and further developed tight junction (TJ) protein interaction assays. Human claudin-4, claudin-5, and claudin-18.2 were expressed in Xenopus oocytes, clustered in pairs to form contact areas, and analyzed in a two-cell model approach, including measurement of the contact area and contact strength. CLDN4/5/18 + CLDN4/5/18 oocyte pairs were incubated with 20 µM CBD or with 40 µM CBD and were compared to cells without CBD treatment (ctrl). For interaction analysis, the contact area was measured after 24 h and 48 h. Whereas CBD did not affect the size of the protein interaction area, Double Orbital Challenge experiments revealed an increased contact strength after 24 h incubation with CBD. In addition, the Xenopus oocyte experiments were accompanied by an analysis of claudin-4, -5, and -18 expression in gastric epithelium by immunoblotting and immunohistochemistry. Claudin-4, -5, and -18 were strongly expressed, indicating a major role for gastric epithelial barrier function. In summary, our study shows direct effects of 40 µM CBD on Xenopus oocytes heterologously expressing a stomach-specific claudin combination, indicating a supportive and beneficial effect of CBD on gastric TJ proteins.

Variation in US acute ischemic stroke treatment by hospital regions: limited endovascular access despite evidence.

BACKGROUND: Although national organizations recognize the importance of regionalized acute ischemic stroke (AIS) care, data informing expansion are sparse. We assessed real-world regional variation in emergent AIS treatment, including growth in revascularization therapies and stroke center certification. We hypothesized that we would observe overall growth in revascularization therapy utilization, but observed differences would vary greatly regionally. METHODS: A retrospective cross-sectional analysis was carried out of de-identified national inpatient Medicare Fee-for-Service datasets from 2016 to 2019. We identified AIS admissions and treatment with thrombolysis and endovascular thrombectomy (ET) with International Classification of Diseases, 10th Revision, Clinical Modification codes. We grouped hospitals in Dartmouth Atlas of Healthcare Hospital Referral Regions (HRR) and calculated hospital, demographic, and acute stroke treatment characteristics for each HRR. We calculated the percent of hospitals with stroke certification and AIS cases treated with thrombolysis or ET per HRR. RESULTS: There were 957 958 AIS admissions. Relative mean (SD) growth in percent of AIS admissions receiving revascularization therapy per HRR from 2016 to 2019 was 13.4 (31.7)% (IQR -6.1-31.7%) for thrombolysis and 28.0 (72.0)% (IQR 0-56.0%) for ET. The proportion of HRRs with decreased or no difference in ET utilization was 38.9% and the proportion of HRRs with decreased or no difference in thrombolysis utilization was 32.7%. Mean (SD) stroke center certification proportion across HRRs was 45.3 (31.5)% and this varied widely (IQR 18.3-73.4%). CONCLUSIONS: Overall growth in AIS treatment has been modest and, within HRRs, growth in AIS treatment and the proportion of centers with stroke certification varies dramatically.

Creating ophthalmology experiences in undergraduate medical education: pilot of a cased-based learning ophthalmology tool.

PURPOSE: To evaluate medical student perceptions of a novel ophthalmology resource delivered through facilitated workshops in the core clerkship curriculum. METHODS: We created www.2020sim.com, a free case-based learning (CBL) ophthalmology tool, adapted from NephSIM (www.nephsim.com). The tool was first piloted with the internal medicine (IM) residents. After confirming a need, we focused on undergraduate medical education (UME) by expanding the 20/20 SIM content and partnering with the neurology (pilot academic year [AY] 2020-2021) and pediatric clerkships (pilot AY 2021-2022) to deliver a facilitated one-hour ophthalmology workshop within each clerkship's didactic curriculum. We evaluated the tool using pre- and post-surveys and knowledge assessments. RESULTS: Of 80 IM residents, 33 (41.3%) completed the needs assessment. Of the 25 residents who attended the workshop, 23 (92.0%) completed the exit survey. IM residents reported discomfort in several ophthalmology domains (9 of 14 rated mean score < 3.0), confirming a need. Most (n = 21/23, 91.3%) rated the tool as good/excellent. Of 145 neurology clerkship students, 125 (86.2%) and at least 88 (60.7%) students completed the pre- and post-test/exit surveys, respectively. On average, participants highly rated the tool, perceiving 20/20 SIM to be relevant to their education [4.1 (0.8)]. Mean pre- to post-test knowledge scores increased from 7.5 to 8.5/10.0 points (p < 0.001). Of the 136 pediatric clerkship students, 67 (49.3%) and 51 (37.5%) completed the pre- and post-surveys, respectively. Respondents perceived increased comfort with ophthalmology topics after the facilitated workshop [3.8 (0.8)]. Mean pre- to post-test knowledge scores trended from 1.8 to 2.0/5.0 points (p = 0.30). Collectively, 20/139 (14.4%) of exit survey respondents visited www.2020sim.com within 1 month after the workshop. CONCLUSION: After identifying areas of greatest need with residents, we partnered with core clerkships to deliver cross-disciplinary ophthalmology content in UME. We found high engagement with 20/20 SIM, with trends toward increased knowledge.

Integrating biogeography and behavioral ecology to rapidly address biodiversity loss.

Addressing climate change and biodiversity loss will be the defining ecological, political, and humanitarian challenge of our time. Alarmingly, policymakers face a narrowing window of opportunity to prevent the worst impacts, necessitating complex decisions about which land to set aside for biodiversity preservation. Yet, our ability to make these decisions is hindered by our limited capacity to predict how species will respond to synergistic drivers of extinction risk. We argue that a rapid integration of biogeography and behavioral ecology can meet these challenges because of the distinct, yet complementary levels of biological organization they address, scaling from individuals to populations, and from species and communities to continental biotas. This union of disciplines will advance efforts to predict biodiversity's responses to climate change and habitat loss through a deeper understanding of how biotic interactions and other behaviors modulate extinction risk, and how responses of individuals and populations impact the communities in which they are embedded. Fostering a rapid mobilization of expertise across behavioral ecology and biogeography is a critical step toward slowing biodiversity loss.

Artificial Intelligence-Assisted Software Significantly Decreases All Workflow Metrics for Large Vessel Occlusion Transfer Patients, within a Large Spoke and Hub System.

INTRODUCTION: Artificial intelligence (AI) software is increasingly applied in stroke diagnostics. Viz LVO (large vessel occlusion) is an AI-based software that is FDA-approved for LVO detection in CT angiography (CTA) scans. We sought to investigate differences in transfer times (from peripheral [spoke] to central [hub] hospitals) for LVO patients between spoke hospitals that utilize Viz LVO and those that do not. METHODS: In this retrospective cohort study, we used our institutional database to identify all suspected/confirmed LVO-transferred patients from spokes (peripheral hospitals) within and outside of our healthcare system, from January 2020 to December 2021. The "Viz-transfers" group includes all LVO transfers from spokes within our system where Viz LVO is readily available, while the "Non-Viz-transfers" group (control group) is comprised of all LVO transfers from spokes outside our system, without Viz LVO. Primary outcome included all available time metrics from peripheral CTA commencement. RESULTS: In total, 78 patients required a transfer. Despite comparable peripheral hospital door to peripheral hospital CTA times (20.5 [24.3] vs. 32 [45] min, p = 0.28) and transfer (spoke to hub) time (23 [18] vs. 26 [13.5], p = 0.763), all workflow metrics were statistically significantly shorter in the Viz-transfers group. Peripheral CTA to interventional neuroradiology team notification was 12 (16.8) versus 58 (59.5), p < 0.001, and peripheral CTA to peripheral departure was 91.5 (37) versus 122.5 (68.5), p < 0.001. Peripheral arrival to peripheral departure was 116.5 (75.5) versus 169 (126.8), p = 0.002, and peripheral arrival to central arrival was 145 (62.5) versus 207 (97.8), p < 0.001. In addition, peripheral CTA to angiosuite arrival was 121 (41) versus 207 (92.5), p < 0.001, peripheral CTA to arterial puncture was 146 (53) versus 234 (99.8), p < 0.001, and peripheral CTA to recanalization was 198 (25) versus 253.5 (86), p < 0.001. CONCLUSION: Within our spoke and hub system, Viz LVO significantly decreased all workflow metrics for patients who were transferred from spokes with versus without Viz.

Patterns in the number of interventionalists for endovascular treatment of acute ischemic stroke in the US.

BACKGROUND: Endovascular thrombectomy (ET) has become the standard of stroke care for large vessel occlusion acute ischemic stroke (AIS) involving the anterior circulation. With continued eligibility expansion, the demand for neuro-intervention is growing. Current estimates indicate inadequate supply of interventionalists. However, there is limited data describing the number of interventionalists per hospital in the US, and correlations with outcomes. METHODS: We used Medicare 100% sample datasets and included all AIS admissions from 2018 to 2019, using validated International Classification of Diseases, 10th Revision, Clinical Modification codes to identify AIS and comorbidities. We utilized National Provider Identifier codes to identify distinct interventionalists at the hospital. We examined outcomes at the hospital level, including percent of AIS treated with thrombolysis, percent of AIS with inpatient mortality, percent of AIS with discharge home, and percent of AIS with death within 30 days. RESULTS: Among 471,427 AIS admissions, 16,253 received ET over the 2-year period of the study. Only 683 of 4576 AIS-treating institutions provided ET (14.9%). These ET centers most frequently only had one interventionalist performing ET and were clustered in large metropolitan areas with high AIS volumes. As AIS volumes, ET volumes, and mean NIHSS scores increased, so did the number of interventionalists. With each additional interventionalist, there was an increased likelihood of poor outcomes including inpatient mortality, discharge home, and 30-day mortality. CONCLUSIONS: We confirmed a relative lack of neuro-interventionalists among US hospitals, with a concentration of interventionalists in urban, high-volume centers. The greater likelihood of poor outcomes associated with increasing number of interventionalists is likely due to increasing complexity and severity of cases at high-volume ET centers, but further study is needed.

Cellular Distribution Pattern of tjp1 (ZO-1) in Xenopus laevis Oocytes Heterologously Expressing Claudins.

Epithelial barriers constitute a fundamental requirement in every organism, as they allow the separation of different environments and set boundaries against noxious and other adverse effectors. In many inflammatory and degenerative diseases, epithelial barrier function is impaired because of a disturbance of the paracellular seal. Recently, the Xenopus laevis oocyte has been established as a heterologous expression model for the analysis of transmembrane tight junction protein interactions and is currently considered to be a suitable screening model for barrier effectors. A prerequisite for this application is a physiological anchoring of claudins to the cytoskeleton via the major scaffolding protein tjp1 (tight junction protein 1, ZO-1). We have analyzed the oocyte model with regard to the interaction of heterologously expressed claudins and tjp1. Our experiments have revealed endogenous tjp1 expression in protein and mRNA analyses of unfertilized Xenopus laevis oocytes expressing human claudin 1 (CLDN1) to claudin 5 (CLDN5). The amphibian cell model can therefore be used for the analysis of claudin interactions.

Risk, Determinants, and Pharmacologic Treatment of Depression Following Acute Ischemic Stroke.

Background and Purpose: We assessed risk and determinants of new-onset depression in acute ischemic stroke (AIS) patients of all ages and no known history of depression. Additionally, we assessed patterns of post-stroke depression (PSD) treatment with pharmacotherapy. Methods: Retrospective cohort study of de-identified Marketscan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits Datasets for adults age ≥18 years admitted with AIS from July 1, 2016-July 1, 2017. We created Kaplan-Meier curves of cumulative risk of PSD up to 1.5 years following index AIS admission. We performed Cox regression to report hazard ratios for determinants of PSD up to 1.5 years following AIS. We summarized proportions treated with pharmacotherapy and identified the most commonly prescribed medications. Results: Of 8089 AIS patients, 1059 were diagnosed with PSD. At 1 year, cumulative risk of PSD was 13.4% (standard error .4) and 15.3% (standard error .5) at 1.5 years. History of anxiety was most strongly associated with PSD and discharge home least. Among those with PSD, 68.8% were prescribed an antidepressant and 8.4% an antipsychotic. The most commonly prescribed antidepressant was sertraline (28.5%). Conclusions: Among AIS patients of all ages, there is a persistently elevated cumulative risk of new diagnosis of PSD in the 1.5 years following AIS. Of the >2/3 treated with an antidepressant, sertraline was most commonly prescribed. Screening and treatment strategies for PSD require further study.

Bulky ligands protect molecular ruby from oxygen quenching.

Chromium(III) complexes can show phosphorescence from the spin-flip excited doublet states 2E/2T1 in the near-infrared with high photoluminescence quantum yields and extremely long lifetimes in the absence of dioxygen. The prototype molecular ruby, [Cr(ddpd)2]3+ (ddpd = N,N'-dimethyl-N,N'-dipyridine-2-ylpyridine-2,6-diamine), has a photoluminescence quantum yield and a luminescence lifetime of 13.7% and 1.1 ms in deaerated acetonitrile, respectively. However, its luminescence is strongly quenched by 3O2via an efficient Dexter-type energy transfer process. To enable luminescence applications of molecular rubies in solution under aerobic conditions, we explored the potential of sterically demanding ddpd ligands to shield the chromium(III) center from O2 using steady state and time-resolved photoluminescence spectroscopy. The structures of the novel complexes with sterically demanding ligands were investigated by single crystal X-ray diffraction and quantum chemically by density functional theory calculations. The O2 sensitivity of the photoluminescence was derived from absolutely measured photoluminescence quantum yields and excited state lifetimes under inert and aerobic conditions and by Stern-Volmer analyses of these data. Optimal sterically shielded chromium(III) complexes revealed photoluminescence quantum yields of up to 5.1% and excited state lifetimes of 518 µs in air-saturated acetonitrile, underlining the large potential of this ligand design approach to broaden the applicability of highly emissive chromium(III) complexes.

Functional Analysis of Gastric Tight Junction Proteins in Xenopus laevis Oocytes.

The epithelial barrier is crucial for proper gastrointestinal function, preventing the unwanted passage of solutes and therefore representing a prerequisite for vectorial transport. Claudin-4 and claudin-18.2, two critical tight junction proteins of the gastric epithelium, seal neighboring cells in a physically and mechanically challenging environment. As the Xenopus laevis oocyte allows the functional and molecular analyses of claudin interaction, we have addressed the hypothesis that this interaction is not only dependent on mechanical force but also on pH. We expressed human claudin-4 and claudin-18 in Xenopus oocytes, and analyzed them in a two-cell model approach. Cells were clustered in pairs to form contact areas expressing CLDN18 + CLDN18, CLDN4/18 + CLDN4/18, and compared to controls, respectively. Contact areas in cells incubated in medium at pH 5.5 and 7.4 were quantified by employing transmitted light microscopy. After 24 h at pH 5.5, clustering of CLDN18 + CLDN18 and CLDN4/18 + CLDN4/18-expressing oocytes revealed a contact area reduced by 45% and 32%, compared with controls, respectively. A further approach, high-pressure impulse assay, revealed a stronger tight junction interaction at pH 5.5 in oocyte pairs expressing CLDN18 + CLDN18 or CLDN4/18 + CLDN4/18 indicating a protective role of claudin-18 for tight junction integrity during pH challenge. Thus, our current analysis of gastric tight junction proteins further establishes oocytes as an expression and two-cell screening model for tight junction integrity analysis of organ- and tissue-specific claudins by the characterization of homo- and heterophilic trans-interaction dependent on barrier effectors.

Barrier Perturbation in Porcine Peyer's Patches by Tumor Necrosis Factor is Associated With a Dysregulation of Claudins.

The proinflammatory cytokine tumor necrosis factor (TNF) has been described as one of the main mediators of intestinal inflammatory diseases, affecting the composition of tight junction (TJ) proteins and leading to a disruption of the epithelial barrier. An intact intestinal barrier is mandatory, because the follicle-associated epithelium of Peyer's patches represents the first defense line of the intestinal immune system and ensures a controlled uptake of antigens from the gut lumen. In the current study, we have analyzed the detailed effects of TNF on the follicle-associated epithelium of porcine Peyer's patches by applying the Ussing chamber technique. Epithelial tissue specimens of Peyer's patches and the surrounding villus epithelium were mounted into conventional Ussing chambers and incubated with TNF for 10 h. The transepithelial resistance, representing epithelial barrier function of the tissue, was recorded. A reduction of transepithelial resistance was detected after 8 h in Peyer's patch tissue specimens, whereas the villus epithelium was not significantly affected by TNF. Subsequent molecular analysis of TJ protein expression revealed a marked decrease of claudin-1 and -4, and an increase of claudin-2. In neighboring villus epithelium, no significant changes in the expression of TJ proteins could be shown. A strong increase of TNF receptor-2 (TNFR-2) could also be detected in Peyer's patches, in agreement with the major role of this receptor in Peyer's patches. Our findings were in accordance with changes detected by confocal laser scanning immunofluorescence microscopy. The regulation of TNF effects via myosin light chain kinase (MLCK) was analyzed in blocking experiments. Our detailed analysis is the first to show that TNF affects the barrier function of the follicle-associated epithelium of porcine Peyer's patches but has no effects on the villus epithelium. These findings reveal not only the basic differences of epithelial barrier function between the two structures, but also the significance of Peyer's patches as a primary mucosal immune defense.

Trends in the Utilization of Teleneurology and Other Healthcare Resources Prior to and During the COVID-19 Pandemic in an Urban, Tertiary Health System.

BACKGROUND: Patient groups traditionally affected by health disparities were less likely to use video teleneurology (TN) care during the initial COVID-19 pandemic surge in the United States. Whether this asymmetry persisted later in the pandemic or was accompanied with a loss of access to care remains unknown. METHODS: We conducted a retrospective cohort study using patient data from a multicenter healthcare system in New York City. We identified all established pediatric or adult neurology patients with at least two prior outpatient visits between June 16th, 2019 and March 15th, 2020 using our electronic medical record. For this established pre-COVID cohort, we identified telephone, in-person, video TN or emergency department visits and hospital admissions for any cause between March 16th and December 15th, 2020 ("COVID period"). We determined clinical, sociodemographic, income, and visit characteristics. Our primary outcome was video TN utilization, and our main secondary outcome was loss to follow-up during the COVID period. We used multivariable logistic regression to model the relationship between patient-level characteristics and both outcomes. RESULTS: We identified 23,714 unique visits during the COVID period, which corresponded to 14,170 established patients from our institutional Neurology clinics during the pre-COVID period. In our cohort, 4,944 (34.9%) utilized TN and 4,997 (35.3%) were entirely lost to follow-up during the COVID period. In the adjusted regression analysis, Black or African-American race [adjusted odds ratio (aOR) 0.60, 97.5%CI 0.52-0.70], non-English preferred language (aOR 0.49, 97.5%CI 0.39-0.61), Medicaid insurance (aOR 0.50, 97.5%CI 0.44-0.57), and Medicare insurance (aOR 0.73, 97.5%CI 0.65-0.83) had decreased odds of TN utilization. Older age (aOR 0.98, 97.5%CI 0.98-0.99), female sex (aOR 0.90 97.5%CI 0.83-0.99), and Medicaid insurance (aOR 0.78, 0.68-0.90) were associated with decreased odds of loss to follow-up. CONCLUSION: In the first 9 months of the COVID-19 pandemic, we found sociodemographic patterns in TN utilization that were similar to those found very early in the pandemic. However, these sociodemographic characteristics were not associated with loss to follow-up, suggesting that lack of TN utilization may not have coincided with loss of access to care.

The overlooked NIR luminescence of Cr(ppy)3.

Cr(ppy)3, a structural analog of the green phosphorescent Ir(ppy)3, emits even in solution at room temperature from a weakly distorted spin-flip state at 910 nm (Hppy = 2-phenylpyridine). The low energy arises from an enhanced covalence of the Cr-C bonds as compared to Cr-N bonds. Lower temperature reduces thermally activated decay increasing the emission intensity.