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We estimate global terrestrial gross primary production (GPP) based on models that use satellite data within a simplified light-use efficiency framework that does not rely upon other meteorological inputs. Satellite-based geometry-adjusted reflectances are from theMODerate-resolution Imaging Spectroradiometer (MODIS) and provide information about vegetation structure and chlorophyll content at both high temporal (daily to monthly) and spatial (~1 km) resolution. We use satellite-derived solar-induced fluorescence (SIF) to identify regions of high productivity crops and also evaluate the use of downscaled SIF to estimate GPP. We calibrate a set of our satellite-based models with GPP estimates from a subset of distributed eddy covariance flux towers (FLUXNET 2015). The results of the trained models are evaluated using an independent subset of FLUXNET 2015 GPP data. We show that variations in light-use efficiency (LUE) with incident PAR are important and can be easily incorporated into the models. Unlike many LUE-based models, our satellite-based GPP estimates do not use an explicit parameterization of LUE that reduces its value fromthe potentialmaximum under limiting conditions such as temperature and water stress. Even without the parameterized downward regulation, our simplified models are shown to perform as well as or better than state-of-the-art satellite data-driven products that incorporate such parameterizations. A significant fraction of both spatial and temporal variability in GPP across plant functional types can be accounted for using our satellite-based models. Our results provide an annual GPP value of ~140 PgCyear-1 for 2007 that is within the range of a compilation of observation-based, model, and hybrid results, but is higher than some previous satellite observation-based estimates.

Increased aridity and human population have reduced tree cover in parts of the African Sahel and degraded resources for local people. Yet, tree cover trends and the relative importance of climate and population remain unresolved. From field measurements, aerial photos, and Ikonos satellite images, we detected significant 1954–2002 tree density declines in the western Sahel of 18 ± 14% (P = 0.014, n = 204) and 17 ± 13% (P = 0.0009, n = 187). From field observations, we detected a significant 1960–2000 species richness decline of 21 ± 11% (P = 0.0028, n = 14) across the Sahel and a southward shift of the Sahel, Sudan, and Guinea zones. Multivariate analyses of climate, soil, and population showed that temperature most significantly (P

Fire is a major disturbance in the boreal forest, and has been shown to release significant amounts of carbon (C) to the atmosphere through combustion. However, less is known about the effects on ecosystems following fire, which include reduced productivity and changes in decomposition in the decade immediately following the disturbance. In this study, we assessed the impact of fire on net primary productivity (NPP) in the North American boreal forest using a 17-year record of satellite NDVI observations at 8-km spatial resolution together with a light-use efficiency model. We identified 61 fire scars in the satellite observations using digitized fire burn perimeters from a database of large fires. We studied the postfire response of NPP by analyzing the most impacted pixel within each burned area. NPP decreased in the year following the fire by 60-260g CM-2 yr-1 (30-80%). By comparing pre- and postfire observations, we estimated a mean NPP recovery period for boreal forests of about 9 years, with substantial variability among fires. We incorporated this behavior into a carbon cycle model simulation to demonstrate these effects on net ecosystem production. The disturbance resulted in a release of C to the atmosphere during the first 8 years, followed by a small, but long-lived, sink lasting 150 years. Postfire net emissions were three times as large as from a model run without changing NPP. However, only small differences in the C cycle occurred between runs after 8 years due to the rapid recovery of NPP. We conclude by discussing the effects of fire on the long-term continental trends in satellite NDVI observed across boreal North America during the 1980s and 1990s.

The Sea-viewing Wide Field-of-view Sensor (SeaWiFS) provides global monthly measurements of both oceanic phytoplankton chlorophyll biomass and light harvesting by land plants. These measurements allowed the comparison of simultaneous ocean and land net primary production (NPP) responses to a major El Niño to La Niña transition. Between September 1997 and August 2000, biospheric NPP varied by 6 petagrams of carbon per year (from 111 to 117 petagrams of carbon per year). Increases in ocean NPP were pronounced in tropical regions where El Niño-Southern Oscillation (ENSO) impacts on upwelling and nutrient availability were greatest. Globally, land NPP did not exhibit a clear ENSO response, although regional changes were substantial.

The United States faces many existing and emerging mosquito-borne disease threats, such as West Nile virus and Rift Valley fever. An important component of strategic prevention and control plans for these and other mosquito-borne diseases is forecasting the distribution, timing, and abundance of mosquito vector populations. Populations of many medically important mosquito species are closely tied to climate, and historical climate-population associations may be used to predict future population dynamics. Using 2003-2005 U.S. Army Center for Health Promotion and Preventive Medicine mosquito surveillance data, we looked at populations of several known mosquito vectors of West Nile virus, as well as possible mosquito vectors of Rift Valley fever virus, at continental U.S. military installations. We compared population changes with concurrent patterns for a satellite-derived index of climate (normalized difference vegetation index) and observed instances of population changes appearing to be direct responses to climate. These preliminary findings are important first steps in developing an automated, climate-driven, early warning system to flag regions of the United States at elevated risk of mosquito-borne disease transmission. [ABSTRACT FROM AUTHOR]

T cell receptor (TCR) engagement triggers T cell responses, yet how TCR-mediated activation is regulated at the plasma membrane remains unclear. Here, we report that deleting the membrane scaffolding protein Flotillin-2 (Flot2) increases T cell antigen-sensitivity, resulting in enhanced TCR signaling and effector function to weak TCR stimulation. T cell-specific Flot2-deficient mice exhibited reduced tumor growth and enhanced immunity to infection. Flot2-null CD4+ T cells exhibited increased T helper 1 polarization, proliferation, Nur77 induction, and phosphorylation of ZAP70 and ERK1/2 upon weak TCR stimulation, indicating a sensitized TCR-triggering threshold. Single cell-RNA sequencing suggested that Flot2-null CD4+ T cells follow a similar route of activation as wild-type CD4+ T cells but exhibit higher occupancy of a discrete activation state under weak TCR stimulation. Given prior reports that TCR clustering influences sensitivity of T cells to stimuli, we evaluated TCR distribution with super-resolution microscopy. Flot2 ablation increased the number of surface TCR nanoclusters on naïve CD4+ T cells. Collectively, we posit that Flot2 modulates T cell functionality to weak TCR stimulation, at least in part, by regulating surface TCR clustering. Our findings have implications for improving T cell reactivity in diseases with poor antigenicity, such as cancer and chronic infections.

The baobab tree (Adansonia digitata L.) is an integral part of rural livelihoods throughout the African continent. However, the combined effects of climate change and increasing global demand for baobab products are currently exerting pressure on the sustainable utilization of these resources. Here we use sub-metre-resolution satellite imagery to identify the presence of nearly 2.8 million (underestimation bias 27.1%) baobab trees in the Sahel, a dryland region of 2.4 million km 2 . This achievement is considered an essential step towards an improved management and monitoring system of valuable woody species. Using Senegal as a case country, we find that 94% of rural buildings have at least one baobab tree in their immediate surroundings and that the abundance of baobabs is associated with a higher likelihood of people consuming a highly nutritious food group: dark green leafy vegetables. The generated database showcases the feasibility of mapping the location of single tree species at a sub-continental scale, providing vital information in times when deforestation and climate change cause the extinction of numerous tree species., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Phosphate (Pi) serves countless metabolic pathways and is involved in macromolecule synthesis, energy storage, cellular signaling, and bone maintenance. Herein, we describe the coordination of Pi uptake and efflux pathways to maintain mammalian cell Pi homeostasis. We discover that XPR1, the presumed Pi efflux transporter, separately supervises rates of Pi uptake. This direct, regulatory interplay arises from XPR1 being a binding partner for the Pi uptake transporter PiT1, involving a predicted transmembrane helix/extramembrane loop in XPR1, and its hitherto unknown localization in a subset of intracellular LAMP1-positive puncta (named "XLPVs"). A pharmacological mimic of Pi homeostatic challenge is sensed by the inositol pyrophosphate IP 8 , which functionalizes XPR1 to respond in a temporally hierarchal manner, initially adjusting the rate of Pi efflux, followed subsequently by independent modulation of PiT1 turnover to reset the rate of Pi uptake. These observations generate a unifying model of mammalian cellular Pi homeostasis, expanding opportunities for therapeutic intervention., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Background: There has been a recent push to transition procedures previously performed at hospital-based outpatient surgical departments (HOPDs) to ambulatory surgery centers (ASCs). However, limited data regarding differences in early postoperative complications and care utilization (eg, emergency department visits and unplanned admissions) may drive increased overall costs or worse outcomes., Purpose/hypothesis: The purpose of this study was to examine differences in early 90-day adverse outcomes and postoperative emergency department visits associated with shoulder surgeries excluding arthroplasties that were performed in HOPDs and ASCs in a closed military health care system. We hypothesized that there would be no difference in outcomes between treatment settings., Methods: We retrospectively evaluated the records for 1748 elective shoulder surgeries from 2015 to 2020. Patients were considered as 1 of 2 cohorts depending on whether they underwent surgery in an ASC or HOPD setting. We evaluated groups for differences incomplexity, surgical time, and medical risk. Outcome measures were emergency department visits, unplanned hospital admissions, and complications within the first 90 days after surgery., Results: There was no difference in 90-day postoperative emergency department visits between procedures performed at HOPDs (n = 606) and ASCs (n = 1142). There was a slight increase in rate of unplanned hospital admission within 90 days after surgery in the HOPD cohort, most commonly for pain or overnight observation. The surgical time was significantly shorter (105 vs. 119 minutes, P < .01) at the ASC, but there was no difference in case complexity between the cohorts (P = .28)., Discussion/conclusion: Our results suggest that in appropriate patients, surgery in ASCs can be safely leveraged for its costs savings, efficiency, patient satisfaction, decreases in operative time, and potentially decreased resource utilization both during surgery and in the early postoperative period., (Published by Elsevier Inc.)

Meniscal injury is common, and despite modern techniques, the failure rate following repair remains high. While there are recent treatment advances in the form of biologics, there is limited evidence and agreement on these emerging therapies and their role in meniscal healing. Amniotic tissue (umbilical cord allograft) is a biologic augmentation therapy that has been utilized in other musculoskeletal applications but has not been reported for use in meniscal repair. We describe a technique to deliver an allograft amniotic membrane into a meniscus tear repair site, potentially optimizing healing., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.M.T. is a board member of the 10.13039/100008542Arthroscopy Association of North America, Orthopedics Today, and Journal of Shoulder and Elbow Surgery; is a consultant or advisor for 10.13039/100004331Johnson & Johnson and Arthrex; receives speaking and lecture fees from Arthrex; and receives funding grants and nonfinancial support from the Journal of Shoulder and Elbow Surgery. C.J.T. is a board member of the Society of Military Orthopaedic Surgeons and is Podcast Editor for Arthroscopy Journal. All other authors (S.M.F., M.W.F., C.F.M., D.F.C.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect/E6E7) exposed to CSC at various concentrations (10 -6 -100 μg/mL). We found CSC (10 -3 or 10 μg/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h. There was increased phosphorylation of receptor tyrosine kinases (RTKs), including Eph receptors, FGFR, PDGFRA/B, and DDR2, with downstream Ras/MAPK/ERK1/2 activation and upregulation of common EMT-related genes, TGFB SNAI2 , PDGFRB , and SMAD2. Our study demonstrated that CSC induces EMT in ectocervical cells with the upregulation of EMT-related genes, expression of protein biomarkers, and activation of RTKs that regulate TGFB expression, and other EMT-related genes. Understanding the molecular pathways and environmental factors that initiate EMT in ectocervical cells will help delineate molecular targets for intervention and define the role of EMT in the initiation and progression of cervical intraepithelial neoplasia and CC.

Purpose: To determine whether activity on Twitter was correlated with increasing impact factor (IF) among 6 orthopaedic sports medicine journals., Methods: Twitonomy software was used to collect account activity for the American Journal of Sports Medicine ; Arthroscopy: The Journal of Arthroscopic and Related Surgery; Knee Surgery, Sports Traumatology, Arthroscopy ; Journal of Shoulder and Elbow Surgery ; Orthopaedic Journal of Sports Medicine ; and Sports Health . Data from 2000 to 2020 were collected. Each journal's annual IF score was collected via scijournal.org. A multivariate regression model was used to predict the influence of different Twitter metrics on IF from 2012 to 2019. The journal name, number of tweets, and interaction of the two were used to predict IF. Additionally, Pearson correlation was used to assess correlations between Twitter account metrics and IF., Results: Over the study period, all IFs increased, with the exception of that for American Journal of Sports Medicine . The effect size between number of tweets and IF was not the same for each journal. For every additional tweet, American Journal of Sports Medicine increased its IF by 0.001 ( P  = .18). Sports Health and Orthopaedic Journal of Sports Medicine increased their IF by 0.01 ( P  = .002) and 0.022 ( P < .001), respectively. Knee Surgery, Sports Traumatology, Arthroscopy would expect a decrease in its IF by 0.004 ( P  = .55) and Journal of Shoulder and Elbow Surgery and Arthroscopy would increase its IF by 0.002 ( P  = .71) and 0.001 ( P  = .99), but this was not significant. There was a statistically significant positive correlation between annual tweets and IF across all journals., Conclusions: Markers of Twitter account activity, specifically the number of annual tweets, were predictive of an increase in IF among the orthopedic sports medicine journals included in this study., Clinical relevance: The findings of this study may allow orthopaedic sports medicine journals to make more effective, targeted, and productive use of their social media accounts to reach a broader audience, increase their influence, and increase the IF of their journal., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.K.M. reports a consulting or advisory role with Arthrex. M.K.M. is also a board or committee member of the American Academy of Orthopaedic Surgeons; American Orthopaedic Association; American Orthopaedic Society for Sports Medicine; Arthroscopy Association of North America; Association of Bone and Joint Surgeons; International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine; and Ruth Jackson Orthopaedic Society. M.K.M. is also a member of the editorial or governing board of American Journal of Sports Medicine Electronic Media, Arthroscopy, Journal of Bone and Joint Surgery (American), and OrthoInfo. C.J.T. is a board member of the Society of Military Orthopaedic Surgeons. C.J.T. also reports travel reimbursement from the Arthroscopy Association of North America. C.J.T. is also a podcast editor for Arthroscopy. All other authors (K.K., T.R.L., S.M.S.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material.

Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-Hydroxycholesterol (25HC), a product of the activity of cholesterol-25-hydroxylase (CH25H) on cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, 25HC can also amplify inflammation and be converted by CYP7B1 (cytochrome P450 family 7 subfamily B member 1) to 7α,25-dihydroxycholesterol, a lipid with chemoattractant activity, via the G protein-coupled receptor EBI2 (Epstein-Barr virus-induced gene 2)/GPR183 (G protein-coupled receptor 183). Here, using in vitro studies and two different murine models of SARS-CoV-2 infection, we investigate the effects of these two oxysterols on SARS-CoV-2 pneumonia. We show that although 25HC and enantiomeric-25HC are antiviral in vitro against human endemic coronavirus-229E, they did not inhibit SARS-CoV-2; nor did supplemental 25HC reduce pulmonary SARS-CoV-2 titers in the K18-human ACE2 (angiotensin-converting enzyme 2) mouse model in vivo . Treatment with 25HC also did not alter immune cell influx into the airway, airspace cytokines, lung pathology, weight loss, symptoms, or survival but was associated with increased airspace albumin, an indicator of microvascular injury, and increased plasma proinflammatory cytokines. Conversely, mice treated with the EBI2/GPR183 inhibitor NIBR189 displayed a modest increase in lung viral load only at late time points but no change in weight loss. Consistent with these findings, although Ch25h and 25HC were upregulated in the lungs of SARS-CoV-2-infected wild-type mice, lung viral titers and weight loss in Ch25h -/- and Gpr183 -/- mice infected with the β variant were similar to those in control animals. Taken together, endogenous 25HCs do not significantly regulate early SARS-CoV-2 replication or pathogenesis, and supplemental 25HC may have proinjury rather than therapeutic effects in SARS-CoV-2 pneumonia.

Aberrant fibroblast function plays a key role in the pathogenesis of idiopathic pulmonary fibrosis, a devastating disease of unrelenting extracellular matrix deposition in response to lung injury. Platelet-derived growth factor α-positive (Pdgfra+) lipofibroblasts (LipoFBs) are essential for lung injury response and maintenance of a functional alveolar stem cell niche. Little is known about the effects of lung injury on LipoFB function. Here, we used single-cell RNA-Seq (scRNA-Seq) technology and PdgfraGFP lineage tracing to generate a transcriptomic profile of Pdgfra+ fibroblasts in normal and injured mouse lungs 14 days after bleomycin exposure, generating 11 unique transcriptomic clusters that segregated according to treatment. While normal and injured LipoFBs shared a common gene signature, injured LipoFBs acquired fibrogenic pathway activity with an attenuation of lipogenic pathways. In a 3D organoid model, injured Pdgfra+ fibroblast-supported organoids were morphologically distinct from those cultured with normal fibroblasts, and scRNA-Seq analysis suggested distinct transcriptomic changes in alveolar epithelia supported by injured Pdgfra+ fibroblasts. In summary, while LipoFBs in injured lung have not migrated from their niche and retain their lipogenic identity, they acquire a potentially reversible fibrogenic profile, which may alter the kinetics of epithelial regeneration and potentially contribute to dysregulated repair, leading to fibrosis.

Background: Individuals with depression symptoms have a harder time quitting smoking. High negative affect and low positive affect are core depression symptoms and arise following cigarette abstinence. Investigating associations of biological markers with negative and positive affect may provide valuable information about factors relevant to smoking cessation in individuals with elevated depression symptoms., Methods: Depression symptoms were measured at a baseline session. Participants then completed two counterbalanced experimental sessions (non-abstinent, abstinent) and completed measures of positive and negative affect, and provided saliva samples. Saliva samples were assayed at the Salimetrics' SalivaLab (Carlsbad, CA) using the Salimetrics Salivary Dehydroepiandrosterone (DHEA) Assay Kit (Cat. No. 1-1202) and Dehydroepiandrosterone-sulfate (DHEA-S) Assay Kit (Cat. No. 1-1252)., Results: There were no main or interactive associations of DHEA with negative affect. However, there were significant DHEAS × experimental session and DHEAS × experimental session × depression symptom level interactions with negative affect. In the high depression symptom group, DHEAS positively associated with negative affect during the non-abstinent experimental session, but DHEAS negatively associated with negative affect during the abstinent experimental session. There were no associations of DHEA or DHEAS with positive affect., Conclusion: This study found that DHEAS negatively associated with negative affect during cigarette abstinence in individuals with elevated depression symptoms. This is important as high negative affect during cigarette abstinence may result in a return to smoking., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

When incorporated into a top-hat electrostatic analyzer, a gate electrode enables the separation of ions by their mass-per-charge with modest mass resolution (M/∆M ∼ 10). Gated-time-of-flight (TOF) instruments avoid the energy straggling and angular scattering effects prevalent in foil-based detection systems, providing more pristine measurements of three-dimensional distribution functions of incident ions. Gated-TOF implementations are ideal for measuring the properties of low-energy (i.e., <100 eV) thermal ions in various space environments. We present an instrument prototype capable of separating H+, He+, O+, and O2+ in Earth's ionosphere and demonstrate that in addition to providing species determination, precise operation of the gate electrode provides an electronically adjustable geometric factor that can extend a single instrument's dynamic range by several orders of magnitude., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Perfluorooctanoic acid (PFOA) is tumorigenic in rats and mice and potentially tumorigenic in humans. Here, we studied long-term PFOA exposure with an in vitro transformation model using the rat liver epithelial cell, TRL 1215. Cells were cultured in 10 μM (T10), 50 μM (T50) and 100 μM (T100) PFOA for 38 weeks and compared to passage-matched control cells. T100 cells showed morphological changes, loss of cell contact inhibition, formation of multinucleated giant and spindle-shaped cells. T10, T50, and T100 cells showed increased LC 50 values 20%, 29% to 35% above control with acute PFOA treatment, indicating a resistance to PFOA toxicity. PFOA-treated cells showed increases in Matrix metalloproteinase-9 secretion, cell migration, and developed more and larger colonies in soft agar. Microarray data showed Myc pathway activation at T50 and T100, associating Myc upregulation with PFOA-induced morphological transformation. Western blot confirmed that PFOA produced significant increases in c-MYC protein expression in a time- and concentration-related manner. Tumor invasion indicators MMP-2 and MMP-9, cell cycle regulator cyclin D1, and oxidative stress protein GST were all significantly overexpressed in T100 cells. Taken together, chronic in vitro PFOA exposure produced multiple cell characteristics of malignant progression and differential gene expression changes suggestive of rat liver cell transformation., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflicts of interest that might be relevant to the content of the manuscript. The authors received no external funding for this work., (Published by Elsevier Ltd.)

The consistent monitoring of trees both inside and outside of forests is key to sustainable land management. Current monitoring systems either ignore trees outside forests or are too expensive to be applied consistently across countries on a repeated basis. Here we use the PlanetScope nanosatellite constellation, which delivers global very high-resolution daily imagery, to map both forest and non-forest tree cover for continental Africa using images from a single year. Our prototype map of 2019 (RMSE = 9.57%, bias = -6.9%). demonstrates that a precise assessment of all tree-based ecosystems is possible at continental scale, and reveals that 29% of tree cover is found outside areas previously classified as tree cover in state-of-the-art maps, such as in croplands and grassland. Such accurate mapping of tree cover down to the level of individual trees and consistent among countries has the potential to redefine land use impacts in non-forest landscapes, move beyond the need for forest definitions, and build the basis for natural climate solutions and tree-related studies., (© 2023. The Author(s).)

Significance: Cross-sectional studies have shown that greater cigarette smoking-related emotion regulation expectancies were associated with retrospectively reported withdrawal during prior quit attempts and greater barriers to cessation. Few studies have investigated the relationship of within-person daily emotion regulation expectancies to factors related to initiating and maintaining a brief quit attempt., Methods: People living in California who smoked cigarettes daily (n = 220, 50 % female; 48.5 % white, 14.6 % Hispanic, 16.7 % Black or African American, 9.6 % Asian, 7.6 % Multi-race, 3.0 % other race; mean age=43.71 years old) completed a practice quit attempt and 28-days of daily diary surveys. In the morning, participants reported non-smoking and smoking emotion regulation expectancies based on the Affective Processing Questionnaire, daily abstinence plan, abstinence self-efficacy, and cigarettes smoked. Successful abstinence plans were calculated as days with an abstinence plan and no cigarettes smoked. Multilevel models investigated whether within-person emotion regulation expectancies were associated with abstinence plan, self-efficacy, and successful abstinence plan., Results: Greater within-person non-smoking emotion regulation expectancies were associated with increased odds of having an abstinence plan, higher self-efficacy, and a successful abstinence plan on a given day (ps < .05). Greater within-person smoking emotion regulation expectancies were associated with lower odds of having an abstinence plan and lower self-efficacy (ps < .001) but did not significantly associate with a successful abstinence plan., Conclusions: These findings show that within-person levels of expectations in emotion regulation abilities may contribute to factors relevant to initiating and achieving daily abstinence during a practice attempt., Competing Interests: Conflict of interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Trees sustain livelihoods and mitigate climate change but a predominance of trees outside forests and limited resources make it difficult for many tropical countries to conduct automated nation-wide inventories. Here, we propose an approach to map the carbon stock of each individual overstory tree at the national scale of Rwanda using aerial imagery from 2008 and deep learning. We show that 72% of the mapped trees are located in farmlands and savannas and 17% in plantations, accounting for 48.6% of the national aboveground carbon stocks. Natural forests cover 11% of the total tree count and 51.4% of the national carbon stocks, with an overall carbon stock uncertainty of 16.9%. The mapping of all trees allows partitioning to any landscapes classification and is urgently needed for effective planning and monitoring of restoration activities as well as for optimization of carbon sequestration, biodiversity and economic benefits of trees., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

A-kinase anchoring protein 79 (AKAP79) is a human scaffolding protein that organizes Ca 2+ /calmodulin-dependent protein phosphatase calcineurin, calmodulin, cAMP-dependent protein kinase, protein kinase C, and the transcription factor nuclear factor of activated T cells (NFAT1) into a signalosome at the plasma membrane. Upon Ca 2+ store depletion, AKAP79 interacts with the N-terminus of STIM1-gated Orai1 Ca 2+ channels, enabling Ca 2+ nanodomains to stimulate calcineurin. Calcineurin then dephosphorylates and activates NFAT1, which then translocates to the nucleus. A fundamental question is how signalosomes maintain long-term signaling when key effectors are released and therefore removed beyond the reach of the activating signal. Here, we show that the AKAP79-Orai1 interaction is considerably more transient than that of STIM1-Orai1. Free AKAP79, with calcineurin and NFAT1 in tow, is able to replace rapidly AKAP79 devoid of NFAT1 on Orai1, in the presence of continuous Ca 2+ entry. We also show that Ca 2+ nanodomains near Orai1 channels activate almost the entire cytosolic pool of NFAT1. Recycling of inactive NFAT1 from the cytoplasm to AKAP79 in the plasma membrane, coupled with the relatively weak interaction between AKAP79 and Orai1, maintain excitation-transcription coupling. By measuring rates for AKAP79-NFAT interaction, we formulate a mathematical model that simulates NFAT dynamics at the plasma membrane.

Purpose: To evaluate the maximal load at failure, cyclic displacement, and stiffness of onlay subpectoral biceps tenodesis (BT) with an intramedullary unicortical metal button (MB) versus a unicortical all-suture button (ASB)., Methods: Eighteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either ASB or MB using a high-strength suture. Specimens were tested on a servohydraulic mechanical testing apparatus under cyclic load for 1,000 cycles and then loaded to failure. The clamp was then adjusted to isolate the suture-anchor point interface and loaded to failure. Maximal load to failure, displacement, and stiffness were compared., Results: There was no significant difference between groups in stiffness, displacement, or yield load. The maximal load to failure for the MB was greater than the ASB (347.6 ± 74.1N vs 266.5 ± 69.3N, P  = .047). Eight specimens in each group failed by suture pull-through on the tendon. When the suture-anchor point interface was isolated, there was no significant difference in maximal load at failure (MB 586.5 ± 215.8N vs ASB 579.6 ± 255.9N, P  = .957)., Conclusions: This study demonstrates that the MB and ASB have similar biomechanical performance when used in subpectoral BT. Although the MB showed statistically significant greater maximal load to failure, there was no difference between the MB and ASB when the suture-tendon interface was eliminated. Suture pull-through was the most common mode of failure for both implants, underscoring the importance of the suture-tendon interface., Clinical relevance: Fixation techniques for the treatment of long head of the biceps brachii tenodesis continue to evolve. The use of an all-suture suspensory button has advantages, but it is important to understand if this implant is a biomechanically suitable alternative to a metal suspensory button.

In many cell types, the rise in cytosolic Ca 2+ due to opening of Ca 2+ release-activated Ca 2+ (CRAC) channels drives a plethora of responses, including secretion, motility, energy production, and gene expression. The amplitude and time course of the cytosolic Ca 2+ rise is shaped by the rates of Ca 2+ entry into and removal from the cytosol. However, an extended bulk Ca 2+ rise is toxic to cells. Here, we show that the plasma membrane Ca 2+ ATPase (PMCA) pump plays a major role in preventing a prolonged cytosolic Ca 2+ signal following CRAC channel activation. Ca 2+ entry through CRAC channels leads to a sustained sub-plasmalemmal Ca 2+ rise but bulk Ca 2+ is kept low by the activity of PMCA4b. Despite the low cytosolic Ca 2+ , membrane permeability to Ca 2+ is still elevated and Ca 2+ continues to enter through CRAC channels. Ca 2+ -dependent NFAT activation, driven by Ca 2+ nanodomains near the open channels, is maintained despite the return of bulk Ca 2+ to near pre-stimulation levels. Our data reveal a central role for PMCA4b in determining the pattern of a functional Ca 2+ signal and in sharpening local Ca 2+ gradients near CRAC channels, whilst protecting cells from a toxic Ca 2+ overload., Competing Interests: A.B.P. holds the position of Executive Editor for Function and is blinded from reviewing or making decisions for the manuscript. The authors declare they have no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Physiological Society.)

Meniscus injuries occur at a higher rate in the military than the general population. Appropriate management and rehabilitation of meniscus injuries is important for maintaining readiness. The purpose of this study was to describe the health burden of meniscus injuries in the Military Health System (MHS) to identify the surgical intervention rate for meniscus injuries, and to determine which injury characteristics and demographic variables were associated with the likelihood of surgery after injury. The U.S. Department of Defense Management Analysis and Reporting Tool, a database of health care encounters by military personnel and dependents, was queried for encounters associated with a meniscal injury diagnosis between January 1, 2010, and December 31, 2011. Meniscus injuries were categorized into (1) isolated medial, (2) isolated lateral, (3) combined medial and lateral, and (4) unspecified cohorts. Patients under 18 and over 51 years were excluded, as well as patients without records at least 1 year prior to diagnosis or 2 years after. Relevant surgical procedures were identified with the Current Procedural Terminology (CPT) codes for arthroscopic surgery of the knee, meniscus repair, meniscectomy, and anterior cruciate ligament (ACL) reconstruction. There were 2,969 meniscus injuries meeting inclusion criteria during the study period. There were 1,547 (52.1%) isolated medial meniscus injuries, 530 (17.9%) isolated lateral meniscus injuries, 452 (15.3%) involved both menisci, and 435 (14.7%) were unspecified. The mean age was 35.5 years (standard deviation [SD] = 9.3). An adjacent ligamentous injury occurred in 901 patients (30.3%). The treatment course led to arthroscopic surgery in 52.8% ( n  = 1,568) of all meniscus injuries. Eighty-five percent ( n  = 385) of combined medial and lateral tears, 54.9% of medial tears, and 51.6% of lateral tears underwent surgery. Partial meniscectomy was the most common procedure performed while 47.2% ( n  = 1,401) of tears were not treated surgically. Bilateral meniscus injuries had 4.57 greater odds of undergoing knee arthroscopy (95% confidence interval [CI]: 3.46, 6.04), 2.42 times odds of undergoing a meniscus repair, and 4.59 times odds for undergoing a meniscus debridement (95% CI: 3.62, 5.82). The closed nature of the MHS allows reliable capture of surgical rates for meniscus injuries within the military population. Meniscus injuries are common in the military and impose a significant burden on the MHS. Appropriate management and rehabilitation of this injury is important for maintaining readiness., Competing Interests: All authors (J.G.T., D.F.C., C.J.T., and D.I.R.) certify that neither he or she nor any member of his or her immediate family have funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article.The authors certify that the human protocol for this investigation received institution approval and that all investigations were conducted in conformity with ethical principles of research.All authors (J.G.T., D.F.C., C.J.T., and D.I.R.) are employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. §101 defined a U.S. Government work as a work prepared by a military service member or employees of the U.S. Government as part of that person's official duties.The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions, or policies of Uniformed Services University of the Health Sciences, the Department of Defense, the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government., (Thieme. All rights reserved.)

Patellar dislocations occur at a much higher rate in military than civilian populations. Past population-level studies have shown that surgical management is as good as or superior to conservative care and may reduce future reoccurrences. Although in acute cases and in civilian clinics, patellar dislocations are usually managed first in an emergent care setting, previous work suggests this can lead to increased costs. This study compared differences in downstream care type and intensity of services based on whether initial care occurred in emergent or non-emergent care settings. In our sample of 1,523 Military Health System (MHS) beneficiaries with patellar dislocation and 2-year follow-up, we found non-significant differences in costs, intensity of services, and rates of surgical repair regardless of whether the patient was initially seen in an emergent versus non-emergent care setting. Although we found significant increases in the use of imaging, patellar dislocation-related medical visits, and frequency of closed treatment approaches in emergent care settings, these values were very small and likely not clinically significant. These findings, which included all the patellar dislocations reported across the entire MHS in a 24-month period, suggest that neither emergent nor non-emergent care settings are likely to influence the long-term care received by the individual., Competing Interests: E.E.C. reports Royalties or licenses from MedBridge, Pearson education. AGENCE EBP; Consulting fees from Hawkins Foundation, South Carolina; and Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from MedBridge, AGENCE EBP.C.J.T. reports participation on a Data Safety Monitoring Board or Advisory Board of Board of Directors—Society of Military Orthopaedic Surgeons (SOMOS), Committee Chairman and SOMOS and AANA (Arthroscopic Association of North American, and Associate Editor—Journal of ArthroscopyD.I.R. reports all support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.) from this research was supported in part by an appointment to the Department of Defense (DOD) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the DOD as funds were paid to the institution, (Thieme. All rights reserved.)

Background: High negative affect and low positive affect are key depression-related states that may be greater following acute tobacco abstinence. This study aimed to test associations between depression symptom levels and acute tobacco abstinence with negative affect and positive affect., Methods: Following a baseline session, participants attended two counterbalanced laboratory sessions (non-abstinent, abstinent) and completed measures of positive and negative affect at rest (i.e., when not completing a task) and during a film clip task., Results: Individuals with elevated depression symptoms had higher negative affect and lower positive affect at rest and during the film clip task compared to individuals with low depression symptoms. There was no interaction of depression symptom levels and abstinence on negative and positive affect at rest. There was an interaction of depression symptom level and abstinence on negative and positive affect during the film clip task. Individuals with elevated depression showed significant differences in positive and negative affect between the abstinent and non-abstinent session, but no significant abstinence effects were noted in individuals with low depression symptoms., Limitations: The study included a non-treatment seeking sample and experimentally induced acute cigarette abstinence. We excluded for the use of smoking cessation medications that are also used to treat depression, classified depression levels using dichotomized CES-D scores, and used self-report measures of affect., Conclusions: Results of this study suggest individuals with elevated depression symptoms who smoke experience elevated negative affect and lower positive affect and cigarette abstinence may uniquely alter affective reactivity in individuals with elevated depression symptoms., (Copyright © 2022 Elsevier B.V. All rights reserved.)

During 2019, an infrared camera, the compact thermal imager (CTI), recorded 15 million images of the Earth from the International Space Station. CTI is based on strained-layer superlattice (SLS) detector technology. The camera covered the spectral range from 3 to 11 µm in two spectral channels, 3.3-5.4 and 7.8-10.7 µm. Individual image frames were 26×21 k m 2 projected on the ground, with 82 m pixel resolution. A frame time of 2.54 s created continuous image swaths with a 13% along-track image overlap. Upper limits determined on the ground and in flight for the electronic offset, read noise, and dark current demonstrated the stability of the SLS detector and camera over many months. Temperature calibration was established using a combination of preflight and in-flight measurements. A narrowband approximation of temperature as a function of photon counts produced an analytic relationship covering a temperature range of 0°-400°C. Examples of CTI images illustrate temperature retrievals over sea ice, urban and agricultural areas, desert, and wildfires.

Case: A 31-year-old US service member presented with a patellar tendon tear that was repaired acutely with 2 biocomposite suture anchors. He presented more than 2 years later with a stress fracture through a suture anchor drill hole and was treated with partially threaded screw fixation., Conclusion: Stress fracture through a suture anchor drill hole after patellar tendon repair is a previously unreported complication. Surgeons should have a high index of suspicion and low threshold to obtain advanced imaging in cases of unexplained pain after patellar tendon repair., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B825)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Cigarette smoking urges, withdrawal, and smoking reinstatement may be especially relevant to people with elevated depression symptoms who smoke. This laboratory study aimed to assess relations between depression symptom level and smoking urges for reward and relief, cigarette withdrawal, and smoking reinstatement in people who smoke cigarettes daily during acute abstinence and while smoking as usual., Methods: Participants with low (n = 51) or elevated (n = 29) baseline depression symptoms underwent two counterbalanced laboratory sessions (i.e., abstinent, non-abstinent). At each session, they completed subjective measures of smoking urges for reward and relief, and withdrawal. They also completed a laboratory smoking reinstatement task measuring whether they would delay smoking and the number of cigarettes smoked., Results: The elevated depression symptom group reported significantly higher withdrawal (p = .01) and smoked more cigarettes than the low depression symptoms group during the smoking reinstatement task self-administration period at the abstinent session (p = .04). Smoking urges for reward and relief were not significantly different by depression symptom group. There were no significant interactions of depression and abstinence with any outcomes., Conclusions: As outcomes were measured at both an abstinent and non-abstinent session, findings identify factors for people with elevated depression symptoms who smoke which may drive smoking behavior and impede smoking cessation efforts. This study provides evidence that people with elevated depression symptoms who smoke may need additional/more pharmacological or behavioral smoking cessation aids targeted at reducing withdrawal and number of cigarettes smoked., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: High negative affect, low positive affect, and low cognitive functioning are depression-related states that may be particularly relevant to females who smoke cigarettes and may be more prominent following overnight tobacco abstinence. This study aimed to assess relations between depression symptom levels and negative affect, positive affect, and subjective cognitive functioning in premenopausal females who smoke. Methods: Premenopausal females who smoke daily with low ( n = 66) or elevated ( n = 33) baseline depression symptoms completed subjective ratings of negative affect, positive affect, and cognitive functioning pre-first cigarette (i.e., after overnight tobacco abstinence) and at random prompts throughout the day via ecological momentary assessment (EMA) for 35 days. Results: Participants with elevated depression symptoms reported overall higher negative affect ( p = .01). Positive affect was significantly lower prior to the first cigarette of the day ( p < .001), but did not significantly differ between depression symptom groups. Subjective cognitive functioning was significantly lower pre-first cigarette of the day ( p < .001). There was a significant Depression Symptom × Prompt Type interaction for subjective cognitive functioning ( p = .01). Subjective cognitive functioning did not significantly differ by depression symptom group pre-first cigarette of the day but was significantly different at random prompts throughout the day. Conclusions: As participants smoked as usual, findings identify naturalistic factors which may influence smoking behavior among premenopausal females who smoke with elevated depression symptoms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Orthopaedic surgery has revolutionized the expectations for restoration of physical function after musculoskeletal injury and, along with physical therapy, has transformed the limits of recovery. Many orthopaedic procedures have a high success rate for improving quality of life and patient-reported outcomes, yet these procedures carry some level of risk, including postoperative complications. The stepped-care model of health care delivery, when applied to musculoskeletal care, recommends implementing less-intense and lower-risk treatments with known efficacy, such as promotion and education of self-management strategies and physical therapy, before more-invasive and higher-risk treatments such as surgery. This model of managing musculoskeletal disability can improve efficiency of care delivery and reduce medical costs at the health system level. Unfortunately, there is a documented lack of implementing an appropriate course of conservative care, especially physical therapy, prior to surgery across multiple orthopaedic disciplines including sports, spine, and trauma medicine and joint arthroplasty. Failure to respond to nonsurgical treatment has been suggested as a requisite component of the surgical appropriateness criteria, yet practical application can be elusive. Multiple barriers to adequate utilization of conservative treatment exist, including U.S. payment models that increase out-of-pocket expense for patients, negative patient perception of therapy, unreasonable patient expectations from therapy versus surgery, and communication barriers between patient, surgeon, and therapist. Surgeons should ensure that high-quality guideline-appropriate care is delivered early and adequately to their patients. Rehabilitation professionals have a responsibility to deliver high-value care, properly documenting the type and extent of treatment to improve surgical decision-making between surgeons and patients. Criteria to determine appropriateness for surgery should include a standardized and extensive assessment of failed therapies prior to certain elective surgeries. Improved collaboration between surgeons and rehabilitation professionals can result in improved outcomes for patients with musculoskeletal disorders., Level of Evidence: V, expert opinion., (© 2021 The Authors.)

Background: Children's exposure to parental violence against another parent has been widely studied as an adverse childhood experience and source of childhood trauma. Exposure to parental violence against a sibling could be equally as traumatizing, but the literature on this exposure is sparse, by comparison. We examined the frequency of exposure to parental assault on a sibling (EPAS) and its demographic distributions. We also investigated the links between EPAS and symptoms of distress., Method: From three combined surveys of the National Survey on Children's Exposure to Violence, based on telephone interviews with parents, and in the case of those 10-17 years old, adolescents, we examined children living with a juvenile sibling (N = 7, 029; 49% female)., Results: Lifetime EPAS was 3.7%, and sibling assault was more common by fathers (70%) than by mothers (30%). Exposure was greatest for boys and adolescents, highest for those whose parents had some college education, and for those living with other non-parental adults, single parents, and stepfamilies. Rates did not differ by ethnicity. Most exposed youth felt afraid (83%), and fear was greater when witnessing fathers than mothers assaulting a sibling. Controlling for child maltreatment and exposure to interparental violence, those exposed to EPAS showed higher current levels of mental distress (anger, depression, and anxiety; F (10, 6146) = 140.44, p = .001; R 2  = 0.19)., Conclusions: Clinical work and parent education programs should address the occurrence of EPAS and the adverse association between EPAS and mental health to reduce its potential negative impact., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Patient-reported outcomes (PROs) measure progression and quality of care. While legacy PROs such as the International Knee Documentation Committee (IKDC) survey are well-validated, a lengthy PRO creates a time burden on patients, decreasing adherence. In recent years, PROs such as the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function and Pain Interference surveys were developed as computer adaptive tests, reducing time to completion. Previous studies have examined correlation between legacy PROs and PROMIS; however, no studies have developed effective prediction models utilizing PROMIS to create an IKDC index. While the IKDC is the standard knee PRO, computer adaptive PROs offer numerous practical advantages., Purpose: To develop a nonlinear predictive model utilizing PROMIS Physical Function and Pain Interference to estimate IKDC survey scores and examine algorithm sensitivity and validity., Study Design: Cohort study (diagnosis); Level of evidence, 3., Methods: The MOTION (Military Orthopaedics Tracking Injuries and Outcomes Network) database is a prospectively collected repository of PROs and intraoperative variables. Patients undergoing knee surgery completed the IKDC and PROMIS surveys at varying time points. Nonlinear multivariable predictive models using Gaussian and beta distributions were created to establish an IKDC index score, which was then validated using leave-one-out techniques and minimal clinically important difference analysis., Results: A total of 1011 patients completed the IKDC and PROMIS Physical Function and Pain Interference, providing 1618 complete observations. The algorithms for the Gaussian and beta distribution were validated to predict the IKDC (Pearson = 0.84-0.86; R 2 = 0.71-0.74; root mean square error = 9.3-10.0)., Conclusion: The publicly available predictive models can approximate the IKDC score. The results can be used to compare PROMIS Physical Function and Pain Interference against historical IKDC scores by creating an IKDC index score. Serial use of the IKDC index allows for a lower minimal clinically important difference than the conventional IKDC. PROMIS can be substituted to reduce patient burden, increase completion rates, and produce orthopaedic-specific survey analogs.

The performance of nonionic surfactants is mediated by the interfacial interactions at the solid-liquid interface. Here we applied sum frequency generation (SFG) vibrational spectroscopy to probe the molecular structure of the silica-nonionic surfactant solution interface in situ, supplemented by quartz crystal microbalance with dissipation monitoring (QCM-D) and molecular dynamics (MD) simulations. The combined studies elucidated the effects of nonionic surfactant solution concentration, surfactant composition, and rinsing on the silica-surfactant solution interfacial structure. The nonionic surfactants studied include ethylene-oxide (EO) and butylene oxide (BO) components with different ratios. It was found that the CH groups of the surfactants at the silica-surfactant solution interfaces are disordered, but the interfacial water molecules are ordered, generating strong SFG OH signals. Solutions with higher concentrations of surfactant lead to a slightly higher amount of adsorbed surfactant at the silica interface, resulting in more water molecules being ordered at the interface, or a higher ordering of water molecules at the interface, or both. MD simulation results indicated that the nonionic surface molecules preferentially adsorb onto silanol sites on silica. A surfactant with a higher EO/BO ratio leads to more water molecules being ordered and a higher degree of ordering of water molecules at the silica-surfactant solution interface, exhibiting stronger SFG OH signal, although less material is adsorbed according to the QCM-D data. A thin layer of surfactants remained on the silica surface after multiple water rinses. To the best of our knowledge, this is the first time the combined approaches of SFG, QCM-D and MD simulation techniques have been applied to study nonionic surfactants at the silica-solution interface, which enhances our understanding on the interfacial interactions between nonionic surfactants, water and silica. The knowledge obtained from this study can be helpful to design the optimal surfactant concentration and composition for future applications.

The heavy metal Cadmium (Cd), a widespread environmental contaminant, poses serious hazards to human health and is considered a metallohormone and carcinogen. In women with uterine fibroids, there is a significant association between blood Cd levels and increased fibroid tumor size. The aim of this study was to determine if benign human uterine leiomyoma (fibroid) cells could be malignantly transformed in vitro by continuous Cd exposure and, if so, explore a molecular mechanism by which this could occur. We found when fibroid cells were exposed to 10 µM CdCl 2 for 8 weeks, a robust and fast-growing Cd-Resistant Leiomyoma (CR-LM) cell culture was established. The CR-LM cells formed viable colonies in soft agar and had increased cytoplasmic glycogen aggregates, enhanced cell motility, a higher percentage of cells in G2/M phase, and increased expression of the proliferation marker Ki-67. NanoString analysis showed downregulation of genes encoding for extracellular matrix (ECM) components, such as collagens, fibronectins, laminins, and SLRP family proteins, whereas genes involved in ECM degradation (MMP1, MMP3, and MMP10) were significantly upregulated. A volcano plot showed that the top differentially genes favored cancer progression. Functional analysis by ingenuity pathway analysis predicted a significant inhibition of TGFB1 signaling, leading to enhanced proliferation and attenuated fibrosis. Prolonged Cd exposure altered phenotypic characteristics and dysregulated genes in fibroid cells predicative of progression towards a cancer phenotype. Therefore, continuous Cd exposure alters the benign characteristics of fibroid cells in vitro, and Cd exposure could possibly pose a health hazard for women with uterine fibroids., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. The FASEB Journal published by Wiley Periodicals, Inc. on behalf of Federation of American Societies for Experimental Biology.)

Perioperative pain control for hip arthroscopy procedures represents a significant challenge for both surgeons and anesthetists. In light of the opioid crisis, greater emphasis has been placed on multimodal pain control techniques. There is considerable debate regarding regional nerve blockade for hip arthroscopy. Although regional anesthesia has a significant role in perioperative pain management strategies, many of the most common techniques present their own risks and limitations. In particular, the less desirable effects of postoperative weakness in the lower extremity and difficulty with ambulation are commonly produced with standard regional blockades. We present a technique for performing a targeted, sensory nerve block that can be done efficiently and safely in the immediate preoperative period. This block can potentially lower the intraoperative and postoperative opioid requirements without the risks of muscle blockade and falls from other regional anesthesia modalities., (© 2021 Published by Elsevier on behalf of the Arthroscopy Association of North America.)

To avoid conflicting and deleterious outcomes, eukaryotic cells often confine second messengers to spatially restricted subcompartments. The smallest signaling unit is the Ca 2+ nanodomain, which forms when Ca 2+ channels open. Ca 2+ nanodomains arising from store-operated Orai1 Ca 2+ channels stimulate the protein phosphatase calcineurin to activate the transcription factor nuclear factor of activated T cells (NFAT). Here, we show that NFAT1 tethered directly to the scaffolding protein AKAP79 (A-kinase anchoring protein 79) is activated by local Ca 2+ entry, providing a mechanism to selectively recruit a transcription factor. We identify the region on the N terminus of Orai1 that interacts with AKAP79 and demonstrate that this site is essential for physiological excitation-transcription coupling. NMR structural analysis of the AKAP binding domain reveals a compact shape with several proline-driven turns. Orai2 and Orai3, isoforms of Orai1, lack this region and therefore are less able to engage AKAP79 and activate NFAT. A shorter, naturally occurring Orai1 protein that arises from alternative translation initiation also lacks the AKAP79-interaction site and fails to activate NFAT1. Interfering with Orai1-AKAP79 interaction suppresses cytokine production, leaving other Ca 2+ channel functions intact. Our results reveal the mechanistic basis for how a subtype of a widely expressed Ca 2+ channel is able to activate a vital transcription pathway and identify an approach for generation of immunosuppressant drugs., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)