Reconstructing 120 years of climate change impacts on Joshua tree flowering.

Quantifying how global change impacts wild populations remains challenging, especially for species poorly represented by systematic datasets. Here, we infer climate change effects on masting by Joshua trees (Yucca brevifolia and Y. jaegeriana), keystone perennials of the Mojave Desert, from 15 years of crowdsourced observations. We annotated phenophase in 10,212 geo-referenced images of Joshua trees on the iNaturalist crowdsourcing platform, and used them to train machine learning models predicting flowering from annual weather records. Hindcasting to 1900 with a trained model successfully recovers flowering events in independent historical records and reveals a slightly rising frequency of conditions supporting flowering since the early 20th Century. This reflects increased variation in annual precipitation, which drives masting events in wet years-but also increasing temperatures and drought stress, which may have net negative impacts on recruitment. Our findings reaffirm the value of crowdsourcing for understanding climate change impacts on biodiversity.

The Impact of Social Deprivation on Anterior Urethral Stricture Recurrence After Urethroplasty - A Trauma and Urologic Reconstructive Network of Surgeons (TURNS) Analysis.

INTRODUCTION AND OBJECTIVES: Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty. METHODS: We performed a retrospective review of patients undergoing urethral reconstruction by surgeons participating in a collaborative research group. Home zip code was used to calculate Social Deprivation Indices (SDI; 0-100), which quantifies the level of disadvantage across several sociodemographic domains collected in the American Community Survey. Patients without zip code data were excluded from the analysis. The Cox Proportional Hazards model was used to study the association between SDI and the hazard of functional recurrence, adjusting for stricture characteristics as well as age and body mass index. RESULTS: Median age was 46.0 years with a median follow up of 367 days for the 1452 men included in the study. Patients in the fourth SDI quartile (worst social deprivation) were more likely to be active smokers with traumatic and infectious strictures compared to the first SDI quartile. Patients in the fourth SDI quartile had 1.64 times the unadjusted hazard of functional stricture recurrence vs patients in the first SDI quartile (95% CI 1.04-2.59). Compared to anastomotic ± excision, substitution only repair had 1.90 times the unadjusted hazard of recurrence. The adjusted hazard of recurrence was 1.08 per 10-point increase in SDI (95% CI 1.01-1.15, P = .027). CONCLUSIONS: Patient social deprivation identifies those at higher risk for functional recurrence after anterior urethral stricture repair, offering an opportunity for preoperative counseling and postoperative surveillance. Addressing these social determinants of health can potentially improve outcomes in reconstructive surgery.

Correlation of Macular Ganglion Cell Layer + Inner Plexiform Layer (GCL + IPL) and Circumpapillary Retinal Nerve Fiber Layer (cRNFL) Thickness in Glaucoma Suspects and Glaucomatous Eyes.

Purpose: The study aimed to correlate macular ganglion cell layer + inner plexiform layer (GCL + IPL) thickness and circumpapillary retinal nerve fiber layer (cRNFL) thickness and to determine the validity of GCL + IPL in the evaluation of glaucoma across different stages using the area under the curve (AUC) analysis in comparison to cRNFL. Patients and Methods: The charts of 260 adult glaucoma suspect and glaucoma patients having macular ganglion cell analysis, optical coherence tomography (OCT) of the cRNFL and automated visual field (AVF) were reviewed. GCL + IPL thickness (average, minimum and sectoral) and sectoral cRNFL thickness were obtained. Glaucomatous eyes were further classified into stages based on the Hodapp-Anderson-Parrish Visual Field Criteria of Glaucoma Severity. AUC analysis was used to compare GCL + IPL parameters with cRNFL in glaucoma suspects and glaucoma patients. Results: A total of 122 eyes were included in the study and were grouped into glaucoma suspects (n = 43), early or mild glaucoma (n = 40), and moderate-to-severe glaucoma (n = 39). Both GCL + IPL and cRNFL thickness parameters showed a significant decline with greater glaucoma severity. In the determination of visual field defects across all glaucoma stages, the highest AUC was obtained by minimum GCL + IPL (AUC = 0.859) with cut-off value at ≤70 µm. Average GCL + IPL had the highest AUC (0.835) in detecting progression from glaucoma suspect to mild glaucoma, while the inferior sector of the cRNFL had the highest AUC (0.937) in discerning mild from moderate-to-severe glaucoma. Conclusion: The results of this study highlight the significance of macular ganglion cell analysis in the screening, detection and staging of glaucoma. Compared to cRNFL, macular ganglion analysis may be more beneficial in glaucoma screening and detecting progression from glaucoma suspect to mild glaucoma.

Early Recanalization after Tenecteplase versus Alteplase: Experience in a Large Stroke Network.

INTRODUCTION: Previously published data are conflicting regarding the ability of tenecteplase versus alteplase to produce early recanalization of an intracranial large vessel occlusion. We compared the performance of each thrombolytic in a stroke network. METHODS: We queried our prospectively collected code stroke registry for basilar, internal carotid, or proximal middle cerebral artery occlusion patients treated with intravenous thrombolysis from 11/17/2021-9/16/2023. The primary outcome was early recanalization, defined using angiographic or clinical criteria. Secondary and safety outcomes included 90-day functional independence and symptomatic intracranial hemorrhage. A multivariable regression analysis was performed to determine independent associations with the primary outcome. RESULTS: 233 patients, with mean age 66.9 (16.6) years and median National Institutes of Health Stroke Scale score 15 (10-21), were included. One-hundred twenty-four of 233 (53.2%) patients were treated with alteplase while 109/233 (46.8%) were treated with tenecteplase. Endovascular thrombectomy was performed in 82% of subjects. Early recanalization rates were similar between the groups (alteplase 22.6%, tenecteplase 14.7%; p=0.14), as were rates of 90-day independent neurological function, symptomatic intracranial hemorrhage, and mortality. Patients with an internal carotid artery occlusion or with higher presenting stroke severity were less likely to achieve early recanalization. CONCLUSIONS: Tenecteplase and alteplase have similar rates of early recanalization, 90-day functional independence, and safety outcomes in large vessel occlusion patients. Occlusion site and stroke severity predict response to thrombolysis. Future studies may investigate other factors associated with a positive response to thrombolytics as expanded treatment indications are explored.

Microbiota and B-1 B cell repertoire development in mice.

Microbiota-derived antigens play a critical role in the development of both the mucosal and systemic B cell repertoires; however, how glycan epitopes promote B cell repertoire selection is only recently being understood. The production of glycan-derived antigens by individual microbes within a host can be dynamic and influenced by interactions within other members of microbial communities, the composition of diet, and host-derived contents, including those of the mucosal immune system. The size and complexity of the emerging neonatal B cell repertoire are paralleled by the acquisition of a diverse microbiota from maternal and environmental sources, which is now appreciated to exert long-lasting influences on the nascent B cell repertoire.

Cutting Edge: Low-dose Recombinant IL-2 Treatment Prevents Autoantibody Responses in Systemic Lupus Erythematosus via Regulatory T Cell-independent Depletion of T Follicular Helper Cells.

The expansion of T follicular helper (Tfh) cells correlates with disease progression in human and murine systemic lupus erythematosus (SLE). Unfortunately, there are no therapies to deplete Tfh cells. Importantly, low-dose rIL-2-based immunotherapy shows potent immunosuppressive effects in SLE patients and lupus-prone mice, primarily attributed to the expansion of regulatory T cells (Tregs). However, IL-2 can also inhibit Tfh cell differentiation. In this study, we investigate the potential of low-dose rIL-2 to deplete Tfh cells and prevent autoantibody responses in SLE. Our data demonstrate that low-dose rIL-2 efficiently depletes autoreactive Tfh cells and prevents autoantibody responses in lupus-prone mice. Importantly, this immunosuppressive effect was independent of the presence of Tregs. The therapeutic potential of eliminating Tfh cells was confirmed by selectively deleting Tfh cells in lupus-prone mice. Our findings demonstrate the critical role of Tfh cells in promoting autoantibody responses and unveil, (to our knowledge), a novel Treg-independent immunosuppressive function of IL-2 in SLE.

Clinical Benefits of DaxibotulinumtoxinA for Injection: Beyond Glabellar Line Effacement?

BACKGROUND: Botulinum toxin type A (BoNTA) is standard of care for glabellar lines ameliorization. DaxibotulinumtoxinA for Injection (DAXI) is a new BoNTA with a unique formulation representing the latest advancement in BoNTA technology. There is an unmet need for patients to understand the full potential of BoNTA treatment and new technologies. OBJECTIVE: To update clinical data supporting the use of DAXI for glabellar lines within the context of clinical experience. MATERIALS AND METHODS: A narrative review of the literature and summary of clinical experience with DAXI. RESULTS: The DAXI clinical trial program reflects clinical experience post-FDA approval, with DAXI demonstrating rapid onset, high patient response rates, and extended treatment duration versus conventional BoNTAs. Clinical observations suggest that DAXI has limited diffusion from the injection site, enabling more localized control of muscle activity and greater improvements in wrinkle severity. DAXI enables practitioners to exert greater finesse in their injections and in predicting changes to eyebrow shape and position and achieve improvement in skin quality. CONCLUSION: Advances in BoNTA technology can provide patients with greater options for treatment outcomes. The potential for enhanced localized effects with DAXI may contribute to more precise and targeted effects on muscle activity and additional aesthetic benefits to patients.

The dynamics of emotion-related impulsivity: An analysis of momentary self-efficacy and daily emotion-driven urges and actions via ecological momentary assessment.

Emotion-related impulsivity-the engagement in impulsive reactions specifically in response to emotions-is considered a transdiagnostic factor underlying psychopathology. The reflexive responding to emotion (RRE) model of emotion-related impulsivity (Carver et al., 2008) suggests that sensitivities to reward and threat in combination with control over emotion are factors that result in internalizing and externalizing psychopathology. In the current study, we adapt the trait-based RRE model to momentary states by evaluating how within-person fluctuations in affect combine with perceptions of momentary emotional control to predict impulsive, rash action and inaction in daily life. Participants (college students and adults recruited from the community: N = 197) completed 8 days of ecological momentary assessment, where we assessed current affect, perceptions of momentary emotional control (via distress intolerance and willpower), and urges for rash action and inaction (5,353 momentary prompts completed). We also assessed subsequent engagement in rash action and inaction. Using multilevel modeling, we found that when people feel greater positive affect and lower negative affect, they also report greater subjective willpower and lower distress intolerance, replicating past ecological momentary assessment findings. Furthermore, we found that momentary perceptions of momentary emotional control moderated the relationship between (a) affect and urges for rash action and (b) affect and engagement in rash action at follow-up. Findings support a dynamic model of the RRE model, confirming that perceptions of momentary emotional control are relevant for both rash action and inaction, particularly when occurring alongside shifts in affect. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A Feature-Space Theory of the Production Effect in Recognition.

Mathematical models explaining production effects assume that production leads to the encoding of additional features, such as phonological ones. This improves memory with a combination of encoding strength and feature distinctiveness, implementing aspects of propositional theories. However, it is not clear why production differs from other manipulations such as study time and spaced repetition, which are also thought to influence strength. Here we extend attentional subsetting theory and propose an explanation based on the dimensionality of feature spaces. Specifically, we suggest phonological features are drawn from a compact feature space. Deeper features are sparsely subselected from a larger subspace. Algebraic and numerical solutions shed light on several findings, including the dependency of production effects on how other list items are encoded (differing from other strength factors) and the production advantage even for homophones. This places production within a continuum of strength-like manipulations that differ in terms of the feature subspaces they operate upon and leads to novel predictions based on direct manipulations of feature-space properties.

Vhl safeguards thymic epithelial cell identity and thymopoietic capacity by constraining Hif1a activity during development.

The thymus is a physiologically hypoxic organ and fulfills its role of generating T cells under low-oxygen conditions. We have therefore investigated how thymic epithelial cells (TECs) cope with physiological hypoxia by focusing on the role of the Hif1a-Vhl axis. In most cell types, the oxygen-labile transcriptional regulator Hif1a is a central player in co-ordinating responses to low oxygen: under normoxic conditions Hif1a is rapidly degraded in a Vhl-guided manner; however, under hypoxic conditions Hif1a is stabilized and can execute its transcriptional functions. Unexpectedly, we find that, although TECs reside in a hypoxic microenvironment, they express little Hif1a protein and do not require Hif1a for their development or function. Instead, we find that Vhl function in TECs is vital to constrain Hif1a activity, as loss of Vhl results in dramatic defects in TEC differentiation and thymopoiesis, which can be rescued by Hif1a co-depletion.

A double ovulation protocol for Xenopus laevis produces doubled fertilisation yield and moderately transiently elevated corticosterone levels without loss of egg quality.

The African claw-toed frog, Xenopus laevis, is a well-established laboratory model for the biology of vertebrate oogenesis, fertilisation, and development at embryonic, larval, and metamorphic stages. For ovulation, X. laevis females are usually injected with chorionic gonadotropin, whereupon they lay typically hundreds to thousands of eggs in a day. After being rested for a minimum of three months, animals are re-used. The literature suggests that adult females can lay much larger numbers of eggs in a short period. Here, we compared the standard "single ovulation" protocol with a "double ovulation" protocol, in which females were ovulated, then re-ovulated after seven days and then rested for three months before re-use. We quantified egg number, fertilisation rate (development to cleavage stage), and corticosterone secretion rate as a measure of stress response for the two protocol groups over seven 3-month cycles. We found no differences in egg number-per-ovulation or egg quality between the groups and no long-term changes in any measures over the 21-month trial period. Corticosterone secretion was elevated by ovulation, similarly for the single ovulation as for the first ovulation in the double-ovulation protocol, but more highly for the second ovulation (to a level comparable to that seen following shipment) in the latter. However, both groups exhibited the same baseline secretion rates by the time of the subsequent cycle. Double ovulation is thus transiently more stressful/demanding than single ovulation but within the levels routinely experienced by laboratory X. laevis. Noting that "stress hormone" corticosterone/cortisol secretion is linked to physiological processes, such as ovulation, that are not necessarily harmful to the individual, we suggest that the benefits of a doubling in egg yield-per-cycle per animal without loss of egg quality or signs of acute or long-term harm may outweigh the relatively modest and transient corticosterone elevation we observed. The double ovulation protocol therefore represents a potential new standard practice for promoting the "3Rs" (animal use reduction, refinement and replacement) mission for Xenopus research.

AL amyloidosis manifesting as a vertebral amyloidoma secondary to an unrecognized plasmacytoma expressing cyclin D1 case report.

INTRODUCTION: Immunoglobin-related (AL) amyloidosis is the production of amyloidogenic immunoglobulin light chains from clonal plasma cells or, rarely, B-cell lymphomas with plasmacytic differentiation. Amyloid deposition causes progressive end organ destruction with profound morbidity. PRESENTATION OF CASE: We present a rare case of a lambda light chain AL amyloidoma localized to a thoracic vertebra of an 87-year-old woman who had a remote history of an unspecified non-Hodgkin B-cell lymphoma (NHL). Our patient presented with upper extremity neuropathy and was found by MRI to have a malignant-appearing lesion throughout the T1 vertebra. Initial biopsy showed amyloid deposition and staging evaluation found localized disease. Prior to planned surgery and radiation the following year, she had worsening neuropathy including multiple falls. Repeat MRI confirmed lesion progression with concern for cord compression. Urgent surgical resection was performed. Histology showed numerous plasma cells with abundant amyloid deposition that was found by amyloid typing to be lambda light chain. An incidental B-cell rich lymphoid aggregate was also seen in a bone marrow fragment that required additional immunohistochemical evaluation, showing the aggregate to be benign while revealing the plasma cells to be positive for cyclin D1. She received localized radiation and has been asymptomatic. DISCUSSION: Amyloidosis and plasma cell neoplasms require appropriate staging evaluation. The cyclin D1-positive plasma cells raises the possibility of the t(11;14)/IGH::CCND1 translocation that portends better prognosis and therapeutic response with venetoclax. CONCLUSION: Amyloidomas are uncommon and may present in nearly any site, requiring a high index of clinical suspicion for proper diagnosis.

Burden re-analysis of neurodevelopmental disorder cohorts for prioritization of candidate genes.

This study aimed to uncover novel genes associated with neurodevelopmental disorders (NDD) by leveraging recent large-scale de novo burden analysis studies to enhance a virtual gene panel used in a diagnostic setting. We re-analyzed historical trio-exome sequencing data from 745 individuals with NDD according to the most recent diagnostic standards, resulting in a cohort of 567 unsolved individuals. Next, we designed a virtual gene panel containing candidate genes from three large de novo burden analysis studies in NDD and prioritized candidate genes by stringent filtering for ultra-rare de novo variants with high pathogenicity scores. Our analysis revealed an increased burden of de novo variants in our selected candidate genes within the unsolved NDD cohort and identified qualifying de novo variants in seven candidate genes: RIF1, CAMK2D, RAB11FIP4, AGO3, PCBP2, LEO1, and VCP. Clinical data were collected from six new individuals with de novo or inherited LEO1 variants and three new individuals with de novo PCBP2 variants. Our findings add additional evidence for LEO1 as a risk gene for autism and intellectual disability. Furthermore, we prioritize PCBP2 as a candidate gene for NDD associated with motor and language delay. In summary, by leveraging de novo burden analysis studies, employing a stringent variant filtering pipeline, and engaging in targeted patient recruitment, our study contributes to the identification of novel genes implicated in NDDs.

Genetic admixture drives climate adaptation in the bank vole.

Genetic admixture introduces new variants at relatively high frequencies, potentially aiding rapid responses to environmental changes. Here, we evaluate its role in adaptive variation related to climatic conditions in bank voles (Clethrionomys glareolus) in Britain, using whole-genome data. Our results reveal loci showing excess ancestry from one of the two postglacial colonist populations inconsistent with overall admixture patterns. Notably, loci associated with climate adaptation exhibit disproportionate amounts of excess ancestry, highlighting the impact of admixture between colonist populations on local adaptation. The results suggest strong and localized selection on climate-adaptive loci, as indicated by steep clines and/or shifted cline centres, during population replacement. A subset, including a haemoglobin gene, is associated with oxidative stress responses, underscoring a role of oxidative stress in local adaptation. Our study highlights the important contribution of admixture during secondary contact between populations from distinct climatic refugia enriching adaptive diversity. Understanding these dynamics is crucial for predicting future adaptive capacity to anthropogenic climate change.

Safe and Effective Restoration of Jawline Definition With Hyaluronic Acid Injectable Gel VYC-25L: Results From a Randomized Controlled Study.

BACKGROUND: A well-defined jawline improves overall facial aesthetics, thus motivating patients to seek jawline augmentation. OBJECTIVES: This study will evaluate the safety and effectiveness of the hyaluronic acid injectable gel VYC-25L for restoring jawline definition. METHODS: A US multicenter, evaluator-blinded study randomized adults with grade 2 (moderate) or 3 (severe) Allergan Loss of Jawline Definition Scale (ALJDS) scores. Participants were randomized to VYC-25L treatment group or control group at study onset, with 12 months follow-up. The control group had the option to receive treatment after 6 months (primary endpoint completion). Effectiveness measures included month 6 ALJDS responders rate (proportion of participants with ≥1-grade improvement from baseline on both sides), FACE-Q Satisfaction With Lower Face and Jawline scores, and Global Aesthetic Improvement Scale (GAIS) responders (improved/much improved) as assessed by the investigator and participants. Injection site responses (ISRs) and adverse events (AEs) were monitored. RESULTS: At month 6, ALJDS responder rates were 69.0% versus 38.0% in the VYC-25L treatment (n = 157) and control (n = 49) groups, respectively (p = .0001). In the VYC-25L treatment group, FACE-Q scores improved by a mean of 45.9 points versus baseline at month 6 (p < .0001). Furthermore, 88.4% and 89.0% of participants in the VYC-25L treatment group were GAIS responders on month 6 by participant- and investigator-assessment, respectively. Most ISRs were mild or moderate and resolved within 2 weeks. Most treatment-related AEs were mild and resolved within a week. CONCLUSIONS: VYC-25L safely and effectively restores jawline definition through 1 year.

Uncovering measurement bias: Differential item functioning by income in the Couples Satisfaction Index.

Relationship satisfaction is among the most popular constructs in family science. As the study of families and romantic couples continues to include more diverse samples, it is imperative to ensure the measures scholars use do not significantly vary in psychometric quality across groups. The goal of this study was to examine the psychometric utility of the four-item Couples Satisfaction Index (CSI-4; Funk & Rogge, 2007) for individuals across the income spectrum. This study uses data from the National Couples' Health and Time Study, which sampled married and cohabiting adults in the United States from late 2020 to early 2021. Differential item functioning in the CSI-4 was assessed based on income (N = 3,497) using item response theory. For individuals experiencing lower incomes, the CSI-4 demonstrated differential functioning compared to their more affluent peers, with a bias against individuals experiencing lower incomes equating to average scores 1.38 units lower than higher income participants on the CSI-4 despite having the same true levels of relationship satisfaction. Differential item functioning was less pronounced when comparing item performance of lower- and middle-income participants, equating to lower income participants scoring .21 units lower than middle-income individuals despite having the same true levels of relationship satisfaction. While advancing diversity in family science, researchers should employ psychometric methods to understand how measures perform across groups, which will help prevent the misinterpretation of statistical bias as real group differences. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Activation of alveolar epithelial ER stress by ß-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure.

COVID-19 syndrome is characterized by acute lung injury, hypoxemic respiratory failure, and high mortality. Alveolar type 2 (AT2) cells are essential for gas exchange, repair, and regeneration of distal lung epithelium. We have shown that the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and other members of the ß-coronavirus genus induce an endoplasmic reticulum (ER) stress response in vitro; however, the consequences for host AT2 cell function in vivo are less understood. To study this, two murine models of coronavirus infection were used-mouse hepatitis virus-1 (MHV-1) in A/J mice and a mouse-adapted SARS-CoV-2 strain. MHV-1-infected mice exhibited dose-dependent weight loss with histological evidence of distal lung injury accompanied by elevated bronchoalveolar lavage fluid (BALF) cell counts and total protein. AT2 cells showed evidence of both viral infection and increased BIP/GRP78 expression, consistent with activation of the unfolded protein response (UPR). The AT2 UPR included increased inositol-requiring enzyme 1α (IRE1α) signaling and a biphasic response in PKR-like ER kinase (PERK) signaling accompanied by marked reductions in AT2 and BALF surfactant protein (SP-B and SP-C) content, increases in surfactant surface tension, and emergence of a reprogrammed epithelial cell population (Krt8+ and Cldn4+). The loss of a homeostatic AT2 cell state was attenuated by treatment with the IRE1α inhibitor OPK-711. As a proof-of-concept, C57BL6 mice infected with mouse-adapted SARS-CoV-2 demonstrated similar lung injury and evidence of disrupted surfactant homeostasis. We conclude that lung injury from ß-coronavirus infection results from an aberrant host response, activating multiple AT2 UPR stress pathways, altering surfactant metabolism/function, and changing AT2 cell state, offering a mechanistic link between SARS-CoV-2 infection, AT2 cell biology, and acute respiratory failure.NEW & NOTEWORTHY COVID-19 syndrome is characterized by hypoxemic respiratory failure and high mortality. In this report, we use two murine models to show that ß-coronavirus infection produces acute lung injury, which results from an aberrant host response, activating multiple epithelial endoplasmic reticular stress pathways, disrupting pulmonary surfactant metabolism and function, and forcing emergence of an aberrant epithelial transition state. Our results offer a mechanistic link between SARS-CoV-2 infection, AT2 cell biology, and respiratory failure.

Atherosclerotic Cardiovascular Disease Risk Estimates Using the Predicting Risk of Cardiovascular Disease Events Equations.

Importance: In 2023, the American Heart Association (AHA) developed the Predicting Risk of Cardiovascular Disease Events (PREVENT) equations to estimate 10-year risk of atherosclerotic cardiovascular disease (ASCVD), as an update to the 2013 pooled cohort equations (PCEs). The PREVENT equations were derived from contemporary cohorts and removed race and added variables for kidney function and statin use. Objective: To compare national estimates of 10-year ASCVD risk using the PCEs and PREVENT equations and how these equations affect recommendations for primary prevention statin therapy. Design, Setting, and Participants: This cross-sectional study included adults aged 40 to 75 years who participated in the National Health and Nutrition Examination Survey from 2017 to March 2020. Adults were defined as eligible for primary prevention statin use based on the 2019 AHA/American College of Cardiology guideline on the primary prevention of cardiovascular disease. Data were weighted to be nationally representative and were analyzed from December 27, 2023, to January 31, 2024. Main Outcomes and Measures: The 10-year ASCVD risk and eligibility for primary prevention statin therapy based on PREVENT and PCE calculations. Results: In the weighted sample of 3785 US adults (mean [SD] age, 55.7 [9.7] years; 52.5% women) without known ASCVD, 20.7% reported current statin use. The mean estimated 10-year ASCVD risk was 8.0% (95% CI, 7.6%-8.4%) using the PCEs and 4.3% (95% CI, 4.1%-4.5%) using the PREVENT equations. Across all age, sex, and racial subgroups, compared with the PCEs, the mean estimated 10-year ASCVD risk was lower using the PREVENT equations, with the largest difference for Black adults (10.9% [95% CI, 10.1%-11.7%] vs 5.1% [95% CI 4.7%-5.4%]) and individuals aged 70 to 75 years (22.8% [95% CI, 21.6%-24.1%] vs 10.2% [95% CI, 9.6%-10.8%]). The use of the PREVENT equations instead of the PCEs could reduce the number of adults meeting criteria for primary prevention statin therapy from 45.4 million (95% CI, 40.3 million-50.4 million) to 28.3 million (95% CI, 25.2 million-31.4 million). In other words, 17.3 million (95% CI, 14.8 million-19.7 million) adults recommended statins based on the PCEs would no longer be recommended statins based on PREVENT equations, including 4.1 million (95% CI, 2.8 million-5.5 million) adults currently taking statins. Based on the PREVENT equations, 44.1% (95% CI, 38.6%-49.5%) of adults eligible for primary prevention statin therapy reported currently taking statins, equating to 15.8 million (95% CI, 13.4 million-18.2 million) individuals eligible for primary prevention statins who reported not taking statins. Conclusions and Relevance: This cross-sectional study found that use of the PREVENT equations was associated with fewer US adults being eligible for primary prevention statin therapy; however, the majority of adults eligible for receiving such therapy based on PREVENT equations did not report statin use.

Long-term duration and safety of Radiesse (+) for the treatment of jawline.

BACKGROUND: Calcium hydroxyapatite (CaHA)-carboxymethylcellulose (CMC)+ has unique properties that make it optimal for lifting, contouring, and defining the jawline. This long-term follow-up of a randomized, multicenter, rater-blinded trial reports efficacy and safety of CaHA-CMC(+) through 48 and up to 60 weeks post-treatment. METHODS: Eligible patients were randomized (2:1) to the treatment or the control/delayed treatment group to receive CaHA-CMC(+) injections in both jawlines. While touch-ups were permitted 4 weeks post-treatment for both groups, only the treatment group was eligible for optional retreatment after 48 weeks. The primary outcome was ≥1-point improvement on both jawlines on the Merz Jawline Assessment Scale (MJAS); secondary endpoints included the Subject Global Aesthetic Improvement Scale (SGAIS) among others. Post hoc analysis included pooling up to 48-week data from the combined treatment and control/delayed groups and 60-week data for the treatment group. RESULTS: Overall, 175 received treatment. MJAS responder rates were 77.9%, 78.7%, and 62.9% at 12, 24, and 48 weeks post-treatment, respectively. Responder rate on the MJAS at 60 weeks was 74.6% for those who received retreatment and 43.5% for those patients who received only the initial and touchup treatments. SGAIS scores demonstrated 93.4%, 85.6%, and 68.5% of patients rated themselves very much improved after 12, 24, and 48 weeks, respectively. Adverse events consisted of procedure or CaHA-CMC(+)-related events that were mostly resolved and overwhelmingly mild. CONCLUSIONS: CaHA-CMC(+) produced clinically meaningful and long-lasting improvements in jawline contour and was well tolerated in patients through 60 weeks. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03583359.

FERONIA orchestrates P2K1-driven purinergic signaling in plant roots.

Extracellular ATP (eATP) orchestrates vital processes in plants, akin to its role in animals. P2K1 is a crucial receptor mediating eATP effects. Immunoprecipitation tandem mass spectrometry data highlighted FERONIA's significant interaction with P2K1, driving us to explore its role in eATP signaling. Here, we investigated putative P2K1-interactor, FERONIA, which is a versatile receptor kinase pivotal in growth and stress responses. We employed a FERONIA loss-of-function mutant, fer-4, to dissect its effects on eATP signaling. Interestingly, fer-4 showed distinct calcium responses compared to wild type, while eATP-responsive genes were constitutively upregulated in fer-4. Additionally, fer-4 displayed insensitivity to eATP-regulated root growth and reduced cell wall accumulation. Together, these results uncover a role for FERONIA in regulating eATP signaling. Overall, our study deepens our understanding of eATP signaling, revealing the intricate interplay between P2K1 and FERONIA impacting the interface between growth and defense.