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Myopericytoma is a rare benign smooth-muscle cell neoplasm of the subcutaneous soft tissues that is primarily found in young adults with a male predominance. We present the clinical, radiologic, and histopathologic features of a longstanding myopericytoma of the hand. We emphasize the features that help the radiologist and pathologist to accurately characterize this entity. Radiologic evaluation, particularly MRI, plays a crucial role in differentiating myopericytoma from other soft tissue masses. Characteristic MR features include a well-demarcated lesion with intense post-contrast enhancement, isointensity to muscle on T1-weighted imaging, and hyperintensity on T2-weighted imaging, often with a central vascular pedicle. Histopathologic examination reveals a concentric perivascular growth pattern, which helps to distinguish myopericytoma from other soft tissue tumors. Immunohistochemically, these myoid cell neoplasms stain positive for alpha-smooth muscle actin and h-caldesmon, lack nuclear atypia, and are not highly proliferative (relatively low Ki-67 index and very low mitotic activity). The vast majority stain negative for desmin and CD34. Treatment typically involves complete surgical resection, with excellent prognosis and rare recurrence. Despite its rarity, awareness of this entity is important for clinicians who encounter soft tissue masses of the extremities., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Rhodium nanoparticles have been recently discovered as good photosensitizers with great potential in cancer photodynamic therapy by effectively inducing cytotoxicity in cancer cells under near-infrared laser. This study evaluates the molecular mechanisms underlying such antitumoral effect through quantitative proteomics. The results revealed that rhodium nanoparticle-based photodynamic therapy disrupts tumor metabolism by downregulating key proteins involved in ATP synthesis and mitochondrial function, leading to compromised energy production. The treatment also induces oxidative stress and apoptosis while targeting the invasion capacity of cancer cells. Additionally, key proteins involved in drug resistance are also affected, demonstrating the efficacy of the treatment in a multi-drug resistant cell line. In vivo evaluation using a chicken embryo model also confirmed the effectiveness of the proposed therapy in reducing tumor growth without affecting embryo viability.

Microbes able to convert gaseous one-carbon (C1) waste feedstocks are increasingly important to transition to the sustainable production of renewable chemicals and fuels. Acetogens are interesting biocatalysts since gas fermentation using Clostridium autoethanogenum has been commercialised. However, most acetogen strains need complex nutrients, display slow growth, and are not robust for bioreactor fermentations. In this work, we used three different and independent adaptive laboratory evolution (ALE) strategies to evolve the wild-type C. autoethanogenum to grow faster, without yeast extract and to be robust in operating continuous bioreactor cultures. Multiple evolved strains with improved phenotypes were isolated on minimal media with one strain, named "LAbrini", exhibiting superior performance regarding the maximum specific growth rate, product profile, and robustness in continuous cultures. Whole-genome sequencing of the evolved strains identified 25 mutations. Of particular interest are two genes that acquired seven different mutations across the three ALE strategies, potentially as a result of convergent evolution. Reverse genetic engineering of mutations in potentially sporulation-related genes CLAU_3129 (spo0A) and CLAU_1957 recovered all three superior features of our ALE strains through triggering significant proteomic rearrangements. This work provides a robust C. autoethanogenum strain "LAbrini" to accelerate phenotyping and genetic engineering and to better understand acetogen metabolism., Competing Interests: Declaration of Competing Interest We declare that LanzaTech has interest in commercial gas fermentation with C. autoethanogenum and Audrey Harris, Steven D. Brown, Grant Hawkins, Jim Daleiden, Loan Tran, Hunter Zeleznik, Rasmus O. Jensen, Vinicio Reynoso, Heidi Schindel, and Michael Köpke are employees of LanzaTech., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The American Society of Pain and Neuroscience (ASPN) identified a significant gap in resources and guidelines that aim to educate healthcare providers for best practices when engaging on social media. As part of the broader initiatives on Spine and Nerve practice, the executive board of ASPN has decided it would be beneficial to include comprehensive guidance for healthcare providers when engaging on social media., Methods: A panel of experts was chosen based on expertise, publications, diversity, and their social media presence. Along with expert guidance, the committee conducted an extensive analysis of peer-reviewed literature in communication and medical journals to determine best practices for healthcare practitioners on social media., Results: Social media messages significantly impact patients' and colleagues' perceptions and actions regarding medical issues. As such, providers and their teams must be aware of legal and ethical considerations in healthcare while maintaining a consistent, educational, and digestible persona online., Conclusion: The advancement of communication and medical technologies and systems necessitates continued education and resources to adapt to our rapidly changing media and medical landscape., Competing Interests: Dr Patrick Buchanan reports personal fees from Painteq, Saluda Medical, Abbott, outside the submitted work. Dr Mehul Desai reports personal fees from Medtronic, Nalu Medical, SPR Therapeutics; stock options from SPR Therapeutics, HypreVention, SynerFuse, Virdio Health, outside the submitted work. Dr Betsy Grunch reports personal fees from Brainlab, GT Medical Technologies, Intrinsic Therapeutics, Nevro, Spineology, Orthofix, OptimaSurgical, Playback Health, Stryker, WebMD, Choice Spine, Alevio, Hyhte Holdings, Inc., Georgia Neurosurgical Society, Georgia Society Of Interventional Pain Physicians, North American Neuromodulation Society - NANS, personal fees from Women In Neurosurgery (WINS), NASS - North American Spine Society, CoreLink, EBI/Zimvie, CNS - Congress of Neurological Surgeons, Orthosummit, Women in Pain Management, Pinnacle Conference, LeadHer Summit, Medtronic, Medacta, Brenau University, SNS - Society of Neurological Surgeons, Mimedx, Centinel Spine, Cerapedics, outside the submitted work. Dr Chad Lavender reports personal fees from Arthrex, outside the submitted work. Dr Morteza Rabii reports personal fees from Abbott, Spinal Simplicity, SI-BONE, InFormed Consent, outside the submitted work. Dr Raj Patel reports personal fees from Abbott, outside the submitted work. Dr Michael Schatman is a Senior Medical Advisor for Apurano Pharma, outside the submitted work. Dr Timothy Deer reports personal fees for consultant, advisory board and/or research from Abbott, Vertos Medical, SpineThera, Saluda, Mainstay, Cornerloc, Boston Scientific, PainTeq, Spinal Simplicity, SPR Therapeutics, Biotronik, Aurora, Nervonik, outside the submitted work; In addition, Dr Timothy Deer has a patent DRG Leads pending to Abbott. The authors report no other conflicts of interest in this work., (© 2024 Giuffrida et al.)

Background: Chronobiology is the scientific field focused on studying periodicity in biological processes. In mammals, most physiological variables exhibit circadian rhythmicity, such as metabolism, body temperature, locomotor activity, and sleep. The biological rhythmicity can be statistically evaluated by examining the time series and extracting parameters that correlate to the period of oscillation, its amplitude, phase displacement, and overall variability., New Method: We have developed a library called CircadiPy, which encapsulates methods for chronobiological analysis and data inspection, serving as an open-access toolkit for the analysis and interpretation of chronobiological data. The package was designed to be flexible, comprehensive and scalable in order to assist research dealing with processes affected or influenced by rhythmicity., Results: The results demonstrate the toolkit's capability to guide users in analyzing chronobiological data collected from various recording sources, while also providing precise parameters related to the circadian rhythmicity., Comparison With Existing Methods: The analysis methodology from this proposed library offers an opportunity to inspect and obtain chronobiological parameters in a straightforward and cost-free manner, in contrast to commercial tools., Conclusions: Moreover, being an open-source tool, it empowers the community with the opportunity to contribute with new functions, analysis methods, and graphical visualizations given the simplified computational method of time series data analysis using an easy and comprehensive pipeline within a single Python object., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marcio Flavio Dutra Moraes reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais. Paula Bargi-Souza reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais. Joao Pedro Carvalho-Moreira reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais. Marcio Flavio Dutra Moraes reports financial support was provided by Lemann Brazil Research Fund. Leonardo de Oliveira Guarnieri reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de Minas Gerais. Marcio Flavio Dutra Moraes reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. Paula Bargi-Souza reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. Marcio Flavio Dutra Moraes reports financial support was provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. If there are other authors, they 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 © 2024 Elsevier B.V. All rights reserved.)

A six-month-old girl presented with feeding intolerance, fever, and left leg swelling. Imaging revealed a proximal left intertrochanteric fracture, along with rib and tibia fractures, raising concerns for non-accidental trauma. Blood cultures confirmed bacteremia caused by ceftriaxone-resistant Serratia marcescens , necessitating a 10-day course of antibiotics. The patient was immobilized with a hip spica cast, and metabolic and genetic evaluations were negative. She was discharged with instructions for follow-up care. This case highlights the importance of thorough evaluation for non-accidental trauma in infants presenting with unexplained fractures and systemic infections., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ponce Health Sciences University Institutional Review Board issued approval 2302135908. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Garcia et al.)

The renin-angiotensin system (RAS) is composed of a series of peptides, receptors, and enzymes that play a pivotal role in maintaining cardiovascular homeostasis. Among the most important players in this system are the angiotensin-II and angiotensin-(1-7) peptides. Our group has recently demonstrated that alamandine (ALA), a peptide with structural and functional similarities to angiotensin-(1-7), interacts with cardiomyocytes, enhancing contractility via the Mas-related G protein-coupled receptor member D (MrgD). It is currently unknown whether this modulation varies along the distinct phases of the day. To address this issue, we assessed the ALA-induced contractility response of cardiomyocytes from mice at four Zeitgeber times (ZTs). At ZT2 (light phase), ALA enhanced cardiomyocyte shortening in an MrgD receptor-dependent manner, which was associated with nitric oxide (NO) production. At ZT14 (dark phase), ALA induced a negative modulation on the cardiomyocyte contraction. β-Alanine, an MrgD agonist, reproduced the time-of-day effects of ALA on myocyte shortening. N G -nitro-l-arginine methyl ester, an NO synthase inhibitor, blocked the increase in fractional shortening induced by ALA at ZT2. No effect of ALA on myocyte shortening was observed at ZT8 and ZT20. Our results show that ALA/MrgD signaling in cardiomyocytes is subject to temporal modulation. This finding has significant implications for pharmacological approaches that combine chronotherapy for cardiac conditions triggered by disruption of circadian rhythms and hormonal signaling. NEW & NOTEWORTHY Alamandine, a member of the renin-angiotensin system, serves critical roles in cardioprotection, including the modulation of cardiomyocyte contractility. Whether this effect varies along the day is unknown. Our results provide evidence that alamandine via receptor MrgD exerts opposing actions on cardiomyocyte shortening, enhancing, or reducing contraction depending on the time of day. These findings may have significant implications for the development and effectiveness of future cardiac therapies.

Ice cream manufacture commonly results in the accumulation of wasted product that contains valuable food-grade quality components, including fat, carbohydrates, and protein. Methods have been developed for recovering the fat from this waste stream, but this results in the generation of a co-product rich in fermentable carbohydrates. This study aimed to investigate the potential for using this co-product as a fermentation substrate for production of antimicrobial peptides, called bacteriocins, by dairy starter cultures. Results showed that Streptococcus thermophilus B59671 and Lactococcus lactis 11454 produced the broad-spectrum bacteriocins thermophilin 110 and nisin, respectively, when the fermentation substrate was melted ice cream, or a co-product generated by a modified butter churning technique. Bacteriocin production varied depending on the brand and variety of vanilla ice cream used in this study. When an alternate enzyme-assisted fat extraction technique was used, S. thermophilus metabolism was impaired within the resulting co-product, and thermophilin 110 production was not observed. Lactococcus lactis was still able to grow in this co-product, but antimicrobial activity was not observed. Results from this study suggest the co-product generated when using the churning technique is a better choice to use as a base medium for future studies to optimize bacteriocin production., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: University spring break carries a two-pronged SARS-CoV-2 variant transmission risk. Circulating variants from universities can spread to spring break destinations, and variants from spring break destinations can spread to universities and surrounding communities. Therefore, it is critical to implement SARS-CoV-2 variant surveillance and testing strategies to limit community spread before and after spring break to mitigate virus transmission and facilitate universities safely returning to in-person teaching., Methods: We examined the SARS-CoV-2 positivity rate and changes in variant lineages before and after the university spring break for two consecutive years. 155 samples were sequenced across four time periods: pre- and post-spring break 2021 and pre- and post-spring break 2022; following whole genome sequencing, samples were assigned clades. The clades were then paired with positivity and testing data from over 50,000 samples., Results: In 2021, the number of variants in the observed population increased from four to nine over spring break, with variants of concern being responsible for most of the cases; Alpha percent composition increased from 22.2% to 56.4%. In 2022, the number of clades in the population increased only from two to three, all of which were Omicron or a sub-lineage of Omicron. However, phylogenetic analysis showed the emergence of distantly related sub-lineages. 2022 saw a greater increase in positivity than 2021, which coincided with a milder mitigation strategy. Analysis of social media data provided insight into student travel destinations and how those travel events may have impacted spread., Conclusions: We show the role that repetitive testing can play in transmission mitigation, reducing community spread, and maintaining in-person education. We identified that distantly related lineages were brought to the area after spring break travel regardless of the presence of a dominant variant of concern., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: SW is currently employed by Illumina. BK, SP, JP, RD, LI, and AS are employed by Labcorp. The other authors declare no competing interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Napolitano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Innovative techniques such as the "omics" can be a powerful tool for the understanding of intracellular pathways involved in homeostasis maintenance and identification of new potential therapeutic targets against endocrine-metabolic disorders. Over the last decades, proteomics has been extensively applied in the study of a wide variety of human diseases, including those involving the endocrine system. Among the most endocrine-related disorders investigated by proteomics in humans are diabetes mellitus and thyroid, pituitary, and reproductive system disorders. In diabetes, proteins implicated in insulin signaling, glucose metabolism, and β-cell activity have been investigated. In thyroid diseases, protein expression alterations were described in thyroid malignancies and autoimmune thyroid illnesses. Additionally, proteomics has been used to investigate the variations in protein expression in adrenal cancers and conditions, including Cushing's syndrome and Addison's disease. Pituitary tumors and disorders including acromegaly and hypopituitarism have been studied using proteomics to examine changes in protein expression. Reproductive problems such as polycystic ovarian syndrome and endometriosis are two examples of conditions where alterations in protein expression have been studied using proteomics. Proteomics has, in general, shed light on the molecular underpinnings of many endocrine-related illnesses and revealed promising biomarkers for both their detection and treatment. The capacity of proteomics to thoroughly and objectively examine complex protein mixtures is one of its main benefits. Mass spectrometry (MS) is a widely used method that identifies and measures proteins based on their mass-to-charge ratio and their fragmentation pattern. MS can perform the separation of proteins according to their physicochemical characteristics, such as hydrophobicity, charge, and size, in combination with liquid chromatography. Other proteomics techniques include protein arrays, which enable the simultaneous identification of several proteins in a single assay, and two-dimensional gel electrophoresis (2D-DIGE), which divides proteins depending on their isoelectric point and molecular weight. This chapter aims to summarize the most relevant proteomics data from targeted tissues, as well as the daily rhythmic variation of relevant biomarkers in both physiological and pathophysiological conditions within the involved endocrine system, especially because the actual modern lifestyle constantly imposes a chronic unentrained condition, which virtually affects all the circadian clock systems within human's body, being also correlated with innumerous endocrine-metabolic diseases., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

This study investigated the impact of long-term heat acclimation (HA) training on mouse thermoregulation, metabolism, and running performance in temperate (T) and hot (H) environments. Male Swiss mice were divided into 1) Sedentary (SED) mice kept in T (22 °C; SED/T), 2) Endurance Trained mice (ET, 1 h/day, 5 days/week, 8 weeks, 60 % of maximum speed) in T (ET/T), 3) SED kept in H (32 °C; SED/H), and 4) ET in H (ET/H). All groups performed incremental load tests (ILT) in both environments before (pre-ET) and after four and eight weeks of ET. In the pre-ET period, H impaired (∼30 %) performance variables (maximum speed and external work) and increased (1.3 °C) maximum abdominal body temperature compared with T. In T, after four weeks, although ET/H exercised at a lower (∼30 %) absolute intensity than ET/T, performance variables and aerobic power (peak oxygen uptake, VO2peak) were similarly increased in both ET groups compared with SED/T. After eight weeks, the external work was higher in both ET groups compared with SED/T. Only ET/T significantly increased VO2peak (∼11 %) relative to its pre-ET period. In H, only after eight weeks, both ET groups improved (∼19 %) maximum speed and reduced (∼46 %) post-ILT blood lactate concentrations compared with their respective pre-ET values. Liver glycogen content increased (34 %) in both ET groups and SED/H compared with SED/T. Thus, ET/H was performed at a lower absolute intensity but promoted similar effects to ET/T on metabolism, aerobic power, and running performance. Our findings open perspectives for applying HA training as part of a training program or orthopedic and metabolic rehabilitation programs in injured or even obese animals, reducing mechanical load with equivalent or higher physiological demand., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Rhythmic regulations are virtually described in all physiological processes, including central nervous system development and immunologic responses. Zika virus (ZIKV), a neurotropic arbovirus, has been recently linked to a series of birth defects and neurodevelopmental disorders. Given the well-characterized role of the intrinsic cellular circadian clock within neurogenesis, cellular metabolism, migration, and differentiation among other processes, this study aimed to characterize the influence of ZIKV infection in the circadian clock expression in human neuronal cells. For this, in vitro models of human-induced neuroprogenitor cells (hiNPCs) and neuroblastoma cell line SH-SY5Y, cultured as monolayer and neurospheres, were infected by ZIKV, followed by RNA-Seq and RT-qPCR investigation, respectively. Targeted circadian clock components presented mRNA oscillations only after exogenous synchronizing stimuli (Forskolin) in SH-SY5Y monolayer culture. Interestingly, when these cells were grown as 3D-arranged neurospheres, an intrinsic oscillatory expression pattern was observed for some core clock components without any exogenous stimulation. The ZIKV infection significantly disturbed the mRNA expression pattern of core clock components in both neuroblastoma cell culture models, which was also observed in hiNPCs infected with different strains of ZIKV. The ZIKV-mediated desynchronization of the circadian clock expression in human cells might further contribute to the virus impairment of neuronal metabolism and function observed in adults and ZIKV-induced congenital syndrome. In vitro models of Zika virus (ZIKV) neuronal infection. Human neuroprogenitor cells were cultured as monolayer and neurospheres and infected by ZIKV. Monolayer-cultured cells received forskolin (FSK) as a coupling factor for the circadian clock rhythmicity, while 3D-arranged neurospheres showed an intrinsic oscillatory pattern in the circadian clock expression. The ZIKV infection affected the mRNA expression pattern of core clock components in both cell culture models. The ZIKV-mediated desynchronization of the circadian clock machinery might contribute to the impairment of neuronal metabolism and function observed in both adults (e.g., Guillain-Barré syndrome) and ZIKV-induced congenital syndrome (microcephaly). The graphical abstract has been created with Canva at the canva.com website., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Untreated mental disorders are important among low- and middle-income country (LMIC) university students in Latin America, where barriers to treatment are high. Scalable interventions are needed. This study compared transdiagnostic self-guided and guided internet-delivered cognitive behavioral therapy (i-CBT) with treatment as usual (TAU) for clinically significant anxiety and depression among undergraduates in Colombia and Mexico., Method: 1,319 anxious, as determined by the Generalized Anxiety Disorder-7 (GAD-7) = 10+ and/or depressed, as determined by the Patient Health Questionnaire-9 (PHQ-9) = 10+, undergraduates (mean [SD] age = 21.4 [3.2]); 78.7% female; 55.9% first-generation university student) from seven universities in Colombia and Mexico were randomized to culturally adapted versions of self-guided i-CBT (n = 439), guided i-CBT (n = 445), or treatment as usual (TAU; n = 435). All randomized participants were reassessed 3 months after randomization. The primary outcome was remission of both anxiety (GAD-7 = 0-4) and depression (PHQ-9 = 0-4). We hypothesized that remission would be higher with guided i-CBT than with the other interventions., Results: Intent-to-treat analysis found significantly higher adjusted (for university and loss to follow-up) remission rates (ARD) among participants randomized to guided i-CBT than either self-guided i-CBT (ARD = 13.1%, χ12 = 10.4, p = .001) or TAU (ARD = 11.2%, χ12 = 8.4, p = .004), but no significant difference between self-guided i-CBT and TAU (ARD = -1.9%, χ12 = 0.2, p = .63). Per-protocol sensitivity analyses and analyses of dimensional outcomes yielded similar results., Conclusions: Significant reductions in anxiety and depression among LMIC university students could be achieved with guided i-CBT, although further research is needed to determine which students would most likely benefit from this intervention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Peripheral artery disease (PAD) and coronary vascular dysfunction are common in patients with cardiometabolic disease. Neither the prevalence of coronary vascular dysfunction among patients with PAD nor the prognostic impact with these two conditions present together has been well studied., Methods: Consecutive patients who underwent PET MPI were analyzed for presence of coronary vascular dysfunction [myocardial blood flow reserve (MBFR) < 2]. Cox regression was used to examine the association of reduced MBFR with mortality in patients with PAD, as well as the association of comorbid MBFR < 2 and PAD with all-cause death., Results: Among 13,940 patients, 1936 (14%) had PAD, 7782 (56%) had MBFR < 2 and 1346 (10%) had both PAD and MBFR < 2. Reduced MBFR was very common (69.5%) and was associated with increased risk of all-cause death (HR 1.69, 95%CI 1.32, 2.16, p < 0.01) in patients with PAD. Patients with both PAD and MBFR < 2, and those with either PAD or reduced MBFR had increased risk of death compared to those with neither condition: PAD + MBFR < 2 [(HR 95%CI), 2.30; 1.97-2.68], PAD + MBFR ≥ 2 (1.37; (1.08-1.72), PAD - MBFR < 2 (1.98; 1.75-2.25), p < 0.001 for all)., Conclusion: Coronary vascular dysfunction was common in patients with PAD and was associated with increased risk of death., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Hypothyroidism is an endocrine-metabolic disorder, and as such it compromises a wide range of physiological functions. Memory deficits and, the most recently described, circadian rhythm disruption are among the impairments caused by thyroid dysfunctions. However, although highly likely, there is no evidence connecting these two effects of hypothyroidism. Here, we hypothesized the time-of-day interferes with the memory deficit caused by hypothyroidism. C57BL/6 J mice from both sexes were subjected to novel object recognition (NOR) task during the rest and active phases, corresponding to ZT 2-4 and 14-16, respectively (ZT: Zeitgeber time; ZT 0: lights on at 07:00 am). First, we showed that neither sex nor ZT altered object recognition memory (ORM) in euthyroid mice. Next, animals were divided into control (euthyroid) and hypothyroid [induced with methimazole (0.01%) and perchlorate (0.1%) treatment in the drinking water for 21 days] groups. Under euthyroid conditions, male and female mice recognized the novel object regardless of the time-of-day. However, hypothyroidism impaired ORM at rest phase (ZT 2-4) in both sexes. Surprisingly, in the active phase (ZT 14-16), the hypothyroid males performed the NOR, though a longer time to execute the task was required. In contrast, female hypothyroid mice showed a greater impairment in ORM. Our results suggest that hypothyroidism may disrupt the circadian rhythm in brain areas related to mnemonic processes since in euthyroid condition ORM is not affected by the time-of-day. Furthermore, our findings in an animal model indicate a pronounced deleterious effect of hypothyroidism in women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could inappropriately influence (bias) the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Importance: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT., Objective: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors., Design, Setting, and Participants: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022., Interventions: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435)., Main Outcomes and Measures: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline., Results: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P = .003) or treatment as usual (40.0% [2.7%]; P = .001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P = .007; self-guided i-CBT: 25.4% [8.8%]; P = .004; treatment as usual: 31.0% [9.4%]; P = .001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P = .14; treatment as usual: 53.0% [6.0%]; P = .25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P = .001; treatment as usual: 41.8% [3.2%]; P < .001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P = .07)., Conclusions and Relevance: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings., Trial Registration: ClinicalTrials.gov Identifier: NCT04780542.

Obesity has become a worldwide public health issue. Many obese patients concomitantly suffer with heart failure with reduced ejection fraction. There have been reports of improvement in left ventricular systolic function following significant weight loss after bariatric surgery. We sought to investigate this phenomenon within our institution. This was a retrospective single-center analysis of patients conducted between 2010 and 2019. The study included patients with morbid obesity (body mass index >35 kg/m 2 and an obesity-related comorbid condition, or a body mass index >40 kg/m 2 ) and left ventricular systolic dysfunction. Analysis was performed based on systolic function recovery after bariatric surgery and advanced heart failure therapy. Of the 190 patients identified, 57 patients had a left ventricular ejection fraction of <40%. Twenty-two patients underwent bariatric surgery, of which at least 54.5% had systolic function recovery. Patients who had systolic function recovery after bariatric surgery were significantly older (51.58 years ± 10.48 vs 32.3 years ± 5.03, P = 0.001). Older age and female sex were predictors of systolic function recovery. In patients with obesity and heart failure with reduced ejection fraction, weight loss following bariatric surgery was shown to be correlated with significant improvement in left ventricular systolic function., (Copyright © 2022. Published by Elsevier Inc.)

Formate is a promising energy carrier that could be used to transport renewable electricity. Some acetogenic bacteria, such as Eubacterium limosum, have the native ability to utilise formate as a sole substrate for growth, which has sparked interest in the biotechnology industry. However, formatotrophic metabolism in E. limosum is poorly understood, and a system-level characterisation in continuous cultures is yet to be reported. Here, we present the first steady-state dataset for E. limosum formatotrophic growth. At a defined dilution rate of 0.4 d -1 , there was a high specific uptake rate of formate (280 ± 56 mmol/gDCW/d; gDCW = gramme dry cell weight); however, most carbon went to CO 2 (150 ± 11 mmol/gDCW/d). Compared to methylotrophic growth, protein differential expression data and intracellular metabolomics revealed several key features of formate metabolism. Upregulation of phosphotransacetylase (Pta) appears to be a futile attempt of cells to produce acetate as the major product. Instead, a cellular energy limitation resulted in the accumulation of intracellular pyruvate and upregulation of pyruvate formate ligase (Pfl) to convert formate to pyruvate. Therefore, metabolism is controlled, at least partially, at the protein expression level, an unusual feature for an acetogen. We anticipate that formate could be an important one-carbon substrate for acetogens to produce chemicals rich in pyruvate, a metabolite generally in low abundance during syngas growth. KEY POINTS: First Eubacterium limosum steady-state formatotrophic growth omics dataset High formate specific uptake rate, however carbon dioxide was the major product Formate may be the cause of intracellular stress and biofilm formation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biological specialization reduces the size of niche space while increasing efficiency in the use of available resources. Specialization often leads to phenotypic changes via natural selection aligning with niche space constraints. Commonly observed changes are in size, shape, behavior, and traits associated with feeding. One often selected trait for dietary specialization is venom, which, in snakes, often shows variation dependent on diet across and within species. The Neotropical Blunt-headed Treesnake (Imantodes cenchoa) is a highly specialized, rear-fanged, arboreal, lizard hunter that displays a long thin body, enlarged eyes, and a large Duvernoy's gland. However, toxin characterization of I. cenchoa has never been completed. Here, we use RNA-seq and mass spectrometry to assemble, annotate, and analyze the venom gland transcriptomes of four I. cenchoa from across their range. We find a lack of significant venom variation at the sequence and expression levels, suggesting venom conservation across the species. We propose this conservation provides evidence of a specialized venom repertoire, adapted to maximize efficiency of capturing and processing lizards. Importantly, this study provides the most complete venom gland transcriptomes of I. cenchoa and evidence of venom specialization in a rear-fanged snake, giving insight into selective pressures of venom across all snake species., 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.)

In the era of human-driven climate change, understanding whether behavioural buffering of temperature change is linked with organismal fitness is essential. According to the 'cost-benefit' model of thermoregulation, animals that live in environments with high frequencies of favourable thermal microclimates should incur lower thermoregulatory costs, thermoregulate more efficiently and shunt the associated savings in time and energy towards other vital tasks such as feeding, territory defence and mate acquisition, increasing fitness. Here, we explore how thermal landscapes at the scale of individual territories, physiological performance and behaviour interact and shape fitness in the southern rock agama lizard ( Agama atra ). We integrated laboratory assays of whole organism performance with behavioural observations in the field, fine-scale estimates of environmental temperature, and paternity assignment of offspring to test whether fitness is predicted by territory thermal quality (i.e. the number of hours that operative temperatures in a territory fall within an individual's performance breadth). Male lizards that occupied territories of low thermal quality spent more time behaviourally compensating for sub-optimal temperatures and displayed less. Further, display rate was positively associated with lizard fitness, suggesting that there is an opportunity cost to engaging in thermoregulatory behaviour that will change as climate change progresses.

Ternary I-III-VI quantum dots (TQDs) are semiconductor nanomaterials that have been gradually incorporated in the fabrication of light-emitting diodes (LEDs) over the last 10 years due to their physicochemical and photoluminescence properties, such as adequate quantum yield values, tunable wavelength emission, and easy synthesis strategies, but mainly because of their low toxicity that allows them to be excellent candidates to compete with conventional Cd-Pb-based QDs. This review addresses the different strategies to obtain TQDs and how synthesis conditions influence their physicochemical properties, followed by the LEDs parameters achieved using TQDs. The second part of the review summarizes how TQDs are integrated into LEDs and white light-emitting diodes (WLEDs). Furthermore, an insight into the state-of-the-art LEDs development using TQDs, including its advantages and disadvantages and the challenges to overcome, is presented at the end of the review., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Islas-Rodriguez, Muñoz, Rodriguez, Vazquez-Garcia and Reyes.)

Commercial laying hens can produce one egg approximately every 24 h. During this process, regulatory systems that control vitamin D 3 metabolism, calcium and phosphorus homeostasis, and intestinal uptake of these minerals work in concert to deliver components required for eggshell calcification and bone mineralization. Commercial production cycles have been extended in recent years to last through 100 weeks of age, and older hens often exhibit an increased prevalence of skeletal fractures and poor eggshell quality. Issues such as these arise, in part, through imbalances that occur in calcium and phosphorus utilization as hens age. As a result, an in-depth understanding of the mechanisms that drive calcium and phosphorus uptake and utilization is required to develop solutions to these welfare and economic challenges. This paper reviews factors that influence calcium and phosphorus homeostasis in laying hens, including eggshell formation and development and roles of cortical and medullary bone. Metabolism and actions of vitamin D 3 and physiological regulation of calcium and phosphorus homeostasis in key tissues are also discussed. Areas that require further research in avian species, such as the role of fibroblast growth factor 23 in these processes and the metabolism and action of bioactive vitamin D 3 , are highlighted and the importance of using emerging technologies and establishing in vitro systems to perform functional and mechanistic studies is emphasized., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sinclair-Black, Garcia and Ellestad.)

Bacterial membrane vesicles (BMVs) are important effectors in the pathogenesis, virulence, and biofilm formation during different bacterial infections. Because of their structure, BMVs can be applied as drug delivery systems (DDS) or in the production of immunogenic vaccines against different untreated diseases. In this sense, different antigens or immune stimulator molecules, such as proteins can be extracted for the development of such vaccines. Here, we describe a protocol adapted to be used in mycobacteria, Gram-positive, and Gram-negative bacteria for the isolation of BMVs, and further mass spectrometry-based characterization of their protein cargo., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m 2 ), and depression (23% vs. 14%; p < 0.001 for all). Over a median (IQR) follow-up after surgery of 722 days (364-993), patients who underwent bariatric surgery had lost an average of 11.8 ± 18.5 kg (23% of excess body weight), 10.2% were on fewer glucose-lowering medications, and 8.4% were on fewer antihypertensives. Despite bariatric surgery being safer and more accessible over the past two decades, less than one in fifty eligible patients with diabetes receive this therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Identifying predictors of dropout is an important step in improving treatment outcomes. The alliance is the most frequently studied psychotherapy process variable, but its relation to dropout in cognitive behavioral therapy (CBT) of depression is not well understood., We evaluated the alliance at session one as reported by clients and therapists as predictors of dropout among 126 clients with major depressive disorder participating in CBT for depression., Over a similar time period, those who dropped out experienced less symptom change than those who did not. Client, but not therapist reported alliance was related to reduced risk for dropout. This relation remained significant even when clients' pre-treatment predictions of the alliance were included as a covariate. Concurrent use of medication did not moderate the alliance-dropout relation., Our findings are consistent with alliance being an important contributor to risk of dropout in CBT for depression. Future research should investigate intervention strategies that might promote the alliance as a means of reducing dropout.

Background: Differences in the incidence of cardiopulmonary resuscitation (CPR) provided by bystanders contribute to survival disparities among persons with out-of-hospital cardiac arrest. It is critical to understand whether the incidence of bystander CPR in witnessed out-of-hospital cardiac arrests at home and in public settings differs according to the race or ethnic group of the person with cardiac arrest in order to inform interventions., Methods: Within a large U.S. registry, we identified 110,054 witnessed out-of-hospital cardiac arrests during the period from 2013 through 2019. We used a hierarchical logistic regression model to analyze the incidence of bystander CPR in Black or Hispanic persons as compared with White persons with witnessed cardiac arrests at home and in public locations. We analyzed the overall incidence as well as the incidence according to neighborhood racial or ethnic makeup and income strata. Neighborhoods were classified as predominantly White (>80% of residents), majority Black or Hispanic (>50% of residents), or integrated, and as high income (an annual median household income of >$80,000), middle income ($40,000-$80,000), or low income (<$40,000)., Results: Overall, 35,469 of the witnessed out-of-hospital cardiac arrests (32.2%) occurred in Black or Hispanic persons. Black and Hispanic persons were less likely to receive bystander CPR at home (38.5%) than White persons (47.4%) (adjusted odds ratio, 0.74; 95% confidence interval [CI], 0.72 to 0.76) and less likely to receive bystander CPR in public locations than White persons (45.6% vs. 60.0%) (adjusted odds ratio, 0.63; 95% CI, 0.60 to 0.66). The incidence of bystander CPR among Black and Hispanic persons was less than that among White persons not only in predominantly White neighborhoods at home (adjusted odds ratio, 0.82; 95% CI, 0.74 to 0.90) and in public locations (adjusted odds ratio, 0.68; 95% CI, 0.60 to 0.75) but also in majority Black or Hispanic neighborhoods at home (adjusted odds ratio, 0.79; 95% CI, 0.75 to 0.83) and in public locations (adjusted odds ratio, 0.63; 95% CI, 0.59 to 0.68) and in integrated neighborhoods at home (adjusted odds ratio, 0.78; 95% CI, 0.74 to 0.81) and in public locations (adjusted odds ratio, 0.73; 95% CI, 0.68 to 0.77). Similarly, across all neighborhood income strata, the frequency of bystander CPR at home and in public locations was lower among Black and Hispanic persons with out-of-hospital cardiac arrest than among White persons., Conclusions: In witnessed out-of-hospital cardiac arrest, Black and Hispanic persons were less likely than White persons to receive potentially lifesaving bystander CPR at home and in public locations, regardless of the racial or ethnic makeup or income level of the neighborhood where the cardiac arrest occurred. (Funded by the National Heart, Lung, and Blood Institute.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Health literacy (HL) is the degree to which individuals can obtain, process, and understand basic health information and services. Although low HL portends greater risk for clinical events, its association with heart failure (HF)-specific health status- patients' symptoms, function and quality of life- is poorly understood. We thus explored the association of low HL with health status outcomes in depressed patients with HF, for whom treatment regimens can be complex., Methods: Participants with HF with reduced ejection fraction and depression, from the Hopeful Heart trial, were categorized as having low or adequate HL at baseline using a validated, 1-item HL screen. HF-specific health status was measured at baseline, 3, 6, and 12 months using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Using serial risk-adjusted linear regression models, we assessed the association of HL with baseline, 12-month and 12-month change in the KCCQ Overall Summary (OS) scores (range 0-100; lower scores = worse health status)., Results: Among 629 participants, 35 % had low HL. Those with low HL had lower health status at all time points, including at 12 months after discharge (-9.8 points, 95%CI [-14.3, -5.3], p < 0.001), with poorer improvements in KCCQ-OS scores after accounting for baseline health status (-6.4 points, 95%CI [-10.5, -2.3], p = 0.002)., Conclusions: In those with HF and depression, low HL was common and associated with worse HF-specific health status and poorer improvement over time. A brief HL screen can identify patients at risk for poorer health status outcomes and for whom additional interventions may be warranted., Competing Interests: Declaration of competing interest All other authors have no further financial or personal relationships to disclose.

The pancreatic β cells circadian clock plays a relevant role in glucose metabolism. NADPH oxidase (NOX) family is responsible for producing reactive oxygen species (ROS), such as superoxide anion and hydrogen peroxide, using NADPH as an electron donor. In pancreatic β-cells, NOX-derived ROS inhibits basal and glucose-stimulated insulin secretion. Thus, we hypothesized that the absence of BMAL1, a core circadian clock component, could trigger an increase of NOX2-derived ROS in pancreatic β cells, inhibiting insulin secretion under basal and stimulated glucose conditions. To test such hypothesis, Bmal1 knockdown (KD) was performed in cultured clonal β-cell line (INS-1E) and knocked out in isolated pancreatic islets, using a tissue-specific β-cells Bmal1 knockout (KO) mice. The insulin secretion was assessed in the presence of NOX inhibitors. The Bmal1 KD within INS-1E cells elicited a rise of intracellular ROS content under both glucose stimuli (2.8 mM and 16.7 mM), associated with an increase in Nox2 expression. Additionally, alterations of glutathione levels, CuZnSOD and catalase activities, reduction of ATP/ADP ratio, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and aconitase activities, followed by glucokinase and Slc2a2 (Glut2) expression were also observed in INS-1E β-cells, reflecting in a diminished insulin secretion pattern. The isolated islets from β-cell Bmal1 -/- mice have shown a similar cellular response, where an increased NOX2-derived ROS content and a reduced basal- and glucose-stimulated insulin secretion were observed. Therefore, together with NOX inhibition (Apocynin), polyethene-glycol linked to superoxide dismutase (PEG-SOD), phorbol myristate acetate (PMA), and diethyldithiocarbamate (DDC) data, our findings suggest a possible BMAL1-mediated NOX2-derived ROS generation in pancreatic β cells, leading to the modulation of both basal- and glucose-stimulated insulin secretion., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Formyl peptide receptor 2 (FPR2) plays an integral role in the transition of macrophages from a pro-inflammatory program to one that is pro-resolving. FPR2-mediated stimulation of resolution post myocardial infarction has demonstrated efficacy in rodent models and is hypothesized to reduce progression into heart failure. FPR2 agonists that promote long-lasting receptor internalization can lead to persistent desensitization and diminished therapeutic benefits. In vitro signaling profiles and propensities for receptor desensitization of two clinically studied FPR2 agonists, namely, BMS-986235 and ACT-389949, were evaluated. In contrast to BMS-986235, pre-stimulation with ACT-389949 led to a decrease in its potency to inhibit cAMP production. Moreover, ACT-389949 displayed greater efficacy for β-arrestin recruitment, while efficacy of Gi activation was similar for both agonists. Following agonist-promoted FPR2 internalization, effective recycling to the plasma membrane was observed only with BMS-986235. Use of G protein-coupled receptor kinase (GRK) knock-out cells revealed a differential impact of GRK2 versus GRK5/6 on β-arrestin recruitment and Gi activation promoted by the two FPR2 agonists. In vivo, decreases of granulocytes in circulation were greatly diminished in mice treated with ACT-389949 but not for BMS-986235. With short-term dosing, both compounds induced a pro-resolution polarization state in cardiac monocyte/macrophages post myocardial infarction. By contrast, with long-term dosing, only BMS-986235 preserved the infarct wall thickness and increased left ventricular ejection fraction in a rat model of myocardial infarction. Altogether, the study shows that differences in the desensitization profiles induced by ACT-389949 and BMS-986235 at the molecular level may explain their distinct inflammatory/pro-resolving activities in vivo., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

Background: The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial randomized participants with chronic coronary disease (CCD) to guideline-directed medical therapy with or without angiography and revascularization. The study examined the association of nonadherence with health status outcomes., Objectives: The study sought to compare 12-month health status outcomes of adherent and nonadherent participants with CCD with an a priori hypothesis that nonadherent patients would have better health status if randomized to invasive management., Methods: Self-reported medication-taking behavior was assessed at randomization with a modified 4-item Morisky-Green-Levine Adherence Scale, and participants were classified as adherent or nonadherent. Twelve-month health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ-7) summary score (SS), which ranges from 0 to 100 (higher score = better). The association of adherence with outcomes was evaluated using Bayesian proportional odds models, including an interaction by study arm (conservative vs invasive)., Results: Among 4,480 randomized participants, 1,245 (27.8%) were nonadherent at baseline. Nonadherent participants had worse baseline SAQ-7 SS in both conservative (72.9 ± 19.3 vs 75.6 ± 18.4) and invasive (71.0 ± 19.8 vs 74.2 ± 18.7) arms. In adjusted analyses, adherence was associated with higher 12-month SAQ-7 SS in both treatment groups (mean difference in SAQ-7 SS with conservative treatment = 1.6 [95% credible interval: 0.3-2.9] vs with invasive management = 1.9 [95% credible interval: 0.8-3.1]), with no interaction by treatment., Conclusions: More than 1 in 4 participants reported medication nonadherence, which was associated with worse health status in both conservative and invasive treatment strategies at baseline and 12 months. Strategies to improve medication adherence are needed to improve health status outcomes in CCD, regardless of treatment strategy. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)., Competing Interests: Funding Support and Author Disclosures Dr Garcia is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number 5T32H110837. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Spertus owns the copyright to the Kansas City Cardiomyopathy Questionnaire and Seattle Angina Questionnaire; unrelated to this work, he has served as a consultant on patient-reported outcomes for Janssen, Pfizer, Bristol Myers Squibb, Bayer, Merck, Novartis, Corvia, Terumo, and Abbott; has received research grants from the American College of Cardiology Foundation, Janssen, MyoKardia, and Abbott Vascular; has served on the scientific advisory board for United Healthcare; and has served on the Board of Directors of Blue Cross Blue Shield of Kansas City. Dr Newman has received funding from the National Heart, Lung, and Blood Institute. Dr Bangalore has served as a consultant to Abbott Vascular, Biotronik, Pfizer, and Amgen; and has received research grants from the National Heart, Lung, and Blood Institute and Abbott Vascular. Dr Stone has received speaker honoraria from Cook and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Reva, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, and Gore; and owns equity or options in Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and MedFocus family of funds. Dr. Reynolds has received funding from the National Heart, Lung, and Blood Institute; and has received in-kind donations for unrelated research from Abbott Vascular, Siemens, and BioTelemetry. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. All rights reserved.)

Background: Although studies have reported variation in out-of-hospital cardiac arrest (OHCA) survival by geographic location, little is known about variation in OHCA survival at the level of emergency medical service (EMS) agencies-which may have modifiable practices, unlike counties and regions. We quantified the variation in OHCA survival across EMS agencies and explored whether variation in 2 specific EMS resuscitation practices were associated with survival to hospital admission., Methods: Within the Cardiac Arrest Registry to Enhance Survival, a prospective registry representing ≈51% of the US population, we identified 258 342 OHCAs from 764 EMS agencies with > 10 OHCA cases annually during 2015 to 2019. Using hierarchical logistic regression, risk-standardized rates of survival to hospital admission were computed for each EMS agency. We quantified inter-agency variation in survival with median odds ratios and assessed the association of 2 resuscitation practices (EMS response time and the proportion of OHCAs with termination of resuscitation without meeting futility criteria) with EMS agency survival rates to hospital admission., Results: Across 764 EMS agencies comprising 258 342 OHCAs, the median risk-standardized rate of survival to hospital admission was 27.3% (interquartile range, 24.5%-30.1%; range: 16.0%-45.6%). The adjusted median odds ratio was 1.35 (95% CI, 1.32-1.39), denoting that the odds of survival of 2 patients with identical covariates varied by 35% at 2 randomly selected EMS agencies. EMS agencies in the lowest quartile of risk-standardized survival had longer EMS response times when compared with the highest quartile (12.0±3.4 versus 9.0±2.6 minutes; P <0.001), and a higher proportion of OHCAs with termination of resuscitation without meeting futility criteria (27.9±16.1% versus 18.9±11.4%; P <0.001)., Conclusions: Survival after OHCA varies widely across EMS agencies. EMS response times and termination of resuscitation practices were associated with agency-level rates of survival to hospital admission, suggesting potentially modifiable practices which can improve OHCA survival.

Objective: To examine the prevalence of ADHD and the association of comorbid disorders, and multivariate disorder classes with role impairment in college students., Method: About 15,991 freshmen (24 colleges, 9 countries, WMH-ICS) (response rate = 45.6%) completed online WMH-CIDI-SC surveys for 6-month ADHD and six 12-month DSM-IV disorders. We examined multivariate disorder classes using latent class analysis (LCA) and simulated a population attributable risk proportions (PARPs) of ADHD-related impairment., Results: About 15.9% had ADHD, of which 58.4% had comorbidities. LCA classified ADHD respondents to pure (42.9%), internalizing (36.0%), bipolar comorbidities (11.3%), and externalizing disorder classes (9.8%). ADHD, comorbidities, and multivariate disorder classes independently predicted severe impairment. PARPs: eliminating ADHD hypothetically reduced severe impairment by 19.2%, 10.1% adjusted for comorbidities, 9.5% for multivariate disorder classes., Conclusions: ADHD and comorbid disorders are common and impairing in college students. Personalized transdiagnostic interventions guided by multivariate disorder classes should be explored.

Formyl peptide receptor 2 (FPR2) agonists have shown efficacy in inflammatory-driven animal disease models and have the potential to treat a range of diseases. Many reported synthetic agonists contain a phenylurea, which appears to be necessary for activity in the reported chemotypes. We set out to find isosteres for the phenylurea and focused our efforts on heteroaryl rings. The wide range of potencies with heterocyclic isosteres demonstrates how electronic effects of the heteroatom placement impact molecular recognition. Herein, we report our discovery of benzimidazole and aminophenyloxadiazole FPR2 agonists with low nanomolar activity., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

AgInS 2 /ZnS quantum dots were synthesized via solvothermal aqueous phase method using 3-mercaptopropionic acid as the stabilizer. AgInS 2 /ZnS quantum dots were employed for acrylamide sensing under two strategies: (1) quenching of the fluorescence signal by the synthesis of polyacrylamide under UV light and (2) use of 2-naphthalenethiol for quenching of the fluorescence signal of quantum dots followed by a recovery of the signal after the addition of acrylamide. Both methodologies display adequate limits of detection, 15.6 and 4.8 μg L -1 , respectively. However, the 2-napthalenethiol based method exhibited better precision and selectivity compared to the other methodology. Both methodologies were applied for acrylamide detection in fried snack products and acceptable accuracy was obtained using 2-napthalenethiol method.

Background: The Model for End-Stage Liver Disease (MELD) score was originally described as a marker of survival in chronic liver disease. More recently, MELD and its derivatives, MELD excluding INR (MELD-XI) and MELD with sodium (MELD-Na), have been applied more broadly as outcome predictors in heart transplant, left ventricular assist device placement, heart failure, and cardiogenic shock, with additional promising data to support the use of these scores for prediction of survival in those undergoing veno-arterial extracorporeal membrane oxygenation (VA ECMO)., Methods: This study assessed the prognostic impact of MELD in patients with cardiogenic shock undergoing VA ECMO via a single-center retrospective review from January 2014 to March 2020. MELD, MELD-XI, and MELD-Na scores were calculated using laboratory values collected within 48 h of VA ECMO initiation. Multivariate Cox regression analyses determined the association between MELD scores and the primary outcome of 90-day mortality. Receiver operating characteristics (ROC) were used to estimate the discriminatory power for MELD in comparison with previously validated SAVE score., Results: Of the 194 patients, median MELD was 20.1 (13.7-26.2), and 90-day mortality was 62.1%. There was a significant association between MELD score and mortality up to 90 days (hazard ratio (HR) = 1.945, 95% confidence interval (95% CI) = 1.244-3.041, p = 0.004) after adjustment for age, indication for VA ECMO, and sex. The prognostic significance of MELD score for 90-day mortality revealed an AUC of 0.645 (95% CI = 0.565-0.725, p < 0.001). MELD-Na score and MELD-XI score were not associated with mortality., Conclusion: MELD score accurately predicts long-term mortality and may be utilized as a valuable decision-making tool in patients undergoing VA ECMO.

Flocculants are used in the primary step of wastewater treatment to precipitate solids. Bovine blood is a slaughterhouse byproduct, and there is limited evidence in the literature demonstrating that it can be used as a flocculant. In this study, native bovine blood (NBB) and three types of chemically modified blood (methylated bovine blood (MeBB), polymerized bovine blood (PolyBB), and polymerized & methylated bovine blood (PMBB)) were tested against suspensions of negatively charged kaolin or positively charged hematite. The methylation reaction had the expected effect of increasing the apparent isoelectric point of MeBB and PMBB relative to that of the NBB starting material, and the polymerization reaction had the intended effect of increasing the average molar mass. NBB and PolyBB performed well with kaolin suspensions at pH ≤5.5, and MeBB showed high and consistent performance, across the pH range of 4.5-8.5. Relative to NBB, MeBB had improved potency and pH independence but also the disadvantage of increased sensitivity to overdosing. The performance of PolyBB was very similar to that of NBB. PMBB had performance enhancements similar to those of MeBB, with a modest improvement in its overdose sensitivity. The performances of MeBB and PMBB with hematite suspensions were poor at all tested doses (2-100 mg/g hematite), whereas a 30 mg/g dose of PolyBB showed 81% precipitation in an hour. The results show that simple chemical treatments can improve the utility of blood as a flocculant for negatively charged solids., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Formyl peptide receptor type 2 (FPR2) regulates the initiation and resolution phases of the inflammatory response. In the setting of heart injury and disease, dysregulated inflammation can potentiate maladaptive healing and pathological remodeling of the heart leading to cardiac dysfunction and failure. The potential to regulate and resolve adverse inflammation is postulated to improve outcome in the setting of heart disease. This review covers emerging concepts on the role of FPR2 in heart disease and strategies to activate pro-resolution processes to limit disease progression. We summarize key preclinical studies that support use of FPR2 agonists in heart disease. Finally, we briefly discuss the status of FPR2 agonists under evaluation in the clinic., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Context.—: Rosai-Dorfman disease is a rare histiocytic proliferative disorder of unknown pathogenesis that may be diagnostically difficult in extranodal sites. It is commonly an unsuspected diagnosis when arising in bone and soft tissue, especially when it presents without associated lymphadenopathy. Its variable clinical presentation and nonspecific imaging findings make the diagnosis quite challenging, particularly in small biopsies. The problem is compounded by its less-characteristic histomorphologic features in comparison with nodal disease. Awareness of the potential diagnostic pitfalls in Rosai-Dorfman disease of bone and soft tissue should raise the degree of diagnostic accuracy., Objective.—: To review the clinical manifestations, imaging characteristics, and histomorphologic features of Rosai-Dorfman disease of bone and soft tissue along with a brief discussion of its differential diagnosis, pathogenesis, and current management., Data Sources.—: Thorough review of the literature with focus on clinical manifestations, imaging findings, key histomorphologic features, pathogenesis, and treatment., Conclusions.—: The diagnosis of Rosai-Dorfman disease of bone and soft tissue may be quite challenging because of its variable clinical presentation and nonspecific imaging findings. It may be asymptomatic without systemic manifestations or associated lymphadenopathy. The definitive diagnosis relies on histopathologic identification of the characteristic S-100-positive histiocytes demonstrating emperipolesis. Bone and soft tissue lesions tend to have lower numbers of characteristic histiocytes and less conspicuous emperipolesis and often demonstrate areas of fibrosis or storiform spindle cell areas resembling fibrohistiocytic lesions. Awareness of these unusual features is necessary in order to consider Rosai-Dorfman disease in the differential diagnosis when confronting these rare and often misleading lesions.

Ultrashort-period (USP) exoplanets have orbital periods shorter than 1 day. Precise masses and radii of USP exoplanets could provide constraints on their unknown formation and evolution processes. We report the detection and characterization of the USP planet GJ 367b using high-precision photometry and radial velocity observations. GJ 367b orbits a bright ( V -band magnitude of 10.2), nearby, and red (M-type) dwarf star every 7.7 hours. GJ 367b has a radius of 0.718 ± 0.054 Earth-radii and a mass of 0.546 ± 0.078 Earth-masses, making it a sub-Earth planet. The corresponding bulk density is 8.106 ± 2.165 grams per cubic centimeter—close to that of iron. An interior structure model predicts that the planet has an iron core radius fraction of 86 ± 5%, similar to that of Mercury’s interior.

To forecast climate change impacts across habitats or taxa, thermal vulnerability indices (e.g., safety margins and warming tolerances) are growing in popularity. Here, we present their history, context, formulation, and current applications. We highlight discrepancies in terminology and usage, and we draw attention to key assumptions underpinning the main indices and to their ecological and evolutionary relevance. In the process, we flag biases influencing these indices that are not always evaluated. These biases affect both components of index formulations, namely: (i) the characterisation of the thermal environment; and (ii) an organism's physiological and behavioural responses to more frequent and severe warming. Presently, many outstanding questions weaken a thermal vulnerability index approach. We describe ways to validate vulnerability index applications and outline issues to be considered in further developing these indices., Competing Interests: Declaration of interests None declared by authors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Left ventricular assist devices (LVADs) are surgically implanted mechanical devices indicated for patients with advanced heart failure and are known to come with several complications. Here we present a case series, and review 1 documented report, of LVAD vasculitis, a presumed new LVAD immune/humoral related phenomenon. ( Level of Difficulty: Advanced. )., Competing Interests: Dr Garcia is supported by the National Heart, Lung, and Blood Institute, Institutes of Health, under Aware Number 5T32HL110837. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Purpose of Review: As medicine strives to become more patient-centered, patient-reported outcomes (PROs) are often used to describe patients' symptoms, function, and quality of life. This review describes the key concepts of PROs specific to heart failure in clinical trials and their potential role in clinical practice., Recent Findings: As the Food and Drug Administration has increasingly emphasized how it values PROs as clinical outcome assessments, including its recent qualification of the Kansas City Cardiomyopathy Questionnaire (KCCQ), clinical trials have increasingly used them to evaluate novel therapies. This has been enhanced by an increasing understanding of how to interpret KCCQ scores. Its use in clinical practice, including the importance of providers sharing results with their patients, is just emerging. PROs provide unique insights into the benefits of treatment from patients' perspectives and while their role in clinical care is just beginning, they offer an important opportunity to improve the patient-centeredness of care.

This study aimed to evaluate the frequency of cryptic Candida species from candidemia cases in 22 public hospitals in São Paulo State, Brazil, and their antifungal susceptibility profiles. During 2017 and 2018, 144 isolates were molecularly identified as 14 species; C. parapsilosis (32.6%), C. albicans (27.7%), C. tropicalis (14.6%), C. glabrata (9.7%), C. krusei (2.8%), C. orthopsilosis (2.8%), C. haemulonii var. vulnera (2.1%), C. haemulonii (1.4%), C. metapsilosis (1.4%), C. dubliniensis (1.4%), C. guilliermondii (1.4%), C. duobushaemulonii (0.7%), C. kefyr (0.7%), and C. pelliculosa (0.7%). Poor susceptibility to fluconazole was identified in 6.4% of C. parapsilosis isolates (0.12 to >64 µg/mL), 50% of C. guilliermondii (64 µg/mL), 66.6% of C. haemulonii var. vulnera (16-32 µg/mL), and C. duobushaemulonii strain (MIC 64 µg/mL). Our results corroborated the emergence of C. glabrata in Brazilian cases of candidemia as previously reported. Importantly, we observed a large proportion of non-wild type C. glabrata isolates to voriconazole (28.6%; <0.015 to 4 µg/mL) all of which were also resistant to fluconazole (28.6%). Of note, C. haemulonii, a multidrug resistant species, has emerged in the Southeast region of Brazil. Our findings suggested a possible epidemiologic change in the region with an increase in fluconazole-resistant species causing candidemia. We stress the relevance of routine accurate identification to properly manage therapy and monitor epidemiologic trends.

Background: Diagnostic and Statistical Manual of Mental Disorders ( DSM -5) included in 2013 Internet gaming disorder (IGD) as a condition for further study, and in 2018, the World Health Organization included gaming disorder (GD) as a mental disorder in the International Classification of Disease ( ICD -11). We aim to compare disorders of gaming in both diagnostic systems using a sample of young adults in Mexico., Methods: Self-administered survey to estimate the prevalence of DSM -5 IGD and ICD -11 GD in 5 Mexican universities; 7,022 first-year students who participated in the University Project for Healthy Students, part of the World Health Organization World Mental Health International College Student Initiative. Cross-tabulation, logistic regression, and item response theory were used to inform on 12- month prevalence of DSM -5 IGD and ICD -11 GD, without and with impairment., Results: The 12-month prevalence of DSM -5 IGD was 5.2% (95% CI, 4.7 to 5.8), almost twice as high as the prevalence using the ICD -11 GD criteria (2.7%; 95% CI, 2.4 to 3.1), and while adding an impairment requirement diminishes both estimates, prevalence remains larger in DSM -5. We found that DSM -5 cases detected and undetected by ICD -11 criteria were similar in demographics, comorbid mental disorders, service use, and impairment variables with the exception that cases detected by ICD -11 had a larger number of symptoms and were more likely to have probable drug dependence than undetected DSM -5 cases., Conclusion: DSM -5 cases detected by ICD -11 are mostly similar to cases undetected by ICD -11. By using ICD -11 instead of DSM -5, we may be leaving (similarly) affected people underserved. It is unlikely that purely epidemiological studies can solve this discrepancy and clinical validity studies maybe needed.

Patient-reported outcomes (PROs) are elicited directly from patients so they can describe their overall health status, including their symptoms, function, and quality of life. While commonly used as end points in clinical trials, PROs can play an important role in routine clinical care, population health management, and as a means for quantifying the quality of patient care. In this review, we propose that PROs be used to improve patient-centered care in the treatment of cardiovascular diseases given their importance to patients and society and their ability to improve doctor- provider communication. Furthermore, given the current variability in patients' health status across different clinics and the fact that PROs can be improved by titrating therapy, we contend that PROs have a key opportunity to serve as measures of healthcare quality., Competing Interests: Dr. Garcia is supported by the National Heart, Lung and Blood Institutes of Health Under Aware Number 5T32H110837. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health (NIH). Dr. Spertus discloses grant funding from NIH and Abbott Vascular. He serves on a scientific advisory board for United Healthcare and Blue Cross Blue Shield of Kansas City and is a consultant for Novartis, Bayer, AstraZeneca, Janssen, Merck, Myokardia, and Amgen. He has intellectual property rights for the Kansas City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire, and Peripheral Artery Questionnaire and an equity interest in Health Outcomes Sciences.

The purpose of this study was to verify whether cooling between sets during high-intensity resistance exercise improves physical performance and to compare performance among different sites of cooling. It is important because delaying the muscular fatigue could improve total volume at a training session which could lead to greater hypertrophy. Nine healthy and recreational resistance training experienced men, performed six tests of a biceps curl exercise on different days. The first test was the one-repetition maximum test (1RM). Following, we applied five sessions, in crossover and randomized (counter-balanced) design. The subjects received different cooling strategies in each session for 1-min (inter-set rest interval): Control (C) (no Cooling); Palm Cooling (PC); Neck Cooling (NC); Local Cooling (LC) or Tunnel Temperature Cooling (TTC). We analyzed the maximum number of repetitions and the rating of perceived exertion (RPE). The Bayesian analysis showed that no cooling strategy was able to improve performance compared to control, and just NC, when compared to control, showed a 71% probability of increasing the total volume of repetitions. Also, RPE was not modulated by any cooling strategy compared to control, but NC has a chance to reduce individuals' RPE by 52%. In conclusion, no cooling strategy was efficient to improve physical performance during a high-intensity resistance exercise.

While Ewing sarcoma of bone is the second most common primary osseous malignancy in childhood where it typically involves the diaphysis or metadiaphyses of long bones of skeletally immature patients, primary epiphyseal involvement of the long bone in skeletally mature patients is rare with no cases reported in the literature to our knowledge, rendering this case the first of its kind. We present the first case of primary Ewing Sarcoma of the epiphyses of the long bones in a skeletally mature 20-year-old male patient. The patient initially presented with left knee stiffness and pain that was empirically treated with non-steroidal anti-inflammatory medications. His pain progressed despite treatment. An x-ray of the left knee was obtained 5 months later demonstrating an irregular lucent lesion in the medial femoral condyle. A subsequent MRI revealed an enhancing lesion in the medial femoral condyle, and when biopsied it was consistent with Ewing sarcoma (positive for EWSR1 gene rearrangement by fluorescence in situ hybridization). The lesion was resected surgically, and the patient underwent neoadjuvant chemotherapy with a good clinical outcome., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)