Search

Abstract The Observing Air–Sea Interactions Strategy (OASIS) is a new United Nations Decade of Ocean Science for Sustainable Development programme working to develop a practical, integrated approach for observing air–sea interactions globally for improved Earth system (including ecosystem) forecasts, CO2 uptake assessments called for by the Paris Agreement, and invaluable surface ocean information for decision makers. Our “Theory of Change” relies upon leveraged multi-disciplinary activities, partnerships, and capacity strengthening. Recommendations from >40 OceanObs’19 community papers and a series of workshops have been consolidated into three interlinked Grand Ideas for creating #1: a globally distributed network of mobile air–sea observing platforms built around an expanded array of long-term time-series stations; #2: a satellite network, with high spatial and temporal resolution, optimized for measuring air–sea fluxes; and #3: improved representation of air–sea coupling in a hierarchy of Earth system models. OASIS activities are organized across five Theme Teams: (1) Observing Network Design & Model Improvement; (2) Partnership & Capacity Strengthening; (3) UN Decade OASIS Actions; (4) Best Practices & Interoperability Experiments; and (5) Findable–Accessible–Interoperable–Reusable (FAIR) models, data, and OASIS products. Stakeholders, including researchers, are actively recruited to participate in Theme Teams to help promote a predicted, safe, clean, healthy, resilient, and productive ocean.

The audibility of patient clinical alarms to nursing personnel was tested during the first shift on a medical/surgical in-patient ward at William Beaumont Army Medical Center. This study was conducted during normal hospital operations, and we tested the Joint Commission on Accreditation of Healthcare Organizations 2004 National Patient Safety Goal, Section 6b to determine whether patient alarms could sufficiently compete against environmental background noises. Patient clinical alarms were audible at distances of > or = 95 feet with room doors open but were not sufficiently audible to hospital staff members when room doors were closed or during floor-buffing activities. This study suggests that, under these circumstances, hospitals may not meet Joint Commission on Accreditation of Healthcare Organizations 2004 National Patient Safety Goal, Section 6b. Because the audibility of patient clinical alarms directly affects patient safety, satisfaction, and quality of care, we provide recommendations for engineering controls and modifications to work routines. [ABSTRACT FROM AUTHOR]

During production, harvested cell culture fluid (HCCF) can degrade due to reductases breaking interchain disulfide bonds, forming low molecular weight (LMW) impurities that contain free sulfhydryl and high molecular weight (HMW) impurities through disulfide shuffling. Thus, detecting and quantifying the free sulfhydryl increase in HCCF is critical. Herein, Raman spectroscopy is implemented as a process analytical technology, and multivariate data analysis is applied to characterize and quantify sulfhydryl formation in HCCF with disulfide-containing indicator molecules. Raman spectra qualitatively probe the presence or absence of disulfide bond breakage in antibodies, consistent with offline non-reduced capillary electrophoresis sodium dodecyl sulfate results. Between two antibodies studied, mAb A was identified for a higher risk of antibody reduction where sulfhydryl formation was observed within 16 h, while mAb B did not show similar concerns even after 1 week. The offline measurement of redox potential is below -100 mV in HCCF for mAb A, while the stable mAb B HCCF shows redox potentials above +20 mV. A multivariate partial least squares (PLS) model for quantification is developed using an offline free sulfhydryl assay, applying Raman spectra to predict free sulfhydryl concentration with high accuracy (R 2 > 0.98) and expected mean error of 0.677 mM from the offline Ellman's Assay. This work confirms the use of Raman PAT to monitor real-time disulfide reduction, enabling improvements to process understanding and product quality., 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 © 2024. Published by Elsevier B.V.)

The renin-angiotensin-aldosterone system (RAAS) is a complex regulator comprising hormones, proteins, and enzymes. The discovery of the RAAS and its pharmacological manipulation has been essential in the management of cardiovascular diseases, including hypertension. Beyond the benefits of hypertension, RAAS inhibition has implications for heart failure, atherosclerotic disease, and kidney disease. This review discusses the history and mechanism of RAAS inhibition, cardiovascular benefits, affordability, and potential future pharmacological therapies.

This pilot study assessed the feasibility and combined effect of aerobic exercise (AE) and mindfulness meditation (MM), compared with MM alone and a control (CON) condition, on stress, anxiety, and depression in high-stress college-based young adults. Thirty-two participants (84.4% F, 20.5 ± 2.7 years, 23.9 ± 5.0 kg/m 2 ) were randomized to a four-week, AE + MM ( n  = 16), MM ( n  = 10), or control intervention ( n  = 6). ANOVA revealed non-significant, but noteworthy group x time interactions (perceived stress: p  = 0.09; anxiety/depression: p  = 0.07). Both AE + MM and MM seem to be feasible strategies to reduce levels of stress, anxiety and depression in college-based young adults.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Recent studies show gut microbiota-dependent metabolism of dietary phenylalanine into phenylacetic acid (PAA) is critical in phenylacetylglutamine (PAGln) production, a metabolite linked to atherosclerotic cardiovascular disease (ASCVD). Accordingly, microbial enzymes involved in this transformation are of interest. Using genetic manipulation in selected microbes and monocolonization experiments in gnotobiotic mice, we identify two distinct gut microbial pathways for PAA formation; one is catalyzed by phenylpyruvate:ferredoxin oxidoreductase (PPFOR) and the other by phenylpyruvate decarboxylase (PPDC). PPFOR and PPDC play key roles in gut bacterial PAA production via oxidative and non-oxidative phenylpyruvate decarboxylation, respectively. Metagenomic analyses revealed a significantly higher abundance of both pathways in gut microbiomes of ASCVD patients compared with controls. The present studies show a role for these two divergent microbial catalytic strategies in the meta-organismal production of PAGln. Given the numerous links between PAGln and ASCVD, these findings will assist future efforts to therapeutically target PAGln formation in vivo., Competing Interests: Declaration of interests S.L.H., Z.W., and J.T.A. report being named as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and/or therapeutics and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, a wholly owned subsidiary of Quest Diagnostics, P&G, and Zehna Therapeutics. S.L.H. and J.T.A. report being paid consultants for Zehna Therapeutics. S.L.H. also reports having received research funds from P&G, Roche Diagnostics, and Zehna Therapeutics. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Infections of the central nervous system (CNS) are complex to treat and associated with significant morbidity and mortality. Historically, antistaphylococcal penicillins such as nafcillin were recommended for the treatment of methicillin-susceptible staphylococcal CNS infections. However, the use of antistaphylococcal penicillins presents challenges, such as frequent dosing administration and adverse events with protracted use. This narrative reviews available clinical and pharmacokinetic/pharmacodynamic (PK/PD) data for cefazolin in CNS infections and produces a recommendation for use. Based on the limited available evidence analyzed, dose optimized cefazolin is likely a safe and effective alternative to antistaphylococcal penicillins for a variety of CNS infections due to methicillin-susceptible Staphylococcus aureus. Given the site of infection and wide therapeutic index of cefazolin, practitioners may consider dosing cefazolin regimens of 2 g IV every 6 h or a continuous infusion of 8-10 g daily instead of 2 g IV every 8 h to optimize PK/PD properties., (© 2023 Pharmacotherapy Publications, Inc.)

Protein lysine carbamylation is an irreversible post-translational modification resulting in generation of homocitrulline (N-ε-carbamyllysine), which no longer possesses a charged ε-amino moiety. Two distinct pathways can promote protein carbamylation. One results from urea decomposition, forming an equilibrium mixture of cyanate (CNO - ) and the reactive electrophile isocyanate. The second pathway involves myeloperoxidase (MPO)-catalyzed oxidation of thiocyanate (SCN - ), yielding CNO - and isocyanate. Apolipoprotein A-I (apoA-I), the major protein constituent of high-density lipoprotein (HDL), is a known target for MPO-catalyzed modification in vivo, converting the cardioprotective lipoprotein into a proatherogenic and proapoptotic one. We hypothesized that monitoring site-specific carbamylation patterns of apoA-I recovered from human atherosclerotic aorta could provide insights into the chemical environment within the artery wall. To test this, we first mapped carbamyllysine obtained from in vitro carbamylation of apoA-I by both the urea-driven (nonenzymatic) and inflammatory-driven (enzymatic) pathways in lipid-poor and lipidated apoA-I (reconstituted HDL). Our results suggest that lysine residues within proximity of the known MPO-binding sites on HDL are preferentially targeted by the enzymatic (MPO) carbamylation pathway, whereas the nonenzymatic pathway leads to nearly uniform distribution of carbamylated lysine residues along the apoA-I polypeptide chain. Quantitative proteomic analyses of apoA-I from human aortic atheroma identified 16 of the 21 lysine residues as carbamylated and suggested that the majority of apoA-I carbamylation in vivo occurs on "lipid-poor" apoA-I forms via the nonenzymatic CNO - pathway. Monitoring patterns of apoA-I carbamylation recovered from arterial tissues can provide insights into both apoA-I structure and the chemical environment within human atheroma., Competing Interests: Conflict of interest S. L. H. reports being named as coinventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, being a paid consultant for Procter & Gamble and Zehna Therapeutics, having received research funds from Procter & Gamble, Zehna Therapeutics, and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, a wholly owned subsidiary of Quest Diagnostics, Procter & Gamble, and Zehna Therapeutics. All the other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Systemic oppression includes inequitable education that historically does not fully prepare students for comprehensive participation in society. The tools of science education, however, uniquely enable students to explore social inequities as well as the natural world. Thus, a role of education can be to embed social justice in science curricula. Presented here are three case studies that investigate pedagogical methods used by experienced teachers to integrate social justice into upper level high-school biology curricula. Two separate semi-constructed interviews were conducted with participants, along with an analysis of their pedagogical materials. Two main themes are identified and explored: (1) delivery methods (pedagogy) and (2) biological science content. Storytelling and culturally responsive pedagogy were reported to be highly effective in engaging students; using these vehicles for delivery, social justice content can be seamlessly introduced alongside organic evolution. This embedded exploratory multiple-case study serves as an example of how science education can become a tool for student empowerment., Supplementary Information: The online version contains supplementary material available at 10.1007/s11191-021-00287-y., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2021.)

INTRODUCTION: It has been well established that patients with darker skin types (Fitzpatrick skin types IV-VI) have an increased incidence of thermal induced side effects from laser and radio frequency (RF) treatments. Complications include a higher risk of post-inflammatory hyperpigmentation, hypopigmentation, and scarring, leading to unsatisfactory clinical outcomes. Fractional technologies improve the safety when treating patients with skin of color by treating only fractions of the skin while leaving a healing reservoir of untreated skin that improves the healing process. Fractional RF tips with coated pins may offer a more advantageous safety profile, particularly in the skin-of-color population (Fitzpatrick skin types IV-VI) by increasing the protection of the epidermal layer by minimizing epidermal heating The current study was intended to evaluate the safety and efficacy of fractional RF technology for the treatment of patients with Fitzpatrick skin type VI. METHODS: 35 subjects with skin type VI received 3 sessions of facial treatments, 4 weeks apart using a fractional RF device with 24 pin coated tip. The treatment's safety and efficacy were evaluated at 2 follow-up visits, 6 and 12 weeks after the last treatment. RESULTS: Skin characteristics evaluations, including Fitzpatrick Wrinkles Classification, acne scars, and overall facial appearance demonstrated improvement in follow-up visits comparing to baseline. No significant unexpected adverse events were detected. CONCLUSION: The current study proves the safety and efficacy of the fractional RF treatment modality with coated pins tips for skin rejuvenation treatments resulting in improved wrinkles, acne scars, and overall skin appearance, in patients with skin type VI. J Drugs Dermatol. 2018;17(11):1169-1172.

Men who have sex with men (MSM) of color are disproportionately affected by HIV in the United States. Pre-exposure prophylaxis (PrEP) using antiretroviral medications is a newer biomedical prevention modality with established efficacy for reducing the risk of acquiring HIV. We conducted formative qualitative research to explore audience reactions and receptivity to message concepts on PrEP as part of the development of prevention messages to promote PrEP awareness among black and Latino MSM in the United States. In 2013, 48 black and 42 Latino (total study sample = 90) mixed HIV serostatus MSM from Chicago, Ft. Lauderdale, and Kansas City participated in either an individual interview or focus group discussion. Men were recruited online and at community-based organizations in each city. We elicited feedback on the comprehensibility, credibility, and relevance of two draft messages on PrEP. The messages included efficacy estimates from iPrEx, a phase III clinical trial to ascertain whether the antiretroviral medication tenofovir/emtricitabine disoproxil fumarate (commercially known as Truvada ® ) could safely and effectively prevent HIV acquisition through sex among MSM and transgender women. With participants' consent, the interviews and focus groups were recorded and transcribed. The data were then summarized and analyzed using a qualitative descriptive approach. The majority of men were unfamiliar with PrEP. It was suggested that additional information about the medication and clinical trials establishing efficacy was needed to enhance the legitimacy and relevancy of the messages. Participants sought to form an opinion of PrEP that was grounded in their own interpretation of the efficacy data. However, confusion about nonadherence among clinical trial subjects and individual versus average risk limited comprehension of these messages. Thematic overlaps suggest that message believability was connected to participants' ability to derive meaning from the PrEP efficacy data. Despite being concerned that other MSM would interpret the messages to mean that condom use was unnecessary while taking PrEP, participants themselves primarily understood PrEP as a supplement rather than a replacement for condoms. Based on their experience with taking antiretroviral medication, HIV-positive men considered condom use a more feasible form of HIV prevention than PrEP. Participants' responses suggest that more information about PrEP and the clinical trial would support the legitimacy of PrEP and the messages as a whole. These details may enhance believability in the concept of PrEP and reinforce confidence in the validity of the efficacy result.

Patterns in expression data conserved across multiple independent disease studies are likely to represent important molecular events underlying the disease. We present the INSPIRE method to infer modules of co-expressed genes and the dependencies among the modules from multiple expression datasets that may contain different sets of genes. We show that INSPIRE infers more accurate models than existing methods to extract low-dimensional representation of expression data. We demonstrate that applying INSPIRE to nine ovarian cancer datasets leads to a new marker and potential driver of tumor-associated stroma, HOPX, followed by experimental validation. The implementation of INSPIRE is available at http://inspire.cs.washington.edu .

The small phenolic compound salicylic acid (SA) plays a critical role in plant defense against broad-spectrum of pathogens. The phosphate transporter gene PHT4;1 was previously shown to affect SA-mediated defense and its expression is regulated by the circadian clock. To further understand how PHT4;1 affects SA accumulation, here we analyzed the genetic interactions between the gain-of-function mutant pht4;1-1 and several known SA mutants, including sid2-1, ald1-1, eds5-3, and pad4-1. The genetic analysis was conducted in the acd6-1 background since the change of acd6-1 dwarfism can be used as a convenient readout for the change of defense levels caused by impairments in some SA genes. We found that compared with the corresponding double mutants, the triple mutants acd6-1pht4;1-1ald1-1, acd6-1pht4;1-1eds5-3, and acd6-1pht4;1-1pad4-1 accumulated lower levels of SA and PR1 transcripts, suggesting that PHT4;1 contributes to acd6-1-conferred defense phenotypes independently of these known SA regulators. Although some triple mutants had wild type (wt)-like levels of SA and PR1 transcripts, these plants were smaller than wt and displayed minor cell death, suggesting that additional regulatory pathways contribute to acd6-1-conferred dwarfism and cell death. Our data further showed that circadian expression of PHT4;1 was dependent on CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), a central oscillator component of Arabidopsis circadian clock. Recombinant CCA1 protein was demonstrated to bind to the PHT4;1 promoter in electrophoretic mobility shift assays, suggesting a direct transcriptional regulation of PHT4;1 by CCA1. Together these results indicate that PHT4;1 is a SA regulator acting independently of several known SA genes and they also implicate a role of the circadian clock mediated by CCA1 in regulating phosphate transport and/or innate immunity in Arabidopsis.

We report a case of acute parotitis due to influenza A in which, unlike other published cases, the diagnosis was confirmed by demonstration of subtyped influenza A, serological evidence of mumps immunity, and full recovery without antibiotic treatment. In the United States, acute infectious parotitis was historically caused primarily by symptomatic paramyxovirus (mumps) infections, but because of the near-universal administration of the measles, mumps and rubella vaccine, other infectious and noninfectious etiologies now predominate. We discuss the differential diagnosis and therapeutic and public health considerations of parotitis and influenza. Due to time-sensitive pharmacologic management and possibly far-reaching public health issues, providers should be aware of atypical influenza presentations, such as parotitis.

Epstein-Barr virus (EBV) and the closely related Herpesvirus papio (HVP) are stably replicated as episomes in proliferating latently infected cells. Maintenance and partitioning of these viral plasmids requires a viral sequence in cis, termed the family of repeats (FR), that is bound by a viral protein, Epstein-Barr nuclear antigen 1 (EBNA1). Upon binding FR, EBNA1 maintains viral genomes in proliferating cells and activates transcription from viral promoters required for immortalization. FR from either virus encodes multiple binding sites for the viral maintenance protein, EBNA1, with the FR from the prototypic B95-8 strain of EBV containing 20 binding sites, and FR from HVP containing 8 binding sites. In addition to differences in the number of EBNA1-binding sites, adjacent binding sites in the EBV FR are typically separated by 14 base pairs (bp), but are separated by 10 bp in HVP. We tested whether the number of binding sites, as well as the distance between adjacent binding sites, affects the function of EBNA1 in transcription activation or plasmid maintenance. Our results indicate that EBNA1 activates transcription more efficiently when adjacent binding sites are separated by 10 bp, the spacing observed in HVP. In contrast, using two separate assays, we demonstrate that plasmid maintenance is greatly augmented when adjacent EBNA1-binding sites are separated by 14 bp, and therefore, presumably lie on the same face of the DNA double helix. These results provide indication that the functions of EBNA1 in transcription activation and plasmid maintenance are separable.