Transmission from vaccinated individuals in a large SARS-CoV-2 Delta variant outbreak.

An outbreak of over 1,000 COVID-19 cases in Provincetown, Massachusetts (MA), in July 2021-the first large outbreak mostly in vaccinated individuals in the US-prompted a comprehensive public health response, motivating changes to national masking recommendations and raising questions about infection and transmission among vaccinated individuals. To address these questions, we combined viral genomic and epidemiological data from 467 individuals, including 40% of outbreak-associated cases. The Delta variant accounted for 99% of cases in this dataset; it was introduced from at least 40 sources, but 83% of cases derived from a single source, likely through transmission across multiple settings over a short time rather than a single event. Genomic and epidemiological data supported multiple transmissions of Delta from and between fully vaccinated individuals. However, despite its magnitude, the outbreak had limited onward impact in MA and the US overall, likely due to high vaccination rates and a robust public health response.

An evolutionarily conserved prion-like element converts wild fungi from metabolic specialists to generalists.

[GAR(+)] is a protein-based element of inheritance that allows yeast (Saccharomyces cerevisiae) to circumvent a hallmark of their biology: extreme metabolic specialization for glucose fermentation. When glucose is present, yeast will not use other carbon sources. [GAR(+)] allows cells to circumvent this "glucose repression." [GAR(+)] is induced in yeast by a factor secreted by bacteria inhabiting their environment. We report that de novo rates of [GAR(+)] appearance correlate with the yeast's ecological niche. Evolutionarily distant fungi possess similar epigenetic elements that are also induced by bacteria. As expected for a mechanism whose adaptive value originates from the selective pressures of life in biological communities, the ability of bacteria to induce [GAR(+)] and the ability of yeast to respond to bacterial signals have been extinguished repeatedly during the extended monoculture of domestication. Thus, [GAR(+)] is a broadly conserved adaptive strategy that links environmental and social cues to heritable changes in metabolism.

Unraveling the biology of a fungal meningitis pathogen using chemical genetics.

The fungal meningitis pathogen Cryptococcus neoformans is a central driver of mortality in HIV/AIDS. We report a genome-scale chemical genetic data map for this pathogen that quantifies the impact of 439 small-molecule challenges on 1,448 gene knockouts. We identified chemical phenotypes for 83% of mutants screened and at least one genetic response for each compound. C. neoformans chemical-genetic responses are largely distinct from orthologous published profiles of Saccharomyces cerevisiae, demonstrating the importance of pathogen-centered studies. We used the chemical-genetic matrix to predict novel pathogenicity genes, infer compound mode of action, and to develop an algorithm, O2M, that predicts antifungal synergies. These predictions were experimentally validated, thereby identifying virulence genes, a molecule that triggers G2/M arrest and inhibits the Cdc25 phosphatase, and many compounds that synergize with the antifungal drug fluconazole. Our work establishes a chemical-genetic foundation for approaching an infection responsible for greater than one-third of AIDS-related deaths.

Cross-kingdom chemical communication drives a heritable, mutually beneficial prion-based transformation of metabolism.

In experimental science, organisms are usually studied in isolation, but in the wild, they compete and cooperate in complex communities. We report a system for cross-kingdom communication by which bacteria heritably transform yeast metabolism. An ancient biological circuit blocks yeast from using other carbon sources in the presence of glucose. [GAR(+)], a protein-based epigenetic element, allows yeast to circumvent this "glucose repression" and use multiple carbon sources in the presence of glucose. Some bacteria secrete a chemical factor that induces [GAR(+)]. [GAR(+)] is advantageous to bacteria because yeast cells make less ethanol and is advantageous to yeast because their growth and long-term viability is improved in complex carbon sources. This cross-kingdom communication is broadly conserved, providing a compelling argument for its adaptive value. By heritably transforming growth and survival strategies in response to the selective pressures of life in a biological community, [GAR(+)] presents a unique example of Lamarckian inheritance.

Global RNA modifications to the MALAT1 triple helix differentially affect thermostability and weaken binding to METTL16.

Therapeutic mRNAs are generated using modified nucleotides, namely N1-methylpseudouridine (m1Ψ) triphosphate, so that the mRNA evades detection by the immune system. RNA modifications, even at a single-nucleotide position, perturb RNA structure, although it is not well understood how structure and function is impacted by globally modified RNAs. Therefore, we examined the metastasis-associated lung adenocarcinoma transcript 1 triple helix, a highly structured stability element that includes single-, double-, and triple-stranded RNA, globally modified with N6-methyladenosine (m6A), pseudouridine (Ψ), or m1Ψ. UV thermal denaturation assays showed that m6A destabilizes both the Hoogsteen and Watson-Crick faces of the RNA by ∼20 °C, Ψ stabilizes the Hoogsteen and Watson-Crick faces of the RNA by ∼12 °C, and m1Ψ has minimal effect on the stability of the Hoogsteen face of the RNA but increases the stability of the Watson-Crick face by ∼9 °C. Native gel-shift assays revealed that binding of the methyltransferase-like protein 16 to the metastasis-associated lung adenocarcinoma transcript 1 triple helix was weakened by at least 8-, 99-, and 23-fold, respectively, when RNA is globally modified with m6A, Ψ, or m1Ψ. These results demonstrate that a more thermostable RNA structure does not lead to tighter RNA-protein interactions, thereby highlighting the regulatory power of RNA modifications by multiple means.

Transcriptomic-Based Microenvironment Classification Reveals Precision Medicine Strategies for Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: The complex tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) has hindered the development of reliable predictive biomarkers for targeted therapy and immunomodulatory strategies. A comprehensive characterization of the TME is necessary to advance precision therapeutics in PDAC. METHODS: A transcriptomic profiling platform for TME classification based on functional gene signatures was applied to 14 publicly available PDAC datasets (n = 1657) and validated in a clinically annotated independent cohort of patients with PDAC (n = 79). Four distinct subtypes were identified using unsupervised clustering and assessed to evaluate predictive and prognostic utility. RESULTS: TME classification using transcriptomic profiling identified 4 biologically distinct subtypes based on their TME immune composition: immune enriched (IE); immune enriched, fibrotic (IE/F); fibrotic (F); and immune depleted (D). The IE and IE/F subtypes demonstrated a more favorable prognosis and potential for response to immunotherapy compared with the F and D subtypes. Most lung metastases and liver metastases were subtypes IE and D, respectively, indicating the role of clonal phenotype and immune milieu in developing personalized therapeutic strategies. In addition, distinct TMEs with potential therapeutic implications were identified in treatment-naive primary tumors compared with tumors that underwent neoadjuvant therapy. CONCLUSIONS: This novel approach defines a distinct subgroup of PADC patients that may benefit from immunotherapeutic strategies based on their TME subtype and provides a framework to select patients for prospective clinical trials investigating precision immunotherapy in PDAC. Further, the predictive utility and real-world clinical applicability espoused by this transcriptomic-based TME classification approach will accelerate the advancement of precision medicine in PDAC.

A single natural RNA modification can destabilize a U•A-T-rich RNA•DNA-DNA triple helix.

Recent studies suggest noncoding RNAs interact with genomic DNA, forming RNA•DNA-DNA triple helices, as a mechanism to regulate transcription. One way cells could regulate the formation of these triple helices is through RNA modifications. With over 140 naturally occurring RNA modifications, we hypothesize that some modifications stabilize RNA•DNA-DNA triple helices while others destabilize them. Here, we focus on a pyrimidine-motif triple helix composed of canonical U•A-T and C•G-C base triples. We employed electrophoretic mobility shift assays and microscale thermophoresis to examine how 11 different RNA modifications at a single position in an RNA•DNA-DNA triple helix affect stability: 5-methylcytidine (m5C), 5-methyluridine (m5U or rT), 3-methyluridine (m3U), pseudouridine (Ψ), 4-thiouridine (s4U), N 6-methyladenosine (m6A), inosine (I), and each nucleobase with 2'-O-methylation (Nm). Compared to the unmodified U•A-T base triple, some modifications have no significant change in stability (Um•A-T), some have ∼2.5-fold decreases in stability (m5U•A-T, Ψ•A-T, and s4U•A-T), and some completely disrupt triple helix formation (m3U•A-T). To identify potential biological examples of RNA•DNA-DNA triple helices controlled by an RNA modification, we searched RMVar, a database for RNA modifications mapped at single-nucleotide resolution, for lncRNAs containing an RNA modification within a pyrimidine-rich sequence. Using electrophoretic mobility shift assays, the binding of DNA-DNA to a 22-mer segment of human lncRNA Al157886.1 was destabilized by ∼1.7-fold with the substitution of m5C at known m5C sites. Therefore, the formation and stability of cellular RNA•DNA-DNA triple helices could be influenced by RNA modifications.

Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations - United States, 2023.

Chronic hepatitis B virus (HBV) infection can lead to substantial morbidity and mortality. Although treatment is not considered curative, antiviral treatment, monitoring, and liver cancer surveillance can reduce morbidity and mortality. Effective vaccines to prevent hepatitis B are available. This report updates and expands CDC's previously published Recommendations for Identification and Public Health Management of Persons with Chronic Hepatitis B Virus Infection (MMWR Recomm Rep 2008;57[No. RR-8]) regarding screening for HBV infection in the United States. New recommendations include hepatitis B screening using three laboratory tests at least once during a lifetime for adults aged ≥18 years. The report also expands risk-based testing recommendations to include the following populations, activities, exposures, or conditions associated with increased risk for HBV infection: persons incarcerated or formerly incarcerated in a jail, prison, or other detention setting; persons with a history of sexually transmitted infections or multiple sex partners; and persons with a history of hepatitis C virus infection. In addition, to provide increased access to testing, anyone who requests HBV testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.

Genotype-by-environment interactions and local adaptation shape selection in the US National Chip Processing Trial.

KEY MESSAGE: We find evidence of selection for local adaptation and extensive genotype-by-environment interaction in the potato National Chip Processing Trial (NCPT). We present a novel method for dissecting the interplay between selection, local adaptation and environmental response in plant breeding schemes. Balancing local adaptation and the desire for widely adapted cultivars is challenging for plant breeders and makes genotype-by-environment interactions (GxE) an important target of selection. Selecting for GxE requires plant breeders to evaluate plants across multiple environments. One way breeders have accomplished this is to test advanced materials across many locations. Public potato breeders test advanced breeding material in the National Chip Processing Trial (NCPT), a public-private partnership where breeders from ten institutions submit advanced chip lines to be evaluated in up to ten locations across the country. These clones are genotyped and phenotyped for important agronomic traits. We used these data to interrogate the NCPT for GxE. Further, because breeders submitting clones to the NCPT select in a relatively small geographic range for the first 3 years of selection, we examined these data for evidence of incidental selection for local adaptation, and the alleles underlying it, using an environmental genome-wide association study (envGWAS). We found genomic regions associated with continuous environmental variables and discrete breeding programs, as well as regions of the genome potentially underlying GxE for yield.

mTBI evaluation, management, and referral to allied healthcare: practices of first-line healthcare professionals.

PRIMARY OBJECTIVE: To gain an understanding of current evaluation practices, post-injury recommendations, and referrals to allied healthcare professions (AHP) by first-line healthcare professionals (FHPs) providing care for people with mild traumatic brain injury (mTBI). RESEARCH DESIGN: Survey study. METHODS AND PROCEDURES: Physicians, physician assistants, nurse practitioners, nurses, and athletic trainers (n = 126) completed an online survey, including Likert scale and free response question relating to mTBI evaluation, management, and referral practices. MAIN OUTCOMES AND RESULTS: FHPs surveyed reported being confident in their ability to evaluate patients with suspected mTBI, relying most heavily on patient-reported symptoms and physical signs as methods of evaluation. Most FHPs reported making recommendations to compensate for the symptoms experienced following mTBI diagnosis. In contrast, FHPs expressed challenges in the evaluation and management of symptoms associated with mTBI along with limited knowledge of and referrals to AHPs. CONCLUSIONS: Overall, FHPs feel confident in the diagnosis of mTBI but experience assessment and management challenges. AHPs are underutilized on mTBI management teams calling for a need for multidisciplinary collaboration on research, education, and rehabilitation efforts to optimally care for people experiencing mTBI symptoms.

Locked Nucleic Acid Oligonucleotides Facilitate RNA•LNA-RNA Triple-Helix Formation and Reduce MALAT1 Levels.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and multiple endocrine neoplasia-ß (MENß) are two long noncoding RNAs upregulated in multiple cancers, marking these RNAs as therapeutic targets. While traditional small-molecule and antisense-based approaches are effective, we report a locked nucleic acid (LNA)-based approach that targets the MALAT1 and MENß triple helices, structures comprised of a U-rich internal stem-loop and an A-rich tract. Two LNA oligonucleotides resembling the A-rich tract (i.e., A9GCA4) were examined: an LNA (L15) and a phosphorothioate LNA (PS-L15). L15 binds tighter than PS-L15 to the MALAT1 and MENß stem loops, although both L15 and PS-L15 enable RNA•LNA-RNA triple-helix formation. Based on UV thermal denaturation assays, both LNAs selectively stabilize the Hoogsteen interface by 5-13 °C more than the Watson-Crick interface. Furthermore, we show that L15 and PS-L15 displace the A-rich tract from the MALAT1 and MENß stem loop and methyltransferase-like protein 16 (METTL16) from the METTL16-MALAT1 triple-helix complex. Human colorectal carcinoma (HCT116) cells transfected with LNAs have 2-fold less MALAT1 and MENß. This LNA-based approach represents a potential therapeutic strategy for the dual targeting of MALAT1 and MENß.

The landscape of BRCA1 and BRCA2 large rearrangements in an international cohort of over 20 000 ovarian tumors identified using next-generation sequencing.

BACKGROUND: Approximately half of ovarian tumors have defects within the homologous recombination repair pathway. Tumors carrying pathogenic variants (PVs) in BRCA1/BRCA2 are more likely to respond to poly-ADP ribose polymerase (PARP) inhibitor treatment. Large rearrangements (LRs) are a challenging class of variants to identify and characterize in tumor specimens and may therefore be underreported. This study describes the prevalence of pathogenic BRCA1/BRCA2 LRs in ovarian tumors and discusses the importance of their identification using a comprehensive testing strategy. METHODS: Sequencing and LR analyses of BRCA1/BRCA2 were conducted in 20 692 ovarian tumors received between March 18, 2016 and February 14, 2023 for MyChoice CDx testing. MyChoice CDx uses NGS dosage analysis to detect LRs in BRCA1/BRCA2 genes using dense tiling throughout the coding regions and limited flanking regions. RESULTS: Of the 2217 PVs detected, 6.3% (N = 140) were LRs. Overall, 0.67% of tumors analyzed carried a pathogenic LR. The majority of detected LRs were deletions (89.3%), followed by complex LRs (5.7%), duplications (4.3%), and retroelement insertions (0.7%). Notably, 25% of detected LRs encompassed a single or partial single exon. This study identified 84 unique LRs, 2 samples each carried 2 unique LRs in the same gene. We identified 17 LRs that occurred in multiple samples, some of which were specific to certain ancestries. Several cases presented here illustrate the intricacies involved in characterizing LRs, particularly when multiple events occur within the same gene. CONCLUSIONS: Over 6% of PVs detected in the ovarian tumors analyzed were LRs. It is imperative for laboratories to utilize testing methodologies that will accurately detect LRs at a single exon resolution to optimize the identification of patients who may benefit from PARP inhibitor treatment.

Nurses You Should Know: The power of online microlearning to decolonize nursing's history.

Black, Hispanic, Indigenous, Native American, Asian, and Pacific Islander nurses have played a critical role in shaping professional nursing and health care. Despite their contributions, the narrative of nursing's origin has predominantly revolved around the legacy of a single white British nurse, Florence Nightingale. This paper presents the development of the Nurses You Should Know (NYSK) project, which sought to decolonize the narrative surrounding nursing's history and highlight the contributions and experiences of past and present-day nurses of color. The NYSK project utilized an Equity-Centered Community Design process, incorporating microlearning strategies, storytelling, and history to develop a digital library of over 100 stories of nurses of color that capture nursing's rich and complex history. Utilized as a resource within nursing curricula, the NYSK project stands as a testament to the power of history in promoting a more inclusive and equitable future for nursing, offering valuable insights for educators, researchers, and practitioners.

Effectiveness and Safety of Resilient Hyaluronic Acid (RHA) Dermal Fillers for the Correction of Moderate-to-Severe Nasolabial Folds in People of Color: Post Hoc Subgroup Analyses of US Pivotal Clinical Data.

BACKGROUND: People of color (POC) are often underrepresented in clinical studies evaluating the safety and effectiveness of aesthetic products, including hyaluronic acid (HA) fillers, for which there is to date limited clinical data in POC. OBJECTIVES: The aim of this study was to assess the safety and effectiveness of a new line of dynamic resilient HA fillers (RHA; Revance, Nashville, TN) for treating moderate-to-severe nasolabial folds (NLFs) in POC vs non-POC. METHODS: Post hoc subgroup analyses compared the efficacy and safety of POC vs non-POC subjects treated with RHA2, RHA3, or RHA4 for correction of moderate-to-severe NLFs in the pooled per-protocol population (N = 217) in 2 clinical trials. Evaluated population cohorts were classified by Fitzpatrick skin type (FST) (high FST [IV-VI] vs low FST [I-III]) and by subject-reported race (non-White vs White) relative to baseline at 6, 9, 12, and 15 months. RESULTS: POC consistently showed greater improvement in wrinkle severity and higher responder rates compared with non-POC, which reached statistical significance at several measured time points. Global Aesthetic Improvement Scale scores and subject satisfaction ratings were similar for POC and non-POC and remained high throughout the course of the study. Treatment-related adverse event rates were generally lower for high FSTs vs low FSTs, with no reported cases of keloidal scarring. CONCLUSION: The RHA line of dynamic fillers is well tolerated and effective for the correction of moderate-to-severe NLFs in POC and can be confidently used in this important and growing patient population.See the abstract translated into Hindi, Portuguese, Korean, German, Italian, Arabic, Chinese, and Taiwanese online here: https://doi.org/10.1093/asj/sjad251.

Elucidating the Kinetic Mechanism of Human METTL16.

Methyltransferase-like protein 16 (METTL16) is one of four catalytically active, S-adenosylmethionine (SAM)-dependent m6A RNA methyltransferases in humans. Well-known methylation targets of METTL16 are U6 small nuclear RNA (U6 snRNA) and the MAT2A mRNA hairpins; however, METTL16 binds to other RNAs, including the 3' triple helix of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). Herein, we investigated the kinetic mechanism and biochemical properties of METTL16. METTL16 is a monomer in complex with either the MALAT1 triple helix or U6 snRNA and binds to these RNAs with respective dissociation constants of 31 nM and 18 nM, whereas binding to the methylated U6 snRNA product is 1.1 µM. The MALAT1 triple helix, on the other hand, is not methylated by METTL16 under in vitro conditions. Using the U6 snRNA to study methylation steps, preincubation and isotope partitioning assays indicated an ordered-sequential mechanism, whereby METTL16 binds U6 snRNA before SAM. The apparent dissociation constant for the METTL16·U6 snRNA·SAM ternary complex is 126 µM. Steady-state kinetic assays established a kcat of 0.07 min-1, and single-turnover assays established a kchem of 0.56 min-1. Furthermore, the methyltransferase domain of METTL16 methylated U6 snRNA with an apparent dissociation constant of 736 µM and a kchem of 0.42 min-1, suggesting that the missing vertebrate conserved regions weaken the ternary complex but do not induce any rate-limiting conformational rearrangements of the U6 snRNA. This study helps us to better understand the catalytic activity of METTL16 in the context of its biological functions.

Characterization of interactions within the Igα/Igß transmembrane domains of the human B-cell receptor provides insights into receptor assembly.

The B-cell receptor (BCR), a complex comprised of a membrane-associated immunoglobulin and the Igα/ß heterodimer, is one of the most important immune receptors in humans and controls B-cell development, activity, selection, and death. BCR signaling plays key roles in autoimmune diseases and lymphoproliferative disorders, yet, despite the clinical significance of this protein complex, key regions (i.e., the transmembrane domains) have yet to be structurally characterized. The mechanism for BCR signaling also remains unclear and has been variously described by the mutually exclusive cross-linking and dissociation activation models. Common to these models is the significance of local plasma membrane composition, which implies that interactions between BCR transmembrane domains (TMDs) play a role in receptor functionality. Here we used an in vivo assay of TMD oligomerization called GALLEX alongside spectroscopic and computational methods to characterize the structures and interactions of human Igα and Igß TMDs in detergent micelles and natural membranes. We observed weak self-association of the Igß TMD and strong self-association of the Igα TMD, which scanning mutagenesis revealed was entirely stabilized by an E-X10-P motif. We also demonstrated strong heterotypic interactions between the Igα and Igß TMDs both in vitro and in vivo, which scanning mutagenesis and computational models suggest is multiconfigurational but can accommodate distinct interaction sites for self-interactions and heterotypic interactions of the Igα TMD. Taken together, these results demonstrate that the TMDs of the human BCR are sites of strong protein-protein interactions that may direct BCR assembly, endoplasmic reticulum retention, and immune signaling.

National Evaluation of HIV Service Resource Allocation in Tanzania.

Using time-driven activity-based costing (TDABC), we examined resource allocation and costs for HIV services throughout Tanzania at patient and facility levels. This national, cross-sectional analysis of 22 health facilities quantified costs and resources associated with 886 patients receiving care for five HIV services: antiretroviral therapy, prevention of mother-to-child transmission, HIV testing and counseling, voluntary medical male circumcision, and pre-exposure prophylaxis. We also documented total provider-patient interaction time, the cost of services with and without inclusion of consumables, and conducted fixed-effects multivariable regression analyses to examine patient- and facility-level correlates of costs and provider-patient time. Findings showed that resources and costs for HIV care varied significantly throughout Tanzania, including as a function of patient- and facility-level characteristics. While some variation may be preferable (e.g., needier patients received more resources), other areas suggested a lack of equity (e.g., wealthier patients received more provider time) and presented opportunities to optimize care delivery protocols.

Metal-Oxo Cluster Formation Using Ammonium and Sulfate to Differentiate MIV (Th, U, Ce) Chemistries.

Isolating isostructural compounds of tetravalent metals MIV (Zr, Hf, Ce, Th, U, Pu, Np) improves our understanding of metal hydrolysis and coordination behavior across the periodic table. These metals form polynuclear clusters typified by the hexamer [MIV6O4(OH)4]12+. Exploiting the ammonium MIV-sulfate (CeIV, ThIV, and UIV) phase space targeting rapid crystallization, we isolate the common hexamer [MIV6(OH)4(O)4]12+ but with different numbers of capping sulfates and water molecules for CeIV, ThIV, and UIV. These phases allowed a direct comparison of bonding trends across the series. Upon cocrystallization with the hexamers, higher complex structures can be identified. Thorium features assemblies with monomer-linked hexamer chains. Uranium features assemblies with sulfate-bridged hexamers and the supramolecular assembly of 14 hexamers into the U84, [U6(OH)4(O)4)14(SO4)120(H2O)42]72-. Last, cerium showcases the isolation from monomers to the Ce62, [Ce62(OH)30(O)58(SO4)71(H2O)33.25]41-. Furthermore, small-angle X-ray scattering (room temperature) shows ammonium-induced cluster assembly for CeIV but minimal reactivity for UIV and ThIV. In this study, because the phases crystallized at elevated temperature demonstrates favorable cluster assembly, these solution phase results were surprising and suggest some other characteristics such as Ce's facile redox behavior, contributes to its solution-phase speciation.

Bridging the Gap: Sustained Treatment Effect of Glabellar Lines With Twice-A-Year Treatment With DaxibotulinumtoxinA.

BACKGROUND: To achieve natural-looking outcomes when treating dynamic lines with botulinum toxin (BoNT), retreatment must be timed such that the patient maintains a relatively constant aesthetic outcome. Although first-generation BoNT products require retreatment with 3- to 4-month frequency to avoid discontinuous correction, the average patient returns for treatment every 6 months, when these toxins have generally fully worn off. OBJECTIVE: To discuss the number of days a typical patient treated with daxibotulinumtoxinA for injection (DAXI) or legacy BoNT products will spend undertreated or uncorrected in a given calendar year. MATERIALS AND METHODS: Median time for maintaining glabellar lines in the "none" or "mild" severity range was compared for approved doses of onabotulinumtoxinA (ONA; 120 days) and DAXI (168 days). RESULTS: The average patient treated with 40U of DAXI every 6 months can expect to be uncorrected (with "moderate" or "severe" glabellar lines) for 14.5 days between visits compared with 61.5 days for 20U of ONA. CONCLUSION: An extended duration BoNT product can be expected to create greater consistency in aesthetic outcome and minimize the discontinuous correction commonly seen with first-generation BoNT products for patients treated twice a year, without requiring a change in patient behavior regarding visit frequency.

Adult Cardiac Surgery-Associated Acute Kidney Injury: Joint Consensus Report.

OBJECTIVES: Acute kidney injury (AKI) is increasingly recognized as a source of poor patient outcomes after cardiac surgery. The purpose of the present report is to provide perioperative teams with expert recommendations specific to cardiac surgery-associated AKI (CSA-AKI). METHODS: This report and consensus recommendations were developed during a joint, in-person, multidisciplinary conference with the Perioperative Quality Initiative and the Enhanced Recovery After Surgery Cardiac Society. Multinational practitioners with diverse expertise in all aspects of cardiac surgical perioperative care, including clinical backgrounds in anesthesiology, surgery and nursing, met from October 20 to 22, 2021, in Sacramento, California, and used a modified Delphi process and a comprehensive review of evidence to formulate recommendations. The quality of evidence and strength of each recommendation were established using the Grading of Recommendations Assessment, Development, and Evaluation methodology. A majority vote endorsed recommendations. RESULTS: Based on available evidence and group consensus, a total of 13 recommendations were formulated (4 for the preoperative phase, 4 for the intraoperative phase, and 5 for the postoperative phase), and are reported here. CONCLUSIONS: Because there are no reliable or effective treatment options for CSA-AKI, evidence-based practices that highlight prevention and early detection are paramount. Cardiac surgery-associated AKI incidence may be mitigated and postsurgical outcomes improved by focusing additional attention on presurgical kidney health status; implementing a specific cardiopulmonary bypass bundle; using strategies to maintain intravascular euvolemia; leveraging advanced tools such as the electronic medical record, point-of-care ultrasound, and biomarker testing; and using patient-specific, goal-directed therapy to prioritize oxygen delivery and end-organ perfusion over static physiologic metrics.