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Abnormal cardiac metabolism precedes and contributes to structural changes in heart failure. Low-level tragus stimulation (LLTS) can attenuate structural remodeling in heart failure with preserved ejection fraction (HFpEF). The role of LLTS on cardiac metabolism is not known. Dahl salt-sensitive rats of 7 weeks of age were randomized into three groups: low salt (0.3% NaCl) diet (control group; n = 6), high salt diet (8% NaCl) with either LLTS (active group; n = 8), or sham stimulation (sham group; n = 5). Both active and sham groups received the high salt diet for 10 weeks with active LLTS or sham stimulation (20 Hz, 2 mA, 0.2 ms) for 30 min daily for the last 4 weeks. At the endpoint, left ventricular tissue was used for RNA sequencing and transcriptomic analysis. The Ingenuity Pathway Analysis tool (IPA) was used to identify canonical metabolic pathways and upstream regulators. Principal component analysis demonstrated overlapping expression of important metabolic genes between the LLTS, and control groups compared to the sham group. Canonical metabolic pathway analysis showed downregulation of the oxidative phosphorylation (Z-score: -4.707, control vs. sham) in HFpEF and LLTS improved the oxidative phosphorylation (Z-score = -2.309, active vs. sham). HFpEF was associated with the abnormalities of metabolic upstream regulators, including PPARGC1α, insulin receptor signaling, PPARα, PPARδ, PPARGC1β, the fatty acid transporter SLC27A2 , and lysine-specific demethylase 5A (KDM5A). LLTS attenuated abnormal insulin receptor and KDM5A signaling. HFpEF is associated with abnormal cardiac metabolism. LLTS, by modulating the functioning of crucial upstream regulators, improves cardiac metabolism and mitochondrial oxidative phosphorylation.

Background: Low-level transcutaneous stimulation of the auricular branch of the vagus nerve at the tragus is antiarrhythmic and anti-inflammatory in animals and humans. Preliminary studies show that transcutaneous vagus nerve stimulation (tVNS) is beneficial in animal models of postural tachycardia syndrome (POTS)., Objectives: In this study the authors conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of tVNS on POTS over a 2-month period relative to sham stimulation., Methods: tVNS (20 Hz, 1 mA below discomfort threshold) was delivered using an ear clip attached to either the tragus (active; n = 12) or the ear lobe (sham; n = 14) for 1 hour daily over a 2-month period. Postural tachycardia was assessed during the baseline and 2-month visit. Heart rate variability based on 5-minute electrocardiogram, serum cytokines, and antiautonomic autoantibodies were measured at the respective time points., Results: Mean age was 34 ± 11 years (100% female; 81% Caucasian). Adherence to daily stimulation was 83% in the active arm and 86% in the sham arm (P > 0.05). Postural tachycardia was significantly less in the active arm compared with the sham arm at 2 months (mean postural increase in heart rate 17.6 ± 9.9 beats/min vs 31.7 ± 14.4 beats/min; P = 0.01). Antiadrenergic autoantibodies and inflammatory cytokines were lower in the active arm compared with the sham arm at 2 months (P < 0.05). Heart rate variability was better in the active arm. No device-related side effects were observed., Conclusions: Our results support the emerging paradigm of noninvasive neuromodulation to treat POTS. Mechanistically, this effect appears to be related to reduction of antiautonomic autoantibodies and inflammatory cytokines, and improvement in autonomic tone. Further studies are warranted. (Autoimmune Basis for Postural Tachycardia Syndrome; NCT05043051)., Competing Interests: Funding Support and Author Disclosures This work was supported by National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute R01HL161008 to Dr Stavrakis and R01HL128393 to Dr Yu, NIH/National Institute of General Medical Sciences 1U54GM10493, and individual donations from Francie Fitzgerald and family through the OU Foundation Fund. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Postural orthostatic tachycardia syndrome (POTS) is a chronic debilitating condition of orthostatic intolerance, predominantly affecting young females. Other than postural tachycardia, symptoms of POTS include a spectrum of non-cardiac, systemic and neuropsychiatric features. Despite the availability of widespread pharmacological and non-pharmacological therapeutic options, the management of POTS remains challenging. Exaggerated parasympathetic withdrawal and sympathetic overdrive during postural stress are principal mechanisms of postural tachycardia in POTS. Non-invasive, transcutaneous, vagus nerve stimulation (tVNS) is known to restore sympathovagal balance and is emerging as a novel therapeutic strategy in cardiovascular conditions including arrhythmias and heart failure. Furthermore, tVNS also exerts immunomodulatory and anti-inflammatory effects. This review explores the effects of tVNS on the pathophysiology of POTS and its potential as an alternative non-pharmacological option in this condition., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © The Author(s), 2023. Published by Radcliffe Group Ltd.)

The impacts of large terrestrial volcanic eruptions are apparent from satellite monitoring and direct observations. However, more than three quarters of all volcanic outputs worldwide lie submerged beneath the ocean, and the risks they pose to people, infrastructure, and benthic ecosystems remain poorly understood due to inaccessibility and a lack of detailed observations before and after eruptions. Here, comparing data acquired between 2015 - 2017 and 3 months after the January 2022 eruption of Hunga Volcano, we document the far-reaching and diverse impacts of one of the most explosive volcanic eruptions ever recorded. Almost 10 km 3 of seafloor material was removed during the eruption, most of which we conclude was redeposited within 20 km of the caldera by long run-out seafloor density currents. These powerful currents damaged seafloor cables over a length of >100 km, reshaped the seafloor, and caused mass-mortality of seafloor life. Biological (mega-epifaunal invertebrate) seafloor communities only survived the eruption where local topography provided a physical barrier to density currents (e.g., on nearby seamounts). While the longer-term consequences of such a large eruption for human, ecological and climatic systems are emerging, we expect that these previously-undocumented refugia will play a key role in longer-term ecosystem recovery., (© 2023. The Author(s).)

Volcanic eruptions on land create hot and fast pyroclastic density currents, triggering tsunamis or surges that travel over water where they reach the ocean. However, no field study has documented what happens when large volumes of erupted volcanic material are instead delivered directly into the ocean. We show how the rapid emplacement of large volumes of erupted material onto steep submerged slopes triggered extremely fast (122 kilometers per hour) and long-runout (>100 kilometers) seafloor currents. These density currents were faster than those triggered by earthquakes, floods, or storms, and they broke seafloor cables, cutting off a nation from the rest of the world. The deep scours excavated by these currents are similar to those around many submerged volcanoes, providing evidence of large eruptions at other sites worldwide.

Viruses can affect coral health by infecting their symbiotic dinoflagellate partners (Symbiodiniaceae). Yet, viral dynamics in coral colonies exposed to environmental stress have not been studied at the reef scale, particularly within individual viral lineages. We sequenced the viral major capsid protein (mcp) gene of positive-sense single-stranded RNA viruses known to infect symbiotic dinoflagellates ('dinoRNAVs') to analyze their dynamics in the reef-building coral, Porites lobata. We repeatedly sampled 54 colonies harboring Cladocopium C15 dinoflagellates, across three environmentally distinct reef zones (fringing reef, back reef, and forereef) around the island of Moorea, French Polynesia over a 3-year period and spanning a reef-wide thermal stress event. By the end of the sampling period, 28% (5/18) of corals in the fringing reef experienced partial mortality versus 78% (14/18) of corals in the forereef. Over 90% (50/54) of colonies had detectable dinoRNAV infections. Reef zone influenced the composition and richness of viral mcp amino acid types ('aminotypes'), with the fringing reef containing the highest aminotype richness. The reef-wide thermal stress event significantly increased aminotype dispersion, and this pattern was strongest in the colonies that experienced partial mortality. These findings demonstrate that dinoRNAV infections respond to environmental fluctuations experienced in situ on reefs. Further, viral productivity will likely increase as ocean temperatures continue to rise, potentially impacting the foundational symbiosis underpinning coral reef ecosystems., (© 2023. The Author(s).)

Methane seeps are highly abundant marine habitats that contribute sources of chemosynthetic primary production to marine ecosystems. Seeps also factor into the global budget of methane, a potent greenhouse gas. Because of these factors, methane seeps influence not only local ocean ecology, but also biogeochemical cycles on a greater scale. Methane seeps host specialized microbial communities that vary significantly based on geography, seep gross morphology, biogeochemistry, and a diversity of other ecological factors including cross-domain species interactions. In this study, we collected sediment cores from six seep and non-seep locations from Grays and Quinault Canyons (46-47°N) off Washington State, USA, as well as one non-seep site off the coast of Oregon, USA (45°N) to quantify the scale of seep influence on biodiversity within marine habitats. These samples were profiled using 16S rRNA gene sequencing. Predicted gene functions were generated using the program PICRUSt2, and the community composition and predicted functions were compared among samples. The microbial communities at seeps varied by seep morphology and habitat, whereas the microbial communities at non-seep sites varied by water depth. Microbial community composition and predicted gene function clearly transitioned from on-seep to off-seep in samples collected from transects moving away from seeps, with a clear ecotone and high diversity where methane-fueled habitats transition into the non-seep deep sea. Our work demonstrates the microbial and metabolic sphere of influence that extends outwards from methane seep habitats., Competing Interests: The authors declare there are no competing interests., (©2023 Cummings et al.)

Ocean manipulation to mitigate climate change may harm deep-sea ecosystems.

Background: A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction (HFpEF). Low-level transcutaneous vagus nerve stimulation (LLTS) suppresses inflammation in animals and humans, mediated by an α7nAchR (alpha7 nicotinic acetylcholine receptor)-dependent pathway. We examined the effects of LLTS on cardiac function, inflammation, and fibrosis in the presence of α7nAchR pharmacological blockade in a rat model of HFpEF., Methods: Dahl salt-sensitive rats at 7 weeks of age were treated with high-salt diet for 6 weeks to induce HFpEF, followed by 4 weeks of (1) LLTS, (2) LLTS with the α7nAchR blocker methyllycaconitine, (3) sham, and (4) olmesartan. Blood pressure, cardiac function by echocardiography, heart rate variability, and serum cytokines were measured at 13 and 17 weeks of age. Cardiac fibrosis, inflammatory cell infiltration, and gene expression were determined at 17 weeks., Results: LLTS attenuated the increase in blood pressure; improved cardiac function; decreased inflammatory cytokines, macrophage infiltration, and fibrosis; and improved survival compared with other groups. Methyllycaconitine attenuated these effects, whereas olmesartan did not improve cardiac function or fibrosis despite maintaining similar blood pressure as LLTS. Heart rate variability was similarly improved in the LLTS and LLTS plus methyllycaconitine groups but remained low in the other groups. LLTS reversed the dysregulated inflammatory signaling pathways in HFpEF hearts., Conclusions: Neuromodulation with LLTS improved cardiac function in a rat model of HFpEF through its anti-inflammatory and antifibrotic effects. These results provide the basis for further clinical trials in humans.

With the COVID-19 pandemic came what media has deemed the "port congestion pandemic". Intensified by the pandemic, the commonplace anchoring of high-tonnage ships causes a substantial geomorphologial footprint on the seabed outside marine ports globally, but isn't yet quantified. We present the first characterisation of the footprint and extent of anchoring in a low congestion port in New Zealand-Aotearoa, demonstrating that high-tonnage ship anchors excavate the seabed by up to 80 cm, with the impacts preserved for at least 4 years. The calcuated volume of sediment displaced by one high-tonnage ship (> 9000 Gross Tonnage) on anchor can reach 2800 m 3 . Scaled-up globally, this provides the first estimates of the footprint of anchoring to the coastal seabed, worldwide. Seafloor damage due to anchoring has far-reaching implications for already stressed marine ecosystems and carbon cycling. As seaborne trade is projected to quadruple by 2050, the poorly constrained impacts of anchoring must be considered to avoid irreversible damage to marine habitats., (© 2022. The Author(s).)

Black adolescent girls and young women (AGYW) are disproportionately affected by HIV in the southern U.S.; however, PrEP prescriptions to Black AGYW remain scarce. We conducted in-depth interviews (IDIs) with Black AGYW ages 14-24 in Alabama to explore opportunities for and barriers to sexual health care including PrEP prescription. Twelve AGYW participated in IDIs with median age 20 (range 19-24). All reported condomless sex, 1-3 sexual partners in the past 3 months, and 6 reported prior STI. Themes included: 1) Stigma related to sex contributes to inadequate discussions with educators, healthcare providers, and parents about sexual health; 2) Intersecting stigmas around race and gender impact Black women's care-seeking behavior; 3) Many AGYW are aware of PrEP but don't perceive it as an option for them. Multifaceted interventions utilizing the perspectives, voices, and experiences of Black cisgender AGYW are needed to curb the HIV epidemic in Alabama and the U.S. South.

Climate change is driving dramatic variability in sea ice dynamics, a key driver in polar marine ecosystems. Projected changes in Antarctica suggest that regional warming will force dramatic shifts in sea ice thickness and persistence, altering sea ice-associated primary production and deposition to the seafloor. To improve our understanding of the impacts of sea ice change on benthic ecosystems, we directly compared the benthic microbial communities underlying first-year sea ice (FYI) and multi-year sea ice (MYI). Using two tractable coastal habitats in McMurdo Sound, Antarctica, where FYI (Cape Evans) and MYI (New Harbour) prevail, we show that the structure and composition of the benthic microbial communities reflect the legacy of sea ice dynamics. At Cape Evans, an enrichment of known heterotrophic algal polysaccharide degrading taxa (e.g., Flavobacteriaceae , unclassified Gammaproteobacteria , and Rubritaleaceae ) and sulfate-reducing bacteria (e.g., Desulfocapsaceae ) correlated with comparatively higher chlorophyll a (14.2±0.8μgg -1 ) and total organic carbon content (0.33%±0.04), reflecting increased productivity and seafloor deposition beneath FYI. Conversely, at New Harbour, an enrichment of known archaeal (e.g., Nitrosopumilaceae ) and bacterial (e.g., Woeseiaceae and Nitrospiraceae ) chemoautotrophs was common in sediments with considerably lower chlorophyll a (1.0±0.24μgg -1 ) and total organic carbon content (0.17%±0.01), reflecting restricted productivity beneath MYI. We also report evidence of a submarine discharge of sub-permafrost brine from Taylor Valley into New Harbour. By comparing our two study sites, we show that under current climate-warming scenarios, changes to sea ice productivity and seafloor deposition are likely to initiate major shifts in benthic microbial communities, with heterotrophic organic matter degradation processes becoming increasingly important. This study provides the first assessment of how legacy sea ice conditions influence benthic microbial communities in Antarctica, contributing insight into sea ice-benthic coupling and ecosystem functioning in a polar environment., 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 © 2021 Currie, Marshall, Lohrer, Cummings, Seabrook and Cary.)

Antarctica is estimated to contain as much as a quarter of earth's marine methane, however we have not discovered an active Antarctic methane seep limiting our understanding of the methane cycle. In 2011, an expansive (70 m × 1 m) microbial mat formed at 10 m water depth in the Ross Sea, Antarctica which we identify here to be a high latitude hydrogen sulfide and methane seep. Through 16S rRNA gene analysis on samples collected 1 year and 5 years after the methane seep formed, we identify the taxa involved in the Antarctic methane cycle and quantify the response rate of the microbial community to a novel input of methane. One year after the seep formed, ANaerobic MEthane oxidizing archaea (ANME), the dominant sink of methane globally, were absent. Five years later, ANME were found to make up to 4% of the microbial community, however the dominant member of this group observed (ANME-1) were unexpected considering the cold temperature (-1.8°C) and high sulfate concentrations (greater than 24 mM) present at this site. Additionally, the microbial community had not yet formed a sufficient filter to mitigate the release of methane from the sediment; methane flux from the sediment was still significant at 3.1 mmol CH 4 m -2 d -1 . We hypothesize that this 5 year time point represents an early successional stage of the microbiota in response to methane input. This study provides the first report of the evolution of a seep system from a non-seep environment, and reveals that the rate of microbial succession may have an unrealized impact on greenhouse gas emission from marine methane reservoirs.

Objectives: The Aboriginal Children's Health and Well-Being Measure© (ACHWM) was developed to assess health from the perspectives of Aboriginal children. The purpose of this paper is to document the screening process, embedded within the ACHWM, and assess its effectiveness., Methods: The ACHWM was implemented in 2014/2015 with children 8 to 18 years of age living on the Wiikwemkoong Unceded Territory. Survey responses were screened to identify potential risk, using an automated algorithm run on computer tablets. Local mental health workers conducted brief mental health assessments to identify and support children at-risk. Data were analyzed to estimate effectiveness of this screening process., Results: A total of 293 children completed the ACHWM. The screening tool identified 35% with potential risk. Mental health workers confirmed 18% of all participants as being at-risk, and all were referred for support. The sensitivity of the tool was 75% while specificity was 79%. Improvements to the screening algorithm resulted in a specificity of 97% and negative predictive value of 95%, with no loss of sensitivity., Conclusion: Responsible population health surveys require a process to recognize and respond to answers indicative of health risks. This paper provides an example of a screening and triage process that enabled our survey team to screen responses in real time, respond to potential risk immediately, and connect participants to local support services. This process proved essential to conducting an ethical survey. The high specificity and negative predictive value make it an effective triage tool that is particularly valuable in Aboriginal communities and with higher-risk populations.

The heterodimeric ligand-binding region of the Bovicola ovis ecdysone receptor has been crystallized either in the presence of an ecdysteroid or a synthetic methylene lactam insecticide. Two X-ray crystallographic structures, determined at 2.7 Å resolution, show that the ligand-binding domains of both subunits of this receptor, like those of other nuclear receptors, can display significant conformational flexibility. Thermal melt experiments show that while ponasterone A stabilizes the higher order structure of the heterodimer in solution, the methylene lactam destabilizes it. The conformations of the EcR and USP subunits observed in the structure crystallized in the presence of the methylene lactam have not been seen previously in any ecdysone receptor structure and represent a new level of conformational flexibility for these important receptors. Interestingly, the new USP conformation presents an open, unoccupied ligand-binding pocket.

Escherichia coli possesses two acyl ornithine aminotransferases, one catabolic (AstC) and the other anabolic (ArgD), that participate in L-arginine metabolism. Although only 58% identical, the enzymes have been shown to be functionally interchangeable. Here we have purified AstC and have obtained X-ray crystal structures of apo and holo-AstC and of the enzyme complexed with its physiological substrate, succinylornithine. We compare the structures obtained in this study with those of ArgD from Salmonella typhimurium obtained elsewhere, finding several notable differences. Docking studies were used to explore the docking modes of several substrates (ornithine, succinylornithine and acetylornithine) and the co-substrate glutamate/α-ketogluterate. The docking studies support our observations that AstC has a strong preference for acylated ornithine species over ornithine itself, and suggest that the increase in specificity associated with acylation is caused by steric and desolvation effects rather than specific interactions between the substrate and enzyme.

Since the early 1990s, Current Procedure Terminology (CPT) has been the gold standard for billing for medical services. After reviewing the historical context of CPT coding, this article presents the coding methodology, discussion of specialty codes (psychiatric and other specialty codes of potential use to child and adolescent psychiatrists), and the evaluation and management (E/M) codes. Various coding options for common clinical encounters are also presented.

Purpose: Pseudophakic corneal edema is the principal indication for penetrating keratoplasty in the United States. Currently, three techniques of intraocular lens (IOL) fixation during penetrating keratoplasty for this condition are commonly used--flexible anterior chamber IOL (AC IOL) implantation, iris suture fixation of a posterior chamber IOL (PC IOL), and transscleral suture fixation of a PC IOL. This study represents the first prospective, randomized comparison of these three techniques., Methods: One hundred seventy-six consecutive patients with pseudophakic corneal edema who underwent penetrating keratoplasty with IOL exchange were randomized to one of the three implantation techniques. Standardized evaluations were performed at baseline and at 6, 12, and 18 months postoperatively. Life-table analysis provided cumulative risk estimates for specific complications., Results: Randomization produced comparable groups at baseline. The cumulative risk of macular edema was significantly less for the iris fixation cohort than for either the AC IOL or scleral fixation group. A complications index was constructed based on the major adverse outcomes of glaucoma escalation, cystoid macular edema, IOL dislocation, and graft failure. A significantly lower risk of complication was found for iris compared with scleral fixation of PC IOLs., Conclusion: The authors conclude that transscleral fixation of the PC IOL at the time of penetrating keratoplasty for pseudophakic corneal edema is associated with a greater risk of adverse outcome than iris fixation of a PC IOL.