Late-Onset Hyponatremia in Premature Infants.

Late-onset hyponatremia (LOH) frequently affects premature infants 2 or more weeks of age due to inadequate sodium intake and excessive kidney loss. Late-onset hyponatremia typically occurs in infants who are physiologically stable and is defined as serum sodium of 132 mEq/L or less or between 133 and 135 mEq/L if receiving sodium supplementation. Recent evidence suggests that spot urine sodium levels may improve the recognition of LOH, as low levels of excreted urine reflect a total body sodium deficit and negative balance. Untreated LOH may result in poor somatic growth, neurodevelopmental delay, higher incidence of bronchopulmonary dysplasia, and more severe retinopathy of prematurity. The primary prevention of LOH is to maintain serum sodium between 135 and 145 mEq/L; however, there are currently no formal protocols guiding sodium supplementation. The purpose of this article is to present on overview of LOH pathophysiology and its effect on somatic growth, neurodevelopment outcomes, and other related sequelae. We further discuss general management strategies and describe a protocol for sodium supplementation that is presently undergoing an evaluation for effectiveness.

Renal Oxygenation (rSO 2 ) Population Parameter Estimates in Premature Infants Routinely Monitored With Near-Infrared Spectroscopy.

BACKGROUND: Currently, reference ranges for renal oxygenation measured by near-infrared spectroscopy (NIRS) in preterm infants beyond the first days of life are lacking, especially those born prior to 29 weeks' gestation. Population estimates of renal oxygenation (rSO 2 ) levels among preterm infants over time have yet to be established, leading to reluctance in clinical application. PURPOSE: To characterize the distribution and estimate population parameters for renal oxygenation measured by NIRS during the first 14 days of life among preterm infants. METHODS: We prospectively observed rSO 2 trends of 37 infants before 34 weeks' gestation and 1800-g or less birth weight for the first 14 days of life. Analyses included distribution fit tests, ordinary least squares (OLS) regression, and t tests. RESULTS: Average daily rSO 2 variation steadily increased with 42% difference through the first 14 days of life. For all infants, renal rSO 2 means peaked during the first 3 days of life and plateaued around 7 days. Daily rSO 2 slopes were significantly lower among males and infants 29 weeks' or less gestation. IMPLICATIONS FOR PRACTICE: Renal rSO 2 during the first 14 days of life reflects normal extrauterine transition reaching stabilization around 7 days of life. Gestational age, birth weight, and gender may predict the early trajectory of rSO 2 patterns. Population estimates provide parameters for renal rSO 2 that may indicate early-onset tissue hypoxia when acute or significant drops from baseline occur. IMPLICATIONS FOR RESEARCH: We present a framework to guide future research using renal NIRS technology in preterm infants to determine deviations from expected trends that may precede renal injury.

Selective small-molecule inhibition of an RNA structural element.

Riboswitches are non-coding RNA structures located in messenger RNAs that bind endogenous ligands, such as a specific metabolite or ion, to regulate gene expression. As such, riboswitches serve as a novel, yet largely unexploited, class of emerging drug targets. Demonstrating this potential, however, has proven difficult and is restricted to structurally similar antimetabolites and semi-synthetic analogues of their cognate ligand, thus greatly restricting the chemical space and selectivity sought for such inhibitors. Here we report the discovery and characterization of ribocil, a highly selective chemical modulator of bacterial riboflavin riboswitches, which was identified in a phenotypic screen and acts as a structurally distinct synthetic mimic of the natural ligand, flavin mononucleotide, to repress riboswitch-mediated ribB gene expression and inhibit bacterial cell growth. Our findings indicate that non-coding RNA structural elements may be more broadly targeted by synthetic small molecules than previously expected.

Inhibitor of intramembrane protease RseP blocks the σE response causing lethal accumulation of unfolded outer membrane proteins.

The outer membrane (OM) of Gram-negative bacteria forms a robust permeability barrier that blocks entry of toxins and antibiotics. Most OM proteins (OMPs) assume a ß-barrel fold, and some form aqueous channels for nutrient uptake and efflux of intracellular toxins. The Bam machine catalyzes rapid folding and assembly of OMPs. Fidelity of OMP biogenesis is monitored by the σE stress response. When OMP folding defects arise, the proteases DegS and RseP act sequentially to liberate σE into the cytosol, enabling it to activate transcription of the stress regulon. Here, we identify batimastat as a selective inhibitor of RseP that causes a lethal decrease in σE activity in Escherichia coli, and we further identify RseP mutants that are insensitive to inhibition and confer resistance. Remarkably, batimastat treatment allows the capture of elusive intermediates in the OMP biogenesis pathway and offers opportunities to better understand the underlying basis for σE essentiality.

Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets.

Here we describe a chemical biology strategy performed in Staphylococcus aureus and Staphylococcus epidermidis to identify MnaA, a 2-epimerase that we demonstrate interconverts UDP-GlcNAc and UDP-ManNAc to modulate substrate levels of TarO and TarA wall teichoic acid (WTA) biosynthesis enzymes. Genetic inactivation of mnaA results in complete loss of WTA and dramatic in vitro ß-lactam hypersensitivity in methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE). Likewise, the ß-lactam antibiotic imipenem exhibits restored bactericidal activity against mnaA mutants in vitro and concomitant efficacy against 2-epimerase defective strains in a mouse thigh model of MRSA and MRSE infection. Interestingly, whereas MnaA serves as the sole 2-epimerase required for WTA biosynthesis in S. epidermidis, MnaA and Cap5P provide compensatory WTA functional roles in S. aureus. We also demonstrate that MnaA and other enzymes of WTA biosynthesis are required for biofilm formation in MRSA and MRSE. We further determine the 1.9Å crystal structure of S. aureus MnaA and identify critical residues for enzymatic dimerization, stability, and substrate binding. Finally, the natural product antibiotic tunicamycin is shown to physically bind MnaA and Cap5P and inhibit 2-epimerase activity, demonstrating that it inhibits a previously unanticipated step in WTA biosynthesis. In summary, MnaA serves as a new Staphylococcal antibiotic target with cognate inhibitors predicted to possess dual therapeutic benefit: as combination agents to restore ß-lactam efficacy against MRSA and MRSE and as non-bioactive prophylactic agents to prevent Staphylococcal biofilm formation.

Fire severity effects on soil carbon and nutrients and microbial processes in a Siberian larch forest.

Fire frequency and severity are increasing in tundra and boreal regions as climate warms, which can directly affect climate feedbacks by increasing carbon (C) emissions from combustion of the large soil C pool and indirectly via changes in vegetation, permafrost thaw, hydrology, and nutrient availability. To better understand the direct and indirect effects of changing fire regimes in northern ecosystems, we examined how differences in soil burn severity (i.e., extent of soil organic matter combustion) affect soil C, nitrogen (N), and phosphorus (P) availability and microbial processes over time. We created experimental burns of three fire severities (low, moderate, and high) in a larch forest in the northeastern Siberian Arctic and analyzed soils at 1, 8 days, and 1 year postfire. Labile dissolved C and N increased with increasing soil burn severity immediately (1 day) postfire by up to an order of magnitude, but declined significantly 1 week later; both variables were comparable or lower than unburned soils by 1 year postfire. Soil burn severity had no effect on P in the organic layer, but P increased with increasing severity in mineral soil horizons. Most extracellular enzyme activities decreased by up to 70% with increasing soil burn severity. Increasing soil burn severity reduced soil respiration 1 year postfire by 50%. However, increasing soil burn severity increased net N mineralization rates 1 year postfire, which were 10-fold higher in the highest burn severity. While fires of high severity consumed approximately five times more soil C than those of low severity, soil C pools will also be driven by indirect effects of fire on soil processes. Our data suggest that despite an initial increase in labile C and nutrients with soil burn severity, soil respiration and extracellular activities related to the turnover of organic matter were greatly reduced, which may mitigate future C losses following fire.

Neutralization of Pathogenic Fungi with Small-Molecule Immunotherapeutics.

Systemic fungal infections represent an important public health concern, and new antifungal agents are highly desirable. Herein, we describe the design, synthesis, and biological evaluation of a novel class of antifungal compounds called antibody-recruiting molecules targeting fungi (ARM-Fs). Our approach relies on the use of non-peptidic small molecules, which selectively bind fungal cells and recruit endogenous antibodies to their surfaces, resulting in immune-mediated clearance. Using the opportunistic fungal pathogen Candida albicans as a model, we identified a highly specific bifunctional molecule able to mediate the engulfment and phagocytosis of C. albicans cells by human immune cells in biologically relevant functional assays. This work represents a novel therapeutic approach to treating fungal illness with significant potential to complement and/or combine with existing treatment strategies.

Discovery of potent wall teichoic acid early stage inhibitors.

The widespread emergence of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically eroded the efficacy of current ß-lactam antibiotics and created an urgent need for novel treatment options. Using an S. aureus phenotypic screening strategy, we have identified small molecule early stage wall teichoic acid (WTA) pathway-specific inhibitors predicted to be chemically synergistic with ß-lactams. These previously disclosed inhibitors, termed tarocins, demonstrate by genetic and biochemical means inhibition of TarO, the first step in WTA biosynthesis. Tarocins demonstrate potent bactericidal synergy in combination with broad spectrum ß-lactam antibiotics across diverse clinical isolates of methicillin-resistant Staphylococci. The synthesis and structure-activity relationships (SAR) of a tarocin series will be detailed. Tarocins and other WTA inhibitors may provide a rational strategy to develop Gram-positive bactericidal ß-lactam combination agents active against methicillin-resistant Staphylococci.

Evidence for key enzymatic controls on metabolism of Arctic river organic matter.

Permafrost thaw in the Arctic driven by climate change is mobilizing ancient terrigenous organic carbon (OC) into fluvial networks. Understanding the controls on metabolism of this OC is imperative for assessing its role with respect to climate feedbacks. In this study, we examined the effect of inorganic nutrient supply and dissolved organic matter (DOM) composition on aquatic extracellular enzyme activities (EEAs) in waters draining the Kolyma River Basin (Siberia), including permafrost-derived OC. Reducing the phenolic content of the DOM pool resulted in dramatic increases in hydrolase EEAs (e.g., phosphatase activity increased >28-fold) supporting the idea that high concentrations of polyphenolic compounds in DOM (e.g., plant structural tissues) inhibit enzyme synthesis or activity, limiting OC degradation. EEAs were significantly more responsive to inorganic nutrient additions only after phenolic inhibition was experimentally removed. In controlled mixtures of modern OC and thawed permafrost endmember OC sources, respiration rates per unit dissolved OC were 1.3-1.6 times higher in waters containing ancient carbon, suggesting that permafrost-derived OC was more available for microbial mineralization. In addition, waters containing ancient permafrost-derived OC supported elevated phosphatase and glucosidase activities. Based on these combined results, we propose that both composition and nutrient availability regulate DOM metabolism in Arctic aquatic ecosystems. Our empirical findings are incorporated into a mechanistic conceptual model highlighting two key enzymatic processes in the mineralization of riverine OM: (i) the role of phenol oxidase activity in reducing inhibitory phenolic compounds and (ii) the role of phosphatase in mobilizing organic P. Permafrost-derived DOM degradation was less constrained by this initial 'phenolic-OM' inhibition; thus, informing reports of high biological availability of ancient, permafrost-derived DOM with clear ramifications for its metabolism in fluvial networks and feedbacks to climate.

Rapid IDH1-R132 genotyping panel utilizing locked nucleic acid loop-mediated isothermal amplification.

While the detection of single-nucleotide variants (SNVs) is important for evaluating human health and disease, most genotyping methods require a nucleic acid extraction step and lengthy analytical times. Here, we present a protocol which utilizes the integration of locked nucleic acids (LNAs) into self-annealing loop primers for the allelic discrimination of five isocitrate dehydrogenase 1 R132 (IDH1-R132) variants using loop-mediated isothermal amplification (LAMP). This genotyping panel was initially evaluated using purified synthetic DNA to show proof of specific SNV discrimination. Additional evaluation using glioma tumor lysates with known IDH1-R132 mutational status demonstrated specificity in approximately 35 min without the need for a nucleic acid extraction purification step. This LNA-LAMP-based genotyping assay can detect single base differences in purified nucleic acids or tissue homogenates, including instances where the variant of interest is present in an excess of background wild-type DNA. The pH-based colorimetric indicator of LNA-LAMP facilitates convenient visual interpretation of reactions, and we demonstrate successful translation to an end-point format using absorbance ratio, allowing for an alternative and objective approach for differentiating between positive and negative reactions. Importantly, the LNA-LAMP genotyping panel is highly reproducible, with no false-positive or false-negative results observed.

The American Association for Thoracic Surgery (AATS) 2023 Expert Consensus Document: Recommendation for the care of children with trisomy 13 or trisomy 18 and a congenital heart defect.

OBJECTIVES: Recommendations for surgical repair of a congenital heart defect in children with trisomy 13 or trisomy 18 remain controversial, are subject to biases, and are largely unsupported with limited empirical data. This has created significant distrust and uncertainty among parents and could potentially lead to suboptimal care for patients. A working group, representing several clinical specialties involved with the care of these children, developed recommendations to assist in the decision-making process for congenital heart defect care in this population. The goal of these recommendations is to provide families and their health care teams with a framework for clinical decision making based on the literature and expert opinions. METHODS: This project was performed under the auspices of the AATS Congenital Heart Surgery Evidence-Based Medicine Taskforce. A Patient/Population, Intervention, Comparison/Control, Outcome process was used to generate preliminary statements and recommendations to address various aspects related to cardiac surgery in children with trisomy 13 or trisomy 18. Delphi methodology was then used iteratively to generate consensus among the group using a structured communication process. RESULTS: Nine recommendations were developed from a set of initial statements that arose from the Patient/Population, Intervention, Comparison/Control, Outcome process methodology following the groups' review of more than 500 articles. These recommendations were adjudicated by this group of experts using a modified Delphi process in a reproducible fashion and make up the current publication. The Class (strength) of recommendations was usually Class IIa (moderate benefit), and the overall level (quality) of evidence was level C-limited data. CONCLUSIONS: This is the first set of recommendations collated by an expert multidisciplinary group to address specific issues around indications for surgical intervention in children with trisomy 13 or trisomy 18 with congenital heart defect. Based on our analysis of recent data, we recommend that decisions should not be based solely on the presence of trisomy but, instead, should be made on a case-by-case basis, considering both the severity of the baby's heart disease as well as the presence of other anomalies. These recommendations offer a framework to assist parents and clinicians in surgical decision making for children who have trisomy 13 or trisomy 18 with congenital heart defect.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.

Synthesis and antifungal evaluation of pentyloxyl-diphenylisoxazoloyl pneumocandins and echinocandins.

Echinocandins and pneumocandins are classes of lipocyclohexapeptides that are broad spectrum antifungal agents. They inhibit fungal specific 1,3-ß-glucan synthase activity which is an essential component of the fungal cell wall. Chemical modifications of these two leads have produced three clinical agents namely caspofungin, micafungin and anidulafungin. The presence of hydroxy-glutamine versus threonine and unsaturated linear fatty acid versus branched chain saturated fatty acid differentiate the two classes of compounds with profound differences in their hemolytic properties. In the current study, we have replaced the side chain of the cyclohexapeptides with a common aromatic heterocyclic acyl side chain and compared the biological activities of the cores head-to-head and for the first time demonstrated the role played by the acyl chain and the hydroxy-glutamine for the antifungal potency.

Rapid extraction-free detection of the R132H isocitrate dehydrogenase mutation in glioma using colorimetric peptide nucleic acid-loop mediated isothermal amplification (CPNA-LAMP).

The R132H isocitrate dehydrogenase one (IDH1) mutation is a prognostic biomarker present in a subset of gliomas and is associated with heightened survival when paired with aggressive surgical resection. In this study, we establish proof-of-principle for rapid colorimetric detection of the IDH1-R132H mutation in tumor samples in under 1 hour without the need for a nucleic acid extraction. Colorimetric peptide nucleic acid loop-mediated isothermal amplification (CPNA-LAMP) utilizes 4 conventional LAMP primers, a blocking PNA probe complementary to the wild-type sequence, and a self-annealing loop primer complementary to the single nucleotide variant to only amplify the DNA sequence containing the mutation. This assay was evaluated using IDH1-WT or IDH1-R132H mutant synthetic DNA, wild-type or IDH1-R132H mutant U87MG cell lysates, and tumor lysates from archived patient samples in which the IDH1 status was previously determined using immunohistochemistry (IHC). Reactions were performed using a hot water bath and visually interpreted as positive by a pink-to-yellow color change. Results were subsequently verified using agarose gel electrophoresis. CPNA-LAMP successfully detected the R132H single nucleotide variant, and results from tumor lysates yielded 100% concordance with IHC results, including instances when the single nucleotide variant was limited to a portion of the tumor. Importantly, when testing the tumor lysates, there were no false positive or false negative results.

Sustained year-round oceanographic measurements from Rothera Research Station, Antarctica, 1997-2017.

Oceanographic changes adjacent to Antarctica have global climatic and ecological impacts. However, this is the most challenging place in the world to obtain marine data due to its remoteness and inhospitable nature, especially in winter. Here, we present more than 2000 Conductivity-Temperature-Depth (CTD) profiles and associated water sample data collected with (almost uniquely) full year-round coverage from the British Antarctic Survey Rothera Research Station at the west Antarctic Peninsula. Sampling is conducted from a small boat or a sled, depending on the sea ice conditions. When conditions allow, sampling is twice weekly in summer and weekly in winter, with profiling to nominally 500 m and with discrete water samples taken at 15 m water depth. Daily observations are made of the sea ice conditions in the area. This paper presents the first 20 years of data collection, 1997-2017. This time series represents a unique and valuable resource for investigations of the high-latitude ocean's role in climate change, ocean/ice interactions, and marine biogeochemistry and carbon drawdown.

Prediction of survival in infants with congenital diaphragmatic hernia based on stomach position, surgical timing, and oxygenation index.

OBJECTIVE: To identify characteristics predictive of survival of patients with congenital diaphragmatic hernia (CDH). STUDY DESIGN: Retrospective analysis of clinical characteristics including severity of lung disease measured by oxygenation index (OI) associated with single-center survival in CDH patients (n = 81) from 1992 to 2008. Data were analyzed using univariate and multivariable logistic regression, effect plots, and receiver operating characteristic (ROC) plots. RESULTS: No patient died if the stomach was located in the abdomen. A left thoracic stomach position predicted decreased survival with ROC area under the curve (AUC) = 0.70. OI of ≤ 26 averaged over the first 12 hours of life predicted ≥ 50% survival for all patients, with AUC = 0.86. OI effect plots allow prediction of survival over a continuous OI range. No patient survived if mean OI was >51 in the first 12 hours of life. Delaying surgery for a median of 6 days improved survival probability for all patients with presurgery OI values ≤ 51. CONCLUSION: Position of the stomach in the abdomen, delayed surgery, and less severe cardiopulmonary disease during the first 12 hours of life, as measured by mean OI, predicted improved survival probability among patients with CDH. Our CDH model, using mean OI, permits specific individual prediction of survival probability over a range of OI values.

Comparison of refractive and visual acuity results after Contoura® Vision topography-guided LASIK planned with the Phorcides Analytic Engine to results after wavefront-optimized LASIK in eyes with oblique astigmatism.

PURPOSE: To compare visual acuity and refractive results between topography-guided laser in situ keratomileusis (LASIK) planned with the Phorcides Analytic Engine (PAE) to results after wavefront-optimized (WFO) LASIK in subjects with preoperative oblique astigmatism in their manifest refraction. METHODS: This was a retrospective chart review of clinical results from eyes treated with topography-guided LASIK planned with PAE compared to eyes treated with WFO LASIK using the same Wavelight® excimer laser system. All included subjects had preoperative oblique astigmatism. Residual refractive error and visual acuity (uncorrected and corrected) were the measures of interest, at the visit closest to 90 days postoperative. RESULTS: A matched data set from 100 WFO and 97 PAE eyes was extracted from clinical records. At the postoperative visit the PAE group showed lower residual refractive cylinder (p = 0.04), uncorrected distance visual acuity (UDVA) (-0.06 PAE vs. -0.02 WFO, p < 0.01) and distance corrected visual acuity (CDVA) (p < 0.01). The percentage of eyes with a mean refraction spherical equivalent (MRSE) magnitude within 0.25 D and 0.50 D of plano was statistically significantly higher in the PAE group (p = 0.04 and 0.01, respectively). A statistically significantly higher percentage of eyes in the PAE group had UDVA better than or equal to -0.10 logMAR (20/16 Snellen, 36% vs 22%, p = 0.04). More eyes gained CDVA after surgery in the PAE group (53% vs 32%, p < 0.01). There were five enhancements in the WFO group versus none in the PAE group, a statistically significant difference (p = 0.03). CONCLUSIONS: Visual acuity and refractive outcomes after LASIK using PAE in eyes with oblique astigmatism in their preoperative refraction were statistically significantly better than those obtained when WFO treatment was used. The number of refractive outliers and the number of retreatments were also significantly lower with PAE treatment.

Clinical and refractive outcomes after topography-guided refractive surgery planned using Phorcides surgery planning software.

PURPOSE: To evaluate prospectively the clinical outcomes of topography-guided laser in situ keratomileusis (LASIK) surgery performed with Contoura Vision using the Wavelight excimer laser and planned with the Phorcides Analytical Engine. SETTING: Four clinical practices in the U.S. DESIGN: Prospective single-arm interventional study. METHODS: 130 eyes of 65 patients with myopia or myopic astigmatism were enrolled in a prospective study of visual and refractive outcomes after treatment with Contoura Vision using the Wavelight EX500 excimer laser to achieve optimal distance vision. At 3 months postoperatively, uncorrected distance visual acuity (UDVA), manifest refraction, and corrected distance visual acuity (CDVA) were measured and compared with previously published studies. RESULTS: At 3 months postoperatively, 100%, 89%, and 28% of eyes achieved UDVA of 20/20, 20/15, and 20/12.5 or better, respectively. 92% of eyes had postoperative UDVA equal to or better than their preoperative CDVA. Postoperative CDVA was equal to, 1 line better, or 2 lines better than the preoperative CDVA in 53%, 40%, and 6% of eyes, respectively. Only 1 eye lost 1 line of CDVA, and no eyes lost more than 1 line of CDVA. A statistically significant decrease was noted in subjective visual complaints, including glare, halos, difficulty driving at night, reading difficulty, starbursts, fluctuation in vision, and light sensitivity. CONCLUSIONS: The Phorcides Analytical Engine can be used to optimize visual outcomes for the correction of myopia and myopic astigmatism.

Degrading permafrost river catchments and their impact on Arctic Ocean nearshore processes.

Arctic warming is causing ancient perennially frozen ground (permafrost) to thaw, resulting in ground collapse, and reshaping of landscapes. This threatens Arctic peoples' infrastructure, cultural sites, and land-based natural resources. Terrestrial permafrost thaw and ongoing intensification of hydrological cycles also enhance the amount and alter the type of organic carbon (OC) delivered from land to Arctic nearshore environments. These changes may affect coastal processes, food web dynamics and marine resources on which many traditional ways of life rely. Here, we examine how future projected increases in runoff and permafrost thaw from two permafrost-dominated Siberian watersheds-the Kolyma and Lena, may alter carbon turnover rates and OC distributions through river networks. We demonstrate that the unique composition of terrestrial permafrost-derived OC can cause significant increases to aquatic carbon degradation rates (20 to 60% faster rates with 1% permafrost OC). We compile results on aquatic OC degradation and examine how strengthening Arctic hydrological cycles may increase the connectivity between terrestrial landscapes and receiving nearshore ecosystems, with potential ramifications for coastal carbon budgets and ecosystem structure. To address the future challenges Arctic coastal communities will face, we argue that it will become essential to consider how nearshore ecosystems will respond to changing coastal inputs and identify how these may affect the resiliency and availability of essential food resources.