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Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites., Methods: Forty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model., Results: In patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline ( p < 0.001), betaine ( p < 0.001), carnitine ( p = 0.007), TMA ( p < 0.001) and trimethylamine N-oxide (TMAO, p < 0.001). Notably, concentrations of P-cresol glucuronide ( p < 0.001), indole-lactic acid ( p = 0.038), 5-hydroxyindoleacetic acid ( p < 0.0001) and 4-hydroxyphenyllactic acid ( p < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC ( p < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis ( p = 0.42)., Conclusions: Gut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications.

Background: Normative changes in right ventricular (RV) structure and function have not been characterized in the context of treatment-associated functional recovery (RV functional recovery [RVFnRec]). The aim of this study is to assess the clinical relevance of a proposed RVFnRec definition., Methods: We evaluated 63 incident patients with pulmonary arterial hypertension by right heart catheterization and cardiac magnetic resonance imaging at diagnosis and cardiac magnetic resonance imaging and invasive cardiopulmonary exercise testing following treatment (≈11 months). Sex, age, ethnicity matched healthy control subjects (n=62) with 1-time cardiac magnetic resonance imaging and noninvasive cardiopulmonary exercise testing were recruited from the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) project. We examined therapeutic cardiac magnetic resonance imaging changes relative to the evidence-based peak oxygen consumption (VO 2peak )>15 mL/(kg·min) to define RVFnRec by receiver operating curve analysis. Afterload was measured as mean pulmonary artery pressure, resistance, compliance, and elastance., Results: A drop in RV end-diastolic volume of -15 mL best defined RVFnRec (area under the curve, 0.87; P =0.0001) and neared upper 95% CI RV end-diastolic volume of controls. This cutoff was met by 22 out of 63 (35%) patients which was reinforced by freedom from clinical worsening, RVFnRec 1 out of 21 (5%) versus no RVFnRec 17 out of 42, 40% (log-rank P =0.006). A therapy-associated increase of 0.8 mL/mm Hg in compliance had the best predictive value of RVFnRec (area under the curve, 0.76; [95% CI, 0.64-0.88]; P =0.001). RVFnRec patients had greater increases in stroke volume, and cardiac output at exercise., Conclusions: RVFnRec defined by RV end-diastolic volume therapeutic decrease of -15 mL predicts exercise capacity, freedom from clinical worsening, and nears normalization. A therapeutic improvement of compliance is superior to other measures of afterload in predicting RVFnRec. RVFnRec is also associated with increased RV output reserve at exercise., Competing Interests: Disclosures Dr Rischard has consulting relationships with Bayer and receives research support from Ismed, United Therapeutics, Bayer, Acceleron, Merck, and Janssen. Dr Naeije reports relationships including consultancies, speakers fees, and membership of advisory boards with AOP Orphan Pharmaceuticals, Johnson & Johnson, Lung Biotechnology Corporation, and United Therapeutics. Dr Garcia is Chief Executive Officer and founder of Aqualung Therapeutics Corporation. Dr Frantz has consulting, steering committee, and advisory board relationships with Altavant Sciences, Bayer, Gossamer Bio, Janssen, Shouti, France Foundation, IQVIA, Tenax, UpToDate, and United Therapeutics. Dr Hassoun has served as consultant for Merck. Dr Hemnes has consulting relationships with Janssen, Merck, Gossamer, Bio, United Therapeutics, Bayer, Tenax. She owns stock in Tenax therapeutics and she has received research support from National Heart, Lung, and Blood Institute and Cardiovascular Medical Research and Education Fund. Dr Hill is the chair for an Aerovate steering committee. He is a consultant for Bellerophon and Liquidia and Merck. Dr Horn has consulting relationships with Biotronik and AADI biosciences. She serves on the DSMB for SoniVie and V-waves Ltd. She receives research support from Merck and Cereno. Dr Leopold Abbott has served as a consultant for Aria. She has research support from Astellas Pharma and United Therapeutics. Dr Rosenzweig has received consulting fees from Acceleron for a scientific advisory board meeting; and her institution receives grant support from Bayer, United Therapeutics, Janssen, and SonVie. Dr Tang served as consultant for Sequana Medical, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics, Renovacor, WhiteSwell, Kiniksa, Boston Scientific, and CardiaTec Biosciences and has received honorarium from Springer Nature and American Board of Internal Medicine. The other authors report no conflicts.

Aims: Iron deficiency is common in pulmonary hypertension, but its clinical significance and optimal definition remain unclear., Methods and Results: Phenotypic data for 1028 patients enrolled in the Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics study were analyzed. Iron deficiency was defined using the conventional heart failure definition and also based upon optimal cut-points associated with impaired peak oxygen consumption (peakVO2), 6-min walk test distance, and 36-Item Short Form Survey (SF-36) scores. The relationships between iron deficiency and cardiac and pulmonary vascular function and structure and outcomes were assessed. The heart failure definition of iron deficiency endorsed by pulmonary hypertension guidelines did not identify patients with reduced peakVO2, 6-min walk test, and SF-36 (P > 0.208 for all), but defining iron deficiency as transferrin saturation (TSAT) <21% did. Compared to those with TSAT ≥21%, patients with TSAT <21% demonstrated lower peakVO2 [absolute difference: -1.89 (-2.73 to -1.04) mL/kg/min], 6-min walk test distance [absolute difference: -34 (-51 to -17) m], and SF-36 physical component score [absolute difference: -2.5 (-1.3 to -3.8)] after adjusting for age, sex, and hemoglobin (all P < 0.001). Patients with a TSAT <21% had more right ventricular remodeling on cardiac magnetic resonance but similar pulmonary vascular resistance on catheterization. Transferrin saturation <21% was also associated with increased mortality risk (hazard ratio 1.63, 95% confidence interval 1.13-2.34; P = 0.009) after adjusting for sex, age, hemoglobin, and N-terminal pro-B-type natriuretic peptide., Conclusion: The definition of iron deficiency in the 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) pulmonary hypertension guidelines does not identify patients with lower exercise capacity or functional status, while a definition of TSAT <21% identifies patients with lower exercise capacity, worse functional status, right heart remodeling, and adverse clinical outcomes., Competing Interests: Conflict of interest P.M. has received consultancy fees from AstraZeneca, Abbott, Bayer, Boehringer-Ingelheim, Daiichi Sankyo, Novartis, Novo Nordisk, and Vifor Pharma. B.A.B. receives research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus, and Tenax Therapeutics, has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer-Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations, and is named inventor (US Patent no. 10307179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. A.R.H. has served as a consultant for GossamerBio, Tenax Therapeutics, United Therapeutics, Merck, and Janssen. She is a stock holder in Tenax Therapeutics. W.H.W.T. is a consultant for Sequana Medical, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics, Renovacor, Kiniksa, WhiteSwell, Boston Scientific, and CardiaTec Biosciences and has received honorarium from Springer Nature and American Board of Internal Medicine. All other authors reported no relevant relationships to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification., Objectives: The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort., Methods: Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1-5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death., Results: A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1-3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1-4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21-24 mm Hg. Transplant-free survival was poorest in group 3 PH., Conclusions: PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1-3 and 1-4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification. (Pulmonary Vascular Disease Phenomics Program PVDOMICS [PVDOMICS]; NCT02980887)., Competing Interests: Funding Support and Author Disclosures The study received grants U01 HL125218 (Principal Investigator: Dr Rosenzweig), U01 HL125205 (Principal Investigator: Dr Frantz), U01 HL125212 (Principal Investigator: Dr Hemnes), U01 HL125208 (Principal Investigator: Dr Rischard), U01 HL125175 (Principal Investigator: Dr Hassoun), U01 HL125215 (Principal Investigator: Dr Leopold), and U01 HL125177 (Principal Investigator: Dr Beck) and was supported by the Pulmonary Hypertension Association. Dr Hemnes has served as a consultant for Bayer, United Therapeutics, Janssen, GossamerBio, and Tenax Therapeutics; holds stock in Tenax Therapeutics; and has received grants from the National Institutes of Health, CMREF, and Imara. Dr Leopold is supported by the National Institutes of Health grant U01 125215 and the American Heart Association 19AIML34980000; receives salary support from the Massachusetts Medical Society; has received research funding (to her institution) from Astellas; has served as a consultant for Abbott Vascular and United Therapeutics; and has served as a site principal investigator for a study sponsored by Aria CV. Dr Abidov is supported by research grants from Astellas Pharma, Boehringer Ingelheim, and Kiniksa outside of the submitted work. Dr Rosenzweig has received consulting fees from Acceleron for a scientific advisory board meeting; and her institution receives grant support from Bayer, United Therapeutics, Janssen, and SonVie. Dr Borlaug has received research grants from National Institutes of Health/NHLBI, AstraZeneca, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and has received consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr Dubrock has received consulting fees from Janssen Pharmaceuticals; and has served on advisory boards for Janssen Pharmaceuticals and United Therapeutics. Dr Finet is a consultant to Wolters Kluwer Health, Clinical Drug Information Ad Honorem. Dr Frantz has consulting, steering committee, and advisory board relationships with Altavant Sciences, Bayer, Gossamer Bio, Janssen, Shouti, France Foundation, IQVIA, Tenax, UpToDate, and United Therapeutics. Dr Garcia is CEO and founder of Aqualing Therapeutics. Dr Hassoun has served as scientific advisor for Merck Sharp & Dohme, an activity unrelated to the current work. Dr Highland has grants/contracts with Acceleron Pharmaceuticals, Actelion Pharmaceuticals (Janssen), Bayer Healthcare, Boehringer Ingelheim, Eiger Pharmaceuticals, Eli Lilly, Gossamer Bio, United Therapeutics, and Viela Bio (Horizon); has served as a consultant and/or member of a steering or advisory committee with Acceleron Pharmaceuticals, Actelion Pharmaceuticals (Janssen), Boehringer Ingelheim, Forsee, Genentech, Gossamer Bio, and United Therapeutics; and has served on the Speakers Bureau for Actelion Pharmaceuticals (Janssen), Bayer Healthcare, Boehringer Ingelheim, and United Therapeutics. Dr Hill has received research grants for Acceleron, Aerovate. Altavant, Gossamer. Liquidia, Merck, and United Therapeutics; and has served on advisory boards for Acceleron, Aerovate, Altavant, Gossamer, and Liquidia. Dr Maron has relationships with Deerfield Corporation, Actelion Sciences, and Tenax Therapeutics; and has U.S. Patent #9,605,047, Patent pending PCT/US2019/059890, Patent application 2021/133937. Dr Mathai has served as a consultant for Acceleron, Actelion, Bayer, and United Therapeutics. Dr Mehra is supported by National Institutes of Health grants U01HL125177 and UH3HL140144 and the American Heart Association AHA 18SFRN34170013; has received royalties from Up to Date; has received compensation from the American Board of Internal Medicine; and has received an honorarium from the American Academy of Sleep Medicine. M.M. Park has served on the Speakers Bureau of Lantheus Medical Imaging (Definity contrast). Dr Rischard has consulting relationships with Acceleron and United Therapeutics; is on a Steering Committee for Acceleron; and receives research support from Ismed, United Therapeutics, Bayer, Acceleron, Janssen, and AADI. Dr Thomas has served as a consultant for GE, Abbott, egnite, EchoIQ, and Caption Health; as well as spouse employment for Caption Health. Dr Horn has served on the Data and Safety Monitoring Board of AADi Biosciences and SoniVie; has served on the Clinical Events Committee for V-wave; and has served as a consultant for Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Management of laryngotracheal stenosis is challenging and laryngotracheal stenosis is generally managed with laryngotracheal reconstruction. Stents are often used as part of the reconstructive surgery. Although most stents adequately stabilize the reconstruction during healing, they often do a poor job of mimicking glottic anatomy, particularly the anterior glottis. Here, we present a modified suprastomal stent designed to stabilize reconstruction after laryngotracheal reconstruction while also improving postoperative glottic anatomy and function. The case of a 15-year-old tracheostomy-dependent patient with glotto-subglottic stenosis who underwent laryngotracheal reconstruction using this modified stent is described. The patient had an excellent outcome with decannulation of her tracheostomy and significant improvement in voice.

Background: Invasive hemodynamic evaluation through right heart catheterization plays an essential role in the diagnosis, categorization, and risk stratification of patients with pulmonary hypertension., Methods: Subjects enrolled in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) program undergo an extensive invasive hemodynamic evaluation that includes repeated measurements at rest and during several provocative physiological challenges. It is a National Institutes of Health/National Heart, Lung, and Blood Institute initiative to reclassify pulmonary hypertension groups based on clustered phenotypic and phenomic characteristics. At a subset of centers, participants also undergo an invasive cardiopulmonary exercise test to assess changes in hemodynamics and gas exchange during exercise., Conclusions: When coupled with other physiological testing and blood -omic analyses involved in the PVDOMICS study, the comprehensive right heart catheterization protocol described here holds promise to clarify the diagnosis and clustering of pulmonary hypertension patients into cohorts beyond the traditional 5 World Symposium on Pulmonary Hypertension groups. This article will describe the methods applied for invasive hemodynamic characterization in the PVDOMICS program. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02980887.

Tree cores were collected and analyzed for trichloroethylene (TCE) on a private property between a former electroplating facility in Asheville, North Carolina (USA), and a contaminated wetland/spring complex. TCE was detected in 16 of 31 trees, the locations of which were largely consistent with a "plume core" delineated by a more detailed subsurface investigation nearly 2 years later. Concentrations in tree cores and nearby soil borings were not correlated, perhaps due to heterogeneities in both geologic and tree root structure, spatial and temporal variability in transpiration rates, or interferences caused by other contaminants at the site. Several tree cores without TCE provided evidence for significantly lower TCE concentrations in shallow groundwater along the margins of the contaminated spring complex in an area with limited accessibility. This study demonstrates that tree core analyses can complement a more extensive subsurface investigation, particularly in residential or ecologically sensitive areas.

αB-crystallin is a small heat shock protein that exhibits chaperone activity and can protect multiple cell types against oxidative stress damage. Altered levels and specific mutations of αB-crystallin are associated with multiple degenerative diseases. We previously found that αB-crystallin translocates to lens and retinal cell mitochondria upon oxidative stress exposure where it provides protection against oxidative stress damage. To date, the role of the chaperone function of αB-crystallin in mitochondrial translocation and protection has not been established. Here, we sought to determine the relationship between the chaperone activity of αB-crystallin and its ability to translocate to and protect retinal cell mitochondria against oxidative stress damage. Our data provide evidence that three forms of αB-crystallin exhibiting different chaperone activity levels including wild-type, R120G (decreased chaperone activity) and M68A (increased chaperone activity) provide comparable levels of mitochondrial translocation and protection to retinal cells exposed to oxidative stress. The results provide evidence that mitochondrial translocation and protection by αB-crystallin is independent of its chaperone activity and that other functions of αB-crystallin may also be independent of its chaperone activity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Ventral tegmental area (VTA) GABA neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in alcohol reward. The aim of this study was to examine the role of midbrain connexin-36 (Cx36) gap junctions (GJs) in ethanol intoxication and consumption. Using behavioral, molecular, and electrophysiological methods, we compared the effects of ethanol in mature Cx36 knockout (KO) mice and age-matched wild-type (WT) controls. Compared to WT mice, Cx36 KO mice exhibited significantly more ethanol-induced motor impairment in the open field test, but less disruption in motor coordination in the rotarod paradigm. Cx36 KO mice, and WT mice treated with the Cx36 antagonist mefloquine (MFQ), consumed significantly less ethanol than their WT controls in the drink-in-the-dark procedure. The firing rate of VTA GABA neurons in WT mice was inhibited by ethanol with an IC₅₀ of 0.25 g/kg, while VTA GABA neurons in KO mice were significantly less sensitive to ethanol. Dopamine neuron GABA-mediated sIPSC frequency was reduced by ethanol (30 mM) in WT mice, but not affected in KO mice. Cx36 KO mice evinced a significant up-regulation in DAT and D2 receptors in the VTA, as assessed by quantitative RT-PCR. These findings demonstrate the behavioral relevance of Cx36 GJ-mediated electrical coupling between GABA neurons in mature animals, and suggest that loss of coupling between VTA GABA neurons results in disinhibition of DA neurons, a hyper-DAergic state and lowered hedonic valence for ethanol consumption., (Copyright © 2010 Wiley-Liss, Inc.)

Connexin-36 (Cx36) gap junctions (GJs) appear to be involved in the synchronization of GABA interneurons in many brain areas. We have previously identified a population of Cx36-connected ventral tegmental area (VTA) GABA neurons that may regulate mesolimbic dopamine (DA) neurotransmission, a system implicated in reward from both natural behaviors and drugs of abuse. The aim of this study was to determine the effect mefloquine (MFQ) has on midbrain DA and GABA neuron inhibition, and the role Cx36 GJs play in regulating midbrain VTA DA neuron activity in mice. In brain slices from adolescent wild-type (WT) mice the Cx36-selective GJ blocker mefloquine (MFQ, 25 μM) increased VTA DA neuron sIPSC frequency sixfold, and mIPSC frequency threefold. However, in Cx36 KO mice, MFQ only increased sIPSC and mIPSC frequency threefold. The nonselective GJ blocker carbenoxolone (CBX, 100 μM) increased DA neuron sIPSC frequency twofold in WT mice, did not affect Cx36 KO mouse sIPSCs, and did not affect mIPSCs in WT or Cx36 KO mice. Interestingly, MFQ had no effect on VTA GABA neuron sIPSC frequency. We also examined MFQ effects on VTA DA neuron firing rate and current-evoked spiking in WT and Cx36 KO mice, and found that MFQ decreased WT DA neuron firing rate and current-evoked spiking, but did not alter these measures in Cx36 KO mice. Taken together these findings suggest that blocking Cx36 GJs increases VTA DA neuron inhibition, and that GJs play in key role in regulating inhibition of VTA DA neurons. Synapse, 2011. © 2011 Wiley-Liss, Inc., (Copyright © 2011 Wiley-Liss, Inc.)

The detection of pharmaceuticals and other organic wastewater contaminants (OWCs) in ground water and surface-water bodies has raised concerns about the possible ecological impacts of these compounds on nontarget organisms. On-site wastewater treatment systems represent a potentially significant route of entry for organic contaminants to the environment. In this study, effluent samples were collected and analyzed from conventional septic systems and from systems using advanced treatment technologies. Six of 13 target compounds were detected in effluent from at least one septic system. Caffeine, paraxanthine, and acetaminophen were the most frequently detected compounds, and estrogenic activity was detected in 14 of 15 systems. The OWC concentrations were significantly lower in effluent after sand filtration (p < 0.01) or aerobic treatment (p < 0.05) as compared with effluent that had not undergone advanced treatment. In general, concentrations in conventional systems were comparable to those measured in previous studies of municipal wastewater treatment plant (WWTP) influent, and concentrations in systems after advanced treatment were comparable to previously measured concentrations in WWTP effluent. These data indicate that septic systems using advanced treatment can reduce OWCs in treated effluent to similar concentrations as municipal WWTPs.

Previous site-specific studies designed to assess the impacts of unsewered subdivisions on ground water quality have relied on upgradient monitoring wells or very limited background data to characterize conditions prior to development. In this study, an extensive monitoring program was designed to document ground water conditions prior to construction of a rural subdivision in south-central Wisconsin. Previous agricultural land use has impacted ground water quality; concentrations of chloride, nitrate-nitrogen, and atrazine ranged from below the level of detection to 296 mg/L, 36 mg/L, and 0.8 microg/L, respectively, and were highly variable from well to well and through time. Seasonal variations in recharge, surface topography, aquifer heterogeneities, surficial loading patterns, and well casing depth explain observed variations in ground water chemistry. This variability would not have been detected if background conditions were determined from only a few monitoring wells or inferred from wells located upgradient of the subdivision site. This project demonstrates the importance of characterizing both ground water quality and chemical variability prior to land-use change to detect any changes once homes are constructed.

Recent advances in the development of chiral derivatizing and solvating agents that facilitate the determination of enantiomeric excess and absolute configuration are reviewed. These include metal-containing species, host-guest systems, donor-acceptor compounds, and liquid crystal discriminating agents. In the aggregate, these reagents can be used to analyze a wide range of compound classes., (Copyright 2003 Wiley-Liss, Inc.)

Calix[4]arenes, calix[4]resorcarenes, and anionic cyclodextrin derivatives were examined as chiral NMR solvating agents. The calix[4]arenes were prepared by attachment of amino acids through the hydroxyl groups of the phenol rings. Chloroform-, methanol-, and water-soluble derivatives were prepared and tested with a range of substrates. Chloroform-soluble chiral calix[4]resorcarenes were prepared by attachment of chiral primary and secondary amines and examined in NMR applications with a variety of substrates. Sulfated and carboxymethylated beta-cyclodextrin are effective at causing enantiomeric discrimination in the (1)H NMR spectra of organic cations. Lanthanide ions associate at the carboxymethyl groups and cause sizeable shifts and enhancements in enantiomeric discrimination in the spectra of organic cations. The enhancements caused by the lanthanide ion are large enough that much lower concentrations of the cyclodextrin can be used as compared to conventional analyses., (Copyright 2003 Wiley-Liss, Inc.)