d-Serine agonism of GluN1-GluN3 NMDA receptors regulates the activity of enteric neurons and coordinates gut motility.

The enteric nervous system (ENS) is a complex network of diverse molecularly defined classes of neurons embedded in the gastrointestinal wall and responsible for controlling the major functions of the gut. As in the central nervous system, the vast array of ENS neurons is interconnected by chemical synapses. Despite several studies reporting the expression of ionotropic glutamate receptors in the ENS, their roles in the gut remain elusive. Here, by using an array of immunohistochemistry, molecular profiling and functional assays, we uncover a new role for d-serine (d-Ser) and non-conventional GluN1-GluN3 N-methyl d-aspartate receptors (NMDARs) in regulating ENS functions. We demonstrate that d-Ser is produced by serine racemase (SR) expressed in enteric neurons. By using both in situ patch clamp recording and calcium imaging, we show that d-Ser alone acts as an excitatory neurotransmitter in the ENS independently of the conventional GluN1-GluN2 NMDARs. Instead, d-Ser directly gates the non-conventional GluN1-GluN3 NMDARs in enteric neurons from both mouse and guinea-pig. Pharmacological inhibition or potentiation of GluN1-GluN3 NMDARs had opposite effects on mouse colonic motor activities, while genetically driven loss of SR impairs gut transit and fluid content of pellet output. Our results demonstrate the existence of native GluN1-GluN3 NMDARs in enteric neurons and open new perspectives on the exploration of excitatory d-Ser receptors in gut function and diseases.

d-Amino Acids and Classical Neurotransmitters in Healthy and Type 2 Diabetes-Affected Human Pancreatic Islets of Langerhans.

The pancreatic islets of Langerhans are clusters of cells that function as endocrine units synthesizing and releasing insulin and a range of additional peptide hormones. The structural and chemical characteristics of islets change during type 2 diabetes development. Although a range of metabolites including neurotransmitters has been reported in rodent islets, the involvement of these cell-to-cell signaling molecules within human pancreatic islets in the pathophysiology of type 2 diabetes is not well known, despite studies suggesting that these molecules impact intra- and inter-islet signaling pathways. We characterize the enigmatic cell-to-cell signaling molecules, d-serine (d-Ser) and d-aspartate (d-Asp), along with multiple classical neurotransmitters and related molecules, in healthy versus type 2 diabetes-affected human islets using capillary electrophoresis separations. Significantly reduced d-Ser percentage and gamma-aminobutyric acid (GABA) levels were found in type 2 diabetes-affected islets compared to healthy islets. In addition, the negative correlations of many of the signaling molecules, such as d-Ser percentage (r = -0.35), d-Asp (r = -0.32), serotonin (r = -0.42), and GABA (r = -0.39) levels, with hemoglobin A1c (HbA1c) levels and thus with the progression of type 2 diabetes further demonstrate the disruption in intra- or inter-islet signaling pathways and suggest that these cell-to-cell signaling molecules may be potential therapeutic targets.

Optimizing test approaches for the detection of exposed metal surfaces within a chromatographic flow path.

It is critical to the success of any chromatography-based assay that the performance of the LC instrument be checked for its readiness and ability to perform the intended analysis. This includes gaging the suitability of a system to fulfill the purpose of different types of methods. One type of analysis that requires special consideration is the analysis of compounds which are prone to a particular form of non-specific binding, namely metal adsorption, where analytes interact and potentially adsorb to metal contained within the chromatographic flow path. For an analysis of compounds which are susceptible to metal adsorption, ideally a system suitability test would be performed to ensure there will not be any sample loss or detrimental peak shape effects resulting from potential analyte-to-metal interactions. To help chromatographers assess system inertness concerns like this, we have developed a method of testing LC systems for metal interactions using adenosine 5'-(α,ß-methylene)diphosphate (AMPcP). This nucleotide analog has been confirmed to have a propensity to adsorb to titanium and stainless-steel frits and is resistant to hydrolysis and stable to long-term storage and repeat use (as is befitting of any reagent proposed for system suitability testing). AMPcP has been used in a flow injection test (no column in-line) to monitor for losses in recovery and peak shape perturbations that can potentially be present in any chromatography system manufactured with one or more metal based components. In this approach, sequential injections of AMPcP were made without a column and various peak attributes were monitored and ultimately correlated to the amount of metal surface area in the flow path. The ability of this method to discriminate between inert chromatographic surfaces versus exposed metal surfaces was verified by comparing peak areas, peak shapes, and injection repeatability for AMPcP using a UHPLC equipped with MP35N metal alloy components versus an equivalent UHPLC equipped with an ethylene bridged hybrid organic-inorganic surface (or so-called hybrid surface technology). Injections of caffeine were also explored to establish a negative control for this system suitability measurement. Caffeine does not interact with metal surfaces and can therefore give an instrument specific representation of peak shape and dispersion as well as an indication of overall mechanical system performance. Additionally, replicate injections of AMPcP and caffeine onto a UHPLC partially configured with hybrid surface technology (HST) readily identified exposed metal surfaces through an increased peak area relative standard deviation as well as a reduction in absolute recovery. Finally, a novel visualization tool was developed to provide an alternative method of determining system inertness without having to perform chromatographic calculations but instead a graphical peak shape comparison between a negative control, caffeine, and the metal sensitive AMPcP test probe.

Characterization of a highly stable zwitterionic hydrophilic interaction chromatography stationary phase based on hybrid organic-inorganic particles.

We have characterized a sulfobetaine stationary phase based on 1.7 µm ethylene-bridged hybrid organic-inorganic particles, which is intended for use in hydrophilic interaction chromatography. The efficiency of a column packed with this material was determined as a function of flow rate, demonstrating a minimum reduced plate height of 2.4. The batch-to-batch reproducibility was assessed using the separation of a mixture of acids, bases, and neutrals. We compared the retention and selectivity of the hybrid sulfobetaine stationary phase to that of several benchmark materials. The hybrid sulfobetaine material gave strong retention for polar neutrals and high selectivity for methyl groups, hydroxy groups, and configurational isomers. Large differences in cation and anion retention were observed among the columns. We characterized the acid and base stability of the hybrid sulfobetaine stationary phase, using accelerated tests at pH 1.3 and 11.0, both at 70°C. The results support a recommended pH range of 2-10. We also investigated the performance of columns packed with this material for metal-sensitive analytes, comparing conventional stainless steel column hardware to hardware that incorporates hybrid surface technology to mitigate interactions with metal surfaces. Compared to the conventional columns, the hybrid surface technology columns showed a greatly improved peak shape.

Using Hybrid Organic-Inorganic Surface Technology to Mitigate Analyte Interactions with Metal Surfaces in UHPLC.

Interactions of analytes with metal surfaces in high-performance liquid chromatography (HPLC) instruments and columns have been reported to cause deleterious effects ranging from peak tailing to a complete loss of the analyte signal. These effects are due to the adsorption of certain analytes on the metal oxide layer on the surface of the metal components. We have developed a novel surface modification technology and applied it to the metal components in ultra-HPLC (UHPLC) instruments and columns to mitigate these interactions. A hybrid organic-inorganic surface, based on an ethylene-bridged siloxane chemistry, was developed for use with reversed-phase and hydrophilic interaction chromatography. We have characterized the performance of UHPLC instruments and columns that incorporate this surface technology and compared the results with those obtained using their conventional counterparts. We demonstrate improved performance when using the hybrid surface technology for separations of nucleotides, a phosphopeptide, and an oligonucleotide. The hybrid surface technology was found to result in higher and more consistent analyte peak areas and improved peak shape, particularly when using low analyte mass loads and acidic mobile phases. Reduced abundances of iron adducts in the mass spectrum of a peptide were also observed when using UHPLC systems and columns that incorporate hybrid surface technology. These results suggest that this technology will be particularly beneficial in UHPLC/mass spectrometry investigations of metal-sensitive analytes.

Characterization of a highly stable mixed-mode reversed-phase/weak anion-exchange stationary phase based on hybrid organic/inorganic particles.

We have characterized Atlantis ethylene-bridged hybrid C18 anion-exchange, a mixed-mode reversed-phase/weak anion-exchange stationary phase designed to give greater retention for anions (e.g., ionized acids) compared to conventional reversed-phase materials. The retention and selectivity of this stationary phase were compared to that of three benchmark materials, using a mixture of six polar compounds that includes an acid, two bases, and three neutrals. The compatibility of the ethylene-bridged hybrid C18 anion-exchange material with 100% aqueous mobile phases was also evaluated. We investigated the batch-to-batch reproducibility of the ethylene-bridged hybrid C18 anion-exchange stationary phase for 27 batches across three different particle sizes (1.7, 2.5, and 5 µm) and found it to be comparable to that of one of the most reproducible C18 stationary phases. We also characterized the acid and base stability of the ethylene-bridged hybrid C18 anion-exchange stationary phase and the results show it to be usable over a wide pH range, from 2 to 10. The extended upper pH limit relative to silica-based reversed-phase/weak anion-exchange materials is enabled by the use of ethylene-bridged hybrid organic/inorganic particles. The improved base stability allows Atlantis ethylene-bridged hybrid C18 anion-exchange to be used with a wider range of mobile phase pH values, opening up a greater range of selectivity options.

Spectral-Spatial Features Integrated Convolution Neural Network for Breast Cancer Classification.

Cancer identification and classification from histopathological images of the breast depends greatly on experts, and computer-aided diagnosis can play an important role in disagreement of experts. This automatic process has increased the accuracy of the classification at a reduced cost. The advancement in Convolution Neural Network (CNN) structure has outperformed the traditional approaches in biomedical imaging applications. One of the limiting factors of CNN is it uses spatial image features only for classification. The spectral features from the transform domain have equivalent importance in the complex image classification algorithm. This paper proposes a new CNN structure to classify the histopathological cancer images based on integrating the spectral features obtained using a multi-resolution wavelet transform with the spatial features of CNN. In addition, batch normalization process is used after every layer in the convolution network to improve the poor convergence problem of CNN and the deep layers of CNN are trained with spectral-spatial features. The proposed structure is tested on malignant histology images of the breast for both binary and multi-class classification of tissue using the BreaKHis Dataset and the Breast Cancer Classification Challenge 2015 Datasest. Experimental results show that the combination of spectral-spatial features improves classification accuracy of the CNN network and requires less training parameters in comparison with the well known models (i.e., VGG16 and ALEXNET). The proposed structure achieves an average accuracy of 97.58% and 97.45% with 7.6 million training parameters on both datasets, respectively.

Focused cardiac ultrasound as a predictor of readmission in acute decompensated heart failure.

Acute decompensated heart failure (ADHF) is a common reason for admission to the hospital, and readmission is frequent. Multiple factors contribute to rehospitalizations, but inadequate assessment of volume status leading to persistent congestion is an important factor. We sought to determine if focused cardiac ultrasound (FCU) of the inferior vena cava (IVC), as a surrogate of volume status, would predict readmission of ADHF patients after index hospitalization. Patients admitted with a primary diagnosis of ADHF were prospectively enrolled. All patients underwent FCU of the IVC on admission and then daily. 82 patients were enrolled. Patients demonstrated improvement in heart failure physical examination findings and symptoms during the hospitalization. There was a reduction in the size of the IVC and a significant increase in patients with small collapsible vena cava. Logistic regression analysis of physical examination, patient symptoms, and IVC parameters at discharge demonstrated IVC collapsibility and patient reported dyspnea improvement as the only significant variables to predict readmission or emergency department visit. FCU assessment of IVC size and collapsibility may be useful in patients with ADHF to predict risk of being readmitted within 30 days of hospital discharge.

Chiral Measurement of Aspartate and Glutamate in Single Neurons by Large-Volume Sample Stacking Capillary Electrophoresis.

d-Amino acids (d-AAs) are endogenous molecules found throughout the metazoan, the functions of which remain poorly understood. Measurements of low abundance and heterogeneously distributed d-AAs in complex biological samples, such as cells and multicellular structures of the central nervous system (CNS), require the implementation of sensitive and selective analytical approaches. In order to measure the d- and l-forms of aspartate and glutamate, we developed and applied a stacking chiral capillary electrophoresis (CE) with laser-induced fluorescence detection method. The achieved online analyte preconcentration led to a 480-fold enhancement of detection sensitivity relative to capillary zone electrophoresis, without impacting separation resolution or analysis time. Additionally, the effects of inorganic ions on sample preconcentration and CE separation were evaluated. The approach enabled the relative quantification of d-aspartate and d-glutamate in individual neurons mechanically isolated from the CNS of the sea slug Aplysia californica, a well characterized neurobiological model. Levels of these structurally similar d-AAs were significantly different in subpopulations of cells collected from the investigated neuronal clusters.

Challenges with Evidence-Based Management of Stable Ischemic Heart Disease.

PURPOSE OF REVIEW: Stable ischemic heart disease (SIHD) is a highly prevalent condition associated with increased costs, morbidity, and mortality. Management goals of SIHD can broadly be thought of in terms of improving prognosis and/or improving symptoms. Treatment options include medical therapy as well as revascularization, either with percutaneous coronary intervention or coronary artery bypass grafting. Herein, we will review the current evidence base for treatment of SIHD as well as its challenges and discuss ongoing studies to help address some of these knowledge gaps. RECENT FINDINGS: There has been no consistent reduction in death or myocardial infarction (MI) with revascularization vs. medical therapy in patients with SIHD in contemporary trials. Angina and quality of life have been shown to be relieved more rapidly with revascularization vs. optimal medical therapy; however, the durability of these results is uncertain. There have been challenges and limitations in several of the trials addressing the optimal treatment strategy for SIHD due to potential selection bias (due to knowledge of coronary anatomy prior to randomization), patient crossover, and advances in medical therapy and revascularization strategies since trial completion. The challenges inherent to prior trials addressing the optimal management strategy for SIHD have impacted the generalizability of results to real-world cohorts. Until the results of additional ongoing trials are available, the decision for revascularization or medical therapy should be based on patients' symptoms, weighing the risks and benefits of each approach, and patient preference.

Improved detection of myocardial damage in sarcoidosis using longitudinal strain in patients with preserved left ventricular ejection fraction.

BACKGROUND: Cardiac infiltration is an important cause of death in sarcoidosis. Transthoracic echocardiography (TTE) has limited sensitivity for the detection of cardiac sarcoidosis (CS). Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is used to diagnose CS but has limitations of cost and availability. We sought to determine whether TTE-derived global longitudinal strain (GLS) may be used to identify individuals with CS, despite preserved left ventricular ejection fraction (LVEF), and whether abnormal GLS is associated with major cardiovascular events (MCE). METHODS: We studied 31 patients with biopsy-proven extra-cardiac sarcoidosis, LVEF>50% and LGE on CMR (CS+ group), and 31 patients without LGE (CS- group), matched by age, sex, and severity of lung disease. GLS was measured using vendor-independent speckle tracking software. Parameters of left and right ventricular systolic and diastolic function were also studied. Receiver-operating characteristic curves were used to identify GLS cutoff for CS detection, and Kaplan-Meier plots to determine the ability of GLS to predict MCE. RESULTS: LGE was associated with reduced GLS (-19.6±1.9% in CS- vs -14.7±2.4% in CS+, P<.01) and with reduced E/A ratio (1.1±0.3 vs 0.9±0.3, respectively, P =.01). No differences were noted in other TTE parameters. GLS magnitude inversely correlated with LGE burden (r=-.59). GLS cutoff of -17% showed sensitivity and specificity 94% for detecting CS. Patients who experienced MCE had worse GLS than those who did not (-13.4±0.9% vs -17.7±0.4%, P=.0003). CONCLUSIONS: CS is associated with significantly reduced GLS in the presence of preserved LVEF. GLS measurements may become part of the TTE study performed to screen for CS.

Prognosis of Myocardial Damage in Sarcoidosis Patients With Preserved Left Ventricular Ejection Fraction: Risk Stratification Using Cardiovascular Magnetic Resonance.

BACKGROUND: Cardiac sarcoidosis is associated with an increased risk of heart failure and sudden death, but its risk in patients with preserved left ventricular ejection fraction is unknown. Using cardiovascular magnetic resonance in patients with extracardiac sarcoidosis and preserved left ventricular ejection fraction, we sought to (1) determine the prevalence of cardiac sarcoidosis or associated myocardial damage, defined by the presence of late gadolinium enhancement (LGE), (2) quantify their risk of death/ventricular tachycardia (VT), and (3) identify imaging-based covariates that predict who is at greatest risk of death/VT. METHODS AND RESULTS: Parameters of left and right ventricular function and LGE burden were measured in 205 patients with left ventricular ejection fraction >50% and extracardiac sarcoidosis who underwent cardiovascular magnetic resonance for LGE evaluation. The association between covariates and death/VT in the entire group and within the LGE+ group was determined using Cox proportional hazard models and time-dependent receiver-operator curves analysis. Forty-one of 205 patients (20%) had LGE; 12 of 205 (6%) died or had VT during follow-up; of these, 10 (83%) were in the LGE+ group. In the LGE+ group (1) the rate of death/VT per year was >20× higher than LGE- (4.9 versus 0.2%, P<0.01); (2) death/VT were associated with a greater burden of LGE (14±11 versus 5±5%, P<0.01) and right ventricular dysfunction (right ventricular EF 45±12 versus 53±28%, P=0.04). LGE burden was the best predictor of death/VT (area under the receiver-operating characteristics curve, 0.80); for every 1% increase of LGE burden, the hazard of death/VT increased by 8%. CONCLUSIONS: Sarcoidosis patients with LGE are at significant risk for death/VT, even with preserved left ventricular ejection fraction. Increased LGE burden and right ventricular dysfunction can identify LGE+ patients at highest risk of death/VT.

Geographic Variation in Cold Ischemia Time: Kidney vs. Liver Transplantation in the United States, 2003-2011.

BACKGROUND: Regional variations in kidney and liver transplant outcomes have been reported, but their causes remain largely unknown. This study investigated variations in kidney and liver cold ischemia times (CITs) across Organ Procurement Organizations (OPO) as potential causes of variations in transplant outcomes. METHODS: This retrospective study analyzed the Standard Transplant Analysis and Research (STAR) data of deceased donor kidney (n=61,335) and liver (n=39,285) transplants performed between 2003 and 2011. CIT variations between the two types of organs were examined and compared. Factors associated with CIT were explored using multivariable regressions. Spearman's rank tests were used to associate CIT with graft failure at the OPO level. RESULTS: Significant CIT variations were found across OPOs for both organs (p < 0.05). The variation was particularly large for kidney CIT. Those OPOs with longer average kidney CIT were likely to have a lower graft survival rate (p=0.01). For liver, this association was insignificant (p=0.23). The regression analysis revealed sharp contrasts between the factors associated with kidney and liver CITs. High risk kidney transplant recipients and marginal kidneys were associated with longer average CIT. The reverse was true for liver transplants. CONCLUSIONS: Large variations in kidney CIT compared to liver CIT may indicate that there is a room to reduce kidney CIT. Reducing kidney CIT through managerial improvements could be a cost effective way to improve the current transplant system.

Determination of galantamine hydrobromide in bulk drug and pharmaceutical dosage form by spectrofluorimetry.

AIM: To develop a simple, accurate, sensitive, rapid and precise method for the determination of galantamine hydrobromide in bulk drug and pharmaceutical dosage form. MATERIAL AND METHODS: The method employs wavelength detection and determination of galantamine hydrobromide at excitation wavelength 282 nm and emission wavelength 607 nm in a solution of simple distilled water. RESULT AND CONCLUSION: The method was found to be linear in the range of 2-14 µg/ml having r (2) = 0.9999. The mean accuracy was found to be 98.12% to 99.67%. The intraday and interday precision was found to be 0.18-0.35% and 0.13-0.46%, respectively. The limit of detection was found to be 0.29 µg/ml. The limit of quantification was found to be 0.89 µg/ml. The method was successfully applied for the determination of galantamine hydrobromide in bulk drug as well as pharmaceutical dosage form.

Non-vena cava venous leiomyosarcomas: a review of the literature.

BACKGROUND: Leiomyosarcoma (LMS) is a rare malignant tumor of smooth muscle origin that generally stems from soft tissues and uterine tissue. However, a small percentage of this sarcoma subset may originate from the smooth muscle of vessel walls, most of which are of venous origin. Although the vena cava (VC) serves as the most likely source for these tumors and has been well described in the literature, there is limited information focused on non-VC LMS derived from large veins. The focus of this study was to consolidate the reports and previously published data of all non-VC LMS of venous origin to better characterize and describe this disease process. METHODS: We reviewed information derived from 143 previously published cases. RESULTS AND CONCLUSIONS: It was determined that women aged 60-69 years were most commonly diagnosed with this particular type of tumor, with the most common tumor site being the renal vein. Metastasis was present in 12% of this population at the time of diagnosis, and 32% of patients were alive 4 years later.

The supraglottic effect of a reduction in expiratory mask pressure during continuous positive airway pressure.

STUDY OBJECTIVES: Patients with obstructive sleep apnea may have difficulty exhaling against positive pressure, hence limiting their acceptance of continuous positive airway pressure (CPAP). C-Flex is designed to improve comfort by reducing pressure in the mask during expiration proportionally to expiratory airflow (3 settings correspond to increasing pressure changes). When patients use CPAP, nasal resistance determines how much higher supraglottic pressure is than mask pressure. We hypothesized that increased nasal resistance results in increased expiratory supraglottic pressure swings that could be mitigated by the effects of C-Flex on mask pressure. DESIGN: Cohort study. SETTING: Sleep center. PARTICIPANTS: Seventeen patients with obstructive sleep apnea/hypopnea syndrome and a mechanical model of the upper airway. INTERVENTIONS: In patients on fixed CPAP, CPAP with different C-Flex levels was applied multiple times during the night. In the model, 2 different respiratory patterns and resistances were tested. MEASUREMENTS AND RESULTS: Airflow, expiratory mask, and supraglottic pressures were measured on CPAP and on C-Flex. Swings in pressure during expiration were determined. On CPAP, higher nasal resistance produced greater expiratory pressure swings in the supraglottis in the patients and in the model, as expected. C-Flex 3 produced expiratory drops in mask pressure (range -0.03 to -2.49 cm H(2)O) but mitigated the expiratory pressure rise in the supraglottis only during a sinusoidal respiratory pattern in the model. CONCLUSIONS: Expiratory changes in mask pressure induced by C-Flex did not uniformly transmit to the supraglottis in either patients with obstructive sleep apnea on CPAP or in a mechanical model of the upper airway with fixed resistance. Data suggest that the observed lack of expiratory drop in supraglottic pressure swings is related to dynamics of the C-Flex algorithm.

Predictors of response to a nasal expiratory resistor device and its potential mechanisms of action for treatment of obstructive sleep apnea.

STUDY OBJECTIVE: A one-way nasal resistor has recently been shown to reduce sleep disordered breathing (SDB) in a subset of patients with Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS). The purpose of this study was to examine characteristics predictive of therapeutic response to the device and provide pilot data as to its potential mechanisms of action. PATIENTS, INTERVENTIONS, AND MEASUREMENTS: 20 subjects (15M/5F, age 54 ± 12 years, BMI 33.5 ± 5.6 kg/m²) with OSAHS underwent 3 nocturnal polysomnograms (NPSG) including diagnostic, therapeutic (with a Provent® nasal valve device), and CPAP. Additional measurements included intranasal pressures and PCO2, closing pressures (Pcrit), and awake lung volumes in different body positions. RESULTS: In 19/20 patients who slept with the device, RDI was significantly reduced with the nasal valve device compared to the diagnostic NPSG (27 ± 29/h vs 49 ± 28/h), with 50% of patients having an acceptable therapeutic response. Among demographic, lung volume, or diagnostic NPSG measures or markers of collapsibility, no significant predictors of therapeutic response were found. There was a suggestion that patients with position-dependent SDB (supine RDI > lateral RDI) were more likely to have an acceptable therapeutic response to the device. Successful elimination of SDB was associated with generation and maintenance of an elevated end expiratory pressure. No single definitive mechanism of action was elucidated. CONCLUSIONS: The present study shows that the nasal valve device can alter SDB across the full spectrum of SDB severity. There was a suggestion that subjects with positional or milder SDB in the lateral position were those most likely to respond.

Awake measures of nasal resistance and upper airway resistance on CPAP during sleep.

STUDY OBJECTIVES: Since on CPAP, the nose is the primary determinant of upper airway resistance, we assess utility of noninvasive measures of nasal resistance during wakefulness as a predictor of directly assessed upper airway resistance on CPAP during sleep in patients with obstructive sleep apnea/hypopnea syndrome. METHODS: Patients with complaints of snoring and excessive daytime sleepiness were recruited. 14 subjects underwent daytime evaluations including clinical assessment, subjective questionnaires to assess nasal symptoms and evaluation of nasal resistance with acoustic rhinometry (AR) and active anterior rhinomanometry (RM) in the sitting and supine positions. Patients underwent nocturnal polysomnography on optimal CPAP with measurements of supraglottic pressure to evaluate upper airway resistance. Comparisons were made between nasal resistance using AR and RM during wakefulness, and between AR and RM awake and upper airway resistance during sleep. RESULTS: Our study shows that measures of awake nasal resistance using AR and RM had little or no correlation to each other in the sitting position, whereas there was significant but weak correlation in the supine position. Upper airway resistance measured while on CPAP during sleep did not show significant relationships to any of the awake measures of nasal resistance (AR or RM). CONCLUSION: Awake measurements of nasal resistance do not seem to be predictive of upper airway resistance during sleep on CPAP.