Lipid Biosynthesis Coordinates a Mitochondrial-to-Cytosolic Stress Response.

Defects in mitochondrial metabolism have been increasingly linked with age-onset protein-misfolding diseases such as Alzheimer's, Parkinson's, and Huntington's. In response to protein-folding stress, compartment-specific unfolded protein responses (UPRs) within the ER, mitochondria, and cytosol work in parallel to ensure cellular protein homeostasis. While perturbation of individual compartments can make other compartments more susceptible to protein stress, the cellular conditions that trigger cross-communication between the individual UPRs remain poorly understood. We have uncovered a conserved, robust mechanism linking mitochondrial protein homeostasis and the cytosolic folding environment through changes in lipid homeostasis. Metabolic restructuring caused by mitochondrial stress or small-molecule activators trigger changes in gene expression coordinated uniquely by both the mitochondrial and cytosolic UPRs, protecting the cell from disease-associated proteins. Our data suggest an intricate and unique system of communication between UPRs in response to metabolic changes that could unveil new targets for diseases of protein misfolding.

Tunnel junction sensing of TATP explosive at the single-molecule level.

Triacetone triperoxide (TATP) is a highly potent homemade explosive commonly used in terrorist attacks. Its detection poses a significant challenge due to its volatility, and the lack of portability of current sensing techniques. To address this issue, we propose a novel approach based on single-molecule TATP detection in the air using a device where tunneling current in N-terminated carbon-nanotubes nanogaps is measured. By employing the density functional theory combined with the non-equilibrium Green's function method, we show that current of tens of nanoamperes passes through TATP trapped in the nanogap, with a discrimination ratio of several orders of magnitude even against prevalent indoor volatile organic compounds (VOCs). This high tunneling current through TATP's highest occupied molecular orbital (HOMO) is facilitated by the strong electric field generated by N-C polar bonds at the electrode ends and by the hybridization between TATP and the electrodes, driven by oxygen atoms within the probed molecule. The application of the same principle is discussed for graphene nanogaps and break-junctions.

Deep Learning Based SWIR Object Detection in Long-Range Surveillance Systems: An Automated Cross-Spectral Approach.

SWIR imaging bears considerable advantages over visible-light (color) and thermal images in certain challenging propagation conditions. Thus, the SWIR imaging channel is frequently used in multi-spectral imaging systems (MSIS) for long-range surveillance in combination with color and thermal imaging to improve the probability of correct operation in various day, night and climate conditions. Integration of deep-learning (DL)-based real-time object detection in MSIS enables an increase in efficient utilization for complex long-range surveillance solutions such as border or critical assets control. Unfortunately, a lack of datasets for DL-based object detection models training for the SWIR channel limits their performance. To overcome this, by using the MSIS setting we propose a new cross-spectral automatic data annotation methodology for SWIR channel training dataset creation, in which the visible-light channel provides a source for detecting object types and bounding boxes which are then transformed to the SWIR channel. A mathematical image transformation that overcomes differences between the SWIR and color channel and their image distortion effects for various magnifications are explained in detail. With the proposed cross-spectral methodology, the goal of the paper is to improve object detection in SWIR images captured in challenging outdoor scenes. Experimental tests for two object types (cars and persons) using a state-of-the-art YOLOX model demonstrate that retraining with the proposed automatic cross-spectrally created SWIR image dataset significantly improves average detection precision. We achieved excellent improvements in detection performance in various variants of the YOLOX model (nano, tiny and x).

Ultrasound-Assisted Water Extraction of Gentiopicroside, Isogentisin, and Polyphenols from Willow Gentian "Dust" Supported by Hydroxypropyl-ß-Cyclodextrin as Cage Molecules.

The residue after sieving ("dust") from the willow gentian underground parts is an unexploited herbal tea by-product, although it contains valuable bioactive compounds. Cyclodextrins as efficient green co-solvents, cage molecules, and multifunctional excipients could improve the extraction and contribute to the added value of the resulting extracts. The objective of this study was to determine the optimal conditions for the extraction of gentiopicroside, isogentisin, and total phenolics (TPC) from willow gentian "dust" using ultrasound-assisted water extraction coupled with hydroxypropyl-ß-cyclodextrin (HPßCD). The influence of extraction temperature (X1: 20-80 °C), time (X2: 20-50 min), and HPßCD concentration (X3: 2-4% w/v) was analyzed employing the response surface methodology (RSM). The optimal extraction conditions for simultaneously maximizing the extraction yield of all monitored responses were X1: 74.89 °C, X2: 32.57 min, and X3: 3.01% w/v. The experimentally obtained response values under these conditions (46.96 mg/g DW for gentiopicroside, 0.51 mg/g DW for isogentisin, and 12.99 mg GAE/g DW for TPC) were in close agreement with those predicted, thus confirming the suitability and good predictive accuracy of the developed RSM models. Overall, the developed extraction system could be an applicable alternative strategy to improve the extraction of bioactive compounds from the underutilized "dust" of willow gentian underground parts.

Field Effect and Local Gating in Nitrogen-Terminated Nanopores (NtNP) and Nanogaps (NtNG) in Graphene.

Functionalization of electrodes is a wide-used strategy in various applications ranging from single-molecule sensing and protein sequencing, to ion trapping, to desalination. We demonstrate, employing non-equilibrium Green's function formalism combined with density functional theory, that single-species (N, H, S, Cl, F) termination of graphene nanogap electrodes results in a strong in-gap electrostatic field, induced by species-dependent dipoles formed at the electrode ends. Consequently, the field increases or decreases electronic transport through a molecule (benzene) placed in the nanogap by shifting molecular levels by almost 2 eV in respect to the electrode Fermi level via a field effect akin to the one used for field-effect transistors. We also observed the local gating in graphene nanopores terminated with different single-species atoms. Nitrogen-terminated nanogaps (NtNGs) and nanopores (NtNPs) show the strongest effect. The in-gap potential can be transformed from a plateau-like to a saddle-like shape by tailoring NtNG and NtNP size and termination type. In particular, the saddle-like potential is applicable in single-ion trapping and desalination devices.

Distributed Spectrum Management in Cognitive Radio Networks by Consensus-Based Reinforcement Learning.

In this paper, we propose a new algorithm for distributed spectrum sensing and channel selection in cognitive radio networks based on consensus. The algorithm operates within a multi-agent reinforcement learning scheme. The proposed consensus strategy, implemented over a directed, typically sparse, time-varying low-bandwidth communication network, enforces collaboration between the agents in a completely decentralized and distributed way. The motivation for the proposed approach comes directly from typical cognitive radio networks' practical scenarios, where such a decentralized setting and distributed operation is of essential importance. Specifically, the proposed setting provides all the agents, in unknown environmental and application conditions, with viable network-wide information. Hence, a set of participating agents becomes capable of successful calculation of the optimal joint spectrum sensing and channel selection strategy even if the individual agents are not. The proposed algorithm is, by its nature, scalable and robust to node and link failures. The paper presents a detailed discussion and analysis of the algorithm's characteristics, including the effects of denoising, the possibility of organizing coordinated actions, and the convergence rate improvement induced by the consensus scheme. The results of extensive simulations demonstrate the high effectiveness of the proposed algorithm, and that its behavior is close to the centralized scheme even in the case of sparse neighbor-based inter-node communication.

On Consensus-Based Distributed Blind Calibration of Sensor Networks.

This paper deals with recently proposed algorithms for real-time distributed blind macro-calibration of sensor networks based on consensus (synchronization). The algorithms are completely decentralized and do not require a fusion center. The goal is to consolidate all of the existing results on the subject, present them in a unified way, and provide additional important analysis of theoretical and practical issues that one can encounter when designing and applying the methodology. We first present the basic algorithm which estimates local calibration parameters by enforcing asymptotic consensus, in the mean-square sense and with probability one (w.p.1), on calibrated sensor gains and calibrated sensor offsets. For the more realistic case in which additive measurement noise, communication dropouts and additive communication noise are present, two algorithm modifications are discussed: one that uses a simple compensation term, and a more robust one based on an instrumental variable. The modified algorithms also achieve asymptotic agreement for calibrated sensor gains and offsets, in the mean-square sense and w.p.1. The convergence rate can be determined in terms of an upper bound on the mean-square error. The case when the communications between nodes is completely asynchronous, which is of substantial importance for real-world applications, is also presented. Suggestions for design of a priori adjustable weights are given. We also present the results for the case in which the underlying sensor network has a subset of (precalibrated) reference sensors with fixed calibration parameters. Wide applicability and efficacy of these algorithms are illustrated on several simulation examples. Finally, important open questions and future research directions are discussed.

Clinical significance of microvessel density and proliferation in prostate cancer core biopsy.

PURPOSE: To investigate the microvessel density (MVD) and proliferation in prostate cancer (PC) core biopsies. METHODS: Core biopsy samples of PC tissue from 45 patients were routinely processed and embedded in paraffin. The samples of PC formed the investigated group (n=25), while samples of benign prostatic hyperplasia (BPH) served as controls (n=20). From paraffin blocks, 3-5 µm-thick sections were made and routine hematoxylin-eosin method and immunohistochemical ABC method with Ki67 and CD34 antibodies were applied. Immunohistochemical expression of Ki67 and CD34 was stereometrically quantified. RESULTS: The median number of Ki67 and CD34 positive cells per mm2 in PC were significantly higher in comparison to the median of these cells in BHP. The average age and Gleason score in patients with high proliferation index (proIDX) and MVD index (mvdIDX) was significantly greater in comparison to those with low proIDX and low mvdIDX. The absolute values of Ki67 expression were in highly positive and significant correlation with the absolute values of CD34 expression. Highly significant correlation was found between Gleason score and proIDX and mvdIDX. CONCLUSION: This study showed that PC expressed significantly higher values of Ki67 and CD34 in comparison to BPH. The values of proIDX and mvdIDX obtained by core biopsy could clearly show the level of cancer progression expressed through highly correlated Gleason score. In this way it is possible to identify the patients at high risk for disease progression.

Endothelial function and sleep: associations of flow-mediated dilation with perceived sleep quality and rapid eye movement (REM) sleep.

Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps < 0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.

The changes in tissue histomorphology and quality of DNA in healthy human autopsied tissues stored at -20 °C and -150 °C.

The aim of this study was to compare the changes in tissue histomorphology and DNA quality in six different healthy tissues (brain, heart, lung, liver, spleen and kidney) exempted during autopsy of healthy individuals and storage at -20 °C and -150 °C three month. Tissue samples were obtained, divided by tissue and temperature group, and for each sample, tissue histomorphology and DNA (isolated from all tissues in duplicated - 72 samples of DNA) quality were analysed. Morphology of tissue samples was studied using H&E staining. DNA was isolated using the phenol-chloroform-isoamyl alcohol method. To assess the concentration and purity of the DNA samples, we used a spectrophotometer to measure absorbance at wavelengths of 280 nm and 260 nm. The fragments of human telomerase reverse transcriptase (hTERT) gene were amplified from the DNA using PCR reaction and then visualised using the 2 % agarose gel. Samples stored at -150 °C sustained the highest degree of histomorphological damage, while samples stored at -20 °C were less degraded, compared to control. The liver samples stored at -20 °C had a mean DNA concentration (1030.4 ± 51.5 ng/µl) higher than the samples of liver tissue stored at -150 °C (497.4 ± 167.1 ng/µl) (p < 0.001). Other tissues did not have statistically significantly different DNA concentration at both temperatures. Liver samples at -20 °C had degraded DNA, showed as the absence of hTERT gene in most of samples. Other tissue samples in both temperature groups had unfragmented DNA. Storing tissue samples at -20 °C is not inferior in terms of DNA yield and integrity, and possibly superior for tissue histomorphology, comparing with samples stored at -150°C.

Spasmolytic, Antimicrobial, and Antioxidant Activities of Spray-Dried Extracts of Gentiana asclepiadea L. with In Silico Pharmacokinetic Analysis.

This study aimed to evaluate the spasmolytic activity of an underground parts extract of Gentiana asclepiadea L. (Gentianaceae), assess its antioxidant and antimicrobial activities, and explore the impact of extract encapsulation on the aforementioned bioactivities. An extract encapsulated by spray drying with whey protein, pure extract, and pure whey protein were comparatively tested. The main compounds identified via HPLC-DAD analysis underwent in silico ADME assessment. The spasmolytic effect was tested on a model of spontaneous rat ileum contractions, and the mechanism of action was further evaluated on acetylcholine-, KCl-, CaCl2-, BaCl2-, histamine-, N(ω)-nitro-L-arginine methyl ester-, and glibenclamide-modified contractions. The most abundant compounds were secoiridoids (dominantly gentiopicroside), followed by C-glycosylated flavonoids and xanthones. Both pure and encapsulated extracts achieved significant spasmolytic effects, despite the spasmogenic activity of pure whey protein. The extract may exert its spasmolytic effect through multiple pathways, predominantly by antagonizing the Ca2+ channel and opening the K+ channel, while the nitric oxide pathway appears not to be involved. The antimicrobial and antioxidant activities of the pure extract were moderate. The extract stabilized by encapsulation retained all of the tested bioactivities of the unencapsulated extract. The obtained results suggest that G. asclepiadea has potential for use in the treatment of some gastrointestinal complaints and that the encapsulated extract could be a valuable functional ingredient in pharmaceutical and food products.

Natural deep eutectic solvents combined with cyclodextrins: A novel strategy for chokeberry anthocyanins extraction.

Innovative eco-friendly methods based on natural deep eutectic solvents (NaDES) coupled with ultrasound-assisted extraction were employed for chokeberry anthocyanins extractions. Nine different NaDES composed of choline chloride as a hydrogen bond acceptor and organic acids (lactic, citric, malic), sugars (glucose, fructose), polyols (glycerol, 1,2-propanediol, sorbitol), and an amide (urea) as hydrogen bond donors were screened. Malic acid-containing NaDES was selected for optimization extraction conditions (time, temperature, water in NaDES) by response surface methodology. Optimal conditions for simultaneously maximizing the anthocyanins extraction (cyanidin-3-O-glucoside, cyanidin-3-O-galactoside, cyanidin-3-O-arabinoside, total anthocyanins) were 42.7 °C, 90 min, and 40 % (w/w) water in NaDES. In the next stage of this study, the possibility to improve anthocyanins extraction at elevated temperatures by incorporating different concentrations of hydroxypropyl-ß-cyclodextrin into selected NaDES was investigated. The extraction was improved at hydroxypropyl-ß-cyclodextrin concentrations up to 3 % (w/w). To clarify the interaction of NaDES components and anthocyanins, a molecular dynamic simulation was conducted.

Endocytic trafficking determines cellular tolerance of presynaptic opioid signaling.

Opioid tolerance is well-described physiologically but its mechanistic basis remains incompletely understood. An important site of opioid action in vivo is the presynaptic terminal, where opioids inhibit transmitter release. This response characteristically resists desensitization over minutes yet becomes gradually tolerant over hours, and how this is possible remains unknown. Here, we delineate a cellular mechanism underlying this longer-term form of opioid tolerance in cultured rat medium spiny neurons. Our results support a model in which presynaptic tolerance is mediated by a gradual depletion of cognate receptors from the axon surface through iterative rounds of receptor endocytosis and recycling. For the µ-opioid receptor (MOR), we show that the agonist-induced endocytic process which initiates iterative receptor cycling requires GRK2/3-mediated phosphorylation of the receptor's cytoplasmic tail, and that partial or biased agonist drugs with reduced ability to drive phosphorylation-dependent endocytosis in terminals produce correspondingly less presynaptic tolerance. We then show that the δ-opioid receptor (DOR) conforms to the same general paradigm except that presynaptic endocytosis of DOR, in contrast to MOR, does not require phosphorylation of the receptor's cytoplasmic tail. Further, we show that DOR recycles less efficiently than MOR in axons and, consistent with this, that DOR tolerance develops more strongly. Together, these results delineate a cellular basis for the development of presynaptic tolerance to opioids and describe a methodology useful for investigating presynaptic neuromodulation more broadly.

Ultrasound-Assisted Natural Deep Eutectic Solvents Extraction of Bilberry Anthocyanins: Optimization, Bioactivities, and Storage Stability.

Bilberry fruits (Vaccinium myrtillus L.) are one of the richest natural sources of anthocyanins and are widely used due to their pharmacological and nutritional properties. To ensure their maximum application potential, it is necessary to overcome the limitations of conventional extraction solvents and techniques. This study aimed to develop a green method for bilberry anthocyanin extraction using natural deep eutectic solvents (NaDES) integrated with ultrasound-assisted extraction (UAE) in order to define extraction conditions that will prevent decomposition of the anthocyanins or the loss of bioactivity. After a screening of ten different NaDES, choline chloride:sorbitol (1:1) was selected as the most effective. Furthermore, the influence analysis and optimization of the NaDES-UAE extraction conditions were carried out employing response surface methodology. The optimal conditions were found to be an extraction time of 37.63 min, a temperature of 48.38 °C, and 34.79% (w/w) water in NaDES. The extraction yields of target compounds under optimized extraction conditions were 0.27 mg/g DW of cyanidin-3-O-glucoside and 2.12 mg CGE/g DW of TAC. The obtained optimized extract showed promising radical scavenging and antimicrobial activity. A stability study with the optimized extract revealed that refrigerated storage at 4 °C in the dark provided the best anthocyanins preservation. Overall, the developed NaDES-UAE method showed promising application potential and can be considered as a high-efficiency green alternative to conventional anthocyanins extraction methods, enabling the preservation of active ingredients and the bioactivity of extracts.

Decoding CAR T cell phenotype using combinatorial signaling motif libraries and machine learning.

Chimeric antigen receptor (CAR) costimulatory domains derived from native immune receptors steer the phenotypic output of therapeutic T cells. We constructed a library of CARs containing ~2300 synthetic costimulatory domains, built from combinations of 13 signaling motifs. These CARs promoted diverse human T cell fates, which were sensitive to motif combinations and configurations. Neural networks trained to decode the combinatorial grammar of CAR signaling motifs allowed extraction of key design rules. For example, non-native combinations of motifs that bind tumor necrosis factor receptor-associated factors (TRAFs) and phospholipase C gamma 1 (PLCγ1) enhanced cytotoxicity and stemness associated with effective tumor killing. Thus, libraries built from minimal building blocks of signaling, combined with machine learning, can efficiently guide engineering of receptors with desired phenotypes.

Depressed mood and flow-mediated dilation: a systematic review and meta-analysis.

OBJECTIVE: This systematic and quantitative review evaluates the literature on associations between depressed mood and flow-mediated dilation (FMD), a measure of endothelial function, in adults. METHODS: Published English-language articles (through December 2010) were identified from literature searches, assessed for data extraction, and evaluated for quality. RESULTS: The literature includes cross-sectional (n = 9) and retrospective examinations (n = 3) of how FMD correlates with clinical or subclinical depression in healthy adults and cardiovascular patients (total N across 12 studies = 1491). FMD was assessed using a variety of methodologies. Samples were predominately older white and Asian subjects with higher socioeconomic status. In eight of the 12 articles selected for this review, at least one significant inverse association was noted between depressed mood and FMD, with primarily moderate effect sizes. The overall meta-analysis (random-effects model) revealed a combined effect size of correlation coefficient r = 0.19 (95% confidence interval = 0.08-0.29, p = .001). Significant combined effects were found for subgroups of studies that a) received better quality ratings (r = 0.29), b) examined patients with cardiovascular disease or with cardiovascular disease risk factors/comorbidity (r = 0.29), c) used maximum vasodilation to quantify FMD (r = 0.27), and d) assessed samples that had a mean age of 55 years and older (r = 0.15). CONCLUSIONS: Diverse studies support the inverse correlation between depressed mood and endothelial function, as measured by FMD. This literature would be strengthened by prospective studies, increased methodological consistency in FMD testing, and broader sampling (e.g., African Americans, younger age, lower socioeconomic status).

Predicting Finite-Bias Tunneling Current Properties from Zero-Bias Features: The Frontier Orbital Bias Dependence at an Exemplar Case of DNA Nucleotides in a Nanogap.

The electrical current properties of single-molecule sensing devices based on electronic (tunneling) transport strongly depend on molecule frontier orbital energy, spatial distribution, and position with respect to the electrodes. Here, we present an analysis of the bias dependence of molecule frontier orbital properties at an exemplar case of DNA nucleotides in the gap between H-terminated (3, 3) carbon nanotube (CNT) electrodes and its relation to transversal current rectification. The electronic transport properties of this simple single-molecule device, whose characteristic is the absence of covalent bonding between electrodes and a molecule between them, were obtained using density functional theory and non-equilibrium Green's functions. As in our previous studies, we could observe two distinct bias dependences of frontier orbital energies: the so-called strong and the weak pinning regimes. We established a procedure, from zero-bias and empty-gap characteristics, to estimate finite-bias electronic tunneling transport properties, i.e., whether the molecular junction would operate in the weak or strong pinning regime. We also discuss the use of the zero-bias approximation to calculate electric current properties at finite bias. The results from this work could have an impact on the design of new single-molecule applications that use tunneling current or rectification applicable in high-sensitivity sensors, protein, or DNA sequencing.

SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma.

Treatment of solid cancers with chimeric antigen receptor (CAR) T cells is plagued by the lack of ideal target antigens that are both absolutely tumor specific and homogeneously expressed. We show that multi-antigen prime-and-kill recognition circuits provide flexibility and precision to overcome these challenges in the context of glioblastoma. A synNotch receptor that recognizes a specific priming antigen, such as the heterogeneous but tumor-specific glioblastoma neoantigen epidermal growth factor receptor splice variant III (EGFRvIII) or the central nervous system (CNS) tissue-specific antigen myelin oligodendrocyte glycoprotein (MOG), can be used to locally induce expression of a CAR. This enables thorough but controlled tumor cell killing by targeting antigens that are homogeneous but not absolutely tumor specific. Moreover, synNotch-regulated CAR expression averts tonic signaling and exhaustion, maintaining a higher fraction of the T cells in a naïve/stem cell memory state. In immunodeficient mice bearing intracerebral patient-derived xenografts (PDXs) with heterogeneous expression of EGFRvIII, a single intravenous infusion of EGFRvIII synNotch-CAR T cells demonstrated higher antitumor efficacy and T cell durability than conventional constitutively expressed CAR T cells, without off-tumor killing. T cells transduced with a synNotch-CAR circuit primed by the CNS-specific antigen MOG also exhibited precise and potent control of intracerebral PDX without evidence of priming outside of the brain. In summary, by using circuits that integrate recognition of multiple imperfect but complementary antigens, we improve the specificity, completeness, and persistence of T cells directed against glioblastoma, providing a general recognition strategy applicable to other solid tumors.

Adverse impact of mood on flow-mediated dilation.

OBJECTIVE: To examine the impact of mood states on endothelial function, as measured noninvasively by brachial artery flow-mediated dilation (FMD). Substantial literature indicates that negative mood is linked to cardiovascular disease (CVD). However, the mechanisms underlying this relationship are not well defined. CVD is often preceded by dysfunction of the endothelium. METHODS: Healthy adults (n = 70; mean age, 36 years) completed the Profile of Mood States (POMS), which contains six subscales (depression/dejection; tension/anxiety; anger/hostility; confusion/bewilderment; fatigue/inertia; vigor/activity) that are used to compute a total mood disturbance score for overall psychological distress. FMD was calculated (maximum percentage change in brachial artery diameter) from ultrasound assessment of arterial diameter at baseline and for 10 minutes after occlusion. RESULTS: Regressions showed that increases in POMS total mood disturbance scores were associated with decreases in endothelial function. Mood disturbance explained 10% of the variance in FMD (p < .01), after controlling for age, sex, mean arterial pressure, body mass index, and socially desirable response bias. An exploratory set of separate regressions conducted to decompose the link between FMD and total mood disturbance revealed that the following POMS subscales were inversely correlated with FMD: depression/dejection, tension/anxiety, anger/hostility, fatigue/inertia (p's < .05), and confusion/bewilderment (p < .01). CONCLUSIONS: Mood disturbance could contribute to CVD via impaired vasodilation. These preliminary results show that even mild levels of adverse psychological states, particularly depressed, anxious, angry, confused, and fatigued states, might be linked to increased cardiovascular risk.

Endothelial function: the impact of objective and subjective socioeconomic status on flow-mediated dilation.

BACKGROUND: Although objective and subjective indicators of socioeconomic status (SES) are linked to cardiovascular disease (CVD), little is known about their relationship to endothelial dysfunction, which often precedes CVD. PURPOSE: This study examined how objective and subjective SES relate to brachial artery flow-mediated dilation (FMD). METHODS: FMD was assessed in 72 healthy adults (mean age 36 years). The MacArthur Scale of Subjective Social Status assessed perceived social standing in the USA (SSS-USA) and local community (SSS-Community). Objective SES measures included income and the Hollingshead Two-Factor Index of Social Position (education, occupation). RESULTS: Adjusted regressions revealed that SSS-Community positively correlated with FMD (p < 0.05) and explained 8% of the variance. No other SES measures were significant for FMD. The association between FMD and SSS-Community remained significant (p < 0.01) after adjustment for objective SES and other covariates. CONCLUSIONS: Lower subjective social status in one's community may be linked to CVD via impaired vasodilation.