1,880 research outputs found

    Hypoxia is an effective stimulus for vesicular release of ATP from human umbilical vein endothelial cells

    Get PDF
    AbstractIntroductionHypoxia induces dilatation of the umbilical vein by releasing autocoids from endothelium; prostaglandins (PGs), adenosine and nitric oxide (NO) have been implicated. ATP is vasoactive, thus we tested whether hypoxia releases ATP from primary Human Umbilical Vein Endothelial Cells (HUVEC).MethodsHUVEC were grown on inserts under no-flow conditions. ATP was assayed by luciferin–luciferase and visualised by quinacrine labeling. Intracellular Ca2+ ([Ca2+]i) was imaged with Fura-2.ResultsATP release occurred constitutively and was increased by hypoxia (PO2: 150–8 mmHg), ∼10-fold more from apical, than basolateral surface. Constitutive ATP release was decreased, while hypoxia-induced release was abolished by brefeldin or monensin A, inhibitors of vesicular transport, and LY294002 or Y27632, inhibitors of phosphoinositide 3-kinases (PI3K) and Rho-associated protein kinase (ROCK). ATP release was unaffected by NO donor, but increased by calcium ionophore, by >60-fold from apical, but <25% from basolateral surface. Hypoxia induced a small increase in [Ca2+]i compared with ATP (10 μM); hypoxia inhibited the ATP response. Quinacrine-ATP fluorescent loci in the perinuclear space, were diminished by hypoxia and monensin, whereas brefeldin A increased fluorescence intensity, consistent with inhibition of anterograde transport.Discussion.Hypoxia within the physiological range releases ATP from HUVEC, particularly from apical/adluminal surfaces by exocytosis, via an increase in [Ca2+]i, PI3K and ROCK, independently of NO. We propose that hypoxia releases ATP at concentrations sufficient to induce umbilical vein dilation via PGs and NO and improve fetal blood flow, but curbs amplification of ATP release by autocrine actions of ATP, so limiting its pro-inflammatory effects

    A role of ATP in modulating vasomotion during hypoxia in umbilical cord blood vessels

    Get PDF
    Previous studies have associated intracellular calcium ([Ca2+]i) oscillations in vascular smooth muscle cells (SMC) with vasomotion in multiple species. In normal and pre-eclamptic pregnancies, there is strong evidence to suggest that the intrauterine environment is hypoxic. The aim of this study was to investigate whether ATP and [Ca2+]i oscillations play a role in modulating vasomotion during hypoxia in human umbilical blood vessels. The results obtained from in vitro studies using firefly luciferase assay and quinacrine staining indicated that human umbilical artery and vein endothelial cell (HUAEC, HUVEC respectively) constitutively released ATP and, in HUVEC at least, the release was accentuated by hypoxia (7.6 mmHg O2, 30 min). This release is dependent on the PI3K/ROCK pathway, and on normal vesicular transport. Further, application of ATP to human umbilical artery SMC induced dose-dependent [Ca2+]i oscillations, which was mediated by P2Y4 receptor. Moreover, ex vivo data from freshly isolated umbilical artery rings showed that acute hypoxia increased the frequency of vasomotion. It is therefore proposed that the findings of the present study is important in the understanding of the behaviour of human umbilical vessels in normal pregnancy, but may also have implications in the pathophysiology of complicated pregnancy such as pre-eclampsia

    Examining Differences Between Asian Americans and Whites for Gambling and Drinking

    Full text link
    Limited research have examined the ethnic differences in gambling and drinking among emerging adults, therefore; little is known about what is placing Asian American at-risk for involvement with these behaviors. The purpose of this study was to examine ethnic differences in risk factors between Asian Americans and White Americans for gambling and drinking at the two levels of involvement: abstinence and problems. The main objective 1) if there are ethnic differences among emerging adults in gambling and drinking involvement, 2) why these differences exist, and 3) which impulsivity and psychological distress variables are specific to each of these ethnic groups. The sample consisted of college students, A total of 823 participants, 414 (50.3%) females and 409 (49.7%) males, with an age range of 18-36 from the psychology subject pool of a large West Coast university were selected for this study. The sample was composed of 464 (56.4%) Asian Americans and 359 (43.6%) White Americans. White Americans were found to abstain less and develop more problems associated with drinking. No ethnic differences were found for gambling abstinence. Asian Americans were developing more problems gambling compared to White Americans. Ethnic differences were also found through risk-factors at each level of involvement with Asian Americans being highly correlated to psychological distress risk-factors and White Americans impulsivity factors. Of these risk factors, depression and belief in good luck (BIGL) mediated for problem gambling and social anxiety mediated for drinking abstinence. Overall, results indicated an increase need for more culturally sensitive and comprehensive based treatment and prevention programs

    First Results from Fermi GBM Earth Occultation Monitoring: Observations of Soft Gamma-Ray Sources Above 100 keV

    Get PDF
    The NaI and BGO detectors on the Gamma-ray Burst Monitor (GBM) on Fermi are now being used for long-term monitoring of the hard X-ray/low energy gamma-ray sky. Using the Earth occultation technique as demonstrated previously by the BATSE instrument on the Compton Gamma-Ray Observatory, GBM can be used to produce multiband light curves and spectra for known sources and transient outbursts in the 8 keV to 1 MeV energy range with its NaI detectors and up to 40 MeV with its BGO detectors. Over 85% of the sky is viewed every orbit, and the precession of the Fermi orbit allows the entire sky to be viewed every ~26 days with sensitivity exceeding that of BATSE at energies below ~25 keV and above ~1.5 MeV. We briefly describe the technique and present preliminary results using the NaI detectors after the first two years of observations at energies above 100 keV. Eight sources are detected with a significance greater than 7 sigma: the Crab, Cyg X-1, SWIFT J1753.5-0127, 1E 1740-29, Cen A, GRS 1915+105, and the transient sources XTE J1752-223 and GX 339-4. Two of the sources, the Crab and Cyg X-1, have also been detected above 300 keV.Comment: 13 pages, 9 figures, submitted to Ap

    Self-Supervised Learning with Limited Labeled Data for Prostate Cancer Detection in High Frequency Ultrasound

    Full text link
    Deep learning-based analysis of high-frequency, high-resolution micro-ultrasound data shows great promise for prostate cancer detection. Previous approaches to analysis of ultrasound data largely follow a supervised learning paradigm. Ground truth labels for ultrasound images used for training deep networks often include coarse annotations generated from the histopathological analysis of tissue samples obtained via biopsy. This creates inherent limitations on the availability and quality of labeled data, posing major challenges to the success of supervised learning methods. On the other hand, unlabeled prostate ultrasound data are more abundant. In this work, we successfully apply self-supervised representation learning to micro-ultrasound data. Using ultrasound data from 1028 biopsy cores of 391 subjects obtained in two clinical centres, we demonstrate that feature representations learnt with this method can be used to classify cancer from non-cancer tissue, obtaining an AUROC score of 91% on an independent test set. To the best of our knowledge, this is the first successful end-to-end self-supervised learning approach for prostate cancer detection using ultrasound data. Our method outperforms baseline supervised learning approaches, generalizes well between different data centers, and scale well in performance as more unlabeled data are added, making it a promising approach for future research using large volumes of unlabeled data

    Rationale for UV-filtered clover fermions

    Full text link
    We study the contributions Sigma_0 and Sigma_1, proportional to a^0 and a^1, to the fermion self-energy in Wilson's formulation of lattice QCD with UV-filtering in the fermion action. We derive results for m_{crit} and the renormalization factors Z_S, Z_P, Z_V, Z_A to 1-loop order in perturbation theory for several filtering recipes (APE, HYP, EXP, HEX), both with and without a clover term. The perturbative series is much better behaved with filtering, in particular tadpole resummation proves irrelevant. Our non-perturbative data for m_{crit} and Z_A/(Z_m*Z_P) show that the combination of filtering and clover improvement efficiently reduces the amount of chiral symmetry breaking -- we find residual masses am_{res}=O(10^{-2}).Comment: 25 pages, 4 figures; v2: typo in eqn. (37) fixed [agrees with published version

    Unloading knee brace is a cost-effective method to bridge and delay surgery in unicompartmental knee arthritis

    Get PDF
    AbstractBackground Unloading knee braces can provide good short-term pain relief for some patients with unicompartmental osteoarthritis (UOA). Their cost is relatively small compared with surgical interventions. However, no previous studies have reported their use over a duration of 5 years or more.Methods Up to 8 years of prospective data were collected from 63 patients who presented with UOA. After conservative management with analgesia and physiotherapy, patients were offered an unloading brace. EQ-5D (EuroQol five dimensions) questionnaires were collected at baseline and after wearing the brace. Cost and quality-adjusted life years (QALYs) were compared with a total knee replacement (TKR) with an 8-month waiting duration and 8 years of results.Results Patients experienced a mean increase in EQ-5D of 0.42 with an average duration of wear of 26.1 months resulting in an increase of 0.44 in QALYs with a mean cost of £625. The adoption of an unloader knee brace was found to be a short-term cost-effective treatment option with an 8-month incremental cost effectiveness ratio of £9599. Compared with no treatment, the unloader knee brace can be considered cost effective at 4 months or more. At 8 years follow-up, the unloader knee brace demonstrated QALYs gain of 0.43 and with an incremental cost-effectiveness ratio of -£6467 compared with TKR.Conclusion Unloading knee braces are cost effective for the management of UOA. These findings strongly support the undertaking of further research into the long-term impact of unloading knee brace. The unloader knee brace has benefits to the National Health Service for capacity, budget, waiting list duration, frequency of surgery and reducing the required severity of surgical intervention

    Vitamin D deficiency is associated with IL-6 levels and monocyte activation in HIV-infected persons

    Get PDF
    Immune activation plays a key role in HIV pathogenesis. Markers of inflammation have been associated with vitamin D deficiency in the general population. Studies have also demonstrated associations of vitamin D deficiency with increased risk of HIV progression and death. The relationship between persistent inflammation and immune activation during chronic HIV infection and vitamin D deficiency remains unclear.Cryopreserved specimens were analyzed from 663 participants at the time of enrollment from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) from 2004 to 2006. Biomarkers of inflammation, atherosclerosis, and coagulation were measured using enzyme-linked immunosorbent assays (ELISAs) and electrochemiluminescence. 25(OH)D, the stable precursor form of vitamin D, was measured using a radioimmunoassay with levels defined as: normal (≥30ng/mL), insufficient (20-29 ng/mL) and deficient (<20 ng/mL). Monocyte phenotypes were assessed by flow cytometry. Linear and logistic regression models were used to determine statistical associations between biomarkers and vitamin D deficiency.25(OH)D levels were deficient in 251 (38%) participants, insufficient in 222 (34%), and normal in 190 (29%). Patients with vitamin D deficiency, when compared to those with insufficient or normal vitamin D levels, had increased levels of IL-6 (23%; p<0.01), TNF-α (21%, p = 0.03), D-dimer (24%, p = 0.01), higher proportions of CD14dimCD16+ (22%, p<0.01) and CX3CR1+ monocytes (48%; p<0.001) and decreased frequency of CCR2+ monocytes (-3.4%, p<0.001). In fully adjusted models, vitamin D associations with abnormal biomarker levels persisted for IL-6 levels and CX3CR1+ and CCR2+ phenotypes.Vitamin D deficiency is associated with greater inflammation and activated monocyte phenotypes. The role of vitamin D deficiency in persistent immune activation and associated complications during chronic HIV disease should be further evaluated as a possible target for intervention

    Benchmarking Image Transformers for Prostate Cancer Detection from Ultrasound Data

    Full text link
    PURPOSE: Deep learning methods for classifying prostate cancer (PCa) in ultrasound images typically employ convolutional networks (CNNs) to detect cancer in small regions of interest (ROI) along a needle trace region. However, this approach suffers from weak labelling, since the ground-truth histopathology labels do not describe the properties of individual ROIs. Recently, multi-scale approaches have sought to mitigate this issue by combining the context awareness of transformers with a CNN feature extractor to detect cancer from multiple ROIs using multiple-instance learning (MIL). In this work, we present a detailed study of several image transformer architectures for both ROI-scale and multi-scale classification, and a comparison of the performance of CNNs and transformers for ultrasound-based prostate cancer classification. We also design a novel multi-objective learning strategy that combines both ROI and core predictions to further mitigate label noise. METHODS: We evaluate 3 image transformers on ROI-scale cancer classification, then use the strongest model to tune a multi-scale classifier with MIL. We train our MIL models using our novel multi-objective learning strategy and compare our results to existing baselines. RESULTS: We find that for both ROI-scale and multi-scale PCa detection, image transformer backbones lag behind their CNN counterparts. This deficit in performance is even more noticeable for larger models. When using multi-objective learning, we can improve performance of MIL, with a 77.9% AUROC, a sensitivity of 75.9%, and a specificity of 66.3%. CONCLUSION: Convolutional networks are better suited for modelling sparse datasets of prostate ultrasounds, producing more robust features than transformers in PCa detection. Multi-scale methods remain the best architecture for this task, with multi-objective learning presenting an effective way to improve performance.Comment: early draft, 7 pages; Accepted to SPIE Medical Imaging 202

    Case report: Co-occurring obsessive-compulsive disorder and affective psychotic disorder complicated by catatonia in an adolescent female patient

    Get PDF
    We present the case of a 16-year-old female patient who experienced the loss of her mother to suicide, leading to post-traumatic stress disorder and prominent mood symptoms. She developed catatonic features during her inpatient psychiatric hospitalization following her own suicide attempt. Over her hospital course, she began to demonstrate signs of co-occurring obsessive-compulsive disorder (OCD) and affective psychotic disorder obfuscated by the severity of her catatonia. After initial workup including neurologic evaluation, laboratory tests, imaging (EEG, MRI), the patient was stabilized on a combination of benzodiazepines, antipsychotics, mood stabilizers, and selective serotonin reuptake inhibitors. The diagnostic challenges of disambiguating multiple concurrent diagnoses in the presence of a syndrome with unclear pathophysiology are discussed. Recommendations are made to thoroughly evaluate thought content during periods of catatonic remission to guide diagnosis and treatment
    • …
    corecore