ABSTRACT
Increased adenosine A2A receptor (A2AR) expression and activation underlies a higher incidence of spontaneous calcium release in atrial fibrillation (AF). Adenosine A3 receptors (A3R) could counteract excessive A2AR activation, but their functional role in the atrium remains elusive, and we therefore aimed to address the impact of A3Rs on intracellular calcium homeostasis. For this purpose, we analyzed right atrial samples or myocytes from 53 patients without AF, using quantitative PCR, patch-clamp technique, immunofluorescent labeling or confocal calcium imaging. A3R mRNA accounted for 9% and A2AR mRNA for 32%. At baseline, A3R inhibition increased the transient inward current (ITI) frequency from 0.28 to 0.81 events/min (p < 0.05). Simultaneous stimulation of A2ARs and A3Rs increased the calcium spark frequency seven-fold (p < 0.001) and the ITI frequency from 0.14 to 0.64 events/min (p < 0.05). Subsequent A3R inhibition caused a strong additional increase in the ITI frequency (to 2.04 events/min; p < 0.01) and increased phosphorylation at s2808 1.7-fold (p < 0.001). These pharmacological treatments had no significant effects on L-type calcium current density or sarcoplasmic reticulum calcium load. In conclusion, A3Rs are expressed and blunt spontaneous calcium release at baseline and upon A2AR-stimulation in human atrial myocytes, pointing to A3R activation as a means to attenuate physiological and pathological elevations of spontaneous calcium release events.
Subject(s)
Atrial Fibrillation , Receptors, Purinergic P1 , Humans , Adenosine/metabolism , Atrial Fibrillation/metabolism , Calcium/metabolism , Calcium Signaling/physiology , Homeostasis , Myocytes, Cardiac/metabolism , Receptors, Purinergic P1/metabolism , RNA, Messenger/metabolism , Sarcoplasmic Reticulum/metabolismABSTRACT
STATEMENT OF PROBLEM: Scientific evidence to determine the optimal method of cleaning and disinfecting removable prostheses is lacking. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the effectiveness of effervescent tablets in the cleaning and sanitizing of removable prostheses compared with other chemical and physical methods by assessing the reduction of biofilm, microbial levels, and material stability. MATERIAL AND METHODS: A systematic literature search and meta-analysis was conducted in August 2021 in the MEDLINE/PubMed, Cochrane, Embase, Scopus, and Web of Science databases. Randomized and nonrandomized controlled clinical trials published in English were included without publication year limits. A total of 23 studies were included in the systematic review and 6 in the meta-analysis, which had been registered in the international prospective register of systematic reviews (PROSPERO) database (CRD42021274019). The Cochrane Collaboration tool was used to assess the risk of bias of randomized clinical trials. The physiotherapy evidence database (PEDro) scale was used to analyze the internal validity of clinical trials by assessing the quality of the data obtained. The studies included in the meta-analysis were combined by using a random-effects model with the inverse variance method. Publication bias was analyzed by using the Duvall and Tweedie trim-and-fill method. RESULTS: With regard to biofilm reduction, the standardized mean difference estimated with the 4 studies combined in the meta-analysis was P=.012: mean difference=-1.92; 95% confidence interval=-3.45 to -0.38, indicating a "large" effect of the combination of brushing and effervescent tablet versus brushing alone. To estimate the reduction in the total bacteria levels in the 3 combined studies, a "large" effect size was obtained for the combination of brushing and using an effervescent tablet versus brushing alone, P<.001: mean difference=-4.43; 95% confidence interval=-8.29 to -0.55. Finally, when the 3 studies were combined to assess the reduction of Candida or fungal infection, a "moderate" effect size was obtained for the combination of brushing combined with the use of an effervescent tablet, P<.001: mean difference=-0.78; 95% confidence interval=-1.19 to -0.37. CONCLUSIONS: The combination of brushing and the use of effervescent tablets versus brushing alone had a significantly higher effect on reducing biofilm and bacterial counts and a moderate effect on reducing Candida. Regarding color and dimensional stability, few studies were found, with the results depending on the concentration of the product and the immersion time of the device.
ABSTRACT
Atrial fibrillation (AF) is the most common form of cardiac arrhythmia seen in clinical practice. While some clinical parameters may predict the transition from paroxysmal to persistent AF, the molecular mechanisms behind the AF perpetuation are poorly understood. Thus, oxidative stress, calcium overload and inflammation, among others, are believed to be involved in AF-induced atrial remodelling. Interestingly, adenosine and its receptors have also been related to AF development and perpetuation. Here, we investigated the expression of adenosine A2A receptor (A2AR) both in right atrium biopsies and peripheral blood mononuclear cells (PBMCs) from non-dilated sinus rhythm (ndSR), dilated sinus rhythm (dSR) and AF patients. In addition, plasma adenosine content and adenosine deaminase (ADA) activity in these subjects were also determined. Our results revealed increased A2AR expression in the right atrium from AF patients, as previously described. Interestingly, increased levels of adenosine content and reduced ADA activity in plasma from AF patients were detected. An increase was observed when A2AR expression was assessed in PBMCs from AF subjects. Importantly, a positive correlation (P=0.001) between A2AR expression in the right atrium and PBMCs was observed. Overall, these results highlight the importance of the A2AR in AF and suggest that the evaluation of this receptor in PBMCs may be potentially be useful in monitoring disease severity and the efficacy of pharmacological treatments in AF patients.
Subject(s)
Atrial Fibrillation/blood , Leukocytes, Mononuclear/cytology , Receptor, Adenosine A2A/blood , Up-Regulation , Adenosine/metabolism , Adenosine Deaminase/metabolism , Aged , Aged, 80 and over , Atrial Remodeling , Female , HEK293 Cells , Heart Atria , Humans , Male , Microscopy, Confocal , Middle AgedABSTRACT
Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 ± 0.1 to 0.6 ± 0.1 Hz; p < 0.01 for beta-adrenergic receptors and from 1.4 ± 0.1 to 0.5 ± 0.1 Hz; p < 0.05 for A2ARs. The latter was linked to increased spontaneous calcium release and after-depolarizations. Moreover, A2AR activation increased the fraction of non-uniformly responding cells in HL-1 myocyte cultures from 19 ± 3 to 51 ± 9 %; p < 0.02, and electrical mapping in perfused porcine atria revealed that adenosine induced electrical alternans at longer cycle lengths, doubled the fraction of electrodes showing alternation, and increased the amplitude of alternations. Importantly, protein kinase A inhibition increased the highest frequency where uniform responses could be maintained from 0.84 ± 0.12 to 1.86 ± 0.11 Hz; p < 0.001 and prevention of A2AR-activation with exogenous adenosine deaminase selectively increased the threshold from 0.8 ± 0.1 to 1.2 ± 0.1 Hz; p = 0.001 in myocytes from patients with AF. In conclusion, A2AR-activation promotes beat-to-beat irregularities in the calcium transient in human atrial myocytes, and prevention of A2AR activation may be a novel means to maintain uniform beat-to-beat responses at higher beating frequencies in patients with atrial fibrillation.
Subject(s)
Atrial Fibrillation/metabolism , Heart Atria/metabolism , Myocytes, Cardiac/metabolism , Receptor, Adenosine A2A/metabolism , Animals , Cells, Cultured , Humans , Microscopy, Confocal , Patch-Clamp Techniques , Sus scrofaABSTRACT
Colorectal cancer is one of the most common cancers in the world. While colonoscopy is an effective screening technique, navigating an endoscope through the colon to detect polyps is challenging. A 3D map of the observed surfaces could enhance the identification of unscreened colon tissue and serve as a training platform. However, reconstructing the colon from video footage remains difficult. Learning-based approaches hold promise as robust alternatives, but necessitate extensive datasets. Establishing a benchmark dataset, the 2022 EndoVis sub-challenge SimCol3D aimed to facilitate data-driven depth and pose prediction during colonoscopy. The challenge was hosted as part of MICCAI 2022 in Singapore. Six teams from around the world and representatives from academia and industry participated in the three sub-challenges: synthetic depth prediction, synthetic pose prediction, and real pose prediction. This paper describes the challenge, the submitted methods, and their results. We show that depth prediction from synthetic colonoscopy images is robustly solvable, while pose estimation remains an open research question.
Subject(s)
Colonoscopy , Imaging, Three-Dimensional , Humans , Imaging, Three-Dimensional/methods , Colorectal Neoplasms/diagnostic imaging , Colonic Polyps/diagnostic imagingABSTRACT
An important step of innate immune response is the recruitment of polymorphonuclear leukocytes (PMN) to injured tissues through chemotactic molecules. Galectins, a family of endogenous lectins, participate in numerous functions such as lymphoid cell migration, homing, cell-cell and cell-matrix interactions. Particularly, galectin-3 (Gal-3) and -9 have been implicated in the modulation of acute and chronic inflammation by inducing the directional migration of monocytes/macrophages and eosinophils, whereas Gal-1 is considered to function as an anti-inflammatory molecule, capable of inhibiting the influx of PMN to the site of injury. In this study, we assessed the effect of Gal-1 on neutrophil recruitment, in the absence of additional inflammatory insults. Contrasting with its capacity to inhibit cell trafficking and modulate the release of mediators described in models of acute inflammation and autoimmunity, we evidenced that Gal-1 has the capacity to induce neutrophil migration both in vitro and in vivo. This effect is not mediated through a G-protein-coupled receptor but potentially through the sialoglycoprotein CD43, via carbohydrate binding and through the p38 mitogen-activated protein kinase pathway. These results suggest a novel biological function for CD43 on neutrophils and highlight that depending on the environment, Gal-1 can act either as chemoattractant or, as a molecule that negatively regulates migration under acute inflammatory conditions, underscoring the potential of Gal-1 as a target for innovative drug development.
Subject(s)
Chemotaxis, Leukocyte , Galectin 1/metabolism , Neutrophils/physiology , Galectin 1/pharmacology , Humans , Immunity, Innate , In Vitro Techniques , Leukosialin/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Analysis of the spatio-temporal distribution of calcium sparks showed a preferential increase in sparks near the sarcolemma in atrial myocytes from patients with atrial fibrillation (AF), linked to higher ryanodine receptor (RyR2) phosphorylation at s2808 and lower calsequestrin-2 levels. Mathematical modeling, incorporating modulation of RyR2 gating, showed that only the observed combinations of RyR2 phosphorylation and calsequestrin-2 levels can account for the spatio-temporal distribution of sparks in patients with and without AF. Furthermore, we demonstrate that preferential calcium release near the sarcolemma is key to a higher incidence and amplitude of afterdepolarizations in atrial myocytes from patients with AF.
ABSTRACT
Computer-assisted systems are becoming broadly used in medicine. In endoscopy, most research focuses on the automatic detection of polyps or other pathologies, but localization and navigation of the endoscope are completely performed manually by physicians. To broaden this research and bring spatial Artificial Intelligence to endoscopies, data from complete procedures is needed. This paper introduces the Endomapper dataset, the first collection of complete endoscopy sequences acquired during regular medical practice, making secondary use of medical data. Its main purpose is to facilitate the development and evaluation of Visual Simultaneous Localization and Mapping (VSLAM) methods in real endoscopy data. The dataset contains more than 24 hours of video. It is the first endoscopic dataset that includes endoscope calibration as well as the original calibration videos. Meta-data and annotations associated with the dataset vary from the anatomical landmarks, procedure labeling, segmentations, reconstructions, simulated sequences with ground truth and same patient procedures. The software used in this paper is publicly available.
ABSTRACT
AIMS: It is unknown how ß-adrenergic stimulation affects calcium dynamics in individual RyR2 clusters and leads to the induction of spontaneous calcium waves. To address this, we analysed spontaneous calcium release events in green fluorescent protein (GFP)-tagged RyR2 clusters. METHODS: Cardiomyocytes from mice with GFP-tagged RyR2 or human right atrial tissue were subjected to immunofluorescent labelling or confocal calcium imaging. RESULTS: Spontaneous calcium release from single RyR2 clusters induced 91.4% ± 2.0% of all calcium sparks while 8.0% ± 1.6% were caused by release from two neighbouring clusters. Sparks with two RyR2 clusters had 40% bigger amplitude, were 26% wider, and lasted 35% longer at half maximum. Consequently, the spark mass was larger in two- than one-cluster sparks with a median and interquartile range for the cumulative distribution of 15.7 ± 20.1 vs 7.6 ± 5.7 a.u. (P < .01). ß2-adrenergic stimulation increased RyR2 phosphorylation at s2809 and s2815, tripled the fraction of two- and three-cluster sparks, and significantly increased the spark mass. Interestingly, the amplitude and mass of the calcium released from a RyR2 cluster were proportional to the SR calcium load, but the firing rate was not. The spark mass was also higher in 33 patients with atrial fibrillation than in 36 without (22.9 ± 23.4 a.u. vs 10.7 ± 10.9; P = .015). CONCLUSIONS: Most sparks are caused by activation of a single RyR2 cluster at baseline while ß-adrenergic stimulation doubles the mass and the number of clusters per spark. This mimics the shift in the cumulative spark mass distribution observed in myocytes from patients with atrial fibrillation.
Subject(s)
Atrial Fibrillation , Ryanodine Receptor Calcium Release Channel , Adrenergic Agents , Animals , Atrial Fibrillation/metabolism , Calcium/metabolism , Calcium Signaling , Humans , Mice , Myocytes, Cardiac/metabolism , Ryanodine Receptor Calcium Release Channel/metabolism , Sarcoplasmic Reticulum/metabolismABSTRACT
PURPOSE: To assess the usefulness of preoperative coronary computed tomographic (CT) angiography in the detection of coronary artery disease (CAD) in nonselected patients scheduled to undergo noncoronary cardiovascular surgery to avoid unnecessary invasive coronary angiography (ICA). MATERIALS AND METHODS: The institutional review board approved the study protocol; informed consent was given. This prospective study involved 161 consecutive patients who underwent coronary calcium scoring and coronary CT angiography before undergoing noncoronary cardiovascular surgery. Seven patients were excluded because of contraindications to CT angiography. The major indication of noncoronary cardiovascular surgery was valvular heart disease (121 patients). Follow-up was performed at a median of 20 months to define ischemic events described as acute coronary syndrome or death secondary to acute coronary syndrome, arrhythmias, or cardiac failure. Multivariate analysis was performed to determine predictors of nondiagnostic coronary CT angiography. Kaplan-Meier analysis was performed to evaluate outcome at follow-up. RESULTS: Twenty-one patients did not undergo surgery, which left 133 patients as the study group. Atrial fibrillation was present in 45 of 133 patients. The interquartile range of the Agatston coronary calcium score was 0-471. Coronary CT angiography was diagnostic in 108 of 133 patients. Of these, 93 of 108 had no significant CAD (≤ 50% stenosis), and noncoronary cardiovascular surgery was performed in them without preoperative ICA. No patients in this group had postoperative ischemic events at follow-up. Coronary CT angiography was nondiagnostic in 25 of 133 patients who were referred for preoperative ICA. Multivariate analysis showed Agatston score to be the only independent predictor of nondiagnostic coronary CT angiography (odds ratio = 1.002; 95% confidence interval: 1.001, 1.003; P = .001). The best Agatston score cutoff for diagnostic coronary CT angiography was 579. CONCLUSION: In nonselected patients scheduled to undergo noncoronary cardiovascular surgery, preoperative coronary CT angiography was diagnostic in 81% of cases. Preoperative ICA could be safely avoided in patients without significant CAD by using coronary CT angiography. The Agatston score, but not the presence of atrial fibrillation, was an independent predictor of nondiagnostic coronary CT angiography. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100384/-/DC1.
Subject(s)
Cardiovascular Surgical Procedures , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Tomography, X-Ray Computed/methods , Aged , Chi-Square Distribution , Contrast Media , Electrocardiography , Female , Humans , Iohexol/analogs & derivatives , Male , Oximetry , Predictive Value of Tests , Preoperative Care , Radiographic Image Interpretation, Computer-Assisted , Statistics, NonparametricABSTRACT
[This corrects the article DOI: 10.3389/fpsyg.2021.607559.].
ABSTRACT
BACKGROUND: Early treatment of aortic valve stenosis is recommended in eligible symptomatic patients with severe aortic valve stenosis who would otherwise have a poor prognosis. The sutureless aortic valve bioprosthesis offers an alternative to standard aortic valve replacement with a sutured valve, but limited data are available in patients who have undergone multiple valve procedures involving the new, sutureless technology. We sought to investigate outcomes in high operative risk patients with previous or concomitant valve surgery who were implanted with a sutureless valve. METHODS: SURE-AVR is an ongoing, prospective, multinational registry of patients undergoing aortic valve replacement. In-hospital and post-discharge outcomes up to 5 years were collected. RESULTS: The study population comprised 78 patients (mean ± SD: age 73.6 ± 7.6 years, logistic EuroSCORE 18.0 ± 17.5) enrolled at 13 sites who presented for concomitant or previous mitral valve repair (n = 45) or replacement (n = 33), with or without additional concomitant procedures, and were implanted with a sutureless valve. Mean ± SD overall aortic cross-clamp time was 109 ± 41 min and cardiopulmonary bypass time was 152 ± 49 min. Mean ± SD aortic pressure gradients decreased from 37.6 ± 17.7 mmHg preoperatively to 13.0 ± 5.7 mmHg at hospital discharge, and peak aortic pressure gradient from 61.5 ± 28.7 to 23.4 ± 10.6 mmHg. Early events included 1 death, 1 transient ischaemic attack, and 1 bleed (all 1.3%); a permanent pacemaker implantation was required in 6 patients (7.7%), and 2 reoperations (not valve related) (2.6%) took place. Over a median follow-up of 55.5 months (Q1 13.4, Q3 68.6), 12 patients died (6 cardiovascular and 6 non-cardiovascular, both 2.1% per patient-year). Five-year survival was 81.3%. Late paravalvular leak occurred in 2 patients (0.7% per patient-year) and permanent pacemaker implantation was required in 3 patients (0.1% per patient-year). There was no apparent rise in mean or peak aortic pressure gradient over the study. CONCLUSIONS: These results suggest that the sutureless implant is a technically feasible procedure during mitral surgery and is associated with good clinical outcomes.
Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Bioprosthesis , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis , Mitral Valve/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Operative Time , Prospective Studies , Prosthesis Design , Registries , Reoperation , Treatment OutcomeABSTRACT
COVID-19 is an acute respiratory illness with higher mortality in older adults. This condition is spread person-to-person through close contact, and among policies employed to decrease transmission are the improvement of hygiene habits and physical distancing. Although social distancing has been recognized as the best way to prevent the transmission, there are concerns that it may promote increased depression symptoms risk and anxiety, mainly in older adults. This cross-sectional study aimed to verify self-concept of social distancing in adults compared to older adults. All participants, over 18 years and residents of São Paulo state (Brazil), were invited to join this research study by a message application and answered an interdisciplinary questionnaire during the period from May 23 to June 23, 2020. The questions were divided into the following aspects: sociodemographic data, financial conditions, routine-related perception, perception of health, physical and emotional state, and eating habits. The younger adult group was composed of 139 participants, with a mean age of 43.15 years (±10.92), and the older adult group was composed of 437 participants with a mean age of 67.59 years (±6.13) of both sex. Changes in routine during the period of social distance were reported by 95% of adults and 96.8% of older adults, but adults indicated more significant alterations in routine. Although there was no difference between groups for several aspects, adults revealed greater alterations in sleep quality, evacuation frequency, and more difficulty to perform daily activities at home. Further studies are necessary to follow up the impacts of social distancing among adults and older adults in different socioeconomic contexts to better understand the long-term alterations and the necessity of interventions.
ABSTRACT
The main presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is respiratory. However, there are extrapulmonary manifestations such as myocardial and pericardial injury. The term long COVID syndrome describes the persistence of symptoms in patients who have recovered from the infection. A 31-year-old man presented with mild coronavirus disease 2019 (COVID-19) symptoms for three days. Two weeks later, he developed chest pain, pericardial rub, and pericardial effusion; he underwent echocardiography showing pericarditis and an MRI which revealed inferoseptal hypokinesia and mild global myocardial hyperintensity, cardiac scintigraphy with Ga-67, and an inflammatory process in the myocardium. He was treated with methylprednisolone pulse (1g IV/day) and tapering prednisone (5 mg/day), with gradual evolution of symptoms for one year. In conclusion, this is a patient without comorbidities with clinical, laboratory, and imaging diagnosis of myopericarditis as a manifestation of long COVID syndrome.
ABSTRACT
OBJECTIVES: Ascertain the oral health status of the adult population in the Valencia region of Spain. STUDY DESIGN: A cross sectional prevalence study was conducted on a sample of 1264 adults, comprising 733 individuals aged 35-44 years and 531 individuals aged 65-74 years. Data collection was carried out in 2006. In both age groups (younger adults and older adults), the clinical examinations were carried out by calibrated dentists (Kappa <0.76). RESULTS: The caries prevalence in the group of 35-44 year-old subjects was 92.2% (DMFT=7.64). In the group of 65-74 year-old subjects, it was 98.3% (DMFT=16.38). The F/DMFT percentage of the younger adults was 66% and that of the older adults was 16.3%. The edentate percentage was 0.1% in the group of 35-44 year-old subjects and 20.7% in the group of 65-74 year-old subjects. Calculus prevalence was almost 60% among the younger adults. Nearly 22% of the younger adults and 26% older adults presented periodontal pockets, although only a minority (4.6% and 4.3%) were CPI score 4. Significant differences in the various indices were found in relation to institutionalization and socio-economic status. CONCLUSIONS: The caries prevalence (DMFT>0) found in the two age groups studied remains very high: over 90%. The worst health status is found in certain groups, such as the institutionalized elderly and adults with a low socio-economic status.
Subject(s)
Health Surveys , Oral Health , Adult , Aged , Cross-Sectional Studies , Dental Caries/epidemiology , Female , Humans , Male , Periodontal Diseases/epidemiology , SpainABSTRACT
OBJECTIVES: Both off-pump coronary artery bypass grafting surgery (OPCABG) and mini-extracorporeal circulation (MECC) have been associated with lower morbidity and mortality and less inflammation than conventional cardiopulmonary bypass. However, studies comparing the 2 techniques are scarce and the results are controversial. We compared the clinical outcomes and inflammatory response of low-risk patients undergoing coronary bypass grafting with MECC versus OPCABG. METHODS: We conducted a prospective, randomized study in patients undergoing coronary heart surgery. Two hundred and thirty consecutive low-risk patients were randomly assigned to either receive OPCABG (n = 117) or MECC (n = 113). Clinical outcomes and postoperative biochemical results were analysed in both groups. We also analysed 19 circulating inflammatory markers in a subgroup of 40 patients at 4 perioperative time points. The area under the curve for each marker was calculated to monitor differences in the inflammatory response. RESULTS: No significant differences were found between groups regarding perioperative clinical complications and no deaths occurred during the trial. Plasma levels in 9 of the 19 inflammatory markers were undetectable or showed no temporal variation, 3 were higher in the MECC group [interleukin (IL)-10, macrophage inflammatory protein-1ß and epidermal growth factor] and 7 were higher in the OPCABG group (growth regulator oncogene, IL-6, IL-8, soluble CD40 ligand, monocyte chemoattractant protein-1, monocyte chemoattractant protein-3 and tumour necrosis factor-α). Differences in 2 proinflammatory cytokines, IL-6 and monocyte chemoattractant protein 1, between the 2 surgical procedures were statistically significant. CONCLUSIONS: No clinical differences were observed between in low-risk patients undergoing MECC or OPCABG surgery, but OPCABG was associated with an increased release of proinflammatory cytokines compared with MECC. Studies in larger cohorts and in patients at higher risk are needed to confirm these findings. CLINICAL TRIAL REGISTRATION NUMBER: NCT02118025.
Subject(s)
Coronary Artery Bypass, Off-Pump , Extracorporeal Circulation , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass, Off-Pump/adverse effects , Extracorporeal Circulation/adverse effects , Humans , Inflammation , Prospective StudiesABSTRACT
Betaglycan is a coreceptor for members of the transforming growth factor beta (TGF-beta) superfamily. Mutagenesis has identified two ligand binding regions, one at the membrane-distal and the other at the membrane-proximal half of the betaglycan ectodomain. Here we show that partial plasmin digestion of soluble betaglycan produces two proteolysis-resistant fragments of 45 and 55 kDa, consistent with the predicted secondary structure, which indicates an intervening nonstructured linker region separating the highly structured N- and C-terminal domains. Amino terminal sequencing indicates that the 45 and 55 kDa fragments correspond, respectively, to the membrane-distal and -proximal regions. Plasmin treatment of membrane betaglycan results in the production of equivalent proteolysis-resistant fragments. The 45 and 55 kDa fragments, as well as their recombinant soluble counterparts, Sol Delta10 and Sol Delta11, bind TGF-beta, but nonetheless, compared to intact soluble betaglycan, have a severely diminished ability to block TGF-beta activity. Surface plasmon resonance (SPR) analysis indicates that soluble betaglycan has K(d)'s in the low nanomolar range for the three TGF-beta isoforms, while those for Sol Delta10 and Sol Delta11 are 1-2 orders of magnitude higher. SPR analysis further shows that the K(d)'s of Sol Delta11 are not changed in the presence of Sol Delta10, indicating that the high affinity of soluble betaglycan is a consequence of tethering the domains together. Overall, these results suggest that betaglycan ectodomain exhibits a bilobular structure in which each lobule folds independently and binds TGF-beta through distinct nonoverlapping interfaces and that linker modification may be an approach to improve soluble betaglycan's TGF-beta neutralizing activity.
Subject(s)
Neutralization Tests , Peptide Fragments/metabolism , Proteoglycans/chemistry , Proteoglycans/metabolism , Receptors, Transforming Growth Factor beta/chemistry , Receptors, Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/metabolism , Amino Acid Sequence , Animals , Base Sequence , COS Cells , Chlorocebus aethiops , Extracellular Space/chemistry , Extracellular Space/metabolism , Fibrinolysin/metabolism , Humans , Molecular Sequence Data , Peptide Fragments/chemistry , Peptide Fragments/genetics , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary/genetics , Proteoglycans/antagonists & inhibitors , Proteoglycans/genetics , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Receptors, Transforming Growth Factor beta/genetics , Recombinant Proteins/antagonists & inhibitors , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Solubility , Structure-Activity Relationship , Transforming Growth Factor beta/chemistryABSTRACT
OBJECTIVE: Working memory impairment is common in schizophrenia and is possibly a cause of multiple features of the disorder. However few studies have replicated such findings of impairment patterns in Brazilian samples. The main target of this study was to assess auditory and visual working memory in patients with schizophrenia, to assess if they work as separate systems, and to correlate working memory deficits with executive functions. METHOD: Twenty subjects with schizophrenia and twenty healthy subjects matched by gender, age, and schooling have participated. The abilities assessed were auditory and visual working memory, selective attention, inhibitory control, cognitive flexibility, and planning. RESULTS: Patients showed declines in all measures evaluated, except for a measure reaction time of inhibitory control. Auditory working memory was correlated to selective attention, inhibition, flexibility and planning while Visual working memory to planning and flexibility. CONCLUSION: The present study suggests that working memory and executive functions deficits are present in patients with schizophrenia in the Brazilian sample evaluated. Alterations in executive functions may lead to incapacity of operation of processes of working memory. These findings may contribute to delineate and develop new strategies of schizophrenia treatment in the Brazilian population.
Subject(s)
Executive Function/physiology , Memory, Short-Term/physiology , Schizophrenia , Schizophrenic Psychology , Acoustic Stimulation , Adolescent , Adult , Auditory Perception/physiology , Brazil , Case-Control Studies , Educational Status , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Reaction Time , Schizophrenia/physiopathology , Visual Perception/physiology , Young AdultABSTRACT
Contemporary endoscopic simultaneous localization and mapping (SLAM) methods accurately compute endoscope poses; however, they only provide a sparse 3-D reconstruction that poorly describes the surgical scene. We propose a novel dense SLAM method whose qualities are: 1) monocular, requiring only RGB images of a handheld monocular endoscope; 2) fast, providing endoscope positional tracking and 3-D scene reconstruction, running in parallel threads; 3) dense, yielding an accurate dense reconstruction; 4) robust, to the severe illumination changes, poor texture and small deformations that are typical in endoscopy; and 5) self-contained, without needing any fiducials nor external tracking devices and, therefore, it can be smoothly integrated into the surgical workflow. It works as follows. First, accurate cluster frame poses are estimated using the sparse SLAM feature matches. The system segments clusters of video frames according to parallax criteria. Next, dense matches between cluster frames are computed in parallel by a variational approach that combines zero mean normalized cross correlation and a gradient Huber norm regularizer. This combination copes with challenging lighting and textures at an affordable time budget on a modern GPU. It can outperform pure stereo reconstructions, because the frames cluster can provide larger parallax from the endoscope's motion. We provide an extensive experimental validation on real sequences of the porcine abdominal cavity, both in-vivo and ex-vivo. We also show a qualitative evaluation on human liver. In addition, we show a comparison with the other dense SLAM methods showing the performance gain in terms of accuracy, density, and computation time.
Subject(s)
Augmented Reality , Endoscopy/methods , Imaging, Three-Dimensional/methods , Abdominal Cavity/diagnostic imaging , Algorithms , Animals , Humans , Liver/diagnostic imaging , SwineABSTRACT
The aim of this study was the characterization of fatty acids, antioxidant activity, some physical properties, nutrient content, sugars, and minerals in the pulp and seeds of the date cultivar 'Medjool' (Phoenix dactylifera L.) grown in Mexico. The samples were obtained at maturity (Tamar) in the 2017 harvest season in the valleys of San Luis Rio Colorado and Mexicali, Mexico. The following average values were obtained on a % dry weight basis for pulp and seeds, respectively: protein, 3.14% and 4.84%; lipids, 0.75% and 9.94%; fiber, 6.34% and 66.79%; total sugars, 75.32% and 5.88%; reducing sugars, 70.26% and 4.40%; and sucrose, 5.06% and 1.46%. Analysis of the minerals revealed that the most abundant elements for the pulp were: potassium, 851.98 mg/100 g; magnesium, 142.97 mg/100 g; and phosphorus, 139.40 mg/100 g, whereas for the seeds, they were potassium, 413.36 mg/100 g; sulfur, 151.36 mg/100 g; and phosphorus, 92.42 mg/100 g. Gas chromatography-mass spectrometry analysis revealed that the major unsaturated fatty acid was oleic acid, at 52.34% and 45.92%, respectively, for pulp and seeds. The main saturated fatty acids were palmitic acid (6.75%) and lauric acid (17.24%) in pulp and seeds, respectively. The total phenolic content was 1.16 and 13.73 mg GAE/100 g for pulp and seeds, respectively. Finally, the antioxidant activities were: b-carotene, 65.50% and 47.75%; DPPH, 0.079 IC50 g/L and 0.0046 IC50 g/L; and ABTS, 13.72 IC50 g/L and 0.238 IC50 g/L, respectively. The results obtained in this study confirm that the 'Medjool' cultivar grown in Mexico has the same quality of nutrients and antioxidants as those grown in the other main date-producing countries.