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Circulation Research Jan 2024Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the...
BACKGROUND
Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitric oxide (NO). Here, we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium. We further define the mechanism through which ceramide exerts beneficial effects and discern key mechanistic differences between arterioles from otherwise healthy adults (non-coronary artery disease [CAD]) and patients diagnosed with CAD.
METHODS
Human arterioles were dissected from discarded surgical adipose tissue (n=166), and vascular reactivity to flow and C2-ceramide was assessed. Shear-induced NO and mitochondrial hydrogen peroxide (HO) production were measured in arterioles using fluorescence microscopy. HO fluorescence was assessed in isolated human umbilical vein endothelial cells.
RESULTS
Inhibition of NSmase in arterioles from otherwise healthy adults induced a switch from NO to NOX-2 (NADPH-oxidase 2)-dependent HO-mediated flow-induced dilation. Endothelial dysfunction was prevented by treatment with sphingosine-1-phosphate (S1P) and partially prevented by C2-ceramide and an agonist of S1P-receptor 1 (S1PR1); the inhibition of the S1P/S1PR1 signaling axis induced endothelial dysfunction via NOX-2. Ceramide increased NO production in arterioles from non-CAD adults, an effect that was diminished with inhibition of S1P/S1PR1/S1P-receptor 3 signaling. In arterioles from patients with CAD, inhibition of NSmase impaired the overall ability to induce mitochondrial HO production and subsequently dilate to flow, an effect not restored with exogenous S1P. Acute ceramide administration to arterioles from patients with CAD promoted HO as opposed to NO production, an effect dependent on S1P-receptor 3 signaling.
CONCLUSION
These data suggest that despite differential downstream signaling between health and disease, NSmase-mediated ceramide formation is necessary for proper functioning of the human microvascular endothelium. Therapeutic strategies that aim to significantly lower ceramide formation may prove detrimental to the microvasculature.
Topics: Adult; Humans; Ceramides; Hydrogen Peroxide; Vascular Diseases; Coronary Artery Disease; Human Umbilical Vein Endothelial Cells; Endothelium
PubMed: 38037825
DOI: 10.1161/CIRCRESAHA.123.323445 -
Journal of Clinical Imaging Science 2023This study aimed to compare the safety and efficacy of balloon and non-balloon (or dilator) gastrostomy devices in radiologically inserted gastrostomy (RIG) for patients...
OBJECTIVES
This study aimed to compare the safety and efficacy of balloon and non-balloon (or dilator) gastrostomy devices in radiologically inserted gastrostomy (RIG) for patients with neurological disease.
MATERIAL AND METHODS
A retrospective analysis of 152 patients was conducted at a tertiary care hospital from July 2017 to September 2020. 104 and 48 patients were included in the balloon and non-balloon groups, respectively. The frequency of complications per specific neurological indication as well as the breakdown of the different complications pertaining to each indication was recorded for analysis. The recovery time, fluoroscopy time, contrast volume, peak radiation, and pain management dosages for each procedure were all reviewed to evaluate for statistical differences between the balloon and non-balloon groups. An adjusted model odds ratio (OR) was conducted to evaluate how each of the variables (type of gastrostomy tube, body mass index [BMI], age, and gender) affected the frequency of complications within our cohort.
RESULTS
This study included 152 patients, with an average age of 65.17 years (interquartile range [IQR] = 12.66) and an average BMI of 26.97 (IQR = 7.19). The majority of patients were male (71.1%). The most common indication for the procedure was stroke (24.3%), followed by post-intubation dysphagia (16.4%) and intracranial hemorrhage (11.8%). Amyotrophic lateral sclerosis (ALS) and altered mental status had a similar prevalence at 9.9%. The overall complication rate was 33.8%, overall mortality rate 3.3%, 30-day mortality rate of 2.6%, and no other major complications according to CIRSE criteria. Notably, patients with neurodegenerative disorders exhibited comparable rates of minor complications: 33.3% in ALS (5/15 patients), 50% in myasthenia gravis (1/2 patients), and 100% in muscular dystrophy (1/1 patient). The study compared two groups: the balloon group (104 patients) and the dilator group (48 patients). The balloon group received significantly lower preoperative sedation in the form of fentanyl (Avg = 4.46 min vs. 6.54 min, = 0.287). The balloon group had shorter fluoroscopy time, lower radiation exposure dose, and shorter operating time compared to the dilator group, though not statistically significant. In the logistic regression model, there was no statistical difference in complication rates between the dilator and balloon groups. BMI, age, and gender did not significantly affect minor complication rates.
CONCLUSION
RIG tube insertions may serve as a valuable, alternative approach in providing enteral support in patients with neurological disease.
PubMed: 37941924
DOI: 10.25259/JCIS_78_2023 -
Diseases of Aquatic Organisms Aug 2023Glomerulocystic kidney (GCK) is defined by a dilatation of the Bowman's space (greater than 2 times the normal size) of more than 5% of all glomeruli. Although GCK has...
Glomerulocystic kidney (GCK) is defined by a dilatation of the Bowman's space (greater than 2 times the normal size) of more than 5% of all glomeruli. Although GCK has been occasionally documented in dogs, cats, and humans with renal failure, in fish, reports of spontaneous GCK are rare. For the present study, 2 captive adult red piranhas Pygocentrus nattereri from a closed population were submitted for post-mortem examination. Clinical history included lethargy, inappetence, dyspnea, and altered buoyancy. Macroscopically, the fish displayed coelomic distension and ascites. The kidneys were markedly enlarged and dark yellow. Histologically, Bowman's space was noticeably dilated, occasionally with atrophic glomerular tufts. Degeneration and necrosis of the tubular epithelium, infiltration, and nephrocalcinosis were also present. To the authors' knowledge, this present study is the first report of spontaneously occurring GCK in red piranhas and freshwater fish in general. Despite being rare, GCK is a condition with the potential to impair the health of fish and mammals, and further studies are needed to shed new light on this condition.
Topics: Humans; Animals; Dogs; Kidney; Nephrocalcinosis; Fresh Water; Necrosis; Characiformes; Mammals; Dog Diseases
PubMed: 37589491
DOI: 10.3354/dao03738 -
Clinical Research in Cardiology :... Nov 2023Aortic size tends to increase with aging but the extent of this dynamic process has not been evaluated in long-term longitudinal population-based studies. We...
BACKGROUND
Aortic size tends to increase with aging but the extent of this dynamic process has not been evaluated in long-term longitudinal population-based studies. We investigated the incidence of new-onset aortic root (AR) dilatation and its principal correlates among middle-aged adults over a 25-year time period.
METHODS
A total of 471 participants with measurable echocardiographic parameters at baseline and after a 25-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute AR diameter, AR diameter indexed to body surface area (BSA) and to height were derived from healthy normotensive PAMELA participants.
RESULTS
New AR dilatation occurred in 7.4% (AR/BSA), 9.1% (AR/height) and 14.6% (absolute AR), respectively. According to the AR/height index, the risk of new dilation was similar in men and women. As for echocardiographic parameters, baseline AR diameter emerged as a key predictor of AR dilation, regardless of the diagnostic criteria and the 10-year change in LVMI was positively associated to new AR/height dilatation. No significant relationship was observed between baseline office and ambulatory systolic/diastolic blood pressure or their changes over time with incident AR dilatation. Baseline and the 25-year change in 24-h pulse pressure were negatively related to new AR dilatation.
CONCLUSIONS
The incidence of AR dilatation from mid to late adulthood occurs in a small but clinically relevant fraction of participants and is unaffected by both office and out-office BP. It is significant related to baseline AR diameter and to the 25-year change in LVMI. Our data suggest that echocardiography performed in middle-aged individuals of both sexes may identify those at increased risk of future AR dilatation; moreover, preventing LVH may reduce the risk of progressive AR enlargement.
Topics: Adult; Male; Middle Aged; Humans; Female; Dilatation; Follow-Up Studies; Blood Pressure; Aorta; Hypertrophy, Left Ventricular; Dilatation, Pathologic
PubMed: 36028778
DOI: 10.1007/s00392-022-02086-z -
European Heart Journal Open Sep 2023Dilation of the ascending aorta (AA) is often asymptomatic until a life-threatening dissection or rupture occurs. An overall increase in the use of thoracic imaging has...
AIMS
Dilation of the ascending aorta (AA) is often asymptomatic until a life-threatening dissection or rupture occurs. An overall increase in the use of thoracic imaging has enabled early and sometimes incidental identification of AA dilation. Still, the prevalence and determinants of AA dilation remain to be clarified. The aim was to identify and characterize persons with AA dilation in a middle-aged Swedish population.
METHODS AND RESULTS
We used the Swedish CardioPulmonary BioImage Study Linköping ( = 5058, age 50-65 years) to identify cases with AA diameter ≥ 40 mm on coronary computed tomography angiography (CCTA) or chest computed tomography. Age- and gender-matched individuals with AA diameter < 40 mm served as controls. Echocardiography, blood pressure (BP) measurements (office and home), pulse wave velocity (PWV), coronary artery calcification (CAC), CCTA-detected coronary atherosclerosis, and carotid ultrasound were used to characterize these subjects. We identified 70 cases (mean AA diameter 44 mm, 77% men) and matched these to 146 controls (mean AA diameter 34 mm). Bicuspid aortic valve and aortic valve dysfunction were more common in cases than in controls (8% vs. 0% and 39% vs. 11%, respectively). Both office and home BP levels were significantly higher among cases. Also, high PWV (>10 m/s) levels were more common in cases (33% vs. 17%). Neither CAC scores nor prevalence or burden of atherosclerosis in coronary and carotid arteries differed between groups.
CONCLUSION
The prevalence of dilated AA was 1.4% and showed positive associations with male gender, aortic valve pathology, and diastolic BP, though not with subclinical atherosclerosis.
PubMed: 37767013
DOI: 10.1093/ehjopen/oead085 -
Frontiers in Psychology 2024Gestalt perception refers to the cognitive ability to perceive various elements as a unified whole. In our study, we delve deeper into the phenomenon of Gestalt...
INTRODUCTION
Gestalt perception refers to the cognitive ability to perceive various elements as a unified whole. In our study, we delve deeper into the phenomenon of Gestalt recognition in visual cubist art, a transformative process culminating in what is often described as an Aha moment. This Aha moment signifies a sudden understanding of what is seen, merging seemingly disparate elements into a coherent meaningful picture. The onset of this Aha moment can vary, either appearing almost instantaneously, which is in line with theories of hedonic fluency, or manifesting after a period of time, supporting the concept of delayed but more in-depth meaningful insight.
METHODS
We employed pupillometry to measure cognitive and affective shifts during art interaction, analyzing both maximum pupil dilation and average dilation across the trial. The study consisted of two parts: in the first, 84 participants identified faces in cubist paintings under various conditions, with Aha moments and pupil dilation measured. In part 2, the same 84 participants assessed the artworks through ratings in a no-task free-viewing condition.
RESULTS
Results of part 1 indicate a distinctive pattern of pupil dilation, with maximum dilation occurring at both trial onset and end. Longer response times were observed for high-fluent, face-present stimuli, aligning with a delayed but accurate Aha-moment through recognition. Additionally, the time of maximum pupil dilation, rather than average dilation, exhibited significant associations, being later for high-fluent, face-present stimuli and correct detections. In part 2, average, not the time of maximum pupil dilation emerged as the significant factor. Face-stimuli and highly accessible art evoked stronger dilations, also reflecting high clearness and negative valence ratings.
DISCUSSION
The study underscores a complex relationship between the timing of recognition and the Aha moment, suggesting nuanced differences in emotional and cognitive responses during art viewing. Pupil dilation measures offer insight into these processes especially for moments of recognition, though their application in evaluating emotional responses through artwork ratings warrants further exploration.
PubMed: 38544509
DOI: 10.3389/fpsyg.2024.1192565 -
Ear and HearingTo assess if a manipulation of copresence was related to speech-in-noise task performance, arousal, and effort of persons with hearing loss. Task-related arousal and...
OBJECTIVES
To assess if a manipulation of copresence was related to speech-in-noise task performance, arousal, and effort of persons with hearing loss. Task-related arousal and effort were measured by means of pupillometry.
DESIGN
Twenty-nine participants (mean age: 64.6 years) with hearing loss (4-frequency pure-tone average [4F-PTA] of 50.2 dB HL [SD = 8.9 dB] in the right ear and 51.3 dB HL [SD = 8.7 dB] in the left ear; averaged across 0.5, 1, 2, and 4 kHz) listened to and repeated spoken Danish sentences that were masked by four streams of continuous speech. Participants were presented with blocks of 20 sentences, during which copresence was manipulated by having participants do the task either alone or accompanied by two observers who were recruited from a similar age group. The task was presented at two difficulty levels, which was accomplished by fixing the signal-to-noise ratio of the speech and masker to match the thresholds at which participants were estimated to correctly repeat 50% (difficult) or 80% (easy) of the sentences in a block. Performance was assessed based on whether or not sentences were repeated correctly. Measures of pupil size (baseline pupil size [BPS], peak pupil dilation [PPD], and mean pupil dilation [MPD]) were used to index arousal and effort. Participants also completed ratings of subjective effort and stress after each block of sentences and a self-efficacy for listening-questionnaire.
RESULTS
Task performance was not associated with copresence, but was found to be related to 4F-PTA. An increase in BPS was found for copresence conditions, compared to alone conditions. Furthermore, a post-hoc exploratory analysis revealed that the copresence conditions were associated with a significantly larger pupil size in the second half of the task-evoked pupil response (TEPR). No change in PPD or MPD did was detected between copresence and alone conditions. Self-efficacy, 4F-PTA, and age were not found to be related to the pupil data. Subjective ratings were sensitive to task difficulty but not copresence.
CONCLUSION
Copresence was not found to be related to speech-in-noise performance, PPD, or MPD in persons with HL but was associated with an increase in arousal (as indicated by a larger BPS). This could be related to premobilization of effort and/or discomfort in response to the observers' presence. Furthermore, an exploratory analysis of the pupil data showed that copresence was associated with greater pupil dilations in the second half of the TEPR. This may indicate that participants invested more effort during the speech-in-noise task while in the presence of the observers, but that this increase in effort may not necessarily have been related to listening itself. Instead, other speech-in-noise task-related processes, such as preparing to respond, could have been influenced by copresence.
Topics: Humans; Middle Aged; Pupil; Acoustic Stimulation; Speech Intelligibility; Noise; Hearing Loss; Deafness; Speech Perception
PubMed: 37012623
DOI: 10.1097/AUD.0000000000001361 -
Asian Journal of Surgery Oct 2023A model that considers the characteristics of dialysis patients may help predict successful fistula maturation. We evaluated factors associated with radiocephalic...
OBJECTIVE
A model that considers the characteristics of dialysis patients may help predict successful fistula maturation. We evaluated factors associated with radiocephalic arteriovenous fistula (RCAVF) maturation at 3 months in dialysis patients with end-stage renal disease (ESRD).
METHODS
A total of 184 patients who received an initial RCAVF at Beijing Haidian Hospital (Haidian Section of Peking University Third Hospital) were recruited. Fistula maturation was assessed within 3 months. Patient characteristics and preoperative vascular assessment indices were examined. Factors associated with fistula maturation were analyzed using logistic regression and least absolute shrinkage and selection operator (LASSO) binary logistic regression. Boostrapping was used for internal validation.
RESULTS
The development data consisted of 184 ESRD patients receiving an initial RCAVF, 140 (76%) of whom achieved fistula maturation. The main predictors of RCAVF maturation in the final model were sex, age-adjusted vein dilation (eVD), radial artery volume (V), and diastolic blood pressure. The difference of vein diameter with and without a tourniquet was significantly larger in the mature RCAVF group (3.0 ± 0.5 vs. 2.2 ± 0.5 mm). The area under receiver operating characteristic (AUROC) curve for prediction of fistula maturation was 0.77, and the Hosmer-Lemeshow statistic indicated agreement between observed and predicted values (P = 0.792). Analysis of internal validation using bootstrapping indicated the C-index was 0.75.
CONCLUSION
The ratio of vein dilation and age were the major predictors of fistula maturation at 3 months in our patients. The resulting online prediction model may help in clinical decision-making for patients receiving a RCAVF.
Topics: Humans; Infant; Arteriovenous Shunt, Surgical; Retrospective Studies; Dilatation; Risk Factors; Kidney Failure, Chronic; Renal Dialysis; Fistula; Treatment Outcome
PubMed: 36805275
DOI: 10.1016/j.asjsur.2023.01.098 -
Therapeutic Advances in Gastroenterology 2024Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures balloon-assisted endoscopy (BAE), specifically regarding the...
BACKGROUND
Despite recent emerging literature involving the utility of endoscopic balloon dilation (EBD) of strictures balloon-assisted endoscopy (BAE), specifically regarding the management of Crohn's disease (CD), the optimal clinical approach with balloon systems has been largely neglected in academic literature.
OBJECTIVES
This study assesses the intra-procedural success and safety of EBD BAE for small bowel CD strictures while detailing our clinical approach and technique. Secondarily, we compare the single-balloon endoscope (SBE) and double-balloon endoscope (DBE) systems for EBD-related outcomes.
DESIGN
Retrospective consecutive patient cohort analysis.
METHODS
We retrospectively assessed a consecutive small bowel CD patient cohort undergoing BAE at the University of Alberta Hospital endoscopy unit from 2013 to 2020. The primary endpoint discerned the safety and immediate success rate of EBD during endoscopy, and comparisons of the dilation parameters and efficacy of SBE DBE were assessed as secondary outcomes.
RESULTS
During the study period, 87 patients (44 male) with a mean age of 56 ± 14.7 years underwent 179 endoscopic procedures (92 DBE and 87 SBE). Of 358 strictures encountered, 320 (89.4%) were successfully dilated and traversed. The mean maximum dilation diameter was 15.76 ± 2.10 mm. There were no perforations or major adverse events.
CONCLUSION
EBD BAE is a safe procedure in small bowel CD with a high intraprocedural success rate. Overall, SBE had a higher success rate in traversing strictures before and after dilation using our technique. This analysis is limited by the retrospective nature of our study and must be balanced against the inherent benefits of the DBE system.
PubMed: 38425369
DOI: 10.1177/17562848241230904 -
BMC Pediatrics Apr 2024Plummer-Vinson syndrome (PVS) is characterized by a triad of symptoms consisting of microcytic hypochromic anaemia, oesophageal webs, and dysphagia. PVS is commonly...
BACKGROUND
Plummer-Vinson syndrome (PVS) is characterized by a triad of symptoms consisting of microcytic hypochromic anaemia, oesophageal webs, and dysphagia. PVS is commonly found in women in the fourth and fifth decades of life and is rarely reported in the paediatric population.
CASE PRESENTATION
We report the case of a 1-year-old male South Asian child who presented with dysphagia and anaemia for 4 months and frequent episodes of vomiting after ingesting semisolid and solid food. A complete blood analysis revealed microcytic hypochromic anaemia. An oesophagogram revealed circumferential narrowing of the upper thoracic oesophagus. Based on these findings, our suspicion was that the patient had an oesophageal web and vascular ring. Oesophageal dilation was performed with a Savary-Gilliard dilator; initially, 5 mm and 7 mm probes were used, and final dilation with a 9 mm probe was performed.
CONCLUSION
Although rare in paediatric patients, a high suspicion of this syndrome is necessary in these patients to provide relief to the patient for better growth and development. Iron supplements increase the haemoglobin level but do not subside dysphagia, and oesophageal dilation is needed to open the blocked enteral pathway.
Topics: Humans; Plummer-Vinson Syndrome; Male; Infant; Deglutition Disorders; Dilatation
PubMed: 38678196
DOI: 10.1186/s12887-024-04750-x