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Scientific Reports Apr 2024Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous...
Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.
Topics: Animals; Swine; Heart Sounds; Dobutamine; Nicardipine; Hemodynamics; Phenylephrine; Propanolamines
PubMed: 38615106
DOI: 10.1038/s41598-024-59362-3 -
International Journal of Molecular... Mar 2024The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory...
The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.
Topics: Animals; Rats; Scopolamine; Dihydroergotamine; Histamine; Amnesia; Brain; Memory Disorders; Histamine H2 Antagonists
PubMed: 38612521
DOI: 10.3390/ijms25073710 -
Journal of Clinical Medicine Apr 2024: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and...
: Systemic lupus erythematosus (SLE) is a prototype autoimmune disease associated with increased cardiovascular (CV) burden. Besides increased arterial stiffness and subclinical atherosclerosis, microvascular dysfunction is considered an important component in the pathophysiology of CV disease. However, there is a lack of data regarding the effect of multiple target organ damage (TOD) on CV health. : This study aimed to evaluate (i) the presence of microvascular changes in SLE in various vascular beds, (ii) the possible associations between the accumulation of microvascular TOD and CV risk and (iii) whether Galectin-3 represents a predictor of combined microvascular TOD. : Participants underwent (i) evaluation of skin microvascular perfusion (laser speckle contrast analysis), (ii) fundoscopy (non-mydriatic fundus camera), (iii) indirect assessment of myocardial perfusion (subendocardial viability ratio) and (iv) determination of urine albumin-to-creatinine ratio (UACR). CV risk was calculated using the QResearch Risk Estimator version 3 (QRISK3). Serum Galectin-3 levels were determined. : Forty-seven SLE patients and fifty controls were studied. SLE patients demonstrated impaired skin microvascular reactivity (160.2 ± 41.0 vs. 203.6 ± 40.1%), retinal arteriolar narrowing (88.1 ± 11.1 vs. 94.6 ± 13.5 μm) and higher UACR levels compared to controls. Furthermore, SLE individuals had significantly higher Galectin-3 levels [21.5(6.1) vs. 6.6(6.6) ng/dL], QRISK3 scores [7.0(8.6) vs. 1.3(3.6)%] and a greater chance for microvascular dysfunction. In the SLE group, patients with multiple TOD exhibited higher QRISK3. In the multivariate analysis, the accumulation of TOD correlated with disease activity and Galectin-3 ( < 0.05). : Our study showed for the first time that SLE patients exhibit a greater number of cases of TOD. The accumulation of TOD was associated with increased CV risk. Clinicians dealing with SLE should be aware and seek microvascular alterations.
PubMed: 38610905
DOI: 10.3390/jcm13072140 -
European Journal of Pediatrics Jul 2024School teachers are often inadequately prepared to use an adrenaline auto-injector (AAI), resulting in potentially dangerous treatment delays. The purpose of this study...
School teachers are often inadequately prepared to use an adrenaline auto-injector (AAI), resulting in potentially dangerous treatment delays. The purpose of this study was to assess the observed competence, and self-reported confidence, of primary school teachers in the Republic of Ireland (RoI) to use an AAI. An evaluation of whether there was a link between confidence and competence was also assessed. Teachers from four primary schools in the RoI completed a questionnaire to assess their prior level of experience, training, and confidence levels with AAI administration. The four steps in administrating trainer AAI to a mannequin simulator were then assessed. A total of 61 teachers participated (out of a population of 80). The mean self-reported confidence was 1.82 out of 5 (SD = 0.96). There was no significant difference in confidence between trained and untrained participants (U = 240.5, NS). Participants who had received AAI administration training performed significantly more of the steps correctly (mean = 3.85, SD = 0.95) as compared to those who had received no training (mean = 2.97, SD = 1.10; U = 180.5, p = 0.008). There was no correlation between confidence in administrating AAI and the percentage of steps in the procedure performed correctly (rho = -0.17, NS). Conclusion: Improvements in readiness to administer AAIs can be achieved through the application of more effective approaches to teaching clinical skills, changes to school policies and practices, and consideration of the design of AAIs in order to make their operation safer and simpler. It is important that teachers have the confidence and competence to safely administer an AAI. What is Known: • Poor ability in adrenaline auto-injector use seen across population groups-healthcare professionals, patients, carers, and school staff • Training in the use of adrenaline auto-injectors has positive impact on competency What is New: • Irish school teachers show poor levels of competency in adrenaline auto-injector use • No observed correlation between reported confidence and competency.
Topics: Humans; Epinephrine; School Teachers; Ireland; Female; Male; Manikins; Surveys and Questionnaires; Adult; Self Administration; Anaphylaxis; Schools; Professional Competence; Child; Injections, Intramuscular; Teacher Training; Middle Aged
PubMed: 38609653
DOI: 10.1007/s00431-024-05562-y -
PloS One 2024Medicine shortages prevail as a worldwide problem causing life-threatening situations for adults and children. Epinephrine auto-injectors are used for serious allergic...
INTRODUCTION
Medicine shortages prevail as a worldwide problem causing life-threatening situations for adults and children. Epinephrine auto-injectors are used for serious allergic reactions called anaphylaxis, and alternative auto-injectors are not always available in pharmacies. Healthcare professionals in Finland use the dedicated internet source, Physician's Database (PD), when seeking medical information in practice, while Health Library (HL) provides health information for citizens (S1 Data). The objectives were to assess whether (1) professionals' searches for epinephrine auto-injectors and (2) citizens' anaphylaxis article openings relate to epinephrine shortages in Finland.
METHODS
Monthly log data on epinephrine auto-injectors (EpiPen®, Jext®, Emerade®) from PD and on openings of anaphylaxis articles from HL were collected during 2016-2022. Professionals' searches of seven auto-injectors and citizens' openings of four anaphylaxis articles were compared to information on epinephrine shortages reported by Finnish Medicines Agency. Professionals' auto-injector prescriptions provided by Social Insurance Institution were also assessed.
RESULTS
Total searches in EpiPen® (N = 111,740), Jext® (N = 25,631), and Emerade® (N = 18,329) could be analyzed during 2016-2022. EpiPen® only could visually show seasonal patterns during summertime, peaking vigorously in the summer of 2018 when the major EpiPen® shortage appeared worldwide. Anaphylaxis articles equaled 2,030,855 openings altogether. Openings of one anaphylaxis article ("Bites and Stings") peaked during summertime, while another article ("Anaphylactic Reaction") peaked only once (three-fold increase) at the end of 2020 when COVID-19 vaccinations started, and auto-injector prescriptions were lowest. Fifty EpiPen®, one Jext®, and twelve Emerade® shortages were reported. Almost a two-fold increase in peaks of auto-injector prescriptions was found during summertime.
CONCLUSION
This study shows that (1) epinephrine shortages related to professionals' searching for auto-injectors, and (2) citizens' information seeking on anaphylaxis related to summertime and shortages with lesser prescriptions. Therefore, the dedicated internet databases aimed at professionals and citizens could be used as additional information sources to detect anaphylactic reactions and auto-injector shortages.
Topics: Adult; Child; Humans; Anaphylaxis; Finland; Information Seeking Behavior; Epinephrine; Data Analysis; Injections, Intramuscular
PubMed: 38603709
DOI: 10.1371/journal.pone.0299092 -
Psychoneuroendocrinology Jul 2024Selective attention to salient emotional information can enable an advantage in the face of danger. The present study aims to investigate the influence of the stress... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Selective attention to salient emotional information can enable an advantage in the face of danger. The present study aims to investigate the influence of the stress neuromodulators, norepinephrine and cortisol, on selective attention processes to fearful faces and its neuronal activation.
METHODS AND MATERIALS
We used a randomized, double-blind, placebo-controlled design. 167 healthy men between 18 and 35 years (mean [SD] age: 25.23 [4.24] years) participated in the study. Participants received either: (A) yohimbine (n= 41), (B) hydrocortisone (n = 41), (C) yohimbine and hydrocortisone (n = 42) or (D) placebo only (n= 43) and participated in a dot-probe task with fearful and neutral faces in an fMRI scanner.
RESULTS
We found an attentional bias toward fearful faces across all groups and related neuronal activation in the left cuneus. We did not find any differences between experimental treatment groups in selective attention and its neuronal activation.
DISCUSSION
Our results provide evidence that fearful faces lead to an attentional bias with related neuronal activation in the left cuneus. We did not replicate formerly reported activation in the amygdala, intraparietal sulcus, dorsal anterior cingulate cortex, and thalamus. Suitability of the dot-probe task for fMRI studies and insignificant treatment effects are discussed.
Topics: Humans; Male; Magnetic Resonance Imaging; Adult; Fear; Hydrocortisone; Facial Expression; Yohimbine; Double-Blind Method; Young Adult; Attention; Adolescent; Attentional Bias; Facial Recognition; Brain; Amygdala; Emotions
PubMed: 38581746
DOI: 10.1016/j.psyneuen.2024.107031 -
Photodiagnosis and Photodynamic Therapy Apr 2024This research evaluates the effectiveness of the Spot Vision Screener (SVS) before and after cycloplegia to detect amblyogenic refractive errors in children.
PURPOSE
This research evaluates the effectiveness of the Spot Vision Screener (SVS) before and after cycloplegia to detect amblyogenic refractive errors in children.
METHODS
Children ages 3 to 10 years old were screened by the SVS before and after cycloplegia. Sensitivity, specificity, positive and negative predictive value, paired t-test, Bland-Altman plot and receiver operating characteristic area under the curve were evaluated by comparing the results of the SVS (v3.0.05) measurements with the results of the cycloplegic Topcon autorefractometer according to the 2021 guidelines of the American Association for Pediatric Ophthalmology and Strabismus.
RESULTS
Both eyes of 211 patients aged 3 to 10 years old were included. Regarding the amblyopia risk factors, the noncycloplegic SVS had 65.7 % sensitivity, 94.9 % specificity, 81.2 % positive predictive value and 89.3 % negative predictive value. The SVS's sensitivity increased from 65.7 % to 81.9 % with cycloplegia compared to noncycloplegic SVS results. The sensitivity detection of hyperopia was improved from 4.2 % to 100 % after cycloplegia. Areas under the receiver operator characteristic curve for noncycloplegic SVS and cycloplegic SVS were 0.506 (95 % CI, 0.395 to 0.646, p = 0737) and 0.905 (95 % CI, 0.915 to 0.971, p < 0.001) for hyperopia, respectively. Using the +1.64 D revised cutoff criteria for hyperopia increased sensitivity from 4.2 % to 78 %.
CONCLUSION
Noncycloplegic SVS measurements showed relatively high specificity in detecting amblyopia risk factors. The fact that noncycloplegic measurements have a very low sensitivity for hyperopia is an important weakness of the SVS, especially because hyperopia is the most frequently encountered refractive error in very young children. It should be noted that amblyogenic hyperopia may be overlooked by an SVS without cycloplegia.
Topics: Humans; Amblyopia; Child, Preschool; Child; Male; Female; Risk Factors; Mydriatics; Vision Screening; Sensitivity and Specificity; ROC Curve; Refractive Errors; Practice Guidelines as Topic; Predictive Value of Tests
PubMed: 38570151
DOI: 10.1016/j.pdpdt.2024.104073 -
Journal of Cardiothoracic Surgery Apr 2024Open repair of thoracoabdominal aortic aneurysm (TAAA) was characterized by significant risk of postoperative mortality and morbidity. The aim of this study was to...
BACKGROUND
Open repair of thoracoabdominal aortic aneurysm (TAAA) was characterized by significant risk of postoperative mortality and morbidity. The aim of this study was to determine the perioperative predictors of early and long-term mortality in patients undergoing open repair of TAAA. Besides, the postoperative outcomes in patients with open repair of TAAA were described.
METHODS
This is a single-center retrospective study, and 146 patients with open repair of TAAA from January 4, 2011, to November 22, 2018 was involved. Categorical variables were analyzed by the Chi-square test or Fisher's exact test, and continuous variables were analyzed by the independent sample t-test and the WilCoxon rank-sum test. Multivariate Logistic regression and Cox regression were applied to identify the predictors of 30-day and long-term mortality, respectively. The Kaplan Meier curves were used to illustrate survival with the Log-rank test.
RESULTS
The 30-day mortality was 9.59% (n = 14). Older than 50 years, the intraoperative volume of red blood cell (RBC) and epinephrine use were independently associated with postoperative 30-day mortality in open repair of TAAA. Long-term mortality was 17.12% (n = 25) (median of 3.5 years (IQR = 2-5 years) of follow-up). Prior open thoracoabdominal aortic aneurysm (TAAA) repair, aortic cross-clamping (ACC) time, intraoperative volume of RBC and use of epinephrine were independently correlated with long-term mortality.
CONCLUSIONS
Identifying perioperative risk factors of early and long-term mortaliy is crucial for surgeons. Intraoperative volume of RBC and use of epinephrine were predictors of both early and long-term mortality. In addition, patients of advanced age, prior open repair of TAAA and prolonged ACC time should be paid more attention.
Topics: Humans; Aortic Aneurysm, Thoracoabdominal; Aortic Aneurysm, Thoracic; Treatment Outcome; Retrospective Studies; Blood Vessel Prosthesis Implantation; Risk Factors; Epinephrine; Postoperative Complications; Endovascular Procedures; Risk Assessment
PubMed: 38566230
DOI: 10.1186/s13019-024-02666-2 -
Biomedicine & Pharmacotherapy =... May 2024A novel small molecule based on benzothiazole-piperazine has been identified as an effective multi-target-directed ligand (MTDL) against Alzheimer's disease (AD)....
A novel small molecule based on benzothiazole-piperazine has been identified as an effective multi-target-directed ligand (MTDL) against Alzheimer's disease (AD). Employing a medicinal chemistry approach, combined with molecular docking, MD simulation, and binding free energy estimation, compound 1 emerged as a potent MTDL against AD. Notably, compound 1 demonstrated efficient binding to both AChE and Aβ1-42, involving crucial molecular interactions within their active sites. It displayed a binding free energy (ΔG) -18.64± 0.16 and -16.10 ± 0.18 kcal/mol against AChE and Aβ1-42, respectively. In-silico findings were substantiated through rigorous in vitro and in vivo studies. In vitro analysis confirmed compound 1 (IC=0.42 μM) as an effective, mixed-type, and selective AChE inhibitor, binding at both the enzyme's catalytic and peripheral anionic sites. Furthermore, compound 1 demonstrated a remarkable ability to reduce the aggregation propensity of Aβ, as evidenced by Confocal laser scanning microscopy and TEM studies. Remarkably, in vivo studies exhibited the promising therapeutic potential of compound 1. In a scopolamine-induced memory deficit mouse model of AD, compound 1 showed significantly improved spatial memory and cognition. These findings collectively underscore the potential of compound 1 as a promising therapeutic candidate for the treatment of AD.
Topics: Alzheimer Disease; Animals; Benzothiazoles; Molecular Docking Simulation; Cholinesterase Inhibitors; Amyloid beta-Peptides; Acetylcholinesterase; Mice; Male; Humans; Piperazines; Scopolamine; Piperazine; Peptide Fragments; Molecular Dynamics Simulation; Computer Simulation; Disease Models, Animal; Maze Learning
PubMed: 38565058
DOI: 10.1016/j.biopha.2024.116484 -
BMC Anesthesiology Apr 2024Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may... (Randomized Controlled Trial)
Randomized Controlled Trial
The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.
BACKGROUND
Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients.
METHODS
Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration.
RESULTS
HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05).
CONCLUSIONS
In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.
Topics: Aged; Humans; Neostigmine; Glycopyrrolate; Atropine; Delayed Emergence from Anesthesia; Neuromuscular Blockade; Cardiovascular System
PubMed: 38561654
DOI: 10.1186/s12871-024-02512-x