Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 470
Filter
1.
Acta Physiol (Oxf) ; : e14197, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958262

ABSTRACT

AIM: How the cerebral metabolic rates of oxygen and glucose utilization (CMRO2 and CMRGlc, respectively) are affected by alterations in arterial PCO2 (PaCO2) is equivocal and therefore was the primary question of this study. METHODS: This retrospective analysis involved pooled data from four separate studies, involving 41 healthy adults (35 males/6 females). Participants completed stepwise steady-state alterations in PaCO2 ranging between 30 and 60 mmHg. The CMRO2 and CMRGlc were assessed via the Fick approach (CBF × arterial-internal jugular venous difference of oxygen or glucose content, respectively) utilizing duplex ultrasound of the internal carotid artery and vertebral artery to calculate cerebral blood flow (CBF). RESULTS: The CMRO2 was altered by 0.5 mL × min-1 (95% CI: -0.6 to -0.3) per mmHg change in PaCO2 (p < 0.001) which corresponded to a 9.8% (95% CI: -13.2 to -6.5) change in CMRO2 with a 9 mmHg change in PaCO2 (inclusive of hypo- and hypercapnia). The CMRGlc was reduced by 7.7% (95% CI: -15.4 to -0.08, p = 0.045; i.e., reduction in net glucose uptake) and the oxidative glucose index (ratio of oxygen to glucose uptake) was reduced by 5.6% (95% CI: -11.2 to 0.06, p = 0.049) with a + 9 mmHg increase in PaCO2. CONCLUSION: Collectively, the CMRO2 is altered by approximately 1% per mmHg change in PaCO2. Further, glucose is incompletely oxidized during hypercapnia, indicating reductions in CMRO2 are either met by compensatory increases in nonoxidative glucose metabolism or explained by a reduction in total energy production.

2.
J Emerg Med ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-39030088

ABSTRACT

BACKGROUND: Salicylate poisoning may lead to critical acid-base disturbances. Tracheal intubation and mechanical ventilation for patients with severe salicylism has been strongly discouraged. STUDY OBJECTIVE: This study aims to describe pH trends, complications, and outcomes in a cohort of salicylate-poisoned patients who were intubated. METHODS: This retrospective observational study included adults presenting to the emergency department (ED) with severe salicylate poisoning (serum salicylate concentration >40 mg/dL and admission to an intensive care unit) over a 14-year period (2007-2021). The primary and secondary outcomes were the change in serum pH and the occurrence of severe complications (systolic blood pressure <80 mm Hg, oxygen saturation <80%, or cardiac arrest), respectively, in the 6 h after presentation. RESULTS: Among 32 adults with severe salicylate poisoning (median serum salicylate level 64.2, interquartile range 52.5-70.7), 11 (34%) underwent tracheal intubation. The initial mean pH (±SD) in the no intubation group was 7.48 ± 0.07 and was 7.36 ± 0.04 in the intubation group. The mean absolute difference in pH measured before and after intubation was -0.02 (95% confidence interval -0.11 to 0.07). No severe complications were observed during or up to 6 h after tracheal intubation and mechanical ventilation. CONCLUSION: In our single-center experience managing adults with severe salicylate poisoning, tracheal intubation and mechanical ventilation were not associated with substantial perturbation of serum pH or severe complications. These findings challenge the current paradigm that these interventions should be avoided in salicylate-poisoned patients.

3.
Disabil Rehabil ; : 1-10, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38910433

ABSTRACT

PURPOSE: To understand the oral health attitudes, knowledge, and practices among non-dental professionals caring for patients with spinal cord injuries, as well as the barriers and facilitators to oral care across acute and rehabilitation hospital settings. MATERIALS AND METHODS: This study was a descriptive qualitative study. Nine focus groups with spinal cord injury clinicians from two Sydney hospitals were conducted (n = 35). A thematic analysis was undertaken. RESULTS: Four themes were constructed: understanding the impact of spinal cord injuries on oral health and wellbeing; limited support in the spinal cord injury unit to promote oral care; strategies that enable oral care promotion; and recommendations to expand scope in oral care and education. Although most clinicians considered oral health to be important there was a lack of guidelines to support standardised oral care practices. Barriers included lack of time, limited oral care resources, low priority and difficulty in accessing treatment. Staff were receptive to an integrated, multidisciplinary approach to oral care. CONCLUSION: This Australian first study provides insight into spinal cord injury clinicians' knowledge and practices of oral care. The findings will help guide future research in developing appropriate models of care to promote oral health among patients with spinal cord injuries.


Individuals with a spinal cord injury are at an increased risk of irregular oral hygiene practices and poor oral health compared to those without a spinal cord injuryProviding access to training and development of a model of care for oral health promotion to support non-dental health professionals working with individuals with a spinal cord injury can improve access to early intervention oral health careImplementing targeted training for staff, developing clear guidelines or protocols, and piloting an integrated multidisciplinary model of care could be potential future solutions to close this gap in care.

4.
Science ; 384(6703): 1447-1452, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38935718

ABSTRACT

Understanding the microscopic origin of the superior electromechanical response in relaxor ferroelectrics requires knowledge not only of the atomic-scale formation of polar nanodomains (PNDs) but also the rules governing the arrangements and stimulated response of PNDs over longer distances. Using x-ray coherent nanodiffraction, we show the staggered self-assembly of PNDs into unidirectional mesostructures that we refer to as polar laminates in the relaxor ferroelectric 0.68PbMg1/3Nb2/3O3-0.32PbTiO3 (PMN-0.32PT). We reveal the highly heterogeneous electric-field-driven responses of intra- and interlaminate PNDs and establish their correlation with the local strain and the nature of the PND walls. Our observations highlight the critical role of hierarchical lattice organizations on macroscopic material properties and provide guiding principles for the understanding and design of relaxors and a wide range of quantum and functional materials.

5.
Sci Data ; 11(1): 682, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918394

ABSTRACT

Immunotherapies are revolutionizing cancer care, but many patients do not achieve durable responses and immune-related adverse events are difficult to predict. Quantifying the hundreds of proteins involved in cancer immunity has the potential to provide biomarkers to monitor and predict tumor response. We previously developed robust, multiplexed quantitative assays for immunomodulatory proteins using targeted mass spectrometry, providing measurements that can be performed reproducibly and harmonized across laboratories. Here, we expand upon those efforts in presenting data from a multiplexed immuno-oncology (IO)-3 assay panel targeting 43 peptides representing 39 immune- and inflammation-related proteins. A suite of novel monoclonal antibodies was generated as assay reagents, and the fully characterized antibodies are made available as a resource to the community. The publicly available dataset contains complete characterization of the assay performance, as well as the mass spectrometer parameters and reagent information necessary for implementation of the assay. Quantification of the proteins will provide benefit to correlative studies in clinical trials, identification of new biomarkers, and improve understanding of the immune response in cancer.


Subject(s)
Antibodies, Monoclonal , Mass Spectrometry , Neoplasms , Humans , Antibodies, Monoclonal/immunology , Immunotherapy , Neoplasms/immunology
6.
J Oral Rehabil ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886619

ABSTRACT

BACKGROUND: Individuals with spinal cord injuries (SCIs) are at an increased risk of poor oral health compared to the general population. However, little is known about the related barriers and facilitators experienced by these individuals within the hospital setting. OBJECTIVES: Understand the oral health knowledge, attitudes and practices of people with SCIs, barriers and facilitators to managing their oral health, and recommendations to improve oral care at acute/rehabilitation hospital settings. METHODS: Semi-structured interviews were conducted with 11 participants, from a major metropolitan hospital in Sydney, Australia. The interviews were thematically analysed. RESULTS: Three themes were constructed. Participants believed that the onus was on them to manage their oral health. Individuals also had limited knowledge of its importance to general health, and placed a lower priority on oral health compared to other aspects of health. All participants identified a combination of factors, such as cost, time, resources and prior negative experiences, that contributed to the neglect of their oral care. Participants also discussed the need of support from the multidisciplinary team and family/carers to facilitate oral care and identified various appropriate oral health education formats. CONCLUSION: This study highlighted some areas where oral health knowledge among people with SCIs could be improved. It also identified the need for oral health training for the multidisciplinary team, as well as carers, to better integrate oral care during rehabilitation in the hospital. The development of oral health interventions would need to utilise a co-design approach to best support clients and their carers to facilitate oral care self-management.

7.
J Occup Environ Hyg ; 21(7): 494-503, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38838303

ABSTRACT

The objective was to study the interaction of the components of a complex liquid mixture on the permeation parameters of its constituents. A firearm cleaning solvent, Hoppes No. 9 Gun Bore Cleaner, was selected to challenge two varieties of disposable nitrile gloves, the thinnest (Kimberly-Clark Lavender) and thickest (Kimberly-Clark Blue), using the closed-loop ASTM F739 cell without recirculation and n-decane collection followed by quantitation of the permeated compounds using capillary gas chromatography-mass spectrometry. The thicker Blue glove resisted the permeation of Hoppe's relative to the thinner Lavender glove as shown by 3.2 times more mass permeated by the Lavender glove at 60 min despite the same standardized breakthrough times (7.5 ± 2.5 min). The kerosene fraction permeated faster at a much higher rate than expected. The Kimberly-Clark disposable nitrile glove chemical resistance guide lists a breakthrough time for kerosene of 82 min for Sterling disposable nitrile glove material. However, for Hoppe's the kerosene components appeared at the standardized breakthrough time. Mixture components that were reported by the glove manufacturer to quickly permeate the disposable nitrile material, such as ethanol, did not permeate at a rate slower than expected, indicative of a possible carrier function. A semiquantitative risk assessment confirmed the unacceptability of both gloves. Persons using personal protective equipment, such as gloves, may not be afforded the expected resistance to chemical permeation when chemicals are in a suitable mixture, hence enhancing the risk of exposure. More research is needed to produce better glove testing measures to ensure the safety of workers.


Subject(s)
Firearms , Gloves, Protective , Nitriles , Permeability , Solvents , Nitriles/chemistry , Occupational Exposure/prevention & control , Occupational Exposure/analysis , Humans , Materials Testing , Gas Chromatography-Mass Spectrometry
9.
Prehosp Emerg Care ; : 1-5, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38781490

ABSTRACT

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

10.
Circ Arrhythm Electrophysiol ; 17(6): e012635, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38804141

ABSTRACT

BACKGROUND: Irrigated radiofrequency ablation with half-normal saline can potentially increase lesion size but may increase the risk of steam pops with the risk of emboli or perforation. We hypothesized that pops would be preceded by intracardiac echocardiography (ICE) findings as well as a large impedance fall. METHODS: In 100 consecutive patients undergoing endocardial ventricular arrhythmia radiofrequency ablation with half-normal saline, we attempted to observe the ablation site with ICE. Radiofrequency ablation power was titrated to a 15 to 20 Ohm impedance fall and could be adjusted for tissue whitening and increasing bubble formation on ICE. Steam pops were defined as audible or a sudden explosion of microbubbles on ICE. RESULTS: Of 2190 ablation applications in 100 patients (82% cardiomyopathy, 50% sustained ventricular tachycardia), pops occurred during 43 (2.0%) applications. Sites with pops had greater impedance decreases of 18 [14, 21]% versus 13 [10, 17]% (P<0.001). ICE visualized 1308 (59.7%) radiofrequency sites, and fewer pops occurred when ICE visualized the radiofrequency ablation site (1.4%) compared with without ICE visualization (2.8%; P=0.016). Of the 18 ICE-visible pops, 7 (39%) were silent but recognized as an explosion of bubbles on ICE. With ICE, 89% of pops were preceded by either tissue whitening or a sudden increase in bubbles. In a multivariable model, tissue whitening and a sudden increase in bubbles were associated with steam pops (odds ratio, 7.186; P=0.004, and odds ratio, 29.93; P<0.001, respectively), independent of impedance fall and power. There were no pericardial effusions or embolic events with steam pops. CONCLUSIONS: Steam pops occurred in 2% of half-normal saline radiofrequency applications titrated to an impedance fall and are likely under-recognized without ICE. On ICE, steam pops are usually preceded by tissue whitening or a sudden increase in bubble formation, which can potentially be used to adjust radiofrequency application to help reduce pops.


Subject(s)
Catheter Ablation , Echocardiography , Saline Solution , Steam , Tachycardia, Ventricular , Therapeutic Irrigation , Humans , Male , Female , Saline Solution/administration & dosage , Middle Aged , Catheter Ablation/adverse effects , Tachycardia, Ventricular/surgery , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/diagnostic imaging , Aged , Embolism, Air/prevention & control , Embolism, Air/etiology , Embolism, Air/diagnostic imaging , Treatment Outcome , Risk Factors , Predictive Value of Tests , Electric Impedance
11.
Nutrients ; 16(8)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38674798

ABSTRACT

The Teruel Orthorexia Scale (TOS) defines two related but distinct constructs: Orthorexia Nervosa (OrNe), a pathological fixation on a healthy diet, and Healthy Orthorexia (HeOr), an interest in a healthy diet independent of psychopathology. Here, we (a) assessed both types of Orthorexia in a large North American sample using the TOS and (b) explored if engaging in regular physical activity was associated with a greater risk of Orthorexia. A cohort of physically active adults (n = 927; 41% men) completed the TOS, as well as the Rapid Assessment of Physical Activity (RAPA), to broadly assess aerobic physical activity level and participation in strength and/or flexibility training. As expected, scores for HeOr and OrNe differed between participants, with lower scores for Orthorexia Nervosa in our physically active non-clinical sample. Higher HeOr scores were associated with lower BMI, and this was true for both men and women. We also found that measures of Orthorexia were associated with self-reported physical activity: active adults reporting more aerobic physical activity had higher HeOr scores, with the most active men having the highest scores. Notably, adults who reported regular strength training had higher scores for both HeOr and OrNe, with men who strength trained showing higher OrNe scores than women. Here, those who participate in regular strength training are more likely to exhibit orthorexic behaviors, and this effect was more pronounced for men than women. Prior work has validated the TOS in young, primarily female samples of non-English speakers outside the United States: present data from an age-diverse, physically active, gender balanced sample support the use of TOS for measurement of Orthorexia Nervosa and Healthy Orthorexia in English speakers and suggest that more work is needed to assess potential gender differences in these constructs.


Subject(s)
Diet, Healthy , Exercise , Health Behavior , Humans , Male , Female , Adult , Exercise/psychology , Diet, Healthy/psychology , Middle Aged , Young Adult , Feeding and Eating Disorders/psychology , Feeding and Eating Disorders/epidemiology , Feeding Behavior/psychology , North America , Surveys and Questionnaires , Adolescent , Body Mass Index
12.
Heart Rhythm ; 21(6): 956-957, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38431023
13.
J Am Heart Assoc ; 13(6): e031029, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38471835

ABSTRACT

BACKGROUND: Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model. METHODS AND RESULTS: Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve. CONCLUSIONS: Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.


Subject(s)
Atrial Fibrillation , Atrial Remodeling , Catheter Ablation , Humans , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Angiopoietin-2 , Interleukin-6 , Models, Statistical , Stroke Volume , Ventricular Remodeling , Risk Factors , Prognosis , Recurrence , Ventricular Function, Left , Biomarkers , Catheter Ablation/adverse effects , Catheter Ablation/methods , Treatment Outcome
14.
J Cardiovasc Electrophysiol ; 35(5): 994-1004, 2024 May.
Article in English | MEDLINE | ID: mdl-38501333

ABSTRACT

INTRODUCTION: When ventricular tachycardia (VT) recurs after standard RF ablation (sRFA) some patients benefit from repeat sRFA, whereas others warrant advanced methods such as intramural needle ablation (INA). Our objectives are to assess the utility of repeat sRFA and to clarify the benefit of INA when repeat sRFA fails in patients with VT due to structural heart disease. METHODS: In consecutive patients who were prospectively enrolled in a study for INA for recurrent sustained monomorphic VT despite sRFA, repeat sRFA was considered first. INA was performed during the same procedure if repeat sRFA failed or no targets for sRFA were identified. RESULTS: Of 85 patients enrolled, acute success with repeat sRFA was achieved in 30 patients (35%), and during the 6-month follow-up, 87% (20/23) were free of VT hospitalization, 78% were free of any VT, and 7 were lost to follow-up. INA was performed in 55 patients (65%) after sRFA failed, or no endocardial targets were found abolished or modified inducible VT in 35/55 patients (64%). During follow-up, 72% (39/54) were free of VT hospitalization, 41% were free of any VT, and 1 was lost to follow-up. Overall, 59 out of 77 (77%) patients were free of hospitalization and 52% were free of any VT. Septal-origin VTs were more likely to need INA, whereas RV and papillary muscle VTs were less likely to require INA. CONCLUSIONS: Repeat sRFA was beneficial in 23% (18/77) of patients with recurrent sustained VT who were referred for INA. The availability of INA increased favorable outcomes to 52%.


Subject(s)
Catheter Ablation , Cicatrix , Recurrence , Reoperation , Tachycardia, Ventricular , Humans , Tachycardia, Ventricular/surgery , Tachycardia, Ventricular/physiopathology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Male , Female , Middle Aged , Aged , Prospective Studies , Catheter Ablation/adverse effects , Cicatrix/physiopathology , Cicatrix/diagnosis , Cicatrix/surgery , Cicatrix/etiology , Time Factors , Action Potentials , Needles , Heart Rate , Risk Factors , Treatment Outcome
15.
J Natl Cancer Inst ; 116(6): 957-965, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38466935

ABSTRACT

BACKGROUND: Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes, which lead to high microsatellite instability and frameshift mutations at coding mononucleotide repeats in the genome. Recurrent frameshift mutations in these regions are thought to play a central role in the increased risk of various cancers, but no biomarkers are currently available for the surveillance of high microsatellite instability-associated cancers. METHODS: A frameshift mutation-based biomarker panel was developed and validated by targeted next-generation sequencing of supernatant DNA from cultured high microsatellite instability colorectal cancer cells. This panel supported selection of 122 frameshift mutation targets as potential biomarkers. This biomarker panel was then tested using matched tumor, adjacent normal tissue, and buffy coat samples (53 samples) and blood-derived cell-free DNA (cfDNA) (38 samples) obtained from 45 high microsatellite instability and mismatch repair-deficient patients. We also sequenced cfDNA from 84 healthy participants to assess background noise. RESULTS: Recurrent frameshift mutations at coding mononucleotide repeats were detectable not only in tumors but also in cfDNA from high microsatellite instability and mismatch repair-deficient patients, including a Lynch syndrome carrier, with a varying range of target detection (up to 85.2%), whereas they were virtually undetectable in healthy participants. Receiver operating characteristic curve analysis showed high sensitivity and specificity (area under the curve = 0.94) of the investigated panel. CONCLUSIONS: We demonstrated that frameshift mutations can be detected in cfDNA from high microsatellite instability and mismatch repair-deficient patients and asymptomatic carriers. The 122-target frameshift mutation panel described here has promise as a tool for improved surveillance of high microsatellite instability and mismatch repair-deficient patients, with the potential to reduce the frequency of invasive screening methods for this high-cancer-risk cohort.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms, Hereditary Nonpolyposis , Frameshift Mutation , Microsatellite Instability , Humans , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/blood , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Male , Female , Middle Aged , Adult , Aged , DNA Mismatch Repair/genetics , High-Throughput Nucleotide Sequencing , ROC Curve , Case-Control Studies , Sensitivity and Specificity
17.
Europace ; 26(2)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38367008

ABSTRACT

AIMS: Failure of radiofrequency (RF) ablation of ventricular arrhythmias is often due to inadequate lesion size. Irrigated RF ablation with half-normal saline (HNS) has the potential to increase lesion size and reduce sodium delivery to the patient if the same volume of RF irrigant were used for normal saline (NS) and HNS but could increase risks related to steam pops and lesion size. This study aims to assess periprocedural complications and acute ablation outcome of ventricular arrhythmias ablation with HNS. METHODS AND RESULTS: Prospective assessment of outcomes was performed in 1024 endocardial and/or epicardial RF ablation procedures in 935 consecutive patients (median age 64 years, 71.2% men, 73.4% cardiomyopathy, 47.2% sustained ventricular tachycardia). Half-normal saline was selected at the discretion of the treating physician. Radiofrequency ablation power was generally titrated to a ≤15â€…Ω impedance fall with intracardiac echocardiography monitoring. Half-normal saline was used in 900 (87.9%) and NS in 124 (12.1%) procedures. Any adverse event within 30 days occurred in 13.0% of patients treated with HNS RF ablation including 4 (0.4%) strokes/transient ischaemic attacks and 34 (3.8%) pericardial effusions requiring treatment (mostly related to epicardial access). Two steam pops with perforation required surgical repair (0.2%). Patients who received NS irrigation had less severe disease and arrhythmias. In multivariable models, adverse events and acute success of the procedure were not related to the type of irrigation. CONCLUSION: Half-normal saline irrigation RF ablation with power guided by impedance fall and intracardiac echocardiography has an acceptable rate of complications and acute ablation success while administering half of the saline load expected for NS irrigation.


Subject(s)
Catheter Ablation , Radiofrequency Ablation , Tachycardia, Ventricular , Male , Humans , Middle Aged , Female , Saline Solution/adverse effects , Steam , Prospective Studies , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/surgery , Catheter Ablation/adverse effects , Catheter Ablation/methods , Tachycardia, Ventricular/surgery , Therapeutic Irrigation/adverse effects
18.
Life Sci Alliance ; 7(4)2024 Apr.
Article in English | MEDLINE | ID: mdl-38253420

ABSTRACT

Cristae are invaginations of the mitochondrial inner membrane that are crucial for cellular energy metabolism. The formation of cristae requires the presence of a protein complex known as MICOS, which is conserved across eukaryotic species. One of the subunits of this complex, MIC10, is a transmembrane protein that supports cristae formation by oligomerization. In Drosophila melanogaster, three MIC10-like proteins with different tissue-specific expression patterns exist. We demonstrate that CG41128/MINOS1b/DmMIC10b is the major MIC10 orthologue in flies. Its loss destabilizes MICOS, disturbs cristae architecture, and reduces the life span and fertility of flies. We show that DmMIC10b has a unique ability to polymerize into bundles of filaments, which can remodel mitochondrial crista membranes. The formation of these filaments relies on conserved glycine and cysteine residues, and can be suppressed by the co-expression of other Drosophila MICOS proteins. These findings provide new insights into the regulation of MICOS in flies, and suggest potential mechanisms for the maintenance of mitochondrial ultrastructure.


Subject(s)
Drosophila Proteins , Drosophila , Animals , Drosophila melanogaster , Mitochondrial Membranes , Cytoskeleton , Mitochondria Associated Membranes , Drosophila Proteins/genetics
19.
Am J Physiol Heart Circ Physiol ; 326(3): H705-H714, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38241007

ABSTRACT

Pentoxifylline is a nonselective phosphodiesterase inhibitor used for the treatment of peripheral artery disease. Pentoxifylline acts through cyclic adenosine monophosphate, thereby enhancing red blood cell deformability, causing vasodilation and decreasing inflammation, and potentially stimulating ventilation. We conducted a double-blind, placebo-controlled, crossover, counter-balanced study to test the hypothesis that pentoxifylline could lower blood viscosity, enhance cerebral blood flow, and decrease pulmonary artery pressure in lowlanders following 11-14 days at 3,800 m. Participants (6 males/10 females; age, 27 ± 4 yr old) received either a placebo or 400 mg of pentoxifylline orally the night before and again 2 h before testing. We assessed arterial blood gases, venous hemorheology (blood viscosity, red blood cell deformability, and aggregation), and inflammation (TNF-α) in room air (end-tidal oxygen partial pressure, ∼52 mmHg). Global cerebral blood flow (gCBF), ventilation, and pulmonary artery systolic pressure (PASP) were measured in room air and again after 8-10 min of isocapnic hypoxia (end-tidal oxygen partial pressure, 40 mmHg). Pentoxifylline did not alter arterial blood gases, TNF-α, or hemorheology compared with placebo. Pentoxifylline did not affect gCBF or ventilation during room air or isocapnic hypoxia compared with placebo. However, in females, PASP was reduced with pentoxifylline during room air (placebo, 19 ± 3; pentoxifylline, 16 ± 3 mmHg; P = 0.021) and isocapnic hypoxia (placebo, 22 ± 5; pentoxifylline, 20 ± 4 mmHg; P = 0.029), but not in males. Acute pentoxifylline administration in lowlanders at 3,800 m had no impact on arterial blood gases, hemorheology, inflammation, gCBF, or ventilation. Unexpectedly, however, pentoxifylline reduced PASP in female participants, indicating a potential effect of sex on the pulmonary vascular responses to pentoxifylline.NEW & NOTEWORTHY We conducted a double-blind, placebo-controlled study on the rheological, cardiorespiratory and cerebrovascular effects of acute pentoxifylline in healthy lowlanders after 11-14 days at 3,800 m. Although red blood cell deformability was reduced and blood viscosity increased compared with low altitude, acute pentoxifylline administration had no impact on arterial blood gases, hemorheology, inflammation, cerebral blood flow, or ventilation. Pentoxifylline decreased pulmonary artery systolic pressure in female, but not male, participants.


Subject(s)
Pentoxifylline , Male , Humans , Female , Young Adult , Adult , Pentoxifylline/pharmacology , Pentoxifylline/therapeutic use , Hemorheology , Tumor Necrosis Factor-alpha , Hypoxia , Oxygen , Acclimatization/physiology , Inflammation/complications , Gases , Cerebrovascular Circulation , Altitude
20.
JACC Clin Electrophysiol ; 10(2): 193-202, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38069975

ABSTRACT

BACKGROUND: Risks of radiofrequency catheter ablation for ventricular arrhythmias include emboli and bleeding complications but data on antithrombotic regimens are limited and guidelines do not specify a systematic approach. OBJECTIVES: This study sought to assess embolic and bleeding complications in relation to pre-periprocedure and post-periprocedure antithrombotic regimens. METHODS: Prospective assessment for complications was performed for 663 endocardial radiofrequency catheter ablation procedures in 616 consecutive patients (median age 64 years [Q1-Q3: 54-73 years], 70.3% men, 71.6% with cardiomyopathy, 44.5% with sustained ventricular tachycardia). RESULTS: There were 2 strokes (0.3%; 95% CI: 0.0%-0.8%), 1 transient ischemic attack (0.15%), and 2 pulmonary emboli (0.3%). There were 39 bleeding complications (5.9%) including 11 pericardial effusions (1.7%), and 28 related to vascular access (4.2%). Consistent with the prevalence of coronary artery disease (47.5%), atrial fibrillation (30.0%), and prior stroke (10.6%), preprocedure, 464 patients (70.0%) were taking antithrombotic agents including 220 (33.2%) taking aspirin alone (ASA), and 163 (24.6%) taking warfarin or a direct acting oral anticoagulant (DOAC). Preprocedure non-ASA antiplatelet use (OR: 2.846; P = 0.011) and DOAC use (OR: 2.585; P = 0.032) were associated with risk of bleeding complications. Following ablation, 49.8% of patients were treated with ASA 325 mg/d and 30.3% received DOACs or warfarin. New DOAC or warfarin administration was initiated in only 6.6% of patients. Overall, 39.7% of patients continued the same preprocedure antithrombotic regimen. CONCLUSIONS: Stroke is a rare complication of radiofrequency catheter ablation for ventricular arrhythmia using ASA 325 mg/d as a minimal postprocedure regimen with more potent regimens for selected patients.


Subject(s)
Atrial Fibrillation , Stroke , Male , Humans , Middle Aged , Female , Warfarin/adverse effects , Anticoagulants/adverse effects , Hemorrhage/etiology , Hemorrhage/chemically induced , Fibrinolytic Agents , Prospective Studies , Stroke/etiology , Stroke/epidemiology , Atrial Fibrillation/surgery , Aspirin/adverse effects
SELECTION OF CITATIONS
SEARCH DETAIL
...